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حَدَّثَنَا يَحْيَى بْنُ يَحْيَى، وَأَبُو بَكْرِ بْنُ أَبِي شَيْبَةَ كِلاَهُمَا عَنْ أَبِي مُعَاوِيَةَ، قَالَ يَحْيَى أَخْبَرَنَا أَبُو مُعَاوِيَةَ، عَنِ الأَعْمَشِ، عَنْ عَبْدِ اللَّهِ بْنِ مُرَّةَ، عَنِ الْبَرَاءِ بْنِ عَازِبٍ، قَالَ مُرَّ عَلَى النَّبِيِّ صلى الله عليه وسلم بِيَهُودِيٍّ مُحَمَّمًا مَجْلُودًا فَدَعَاهُمْ صلى الله عليه وسلم فَقَالَ ‏"‏ هَكَذَا تَجِدُونَ حَدَّ الزَّانِي فِي كِتَابِكُمْ ‏"‏ ‏.‏ قَالُوا نَعَمْ ‏.‏ فَدَعَا رَجُلاً مِنْ عُلَمَائِهِمْ فَقَالَ ‏"‏ أَنْشُدُكَ بِاللَّهِ الَّذِي أَنْزَلَ التَّوْرَاةَ عَلَى مُوسَى أَهَكَذَا تَجِدُونَ حَدَّ الزَّانِي فِي كِتَابِكُمْ ‏"‏ ‏.‏ قَالَ لاَ وَلَوْلاَ أَنَّكَ نَشَدْتَنِي بِهَذَا لَمْ أُخْبِرْكَ نَجِدُهُ الرَّجْمَ وَلَكِنَّهُ كَثُرَ فِي أَشْرَافِنَا فَكُنَّا إِذَا أَخَذْنَا الشَّرِيفَ تَرَكْنَاهُ وَإِذَا أَخَذْنَا الضَّعِيفَ أَقَمْنَا عَلَيْهِ الْحَدَّ قُلْنَا تَعَالَوْا فَلْنَجْتَمِعْ عَلَى شَىْءٍ نُقِيمُهُ عَلَى الشَّرِيفِ وَالْوَضِيعِ فَجَعَلْنَا التَّحْمِيمَ وَالْجَلْدَ مَكَانَ الرَّجْمِ ‏.‏ فَقَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم ‏"‏ اللَّهُمَّ إِنِّي أَوَّلُ مَنْ أَحْيَا أَمْرَكَ إِذْ أَمَاتُوهُ ‏"‏ ‏.‏ فَأَمَرَ بِهِ فَرُجِمَ فَأَنْزَلَ اللَّهُ عَزَّ وَجَلَّ ‏{‏ يَا أَيُّهَا الرَّسُولُ لاَ يَحْزُنْكَ الَّذِينَ يُسَارِعُونَ فِي الْكُفْرِ‏}‏ إِلَى قَوْلِهِ ‏{‏ إِنْ أُوتِيتُمْ هَذَا فَخُذُوهُ‏}‏ يَقُولُ ائْتُوا مُحَمَّدًا صلى الله عليه وسلم فَإِنْ أَمَرَكُمْ بِالتَّحْمِيمِ وَالْجَلْدِ فَخُذُوهُ وَإِنْ أَفْتَاكُمْ بِالرَّجْمِ فَاحْذَرُوا ‏.‏ فَأَنْزَلَ اللَّهُ تَعَالَى ‏{‏ وَمَنْ لَمْ يَحْكُمْ بِمَا أَنْزَلَ اللَّهُ فَأُولَئِكَ هُمُ الْكَافِرُونَ‏}‏ ‏{‏ وَمَنْ لَمْ يَحْكُمْ بِمَا أَنْزَلَ اللَّهُ فَأُولَئِكَ هُمُ الظَّالِمُونَ‏}‏ ‏{‏ وَمَنْ لَمْ يَحْكُمْ بِمَا أَنْزَلَ اللَّهُ فَأُولَئِكَ هُمُ الْفَاسِقُونَ‏}‏ فِي الْكُفَّارِ كُلُّهَا ‏.‏

Al-Bara' b. 'Azib reported:There happened to pass by Allah's Apostle (ﷺ) a Jew blackened and lashed. Allah's Apostle (ﷺ) called them (the Jews) and said: Is this the punishment that you find in your Book (Torah) as a prescribed punishment for adultery? They said: Yes. He (the Holy Prophet) called one of the scholars amongst them and said: I ask you in the name of Allah Who sent down the Torah on Moses if that is the prescribed punishment for adultery that you find in your Book. He said: No. Had you not asked me in the name of Allah, I would not have given you this information. We find stoning to death (as punishment prescribed in the Torah). But this (crime) became quite common amongst our aristocratic class. So when we caught hold of any rich person (indulging in this offence) we spared him, but when we caught hold of a helpless person we imposed the prescribed punishment upon him. We then said: Let us argree (on a punishment) which we can inflict both upon the rich and the poor. So We decided to blacken the face with coal and flog as a substitute punishment for stoning. Thereupon Allah's Messenger (ﷺ) said: O Allah, I am the first to revive Thy command when they had made it dead. He then commanded and he (the offender) was stoned to death. Allah, the Majestic and Glorious, sent down (this verse):" O Messenger, (the behaviour of) those who vie with one another in denying the truth should not grieve you..." up to" is vouchsafed unto you, accept it" (v. 41) 2176 It was said (by the Jews): Go to Muhammad; it he commands you to blacken the face and award flogging (as punishment for adultery), then accept it, but it he gives verdict for stoning, then avoid it. It was (then) that Allah, the Majestic and Great, sent down (these verses):" And they who do not judge in accordance with what Allah has revealed are, indeed, deniers of the truth" (v. 44) ;" And they who do not judge in accordance with what Allah has revealed-they, they indeed are the wrongdoers" (v. 45) ;" And they who do not judge in accordance with what God has revealed-they are the iniquitous (v. 47). (All these verses) were revealed in connection with the non-believers

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Randomized controlled trial of prolonged exposure using imaginal exposure vs. virtual reality exposure in active duty soldiers with deployment-related posttraumatic stress disorder (PTSD).

OBJECTIVE: Prolonged exposure (PE) is an evidence-based psychotherapy for posttraumatic stress disorder (PTSD) but there is limited research with active-duty military populations. Virtual reality exposure (VRE) has shown promise but randomized trials are needed to evaluate efficacy relative to existing standards of care. This study evaluated the efficacy of VRE and PE for active duty soldiers with PTSD from deployments to Iraq and Afghanistan. METHOD: Active-duty soldiers (N = 162) were randomized to 10-sessions of PE, VRE, or a minimal attention waitlist (WL). Blinded assessors evaluated symptoms at baseline, halfway through treatment, at posttreatment, and at 3- and 6-month follow-ups using the Clinician Administered PTSD Scale (CAPS). RESULTS: Intent-to-treat analyses found that both PE and VRE resulted in significant reductions in PTSD symptoms relative to those in the WL. The majority of patients demonstrated reliable change in PTSD symptoms. There was no difference between PE and VRE regarding treatment drop out before completing 10 sessions (44 and 41% for VRE and PE, respectively). Contrary to hypotheses, analyses at posttreatment did not show that VRE was superior to PE. Post hoc analyses found that PE resulted in significantly greater symptom reductions than VRE at 3- and 6-month follow-up. Both treatments significantly reduced self-reported stigma. CONCLUSIONS: PE is an efficacious treatment for active-duty Army soldiers with PTSD from deployments to Iraq or Afghanistan. Results extend previous evidence supporting the efficacy of PE to active-duty military personnel and raise important questions for future research on VRE. (PsycINFO Database Record

Journal of Consulting and Clinical Psychology · randomised controlled trial · 225 citationsread the source →

Does active referral by a doctor or 12-Step peer improve 12-Step meeting attendance? Results from a pilot randomised control trial.

Background: Active engagement in 12-Step self-help groups (SHG) is associated with improvements in substance use outcomes during and after treatment, yet levels of participation in SHG meetings in the U.K. remain low. Method: An RCT investigating the impact of active referral to SHG, delivered by doctors or 12-Step peers during inpatient treatment on both inpatient and post-treatment meeting attendance was conducted. 151 inpatients with alcohol, opiate, crack-cocaine or benzodiazepine dependence undergoing detoxification, received one of two active referral interventions: 12-Step peer intervention (PI), doctor intervention (DI), or no intervention (NI). 83% of the sample was followed up, 2-3 months following discharge. Results: Active referral interventions significantly increased attendance at 12-Step meetings during inpatient treatment (88% versus 73%, p<.05). Rates of post-discharge meeting attendance were PI=64%, DI=48%, NI=33%, with those in the PI group significantly (OR=3.6; CI=1.3, 9.8) more likely to have attended. Inpatient meeting attenders were three times as likely to have attended meetings post-discharge (59% versus 20%, p<.01), and post-discharge meeting attenders reported significantly higher abstinence rates (60.8% versus 39.2%, p<.05) at follow-up. However, abstinence rates did not differ significantly across intervention groups (44% [PI], 41% [DI] and 36% [NI]). Conclusion: Attendance at 12-Step SHGs is associated with greater rates of abstinence and active referral, especially by 12-Step peers, increases 12-Step SHG attendance rates. However, improved clinical outcomes among attendees might not occur until stronger recovery peer support networks are established. These results show promise for the benefit of incorporating Twelve Step Facilitation into U.K. treatment settings.

Drug and alcohol dependence · randomised controlled trial · 43 citationsread the source →

Randomised clinical non-inferiority trial of breathing-based meditation and cognitive processing therapy for symptoms of post-traumatic stress disorder in military veterans.

Objective: Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial. Setting: Outpatient Veterans Affairs healthcare centre. Participants: 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study. Interventions: SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks. Measures: The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS). Results: Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6 weeks (end of treatment) relative to baseline (SKY, -5.6, d=0.41, n=41: CPT, -6.8, d=0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (-1.2, 95% CI -5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT-SKY: -2.1, 95% CI -6.9 to 2.8) and 1-year (CPT-SKY: -1.8, 95% CI -6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1 month, but SKY was inferior to CPT on both BDI-II and PANAS at 1 year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95% CI 0.51 to 3.62, p=0.54). Conclusions: SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD. Trial registration number: NCT02366403.

BMJ open · randomised controlled trial · 15 citationsread the source →

Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer.

Purpose: Cancer-related fatigue (CRF) is the most common symptom in patients with advanced cancer. The primary objective of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF. Patients and methods: Patients with advanced cancer with ≥ three CRF-related symptoms (ie, fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days. The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale from baseline to day 15. Secondary outcomes included anorexia, anxiety, depression, and symptom distress scores. Results: A total of 84 patients were evaluable (dexamethasone, 43; placebo, 41). Mean (± standard deviation) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group (9 [± 10.3] v 3.1 [± 9.59]; P = .008). The improvement in FACIT-F total quality-of-life scores was also significantly better for the dexamethasone group at day 15 (P = .03). The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group (P = .013, respectively). No differences were observed for ESAS overall symptom distress (P = .22) or psychological distress score (P = .76). Frequency of adverse effects was not significantly different between groups (41 of 62 v 44 of 58; P = .14). Conclusion: Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 216 citationsread the source →

Treatment of Opioid Use Disorder in Pregnant Women via Telemedicine: A Nonrandomized Controlled Trial.

Importance: There are high rates of maternal and newborn morbidity and mortality associated with opioid use disorder (OUD). Integrating OUD treatment in obstetric practices for pregnant and postpartum women via telemedicine can increase access to care and reduce the consequences of OUD. Evaluation of this care delivery model, however, is needed before widespread adoption. Objective: To compare maternal and newborn outcomes among pregnant women with OUD receiving care via telemedicine vs in person. Design, setting, and participants: A nonrandomized controlled trial including 98 women receiving perinatal OUD treatment in 4 outpatient obstetric practices by telemedicine or in person and followed up until 6 to 8 weeks post partum was conducted from September 4, 2017, to December 31, 2018. Logistic regression with propensity score adjustment was applied to reduce group selection bias and control for potentially confounding variables. Interventions: Participants were seen weekly for 4 weeks, every 2 weeks for 4 weeks, and monthly thereafter and provided relapse prevention therapy and buprenorphine. Main outcomes and measures: The outcomes were retention in treatment, defined as uninterrupted addiction treatment during pregnancy through 6 to 8 weeks post partum; urine drug screen results at delivery and 6 to 8 weeks post partum; and a neonatal abstinence syndrome (NAS) diagnosis collected via electronic health records. Results: The mean (SD) age of the 98 pregnant women was 30.23 (5.12) years. Of these, 41 of 44 women (93.2%) in the telemedicine group and 48 of 54 women (88.9%) in the in-person group chose to continue treatment in the program after an initial evaluation. After propensity score weighting and doubly robust estimation, no significant differences were found between groups in retention in treatment at 6 to 8 weeks post partum (telemedicine: 80.4% vs in person: 92.7%; treatment effect, -12.2%; 95% CI, -32.3% to -4.4%). Similarly, after propensity score weighting and doubly robust estimation, there were no significant group differences in rates of NAS (telemedicine: 45.4% vs in person: 63.2%; treatment effect, -17.8%; 95% CI, -41.0% to 8.9%). Conclusions and relevance: In this nonrandomized controlled trial, virtually integrated OUD care in obstetric practices produced similar maternal and newborn outcomes compared with in-person care. These findings may have important public health implications for combatting the opioid crisis and its consequences on pregnant women and their families. Future large randomized clinical trials are needed. Clinical trial registration: ClinicalTrials.gov identifier: NCT04049032.

JAMA network open · cohort or longitudinal · 43 citationsread the source →

A randomized controlled trial of family therapy and cognitive behavior therapy guided self-care for adolescents with bulimia nervosa and related disorders.

Objective: To date no trial has focused on the treatment of adolescents with bulimia nervosa. The aim of this study was to compare the efficacy and cost-effectiveness of family therapy and cognitive behavior therapy (CBT) guided self-care in adolescents with bulimia nervosa or eating disorder not otherwise specified. Method: Eighty-five adolescents with bulimia nervosa or eating disorder not otherwise specified were recruited from eating disorder services in the United Kingdom. Participants were randomly assigned to family therapy for bulimia nervosa or individual CBT guided self-care supported by a health professional. The primary outcome measures were abstinence from binge-eating and vomiting, as assessed by interview at end of treatment (6 months) and again at 12 months. Secondary outcome measures included other bulimic symptoms and cost of care. Results: Of the 85 study participants, 41 were assigned to family therapy and 44 to CBT guided self-care. At 6 months, bingeing had undergone a significantly greater reduction in the guided self-care group than in the family therapy group; however, this difference disappeared at 12 months. There were no other differences between groups in behavioral or attitudinal eating disorder symptoms. The direct cost of treatment was lower for guided self-care than for family therapy. The two treatments did not differ in other cost categories. Conclusions: Compared with family therapy, CBT guided self-care has the slight advantage of offering a more rapid reduction of bingeing, lower cost, and greater acceptability for adolescents with bulimia or eating disorder not otherwise specified.

The American journal of psychiatry · randomised controlled trial · 154 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis.

Background: Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder. Methods: For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features. Findings: We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21-3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25-1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10-2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45-5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39-2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41-2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13-1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43-2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45-2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09-1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07-1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88-2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality. Interpretation: Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder. Funding: None.

The lancet. Psychiatry · meta-analysis · 278 citationsread the source →

A review of popular smartphone apps for depression and anxiety: Assessing the inclusion of evidence-based content.

Smartphone applications for the treatment of depression and anxiety have acquired millions of users, yet little is known about whether they include evidence-based therapeutic content. We examined the extent to which popular mental health applications (MH apps) for depression and anxiety contain treatment elements found in empirically supported psychotherapy protocols (i.e., "common elements"). Of the 27 MH apps reviewed, 23 included at least one common element, with a median of three elements. Psychoeducation (in 52% of apps), relaxation (44%), meditation (41%), mindfulness (37%), and assessment (37%) were the most frequent elements, whereas several elements (e.g., problem solving) were not found in any apps. We also identified gaps between app content and empirically supported treatments. Cognitive restructuring was more common in depression protocols than in depression apps (75% of protocols vs. 31% of apps), as was problem solving (34% vs. 0%). For anxiety, exposure (85%, 12%), cognitive restructuring (60%, 12%), and problem solving (25%, 0%) were more common in protocols than apps. Overall, our findings highlight empirically supported treatment elements that are poorly represented in current MH apps. The absence of several core treatment elements underscores the need for future research, including randomized trials testing the effectiveness of popular MH apps.

Behaviour research and therapy · 85 citationsread the source →

A planetary health model for reducing exposure to faecal contamination in urban informal settlements: Baseline findings from Makassar, Indonesia.

Background: The intense interactions between people, animals and environmental systems in urban informal settlements compromise human and environmental health. Inadequate water and sanitation services, compounded by exposure to flooding and climate change risks, expose inhabitants to environmental contamination causing poor health and wellbeing and degrading ecosystems. However, the exact nature and full scope of risks and exposure pathways between human health and the environment in informal settlements are uncertain. Existing models are limited to microbiological linkages related to faecal-oral exposures at the individual level, and do not account for a broader range of human-environmental variables and interactions that affect population health and wellbeing. Methods: We undertook a 12-month health and environmental assessment in 12 flood-prone informal settlements in Makassar, Indonesia. We obtained caregiver-reported health data, anthropometric measurements, stool and blood samples from children < 5 years, and health and wellbeing data for children 5-14 years and adult respondents. We collected environmental data including temperature, mosquito and rat species abundance, and water and sediment samples. Demographic, built environment and household asset data were also collected. We combined our data with existing literature to generate a novel planetary health model of health and environment in informal settlements. Results: Across the 12 settlements, 593 households and 2764 participants were enrolled. Two-thirds (64·1%) of all houses (26·3-82·7% per settlement) had formal land tenure documentation. Cough, fever and diarrhoea in the week prior to the survey were reported among an average of 34.3%, 26.9% and 9.7% of children aged < 5 years, respectively; although proportions varied over time, prevalence among these youngest children was consistently higher than among children 5-14 years or adult respondents. Among children < 5 years, 44·3% experienced stunting, 41·1% underweight, 12.4% wasting, and 26.5% were anaemic. There was self- or carer-reported poor mental health among 16.6% of children aged 5-14 years and 13.9% of adult respondents. Rates of potential risky exposures from swimming in waterways, eating uncooked produce, and eating soil or dirt were high, as were exposures to flooding and livestock. Just over one third of households (35.3%) had access to municipal water, and contamination of well water with E. coli and nitrogen species was common. Most (79·5%) houses had an in-house toilet, but no houses were connected to a piped sewer network or safe, properly constructed septic tank. Median monthly settlement outdoor temperatures ranged from 26·2 °C to 29.3 °C, and were on average, 1·1 °C warmer inside houses than outside. Mosquito density varied over time, with Culex quinquefasciatus accounting for 94·7% of species. Framed by a planetary health lens, our model includes four thematic domains: (1) the physical/built environment; (2) the ecological environment; (3) human health; and (4) socio-economic wellbeing, and is structured at individual, household, settlement, and city/beyond spatial scales. Conclusions: Our planetary health model includes key risk factors and faecal-oral exposure pathways but extends beyond conventional microbiological faecal-oral enteropathogen exposure pathways to comprehensively account for a wider range of variables affecting health in urban informal settlements. It includes broader ecological interconnections and planetary health-related variables at the household, settlement and city levels. It proposes a composite framework of markers to assess water and sanitation challenges and flood risks in urban informal settlements for optimal design and monitoring of interventions.

Environment international · 23 citationsread the source →

Mindfulness-based stress reduction for healthy individuals: A meta-analysis.

Background: An increasing number of mindfulness-based stress reduction (MBSR) studies are being conducted with nonclinical populations, but very little is known about their effectiveness. Objective: To evaluate the efficacy, mechanisms of actions, and moderators of MBSR for nonclinical populations. Data sources: A systematic review of studies published in English journals in Medline, CINAHL or Alt HealthWatch from the first available date until September 19, 2014. Study selection: Any quantitative study that used MBSR as an intervention, that was conducted with healthy adults, and that investigated stress or anxiety. Results: A total of 29 studies (n=2668) were included. Effect-size estimates suggested that MBSR is moderately effective in pre-post analyses (n=26; Hedge's g=.55; 95% CI [.44, .66], p<.00001) and in between group analyses (n=18; Hedge's g=.53; 95% CI [.41, .64], p<.00001). The obtained results were maintained at an average of 19 weeks of follow-up. Results suggested large effects on stress, moderate effects on anxiety, depression, distress, and quality of life, and small effects on burnout. When combined, changes in mindfulness and compassion measures correlated with changes in clinical measures at post-treatment and at follow-up. However, heterogeneity was high, probably due to differences in the study design, the implemented protocol, and the assessed outcomes. Conclusions: MBSR is moderately effective in reducing stress, depression, anxiety and distress and in ameliorating the quality of life of healthy individuals; however, more research is warranted to identify the most effective elements of MBSR.

Journal of psychosomatic research · meta-analysis · 738 citationsread the source →

Oxytocin receptor DNA methylation and alterations of brain volumes in maltreated children.

Although oxytocin (OXT) plays an important role in secure attachment formation with a primary caregiver, which is impaired in many children with childhood maltreatment (CM), epigenetic regulation in response to CM is a key factor in brain development during childhood. To address this issue, we first investigated differences in salivary DNA methylation of the oxytocin receptor (OXTR) between CM and Non-CM groups of Japanese children (CM: n = 44; Non-CM: n = 41) and its impact on brain structures in subgroup analysis using brain imaging and full clinical data (CM: n = 24; Non-CM: n = 31). As a result, we observed that the CM group showed higher CpG 5,6 methylation than did the Non-CM group and confirmed negative correlations of gray matter volume (GMV) in the left orbitofrontal cortex (OFC) with CpG 5,6 methylation. In addition, the CM group showed significantly lower GMV in the left OFC than did the Non-CM group. Furthermore, as a result of examining the relationship between GMV in the left OFC and psychiatric symptoms in CM, we observed a negative association with insecure attachment style and also confirmed the mediation effect of left-OFC GMV reduction on the relationship between OXTR methylation and insecure attachment style. These results suggest that any modulation of the oxytocin signaling pathway induced by OXTR hypermethylation at CpG 5,6 leads to atypical development of the left OFC, resulting in distorted attachment formation in children with CM.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 57 citationsread the source →

The prevalence and risk factors of mental problems in medical students during COVID-19 pandemic: A systematic review and meta-analysis.

Background: This meta-analysis and systematic review aimed to evaluate the global prevalence and risk factors of mental problems (i.e., depression, anxiety, stress, sleep disorder, posttraumatic stress disorder (PTSD), burnout, psychological distress, and suicidal ideation) among medical students during the COVID-19 pandemic. Method: We searched PubMed, Embase, Web of Science, psycARTICLES, PsycINFO, CNKI, and Wan Fang for studies on the prevalence of mental problems among medical students from January 1, 2020, to April 1, 2022. The pooled prevalence was calculated by random-effect models. We performed a narrative review to identify the risk factors. Results: The meta-analysis included 201 studies (N = 198,000). The prevalence of depression (41 %, 95 % CI, 37-45 %,), anxiety (38 %,95 % CI, 34 %-42 %), stress (34 %, 95 % CI, 27 %-42 %), sleep disorder (52 %, 95 % CI, 44 %-60 %), psychological distress (58 %, 95 % CI, 51 %-65 %), PTSD (34 %, 95 % CI, 22 %-46 %), suicidal ideation (15 %, 95 % CI, 11 %-18 %) and burnout (38 %, 95 % CI, 25 %-50 %) was high. The major risk factors were being female, being junior or preclinical students, exposure to COVID-19, academic stress, psychiatric or physical disorders history, economic trouble, fear of education impairment, online learning trouble, fear of infection, loneliness, low physical activity, low social support, problematic internet or smartphone use, and young age. Limitations: Most studies were cross-sectional. Few studies provided a reasonable response rate, suggesting potential selection bias. Conclusions: The study demonstrated a high prevalence and risk factors for mental problems during COVID-19, calling for mental health services. Our findings are valuable for college and health authorities to identify high-risk students and provide targeted intervention.

Journal of affective disorders · meta-analysis · 154 citationsread the source →

The relevance of cognitive emotion regulation to psychotic symptoms - A systematic review and meta-analysis.

Numerous studies emphasise the pivotal role of negative affect in the formation and maintenance of positive symptoms, which moves emotion regulation (ER) as a contributing factor into focus. We systematically reviewed and meta-analysed case-control studies reporting cross-sectional, correlative and experimental data of ER strategies in patients with psychotic disorders. In total, 42 studies were eligible, providing data for 2498 subjects and 3381 healthy controls. Questionnaire-based cross-sectional data (k=39) indicated strongest effects for rumination (g=-0,67 [-0,85 to -0,48]), self-blaming (g=-0,56; [-0,76 to -0,37]) and distraction (g=0,55 [0,11 to 0,98]). Suppression was more frequently (g=-0,36 [-0,56 to -0,16]) and cognitive reappraisal less frequently used (g=0,41 [0,28 to 0,55]), but heterogeneity was high. Correlative data (k=6) supported the assumption of an association between maladaptive strategies and positive symptoms (r=0,34 [0,22 to 0,44]). Less evidence of group differences was found in the experimental studies (k=3). The findings support the notion that ER is markedly impaired in patients with psychotic disorders. However, future research will need to further clarify the extent to which difficulties continue to exist after controlling for context and emotion intensity. The large effects for rumination and self-blaming point to promising treatment targets but also raise questions concerning the specifity of findings.

Clinical psychology review · meta-analysis · 81 citationsread the source →

Interactive telemedicine: effects on professional practice and health care outcomes.

Background: Telemedicine (TM) is the use of telecommunication systems to deliver health care at a distance. It has the potential to improve patient health outcomes, access to health care and reduce healthcare costs. As TM applications continue to evolve it is important to understand the impact TM might have on patients, healthcare professionals and the organisation of care. Objectives: To assess the effectiveness, acceptability and costs of interactive TM as an alternative to, or in addition to, usual care (i.e. face-to-face care, or telephone consultation). Search methods: We searched the Effective Practice and Organisation of Care (EPOC) Group's specialised register, CENTRAL, MEDLINE, EMBASE, five other databases and two trials registers to June 2013, together with reference checking, citation searching, handsearching and contact with study authors to identify additional studies. Selection criteria: We considered randomised controlled trials of interactive TM that involved direct patient-provider interaction and was delivered in addition to, or substituting for, usual care compared with usual care alone, to participants with any clinical condition. We excluded telephone only interventions and wholly automatic self-management TM interventions. Data collection and analysis: For each condition, we pooled outcome data that were sufficiently homogenous using fixed effect meta-analysis. We reported risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) for continuous outcomes. Main results: We included 93 eligible trials (N = 22,047 participants), which evaluated the effectiveness of interactive TM delivered in addition to (32% of studies), as an alternative to (57% of studies), or partly substituted for usual care (11%) as compared to usual care alone. The included studies recruited patients with the following clinical conditions: cardiovascular disease (36), diabetes (21), respiratory conditions (9), mental health or substance abuse conditions (7), conditions requiring a specialist consultation (6), co morbidities (3), urogenital conditions (3), neurological injuries and conditions (2), gastrointestinal conditions (2), neonatal conditions requiring specialist care (2), solid organ transplantation (1), and cancer (1).Telemedicine provided remote monitoring (55 studies), or real-time video-conferencing (38 studies), which was used either alone or in combination. The main TM function varied depending on clinical condition, but fell typically into one of the following six categories, with some overlap: i) monitoring of a chronic condition to detect early signs of deterioration and prompt treatment and advice, (41); ii) provision of treatment or rehabilitation (12), for example the delivery of cognitive behavioural therapy, or incontinence training; iii) education and advice for self-management (23), for example nurses delivering education to patients with diabetes or providing support to parents of very low birth weight infants or to patients with home parenteral nutrition; iv) specialist consultations for diagnosis and treatment decisions (8), v) real-time assessment of clinical status, for example post-operative assessment after minor operation or follow-up after solid organ transplantation (8) vi), screening, for angina (1).The type of data transmitted by the patient, the frequency of data transfer, (e.g. telephone, e-mail, SMS) and frequency of interactions between patient and healthcare provider varied across studies, as did the type of healthcare provider/s and healthcare system involved in delivering the intervention. We found no difference between groups for all-cause mortality for patients with heart failure (16 studies; N = 5239; RR:0.89, 95% CI 0.76 to 1.03, P = 0.12; I(2) = 44%) (moderate to high certainty of evidence) at a median of six months follow-up. Admissions to hospital (11 studies; N = 4529) ranged from a decrease of 64% to an increase of 60% at median eight months follow-up (moderate certainty of evidence). We found some evidence of improved quality of life (five studies; N = 482; MD:-4.39, 95% CI -7.94 to -0.83; P < 0.02; I(2) = 0%) (moderate certainty of evidence) for those allocated to TM as compared with usual care at a median three months follow-up. In studies recruiting participants with diabetes (16 studies; N = 2768) we found lower glycated haemoglobin (HbA1c %) levels in those allocated to TM than in controls (MD -0.31, 95% CI -0.37 to -0.24; P < 0.00001; I(2)= 42%, P = 0.04) (high certainty of evidence) at a median of nine months follow-up. We found some evidence for a decrease in LDL (four studies, N = 1692; MD -12.45, 95% CI -14.23 to -10.68; P < 0.00001; I(2 =) 0%) (moderate certainty of evidence), and blood pressure (four studies, N = 1770: MD: SBP:-4.33, 95% CI -5.30 to -3.35, P < 0.00001; I(2) = 17%; DBP: -2.75 95% CI -3.28 to -2.22, P < 0.00001; I(2) = 45% (moderate certainty evidence), in TM as compared with usual care. Seven studies that recruited participants with different mental health and substance abuse problems, reported no differences in the effect of therapy delivered over video-conferencing, as compared to face-to-face delivery. Findings from the other studies were inconsistent; there was some evidence that monitoring via TM improved blood pressure control in participants with hypertension, and a few studies reported improved symptom scores for those with a respiratory condition. Studies recruiting participants requiring mental health services and those requiring specialist consultation for a dermatological condition reported no differences between groups. Authors' conclusions: The findings in our review indicate that the use of TM in the management of heart failure appears to lead to similar health outcomes as face-to-face or telephone delivery of care; there is evidence that TM can improve the control of blood glucose in those with diabetes. The cost to a health service, and acceptability by patients and healthcare professionals, is not clear due to limited data reported for these outcomes. The effectiveness of TM may depend on a number of different factors, including those related to the study population e.g. the severity of the condition and the disease trajectory of the participants, the function of the intervention e.g., if it is used for monitoring a chronic condition, or to provide access to diagnostic services, as well as the healthcare provider and healthcare system involved in delivering the intervention.

The Cochrane database of systematic reviews · meta-analysis · 456 citationsread the source →

How common is sleep-disordered breathing in patients with idiopathic pulmonary fibrosis?

Background and aim: The frequency of obstructive sleep apnea-hypopnea syndrome (OSAHS) in patients with idiopathic pulmonary fibrosis (IPF) remains controversial. The aim of this study was to assess the frequency of OSAHS in newly diagnosed IPF patients and to identify possible correlations with body mass index and pulmonary function testing parameters. Materials and methods: Thirty-four newly diagnosed IPF patients were included. All subjects underwent attended overnight PSG. None of the included subjects was under any of the currently available IPF treatments or nocturnal supplemental oxygen therapy. Results: Total apnea-hypopnea index (AHI) was <5, 5-15, and ≥ 15/h of sleep in 14 (41%), 15 (44%), and five patients (15%), respectively. REM AHI was statistically significant correlated with TLC [Total lung capacity] (p=0.03, r= -0.38). Diffusing capacity of the lung for carbon monoxide was correlated with mean oxygen saturation during sleep (p=0.02, r=0.39). Conclusions: Sleep-disordered breathing seems frequent, although remains usually under diagnosed in IPF patients. A decrease in TLC, reflecting the severity of pulmonary restriction, might predispose IPF patients in SDB, especially during the vulnerable REM sleep period.

Sleep & breathing = Schlaf & Atmung · 100 citationsread the source →

Long-term family outcomes in grade 2 IDH-mutated glioma patients treated with awake-guided surgery: Biological, professional, and therapeutic interactions.

Background: Maintaining quality of life is a priority of the oncological management in IDH-mutated low-grade gliomas (IDHm-LGGs). Yet, family outcomes have received limited attention. This study aims to provide an overview of long-term family outcomes in IDHm-LGG patients. Methods: We retrospectively studied a consecutive cohort of IDHm-LGGs treated with awake functional-based resection (AwFR). The main outcomes were union/marriage, separation/divorce, and parenthood before/after surgery. We tested interactions with overall survival (OS), histomolecular data, therapeutics, occupations, and tumor locations. Results: A total of 538 patients were included (median age: 36 years [IQR: 30-44], 1p19q-codeletion: 237 [44.1%], median follow-up: 7.7 years [95% CI: 7.1-8.3]). Unions/marriages were observed in 374 (69.5%) patients preoperatively and were maintained in 329(61.2%) patients. Separations/divorces were observed in 41 (7.8%) patients. A total of 44 (8.2%) patients had new child/children, and 48 (9.1%) had new unions/marriages. Family status was stable in 399 (74.2%) patients. Prolonged single status was predicted by age (OR: 0.94, 95% CI: 0.91-0.98), female gender (OR: 0.48, 95% CI: 0.25-0.91), and previous child/children (OR: 0.23, 95% CI: 0.11-0.45). Total resection predicted new union/marriage and/or new child/children (OR: 2.59, 95% CI: 1.04-7.10). Occupational skill level (OR: 0.27, 95% CI: 0.05-0.95) predicted stable union/marriage, while previous parenthood predicted separation/divorce (OR: 2.73, 95% CI: 1.07-7.83). Lesion-symptom mapping revealed that right pars orbitalis/triangularis infiltrations (Liebermeister measures, p corrected < 0.05, 10 000 permutations) were associated with separation/divorce. Family status did not impact OS, as assessed by multivariable proportional hazard and propensity matching-based survival analyses. Conclusions: This study offers a unique overview of the long-term family outcomes in IDHm-LGG patients. Critical interactions between familial, socio-professional, and oncological factors were highlighted. Despite the onset of the disease and the surgical approach, most patients had a stable family status.

Neuro-oncology advances · 1 citationsread the source →

Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials.

Background: The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes. Methods: We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy. Findings: Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction. Interpretation: Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials. Funding: Foundation for National Institutes of Health.

The lancet. Diabetes & endocrinology · systematic review · 165 citationsread the source →

Telephone-Based Cognitive Behavioral Therapy for Insomnia in Perimenopausal and Postmenopausal Women With Vasomotor Symptoms: A MsFLASH Randomized Clinical Trial.

Importance: Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women's specialty care settings. Objective: To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). Design, setting, and participants: A single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, ≥12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted. Interventions: Six CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women's health. Main outcomes and measures: Primary outcome was scores on the ISI (score range, 0-28; scores ≥15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference. Results: At 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, -6.1 to -3.3; P < .001). Pittsburgh Sleep Quality Index scores decreased 4.0 points in women receiving CBT-I and 1.4 points in women receiving MEC, a mean between-group difference of 2.7 points (95% CI, -3.9 to -1.5; P < .001). Significant group differences were sustained at 24 weeks. At 8 and 24 weeks, 33 of 47 women (70%) and 37 of 44 (84%) in the CBT-I group, respectively, had ISI scores in the no-insomnia range compared with 10 of 41 (24%) and 16 of 37 (43%) in the MEC group, respectively. The CBT-I group also had greater improvements in diary-reported sleep latency, wake time, and sleep efficiency. There were no between-group differences in frequency of daily hot flashes, but hot flash interference was significantly decreased at 8 weeks for the CBT-I group (-15.7; 95% CI, -20.4 to -11.0) compared with the MEC group (-7.1; 95% CI, -14.6 to 0.4) (P = .03), differences that were maintained at 24 weeks for the CBT-I group (-22.8; 95% CI, -28.6 to -16.9) and MEC group (-11.6; 95% CI, -19.4 to -3.8) (P = .003). Conclusions and relevance: Telephone-based CBT-I improved sleep in perimenopausal and postmenopausal women with insomnia and hot flashes. Results support further development and testing of centralized CBT-I programs for treating menopausal insomnia. Trial registration: clinicaltrials.gov Identifier: NCT01936441.

JAMA internal medicine · randomised controlled trial · 114 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →

Efficacy and cost-effectiveness of therapist-guided internet cognitive behavioural therapy for paediatric anxiety disorders: a single-centre, single-blind, randomised controlled trial.

Background: Paediatric anxiety disorders are associated with substantial disability and long-term adverse consequences, but only a small proportion of affected children have access to evidence-based treatment. Internet-delivered cognitive behavioural therapy (ICBT) could help increase accessibility but needs further rigorous assessment. We aimed to assess the efficacy and cost-effectiveness of ICBT in the treatment of paediatric anxiety disorders. Methods: We did a single-blind randomised controlled trial in a clinical research unit within the Child and Adolescent Mental Health Services in Stockholm (Sweden). Eligible participants were children aged 8-12 years with a diagnosis of a principal anxiety disorder (seperation anxiety disorder, generalised anxiety disorder, specific phobia, social anxiety disorder, or panic disorder) of at least moderate severity. We randomly allocated participants (1:1) to ICBT or internet-delivered child-directed play, an active comparator aimed to improve parent-child relationships and increase a child's self-esteem without directly targeting anxiety. Block sizes for the randomisation varied between four and six and were generated using a computer random-number generator, and the allocation was concealed from the researchers by opaque sealed envelopes. Both treatment programmes comprised 12 modules presented over 12 weeks with weekly asynchronous online therapist support, and consisted of texts, films, illustrations, and exercises. The primary outcome was severity rating of the principal anxiety disorder 12-weeks post-treatment, via the Anxiety Disorder Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders-IV (a rating of at least 4 corresponds to meeting the criteria for the principal diagnosis), assessed by clinicians masked to treatment allocation. All participants were included in the primary analysis (intention-to-treat). This trial is registered at ClinicalTrials.gov, number NCT02350257. Findings: Between March 11, 2015, and Oct 21, 2016, 131 participants were recruited and allocated to either ICBT (n=66) or internet-delivered child-directed play (n=65). The clinician-assessed severity rating of the principal anxiety disorder improved significantly after the 12-weeks treatment period for participants in both ICBT (within-group effect size 1·22, 95% CI 0·78-1·65) and the active control (0·72, 0·44-1·00) groups. However, greater improvement was seen with ICBT than with the active control (estimated mean difference 0·79, 95% CI 0·42-1·16, p=0·002; between-group effect size 0·77, 95% CI 0·40-1·15). 29 (48%) participants in the ICBT group no longer had their principal diagnosis, compared to nine (15%) in the active control group (odds ratio 5·41, 95% CI 2·26 to 12·90, p<0·0001); the number needed to treat for ICBT to gain one additional participant in remission was three (95% CI 2·85 to 3·15). ICBT resulted in an average societal-cost saving of €493·05 (95% CI 477·17 to 508·92) per participant. No severe adverse events were reported. Interpretation: ICBT is an efficacious and cost-effective treatment for paediatric anxiety disorders that should be considered for implementation in routine clinical care. Funding: The Swedish Research Council for Health, Working Life and Welfare, and Stockholm County Council.

The Lancet. Child & adolescent health · randomised controlled trial · 51 citationsread the source →

Effectiveness of Integrated Palliative and Oncology Care for Patients With Acute Myeloid Leukemia: A Randomized Clinical Trial.

Importance: Patients with acute myeloid leukemia (AML) receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). However, the role of specialty palliative care for improving the QOL and care for this population is currently unknown. Objective: To assess the effect of integrated palliative and oncology care (IPC) on patient-reported and EOL outcomes in patients with AML. Design, setting, and participants: We conducted a multisite randomized clinical trial of IPC (n = 86) vs usual care (UC) (n = 74) for patients with AML undergoing intensive chemotherapy. Data were collected from January 2017 through July 2019 at 4 tertiary care academic hospitals in the United States. Interventions: Patients assigned to IPC were seen by palliative care clinicians at least twice per week during their initial and subsequent hospitalizations. Main outcomes and measures: Patients completed the 44-item Functional Assessment of Cancer Therapy-Leukemia scale (score range, 0-176) to assess QOL; the 14-item Hospital Anxiety and Depression Scale (HADS), with subscales assessing symptoms of anxiety and depression (score range, 0-21); and the PTSD Checklist-Civilian version to assess posttraumatic stress disorder (PTSD) symptoms (score range, 17-85) at baseline and weeks 2, 4, 12, and 24. The primary end point was QOL at week 2. We used analysis of covariance adjusting and mixed linear effect models to evaluate patient-reported outcomes. We used Fisher exact test to compare patient-reported discussion of EOL care preferences and receipt of chemotherapy in the last 30 days of life. Results: Of 235 eligible patients, 160 (68.1%) were enrolled; of the 160 participants, the median (range) age was 64.4 (19.7-80.1) years, and 64 (40.0%) were women. Compared with those receiving UC, IPC participants reported better QOL (adjusted mean score, 107.59 vs 116.45; P = .04), and lower depression (adjusted mean score, 7.20 vs 5.68; P = .02), anxiety (adjusted mean score, 5.94 vs 4.53; P = .02), and PTSD symptoms (adjusted mean score, 31.69 vs 27.79; P = .01) at week 2. Intervention effects were sustained to week 24 for QOL (β, 2.35; 95% CI, 0.02-4.68; P = .048), depression (β, -0.42; 95% CI, -0.82 to -0.02; P = .04), anxiety (β, -0.38; 95% CI, -0.75 to -0.01; P = .04), and PTSD symptoms (β, -1.43; 95% CI, -2.34 to -0.54; P = .002). Among patients who died, those receiving IPC were more likely than those receiving UC to report discussing EOL care preferences (21 of 28 [75.0%] vs 12 of 30 [40.0%]; P = .01) and less likely to receive chemotherapy near EOL (15 of 43 [34.9%] vs 27 of 41 [65.9%]; P = .01). Conclusions and relevance: In this randomized clinical trial of patients with AML, IPC led to substantial improvements in QOL, psychological distress, and EOL care. Palliative care should be considered a new standard of care for patients with AML. Trial registration: ClinicalTrials.gov Identifier: NCT02975869.

JAMA oncology · randomised controlled trial · 151 citationsread the source →

Drug therapy for obstructive sleep apnoea in adults.

Background: The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of REM sleep, an increase in cholinergic tone during sleep, a reduction in airway resistance and a reduction in surface tension in the upper airway. Objectives: To determine the efficacy of drug therapies in the treatment of sleep apnoea. Search strategy: We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2005. Selection criteria: Randomised, placebo controlled trials involving adult patients with confirmed OSA . We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration. Data collection and analysis: Two reviewers independently assessed studies for inclusion, undertook data extraction according to pre-specified entry criteria, and quality assessment of studies. No response for further information was forthcoming from study authors. Results were expressed as mean differences and 95% Confidence Intervals (CI). Main results: Twenty-six trials of 21 drugs, involving 394 participants contributed data to the review. Most of the studies were small and many trials had methodological limitations. Each of the studies states that the subjects had OSA but diagnostic criteria were not always explicit and it is possible that some patients with central apnoeas may have been recruited. Six drugs had some impact on OSA severity and two altered daytime symptoms. One study reported that apnoea hypopnea index (AHI) was lower following treatment with intranasal fluticasone compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10 participants). Topical nasal lubricant given twice overnight resulted in an AHI of 14 compared to 24 with placebo (10 participants). These three latter studies were of single night crossover design and so there are no data on the acceptability of these treatments or their effect on symptoms. Paroxetine was shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20 participants tolerated the treatment but there was no improvement in daytime symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic benefit from the drug and it was poorly tolerated in the long term. Protriptyline led to a symptomatic improvement (improved versus not improved) in two out of three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to 301.1) but there was no change in the apnoea frequency. In one trial naltrexone did reduce AHI, but total sleep time favoured placebo. No significant beneficial effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril, buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole. Authors' conclusions: There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcome. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24 and 45%. For fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer duration are required to establish whether this has an impact on daytime symptoms. Individual patients had more complete responses to particular drugs. It is likely that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.

The Cochrane database of systematic reviews · meta-analysis · 52 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Social epidemiology is defined as the study of the distribution of health outcomes and their social determinants (1). It builds on the classic epidemiologic triangle of host, agent, and environment to focus explicitly on the role of social determinants in infectious disease transmission and progression. These determinants are the “features of and pathways by which societal conditions affect health” (2, p. 697). Early studies of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) focused on individual characteristics and behaviors in determining HIV risk, an approach that Fee and Krieger (3) refer to as “biomedical individualism.” Biomedical individualism is the basis of risk factor epidemiology; by contrast, the social epidemiology perspective emphasizes social conditions as fundamental causes of disease (4) (table 1). Social epidemiologists examine how persons become exposed to risk or protective factors and under what social conditions individual risk factors are related to disease. Social factors are thus the focus of analysis and are not simply adjusted for as potentially confounding factors or used as proxies for unavailable individual-level data. Social factors are indeed critical to understanding nonuniform infectious disease patterns that emerge as a result of the dependent nature of disease transmission or the idea that an outcome in one person is dependent upon outcomes and exposures in others (5, 6). Contact patterns that enhance HIV/AIDS vulnerability may be conceptualized at multiple levels. Figure 1 distinguishes determinants of HIV/AIDS at three levels: individual, social, and structural. Individual factors include biologic, demographic, and behavioral risk factors that may influence the risk of HIV acquisition and disease progression. Social-level factors include critical pathways by which community and network structures link persons to society. These structures are central to understanding the diffusion and differential distribution of HIV/AIDS in population subgroups. Structural-level factors include social and economic factors, as well as laws and policies. These factors, in turn, affect HIV transmission dynamics and the differential distribution of HIV/AIDS. Infectious disease epidemiology provides models of the mechanisms through which social determinants affect HIV transmission (7). For example, the basic reproductive number of an infectious disease, R0 (8), describes secondary infections that arise from a primary infection. In the equation R0 = βCD, β is the probability of infection per contact, C is the number of contacts, and D is the duration of infectivity. The goal of intervention efforts is to reduce the empirical value of these terms by modifying the social conditions under which individual risk factors lead to disease. Examples of factors that affect the component terms of R0 in HIV epidemiology are presented in table 2. In this review, we present existing evidence linking social and structural determinants to HIV/AIDS. In addition, we discuss the implications of these findings for future social epidemiology research on HIV/AIDS as well as the design of more effective HIV/AIDS interventions. We searched the published literature to identify conceptual and empirical research reports on the social epidemiology of HIV/AIDS. Five databases were searched: PsycINFO (American Psychological Association, Washington, DC), PubMed (MEDLINE; National Institutes of Health, Bethesda, Maryland), Social Science Citation Index (Web of Science; Thomson ISI, Stamford, Connecticut), Sociological Abstracts (CSA, Bethesda, Maryland), and Digital Dissertations (ProQuest; UMI, Ann Arbor, Michigan). Searches were designed to include the factors we specified in our framework as social or structural factors (figure 1). Searches were limited to published articles in the English language for the period 1981–2003. The following keywords were included in each search: AIDS/acquired immunodeficiency syndrome, HIV, and epidemiol*. Additional searches were conducted by using combinations of keywords listed in Appendix table 1 corresponding with our framework. We identified four categories of social-level factors of importance to HIV/AIDS epidemiology: cultural context, social networks, neighborhood effects, and social capital. Each uses different conceptual and methodological approaches to examine the effects of social forces on population HIV/AIDS vulnerability. Anthropologist Edward Tylor defined culture as “that complex whole which includes knowledge, belief, art, law, morals, custom, and any other capabilities and habits acquired by man as a member of society” (9, p. 1). Anthropologic and epidemiologic approaches may be integrated in a variety of ways to identify features of the social environment that affect HIV/AIDS risk. One way to explore how the social environment affects HIV/AIDS epidemiology is through the use of mixed research methods. Mixed-methods study designs integrate qualitative and quantitative research methods either sequentially or concurrently (10). In sequential study designs, qualitative methods may be used to explore a topic under study or to explain quantitative epidemiologic findings. Concurrent study designs are meant to confirm, cross-validate, or corroborate findings within a single study. A common type of concurrent mixed methods study is “triangulation,” and this approach has been used extensively in rapid assessments of illicit drug use and HIV/AIDS (11–13). Mixed methods approaches are particularly well suited to the investigation of the often hidden and stigmatizing behavioral and social factors underlying HIV epidemics. One exemplary study combining qualitative methods with quantitative methods was conducted by Beyrer et al. (14) to examine the role of overland heroin trafficking routes in shaping explosive HIV/AIDS epidemics among injection drug users in Southeast Asia. Piecing together data from a variety of sources, including existing epidemiologic data, key informant interviews, and laboratory data, this study revealed that distinct HIV subtypes emerged and recombined along drug trafficking routes originating in Myanmar, one of the world’s largest heroin producers. Along these trafficking routes, communities of injection drug users formed, facilitating the spread of HIV into local communities in Laos, Thailand, Vietnam, India, and China (refer, for example, to Panda et al. (15)). This illustration highlights the broader understanding of HIV/AIDS epidemiology that can be achieved by examining the interplay between contextual factors and social and behavioral factors. Investigation of social networks in HIV/AIDS began with the mapping of relationships between one of the first identified AIDS cases, an airline steward, and a large number of his male sex partners in the early 1980s (16). Social network analysis generates measures of the quality, density, position, and structure of relationships between persons, including dyads (partnerships), personal networks (“egocentric” networks), and larger communities (“sociometric” networks) (17, 18). Social networks can influence health outcomes in direct and indirect ways, including 1) social influence, 2) social engagement and participation, 3) prevalence of infectious disease and network member mixing, 4) access to material goods and informational resources, and 5) social support (19). Researchers have demonstrated that patterns in the structure of relationships—rather than differences in individual risk behaviors alone—explain observed HIV patterns (20, 21). The theoretical foundation for examining social networks in HIV research is closely tied to advances in sexually transmitted disease (STD) epidemiology. A key concept from STD epidemiology is the notion of the “core group,” a small group of disease transmitters responsible for a large proportion of cases (22). Friedman et al. (23) found that individuals’ locations within sociometric risk networks were associated with HIV risk among a group of injection drug users in New York City. Other concepts from STD epidemiology, such as partner concurrency, bridging, and mixing patterns, are also important in understanding HIV risk (24–29). Specific network characteristics that have been associated with HIV/AIDS include the size of subgroups and their distribution in a network (23), the centrality of HIV-positive persons within networks (30), partner selection patterns (24, 31–33), and concurrent sexual partnerships (28). Inclusion of these variables has been shown to improve transmission estimates in mathematical modeling (34, 35). Social and normative influences have also been associated with individual HIV risks (36, 37). Network-related social and normative influences are predictive of illicit drug use (38) and condom use behavior (37, 39), highlighting the importance of network-based interventions for HIV prevention (18). Kelly et al. (40, 41) developed a popular opinion leader model that has been effective in reducing HIV risk in several populations, including men who have sex with men and women in low-income housing (42). The success of this model has led to its adaption for international use by the National Institute of Mental Health Collaborative HIV/STD Prevention Trial in China, India, Peru, Russia, and Zimbabwe. Neighborhoods represent the intersection of social networks and physical spatial locations, a confluence Wallace (43) has called the “sociogeographic networks” through which infectious diseases spread. Early interest in the role of neighborhood social environment in disease transmission was sparked by a study in Colorado Springs, Colorado, in which researchers found that gonorrhea was highly focused geographically in core residential neighborhoods (44). Both direct and indirect mechanisms may determine how neighborhood-level factors shape population HIV/AIDS patterns. Direct mechanisms are those that increase the likelihood of a person coming into contact with someone who is HIV positive, for example, through residential segregation and the social isolation of marginalized populations. Indirect mechanisms include those that increase population vulnerability to HIV/AIDS, such as exposure to poor socioeconomic conditions, high unemployment, or the proliferation of illicit drug markets. A range of neighborhood-level factors have been examined in relation to infectious disease, including poverty and income (45, 46), residential segregation (47), and neighborhood physical environment (48, 49). Current research in neighborhood and area effects on health emphasizes the importance of moving beyond documentation of associations to analyze the social and epidemiologic mechanisms through which neighborhood effects might operate (50–54). Increasing concentrations of affluence and poverty are contributing to what demographer Douglas Massey has called “a radical change in the geographic basis of human society” (55, p. 395). Powerful social and economic forces in US cities are increasing neighborhood segregation by class and race/ethnicity (56, 57). Resulting social disorganization and loss of resources and services in poor neighborhoods are in turn shaping HIV/AIDS patterns at the neighborhood level. In a number of studies in New York City, for example, Wallace (58–63) has examined the complex interplay of public policies such as “planned shrinkage” with HIV epidemic dynamics in the Bronx, documenting the “synergy of plagues” that has accompanied rapid social change and the destruction of essential protective networks in poor communities. Using AIDS surveillance data, ecologic studies conducted in various US cities have also consistently found significant associations between income and poverty measures and neighborhood-level AIDS incidence and prevalence rates, and these findings have been consistent across census block groups (46), census tracts (64), and zip codes (65, 66). Length of survival an AIDS has also been with neighborhood measures of income and the of highly a of health at the population may also a role in shaping HIV/AIDS patterns, associations between HIV/AIDS and income at the neighborhood have not been well segregation by race/ethnicity is neighborhood-level that may an important role in HIV/AIDS may affect infectious disease patterns through the and isolation of persons in one increasing the probability of transmission within that For example, found that measures of residential isolation were protective for at risk of disease. 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on the basis of drug and in this study into the drug of income of and in behaviors in an to HIV to studies of the associations between social policies and HIV/AIDS are to the human of policies of with the of those to HIV/AIDS and to identify drug also has a significant on HIV/AIDS. drug particularly of is HIV epidemics in the The on has focused on to the of which of prevention and measures policies for those trafficking or illicit have in of persons for drug The direct of patterns to be For example, et al. found that on policies such as the of and of those with use from Social were associated with in is a risk factor for HIV risk behaviors have been shown to associated with of and HIV risk of in have access to can increase HIV/AIDS risk and by social and risk networks, or and increasing poverty and social in in risk behaviors in of have been For example, et al. found that the in was associated with among injection drug users in of the of heroin trafficking from In the of the of has 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Epidemiologic Reviews · meta-analysis · 394 citationsread the source →

Do treatment outcomes differ after 3 months DBT inpatient treatment based on borderline personality disorder subtypes?

Heterogeneity in borderline personality disorder (BPD) drives the search for BPD subtypes to optimize the assessment and treatment of these patients. Therefore, the aims of the present study were (1) to replicate previously identified BPD subtypes based on reactive and regulative temperament; (2) to compare them on symptomatology and coping; and (3) to investigate whether these subtypes show different treatment responses after 3 months of inpatient dialectical behaviour therapy (DBT). A total of 145 BPD inpatients were assessed by means of measures of temperament, symptomatology and coping. Through model-based clustering on the Behavioural Inhibition and Behavioural Activation Scales (BISBAS) and Effortful Control Scale (ECS), we identified three BPD subtypes: an Emotional/Disinhibited subtype (15%, high BAS and low ECS); a Low Anxiety subtype (41%, low BIS) and an Inhibited subtype (44%, low BAS). After 3 months of DBT, 75 patients completed the measures for a second time. Repeated measure ANOVAs demonstrated a general improvement on all symptoms and coping strategies. In addition, the BPD subtypes showed trajectory differences in clinical and borderline specific symptomatology and dissociation. These findings indicate that BPD subtypes based on temperament demonstrate different treatment responses, which can contribute to the search of more BPD subtype tailored treatment interventions. © 2018 John Wiley & Sons, Ltd.

Personality and mental health · 6 citationsread the source →

Childhood eating disorders: British national surveillance study.

Background: The incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse. Aims: To identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes. Method: Surveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose. Results: Overall incidence was 3.01/100,000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year. Conclusions: Childhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence.

The British journal of psychiatry : the journal of mental science · 174 citationsread the source →

Intensive smoking cessation intervention reduces mortality in high-risk smokers with cardiovascular disease.

Purposes: To compare an intensive smoking cessation intervention against usual care in hospitalized high-risk smokers with acute cardiovascular disease. Methods: A total of 209 hospitalized smokers were randomized to the intensive intervention (n = 109) or to usual care (n = 100). Usual care consisted only of counseling and printed educational material provided prior to hospital discharge. Intensive treatment consisted of a minimum of 12 weeks of behavior modification counseling and individualized pharmacotherapy provided at no cost to the participant. Smoking status in all subjects was confirmed biochemically (ie, by measuring expired carbon monoxide) at 3, 6, 12, and 24 months after randomization. Outcomes included point prevalence and continuous abstinence smoking cessation rates, hospitalizations, and all-cause mortality. Results: At each follow-up interval, point prevalence and continuous abstinence smoking cessation rates were significantly greater in the intensive-treatment group compared to the usual-care group. At 24 months, continuous abstinence smoking cessation rates were 33% in the intensive-treatment group and 9% in the usual-care group (p < 0.0001). Over the 2-year follow-up period, 41 patients in the usual-care group were hospitalized compared to 25 patients in the intensive-treatment group (relative risk reduction [RRR], 44%; 95% confidence interval [CI], 16 to 63%; p = 0.007). The all-cause mortality rate was 2.8% in the intensive-treatment group and 12.0% in the usual-care group (RRR, 77%; 95% CI, 27 to 93%; p = 0.014). The absolute risk reduction in mortality was 9.2% with a number needed to treat of 11. Conclusion: Hospitalized smokers, especially those with cardiovascular disease, should undergo treatment with a structured intensive cessation intervention. The duration of the initial treatment should be 3 months.

Chest · randomised controlled trial · 157 citationsread the source →

From internal timing to external clock-checking: the impact of ego depletion on dual-path attention in TBPM and the precise remediation by reminders.

Ego depletion refers to a temporary state of resource exhaustion that occurs after an individual excessively utilizes their limited self-control resources. As a result, performance on subsequent cognitive tasks, including prospective memory (PM), may be impaired. The present study examined how ego depletion influences time-based prospective memory (TBPM) across two experiments. In Experiment 1, 164 participants (aged 18-25, M = 21.09, SD = 1.24) were assigned to a low-difficulty control group (N = 44), a high-difficulty control group (N = 41), a low-difficulty depletion group (N = 37), or a high-difficulty depletion group (N = 42). Results showed that ego depletion impaired TBPM performance, and this effect was not moderated by task difficulty. The impairment appeared to result primarily from reduced effectiveness of both internal and external attention. Experiment 2 investigated whether reminders could ameliorate TBPM deficits following depletion. Seventy-six participants (aged 18-25, M = 22.50, SD = 1.09) were assigned to a control group (N = 24), a recent reminder group (N = 26), or a distant reminder group (N = 26). Results indicated that recent reminders significantly improved TBPM performance, suggesting that explicit cues can markedly enhance prospective memory under ego-depletion conditions. This finding provides a low-cost and highly efficient cognitive strategy for contexts characterized by high cognitive load and low motivation (e.g., intensive work, learning, or clinical rehabilitation training). By optimizing the design of external cues, such strategies can help individuals maintain effective goal-directed task performance even when self-control resources are limited.

Psychological researchread the source →

Improving community health networks for people with severe mental illness: a case study investigation

Introduction: Policy drivers in mental health to address personal recovery, stigma and poor physical health indicate that new service solutions are required. This study aimed to understand how connections to people, places and activities were utilised by individuals with severe mental illness (SMI) to benefit health and wellbeing. Methods: A five-module mixed-methods design was undertaken in two study sites. Data were collected from 150 network-mapping interviews and 41 in-depth follow-up interviews with people with SMI; in-depth interviews with 30 organisation stakeholders and 12 organisation leaders; and 44 telephone interviews with practitioners. We undertook a three-stage synthesis process including independent lived experience feedback, and a patient and public involvement team participated in tool design, data collection, analysis and write-up. Results: Three personal network types were found in our study using the community health network approach: diverse and active; family and stable; formal and sparse. Controlled for other factors we found only four variables significantly associated with which network type a participant had: living alone or not; housing status; formal education; long-term sickness or disability. Diagnosis was not a factor. These variables are challenging to address but they do point to potential for network change. The qualitative interviews with people with SMI provided further understanding of connection-building and resource utilisation. We explored individual agency across each network type, and identified recognition of the importance and value of social support and active connection management alongside the risks of isolation, even for those most affected by mental illness. We identified tensions in personal networks, be that relationships with practitioners or families, dealing with the impact of stigma, or frustrations of not being in employment, which all impact on network resources and well-being. The value of connectedness within personal networks of people, place and activity for supporting recovery was evident in shaping identity, providing meaning to life and sense of belonging, gaining access to new resources, structuring routines and helping individuals ‘move on’ in their recovery journey. Health-care practitioners recognised that social factors were important in recovery but reported system-level barriers (workload, administrative bureaucracy, limited contact time with clients) in addressing these issues fully. Even practitioners working in third-sector services whose remit involved increasing clients’ social connection faced restrictions due to being evaluated by outcome criteria that limited holistic recovery-focused practices. Service providers were keen to promote recovery-focused approaches. We found contrasts between recovery ideology within mental health policy and recovery practice on the ground. In particular, the social aspects of supporting people with SMI are often underprioritised in the health-care system. In a demanding and changing context, strategic multiagency working was seen as crucial but we found few examples of embedded multisector organisation partnerships. Conclusion: While our exploratory study has limitations, findings suggest potential for people with SMI to be supported to become more active managers of their personal networks to support well-being regardless of current network type. The health and social care system does not currently deliver multiagency integrated solutions to support SMI and social recovery. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

review · 3 citationsread the source →

Methods of usability testing in the development of eHealth applications: A scoping review.

Background: The number of eHealth applications has exponentially increased in recent years, with over 325,000 health apps now available on all major app stores. This is in addition to other eHealth applications available on other platforms such as PC software, web sites and even gaming consoles. As with other digital applications, usability is one of the key factors in the successful implementation of eHealth apps. Reviews of the literature on empirical methods of usability testing in eHealth were last published in 2015. In the context of an exponentially increasing rate of App development year on year, an updated review is warranted. Objective: To identify, explore, and summarize the current methods used in the usability testing of eHealth applications. Methods: A scoping review was conducted on literature available from April 2014 up to October 2017. Four databases were searched. Literature was considered for inclusion if it was (1) focused on an eHealth application (which includes websites, PC software, smartphone and tablet applications), (2) provided information about usability of the application, (3) provided empirical results of the usability testing, (4) a full or short paper (not an abstract) published in English after March 2014. We then extracted data pertaining to the usability evaluation processes described in the selected studies. Results: 133 articles met the inclusion criteria. The methods used for usability testing, in decreasing order of frequency were: questionnaires (n = 105), task completion (n = 57), 'Think-Aloud' (n = 45), interviews (n = 37), heuristic testing (n = 18) and focus groups (n = 13). Majority of the studies used one (n = 45) or two (n = 46) methods of testing. The rest used a combination of three (n = 30) or four (n = 12) methods of testing usability. None of the studies used automated mechanisms to test usability. The System Usability Scale (SUS) was the most frequently used questionnaire (n = 44). The ten most frequent health conditions or diseases where eHealth apps were being evaluated for usability were the following: mental health (n = 12), cancer (n = 10), nutrition (n = 10), child health (n = 9), diabetes (n = 9), telemedicine (n = 8), cardiovascular disease (n = 6), HIV (n = 4), health information systems (n = 4) and smoking (n = 4). Further iterations of the app were reported in a minority of the studies (n = 41). The use of the 'Think-Aloud' (Pearson Chi-squared test: χ2 = 11.15, p < 0.05) and heuristic walkthrough (Pearson Chi-squared test: χ2 = 4.48, p < 0.05) were significantly associated with at least one further iteration of the app being developed. Conclusion: Although there has been an exponential increase in the number of eHealth apps, the number of studies that have been published that report the results of usability testing on these apps has not increased at an equivalent rate. The number of digital health applications that publish their usability evaluation results remains only a small fraction. Questionnaires are the most prevalent method of evaluating usability in eHealth applications, which provide an overall measure of usability but do not pinpoint the problems that need to be addressed. Qualitative methods may be more useful in this regard. The use of multiple evaluation methods has increased. Automated methods such as eye tracking have not gained traction in evaluating health apps. Further research is needed into which methods are best suited for the different types of eHealth applications, according to their target users and the health conditions being addressed.

International journal of medical informatics · review · 297 citationsread the source →

Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. 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American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

Clinical Presentation of Left Atrial Cardiac Myxoma

Introduction Cardiac myxoma is the most frequent “benign” tumor of the heart and presents an important diagnostic challenge (4,43,47). Myxomas may resemble many cardiovascular or systemic diseases, and can arise in any of the cardiac chambers, although 75% occur in the left atrium. Most cases of atrial myxomas are now diagnosed in living patients, allowing successful surgical extirpation (1,3,30,44,53). Before the introduction of angiocardiography in 1951, cardiac myxoma diagnosis was made only at autopsy (22). The first successful surgical removal of an atrial myxoma was performed in 1954 (35,47). In 1959, the first M-mode echocardiogram of a left atrial myxoma was reported (16). Indeed, the introduction of echocardiography has provided an important noninvasive means of diagnosis for cardiac myxomas (55). Thus, the diagnosis of small myxomas (less than 5 cm in size and asymptomatic) is becoming easier. We report here the experience of a French cardiovascular center in the clinical presentation of left atrial myxomas. The large number of patients in this series allowed us to perform an analytic, clinicopathologic study. Patients and Methods We reviewed the 112 cases of left atrial myxoma seen at 1 institution (Hôpital Louis Pradel, Lyons, France) over a 40-year period (1959–1998). In all cases the diagnosis was established before surgical removal. The patients’ medical records were reviewed, and data concerning clinical presentation, diagnostic methods, and postoperative course were collected. Histopathologic slides were reviewed for all cases by the same pathologist (RL). Other locations where cardiac myxoma occurred during that time period were the right atrium (15 cases), left ventricle (2 cases), and right ventricle (1 case). Follow-up information was obtained by contacting either the patients or the attending physicians, and a standardized questionnaire was completed for each case. Statistical analysis A chi-square test, or the Fisher exact test when required, was performed for all qualitative variables, and odds ratios (OR) with 95% confidence intervals (95% CI) were computed. For ordinal variables a Wilcoxon rank sum test was used. Data analysis was performed using SAS (Statistical Analysis System, SAS Institute Inc., Cary, NC). The variables studied in the statistical analysis were 1) sex and age, period of diagnosis (before or after echocardiography was available), delay to diagnosis (delay between the first symptoms and diagnosis), possible systematic (serendipitous) discovery; 2) size of the tumor (> or < 5 cm), tumor surface appearance (smooth or villous); 3) the main symptoms: cardiac (cardiac failure, malaise or syncope, chest pain or palpitations), embolic (cerebral, coronary, or peripheral artery), systemic (fever, weight loss, or pseudo-connective tissue disease signs), or neurologic (stroke, vertigo, epilepsy, coma, or other signs); 4) cardiac auscultation modifications (pseudo-mitral signs, “tumor plop”, nonspecific other signs); 5) possible chest X-ray abnormalities (left cardiac failure signs, cardiomegaly, pleural effusion, left atrium enlargement, visible myxoma when calcified), electrocardiogram (ECG) alterations (arrhythmias or conduction disturbances, ST-segment and T-wave shifts, left atrial hypertrophy, and nonspecific signs), or serologic test abnormalities (elevated erythrocyte sedimentation rate [ESR], anemia). Results Patient characteristics The study group included 72 women, (64% of the whole sample; median age, 53 yr; range, 23–84 yr) and 40 men (36% of the sample; median age, 58 yr, range, 5–77 yr). Forty-six patients (41% of the sample, 31 women, 15 men) were less than 50 years old, 47 (42%, 31 women, 16 men) were between 50 and 70 years, and 19 (17%, 10 women, 9 men) were older than 70. Age distribution was homogenous in men, but most female patients were between 40 and 60 years old (Figure 1).Fig. 1: Age distribution of 112 patients with left atrial myxoma. The clinical and laboratory features of left atrial myxoma in our series are presented in Table 1. The different frequencies of clinical and laboratory signs according to sex and age are detailed in Table 2. Male patients were more at risk than females for embolic complications and for neurologic symptoms; females were more at risk than males to develop systemic symptoms such as fever; younger patients (age <50 yr) had more neurologic symptoms and cardiac auscultation abnormalities than older patients (age >50 yr).TABLE 1: Clinical and laboratory features of left atrial myxoma (112 cases)TABLE 2: Frequencies of clinical and laboratory signs by sex and age*We divided the patients into 2 groups according to the pre-and post-echocardiography periods: 1) between 1959 and 1977, when the only diagnostic methods were angiocardiography and cardiac cathe-terization, only 14 patients (12.5%) underwent surgery; 2) since 1977, with 2-dimensional echocardiography use (transthoracic, then transesophageal), about 5 patients per year have undergone surgery for left atrial myxoma (98 patients, 87.5%). The sex ratio and age ranges are similar in these 2 patient groups, but other differences can be identified (Table 3). Before 1977, most patients were diagnosed on the basis of serologic or blood test abnormalities (particularly elevated ESR) and radiologic abnormalities; chest X-ray evidence of cardiac failure or left atrium enlargement was particularly prevalent in patients diagnosed before 1977 compared with those diagnosed after 1977 (p = 0.006 and p = 0.02, respectively).TABLE 3: Symptoms by year of diagnosis*Delay before surgery In our series, the time interval between symptoms onset and diagnosis (surgical removal) varied from 0 to 126 months (median, 4 mo). The median delay before surgery was 5.5 months before 1977, and 3 months after 1977; the difference is not significant. The median delay to diagnosis increased significantly when cardiac symptoms were present; there was no significant difference for the other symptoms (Table 4).TABLE 4: Delay to diagnosis by year and by principal clinical symptoms*Initial symptoms ( Figure 2) For 11 patients, the left atrial myxoma diagnosis was a mere chance, or serendipitous, discovery (“systematic findings” in Figure 2). Among these patients, in 9 cases echocardiography (8 cases) or computed tomography (CT) (1 case) was performed for another indication and allowed a diagnosis of myxoma. For 2 patients, echocardiography had been systematically performed during follow-up for surgery on a right atrial myxoma. Fig. 2: Initial symptoms of left atrial myxoma (112 cases).The most common initial symptoms of left atrial myxoma in our series were related to mitral valve obstruction: dizziness and occasionally syncope, palpitations, dyspnea, cough, pulmonary edema, or congestive heart failure were observed in 58 patients. Eight patients showed atypical paroxysmal clinical manifestations: chest pain, hemoptysis, limb claudication, thoracic noise, shortness of breath, or syncope when reclining. Embolic manifestations suggested myxoma in 18 patients. Constitutional or general systemic signs appeared as initial manifestations for 17 patients: myalgia, muscle weakness, arthralgia, fever, weight loss, fatigue, and Raynaud syndrome. Clinical features at diagnosis All patients presented with at least 1 or more symptoms of the classic triad: 1) obstructive cardiac signs; 2) embolic signs; and 3) constitutional or systemic manifestations (See Table 1). 1) Intracardiac obstruction signs occurred in 75 patients. Pulmonary edema or progressive congestive cardiac failure (dyspnea, orthopnea) were the most common symptoms (n = 48). Malaise or syncope occurred in 16 cases. Two patients experienced cardiac arrest before surgery and fully recovered after resuscitation. Other nonspecific cardiac symptoms were present in 34 patients: cough, thoracic pain, palpi-tations, myocardial infarction due to coronary embolism. Malaise, palpitations, or thoracic pain could vary with body postural changes. 2) Signs of embolism were present in 33 patients, either with 1 (n = 25) or several (n = 8) locations. Embolic locations were the central nervous system (n = 24), in 1 case in the retinal artery, the upper and lower extremities (n = 15), and the coronary arteries (n = 4). 3) Thirty-eight patients presented with systemic or constitutional symptoms. These symptoms were obviously nonspecific, including fever (n = 22), weight loss or fatigue (n = 20), and immunologic diseases mimicking symptoms such as myalgia, muscle weakness, arthralgia, or Raynaud syndrome (n = 6). 4) Other clinical presentations 4.1) Twenty-nine patients had neurologic symptoms, particularly transient or permanent motor or sensory neurologic deficiencies (n = 23), when cerebral emboli were present (stroke). Three of these patients developed multiple cerebral aneurysms, induced by cerebral emboli. Three patients had epileptic fits, or multilocular sclerosis mimicking symptoms. Six patients also suffered from other neurologic manifestations, such as vertigo or coma. One patient with streptococcal meningitis underwent surgery for a supposed antibiotic-resistant endocarditis suggested by echocardiographic findings, but surgery uncovered an incidental noninfected myxoma. 4.2) One patient had fever and positive blood cultures for Streptococcus viridans. 4.3) Three patients were investigated for liver abnormalities connected in fact with right cardiac failure. 4.4) For 3 patients, the main symptoms were abdominal pain or hemoptysis. Physical examination (cardiac auscultation) On cardiac auscultation 72 patients (64%) had abnormal findings, 18 (16%) of them with postural changes or with time examination modifications. These murmurs looked like significant mitral stenosis findings: apical diastolic or presystolic murmur (n = 60, 53%). A tumor plop was heard in 17 patients (15%), all before 1989. Other auscultatory features were changes in preexisting murmurs, gallops, or modification of the first (split) or second heart sound (n = 12, 11%). A significant was observed between cardiac auscultation abnormalities and 1) systemic symptoms (fever, weight loss or and 2) cardiac symptoms and signs (cardiac failure, (Table no between auscultatory signs and embolic or neurologic symptoms was between clinical The most frequent laboratory was in patients Table 1). in men, in was observed in 15 patients. blood or was present in patients. The between these serologic abnormalities and systemic manifestations was significant Table there was no significant between serologic signs and or neurologic symptoms. abnormalities of the patients (n = had abnormal Table 1). atrial was the most frequent (n = or or conduction were Other were ST-segment abnormalities (n = or nonspecific abnormalities (n = hypertrophy, The of abnormalities with systemic manifestations and cardiac signs was significant Table was no significant with embolic or neurologic symptoms. were abnormal in patients Table 1). included pulmonary or congestive heart failure signs (n = and nonspecific (n = atrial enlargement (n = that made the tumor visible (n = and pleural were (n = The of radiologic abnormalities with systemic and cardiac manifestations was significant Table X-ray abnormalities were significantly less frequent in patients with embolic or neurologic methods Before 1977, all cases were diagnosed by angiocardiography with left heart (n = 1977, echocardiography was the diagnostic (n = only M-mode echocardiography was (Figure 3). 2-dimensional and particularly echocardiography the methods in many cases. For 2 patients the diagnosis was established by or 3: A myxoma is seen in the left The diagnosis of myxoma was obtained after surgical tumor for all cases. On the tumor from 1 cm to 15 The size was for was than 5 cm in and in cases had been during The weight of the from 15 to In our series of the myxomas were with a cm), and were the left atrial myxomas in our series, the and from the left atrial with only a other left and small mitral valve The myxoma surface was studied in was or in of these (n = and (Figure 4) in the other cases (n = The less common or (Figure 5) myxomas had a surface that of multiple or and with a to (Figure 4: left atrial myxoma after left atrial were on the of myxoma in an of an The myxoma had a or an and a were the The surface of the tumor was by a of was observed in of the cases. We with a myxoma from with a and or different of 1) (Figure with or by then by 2) (Figure with many or in the of the cases were left atrial of them with and with were myxomas with All were observed in patients with myxoma and atrial myxoma with with myxoma in atrial myxoma with or myxoma in significant could be between myxoma size or 5 and diagnosis or or of or serologic symptoms or signs (Table 6). a myxoma size cm was significantly with cardiac symptoms, auscultatory signs, and and chest X-ray of myxomas appeared to be more and the delay to diagnosis was for small than for large Table of clinical features to myxoma size was significantly with neurologic symptoms, embolic and cardiac auscultation there was no significant between and or X-ray signs or symptoms; discovery; or delay in diagnosis (Table of clinical features to myxoma surface course All patients had patients during the 1 patient in during a second surgical for a of myxoma years after the first surgical a on in with cardiac and on the second postoperative from a in from mitral by a mitral and a in from meningitis with the the incidental tumor had been 1 patient a mitral valve endocarditis was with the myxoma. The most frequent postoperative was transient or atrial in patients A permanent cardiac for was for only 2 patients. Follow-up the postoperative patients were to patients to and not our Among the other patients, 4 and were during the follow-up Patients presented with peripheral fully The follow-up for patients with multiple cerebral is 14 years a In the present series, were for a median of 3 years 1 yr). Six patients had a of myxoma. Three patients with myxoma in the left and 17 years Three other patients had One of them suffered 2 in the left 16 and months The other 2 patients with had an initial myxoma in the right for 1 of them the was in the left atrium 3 years and for the other the were multiple in the left atrium and years and then in the right atrium years We report here the series of patients with left atrial myxoma diagnosed in a to our The patients presented over a 40-year ratio is with other in this ratio from to Myxomas can occur in all but are most frequent between the and of occur in although there is no for this female due in to In our series, younger age is significantly with neurologic signs or cardiac auscultation and is with neurologic or embolic symptoms in men and systemic symptoms in Clinical features The clinical features of these are by and there are no signs and symptoms that the of a myxoma In a of there are no symptoms at all in our there is no significant between the size of the tumor or 5 and the of discovery or atrial myxomas when the mitral or systemic 1) symptoms occur in of patients in our cases as mitral valve in mitral atrial and of fever are only of patients had in our study. Cardiac obstruction can be by progressive congestive cardiac failure on or or by syncope, or to mitral valve obstruction by the myxoma or coronary arteries The of obstruction may vary with body and these postural changes are particularly of myxoma (35,47). Cardiac failure the most frequent in our In our the of cardiac signs increased the diagnosis to that clinical symptoms are by another more common disease due to 2) emboli are the second of the classic in of myxoma patients in our study. than of emboli to the central nervous system in our but any may be to a of symptoms and cases emboli in the upper and lower coronary and more emboli may to aneurysms, as of cardiac myxomas as in 3 patients in our was 12, yr, We that the of an or surface is significantly with cerebral and peripheral 3) Constitutional signs are the of the classic these symptoms are may occur in to of cases The is lower in our series studied a at a cardiovascular These signs and symptoms myalgia, muscle weakness, arthralgia, fever, weight loss, and are obviously nonspecific and may occur in a of or or immunologic diseases tissue manifestations have also been reported in myxoma patients Cardiac auscultation Cardiac auscultatory may vary between and may on body presystolic or diastolic murmurs, significant mitral may be heard in more than of the patients in our The auscultatory of myxoma is “tumor is a heart sound of heard after the second heart sound may be with a heart sound or a mitral The tumor plop is in only of patients in our We established a significant between cardiac auscultation abnormalities and cardiac or systemic symptoms. and are abnormal in only of the patients those with systemic symptoms significant was in our The main but nonspecific laboratory abnormalities are and elevated or is or may occur by on the has also been common are and that the and of a by the tumor may be for systemic and manifestations has been with of in patients with myxoma that to after surgical removal A between the size of the tumor and the of has also been suggested have also been in myxoma tissue myxoma tissue in cases by and are nonspecific but observed in our atrial in of patients, the alterations by the is (less than of cases) in to the in mitral valve We observed a significant between signs and the of cardiac or systemic symptoms. also nonspecific features in the patients and are not for when the tumor is in our a left atrium enlargement and signs of pulmonary may be In our series, chest X-ray abnormalities were significantly with cardiac or systemic symptoms, but there were radiologic signs when the myxoma was by embolic or neurologic In cardiac signs or symptoms are more prevalent with large and may that embolic becoming are diagnosed before the the size 5 that to cardiac and radiologic data a positive between small tumor size and embolic Table 6). methods is the and diagnostic of is and not any risk of tumor and and cardiac examination may be by the echocardiography is less with an to but echocardiography the for surgery is only on echocardiographic evidence of the in our series angiocardiography has not been since coronary in patients over 40 years old is in to coronary disease Other diagnostic methods and The of and over echocardiography is that of and thoracic are also more in tumor and tumor and size data that most left atrial myxomas arise from the atrial or the on the of and on the appearance is or with a or or is and the surface is either or and in our myxomas with constitutional symptoms, or In the such as and surface are seen in older that In our series, there was no significant between and The size and weight of myxomas but in our the of symptoms was in patients with on could or myxomas and or myxomas according to the of the that all occurred in patients with and myxomas. the of cardiac myxomas have been The of most is that myxomas are of is no that myxomas are myxomas may have a of that at first may be the of multiple surface or is not with or any of presentation, and is important not to an on the basis of these atypical are cardiac not be with myxomas The to the tumor are to be and analysis has that myxoma as tumor = and are and may be for and cases with is as is the showed that was by is also a for the that myxomas arise from the to A study that myxomas with a between tumor size and the of this a in Myxomas may to the but these not have any The myxoma tissue emboli may may the and may or may but any cerebral tissue years the may to Three patients in our series had embolic that into the with of multiple aneurysms, any or during and follow-up The of for myxomas is surgical removal the diagnosis is of the tumor is Embolic complications or are in patients: of patients in the time of our series, not due to cardiac but 2 patients had cardiac arrest in the before surgery with successful resuscitation. surgery is a as most are can be The may according to In our series, was 3 patients during the postoperative period before and another patient in of meningitis not to myxoma. The most frequent postoperative was transient or with an of Cardiac myxomas occur but or cases have been The reported rate ranges from to in the in our are reported from as as a months to as as years after of the myxoma in our The of is not but risk or of tumor of the a of tumor in the In most cases of of the to be the of Patients with abnormalities are at risk of and from 2 or more of the cardiac and myxomas or of the with and are as or The risk of for and myxomas is about and is only for In our series, 3 cases the cardiac myxoma the time of myxoma patients are younger than myxoma patients. myxomas of the 2 patient groups are not A to has been identified The is In the the rate is and after of myxomas ranges from 0 to in our may surgical removal in our A patients may permanent cardiac for conduction 2 patients in our In of the of a tumor that with mitral valve to in heart failure, the mitral valve is In our only 1 patient mitral valve for endocarditis with left atrial myxoma. the myxoma patients to be and cases. echocardiogram is over the period at diagnosis The mitral valve other and heart more common than and occur in patients with myocardial infarction or systemic symptoms are present (fever, weight loss, the diagnosis heart and tissue disease or The of embolic and constitutional symptoms is due more to but may also myxoma. The of or syndrome to the 2 diseases, as these are in myxoma. myxomas are occasionally the clinical of myxoma and endocarditis more of cardiac myxomas reported 40 cases with a presentation similar to is no clinical between and noninfected myxoma cardiac symptoms and the rate of systemic or cerebral constitutional symptoms significantly in patients with myxoma (fever, elevated and men are more than series of 112 cases of left atrial myxoma clinical that this tumor may a of clinical symptoms not only such as cardiac but also or neurologic is made only on clinical there are no signs or symptoms. but or cases have been that and of the by the tumor may be for or including the is the of for diagnosis and follow-up of this myxomas are be in the diagnosis of mitral valve disease and congestive heart failure, in patients with is also for any patient with embolic embolic in in the of signs or symptoms of endocarditis or to a of myxoma as the embolic The obtained by be are to the clinical features of in in myxoma or be studied for embolic myxomas with of could be performed to for the ratio and age We a series of 112 cases of left atrial myxoma diagnosed in a French and 40 age range, yr) over 40 years, from 1959 to Symptoms of mitral valve the first of the classic of myxoma presentation, were present in 75 patients with cardiac failure or Symptoms of the second frequent presentation in the classic were observed in 33 cases with 1 or several cerebral emboli with are at risk than females of embolic The of the classic of constitutional symptoms with fever, weight loss, or symptoms tissue due to and patients have more neurologic symptoms, and female patients have more systemic symptoms. patients (64%) had cardiac auscultation valve disease and more the tumor plop The most frequent was left atrial were The number of myxoma patients diagnosed after 1977 the introduction of echocardiography as a noninvasive diagnostic there was no significant in the time from onset of symptoms to between patients seen in the before and after The tumor from 1 to 15 cm with a weight of between 15 and The myxoma surface was or in of the and in the other cases. Myxomas in patients with embolism have a those in patients with cardiac symptoms, auscultation signs, tumor and electrocardiogram or radiologic signs of left atrium and are significantly the The is and only 4 occurred our 112 cases over a median follow-up of 3 The rate is but follow-up and echocardiography are for patients. The surgical were performed during the 40-year period by We are to for the

Medicine · review · 878 citationsread the source →

Hospital transfers of nursing home residents with advanced dementia.

Objectives: To describe diagnoses and factors associated with hospital transfer in nursing home (NH) residents with advanced dementia. Design: Prospective cohort study. Setting: Twenty-two Boston, Massachusetts-area NHs. Participants: Three hundred twenty-three NH residents with advanced dementia. Measurements: Data were collected quarterly for up to 18 months. Data regarding transfers were collected with regard to hospitalization or emergency department (ED) visit, diagnosis, and duration of inpatient admission. Information on the occurrence of any acute medical event (pneumonia, febrile episode, or other acute illness) in the prior 90 days was obtained quarterly. Logistic regression conducted at the level of the acute medical event identified characteristics associated with hospital transfer. Results: The entire cohort experienced 74 hospitalizations and 60 ED visits. Suspected infections were the most common reason for hospitalization (44, 59%), most frequently attributable to a respiratory source (30, 41%). Feeding tube-related complications accounted for 47% of ED visits. In adjusted analysis conducted on acute medical events, younger resident age, event type (pneumonia or other event vs febrile episode), chronic obstructive pulmonary disease, and the lack of a do-not-hospitalize (DNH) order (adjusted odds ratio = 5.22, 95% confidence interval = 2.31-11.79) were associated with hospital transfer. Conclusion: The majority of hospitalizations of NH residents with advanced dementia were due to infections and thus were potentially avoidable, because infections are often treatable in the NH. Feeding tube-related complications accounted for almost half of all ED visits, representing a common but underrecognized burden of this intervention. Advance care planning in the form of a DNH order was the only identified modifiable factor associated with avoiding hospitalization.

Journal of the American Geriatrics Society · 124 citationsread the source →

Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding: National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation: For the Chinese translation of the abstract see Supplementary Materials section.

The lancet. Psychiatry · 591 citationsread the source →

Factor associated with experience of modern contraceptive use before pregnancy among women who gave birth in Kersa HDSS, Ethiopia.

Background: Worldwide, every year 289,000 women die related to pregnancy and its complications. Nearly, all of these deaths occur in developing countries and more than half of this deaths occur in sub-Saharan Africa. Report suggested that using contraceptives can reduce this maternal mortality by 44 %. Even if, Ethiopia is one of the countries with highest maternal mortality, only 41 % of married women are using family planning. This analysis aimed at assessing factor associated with experience of contraceptive use before pregnancy among women who gave birth in Kersa Health and Demographic Surveillance System, Ethiopia. Methods: This study was part of data generated for Kersa Health and Demographic Surveillance System. Women who gave birth during October 2011 to September 2012 were asked whether they had used contraceptive before getting their last pregnancy. Data were collected by using Kersa Health and Demographic Surveillance System questionnaire. Both bi-variate and multivariate analysis were used to identify associated factors. Results: The proportion of modern contraceptive before pregnancy among the study participants was found to be 383 (40.9 %). The most commonly used modern contraceptives was Injectable contraceptive 270 (70.0 %) followed by oral contraceptives, 66 (17.23 %). Modern contraceptive use was negatively association with being Muslim (AOR = 0.2, 95 % CI = 0.05, 0.72) and being young mother (AOR = 0.44, 95 % CI = 0.22, 0.86). Rural town residence (AOR = 2.23, 95 % CI = 1.15, 4.35) was found to have positive association with utilization of modern contraceptives. Conclusions: Among women giving birth, only a minority had attempted to delay or prevent their recent birth by using contraception. Being young, being Muslim and living in rural area were significantly associated with low utilization of modern contraceptive. Increasing family planning education and involving religious leaders in family planning promotion would improve utilization of modern contraceptive use.

BMC public health · 24 citationsread the source →

Time Spent Gaming, Device Type, Addiction Scores, and Well-being of Adolescent English Gamers in the 2021 OxWell Survey: Latent Profile Analysis.

Background: The shift in the last decades to screen-based and increasingly web-based gaming activity has raised concerns about its impact on the development of children and adolescents. Despite decades of research into gaming and related psychosocial effects, the question remains how best to identify what degree or context of gaming may be a cause for concern. Objective: This study aimed to classify adolescents into gamer profiles based on both gaming behaviors and well-being. Once we distinguished the different gamer profiles, we aimed to explore whether membership to a specific profile could be predicted based on a range of personal characteristics and experiences that could then help identify those at risk. Methods: We explored gaming and well-being in an adolescent school population (aged 12-18 years) in England as part of the 2021 OxWell student survey. Self-report measures of time spent playing games on computers or consoles, time spent playing games on mobile phones, the Game Addiction Scale, and the Warwick-Edinburgh Mental Well-being Scale were used to classify adolescent heavy gamers (playing games for at least 3.5 hours a day) using latent profile analysis. We used multinomial logistic regression analysis to predict the profile membership based on a range of personal characteristics and experiences. Results: In total, 12,725 participants answered the OxWell gaming questions. Almost one-third (3970/12,725, 31.2%) indicated that they play games for at least 3.5 hours a day. The correlation between time spent playing video games overall and well-being was not significant (P=.41). The latent profile analysis distinguished 6 profiles of adolescent heavy gamers: adaptive computer gamers (1747/3970, 44%); casual computer gamers (873/3970, 22%); casual phone gamers (595/3970, 15%); unknown device gamers (476/3970, 12%); maladaptive computer gamers (238/3970, 6%); and maladaptive phone gamers (79/3970, 2%). In comparison with adaptive computer gamers, maladaptive phone gamers were mostly female (odds ratio [OR] 0.08, 95% CI 0.03-0.21) and were more likely to have experienced abuse or neglect (OR 3.18, 95% CI 1.34-7.55). Maladaptive computer gamers, who reported gaming both on their mobile phones and on the computer, were mostly male and more likely to report anxiety (OR 2.25, 95% CI 1.23-4.12), aggressive behavior (OR 2.83, 95% CI 1.65-4.88), and web-based gambling (OR 2.18, 95% CI 1.24-3.81). Conclusions: A substantial number of adolescents are spending ≥3.5 hours gaming each day, with almost 1 in 10 (317/3970, 8%) reporting co-occurring gaming and well-being issues. Long hours gaming using mobile phones, particularly common in female gamers, may signal poorer functioning and indicate a need for additional support. Although increased time gaming might be changing how adolescents spend their free time and might thus have public health implications, it does not seem to relate to co-occurring well-being issues or mental ill-health for the majority of adolescent gamers.

JMIR pediatrics and parenting · 11 citationsread the source →

Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms.

Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date has evaluated abuse and methylation of the oxytocin receptor (OXTR). However, studies support a role for OXTR in the link between abuse and adverse adult outcomes, showing that abuse can confer greater risk for psychiatric symptoms in those with specific OXTR genotypes. This study therefore sought to (a) assess the role of epigenetics in the link between abuse and psychopathology and (b) begin to integrate the genetic and epigenetic literature by exploring associations between OXTR genotypes and DNA CpG methylation. Data on 18 OXTR CpG sites, 44 single nucleotide polymorphisms, childhood abuse, and adult depression and anxiety symptoms were assessed in 393 African American adults (age = 41 ± 12.8 years). Overall, 68% of genotypes were associated with methylation of nearby CpG sites, with a subset surviving multiple test correction. Child abuse associated with higher methylation of two CpG sites yet did not survive correction or serve as a mediator of psychopathology. However, abuse interacted with CpG methylation to predict psychopathology. These findings suggest a role for OXTR in understanding the influence of early environments on adult psychiatric symptoms.

Child development · 114 citationsread the source →

Parenting style and obesity risk in children.

Background: Parents play a critical role in their children's lifestyle habits. The objective was to assess the effect of parenting style on the risk of childhood obesity, and to determine whether poverty was a moderator of the association. Methods: Participants were from the 1994-2008 cross-sectional samples of the National Longitudinal Survey of Children and Youth (NLSCY), a nationally representative survey of Canadian youth. Factor and cluster analyses identified four parenting styles consistent with Baumrind's parenting style prototypes. Multivariable logistic regression assessed the risk of obesity based on parenting style after adjusting for covariates. Analyses were stratified by age (preschool: 2-5years of age, n=19,026; school-age: 6-11years of age, n=18,551) and the moderating effect of poverty (household income<low income cut-offs adjusted for household size and geographic region) was assessed. Analyses used sampling and bootstrap weights. Results: In multivariable analyses, compared to authoritative parenting, preschool- and school-age children with authoritarian parents were 35% (95% CI: 1.2-1.5) and 41% (CI: 1.1-1.8) more likely to be obese, respectively. In preschool children, poverty moderated this association: authoritarian and negligent parenting was associated with 44% (CI: 1.3-1.7) and 26% (CI: 1.1-1.4) increased likelihood of obesity, respectively, but only among the children not living in poverty. In school-age children, poverty was not a moderator. Conclusions: Parenting style is associated with childhood obesity, but may be moderated by poverty. Successful strategies to combat childhood obesity should reflect the independent and interactive associations of sociodemographic and social-familial influences on health especially in early childhood.

Preventive medicine · 46 citationsread the source →

A Framework to Improve Surgeon Communication in High-Stakes Surgical Decisions: Best Case/Worst Case.

Importance: Although many older adults prefer to avoid burdensome interventions with limited ability to preserve their functional status, aggressive treatments, including surgery, are common near the end of life. Shared decision making is critical to achieve value-concordant treatment decisions and minimize unwanted care. However, communication in the acute inpatient setting is challenging. Objective: To evaluate the proof of concept of an intervention to teach surgeons to use the Best Case/Worst Case framework as a strategy to change surgeon communication and promote shared decision making during high-stakes surgical decisions. Design, setting, and participants: Our prospective pre-post study was conducted from June 2014 to August 2015, and data were analyzed using a mixed methods approach. The data were drawn from decision-making conversations between 32 older inpatients with an acute nonemergent surgical problem, 30 family members, and 25 surgeons at 1 tertiary care hospital in Madison, Wisconsin. Interventions: A 2-hour training session to teach each study-enrolled surgeon to use the Best Case/Worst Case communication framework. Main outcomes and measures: We scored conversation transcripts using OPTION 5, an observer measure of shared decision making, and used qualitative content analysis to characterize patterns in conversation structure, description of outcomes, and deliberation over treatment alternatives. Results: The study participants were patients aged 68 to 95 years (n = 32), 44% of whom had 5 or more comorbid conditions; family members of patients (n = 30); and surgeons (n = 17). The median OPTION 5 score improved from 41 preintervention (interquartile range, 26-66) to 74 after Best Case/Worst Case training (interquartile range, 60-81). Before training, surgeons described the patient's problem in conjunction with an operative solution, directed deliberation over options, listed discrete procedural risks, and did not integrate preferences into a treatment recommendation. After training, surgeons using Best Case/Worst Case clearly presented a choice between treatments, described a range of postoperative trajectories including functional decline, and involved patients and families in deliberation. Conclusions and relevance: Using the Best Case/Worst Case framework changed surgeon communication by shifting the focus of decision-making conversations from an isolated surgical problem to a discussion about treatment alternatives and outcomes. This intervention can help surgeons structure challenging conversations to promote shared decision making in the acute setting.

JAMA surgery · 139 citationsread the source →

AML versus ICU: outcome of septic AML patients in an intensive care setting.

Purpose: Intensive therapy regimens in patients with acute myeloid leukemia (AML) frequently result in sepsis and septic shock. In this study, we investigated the prognostic outcome of AML patients requiring intensive care treatment due to severe sepsis or septic shock. Design: We present a retrospective cohort study in a medical intensive care unit (ICU) of a university hospital that serves as a tertiary care center. Materials and methods: Here we present data from 44 AML patients of our ICU with 29 requiring invasive mechanical ventilation due to sepsis and compared multiple clinical and laboratory parameters of ICU survivors and non-survivors. Results: Mean age was 59.5 years, the overall mortality rate was 41% (18/44), and the mortality rate among patients who received mechanical ventilation was 55% (16/29). The mortality rate among younger patients (aged 60 years or less) was 17% (3/18), while 58% of the older patients died (15/26). The mortality rate among younger patients who received mechanical ventilation was 23% (3/13) compared with 81% (13/16) of the older patients. The mean invasive ventilation time was 415 h in non-survivors compared with 667 h in survivors. No differences could be identified between survivors and non-survivors, concerning multiple laboratory parameters or AML prognostic and therapeutic parameters; our analysis, however, confirmed a statistically significant difference in the patients' age. Conclusions: In previous studies, age was one of the most important prognostic factors in AML patients receiving mechanical ventilation due to severe sepsis or septic shock. In spite of improvements in diagnostic and treatment over the last couple of years, our study indicates that this fact still is true. However, the overall outcome has improved over the years due to improvements in intensive care medicine.

Journal of cancer research and clinical oncology · 14 citationsread the source →

A review of patients with advanced cervical cancer presenting to palliative care services at Queen Elizabeth Central Hospital in Blantyre, Malawi.

Background: Cervical cancer is the commonest cancer affecting women in Malawi, which has the highest rate of this disease in the world. Most cases are diagnosed at an advanced stage. Aim: To describe the symptom burden, palliative care interventions, and outcomes of cervical cancer patients who entered care at Tiyanjane Clinic in Blantyre, Malawi, between January and December 2012. Methods: We reviewed the case files of 72 patients presenting to our hospital-based palliative care service over one year. Results: The mean age was 49.5 years. Twenty-six patients (36%) were HIV-positive and the majority of these (n = 22; 85%) were on antiretroviral medication at presentation to palliative care. Pain (n = 66; 92%), vaginal discharge (n = 44; 61%), and unpleasant odour (n = 37; 51%) were commonly reported. Over a third of patients (n = 26; 36%) reported pain in two or more sites. Fourteen patients (19%) reported vaginal bleeding. Spousal breakdown (through widowhood or divorce) was noted in over half (n = 41; 57%) of all cases. Pain relief was provided to 69 (96%) of the patients (morphine to 40 patients; 56%). Common interventions provided included metronidazole tablets (used vaginally), sanitary items, and counselling. At the end of the study period, 18 patients (25%) were still under the care of palliative services. Conclusions: Access to medications such as morphine, metronidazole and tranexamic acid can improve quality of life, even when radiotherapy is limited. Health care teams require necessary skills and training, including how to perform a comprehensive assessment, with an emphasis on the provision of psychosexual counselling, to assist with the complexity of symptoms occurring in this vulnerable group.

Malawi medical journal : the journal of Medical Association of Malawi · 24 citationsread the source →

Prevalence and Nature of Sexist and Racial/Ethnic Microaggressions Against Surgeons and Anesthesiologists.

Importance: Workplace mistreatment can manifest as microaggressions that cause chronic, severe distress. As physician burnout becomes a global crisis, quantitative research to delineate the impact of microaggressions is imperative. Objectives: To examine the prevalence and nature of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists and assess the association with physician burnout. Design, setting, and participants: This cross-sectional survey evaluated microaggressions and physician burnout within a diverse cohort of surgeons and anesthesiologists in a large health maintenance organization. A total of 1643 eligible participants were sent a recruitment email on January 8, 2020, 1609 received the email, and 652 replied, for a response rate of 41%. The study survey remained open until February 20, 2020. A total of 588 individuals (37%) were included in the study after exclusion criteria were applied. Exposures: The Maslach Burnout Inventory, the Racial Microaggression Scale, and the Sexist Microaggression Experience and Stress Scale. Main outcomes and measures: The primary outcomes were prevalence and nature of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists using the Sexist Microaggression Experience and Stress Scale and Racial Microaggression Scale. Secondary outcomes were frequency and severity of microaggressions, prevalence of physician burnout, and associations between microaggressions and physician burnout. Results: Data obtained from 588 respondents (249 [44%] female, 367 [62%] racial/ethnic minority, 224 [38.1%] 40-49 years of age) were analyzed. A total of 245 of 259 female respondents (94%) experienced sexist microaggressions, most commonly overhearing or seeing degrading female terms or images. Racial/ethnic microaggressions were experienced by 299 of 367 racial/ethnic-minority physicians (81%), most commonly reporting few leaders or coworkers of the same race/ethnicity. Criminality was rare (18 of 367 [5%]) but unique to and significantly higher for Hispanic and Black physicians. Individuals who identified as underrepresented minorities were more likely to experience environmental inequities (odds ratio [OR], 4.21; 95% CI, 1.6-10.75; P = .002) and criminality (OR, 14.93; 95% CI, 4.5-48.5; P < .001). The prevalence of physician burnout was 47% (280 of 588 physicians) and higher among female physicians (OR, 1.60; 95% CI, 1.03-2.47; P = .04) and racial/ethnic-minority physicians (OR, 2.08; 95% CI, 1.31-3.30; P = .002). Female physicians who experienced sexist microaggressions (racial/ethnic-minority female physicians: OR, 1.84; 95% CI, 1.04-3.25; P = .04; White female physicians: OR, 1.99; 95% CI, 1.07-3.69; P = .03) were more likely to experience burnout. Racial/ethnic-minority female physicians (OR, 1.86; 95% CI, 1.03-3.35; P = .04) who experienced racial microaggressions were more likely to report burnout. Racial/ethnic-minority female physicians who had the compound experience of sexist and racial/ethnic microaggressions (OR, 2.05; 95% CI, 1.14-3.69; P = .02) were more likely to experience burnout. Conclusions and relevance: The prevalence of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists was high and associated with physician burnout. This study provides a valuable response to the increasing call for evidence-based data on surgical workplace mistreatment.

JAMA surgery · 99 citationsread the source →

Mindful Self-Compassion Training Reduces Stress and Burnout Symptoms Among Practicing Psychologists: A Randomized Controlled Trial of a Brief Web-Based Intervention

Objective: The purpose of this study was to examine the effects of a six-week web-based mindful self-compassion program on stress and burnout symptoms in a group of helping professionals. Method: In a randomized controlled trial 101 practicing psychologists were assigned to a training group (n = 51) and a wait-list control group (n = 49). The training program involved 15 min exercises per day, six days a week, for six weeks. The participants completed the Self-Compassion Scale (SCS), the Five Facets of Mindfulness Questionnaire (FFMQ), the Perceived Stress Scale (PSS), and the Shirom Melamed Burnout Questionnaire (SMBQ) pre and post intervention. Results: Eighty-one participants (n = 40 in the training group, n = 41 in the control group) took part in the pre and post assessments. Selective gains for the intervention group were observed for SCS total score (d = 0.86; d = .94 for the self-compassion scale). Levels of self-coldness were reduced following the training and mindfulness scores increased (d = 0.60). Most important, levels of perceived stress (d = .59) and burnout symptoms (d = .44 for SMBQ total, mental aspects in particular) were lower post intervention. The results largely confirmed the hypothesis that the measures of distress would be more strongly related to self-coldness than self-compassion, a pattern seen in cross-sectional analyses and longitudinal analyses, at least for burnout. Conclusions: The mindful self-compassion program appeared effective to increase self-compassion/reduce self-coldness, and to alleviate stress and symptoms of burnout in the study sample. Additional studies, preferably three-armed RCTs with long-term follow-up, are warranted to further evaluate the effectiveness of the program.

Frontiers in Psychology · 231 citationsread the source →

Psychosexual health in gynecological cancer

The literature surrounding psychosexual health and cancer patients has primarily considered the functional aspects of the disease and its treatment at the major expense of the emotional sequelae. Sexual health is defined by WHO as: "a state of physical, emotional, mental, and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination and violence" [1]. A principle goal of WHO is to assist its member states in achieving the highest attainable standard of health care for all, including sexual and reproductive health [2]. Global statistics show that the world's female population is carrying an overwhelming burden of need in this area. Over 200 million women cannot access modern contraception, and millions of women suffer rape, domestic violence, and sexual abuse, not only in the context of wars and criminal activities, but also in their own homes [2]. Although the physical sequelae of these disasters can be treated, such as treatment for sexually transmitted infections, the emotional impact can frequently be hidden, ignored, or may not reveal its impact until many years after the event. Any illness or traumatic life event, past or present, can lead to sexual problems in the lifetime of a woman, and gynecological cancer is no exception. It is the root cause or trigger for sexual difficulties in at least 50% of women affected [3]. In 2012, the estimated number of women living with gynecological cancers was over three million, which means that potentially 1.5 million gynecological cancer survivors could be affected by an associated sexual difficulty [4]. Within the context of gynecological cancer, many of these problems can be alleviated if recognized and acknowledged early in the cancer journey, therefore contributing dramatic improvements to a woman's overall well-being. It is now estimated that half of the population of either sex will develop cancer at some time in their life. Globally, 40% − 45% of women will have a sexual problem at some stage, with the prevalence increasing with age [5]. Between 10% and 90% of women with any cancer will have sexual problems [6] and over 50% of women with gynecological cancer will have either temporary or persistent sexual difficulties [3]. As diagnosis and treatments improve, the number of women surviving cancer will increase, and survivorship issues including quality of life have become increasingly important. Sexuality is a key component of most subjective measurable quality of life indicators [7]. Sexual function and enjoyment are important components of survivorship and should not be ignored. The most common sexual problems can be divided into two groups: problems of function and/or problems of desire. There is, however, a complex interplay of organic disorders with emotional and psychosocial issues, and these divisions are merely artificial. Formal definitions of female sexual dysfunction have been adopted, including the US classifications in the Diagnostic and Statistical Manual of Mental Disorders [8], although having a sexual difficulty does not constitute having a mental health disorder. Basson et al. [9] published a useful classification of the problems. Such classifications are useful for research purposes, but may often be less helpful when treating women. The predominant functional female sexual problem is pain on sexual intercourse, or dyspareunia. Deep dyspareunia describes intracoital pelvic pain, and superficial dyspareunia is pain on vaginal entry. Either could signify organic disease, and should be appropriately investigated. If no pathology is demonstrated, and the pain persists, then an emotional cause must be considered and pursued. Vaginismus, or involuntary spasm of the pubococcygeal and related musculature, can prevent sexual intercourse taking place. Good history taking can clarify whether there has been any penetration of the vagina, not only penile, but by fingers, sex toys, or tampons. If not, this is diagnostic of primary vaginismus, and apart from close inspection of the vulva and offer of gentle digital vaginal examination to determine the extent of the vaginismus, no further clinical investigation is warranted. Women with gynecological cancer are more likely to have secondary vaginismus caused by pain experienced from the disease or its treatment, and fear of the pain occurring during sex [10]. Loss of libido or loss of sexual interest on the other hand is a problem of desire. There are no physiological markers for loss of desire when its origins are psychogenic, with psychosocial contributions, past and present relationships, traumas, and emotional factors all inhibiting the woman's wish to be sexual. One of the key ways to determine the origins of the sexual difficulty is to ask about the sexual and emotional relationship between the woman and her partner before the cancer diagnosis. It should not be assumed that problems are all due to the cancer, as long-standing relationship problems may be disclosed, and need to be incorporated into any counselling. The exception to this is the woman who suddenly becomes menopausal following cancer treatment, who had no problems with sex or desire prior to her cancer therapy. Appropriate standard therapy for her menopausal symptoms should be considered; however, the impact of a cancer diagnosis will be life changing, and drug treatment of hormonal deprivation symptoms may not be sufficient without some psychological or counselling support, or may be contraindicated as in the case of breast and endometrial cancer [11]. A diagnosis of gynecological cancer is overwhelming. While the instinctive professional response from clinicians is to ensure long-term survival, sexual issues are important for quality of life and should be considered in the decision-making process [12]. Sexual dysfunction is one of the most common and distressing consequences of cancer treatment [13]. Many treatments are shown to have sexual impacts, both positive and negative, and should be discussed fully with the woman pre-treatment so that she can make an autonomous decision about her care. Early offer of discussion of sexual issues in the cancer journey can lead to better sexual outcomes. Cervical cancer is the most common gynecological cancer worldwide. Cervical cancer survivors are at risk of sexual pain disorders, no matter which modality of treatment is used. A small study of patients who underwent radical vaginal trachelectomy for early stage cervical cancer showed sexual dysfunction, including loss of libido, for up to one year following treatment; however, by 12 months, sexual activity had reached that of healthy women [14]. Following radical hysterectomy for locally advanced cervical cancer, there was no significant difference in sexual activity and enjoyment between women with benign or malignant disease; however, the cancer group had worse problems than healthy controls with body image and vaginal functioning [15]. In women with advanced cervical cancer given chemoradiotherapy, pain during intercourse was in fact reduced after treatment [16]. This may have been a result of the resolution of bleeding, discharge, and pelvic pain. However, the anxiety surrounding cancer remains for many women. Women surviving up to 15 years following cervical cancer treatment showed poorer quality of life than healthy controls, and those who had received radiotherapy were significantly more affected by sexual dysfunction than those who had surgery alone [17]. Despite this however, orgasm may be unimpaired following radiation [18]. Many additional needs were expressed by women with cervical cancer; however, sexuality and intimacy came to the fore as a predominant issue for survivorship [19]. It has been known for some time that the physical and emotional impact of ovarian cancer can be devastating, leading to sexual as well as global quality of life issues [20]. One study has shown a prevalence of 63% for sexual difficulties among women with a diagnosis of ovarian cancer [3]. The effects of chemotherapy and surgery, combined with the anxiety about survival can have a dramatic negative effect on the woman's libido, and even women who undertake risk-reducing salpingo-oophorectomy can suffer sexual dysfunction [21]. Many of these women are totally unprepared for the devastating effects of sudden menopause, with hot flushes, vaginal dryness, and loss of libido replacing a previously healthy sex life. This could be helped by more realistic counselling before the procedure, and increased postoperative emotional support. One study has shown that women who had surgery for endometrial cancer had no differences in their own sexual experience postoperatively, but compared with healthy controls, they had more sexual difficulties overall [22]. Women with Lynch syndrome who opt for preventive surgery tend to be happy overall with the surgery, but are often unprepared for the physical adverse effects of menopause [23]. In contrast, Moldovan et al. [24] has reported that, despite sometimes debilitating menopausal symptoms, there were no significant sexual difficulties associated with the procedure. Vulvectomy is a common treatment for vulvar malignancy. This is increasingly affecting younger women, who are HIV positive. Women with vulvar cancer can have many years of difficulties with sex due to often distressing vulvar symptoms and bleeding. Following treatment they still suffer severe dyspareunia and body image distortion due to the effects of treatment. Although a recent study showed no differences in psychosocial and sexual functioning before and after vulvectomy, it was acknowledged that women with vulvar malignancy have a high risk for sexual problems compared with healthy controls [25]. Factors associated with postoperative sexual difficulties are increased age, poor overall physical and mental health well-being, and extent of the surgical excision [25]. This often elderly group of patients is usually neglected from the psychosexual point of view. The majority of the literature related to sexuality and cancer stems from high-resource countries. Although most of these studies encompass all women, there is a lack of good published evidence on the treatment of the sexual sequelae of cancer in relation to ethnic minority groups, within a majority culture [26]. Furthermore, data from low- and middle-income countries are scant. Much of the literature focuses on sexual distress and activity in relation to HIV and AIDS which, of course, is a global priority; however, this focus on infection transmission should not take away from the emotional needs of the woman who suffers from gynecological cancer. Sexuality research around the globe must be perceived and researched in terms of cultural, spiritual, ethnic, and religious contexts. Sexual problems in women with gynecological cancer may be associated with adverse effects of surgical, hormonal, and chemical treatments, as well as by the cancer itself. Fortunately, emotional, sexual, and quality of life outcomes improve as less morbid, more minimally invasive surgical treatments for gynecological cancers develop [12]. Chemotherapy-induced ovarian failure in cancer patients is associated with all the possible symptoms of a sudden menopause, combined with the emotional impact not only of the cancer, but loss of physical well-being and fertility all at the same time. Vaginal dryness can be a major problem to those women who wish to have sex [27], and appropriate vaginal moisturizers and lubricants can help. The issue of vaginal estrogen is still debated, but should be discussed with the patient, weighing up the risk − benefit ratio for each individual. Vaginal estrogen will, in most cases, alleviate the dryness, but there may be concerns about using hormones, especially in relation to breast cancer where the evidence is unclear. The scientific data, however, support the safety of low dose vaginal estrogen therapy [28]. It is not well understood that following a few weeks of vaginal estrogen, the vagina thickens and cornifies and estrogen is not absorbed as a result. Newer treatments such as selective estrogen receptor modulators have been used in place of vaginal estrogen in women without cancer [29], and may prove good alternatives in the future [30]. There are non-hormonal vaginal moisturizers and lubricants to make sexual intercourse more comfortable. Unfortunately, some commercial sexual lubricants can be hyperosmolar and could cause epithelial disruption, facilitating HIV transmission [31]. Simple lubricants such as olive oil or liquid glycerin have been used successfully in interventions to alleviate pain on intercourse due to vaginal dryness, combining their use with physiotherapy and psychosexual counselling. Treatments with pelvic external beam radiotherapy and/or with brachytherapy may cause vaginal shortening, tightening, and lack of pliability. The use of vaginal dilators to overcome these complications is widespread, despite lack of conclusive evidence, either for or against, either with or without a coating of estrogen cream [32]. Unsurprisingly, the intrusion of inserting a plastic (or sometimes glass) tube into a tender vagina after treatment is a task that may carry a deep psychological and emotional impact [33], and will have resultant poor compliance. Radiation oncologists agree that information about dilator use should be given before treatment [34], and that sufficient patient information and support are essential to improve compliance. Sensitivity to emotions and women's views and personal values in relation to sexuality are essential supports to encouraging dilator use [35]. Any of the above problems cannot fail to have an emotional impact on the woman and on her partner. Many sexual difficulties are automatically blamed on the organic disruption caused by cancer and its treatments; however, once any clearly indicated treatments have been given, in a sizable proportion of cases, the sexual difficulty will remain unresolved. Many sexual difficulties are psychogenic, and no amount of skilled clinical treatments will help if not linked closely to appropriate counselling, psychological, or psychosexual therapy. This form of intervention will enable the woman to expose and reflect on her sexual difficulties, in the context of her life and relationship not only since the cancer, but beforehand. This is often a time when past problems, such as childhood abuse, or problems with her current partner will surface. Some partners are disgusted by the physical impacts of cancer, and the relationship will suffer. On the other hand, some partners become more supportive and the cancer leads to stronger relationships [36]. Classic psychosexual therapy, using brief, focused psychotherapeutic techniques is the mainstay of treatment. It can be used with an individual or a couple, of any sexual orientation or cultural or religious background. This is a way of listening reflectively to the patient, so that they can gain their own insights into their sexual problem. The issue of genital examination is considered if relevant, as it enables the woman to connect with her genital area, and may trigger deep-seated thoughts or anxieties that the woman had blocked emotionally. This, of course, is a technique used only by clinicians who are qualified to examine the patient [37]. Clinical psychologists and counsellors trained in psychosexual work also treat women with sexual problems. Globally, because the availability of trained personnel differs, many simple innovative treatment interventions have been tried. A brief intervention using a well-accepted treatment, cognitive behavioral therapy (CBT), combined with sexual health education had positive results on patients who had risk-reducing salpingo-oophorectomy [21]. Psychosexual interventions work [38], and like all psychodynamic interventions only require a trained counsellor and a means of allowing access to the patient. The internet has enabled access to health care for many people around the world who are not able to travel long and difficult land journeys to direct provision of health care. An online intervention with a professional moderator has proven acceptable to gynecological cancer patients with a sexual difficulty [39], and another internet-based sexual difficulties intervention with counselling sessions proved more successful in improving sexuality issues than without a counsellor; however, there was no difference between the two groups in relation to emotional distress and quality of life [40]. Elsewhere, telephone interventions are being used, also with some success; however, it is clear that the knowledge, skills, and training of the health professional providing the intervention are relevant to the patient outcome. Multidisciplinary care should form the backbone of treatment of sexual difficulties in women with gynecological cancer, incorporating physical, psychoeducational, and psychosexual input. Team discussions, including clinicians, psychosexual therapists, and physiotherapists are well within the capabilities of many cancer centers, remembering that the patient and her partner are the focal point and should always be consulted. It is impossible to diagnose and treat a sexual problem if one does not acknowledge that it exists. Many studies in the past have identified lack of willingness of doctors and nurses to discuss sex, but sadly recent research has shown that not much has changed. For instance, in a cohort sample of 1154 US obstetrician − gynecologists, 60% did not ask patients about sexual problems [41]. Too often clinicians make value judgements about their patients including whether sexuality is an important part of their lives. Such assumptions may include biases about age, appearance, sexual preferences, and marital status of people who have sex. People with cancer and their partners have unmet sexual information and support needs [42], often due to the unwillingness of healthcare professionals to discuss sexual issues, even though they recognize it may be important to the patient. There are many barriers to talking about sex, affecting both the patient and the clinician, such as cultural background, and age and gender discrepancies between doctor and patient. There may be simple barriers, such as lack of privacy in a consultation, as often cancer patients are accompanied by family or close friends. Patients often state that they feel it is trivial to take up the doctor's time with non-life-threatening issues such as sex. Clinicians often cite lack of training as a reason that they are uncomfortable talking about sex and poor provision of this training has been noted [13]. Different models of communication skills training have been used and those undertaking the training have shown greater empathy and were more inclined to use open questions [43]. This technique of speaking to the patient in an open rather than interrogative manner can easily facilitate discussion of intimate issues. An even greater challenge in communication is the recognition that individuals are sexual beings up to the end of life. To some women in the palliative phase, sexual touch and closeness to their partner is of vital importance. Sadly this is rarely recognized and addressed by palliative care physicians [44]. It is important to remember that a minority of the female population identifies as lesbian, and that about 8% of the population is bisexual. While this should make no difference to the quality of sexual health care they receive, lesbians and bisexuals find it difficult to disclose their sexuality to clinicians, often inhibited by their cultural or religious background, and fears of facing discrimination [45]. If the clinician asks the patient at the outset if they have a sexual partner, and whether the partner is male or female, it will greatly enhance the quality of the doctor − patient interaction. Lesbian partners in particular can be very supportive during the cancer journey, and should be given the opportunity to be present if the patient wishes. Despite the recognized need for treatment of sexual problems in menopause and gynecological cancer, there is poor provision of specialist training to ensure that this important area of service provision is met [46]. Undergraduate teaching is important, but it is only by recognizing psychosexual medicine in formal gynecology or oncology training, as a compulsory requirement of the course, that this situation will begin to be addressed. Innovative online programs [47] can make a major impact on global training opportunities and give trainees around the world an opportunity to gain some skills and insight into treating sexual difficulties in a nonjudgmental way. Owing to the global prevalence of sexual problems associated with gynecological cancer, it should be within every gynecologist's or oncologist's duty of care to the patient to be aware of and have some understanding of how to diagnose and facilitate treatment for sexual problems in a nonjudgmental manner. This is true holistic medicine, recognizing not only the cancer, but the woman behind the symptoms, and requires awareness of the emotional, social, and relationship aspects of the patient's life. The ability of any person to enjoy a sexual life free of coercion, shame, disease, or pain in a consensual manner is a fundamental element of the human rights of women, and should be an unequivocally accepted as part of her gynecological cancer care. To make a difference, even in the absence of expensive and sophisticated cancer treatments, just acknowledging, listening, and offering support to the woman with sexual difficulties related to cancer will ultimately have a major benefit to her quality of life. The author has no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

International Journal of Gynecology & Obstetrics · 17 citationsread the source →

Combat sports and wellbeing: advancing health and inclusion in athletes and practitioners. An opinion paper

Historically, combat sports have been predominantly conceptualized within the framework of elite competition, emphasizing physical aptitude, technical proficiency, and strategic execution (1-3). Despite their traditional and peculiar constitutions and developments, disciplines such as judo, karate, taekwondo, wrestling, fencing, boxing, and mixed martial arts have commonly been associated with high-performance athletes striving for competitive excellence on national and international stages (1, 4-6). However, contemporary discourse increasingly recognizes their expansive role in contributing to physical and psychological well-being, and social inclusion of the practitioners (7, 8). This paradigmatic shift underscores the capacity of combat sports to function as inclusive and accessible modalities for fostering multidimensional health benefits across diverse populations, including individuals with disabilities and other marginalized groups (9-13).The interdisciplinary exploration of physical activity and health highlights the intricate interrelationship between structured sports engagement and holistic well-being (14). Whilst conventional team and individual sports have long been acknowledged for their physiological and psychosocial benefits, combat sports exhibit distinct characteristics that might amplify these advantages (15, 16). Within combat sports, the synergistic interplay of rigorous physical conditioning, the cognitive engagement, adherence to rules, competition dynamics, respect, externalizing emotions regulation, are intertwined with pedagogical and philosophical values, thus presenting a unique framework for enhancing psychological resilience, cognitive adaptability, and emotional control. Consequently, the systematic practice of combat sports has been increasingly examined as a way of promoting mental health, stress modulation, and social cohesion (17, 18).The inclusive nature of many combat sports programmes further accentuates their relevance in dismantling stereotypes, facilitating integration, and fostering equity and social integration (19-21). In fact, they demonstrated significant adaptability to accommodate individuals with disabilities (e.g., physical impairments, developmental, emotional, intellectual disorders), thereby ensuring equitable access and fostering empowerment (9, 22). Adapted judo, para-taekwondo, and other modified combat disciplines provide individuals with disabilities a structured platform to engage in physical activity, cultivate self-efficacy, and develop meaningful social connections within a supportive and adaptive environment (23). From a public health perspective, the integration of combat sports within community-based health initiatives offers a compelling opportunity to engage populations that may not traditionally participate in structured physical activity programmes (7, 8, 19). The distinctive accessibility of combat sports, which cater to practitioners of all skill levels (e.g., from novices to elite athletes) sets them apart from many other sports. While their structured progression, adaptability, and emphasis on holistic development make them a viable option for lifelong and intergenerational participation (19, 24, 25), the mentorship and pedagogical frameworks cultivate positive role modeling, discipline, and intrinsic motivation, which are integral for sustaining long-term adherence to health-promoting behaviors (8).Furthermore, the intersection between combat sports and mental health has increasingly emerged as a focal point within academic and clinical research (17) with empirical evidence suggesting an association between participation and enhanced self-regulation and self-efficacy, and reduction in anxiety and depressive symptomatology (8, 26, 27). In necessitating sustained focus, adaptability, and emotional equilibrium, combat sports inherently require cognitive and affective demands, which align closely with established psychological frameworks that underpin mental well-being (28, 29). Moreover, the integration of mindfulness techniques, stress management strategies, and resilience-building paradigms within combat sports training substantiates their potential as a non-pharmacological intervention for addressing various mental health challenges (e.g., autism spectrum and oppositional defiant disorders) (30, 31).Despite these advantages, the discourse surrounding combat sports and well-being necessitates a critical examination of inherent risks and potential challenges. Issues related to injury risk, hypercompetitive environments, eating disorders, sexual harassment, and the psychological stressors associated with high-intensity training warrant careful scrutiny (32-36). The implementation of evidence-based injury prevention protocols, the establishment of ethically responsible coaching methodologies, and the promotion of safe training environments are imperative to ensure that the benefits of combat sports are maximized while minimizing adverse outcomes. Against this backdrop, this opinion paper seeks to examine the role of combat sports in advancing health and social inclusion among athletes and practitioners. Through a synthesis of contemporary empirical findings, theoretical paradigms, and applied insights, this paper aims to contribute to the evolving discourse on the potential of combat sports as a catalyst for holistic well-being. By delineating the multidimensional impact of combat sports on physical, psychological, and social health, this paper endeavors to underscore their transformative potential as an instrument for fostering individual and community well-being within different populations. DiscussionWhilst an expanding body of research and an evolution in scholarly discourse is recognizing the combat sports’ broader implications for holistic well-being (30, 37), a rigorous evaluation of the investigation methodologies, the validity of hypotheses, and the translational potential of recent findings is necessary to contextualize their significance within the sports and public health sciences, considering their strengths, weaknesses, opportunities, and threats (Figure 1).----------------------------------------ADD FIGURE 1 ABOUT HERE----------------------------------------Empirical evidence robustly shows the positive impact of combat sports on physical fitness, motor coordination, and cardiovascular health (3, 38). These benefits are attributed to the high-intensity, intermittent nature of combat sports training, which enhances aerobic and anaerobic endurance, muscular strength, and neuromuscular control (39). However, concerns regarding injury risk, particularly in striking and contact-intensive disciplines such as boxing, taekwondo, and mixed martial arts, necessitate continued research into injury mitigation strategies, particularly those targeting concussion and repetitive head trauma (6, 35, 40, 41). Moreover, many combat sports have developed styles with reduced or simulated contact to minimize injury risk. For example, the French "boxe éducative" emphasizing technique and control, penalizing any violent behaviors (42) and the value and application of kata (i.e., forms; prearranged, pattern practices) to learning and adopting judo technique in a safe way educating the athlete culturally, to enrich her/him as a person (43).Beyond physical health, recent studies highlight the psychological benefits of combat sports, including reductions in anxiety and depression and improvements in self-efficacy, emotional regulation, resilience, and stress management (27, 44-47). Therefore, combat sports-based interventions for individuals with mental health conditions have yielded promising outcomes (23). Despite these encouraging findings, variability in study designs, participant demographics, and intervention protocols limits their external validity, underscoring the need for further rigorously controlled investigations. Furthermore, some authors claimed that combat sport athletes might present symptoms of low energy availability and high anxiety levels associated with competition- and injury-related psychological stressors, deficits in executive functions and neuropsychological impairments associated with occurrence of concussions, disordered eating and eating disorders associated with weight-loss, and might suffer offensive, frightening, hostile, degrading, humiliating experiences, or sexual harassment, which urge safeguarding actions (32-36).The role of combat sports in fostering social inclusion has gained empirical support, particularly in programmes aimed at individuals with disabilities and marginalized communities (25, 48). For instance, a recent systematic review shows that judo interventions adapted for intellectual disabilities help improve social integration and self-perception and enhance participants' quality of life (49). The development of para-combat sports demonstrates enhanced physical and motor abilities while providing psychosocial benefits to various populations with different disabilities, promoting social integration, self-perception, and community belonging (50, 51). However, longitudinal research is needed to assess the long-term retention rates and sustainability of these benefits. Furthermore, there is a need of studies focused on the most appropriate adapted rules to achieve a fairer competition for ensuring a sense of success in individuals with physical, emotional, mental, hearing or visual impairments participating in adapted sports competitions at local, national, and international levels. Methodological approaches in combat sports research encompass experimental, longitudinal, qualitative, and systematic review designs. While randomized controlled trials remain the gold standard for establishing causality, their application in combat sports research is constrained by ethical concerns, logistical challenges, and the inherently dynamic nature of training environments (52, 53). Consequently, many studies rely on observational designs, which, despite their value in identifying associations, are susceptible to confounding variables and biases (24, 54).Qualitative methodologies have provided critical insights into the lived experiences of combat sports practitioners, offering perspectives on psychological and social dimensions that are often overlooked in quantitative studies (28). Ethnographic research has been particularly instrumental in elucidating the role of combat sports in shaping identity, discipline, and personal development (55). However, limitations in reproducibility and generalizability highlight the need for mixed-methods approaches to generate a more comprehensive understanding of combat sports' impact (25, 56).Additionally, the incorporation of biometric and neurocognitive assessments, such as heart rate variability analysis, functional MRI, and salivary cortisol measurements, has advanced our understanding of the physiological and psychological mechanisms underlying combat sports participation (47, 57, 58). Despite their objective precision, these techniques often face challenges related to cost, accessibility, and limited sample sizes, necessitating the development of scalable and cost-effective methodologies for broader research application. Finally, recent studies show that virtual reality (VR) technology and digital platforms are increasingly becoming part of combat sports training methods. Due to COVID-19 restrictions, martial arts schools and organizations implemented hybrid or online training models, which allowed athletes to stay engaged. VR boxing programmes provide users with virtual sparring simulations to enhance their motor skills without needing physical interaction. Initial results indicate that VR training enhances response behavior in karate athletes (59). Digital adaptations offer great potential, especially for people with limited mobility or remote locations. However, further studies are necessary to prove their enduring effects on physical health and psychological and social aspects (59-61).Strengths and Weaknesses of Scientific HypothesesThe hypothesis that combat sports confer multidimensional health benefits is strongly supported by empirical evidence spanning physiological, psychological, and social domains (8, 62-64). The integration of physical exertion, cognitive engagement, and structured discipline inherent in combat sports aligns with established theories of exercise psychology, neuroplasticity, and social identity formation (65, 66). This multidimensional perspective provides a robust theoretical foundation for advocating combat sports as a health-promoting activity. Nevertheless, several limitations warrant consideration. The heterogeneity of disciplines, which vary highly in intensity, contact level, and training methodologies, is often inadequately addressed in research, leading to overgeneralized conclusions (17, 39). Often underexamined, individual differences in personality, motivation, and previous trauma history may strongly moderate the psychological outcomes of combat sports participation (35, 67, 68).Additionally, a research focus is needed on concerns regarding the potential for adverse psychological effects (e.g., anxiety, depression, disordered eating behaviors, burnout, and decreased self-esteem), particularly in competitive environments where performance pressure, extreme weight-cutting practices, and aggressive coaching styles are prevalent (69, 70). Indeed, a balanced perspective that considers both benefits and risks is essential for the development of evidence-based recommendations (10, 71).Future DirectionsTo enhance the field, future research should prioritize well-structured longitudinal studies that assess the long-term impact of combat sports participation on physical, psychological, and social health. Standardization of outcome measures, intervention protocols, and participant demographics would facilitate cross-study comparisons and strengthen the reliability of findings (72, 73). Moreover, interdisciplinary collaborations incorporating sports science, psychology, and sociology could provide a more holistic perspective on combat sports' broader implications on practitioners (74).From a policy perspective, to yield valuable insights into combat sports’ practical applications research should investigate their efficacy within public health, educational, and rehabilitation initiatives, particularly for underserved and vulnerable populations (23, 75, 76).Furthermore, while safety remains a primary concern, advancements in protective equipment, training methodologies, education for athletes, coaches, referees and tournament directors, and regulatory frameworks should be continually evaluated to optimize benefits while mitigating risks (40, 41, 58, 77, 78). Ethical considerations, particularly concerning athlete well-being and inclusive participation, should remain a central focus in both research and practical implementation (17, 34, 36).Therefore, key research challenges to be addressed are: 1. Injury risk and safety: a need for injury prevention strategies, especially for concussions and head trauma in striking sports. 2. Psychological wellbeing: risks of stress, anxiety, burnout, and negative self-perception in competitive environments. 3. Inclusion and accessibility: a need for more research on long-term social and psychological benefits for marginalized groups and individuals with disabilities. 4. Methodological limitations: lack of standardized protocols, variability in study designs, and limited reproducibility of findings. 5. Ethical and regulatory issues: concerns over coaching practices, extreme weight-cutting, and athlete wellbeing in high-pressure environments. 6. Technological innovations: more research required on the effectiveness of VR and digital training tools in combat sports. 7. Public health and policy: exploration of combat sports' role in health initiatives, rehabilitation, and educational programs. ConclusionThe evolving discourse on combat sports highlights their potential as a multidimensional tool for well-being promotion. While a substantial body of evidence supports their benefits, a critical examination of methodological limitations, scientific hypotheses, and practical applications is essential for further refine our understanding and enhance their effectiveness. Finally, this article makes a significant contribution not only to the field of martial arts but also to public health and sports psychology. Its interdisciplinary approach calls for scientific collaboration and methodological rigor, reinforces the need for evidence-based policies and can serve as a valuable guide for researchers and policymakers looking to integrate combat sports into strategies for promoting health and social inclusion.

Frontiers in Psychology · 12 citationsread the source →

Social inequalities in multimorbidity, frailty, disability, and transitions to mortality: a 24-year follow-up of the Whitehall II cohort study.

Background: Social inequalities in mortality persist in high-income countries with universal health care, and the mechanisms by which these inequalities are generated remain unclear. We aimed to examine whether social inequalities were present before or after the onset of adverse health conditions (multimorbidity, frailty, and disability). Methods: Our analysis was based on data from the ongoing Whitehall II cohort study, which enrolled British civil servants aged 35-55 years in 1985-88. Participants were assessed for three indicators of socioeconomic status (education, occupational position, and literacy) at age 50 years. Participants underwent clinical examinations (in 2002-04, 2007-09, 2012-13, and 2015-16) for assessment of frailty (two or more of low physical activity, slow walking speed, poor grip strength, weight loss, and exhaustion) and disability (two or more difficulties in bathing, dressing, going to the toilet, transferring, feeding, and walking). In addition, electronic health records were used to assess the incidence of multimorbidity (two or more of diabetes, coronary heart disease, stroke, chronic obstructive pulmonary disease, depression, arthritis, cancer, dementia, and Parkinson's disease) and mortality. In analyses adjusted for sociodemographic factors, we used multistate models to examine social inequalities in transitions from healthy state to adverse health conditions and subsequently to mortality. Findings: Of 10 308 individuals in the Whitehall II study cohort, 6425 had relevant data available at 50 years and to the end of follow-up on Aug 31, 2017, and were included in our analysis. Participants were followed up for a median of 23·6 years (IQR 19·6-28·9). 1694 (26·4%) of 6425 participants developed multimorbidity, 1733 (27·0%) became frail, 692 (10·8%) had a disability, and 611 (9·5%) died. Multimorbidity (hazard ratio [HR] 4·12 [95% CI 3·41-4·98]), frailty (HR 2·38 [95% CI 1·93-2·93]), and disability (HR 1·73 [95% CI 1·34-2·22]) were associated with increased risk of mortality; these associations were not modified by socioeconomic status. In multistate models, occupation was the socioeconomic status indicator that was most strongly associated with inequalities in the transition from healthy state to multimorbidity (HR 1·54 [95% CI 1·37-1·73]), to frailty (HR 2·08 [95% CI 1·85-2·33]), and to disability (HR 1·44 [95% CI 1·18-1·74]). Socioeconomic status indicators did not affect transitions to mortality in those with multimorbidity, frailty, or disability. Interpretation: Socioeconomic status affects the risk of multimorbidity, frailty, and disability, but does not affect the risk of mortality after the onset of these adverse health conditions. Therefore, primary prevention is key to reducing social inequalities in mortality. Of the three adverse health conditions, multimorbidity had the strongest association with mortality, making it a central target for improving population health. Funding: UK Medical Research Council; National Institute on Aging, National Institutes of Health; British Heart Foundation.

The Lancet. Public health · 239 citationsread the source →

The impact of end-stage kidney disease (ESKD) on close persons: a literature review

Kidney disease is defined as end-stage when a patient's glomerular filtration rate has fallen to <15 ml/min/ 1.73 m2 [1]. Mortality associated with end-stage kidney disease (ESKD) is high [2]. The incidence of treated ESKD is rising in the western world, with a corresponding increase in the incidence of diabetes and cardiovascular disease, especially in ethnic minority groups. Survival on dialysis has been shown to be poorer in the older age group, especially in patients with increased comorbidity and in those whose functional status at the start of dialysis is poor [3]. Whilst renal transplant rates vary between different countries [4], the liberalization in the acceptance of older people into renal replacement therapy (RRT) programmes, together with changes in population demographics and the fact that kidney transplantation is less suitable for this group of older patients, means that dialysis may be the only treatment option available for an increasing number of patients aged 65 years and over [5]. Recent health policy changes in the OECD countries [6,7] acknowledge that end of life care may be more appropriate for some of these people, and maximum conservative management programmes (where residual renal function is supported, haemoglobin levels maintained and symptoms relieved) have been introduced into many renal units, particularly in the United Kingdom [6]. The onset of ESKD and subsequent recommendation of dialysis as a treatment option involves a change in lifestyle for both patients and close persons [8]. Even before end-stage disease is reached, as renal function deteriorates, patients frequently require additional support, and it is often family members who provide this [9]. In the UK it is estimated that 9 out of 10 carers of patients with either physical or neurological disabilities will be close relatives. In particular when home haemodialysis is undertaken, family members have been involved in supporting patients [10,11]. Studies have shown that good family support is associated with successful adaptation to dialysis and compliance with dietary restrictions [12,13]. Conversely, one of the main factors associated with patients discontinuing dialysis is patients’ perception that they have become a ‘burden’ to close family members [14]. There is therefore a need for health professionals to be aware of the important contribution that close persons make to the care of renal patients, to communicate effectively with them and to provide bereavement support for this group when appropriate [15]. The literature on close persons of patients with renal disease has identified two main areas of impact. Firstly, both haemodialysis and peritoneal dialysis may have a disruptive influence on family members’ social lives [16] and the structure of the week may be geared towards dialysis sessions. Secondly, some patients become frail and lose functional independence, leaving family members to provide greater physical support. Family members may have health and social care needs of their own that need to be addressed [16,17]. Qyinan [18] reported that close persons commonly felt overwhelmed and stressed, although this review was limited to an evidence base of four articles and considered home dialysis only. Campbell [19] used findings from the general carer literature to illustrate demands of ageing partners with ESKD. In other chronic illnesses such as stroke [20] or in palliative care for cancer and mental health [21], interventions aimed at providing family members with training to support patients with their rehabilitation, or to address unmet needs as a result of the patient's illness, have been developed and evaluated. Results have been mixed. In the case of stroke, carers in the intervention group experienced less depression and anxiety and better quality of life [20], whilst in the palliative care study, no statistically significant differences were found between the intervention and control group on carers’ psychological outcomes [21]. However, before such interventions can be developed in ESKD, it is important to understand better the emotional and physical needs of close persons. This review aims to identify all studies involving close persons caring for ESKD patients, to describe the main findings and critique the methodology. Specific attention has been paid to (a) studies exploring the impact of ESKD on close persons, in particular for those close persons where the patients are either withdrawing from dialysis or being provided with end of life care and (b) studies looking at the provision of health care for close persons. A literature search for relevant articles was conducted in five databases: Medline (1950–2006), Embase (1991–2006), CINAHL (1982–2006), PsycINFO (1970–2006) and AMED (1985–2006), employing the following key words: carers, caregivers, end-stage kidney disease, end-stage renal disease, haemodialysis, peritoneal dialysis and renal replacement therapy. These keywords were used both in word search options and exploded as thesaurus terms to obtain the maximum number of articles. The abstracts for each article were read to check for inclusion into the main review, using the following criteria: Published in peer-reviewed journals. Research studies with an introduction, a methodology and results section and a conclusion. Involve close persons, defined as either a family member or the person identified by the patient as an informal carer. By an informal carer, we mean a person who provides the majority of a patient's physical and emotional care needs and who is neither a volunteer nor in the employment of statutory services. Use a sample of close persons caring for adult ESKD patients (over 18 years). Non-English language articles were considered if the English translation of the abstract met the above criteria. Using these criteria, 334 articles were identified from the five databases (139 in Medline, 121 in Embase, 80 in CINAHL, 8 in AMED and 34 in PsycINFO). J.L. went through the abstracts of each of the 382 articles, of which 37 initially met the inclusion criteria. One was later excluded on closer inspection, as it was specifically a validation study of a fatigue severity scale. Of the remaining 36 studies, 16 exclusively looked at family members, 12 specifically at the patient-family dyad and 3 at the family-health professional dyad. Whilst the latter two types of studies did not concentrate solely on family concerns, we decided to include them in the analysis, because these findings further contribute to the limited number of studies in this field. Thirty-six studies were included in the review. Both J.L. and G.S. first went through the remaining 36 studies independently and extracted the following information for each study: the number of carers in the study sample, the RRT population they were caring for, authors’ definition of a carer, demographic details of the sample, patients’ dialysis history, caring history, study design, outcome measures used and main findings. J.L. and G.S. then met together to discuss these findings and obtain an initial consensus before meeting with A.B. and L.J. to obtain a final consensus. We undertook an exploration of the aims of these studies, their study design, the sample of participants and the outcome measures highlighted in the quantitative studies. The three main themes explored were (a) the impact of caring for a patient with ESKD on dialysis on close persons, in particular quality of life, psychological morbidity, close person responsibilities—which authors often referred to as ‘burden’ or ‘carer burden’—and their life situation; (b) the coping strategies employed by these close persons and (c) factors that influence psychological morbidity. No studies of health provision for close persons of patients with ESKD were identified. Four studies looking at end of life issues explored the following themes for close persons: (a) their perceptions of patients’ terminal symptoms; (b) their reasons for why patients decided to stop dialysis; (c) the long-term impact of patient death following dialysis cessation and (d) their perceptions of advance directives. End of life care may be provided by the renal multi-disciplinary team alone, or it may involve referral for specialist palliative care advice. Such advice is likely to include symptom control, attention to spiritual and psychological issues for patients and, where possible, involvement of their families in decision-making. Whilst most studies were interested in the direct impact on close persons only, one triangulated close person data with patient data. The majority of studies reviewed used a cross-sectional design; there was only one longitudinal study. Whilst most were quantitative (24/36), there were some qualitative studies (11/36) and one used a mixed methods approach. The total sample was predominantly female, with mean ages ranging from 41 to 68 years (analysis possible in only 18 studies). Sample sizes also tended to be small, with a median sample of 55 participants for the quantitative and 15 participants for the qualitative studies. Most of the sample was recruited in studies where associated patients were undergoing haemodialysis or peritoneal dialysis. Three studies also involved kidney transplant patients. Only five studies looked at close persons dealing with end of life issues or with patients withdrawing from dialysis. Many studies did not focus on close persons in their potential role as ‘informal carers’. Thirteen studies actively sought close persons who also considered themselves to be informal carers, of which eight provided full definitions of what they meant by this term. All studies included spouses as part of their sample, of which eight specifically concentrated on this group alone. Adult children were included in seven of these studies and parents in five. A wide variety of outcome measures were used to rate health-related quality of life, anxiety, depression, coping strategies and patient disease severity. Some studies used standardized outcome measures; others used simple self-rated tools. The most commonly used standardized measures were the Zarit Burden Interview [22] to evaluate the sense of carer responsibility (3/8), the Beck Depression Scale [23] to evaluate depression (2/5), SF-36 [24] to evaluate health-related quality of life (3/8), Jalowiec Coping Scale [25] to evaluate close persons’ use of coping strategies (3/3) and End-Stage Renal Disease Severity Index [26] to evaluate patients’ disease severity (2/4). A breakdown of the country of origin for each study showed that over half originated from either the USA (11/36) or Canada (7/36), with five originating from Australia and only seven from the European Union, of which only one was conducted in the UK. The remaining six studies came from the following countries: Japan (2/36), Brazil (2/36), China (1/36) and Turkey (1/36). The 36 studies have shown mixed results. They have mainly explored the following areas associated with caring for an ESKD patient: the impact on close persons and their social life and the factors affecting close persons’ psychological health. There have been very few studies looking at palliative care issues and these have primarily concentrated on dealing with end of life issues rather than the provision of supportive care in the pre-terminal phase. In only one study, close persons rated their quality of life as excellent and reported few pressures resulting from their carer responsibilities [27], whilst in all others, ESKD and dialysis were shown to increase the close person's sense of responsibility and lead to a poorer quality of life when compared with age-matched controls [28]. Close persons found living with an ESKD patient on dialysis stressful [29] and experienced increased fatigue [30]. The dominating effect of caring for an ESKD patient often led close persons to neglect their own health. For those who took time to have a break from their carer responsibilities, there were health benefits [31]. Other issues that close persons reported included isolation through the loss of social activity [30–36], life restrictions [36–38], increased workload, negative economic consequences [39,40], changed relationship with the patient [30,34] and sexual problems for spouses [41]. Impact on family life (quantitative and mixed methods studies) CAPD = Continuous Ambulatory Peritoneal Dialysis; CBI = Caregivers Burden Interview; FES = Family Environment Scale; HD = Haemodialysis; IIRS = Illness Intrusiveness Ratings Scale; MAES = Marital Attitudes Evaluation Scale; NGQ = Norris & Groves Questionnaire; PAF = Physicians’ Assessment Form; PAIS = Psychosocial Adjustment to Illness Scale; SF-36 = Short-Form 36; SwQoL = Swedish Health-Related Quality of Life Survey; VAS = Visual Analogue Scale; ZBI = Zarit Burden Interview. Impact on family life (quantitative and mixed methods studies) CAPD = Continuous Ambulatory Peritoneal Dialysis; CBI = Caregivers Burden Interview; FES = Family Environment Scale; HD = Haemodialysis; IIRS = Illness Intrusiveness Ratings Scale; MAES = Marital Attitudes Evaluation Scale; NGQ = Norris & Groves Questionnaire; PAF = Physicians’ Assessment Form; PAIS = Psychosocial Adjustment to Illness Scale; SF-36 = Short-Form 36; SwQoL = Swedish Health-Related Quality of Life Survey; VAS = Visual Analogue Scale; ZBI = Zarit Burden Interview. Impact on family life (qualitative studies) CAPD = continuous ambulatory peritoneal dialysis; HD = haemodialysis; PD = peritoneal dialysis. Impact on family life (qualitative studies) CAPD = continuous ambulatory peritoneal dialysis; HD = haemodialysis; PD = peritoneal dialysis. The treatment modality may also have an impact on family members. Studies have highlighted that spouses of transplant patients were more assertive, self-sufficient and able to handle the physical, social and existential aspects of the illness better than dialysis spouses [33,42]. Despite these pressures, close persons recognized that they play a positive role in promoting patients’ well-being [11,43]. They recognized that health care professionals were important in providing support to discuss their problems [39] and would like to have more information about the care being provided to patients [44]. However, they also reported poor communication with professionals, felt that their needs were not always addressed [30,39,45] and felt themselves uneducated and poorly equipped to deal with the regimented lifestyle associated with the dialysis regimen [14]. Whilst some studies have shown that close persons display few signs of psychological distress [40,46–49], others have identified the following: Caring and psychological health ABS = Affect Balance Scale; BDI = Beck Depression Inventory; BI = Barthel Index; CAPD = Continuous Ambulatory Peritoneal Dialysis; CAS = Clinical Anxiety Scale; CBI = Caregivers Burden Interview; CBS = Caregiver Burden Scale; CES-D = Center for Epidemiologic Studies Depression Scale; CID = Cognitive Index of Depression; DAS = Adjustment Scale; = = Anxiety and Scale; = Questionnaire; = Depression Questionnaire; = Questionnaire; = End-Stage Renal Disease Severity Index; = End-Stage Renal Disease Severity = Family Questionnaire; = Scale; = = Index; HD = haemodialysis; = Scale; = Impact on Family Scale; = Jalowiec Coping Scale; = Scale; = of control of = Marital Adjustment = Marital Questionnaire; = Scale of = Psychosocial Adjustment to Illness PD = peritoneal dialysis; = Scale; = for and Family Scale; = Quality of Life Index; = Scale; = Inventory; SF-36 = Short-Form 36; = = Anxiety Inventory; = with Life Scale; = ZBI = Zarit Burden Interview. Caring and psychological health ABS = Affect Balance Scale; BDI = Beck Depression Inventory; BI = Barthel Index; CAPD = Continuous Ambulatory Peritoneal Dialysis; CAS = Clinical Anxiety Scale; CBI = Caregivers Burden Interview; CBS = Caregiver Burden Scale; CES-D = Center for Epidemiologic Studies Depression Scale; CID = Cognitive Index of Depression; DAS = Adjustment Scale; = = Anxiety and Scale; = Questionnaire; = Depression Questionnaire; = Questionnaire; = End-Stage Renal Disease Severity Index; = End-Stage Renal Disease Severity = Family Questionnaire; = Scale; = = Index; HD = haemodialysis; = Scale; = Impact on Family Scale; = Jalowiec Coping Scale; = Scale; = of control of = Marital Adjustment = Marital Questionnaire; = Scale of = Psychosocial Adjustment to Illness PD = peritoneal dialysis; = Scale; = for and Family Scale; = Quality of Life Index; = Scale; = Inventory; SF-36 = Short-Form 36; = = Anxiety Inventory; = with Life Scale; = ZBI = Zarit Burden Interview. A negative between close persons’ psychological health and their sense of carer responsibility their use of coping strategies strategies that the symptoms of the of the the close person's age and the social and changes as a result of ESKD A positive between good mental health and the following a of of dialysis the of dialysis patients are on of social support and sense of carer responsibility The sense of carer responsibilities are if patients are in of living have less or comorbidity This was further in studies in patients home haemodialysis or transplant where close persons not anxiety or depression felt less by their carer responsibility and a quality of life to the age-matched population were found between levels of responsibility and other outcomes such as quality of life and The use of coping was found to have a negative with a positive with the number of years on dialysis Close persons were more likely to have negative towards patients if they no of the dialysis and a high of involvement with the caring whilst living in a We identified five studies that explored end of life only one specifically on close persons. This study the long-term impact of death on families when dialysis was found that most families felt that patients a good death as at and with close people and most family members showed only levels of However, carers and those with levels of caring responsibility for the did End of life care HD = End of life care HD = The remaining four studies on patient outcomes such as reasons for withdrawing from dialysis the quality of death the of close persons in ESKD patients’ to and care and use of advance as a in advance by patients, which the of treatment to be by health care a patient is to provide to that person's of These studies found that close persons that whilst most patients a many patients were to be in and from fatigue care family members in that patients’ were and most recognized the of living which they felt were health care professional Close persons were poorly for caring for a dialysis and patients did not to be a on their families [14]. They were also poor at both patients’ and for or dialysis No studies were identified for carers of patients with supportive care those on maximum conservative management The main of most studies included in this review is the of and of the demographic over half of the studies demographic details of close persons’ ages and or details of their relationship to patients of other relevant demographic such as employment status or social is and only seven studies the time that close persons as Whilst all studies the of dialysis half reported the of time a patient has been on with very few patients’ functional although carer studies in other that this has an impact on carers’ quality of life In only 18 9 qualitative and mixed methods study details of their sample of the quantitative studies included in the used cross-sectional and were predominantly Such studies are in exploring between are limited as they not to be only five studies provide the full details of sample it is therefore not possible to rates or the sample The sample sizes were with a median of 55 and details of were reported in only one study. the of the used to the different outcomes it to between the different studies. We identified that most studies poor of their methods and a of of their data Most used of family members with five studies using only one details of their studies with their studies with their one a of their their approach. One study no details of their the studies were poorly that the was and authors were as to to use qualitative data with the and of the qualitative data demographic of data and poor use of supporting This study reviewed the literature exploring the of close persons of patients with ESKD, from which can be the quality of and for the of in this Firstly, studies exploring end of life issues are with only four identified. these four studies are they that health are the time for informal carers to discuss patients’ about end of life care and, long-term distress of close persons resulting from the patients’ However, about such end of life issues close persons, and we studies in this Secondly, definitions of close persons were there were some differences identified between the different groups. the literature the that most close persons are to patients, the in to patients who were and those with family and relationship were not not all close persons to on the role of the informal carer, and the of this role can be a as illness review did not identify differences between informal carers and family carers in the outcome measures used included both the of differences may in their with ‘informal carers’ a more members’ may be as being more this needs further issues that need to be addressed the use of methodology were identified in the Most quantitative studies were and with no intervention studies being identified. Studies of demographic details and rates and all were cross-sectional with sample sizes that used standardized Whilst the use of standardized measures the of the the findings from cross-sectional studies are limited in that they can only between We the use of longitudinal methods in that would that between key be explored in more This would also into the long-term of close persons. In those studies using qualitative most used with poor and of demographic and social and Many authors used the ‘burden’ or ‘carer such terms may influence of the relationship between close person and was not they were by close persons to use the ‘burden’ or it was a by the authors to describe the responsibilities of Such and the of study findings the half of the studies originated from either the USA (11/36) or Canada This it to the results of these studies their to in the of health care provision in other there is evidence that the psychological health of close persons them to to care which in can the mental health of patients, we to identify studies in review that looked specifically at health close persons of patients with ESKD. review has identified in the literature that need to be is therefore to the relationship between health and close persons in to We would like to acknowledge for this review and for support in this of

Clinical Kidney Journal · editorial or comment · 83 citationsread the source →

Understanding nutrition, depression and mental illnesses

INTRODUCTION Few people are aware of the connection between nutrition and depression while they easily understand the connection between nutritional deficiencies and physical illness. Depression is more typically thought of as strictly biochemical-based or emotionally-rooted. On the contrary, nutrition can play a key role in the onset as well as severity and duration of depression. Many of the easily noticeable food patterns that precede depression are the same as those that occur during depression. These may include poor appetite, skipping meals, and a dominant desire for sweet foods.[1] Nutritional neuroscience is an emerging discipline shedding light on the fact that nutritional factors are intertwined with human cognition, behavior, and emotions. The most common mental disorders that are currently prevalent in numerous countries are depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder (OCD).[2] The dietary intake pattern of the general population in many Asian and American countries reflects that they are often deficient in many nutrients, especially essential vitamins, minerals, and omega-3 fatty acids.[3] A notable feature of the diets of patients suffering from mental disorders is the severity of deficiency in these nutrients.[3] Studies have indicated that daily supplements of vital nutrients are often effective in reducing patients' symptoms.[4] Supplements containing amino acids have also been found to reduce symptoms, as they are converted to neurotransmitters which in turn alleviate depression and other mental health problems.[4] On the basis of accumulating scientific evidence, an effective therapeutic intervention is emerging, namely nutritional supplement/treatment. These may be appropriate for controlling and to some extent, preventing depression, bipolar disorder, schizophrenia, eating disorders and anxiety disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), autism, and addiction.[4] Most prescription drugs, including the common antidepressants lead to side effects.[4] This usually causes the patients to skip taking their medications. Such noncompliance is a common occurrence encountered by psychiatrists. An important point to remember here is that, such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. In some cases, chronic use or higher doses may lead to drug toxicity, which may become life threatening to the patient.[4] An alternate and effective way for psychiatrists to overcome this noncompliance is to familiarize themselves about alternative or complementary nutritional therapies. Although further research needs to be carried out to determine the best recommended doses of most nutritional supplements in the cases of certain nutrients, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained by closely observing the changes in the patient.[4] When we take a close look at the diet of depressed people, an interesting observation is that their nutrition is far from adequate. They make poor food choices and selecting foods that might actually contribute to depression. Recent evidence suggests a link between low levels of serotonin and suicide.[5] It is implicated that lower levels of this neurotransmitter can, in part, lead to an overall insensitivity to future consequences, triggering risky, impulsive and aggressive behaviors which may culminate in suicide, the ultimate act of inwardly directed impulsive aggression. Depression is a disorder associated with major symptoms such as increased sadness and anxiety, loss of appetite, depressed mood, and a loss of interest in pleasurable activities. If there is no timely therapeutic intervention, this disorder can lead to varied consequences. Patients who are suffering from depression exhibit suicidal tendency to a larger degree and hence are usually treated with antidepressants and/or psychotherapy.[6] Deficiencies in neurotransmitters such as serotonin, dopamine, noradrenaline, and γ-aminobutyric acid (GABA) are often associated with depression.[6–11] As reported in several studies, the amino acids tryptophan, tyrosine, phenylalanine, and methionine are often helpful in treating many mood disorders including depression.[12–17] When consumed alone on an empty stomach, tryptophan, a precursor of serotonin, is usually converted to serotonin. Hence, tryptophan can induce sleep and tranquility. This implies restoring serotonin levels lead to diminished depression precipitated by serotonin deficiencies.[8] Tyrosine and sometimes its precursor phenylalanine are converted into dopamine and norepinephrine.[18] Dietary supplements containing phenyl alanine and/or tyrosine cause alertness and arousal. Methionine combines with adenosine triphosphate (ATP) to produce S-adenosylmethionine (SAM), which facilitates the production of neurotransmitters in the brain.[19–22] The need of the present paradigm is, more studies shedding light on the daily supplemental doses of these neurochemicals that should be consumed to achieve antidepressant effects. Researchers attribute the decline in the consumption of omega-3 fatty acids from fish and other sources in most populations to an increasing trend in the incidence of major depression.[23] The two omega-3 fatty acids, eicosapentaenoic acid (EPA) which the body converts into docosahexanoic acid (DHA), found in fish oil, have been found to elicit antidepressant effects in human. Many of the proposed mechanisms of this conversion involve neurotransmitters. For instance, antidepressant effects may be due to bioconversion of EPA to leukotrienes, prostaglandins, and other chemicals required by the brain. Others hypothesize that both EPA and DHA influence neuronal signal transduction by activating peroxisomal proliferator-activated receptors (PPARs), inhibiting G-proteins and protein kinase C, in addition to calcium, sodium, and potassium ion channels. Whichever may be the case, epidemiological data and clinical studies have clearly shown that omega-3 fatty acids can effectively treat depression.[24] In depressed patients, daily consumption of dietary supplements of omega-3 fatty acid that contain 1.5-2 g of EPA has been shown to stimulate mood elevation. Nevertheless, doses of omega-3 higher than 3 g do not show better effects than placebos and may be contraindicative in cases, such as those taking anticlotting drugs.[25] In addition to omega–3 fatty acids, vitamin B (e.g., folate) and magnesium deficiencies have been linked to depression.[26–28] Randomized, controlled trials that involve folate and vitamin B12 suggest that patients treated with 0.8 mg of folic acid/day or 0.4 mg of vitamin B12/day will exhibit decreased depression symptoms.[27] In addition, the results of several case studies where patients were treated with 125-300 mg of magnesium (as glycinate or taurinate) with each meal and at bedtime led to rapid recovery from major depression in < 7 days for most of the patients. Previous research has revealed the link between nutritional deficiencies and some mental disorders.[232529–32] The most common nutritional deficiencies seen in patients with mental disorders are of omega–3 fatty acids, B vitamins, minerals, and amino acids that are precursors to neurotransmitters.[20232427283033] Accumulating evidence from demographic studies indicates a link between high fish consumption and low incidence of mental disorders; this lower incidence rate being the direct result of omega–3 fatty acid intake.[233132] One to two grams of omega-3 fatty acids taken daily is the generally accepted dose for healthy individuals, but for patients with mental disorders, up to 9.6 g has been shown to be safe and effective.[34–36] Majority of Asian diets are usually also lacking in fruits and vegetables, which further lead to mineral and vitamin deficiencies. The significance of various nutrients in mental health, with special relevance to depression has been discussed below. CARBOHYDRATES Carbohydrates are naturally occurring polysaccharides and play an important role in structure and function of an organism. In higher organisms (human), they have been found to affect mood and behavior. Eating a meal which is rich in carbohydrates triggers the release of insulin in the body. Insulin helps let blood sugar into cells where it can be used for energy and simultaneously it triggers the entry of tryptophan to brain. Tryptophan in the brain affects the neurotransmitters levels. Consumption of diets low in carbohydrate tends to precipitate depression, since the production of brain chemicals serotonin and tryptophan that promote the feeling of well being, is triggered by carbohydrate rich foods. It is suggested that low glycemic index (GI) foods such as some fruits and vegetables, whole grains, pasta, etc. are more likely to provide a moderate but lasting effect on brain chemistry, mood, and energy level than the high GI foods - primarily sweets - that tend to provide immediate but temporary relief. PROTEINS Proteins are made up of amino acids and are important building blocks of life. As many as 12 amino acids are manufactured in the body itself and remaining 8 (essential amino acids) have to be supplied through diet. A high quality protein diet contains all essential amino acids. Foods rich in high quality protein include meats, milk and other dairy products, and eggs. Plant proteins such as beans, peas, and grains may be low in one or two essential amino acids. Protein intake and in turn the individual amino acids can affect the brain functioning and mental health. Many of the neurotransmitters in the brain are made from amino acids. The neurotransmitter dopamine is made from the amino acid tyrosine and the neurotransmitter serotonin is made from the tryptophan.[5] If there is a lack of any of these two amino acids, there will not be enough synthesis of the respective neurotransmitters, which is associated with low mood and aggression in the patients. The excessive buildup of amino acids may also lead to brain damage and mental retardation. For example, excessive buildup of phenylalanine in the individuals with disease called phenylketonuria can cause brain damage and mental retardation. ESSENTIAL FATTY ACIDS Omega-3 fatty acids The brain is one of the organs with the highest level of lipids (fats). Brain lipids, composed of fatty acids, are structural constituents of membranes. It has been estimated that gray matter contains 50% fatty acids that are polyunsaturated in nature (about 33% belong to the omega-3 family), and hence are supplied through diet. In one of the first experimental demonstrations of the effect of dietary substances (nutrients) on the structure and function of the brain, the omega-3 fatty acids (specially alpha-linolenic acid, ALA) were the member to take part. An important trend has been observed from the findings of some recent studies that lowering plasma cholesterol by diet and medications increases depression. Among the significant factors involved are the quantity and ratio of omega-6 and omega-3 polyunsaturated fatty acids (PUFA) that affect serum lipids and alter the biochemical and biophysical properties of cell membranes. It has been hypothesized that sufficient long chain PUFAs, especially DHA, may decrease the development of depression.[37] The structural and functional components of membrane in cells of brain which is a lipid-rich organ, include polar phospholipids, spingolipids, and cholesterol. The glycerophospholipids in brain consist of high proportion of PUFA derived from the essential fatty acids (EFAs), linoleic acid and α-linolenic acid. The main PUFA in the brain are DHA, derived from the omega-3 fatty acid α-linolenic acid, arachidonic acid (AA) and docosa tetraenoic acid, both derived from omega-6 fatty acid linoleic acid. Experimental studies have revealed that diets lacking omega-3 PUFA lead to considerable disturbance in neural function.[38] Studies by Marszalek and Lodish indicate that despite their abundance in the nervous system, DHA and AA cannot be synthesized by mammals de novo and hence they or their precursors have to be supplied through the diet and transported to the brain. During late gestation and the early postnatal period, neurodevelopment occurs at significantly rapid rates which make the supply of adequate quantity of PUFAs, particularly DHA, imperative to ensure neurite outgrowth in addition to appropriate development of brain and retina.[39] Bruinsma and Taren of University of Arizona College of Public Health, Tucson, USA explored the involvement of dieting-related psychological factors as potential confounders.[40] They discussed studies that have both supported and contested the proposition that lowering plasma cholesterol by diet and medications contributes to depression. Research findings point out that an imbalance in the ratio of the EFAs, namely the omega-6 and omega-3 fatty acids, and/or a deficiency in omega-3 fatty acids, may be responsible for the heightened depressive symptoms associated with low plasma cholesterol. These relationships may explain the inconsistency in the results of trials on cholesterol-lowering interventions and depression. On similar lines, dieting behaviors have been associated with alterations in moods.[41] Dietary omega-3 fatty acids play a role in the prevention of some disorders including depression. Their deficiency can accelerate cerebral aging by preventing the renewal of membranes. However, the respective roles of the vascular component on one hand (where the omega-3s are active) and the cerebral parenchyma itself on the other, have not yet been clearly resolved. The role of omega–3 in certain diseases such as dyslexia and autism is suggested. It was omega–3 fatty acids that participated in the first coherent experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out on x-vivo cultured brain cells (1), then on in vivo brain cells (2), finally on physicochemical, biochemical, physiological, neurosensory, and behavioral parameters (3). These findings indicated that the nature of polyunsaturated fatty acids (in particular omega–3) present in formula milks for infants (both premature and term) determines the visual, cerebral, and intellectual abilities.[16] VITAMINS B-complex vitamins Nutrition and depression are intricately and undeniably linked, as suggested by the mounting evidence by researchers in neuropsychiatry. According to a study reported in Neuropsychobiology,[42] supplementation of nine vitamins, 10 times in excess of normal recommended dietary allowance (RDA) for 1 year improved mood in both men and women. The interesting part was that these changes in mood after a year occurred even though the blood status of nine vitamins reached a plateau after 3 months. This mood improvement was particularly associated with improved vitamin B2 and B6 status. In women, baseline vitamin B1 status was linked with poor mood and an improvement in the same after 3 months was associated with improved mood. Thiamine is known to modulate cognitive performance particularly in the geriatric population.[43] Vitamin B12 (Cynocobalamin) Clinical trials have indicated that Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), if it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin enhances cerebral and cognitive functions in the elderly; it frequently promotes the functioning of factors related to the frontal lobe, in addition to the language function of people with cognitive disorders. Adolescents who have a borderline level of vitamin B12 deficiency develop signs of cognitive changes.[43] Folate It has been observed that patients with depression have blood folate levels, which are, on an average, 25% lower than healthy controls.[44] Low levels of folate have also been identified as a strong predisposing factor of poor outcome with antidepressant therapy. A controlled study has been reported to have shown that 500 mcg of folic acid enhanced the effectiveness of antidepressant medication.[45] Folate's critical role in brain metabolic pathways has been well recognized by various researchers who have noted that depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency.[46] It is not clear yet whether poor nutrition, as a symptom of depression, causes folate deficiency or primary folate deficiency produces depression and its symptoms. MINERALS Calcium A recent study showed that selective serotonin uptake inhibitors (SSRIs) inhibit absorption of calcium into bones. In addition to this, the SSRIs can also lower blood pressure in people, resulting in falls which may lead to broken bones. Indiscriminate prescription of SSRIs by doctors and ingestion by patients at risk of depression or other mental health problems may put them at increased risk of fractures. Compounded by the fact that they may be aging and already taking other medications, may also predispose them to osteoporosis.[47] Chromium Many studies on the association of chromium in humans depression have been recorded[4849] which indicate the significance of this micronutrient in mental health. Iodine Iodine plays an important role in mental health. The iodine provided by the thyroid hormone ensures the energy metabolism of the cerebral cells. During pregnancy, the dietary reduction of iodine induces severe cerebral dysfunction, eventually leading to cretinism. Iron Iron is necessary for oxygenation and to produce energy in the cerebral parenchyma (through cytochrome oxidase), and for the synthesis of neurotransmitters and myelin. Iron deficiency is found in children with attention-deficit/hyperactivity Iron in the are critical during the development of the and in with the in the with its associated deficiency is associated with disturbance in the development of cognitive Research findings out that as many as men are This in and more with of more depression than during other times in their These indicate the of in the of depression since its deficiency is known to cause and depression. Iron deficiency is for instance, with depression, and rapid a was first and by in while an of the mineral The role of has been well known in a into its its for bipolar disorder with and The therapeutic use of also its as an in depression, disorder, disorder, eating disorders, and in certain of adequate has to be taken while the mood in the can be used in patients with and The use of during and in and geriatric population needs observation about its In a of the of identified at studies, which indicate that low intake is associated with mood studies with with other populations that mood and in the of studies have shown that levels are lower in those with clinical intervention research that can influence the effectiveness of antidepressant also the brain cells the potential damage by studies have revealed the potential of the for physical development and mental development may be due to deficiency of When children and with poor nutritional status are to alterations of mental and behavioral they can be by dietary but to certain It has been observed that, of diet and meal pattern can have or immediate or effects. Dietary deficiencies of and nutrients vitamins, and such as during aging may precipitate brain which may be due to for of diet and depression which is a of to a factor that is often linked to increased and premature of aging may play an important role in this, by reducing food intake or reducing food intake in to such factors as in and poor use of prescription drugs, and and occurring in the in both and due to to They suggest changes associated with mental disorders such as dementia and depression, and and as to the of depression, people are the alternative and complementary are by the for and as a of and health and that are not currently to be a part of health need to be aware that it is likely that a of their patients with bipolar disorder might use these interventions to be and safe or to research in and brain indicates the of pathways that can provide a of the association between nutritional nervous system, and function an psychological health status. These findings may lead to of the therapeutic of dietary intervention health and health depression and other psychological disorders.

Indian Journal of Psychiatry · editorial or comment · 409 citationsread the source →

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.

World Psychiatry · editorial or comment · 607 citationsread the source →

The effectiveness of web-based programs on the reduction of childhood obesity in school-aged children: A systematic review.

Review objective: The objective of this review is to synthesise the best available evidence on the effectiveness of web-based programs on the reduction of childhood obesity in school age children. Background: Childhood obesity is one of the most serious public health challenges of the 21st century. The problem is global and is steadily affecting many low- and middle-income countries, particularly in urban settings.[1] The prevalence has increased at an alarming rate globally.[2] The International Association for the Study of Obesity; estimates that up to 200 million school aged children are either overweight or obese, of those 40-50 million are classified as obese. Obesity has negative health impact in childhood, as well as in the long term. Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health. Body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity. It is defined as a person's weight in kilograms divided by the square of his/her height in meters (kg/m). The World Health Organization defines overweight as BMI greater than or equal to 25 and BMI greater than or equal to 30 as obesity. Children two years of age or older with a BMI between the 85 and 94 percentile on age-growth charts are considered overweight; children with a BMI greater than the 95 percentile are considered obese. BMI provides the most useful population-level measure of overweight and obesity as it is the same for both sexes and for all ages worldwide. Measures of central obesity such as the waist:hip ratio and waist circumference can provide more robust indices of overall obesity-related health risk than BMI alone. A BMI z-score is a quantitative measure of the deviation of a specific BMI percentile from the mean of that population. A positive z-score indicates a child is heavier than the mean and a negative z-score indicates a child is lighter than the mean. Thus, a z-score compares the BMI of a given child to the BMI distribution for a population of children of the same age and sex. The incidence of obesity has more than doubled since 1980. Overweight and obesity now ranks as the fifth leading global risk for mortality. Sixty-five percent of the world's population lives in countries where childhood overweight and obesity kills more people than being underweight. In addition, 44% of the diabetes burden, 23% of the ischemic heart disease burden, and between 7% and 41% of certain cancer burdens are attributable to overweight and obesity. Childhood obesity continues to be a significant health problem in the United States. There has been a rapid rise in obesity among the school-age population despite efforts made by Healthy People 2010 in promoting weight management and physical activity. These on-going efforts have been extended to be part of the goals for Healthy People 2020. The United States Centers for Disease Control and Prevention calculated that approximately 17% children between the ages of two to nineteen years of age were at or above the 97 percentile for being obese. These figures are more than three times the anticipated 5% set in the Healthy People 2010 report. Overweight and obese children are likely to stay obese into adulthood and are more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age. In addition to a higher risk of obesity and non-communicable diseases later in life, affected children experience adverse outcomes such as breathing difficulties, increased risk of fractures, hypertension, and early markers of cardiovascular disease, different forms of cancers, insulin resistance, and psychological effects. Childhood obesity is associated with a higher chance of obesity, premature death, and disability in adulthood. If a child is overweight before eight years of age, obesity in adulthood is likely to be more severe. Child and adolescent obesity is also associated with increased risk of emotional problems. Teens with weight problems tend to have much lower self-esteem and are less popular with their peers. Depression, anxiety, and obsessive compulsive disorder can also occur as a result of childhood obesity. In addition to the diseases associated with obesity, the economic consequences of obesity are enormous for families, health care systems, and the global economy. Direct medical costs include preventative, diagnostic, and treatment services related to overweight and associated co-morbidities. European nations spend 2-8% of their health care budgets on obesity, equating to 0.6% of their gross domestic product. In the United States, estimates based on 2008 data indicated that overweight and obesity account for $147 billion in total medical expenditure. This shows an increase from the $117 billion spent in the year 2000.While indirect costs of overweight and obesity on society can be significantly higher, they are often overlooked. These costs stem from childhood obesity continuing on to obesity in adulthood, which can then results in income lost from decreased productivity, reduced opportunities and restricted activity, illness, absenteeism, and premature death. In addition, there are high costs associated with the numerous infrastructure changes that societies must make to cope with obese people such as reinforced beds, operating tables and wheel chairs; enlarged turnstiles and seats in in public gathering spaces; and modifications to transportation safety standards. Obesity is reaching pandemic proportions across much of the world, and its consequences are set to impose unparalleled health, financial and social burdens on global society unless effective actions are taken to reverse the trend. Reducing the incidence of obesity in childhood can help children grow into adults with normal body weights and the tools necessary to sustain a health weight. Haerens, et al. explains the importance of school-based programs in dealing with the serious problem of childhood obesity and overweight. The school setting is known as having a powerful influence on student's eating and physical activities. Programs that may have a more positive impact are those that help increase physical activity and promote healthy foods in youth. Previous studies looking at the implementation of diet and exercise programs in schools were effective in changing food habits and increasing physical activity; however, few of these studies showed a reduction in body weight. The Planet Health study, conducted over a period of two years, focused on healthy life style and showed a reduction in obesity in girls but not in boys. The M-span study, a two-year study involving proper diet, exercise, and parental support showed a reduction of BMI only in boys. Haerens, et al. further explains that the above mentioned studies needed to be done in a more personalised manner in order to achieve more positive result; however, they are limited by the time consumption and financial demands necessary to carry out the proposed intervention. Haerens, et al. conducted a two year study of the effect of a program including physical activity, healthy eating, and parental support with a computer-tailored component on BMI and BMI z-score in boys and girls. This intervention resulted in significant reduction in BMI in girls only. Carlson, et al. conducted a 12-month web-based weight loss intervention program which included physical activity and dietary behaviour. The program was found to be a potential low cost method to positively impact public health and health behaviours. Furthermore, 55% of the participants in the intervention group compared with 35% in the control group made an improvement in moderate-to-vigorous physical activity and diet. Doyle, et al. conducted an randomised controlled trial evaluating the effects of an Internet delivered program targeting weight loss on 80 overweight ethnically diverse 12-17 year olds. BMI z-scores were reduced in the intervention group compared with the usual care group post intervention and the intervention group maintained their reduction in BMI z-score at the four month follow up; however, statistical significance was not achieved at the four month follow up due to improvements in weight loss in the usual care group over time. The United States Department of Health and Human Services report of 2009 indicates that school aged children spend an average of 7 hours and 11 minutes per day watching television, using a computer, and playing video games. Using these technology devices as educational tools could have significant impact by increasing knowledge about healthy choices. Web-based technology has become part of our children's life in the last decade providing the foundation to a large number of daily activities. The use of web-based technology may be one method to provide a more personalised intervention to reduce obesity in school-aged children. The search for previously conducted systematic reviews on the effectiveness of web based programs on obesity in children identified a systematic review conducted by An, et al., which included studies published between 1995 and April 2009. A critical appraisal of this systematic review determined it to be of reduced quality due to lack of transparency in reporting the details of the search strategy, inclusion and exclusion criteria, and assessment of the primary studies' methodological quality. The proposed systematic review will expand on the prior systematic review using the rigorous search strategy and assessment for methodological quality outlined below to identify the best available research to determine the effectiveness of web-based programs on childhood obesity. The current review will also seek to identify any more current research on the topic while expanding the inclusion criteria from the internet-based interventions included in An, et al. to other forms for web-based technologies, such as smart phones, that have become increasingly popular with this population. The use of the web for communication purposes came into existence in 1991, but it was not really until the mid to late 1990's that information professionals understood its usefulness and the magnitude of a medium that would have far-reaching positive consequences. This systematic review will include studies published from 1991 to the present date to identify all relevant studies on this topic.

JBI library of systematic reviews · 33 citationsread the source →

Positive Traits Linked to Less Pain through Lower Pain Catastrophizing.

The present study examined the association between positive traits, pain catastrophizing, and pain perceptions. We hypothesized that pain catastrophizing would mediate the relationship between positive traits and pain. First, participants (n = 114) completed the Trait Hope Scale, the Life Orientation Test- Revised, and the Pain Catastrophizing Scale. Participants then completed the experimental pain stimulus, a cold pressor task, by submerging their hand in a circulating water bath (0º Celsius) for as long as tolerable. Immediately following the task, participants completed the Short-Form McGill Pain Questionnaire (MPQ-SF). Pearson correlation found associations between hope and pain catastrophizing (r = -.41, p < .01) and MPQ-SF scores (r = -.20, p < .05). Optimism was significantly associated with pain catastrophizing (r = -.44, p < .01) and MPQ-SF scores (r = -.19, p < .05). Bootstrapping, a non-parametric resampling procedure, tested for mediation and supported our hypothesis that pain catastrophizing mediated the relationship between positive traits and MPQ-SF pain report. To our knowledge, this investigation is the first to establish that the protective link between positive traits and experimental pain operates through lower pain catastrophizing.

Personality and individual differences · 49 citationsread the source →

Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis.

Background: Social anxiety disorder-a chronic and naturally unremitting disease that causes substantial impairment-can be treated with pharmacological, psychological, and self-help interventions. We aimed to compare these interventions and to identify which are most effective for the acute treatment of social anxiety disorder in adults. Methods: We did a systematic review and network meta-analysis of interventions for adults with social anxiety disorder, identified from published and unpublished sources between 1988 and Sept 13, 2013. We analysed interventions by class and individually. Outcomes were validated measures of social anxiety, reported as standardised mean differences (SMDs) compared with a waitlist reference. This study is registered with PROSPERO, number CRD42012003146. Findings: We included 101 trials (13 164 participants) of 41 interventions or control conditions (17 classes) in the analyses. Classes of pharmacological interventions that had greater effects on outcomes compared with waitlist were monoamine oxidase inhibitors (SMD -1·01, 95% credible interval [CrI] -1·56 to -0·45), benzodiazepines (-0·96, -1·56 to -0·36), selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs; -0·91, -1·23 to -0·60), and anticonvulsants (-0·81, -1·36 to -0·28). Compared with waitlist, efficacious classes of psychological interventions were individual cognitive-behavioural therapy (CBT; SMD -1·19, 95% CrI -1·56 to -0·81), group CBT (-0·92, -1·33 to -0·51), exposure and social skills (-0·86, -1·42 to -0·29), self-help with support (-0·86, -1·36 to -0·36), self-help without support (-0·75, -1·25 to -0·26), and psychodynamic psychotherapy (-0·62, -0·93 to -0·31). Individual CBT compared with psychological placebo (SMD -0·56, 95% CrI -1·00 to -0·11), and SSRIs and SNRIs compared with pill placebo (-0·44, -0·67 to -0·22) were the only classes of interventions that had greater effects on outcomes than appropriate placebo. Individual CBT also had a greater effect than psychodynamic psychotherapy (SMD -0·56, 95% CrI -1·03 to -0·11) and interpersonal psychotherapy, mindfulness, and supportive therapy (-0·82, -1·41 to -0·24). Interpretation: Individual CBT (which other studies have shown to have a lower risk of side-effects than pharmacotherapy) is associated with large effect sizes. Thus, it should be regarded as the best intervention for the initial treatment of social anxiety disorder. For individuals who decline psychological intervention, SSRIs show the most consistent evidence of benefit. Funding: National Institute for Health and Care Excellence.

The lancet. Psychiatry · 328 citationsread the source →

Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer's disease mouse.

Polyphenols extracted from grape seeds are able to inhibit amyloid-beta (Abeta) aggregation, reduce Abeta production and protect against Abeta neurotoxicity in vitro. We aimed to investigate the therapeutic effects of a polyphenol-rich grape seed extract (GSE) in Alzheimer's disease (AD) mice. APP(Swe)/PS1dE9 transgenic mice were fed with normal AIN-93G diet (control diet), AIN-93G diet with 0.07% curcumin or diet with 2% GSE beginning at 3 months of age for 9 months. Total phenolic content of GSE was 592.5 mg/g dry weight, including gallic acid (49 mg/g), catechin (41 mg/g), epicatechin (66 mg/g) and proanthocyanidins (436.6 mg catechin equivalents/g). Long-term feeding of GSE diet was well tolerated without fatality, behavioural abnormality, changes in food consumption, body weight or liver function. The Abeta levels in the brain and serum of the mice fed with GSE were reduced by 33% and 44%, respectively, compared with the Alzheimer's mice fed with the control diet. Amyloid plaques and microgliosis in the brain of Alzheimer's mice fed with GSE were also reduced by 49% and 70%, respectively. Curcumin also significantly reduced brain Abeta burden and microglia activation. Conclusively, polyphenol-rich GSE prevents the Abeta deposition and attenuates the inflammation in the brain of a transgenic mouse model, and this thus is promising in delaying development of AD.

Neurotoxicity research · 143 citationsread the source →

Problematic Internet use: an overview

The “global village”, a metaphor used to describe how the Internet has shortened distances and facilitated the flow of information, has grown to over one billion users 1. Statistics from across the world highlight its reach and penetrance: 90% of South Korean households connect to high-speed, inexpensive broadband 2; Londoners spend an average of 45 days a year online, more than they spend watching TV 3; and the rate of increase in the number of Internet users in Africa and the Middle East exceeded 1,300% between 2000 and 2009 4. For the majority of Internet users, the World Wide Web represents a tremendous wellspring of opportunity that enhances well-being. For others, however, it can lead to a state that appears to meet the DSM definition of a mental disorder, described as a “clinically significant behavioral or psychological syndrome…that is associated with present distress… or with a significantly increased risk of suffering death, pain, disability, or an important loss of freedom” 5. Scientific understanding of that state has lagged behind media attention 6, in part because of inconsistency in defining the problem 7, disagreement about its very existence 8, and the variable research methodology used in studying it. Still, a body of data by scientists from the East and West (with the East increasingly leading the way) tells a cautionary tale about the Internet's potential to bring about psychological harm. In 1996, the psychologist K. Young became the first to publish a detailed case report of problematic Internet use 9. Her “patient zero” was a non-technologically oriented 43-year-old homemaker with a “content home life and no prior addiction or psychiatric history”, who, within three months of discovering chat rooms, was spending up to 60 hours per week online. She reported feeling excited in front of the computer, and depressed, anxious, and irritable when she would log off. She described having an addiction to the medium “like one would to alcohol”. Within one year of purchasing her home computer, she was ignoring household chores, had quit social activities she used to enjoy, and had become estranged from her two teenage daughters and her husband of 17 years. Based on this and other patients she interviewed, Young proposed the first set of diagnostic criteria for what she termed “Internet addiction”. She modeled them on the DSM-IV definition for substance dependence because of similarities she observed with the states of tolerance (needing more of the substance to achieve the same effect) and withdrawal (psychological and physical discomfort upon reducing or stopping the substance) 9. Others conceptualized problematic Internet use as a behavioral addiction not involving an intoxicant 10, and Young subsequently updated her definition, adapting the DSM-IV criteria for pathological gambling, an impulse control disorder often described as a behavioral addiction, into her Diagnostic Questionnaire 11 (Table 1). The questionnaire, which required at least five of the eight criteria be met for the Internet addiction diagnosis, has not received adequate psychometric testing. Shapira et al 12 proposed five years later a more inclusive diagnostic schema in the general style of the impulse control disorders. They argued that definitions based solely on substance dependence or pathological gambling were too narrow to capture the population of problematic Internet users and could lead to premature conclusions about the new disorder and the patients. They eschewed the “Internet addiction” label for lack of scientific proof for true addiction and favored the less controversial “problematic Internet use”, defining it as: a) maladaptive preoccupation with Internet use, experienced as irresistible use for periods of time longer than intended; b) significant distress or impairment resulting from the behavior; and c) the absence of other Axis I pathology that might explain the behavior, such as mania or hypomania. To date, only two studies have attempted to develop diagnostic criteria empirically by testing them against the diagnosis made on the basis of a systematic psychiatric interview. Ko et al 13 tested a set of criteria in 468 Taiwanese high school students. Starting with 13 candidate criteria, they eliminated those with low diagnostic accuracy, and determined that a cutoff of six out of the nine remaining criteria had the best diagnostic accuracy while maintaining high specificity (97.1%) and acceptable sensitivity (87.5%). The criterion for functional impairment was listed separately as criterion B and was required for the diagnosis (Table 2). In a second study, Ko et al 14 confirmed the diagnostic accuracy of their criteria in an older cohort of 216 Taiwanese college students. However, the relatively small size of both studies and the non-representative nature of the groups studied limit the applicability of the proposed criteria to the general population. Several assessment scales have been proposed to screen for, and help diagnose, problematic Internet use. As a group, these instruments show no consensus on the underlying dimensions that constitute the condition 6,15. In addition to Young's Diagnostic Questionnaire, two are in relatively common use in research and/or clinical settings: Young's Internet Addiction Test 16 and the Chen Internet Addiction Scale 17. Young's Internet Addiction Test 16 consists of 20 “how-often” questions, each rated on a scale of 1 to 5 (1=rarely; 2=occasionally; 3=frequently; 4=often; 5=always.) A score of 80 or above is consistent with problematic use (Table 3). The psychometric properties of the instrument were studied in 86 subjects 18. Six factors were extracted from the questionnaire: salience, excessive use, neglect of work, anticipation, lack of control, and neglect of social life. These factors showed good concurrent validity and internal consistency. Salience explained most of the variance and was also found to be the most reliable as indicated by its Cronbach's alpha. However, the selection bias introduced by online recruitment and the small size of the study limit its value. The Chen Internet Addiction Scale 17 is a self-report instrument composed of 26 items rated on a 4-point Likert scale (adapted in Table 4). It assesses five domains of Internet-related problems: compulsive use, withdrawal, tolerance, interpersonal and health consequences, and time management difficulties. Scores range from 26 to 104. In a study of 454 Taiwanese adolescents who completed the scale and received a structured diagnostic interview, a cutoff of 64 was shown to have high diagnostic accuracy and specificity (88% and 92.6%, respectively) 19. The internal reliability of the scale and subscales in the original study ranged from 0.79 to 0.93 17. Due to the lack of consensus on diagnostic criteria and the dearth of large epidemiological studies, the prevalence of problematic Internet use in the general population has not been established. Overall, prevalence surveys conducted in various countries fall into two main categories, online vs. offline studies, with the former typically yielding higher rates, most likely because of inherent selection bias 20. Only two epidemiological studies exploring the prevalence of problematic Internet use in the general population have been published. One was conducted in the US, the other in Norway 20,21. The US study used random-digit telephone dialing (cellular phone numbers were not included) to interview 2,513 adults taken from all 50 states in a manner proportional to the population in each state 20. More than half of the people reached agreed to be interviewed. Participants’ average age was 48, and 51% fell in the middle class socioeconomic stratum. 68.9% were regular Internet users. The authors’ diagnostic definition, based on published criteria and on similarities with impulse control disorders, substance dependence and obsessive-compulsive disorder, required: a) Internet use that interferes in personal relationships; b) preoccupation with the Internet when offline; c) unsuccessful attempts at quitting or cutting down; and d) staying online longer than intended. This definition yielded a point prevalence of 0.7%. Less stringent definitions yielded higher prevalence rates, and individual features consistent with problematic Internet use were endorsed by as many as 13.7% (respondents who found it hard to stay offline for days in a row). In the second study, Bakken et al 21 mailed Young's Diagnostic Questionnaire to 10,000 inhabitants of Norway, randomly selected from a database of the entire population. 3,399 completed questionnaires were returned (a somewhat lower response rate than the US study). Recipients of the mailed questionnaire also had the option of completing it online. Among respondents, 87% were Internet users. The prevalence of “addicted Internet use” (≥5 questions answered “yes”) was calculated to be 1%, whereas the prevalence of “at risk” Internet use (3–4 questions answered “yes”) was 5.2%. Multivariate analysis showed young age, male gender, higher educational achievement, and financial stress to be positively associated with “problematic Internet use” (defined by the authors to include both “Internet addicts” and “at risk” respondents). Prevalence rates among adolescents have been researched more extensively, perhaps because the so-called “digital natives” grew up incorporating the Internet in many aspects of life and as a result are perceived to be at higher risk. However, even when online-based surveys are excluded, the results can vary widely and are difficult to compare, due to differences in Internet access, recruitment methodology, the exact age bracket studied, and the definitions utilized. Considering only relatively large and offline studies, research from China 22, South Korea 23,24, Greece 25, Norway 26, and Iran 27 has yielded prevalence estimates ranging between 2% and 11%. Problematic Internet use has not been incorporated into large-scale epidemiological studies aimed at estimating the relative prevalence of mental disorders. Still, a review of published studies reveals that the presence of other psychiatric conditions in patients with problematic Internet use is the rule rather than the exception 6. The studies, however, were not designed or statistically powered to detect the nature of the association (cause, effect, or independent). In Bakken's general-population study 21, based on subjects’ self-report, 41.4% of Internet “addicts” reported feelings of depression in the 12-month period prior to the study, compared to 15.8% of non-problematic users. Sleep disturbances, anxious feelings, and alcohol and substance abuse were also more common (38.6% vs. 26.4%, 36.4% vs. 5%, and 13.6% vs. 1.1%, respectively). However, the questions used to assess co-occurring psychological impairment were not based on established criteria for mood, sleep, anxiety, or substance use disorders. Two US case series involved face-to-face interviews of adult patients with problematic Internet use. Black et al 28 assessed 21 subjects with the Diagnostic Interview Schedule and found the lifetime prevalence of mood disorders and major depression to be 33% and 15%, respectively. Further, 38% had a lifetime substance use disorder and 19% had a lifetime diagnosis of anxiety disorder. In a case series that included 20 patients, Shapira et al 29 found a very high (70%) lifetime prevalence for bipolar affective disorder, type I or II, compared with 15% for major depression. Fifty-five percent had a lifetime prevalence of substance abuse, and 45% met criteria for social anxiety disorder. Fifty percent of subjects had a lifetime diagnosis of an impulse control disorder. The authors highlight their observation that patients’ Internet-related symptoms were more impulsive and egosyntonic than compulsive and egodystonic, concluding that problematic Internet use resembles the DSM-IV definition of an impulse control disorder more closely than that of obsessive-compulsive disorder. Our clinical experience supports this conclusion. As a group, surveys conducted among high school and college students show similarly high comorbidity rates with mood and anxiety disorders, but a link between attention-deficit/hyperactivity disorder (ADHD) and problematic Internet use seems more obvious than among adults. One study in 752 South Korean elementary students found that 33% of those with ADHD also met criteria for problematic Internet use 30. Another study in 216 Taiwanese college students showed that 32% subjects with problematic Internet use also had ADHD compared to only 8% of regular Internet users 31. Whether Web-based activities appeal to the short attention span of ADHD sufferers or whether excessive Internet use may cause inattention remains to be elucidated. The clinical evaluation of the patient with problematic Internet use should include a careful assessment of the comorbid conditions frequently present. Those should then be treated according to established treatment guidelines. To the extent that the Internet-related problem may stem from another diagnosis (e.g., a patient with severe social anxiety who starts leading a “virtual” life at the expense of offline interactions), it might improve as the primary condition is addressed. Pharmacotherapeutic and psychotherapeutic interventions specific to problematic Internet use have not yet received adequate testing in large, rigorous studies. Pharmacotherapy often begins with selective serotonin reuptake inhibitors (SSRIs). However, while effective in treating obsessive-compulsive disorder, SSRIs have shown mixed results in impulse control disorders 32,33,34,35–36. In light of the greater similarity between problematic Internet use and impulse control disorders compared to obsessive-compulsive disorder 29, it is unclear whether SSRIs will ultimately prove beneficial, and no double-blind placebo-controlled studies have been published so far. One discontinuation study tested escitalopram, 20 mg/day, in 19 subjects with problematic Internet use 37. During the 10-week open-label phase, subjects showed significant decreases in weekly hours spent online (from a mean of 36.8 hours to 16.5 hours) and improvement in global functioning. At the end of the 10 weeks, subjects were blindly randomized to either continued escitalopram treatment or to placebo. Beyond that, they were followed for 9 weeks. No significant difference was seen between the two groups at the end of the second phase, as gains achieved at week 10 were maintained in both treatment groups. The authors speculate that nine weeks may have not been sufficient for the effect to be lost in the placebo group or for additional gains to be made in the escitalopram group, but do not rule out the possibility that the improvement seen in the open-label phase may have been a placebo response. One case study reported successful treatment with naltrexone 38, a drug that has shown benefit in other impulse control disorders 39,40. The patient was a 31 year old male with compulsive cybersexual behavior who had failed antidepressants, group and individual psychotherapy, Sexual Addicts Anonymous, and pastoral counseling. Naltrexone (150 mg/day), gradually added to a stable dose of sertraline which on its own had been ineffective in treating his problematic Internet use, helped induce a three-year remission. The authors hypothesize that, by blocking the capacity of endogenous opioids to trigger dopamine release in response to reward, naltrexone may block the reinforcing nature of compulsive Internet sexual activity. Another case study reported the successful use of an atypical antipsychotic, quetiapine, 200 mg/day, gradually added to citalopram, in a 23 year old subject with problematic Internet use 41. The improvement was maintained at four-month follow-up. More recently, a study tested methylphenidate in 62 children with ADHD who were Internet video game players 42. Participants’ average age was around 9. After 8 weeks of treatment (average dose 30.5 mg/day), Internet usage decreased significantly and correlated with reduction in ADHD symptoms. The authors cautiously suggest that methylphenidate might be beneficial as a treatment for problematic Internet use, especially when co-occurring with ADHD. Of the psychotherapy approaches used, cognitive behavioral therapy (CBT) has received the most empiric investigation. The largest study enrolled 114 adult subjects and employed CBT interventions including: keeping a daily log of Internet activity, teaching time management skills, and confronting cognitive distortions and rationalizations frequently used by patients to justify continued Internet usage, such as “just a few more minutes won't hurt” 43. Most subjects were able to control their symptoms by the eighth session, and improvement was sustained over a 6-month follow-up. For children and adolescents, family-based interventions that improve communication and teach family monitoring of Internet use can be helpful 44. However, the intensive (and typically very expensive) residential treatment options that have received much media attention have undergone little empiric investigation to warrant a strong recommendation 2,45. The same applies to online treatment websites that encourage the person with problematic Internet use to “click here if you are addicted to the Internet”. For a medium that has so radically changed the way we conduct our lives, the Internet's effects on our psychological health remain understudied. Simply stating that similar fears were raised when the radio, movies and early video games were introduced is not sufficient: the immersive and interactive qualities of the virtual world, and its sheer penetrance, make it potentially more serious. Also deserving of exploration are the more subtle psychological changes that occur in the virtual world, such as online disinhibition and increased risk-taking 46. Those changes are not necessarily evidence of “Internet addiction”, and may not be pathological, but, as important features of the new virtual psychology, should also be studied. As our field continues to debate whether their condition belongs in the next edition of the DSM 47, patients continue to present with symptoms born out of the digital age, and their symptoms are changing as the technology evolves from browsers, to “crackberries”, to “smart phones” that combine texting, talking, video games, and browsing in one device that to many is like a new appendage. Even the “problematic Internet use” designation now seems outdated, which is why some have wisely opted for “pathological use of electronic media”, instead 47. Technology, like media outlets, remains far ahead of scientific investigation. Given the dramatic changes that our society is undergoing as a result of the Internet revolution, it behooves us to try to bridge the gap.

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Taking a Spiritual History Allows Clinicians to Understand Patients More Fully

Journal of Palliative MedicineVol. 3, No. 1 Innovations in End-of-Life CareTaking a Spiritual History Allows Clinicians to Understand Patients More FullyDr. Christina Puchalski and Anna L. RomerDr. Christina Puchalski and Anna L. RomerPublished Online:19 Apr 2005https://doi.org/10.1089/jpm.2000.3.129AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byVerbalizing spiritual needs in palliative care: a qualitative interview study on verbal and non-verbal communication in two Danish hospices4 January 2022 | BMC Palliative Care, Vol. 21, No. 1Implementation of an Educational Toolkit to Increase Nurse Competence in Spirituality and Spiritual Care of Oncology Patients8 November 2022 | Journal of Holistic Nursing, Vol. 5Posicionamento sobre a Saúde Cardiovascular nas Mulheres – 2022Arquivos Brasileiros de Cardiologia, Vol. 119, No. 5Experiences of German health care professionals with spiritual history taking in primary care: a mixed-methods process evaluation of the HoPES3 intervention15 October 2022 | Family Practice, Vol. 29Religious and spiritual journeys of LGBT older adults in rural Southern Appalachia25 October 2021 | Journal of Religion, Spirituality & Aging, Vol. 34, No. 4The CASH assessment tool: A window into existential suffering19 May 2021 | Journal of Health Care Chaplaincy, Vol. 28, No. 4Integrating religion/spirituality into professional social work practice27 July 2022 | Journal of Religion & Spirituality in Social Work: Social Thought, Vol. 41, No. 4The Concept of Spirituality in the Health Sector: Contributions from the Study of Religion27 September 2022 | International Journal of Latin American Religions, Vol. 12Systematic review: The relationship between religion, spirituality and mental health in adolescents who identify as transgender13 September 2022 | Journal of Gay & Lesbian Mental Health, Vol. 26„Des Lebens Ruf an uns wird niemals enden“ – Sinnzentrierte Interventionen im Überblick30 August 2022 | Zeitschrift für Palliativmedizin, Vol. 23, No. 05Case discussion: The critically ill older adult in spiritual distressGeriatric Nursing, Vol. 47Australian Patient Preferences for the Introduction of Spirituality into their Healthcare Journey: A Mixed Methods Study3 August 2022 | Journal of Religion and Health, Vol. 27Religion, Spirituality, and Ethics in Psychiatric Practice30 March 2022 | Journal of Nervous & Mental Disease, Vol. 210, No. 8Spiritual distress in dialysis: A case report21 July 2022 | Progress in Palliative Care, Vol. 211Interprofessional communication training to address spiritual aspects of cancer care19 July 2022 | Journal of Health Care Chaplaincy, Vol. 29Spirituality in Serious Illness and HealthJAMA, Vol. 328, No. 2What is the role of spiritual care specialists in teaching generalist spiritual care? 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September | Journal of Palliative Medicine, Vol. 20, No. in Patients with A Qualitative September | Journal of Research in Nursing and Vol. 14, No. theory on the and in an exploratory case study September | Vol. 69, No. of the of Spirituality and Palliative Care Research and of Pain and Symptom Management, Vol. No. of a spiritual care training program for staff on November | Palliative and Supportive Care, Vol. 15, No. 4Spiritual distress and spiritual care in advanced heart July | Reviews, Vol. and Spiritual Patient Simulation in Nursing, Vol. No. Vol. 42, No. 4The impact of a spiritual in patients with and and their support December | Vol. 26, No. 3The Importance of a Spiritual History in Healthcare Vol. No. About Substance Use DisordersJournal of Psychosocial Nursing and Mental Health Services, Vol. No. and Spiritual Beliefs of April | Journal of Religion and Health, Vol. No. Care Perceptions of and With of Hospice & Palliative Nursing, Vol. 19, No. in Substance Use What to Know to Practice30 November | in Mental Health Nursing, Vol. 38, No. End-of-Life Care to Religious and Vol. No. of Social Education, Vol. 53, No. Nursing Care and of Christian Nursing, Vol. 34, No. 1The of taking a religious and spiritual July | Psychiatry, Vol. 24, No. religion and spirituality in Vol. No. the role of religious in the at the of of Vol. No. care spiritual March | Supportive Care in Cancer, Vol. 24, No. Spiritual Care and the Role of An Review of Literature and April | Journal of Religion and Health, Vol. No. of the Spiritual Needs of of with Is in the June | Journal of Palliative Medicine, Vol. 19, No. Impact of a Tool for Comprehensive Assessment of Palliative Care on Assessment at and of Pain and Symptom Management, Vol. No. from Healthcare Students to Understand Spiritual Assessment in Clinical Practice29 October | Journal of Religion and Health, Vol. No. Spirituality in January | Journal of Religion and Health, Vol. No. 3Development and of to Assess Nurse Provision of Spiritual August 2014 | Journal of Holistic Nursing, Vol. 34, No. and Validation of the Practice Assessment September 2014 | Research on Social Practice, Vol. 26, No. and the Medical A of July | Journal of Health Care Chaplaincy, Vol. 22, No. history taking in palliative care: A controlled September | Palliative Medicine, Vol. 30, No. Is Is Using A and the Life With American in Spiritual March | Journal of in Mental Health, Vol. 11, No. and spiritual in September | International Journal of and Mental Health, Vol. No. 1The of Hospital to and Patients’ Spiritual A May | Journal for the Study of Spirituality, Vol. No. 1The and to March End-of-Life Spiritual March in Holistic Patient Journal of Nursing, Vol. No. of spiritual assessment for older September 2014 | and Vol. No. und der der Care, Vol. No. Spirituality and A for Holistic January | Journal of Religion and Health, Vol. No. and Belief, in Care spiritual history tool by C. M. Puchalski as an for an interdisciplinary in January | Journal for of and Social Vol. 21, No. the of Spiritual A Pain and Palliative Care Service Quality of Pain and Symptom Management, Vol. No. of Spiritual Assessment in September | Vol. No. the of Christian Nursing, Vol. 32, No. 4Spiritual care: is the assessment tool for palliative Journal of Palliative Nursing, Vol. 21, No. und Spiritualität in der September | Vol. 60, No. of September of spirituality assessment in palliative care patients in November 2014 | Progress in Palliative Care, Vol. 23, No. 4The for Spiritual A Mixed-Methods July | Oncology Nursing Vol. 42, No. 4The Integration of Religion and Spirituality in Social Practice: A May | Social Vol. 60, No. 3The and Educational of a Spiritual Life Review for Patients with and June 2014 | Journal of Cancer Education, Vol. 30, No. in Geriatric Palliative in Geriatric Medicine, Vol. No. An for Spiritual Well-Being May | Journal of Religion & Spirituality in Social Work: Social Thought, Vol. 34, No. Spiritual Assessment March | Journal of Health Care Chaplaincy, Vol. 21, No. American on Mental Health, and Help April | and Vol. 60, No. of Christian Nursing, Vol. 32, No. the Spiritual Needs and of Oncology Patients in Nursing Practice, Vol. 29, No. Care Training to Healthcare Professionals: A Systematic April | Journal of Pastoral Care & Counseling: Advancing theory and professional practice through scholarly and reflective publications, Vol. 69, No. analysis of spiritual

Journal of Palliative Medicine · 741 citationsread the source →

Cohort Profile: The biopsychosocial religion and health study (BRHS)

In The Secrets of Long Life in the National Geographic1 Buettner explored longevity among three communities in Sardinia Italy, Okinawa Japan, and Loma Linda California. Loma Linda is largely a community of 7th-day Adventists. In 1969 initial research2 found that among individuals surviving past age 35 Adventist women in California lived 3.7 years longer than their counterparts and Adventist men 6.2 years longer. In a later, larger California sample3 the differences were even stronger—4.4 years for women and 7.3 years for men. Exercise, vegetarian diet, not smoking, eating nuts and social support have been found to predict longevity in Adventists.4 Yet even when these and several psychological variables are controlled church attendance still predicts greater longevity.5 Interest has been increasing regarding the association of both mental and physical health with religion or spirituality.6 There have been a number of literature reviews that have concluded that the associations of religion and health are largely positive.7–9 In fact, Hall10 concluded religious attendance was more cost-effective in increasing longevity than statin-type medications. While some have questioned the quality of these research conclusions11 and others have pointed out that the benefits or costs of religion may vary depending on the indicator of religious involvement,12,13 there is general agreement regarding the need for more and better research on the subject. Nonetheless, Hummer and his colleagues14 concluded there was consistent evidence that religious attendance was associated with lower mortality risk in cross-sectional and prospective studies. They also concluded there was a need for more diverse measures of religious involvement, comparison among specific subpopulations, and a better understanding of the pathways by which religion might influence health (p. 1226). It was with this goal in mind that this Biopsychosocial Religion and Health Study was developed. The coverage of the study is best understood in the framework of our conceptual model. Two central concepts in this model are allostatic load and cumulative risk exposure. Allostasis is the process of achieving biologic stability through change—specifically, dynamic adjustments in multiple physiological systems to maintain equilibrium and set points (homeostasis) when responding to environmental demands.15 Healthy functioning requires allostasis, which is adaptive and protective over the short term. However, allostasis ‘has a potential cost to the body when allostasis is either called upon too often or is inefficiently managed, and that cost is referred to as “allostatic load” ’ (p. 174).16 Allostatic load can occur when chronic stressors place a burden on the organism but can also result from a lifetime of exposure to events demanding allostatic adjustment. We refer to this lifetime exposure as cumulative risk exposure. Allostatic load, over the life course, ultimately results in increased morbidity and mortality.17,18 In our model cumulative risk exposure aggregates an individual's risk level across physical risks such as poverty, poor housing quality, and violence exposure (which often co-occur), as well as psychosocial risks such as poor parental or marital bond, or poor job satisfaction.19 Cumulative risk exposure influences allostasis to affect allostatic load. Allostatic load, in turn, produces changes in morbidity, mortality and quality of life. However, the effects of cumulative risk exposure are both mediated and moderated by positive and negative aspects of religion. These positive and negative aspects have at least part of their influence by causing changes in lifestyle, psychological and social factors. We use the term manifestations to refer to beliefs and behaviors as they show themselves in psychosocial and biological responses. Our primary aims were to examine: (i) how religious experience moderates the impact of cumulative risk exposure on quality of life, health, and mortality; (ii) the mechanisms by which these manifestations of religion might operate; (iii) how manifestations of religious experience relate to biologic indicators of allostatic load within the context of cumulative risk exposure, and (iv) whether these manifestations operate differently in non-Blacks and Blacks—Blacks being a group for whom religion may be more central in life and, perhaps, in health.13,20,21 We could answer aims i, ii and iv with new questionnaire data and with the mortality and hospitalization data being collected by AHS-2.22 However, obtaining biologic samples as required by aim iii is much more difficult and expensive. Hence, we divided our study into two sub-studies: the Psychosocial Manifestations of Religion Sub-study (PsyMRS) and the Biological Manifestations of Religion Sub-study (BioMRS). PsyMRS is a large prospective study of approximately 11 000 individuals from the AHS-2 population who completed the supplemental PsyMRS questionnaire. Figure 1 shows our sampling plan. The sample will be surveyed at 3-year intervals while the study continues. AHS-2 will provide data on mortality and hospitalizations as described later. BioMRS is an approximately 530-person sub-study embedded within the larger PsyMRS. All members of BioMRS complete the PsyMRS questionnaire and, in addition, attend a clinic where biologic indicators are assessed. All individuals in both PsyMRS and BioMRS were selected from those participating in AHS-2. The AHS-2 recruitment methods and sampling strategy are described elsewhere.22 Sampling plan. AHS-2 is the Adventist Health Study 2. PsyMRS is the Psychosocial Manifestations of Religion Sub-study involving collection of questionnaire data. BioMRS is the Biological Manifestations of Religion Sub-study that includes assessment of biometrics, blood/saliva/urine markers, and memory/learning ability. Numbers are targets. For example, while our year one target for PsyMRS was 10 000, as August 2007, 11 004 were in the dataset We randomly sampled 20 000 AHS-2 participants and sent each the 20-page religion and health questionnaire with up to three reminder cards. Based on pilot studies we expected response rates of 55% from Caucasian and 26% from African American participants. Our goal was to enroll 3400 Blacks and 6600 Caucasians. Data collection started in September 2006 and was largely completed by August 2007. Our return rate was higher than expected with 60% from Caucasians and 31% from Blacks. Recruitment for BioMRS was through an initial letter followed by phone calls. Our goal was to obtain 300 non-Black and 200 Black participants; this moderately overweighs Black participants when compared with the overall AHS-2 sample and the PsyMRS study. Only individuals living within driving distance of our clinic sites in Loma Linda, Riverside, and Los Angeles were contacted. There were 536 participants (296 Whites, 239 Blacks, and 1 Hispanic). In the 3rd year after the initial sample we aim for a minimum of 3000 PsyMRS participants and 400 BioMRS participants. If further funding is obtained, both PsyMRS and BioMRS data will be collected at additional time points to allow latent growth curve modelling of the relations among study variables.23 Our conceptual framework suggested four categories of variables relevant to the PsyMRS questionnaire: cumulative risk exposure, religion, mediating and outcome variables. Allostatic load cannot be directly assessed from the questionnaire. In almost all cases we have used scales which have been validated in other studies or, where they are not available, validated our own. Cumulative risk exposure variables are included to assess a broad spectrum of cumulative and acute stressors that have been associated with health or quality of life.19,24 Most available single measures do not assess risk exposure at more than one point in the person's life so we broadly sampled cumulative risk across the life course. The measures include physical and socioeconomic stress: housing quality, family size, and poverty; and psychosocial stress: perceived stress, job stress/control/satisfaction, unfair treatment and discrimination, parent bonding, marital satisfaction, and trauma exposure. Religion variables were selected to include four aspects of religion: (i) affective—gratitude, forgiveness, loving vs controlling God, positive and negative eschatological attitudes; (ii) cognitive—intrinsic religiosity, some forms of religious coping, spiritual meaning; (iii) behavioural—church attendance, Sabbath keeping, prayer types, church organizational activity; and (iv) social—congregational sense of community, religious support. Mediating variables were selected based on Ellison and Levin's typology of six mechanisms for the religion/health connection25—(i) health behaviors and personal lifestyle variables (from AHS-2), (ii) social integration and social support, (iii) self-esteem and personal efficacy, (iv) positive vs negative emotions, (v) healthy beliefs (e.g. optimism) and (vi) coping resources and behaviors. Additionally we included measures of neuroticism, impression management and self-deception to serve as control variables. Outcome variables included health related quality of life (the SF-12)26 and life satisfaction as well as various medical history, symptom frequency, medication use and sleep disturbance questions and an adaptation of the Charlson comorbidity index.27 Finally, total and coronary disease mortality will be available on followup. All BioMRS participants completed a PsyMRS questionnaire, provided a waking saliva sample and a 12-h, overnight urine sample. At the clinic, fasting blood and adipose samples were taken; biometrics and percentage body fat (bioimpedence) were also assessed. Participants then provided physical and cognitive function data—Independent Activities of Daily Living; physical performance, based on five separate tests of physical ability—balance, gait, chair stands, manual ability, and grip strength; and the California Verbal Learning Test.28 Our measure of allostatic load (Table 1) is designed to summarize levels of physiological activity across a wide range of regulatory systems pertinent to disease risk, as previously described.29–31 Biological parameters used to determine the allostatic load index Biological parameters used to determine the allostatic load index The AHS-2 questionnaire was completed by BRHS participants 1–3 years before the PsyMRS questionnaire. The AHS-2 data set includes 130 food frequency items, daily physical activity, detailed ethnicity and other demographics, country of birth, religion of mother and father who raised participant, religion at age 15–25, age at baptism, medical history, women's health conditions and history, alcohol and tobacco use, and medications used at baseline. AHS-2 will provide hospitalization history information based on a biennial survey and causes of mortality by matching the sample with the National Death Index.22 Based on previous studies of Adventists in California32 we expect good retention in our sample. With the planned cohort maintenance and retention activities of AHS-222 we hope to trace a high percentage of the participants over at least a 3-year period. The demographics of the PsyMRS sample are shown in Table 2 along with comparisons with the 2006 General Social Survey, a survey based on national probability sample.33 Ages below 35 are omitted as the inclusion criteria for AHS-2 in the first several years was age 35+ for non-Blacks and age 30+ for Blacks. Comparison of demographics in the biopsychosocial religion and health study (BRHS) and the general social survey (GSS) by ethnicity and gender Notes: Only individuals older than 35 were included from both samples since that was an initial inclusion criteria for BRHS. All GSS vs BRHS comparisons on education, marital status, and age within genders are statistically significant. Comparison of demographics in the biopsychosocial religion and health study (BRHS) and the general social survey (GSS) by ethnicity and gender Notes: Only individuals older than 35 were included from both samples since that was an initial inclusion criteria for BRHS. All GSS vs BRHS comparisons on education, marital status, and age within genders are statistically significant. One concern is the relatively small number of Black male Adventist participants. However, there are sufficient numbers for data analysis in the middle ranges of age, education and income. There are no large education differences between male and female or Black and White Adventists. While not shown in Table 2 there are no large percentage differences in income though females and Black Adventists have slightly lower income than males and White Adventists respectively. One interesting figure is the relatively low number of Black Adventist women who are married and a correspondingly high number who are divorced or never married relative to both Black male Adventists and to both male and female White Adventists. Comparing the PsyMRS sample and the GSS sample, the BRHS sample has more females, more college educated individuals especially among the Blacks, more married individuals and more individuals above age 65 in all genders and ethnicities. The educational difference may be the result of the literacy level implied by being able to fill out the 50 page AHS-2 questionnaire and possibly the emphasis on education among 7th-day Adventists—e.g. though in the 2000 Census only the 18th largest denominational group,34 Adventists have the 5th largest number of denominational schools35 and the 9th largest number of students enrolled in such schools.36 The difference between Adventists and the GSS sample is consistently larger for Black males than other groups. Adventists are more likely to be married and less likely to be divorced than the GSS sample. Black Adventist women are also less likely to be widowed (P = 0.022 by Fisher's exact Test) and never married (P < 0.0005) than Black women in the GSS sample. Table 3 compares the BRHS and GSS data for two religious questions. BRHS participants were much more likely to report attending church. On the other hand, while prayer was more frequent for Adventists than for those in the GSS participants, the frequency of daily prayer for Black Adventist females was similar to that found in GSS Black females. Comparison of religion variables in the biopsychosocial religion and health study and the general social survey by ethnicity and gender Notes: All GSS versus BRHS comparisons on church attendance and prayer frequency within genders are statistically significant except for prayer in Black females. Comparison of religion variables in the biopsychosocial religion and health study and the general social survey by ethnicity and gender Notes: All GSS versus BRHS comparisons on church attendance and prayer frequency within genders are statistically significant except for prayer in Black females. Previous research with earlier Adventist cohorts has shown that 7th-day Adventists have lower mortality rates than the general population.4 However, until now we have had no data on quality of life. Figure 2 shows physical and mental quality of life on the SF-12v2 for Black and White Adventists compared with the national norms taken from the 2002 SF-12v2 manual based on data collected in 1999 and 2000.37 Unfortunately, national norms for the SF-12v2 are not available by ethnicity but the comparisons are nonetheless interesting. It appears that both Black and White Adventists in our sample report better physical and mental health than the national norms but the patterns differ by age group. For physical health Adventist females tend to be higher than national norms in the 45–54 age group and the differences tend to get smaller as the age of the groups increase. For males the differences tend to be there at all ages but are more pronounced in the 55- to 74-year old age range. Adventists and non-Adventists have similar levels of mental health in the 35- to 44-year old age group but the mental health of both Black and White Adventists is better in the older age groups. Interestingly, Black Adventists at some ages seem to report better mental health than even White Adventists. Physical and Mental Health based on SF-12 composite scores for 7th-day Adventist Blacks and Whites and for SF-12 national norms.38 Numbers are scale scores (mean 50, SD 10) for individuals over 35 years of age The overall better level of physical and mental health for Adventists could be a volunteer effect since our respondents had to fill out long questionnaires. On the other hand, the national norms were also based on volunteers though the questionnaires involved were not as extensive. Still, the fact that the gaps were bigger for mental health and that that gap is greater at older ages is interesting and harder to explain as a volunteer bias alone. These patterns will warrant further examination as our study progresses. The better physical health of Black Adventists than the national norms also warrants attention given the data on health disparities suggests Blacks score lower on physical health measures.38 One potential weakness of this study is that the data are collected exclusively on 7th-day Adventists. While this means that cross-denominational differences cannot be explored this is no different from other studies which have focused on single denominations such as Baptists,39,40 Catholics,41 Mormons,38–40 and Presbyterians.43 Additionally, our preliminary examination of the data shows a wide range of responses on most religion variables. While other approaches are useful,43–45 examination of the religion-health association within a single denomination has several strengths: (i) single denomination studies eliminate the need to control for denominational differences; (ii) because members of a single denomination have a shared religious tradition they will have less variation in how they interpret more nuanced religious questions, even as they differ in their responses to such questions; (iii) in addition, the examination of Blacks is easier because confounding by socio-economic status is less pronounced and thus easier to control than in the U.S. population due to the Adventist education emphasis;46 (iv) finally, just as one cannot learn about economic mobility and success solely by studying the urban underclass and focusing on barriers to achievement, one cannot learn about health and longevity by focusing exclusively on causes of death and studying persons who die prematurely. It behoves us to examine groups that defy the odds and enjoy better-than-average health and longevity; there is no better source of good biopsychosocial, quality of life and religious data on one of these strategically important groups, the 7th-day Adventists, than the data from this study. This study has a number of strengths. First, it includes a much wider range of religious variables than previous epidemiological studies.14,43–45 Second, we used a systematic theoretical scheme for inclusion of possible mediators of the religion and health relationship and, hence, the study includes a wide range of potential psychosocial- and lifestyle-mediating variables. Third, it includes a variety of biologic and functional assessments of allostatic load that have not been incorporated in previous studies of the religion and health connection. Fourth, the quality of life measures, assessed for the first time on an Adventist population, will allow us to determine whether the longer lives of Adventists are accompanied by a longer span of high quality life or whether these longer lives just stretch out the period of poor quality life. The Biopsychosocial Religion and Health Study has potential to greatly increase our understanding of the religion-health relationship and its implications for public health. We are still in the process of cleaning data and prospective data collection has yet to begin. Thus, the data are not freely available. However, BRHS researchers would welcome contacts from other investigators interested in collaboration on projects relating to specific aspects of the data we are can be through the of this or through the Adventist Health Study at Loma Linda National on for their support of this National for their support of the Adventist Health Study 2 which is the parent study for the Biopsychosocial Religion and Health and have been as on this and to the that the we have in and assessment are good we a We would to a to and for the on the BioMRS biological and to for all aspects of the BioMRS We would also to the students who have in our and on the participants. of

International Journal of Epidemiology · 63 citationsread the source →

Prediction and prevention of schizophrenia: what has been achieved and where to go next?

Since the traditional clinical paradigm has been replaced by the modern molecular one, medicine set off into new directions. “Prediction”, “prevention” and “personalization” are the programmatic key words of this new approach. Like other medical disciplines, psychiatry has broadened its focus from diagnosis and treatment to the detection and estimation of the risk of disease development, the prediction of its onset and strategies to avoid its manifestation 1,2,3,4. Although treatment of schizophrenia has greatly advanced over the last decades, a significant number of patients continue to take an unfavorable chronic course 5,6. This makes schizophrenia the leading cause for permanent occupational disability among people under 40 years of age in Germany 7, and the 8th most common cause for disability adjusted life years (DALYs) lost among the 15 to 34-year olds worldwide 8, despite its low prevalence. Moreover, schizophrenia involves tremendous direct and indirect societal costs 9 and a huge burden on patients and their families 8,10. It is becoming increasingly clear that schizophrenia is a complex disorder with polygenic heredity and that its pathogenesis is greatly influenced by interactions between different genes and between genes and environment. Associations to variants of the genes for dysbindin and neuregulin-1, the genetic locus G72 and the DAOA (D-amino acid oxidase activator) gene have now been repeatedly confirmed. As with all other complex diseases, research is focusing now on characterizing the polygenetic predisposition and clarifying its influence on the development of the phenotype 11. Research methods range from molecular genetics via proteome research to cell biology, neurophysiology, brain structural and functional imaging and neuropsychology. With all these methods, several indicators for an increased risk of schizophrenia have been identified. However, the currently recognized neurobiological risk factors are not sufficiently predictive to allow the development and application of “selective” prevention measures targeting asymptomatic persons at risk. For neuro-psychological risk factors, this has just become evident in the large-scale attempt of the North American Prodrome Longitudinal Study (NAPLS) group to improve their multivariate model by integrating the examined neurocognitive variables 12. There are also established environmental risk factors for schizophrenia, such as pregnancy or birth complications, growing up in a large city, IQ low but normal and drug consumption. However, with odds ratios around 2, each of these factors appears to increase the lifetime risk of the disease only slightly 13. Thus, the currently known risk factors, either alone or taken together, cannot be used for prediction and prevention without knowledge of the complete predispositional basis and the gene-gene and gene-environment interactions, which are probably numerous. In view of this situation, it may be argued that the current efforts towards prediction and prevention are still premature and that further progress of etiological research is needed. However, a different perspective has emerged from the work of the centers for early recognition and prevention, established first in Melbourne, Australia and in Cologne, Germany in the mid 1990s, and later on in many other places around the world. This resulted from retrospective research of the early course of psychosis, in which the pathophysiologically active disturbances in brain development extend beyond early abnormalities in behavior into psychopathologically definable early risk and ultra high risk (UHR) symptoms, depending on the individual combination of stressors and resilience factors. First episode psychosis (FEP) research has shown that the outbreak of the disease is preceded in about 70% to nearly 100% of cases by an initial prodrome, which lasts for an average of five to six years. Even in highly developed health care systems, an average of one year thereafter elapses from the first manifestation of psychotic positive symptoms to the initiation of adequate treatment 14,15. The period over which the FEP remains untreated (duration of untreated psychosis, DUP) correlates with: delayed and incomplete remission of the symptoms; necessity of more protracted treatment and greater risk of relapse; lower compliance, greater burden on the family, and a higher level of “expressed emotion”; increased risk of depression and suicide; greater impact on the individual's employment or education; increased drug abuse and delinquent behavior; markedly increased costs of treatment 16. These correlations have recently been confirmed by a meta-analysis 17, with coefficients ranging from 0.285 to 0.434 (95% CI). This does not only provide strong arguments in favor of treating the FEP as early as possible, but has also led to a systematic effort to decrease the incidence of psychosis through indicated prevention. Two important studies concerning the early stage prior to the conversion to FEP have demonstrated that the earliest and most common symptoms, which generally dominate during the prodrome, are unspecific and cannot be distinguished from impairment in mood, drive, contact, and concentration of depressive episodes. These are the Age-Beginning-Course (ABC) study of schizophrenia, a retrospective study with optimized methods 14, and the Cologne Early Recognition (CER) Study, a long-term prospective study with an average follow-up period just below 10 years 18. These studies also found striking cognitive impairments in the form of self-experienced disturbances in thought, speech, and perception processes. This subgroup of so-called basic symptoms, which were found in more than a quarter of patients, had high specificity and a high positive predictive power, accompanied by only low rates of false positive predictions 19,20,21. Basic symptoms were first operationalized in the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Shorter versions of the scale for adults and for children and adolescents — the Schizophrenia Proneness Instrument, Adult version (SPI-A) and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY) — were later developed from dimensional analyses 22,23,24. While the BSABS only allows an assessment of the current state, the SPI-A and the SPI-CY also allow severity ratings according to the maximum frequency of occurrence within the past 3 months. In the CER study, 385 patients who were presumably in the prodromal phase of schizophrenia were followed up for an average of 9.6 (±7.6) years past baseline. Twenty percent of the initial criterion-positive cases (1 of 66 basic symptoms) who agreed to be followed up developed schizophrenia after 12 months, a further 17% after 24 months, a further 13% after 36 months, and finally a total of 70% after an average of 4.5 years. Thus, only 30% did not convert to schizophrenia. The overall presence/absence of at least one basic symptom correctly predicted presence/absence of a subsequent transition to schizophrenia in 78.1% of cases. From further analyses, two partially overlapping basic symptom criteria for defining at risk mental states (ARMS) for psychosis, primarily schizophrenia, were developed (Table 1). The first criterion, which consists of ten cognitive-perceptive basic symptoms and is abbreviated as COPER, was based on findings concerning the predictive accuracy of individual basic symptoms 18,25. The second was based on a methodological re-analysis of the same data set, in which a cluster of nine cognitive basic symptoms had repeatedly been selected as the most predictive. This cluster was called “cognitive disturbances” (COGDIS). In terms of general predictive accuracy, the two criteria slightly differed in the CER study, as COGDIS tended to be more conservative than COPER, i.e. to perform better in ruling in subsequent schizophrenia at the cost of performing worse in ruling it out. The transition rate throughout the average follow-up period of roughly 10 years was 65% for COPER and 79% for COGDIS, with the majority of transitions occurring within the first 3 years past baseline. In a second prospective study 26, conducted with the SPI-A and with a systematic follow-up of 24 months, 38% of the initially included 146 at-risk subjects developed a frank psychosis, mainly schizophrenia, within 12.3 (±10.4) months on average (1–48; median=9) according to COPER. Thus, the positive results of the CER study were confirmed. Again, COGDIS appeared to be more specific but less sensitive than COPER. As a consequence of these findings, predictive basic symptoms have been established as a set of criteria for risk assessment in international research on the early recognition of psychosis. In particular, the German Research Network on Schizophrenia used these symptoms, together with a combined criterion of functional deterioration and biological risk, in defining an “early at-risk of psychosis state” (ERPS), thereby suggesting a clinical risk staging model (Figure 1). Early and late initial prodromal state: a clinical staging approach The positive symptoms typical of schizophrenia — such as delusions, hallucinations or formal thought disorders — often first appear in an attenuated or transient form during the initial prodromal phase. These symptoms provide a valid prediction of conversion into FEP, particularly in the short term. Warning signs of this sort have been used as ultra-high risk (UHR) criteria 27,28. Notwithstanding their differences across studies, these criteria are generally composed of three alternative elements: attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), or a combination of one or more risk factors (always including genetic risk) and functional decline within a certain recent period. For the ascertainment of the UHR criteria, the Melbourne group gradually developed a specific instrument, the Comprehensive Assessment of At Risk Mental States (CAARMS) 29. Based on the Australian definition of the UHR criteria, the Structured Interview for Prodromal Syndromes (SIPS), the Scale for Prodromal Syndromes (SOPS) and, subsequently, the Criteria of Prodromal Syndromes (COPS) were developed 30,31. Different UHR-related approaches to an early detection of FEP, particularly schizophrenia, were developed by the Hillside Recognition and Prevention (RAP) program in New York 32 and the Basel Früherkennung von Psychosen (FEPSY) study 33. There have been at least 15 prediction studies using UHR criteria, some of which with large samples 34,35,36,37,38,39,40,41. The 12-month rates of transition into FEP published so far range between approximately 13% and 50%. A substantial variance is even observed with comparable observation periods in the same center 34,35. Yet, as the annual incidence for all forms of psychosis in the general population is only about 0.034% 42, even the lowest conversion rates still indicate a dramatic increase in the relative risk of illness, at least in the help-seeking samples of specialized centers. Table 2 depicts the predictive accuracy measures published so far, with the last five listed studies representing secondary predictor analyses of samples meeting at risk criteria. As a result, in the German Research Network on Schizophrenia, the UHR approach was combined with the basic symptom approach and applied in a slightly modified form for the definition of “late at-risk of psychosis state” (LRPS) (Figure 1). This clinical staging model, which suggests a syndromal sequence for the development of FEP progressing from unspecific prodromal symptoms to predictive basic symptoms, and then to APS, to BLIPS and to full-blown psychotic symptoms, was recently strongly supported 15. Universal or selective prevention measures target healthy population groups or clinically still healthy risk carriers, respectively 43. Indicated prevention, instead, targets individuals with basic symptoms and UHR symptoms. Even at the early stages when these individuals seek advice and help at the early recognition and prevention centers, they must be regarded as ill and in need of treatment. Furthermore, the impending deterioration of psychosocial performance in schizophrenia often already occurs in the initial prodromal phase, even prior to the conversion into FEP 14,15. These clinical and psychosocial impairments justify defining the interventions in EPRS and LPRS as indicated prevention, pursuing the following three objectives: a) improvement in the current burden of prodromal symptoms; b) avoidance or perhaps delay in the development of psychosocial handicap; c) prevention of or at least delay or attenuation of psychosis. Five international intervention studies have attempted to find out whether or to what extent these three objectives can be reached 44,45,46,47,48,49,50,51 (Table 3). The preventive measures used were either cognitive behavioral therapy (CBT), adapted to the requirements of the persons at risk, or atypical antipsychotics (risperidone, olanzapine, and amisulpride). These were randomized controlled studies, but there were problems with the blinding condition in the two CBT interventions. This and other methodological shortcomings currently limit conclusions and have encouraged the research groups working in this area to set up new, optimized intervention studies. For example, the protocol of the ongoing parallel group PREVENT study includes careful comparative analyses and superiority and inferiority tests of the psychological and pharmacological treatments 52. A staging of risk, thereby implying a temporal dimension, was considered for the first time in the two intervention studies of the German Research Network on Schizophrenia. One of these studies covered ERPS and only offered CBT as a preventive measure 49,50. The other study was designed for LRPS and used only preventive treatment with amisul-pride 51. When the symptom development in the initial prodromal state follows the sequence shown in Figure 1, it would be beneficial for scientific and especially ethical reasons to focus on psychological interventions in ERPS, which are well tolerated and highly accepted. As soon as the first attenuated or transient psychotic symptoms occur, it seems justifiable to apply well tolerated antipsychotics with few side effects. This differential prevention strategy is now pursued in all German early recognition centers and is also increasingly gaining support in other countries. Another pharmacological option is aripiprazole, tested in a pilot study in UHR states 53. Its possible preventive effects are currently being analyzed in the PREVENT study. Antidepressants were used in a naturalistic, non-randomized observational study of an adolescent sample employing only the APS criterion for inclusion, but, for methodological reasons, this study does not allow any conclusion about differential preventive effects of these medications 54. A critical evaluation of the achievements over the past 15 years through continuous efforts to enhance prediction and prevention of psychoses, particularly of schizophrenia, reveals quite impressive results. However, the results achieved thus far need to be evaluated in the light of the ambitious, initially mentioned objectives of modern predictive and preventive medicine. Once predictive basic symptoms and UHR symptoms have occurred, the underlying pathophysiological process might have already progressed. For such a complex disease with a long-term course and a pre-dispositional basis, this kind of risk identification and risk-oriented prevention may possibly come too late. A more substantial reduction in incidence could be reached with selective and universal prevention measures. Therefore, symptom-based prediction and prevention need to be further developed into the direction of selective prevention for symptom-free risk carriers. In the future, it is necessary to strive for: a) an improvement of risk enrichment with the inclusion of biological risk factors; b) a stronger individualization of the risk estimation by stratification; c) the inclusion of sub-psychotic mental states, as cross-sectionally by current at risk criteria, in the the application of prevention strategies more with the of the the initial prodromal phase for as as then most of the follow-up periods shown in Table 2 are not to the transition A significant number of later may be as and, the predictive of the risk may be 12. Therefore, the first and most important is to out new, optimized large-scale studies with follow-up periods the of the initial prodromal phase, as in the CER study 18. The risk enrichment can also be advanced through the inclusion of following the of recent research on the prediction of through the cognitive impairment This condition a risk for with a conversion rate comparable to the risk for the patients certain imaging and the predictive risk enrichment may be possible for using brain but also impairments of and which are with the psychosis risk and are more and in cases with a later transition to schizophrenia and other new large-scale studies with sufficiently observation periods could whether the risk enrichment can be achieved by of such The of this strategy is on the progress of research on biological and environmental risk factors and their interactions, as is currently attempted in the Network of schizophrenia study In other medical disciplines, such as or a risk which does not in a of is using for multivariate clinical staging by risk In the of study, this approach was into psychosis prediction research for the first time A clinical model was developed based on a including six variables positive disturbances Assessment of in the past and years of Based on the individual a multivariate for further the risk of transition to psychosis into risk was each a increased relative risk to the general with each This model was argued to improve the prediction of psychosis by a of the individual risk in terms of and a more risk estimation or clinical staging of risk, in studies, could the development of risk adapted inclusion criteria for randomized preventive In the first application of this approach in the only clinical and variables were It remains to be whether a model including or environmental variables would increase the predictive accuracy even In studies have to whether such can also be applied to the prediction of psychosis within different time The currently ongoing of the has a about the inclusion of a risk for psychosis in to prevention initially argued this and to the that the application of as criteria could that the high rate of predictions in would be to increase up to in general This is and prior to whether to the in the of the The on the predictive of at risk criteria, thereby the persons meeting at risk criteria already from mental and functional for which they seek Moreover, they psychological and cognitive with and functional the majority of help-seeking at risk persons general criteria for mental disorder a clinically significant behavioral or psychological with disability and have to be considered as i.e. as people with the need and to be these in there are reasons for the inclusion of a clinical in the as by current at risk criteria, not as a prodromal risk for first psychosis, but as an to medical the of such an diagnosis would have the of the by the current mental state to a and Although an increased risk of psychosis would continue to be a of such a the psychological and medical focus would be from an to and At this current state of the criteria would be the for the inclusion of this A for the and of a new of international and studies would be with this inclusion in and later on also in A new prevention approach is by the of and studies a of the onset of psychosis the with the first results are for and The transition rate was lower in an group of UHR adolescents than in a group and this was at a an was evaluated in 10 patients in an pilot and a significant improvement in different was In an study, time was in an UHR group with as with a group suggesting a of This was the first study imaging data on effects in individuals at risk. The preventive of is currently in the process of in the Australian Prodrome study With the of schizophrenia is the first mental disorder to which the prediction and prevention program of modern medicine has been The results are and justify the that in the years to come it be possible to provide preventive strategies to the individual risk of of each In to a reduction in risk assessment has to be by neurobiological and psychosocial risk factors, and indicated prevention has to be further developed towards selective prevention. This a new of large sample studies for prediction as well as prevention, with observation In these studies, of risk selected to predictive must be psychological and pharmacological interventions need to be on a long-term basis, more prevention strategies have to be In to be to and such studies, it would be to mental states, as by the currently used risk symptoms, in the of the

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Adjustment disorders: the state of the art

The diagnostic category of adjustment disorder was introduced in the DSM-III-R 1. Prior to that, it was called transient situational disturbance. The DSM-IV 2 and ICD-10 3 descriptions of adjustment disorder are broadly similar. The main features are the following: a) the symptoms arise in response to a stressful event; b) the onset of symptoms is within 3 months (DSM-IV) or 1 month (ICD-10) of exposure to the stressor; c) the symptoms must be clinically significant, in that they are distressing and in excess of what would be expected by exposure to the stressor and/or there is significant impairment in social or occupational functioning (the latter is mandatory in ICD-10); d) the symptoms are not due to another axis I disorder (or bereavement in DSM-IV); e) the symptoms resolve within 6 months once the stressor or its consequences are removed. Adjustment disorders are divided into subgroups based on the dominant symptoms of anxiety, depression or behaviour. Since its introduction, the category of adjustment disorder has been the subject of criticism on three fronts. The first was that it constituted an attempt to medicalize problems of living and did not conform to the criteria for traditional disorders such as having a specific symptom profile 4. The second was that it was a “wastebasket diagnosis” which was assigned to those who failed to meet the criteria for other disorders 5. The third was on its diagnostic instability 6 and that its main utility was to serve as a “justification” for diagnosis-based reimbursement operating in the healthcare system of the US. Despite this, the category has been retained in the further classifications, in large measure due to its clinical utility. Adjustment disorder continues to be diagnosed in a range of clinical settings. Consultation-liaison psychiatry is the context in which the diagnosis is most likely to be made. Around 12% of referrals are so diagnosed in university hospitals in the US 7, a figure that resembles that in European hospitals 8. Nevertheless, the frequency with which adjustment disorder is now diagnosed seems to be declining, in parallel with an increase in the diagnosis of major depression 9, possibly due to the availability of psychotropic drugs, especially selective serotonin reuptake inhibitors (SSRIs), that are safer in those who are medically ill than the older agents. So, changes in the prevalence of adjustment disorders may reflect a change in the “culture of prescribing”, stimulating changes in the “culture of diagnosis” 10. Adjustment disorder has been reported to be almost three times as common as major depression (13.7 vs. 5.1%) in acutely ill medical in-patients 11 and to be diagnosed in up to one third of cancer patients experiencing a recurrence 12. In obstetric/gynaecology consultation-liaison 13, adjustment disorders predominated over other mood disorders. Among those assessed in an emergency department following self harm, a diagnosis of adjustment disorder was made in 31.8% of those interviewed, while a diagnosis of major depression was made in 19.5% of cases 14. None of the major epidemiological studies carried out in the community, such as the Epidemiological Catchment Area Study 15, the National Comorbidity Survey Replication 16 or the National Psychiatric Morbidity Surveys 17 included adjustment disorder among the conditions examined. An exception was the Outcome of Depression International Network (ODIN) study 18, which found a prevalence of only 1% for adjustment disorder in five European countries. A possible reason for this was that mild depression was included in the depressive episode category, inflating that category at the expense of adjustment disorder. By contrast, a study of elderly people from the general population 19 found the prevalence of adjustment disorder to be 2.3%, similar to that of major depression. Adjustment disorder is reported to be very common in primary care, but relevant epidemiological studies in this setting are rare and report rates of the disorder range from 1 to 18% 20,21 among consulters with mental health problems. Concerning psychiatric settings, a study of intake diagnoses into outpatient clinics 22, combining clinical evaluation and the use of the Structured Clinical Interview for DSM-IV (SCID, 23), found that adjustment disorder was the most common clinical diagnosis, made in 36% of patients, whereas the diagnosis was made in about 11% of cases using SCID. Among psychiatric inpatients, 9% of consecutive admissions to an acute public sector unit were diagnosed with adjustment disorder 24. Quantifying the prevalence of adjustment disorder in child and adolescent populations is difficult, due to changes in the diagnostic criteria over time 25. In the younger age groups, unlike adults, adjustment disorder carries with it significant morbidity and a poor outcome, frequently developing into major psychiatric illness 25,26. A general population study in Puerto Rico 27 found a rate of 4.2% among 14–16 year old people, while the total psychiatric morbidity was 17.8%. A similar rate was found in children aged 8–9 in Finland 28. Among outpatients, figures of 5.9–7% have been reported 29,30. In child liaison psychiatry, over one third of those with recent onset diabetes were so diagnosed 31, making it the most common psychiatric disorder to follow this well defined stressor. The current diagnosis of adjustment disorder assumes that there is a stressor which acts as a trigger and that the condition is self-limiting. So, adjustment disorder is closer to the definition of a discrete disorder as proposed by Kendell 32 than most other disorders in psychiatry, since its etiology and course are encapsulated within the diagnosis, while the definition of many other mental disorders is cross-sectional and based on symptoms alone. Yet, the current classifications impose a hierarchical model that assumes equivalence in how adjustment disorder and other diagnoses are construed. As currently classified, adjustment disorder is a sub-threshold diagnosis, that is trumped once the symptom threshold for another diagnosis is met. There is an inherent belief that a sub-threshold condition is less severe than a full-blown disorder such as major depression, the diagnosis by which adjustment disorder is most often superseded. Yet, the evidence for this is lacking, and there is empirical data 33 that, when measures of symptom severity or social functioning are examined, there is no difference between those with mood disorders and adjustment disorder. Furthermore, up to 25% of adolescents with a diagnosis of adjustment disorder engage in suicidal behaviour 34, while among adults with this disorder the figure is 60% 35. Adjustment disorder is the diagnosis in up to one third of young people who die by suicide 36, while among all suicide deaths in the developing world it is the most common diagnosis 37. These data show that, far from being a mild condition, adjustment disorder has a significant impact on behaviour. On the other hand, the current classifications fail to distinguish between adaptive and maladaptive reactions to stress. The DSM-IV tries to address this problem by stating that a diagnosis of adjustment disorder is only made when the distress is of clinical significance 38. There are two components to this: the distress must be in excess of what would normally be expected and/or there is an impairment in social or occupational function. In relation to the first of these, one of the most insightful critics of the DSM-IV, J. Wakefield 39, points out that it would allow the top third in the normal distribution of mood reactivity to be classified as disordered, and that it does not take into account the contextual factors that might cause this excess in distress. For example, the loss of a job for one person might be manageable while for another it could heap poverty on a family resulting in distress that might not be inappropriate under the circumstances. Cultural differences in the expression of emotion also need to be considered. In liaison psychiatry, where the diagnosis of adjustment disorder is most frequently made, a knowledge of “normal” coping with illness in that specific culture is essential and the diagnostic process will be guided by the extent to which an individual's symptoms are in excess of this. Some might argue that the fact of visiting a doctor indicates abnormal distress, yet the tendency to consult is also determined by factors additional to illness, including cultural and personal attitudes to symptoms. So, the mere fact of a consultation should not of itself be taken as a proxy measure of excessive distress. Neither should the decision to refer to psychiatric services, since this too is governed by factors that are not always related to symptom severity (e.g., a wish “to do something” under pressure from a patient in the face of continuing distress). Because adjustment disorder is a diagnosis made in the context of a stressor, there is a danger that any distress following such an event might be labelled as a disorder 40. Clinical judgement, therefore, plays a large part in making the diagnosis of adjustment disorder in the current criterion vacuum and future classifications should accord weight to culture, context and personal circumstances in differentiating normal from pathological distress. The second criterion, requiring impairment in functioning, is arguably a more robust indicator of disorder, since it is this which leads to treatment seeking. For example, the inability to work is potentially a significant indicator of impairment. However, there may be situations where functioning is reduced in the presence of non-pathological reactions. For instance, if the circumstances are especially traumatic, such as the loss of a child, the period of impaired function may be longer than anticipated in those with non-pathological responses. The evaluation of functioning in children places special demands on the assessor, since it has to be set against the demands of the developmental stage, and the degree of dependency and autonomy in key relationships. The presence of pre-existing impairment and extant vulnerabilities, such as learning disability and developmental disorders, must also be considered when making the evaluation. The ICD-10, contrary to the DSM-IV, requires the presence of both excessive symptoms and functional impairment for the diagnosis of adjustment disorder, thus narrowing the application of this category. Because of the hierarchical nature of ICD-10 and DSM-IV, adjustment disorder cannot be diagnosed once the criteria for another condition are met. The condition that most frequently trumps adjustment disorder is major depression/depressive episode. This is evident from studies that compare the clinical with the research approach. For example, in a study of those presenting because of self-harm, a clinical diagnosis of adjustment disorder was made in 31.8% and one of major depression in 19.5% of cases, but using SCID the proportions changed to 7.8% and 36.4% respectively 14. However, there is a point of departure between the two conditions when other variables are considered. Suicidal behaviour occurs earlier in the course of adjustment disorder as compared to major depression 41 and the interval from suicidal communication to completion of suicide is shorter 42. The socio-demographic profile and childhood risk variables differ between the two groups 41. Among adolescents dying by suicide, there is much less evidence of prior emotional or behavioural problems 42. In addition, the readmission rates for those with adjustment disorder are significantly lower than for those with major depression, generalized anxiety or dysthymia 43 and hospitalization is also shorter 6. This highlights the need for the clearer operationalization of adjustment disorder in future classifications. A further but lesser area of potential overlap is with post-traumatic stress disorder (PTSD). The conflation is not so much related to the symptoms of these disorders but to the stressors themselves. There has been an expansion in the stressors that are deemed to trigger PTSD, from those that are potentially life threatening, as originally described, to events that are less traumatic, such as financial problems or watching distressing images on television – a phenomenon called “criterion creep” 44. In clinical practice, a diagnosis of PTSD is often made reflexively 45 once such an event is identified, although adjustment disorder might be a more appropriate diagnosis. Overall, it is clear from the data available that adjustment disorder is sufficiently severe and distinct from other disorders, especially major depression, to from its to that of a full-blown and mental disorder. for the DSM-IV have been The Clinical Interview and the International Interview do not adjustment disorder at The for Clinical in do adjustment disorder, but only at the of the in 13, which with and This the criteria for all other disorders have been and there are no specific with to adjustment disorder to the on clinical The SCID also a with adjustment disorder, but the to that this diagnosis is not made if the criteria for any other mental disorder are with the of it to a In of the very threshold for major depression, in studies using SCID and to be of adjustment disorder, major depression will often adjustment disorder, of the context in which the symptoms have The International Interview also a on adjustment disorder as in that disorder is trumped when any other diagnosis is made. So, while have epidemiological research in psychiatry, the that they are having been for use by cannot be This is especially for a diagnosis such as adjustment disorder, which on clinical judgement, context and course than symptoms alone. As a of the problems with the current of diagnostic have been made to for adjustment disorder. Because there is symptom overlap with major depression, there is a that which for depression might people with adjustment disorder. A of have been for this including the Depression which has been to be an for adjustment disorder and major depression but when compared to SCID has and A study of health with an diagnosis but one which the of adjustment disorder most found with the to a using a coping measure have also been The and Depression has been for in cancer patients, but it does not distinguish between major depression and adjustment disorder problems when the Interview and the were for to for adjustment disorder. The of might have a in adjustment disorder from major depression and has been in one study that disorder more symptoms and a to the mood changes compared to disorder of this is Adjustment disorder cannot be diagnosed in the of a stressor. The event must be and in time to the onset of symptoms. The longer the time period between the event and the onset of the less likely is the diagnosis to be adjustment disorder. For this a period between the event and symptom onset of 3 months in DSM-IV and 1 month in ICD-10 is must be when this is for two those who are often significance to that in were in at the in an at may to an of the The 3 month may to be and it is to the empirical data on which this is Concerning the of there is to the in adjustment disorder from major depression. of those with a diagnosis of adjustment disorder have recent life of those with major depression also report such with more related to problems and to occupational or family stressors in the adjustment disorder while significant, are to be clinically in an since they are not as to major depression or adjustment disorder. the events range in severity from those that are as such as a with a to those that are more This will be by In the to the on adjustment disorder, the ICD-10 that and risk plays a than in other such as PTSD or acute stress reactions. However, it is on what evidence this is By contrast, the DSM-IV is on this The that a model is of and is arguably the most There have been studies adjustment disorder against other disorders to allow about the of and is in the current of The relevant studies be classified in two those adjustment disorder and those diagnoses to adjustment disorder. The prevalence of disorder among those with adjustment disorder in to those with other depressive disorders seems to be not although studies are and Among as a to adjustment disorder in a has also been examined, and was found to be a risk for adjustment disorder while was with the severity of the disorder using that a diagnosis of adjustment disorder, such as or depression, are also of although there is a that these conditions may not be to adjustment disorder due to differences in the in the earlier classifications. such study found that the was between and a symptom and evidence of The in relation to and a of symptoms were by in studies of and The of clear criteria for adjustment disorder in DSM-IV or ICD-10 that weight is to clinical than in most other current of anxiety, poor having onset following a recent stressful event are likely of a diagnosis of adjustment disorder, although it must be in that major depression also is often more when the person is with the such as when about while at other times mood is normal and The of the person from the stressful is with a general in symptoms. In the of those who adjustment disorder in response to illness, changes in mood are related to changes in the illness The more the symptoms are loss of mood reactivity the less likely is the diagnosis of adjustment disorder. A family of depression might also a depressive episode. to the symptom threshold for major depression, it is to a diagnosis of this condition than adjustment disorder. the National for Clinical on depression a period of so as to allow for the of under pressure from the patient and or the “to do a diagnosis of major depression (or generalized may be made and also arise when the stressor, and the is and has of may be on as there is no of if the symptoms are likely to or if they are now of the trigger and major depression. The of a response to should the that this is an adjustment disorder, so that are than in of A further is that what to be a stressor (e.g., a diagnosis of a may be with symptoms as of the diagnosis the patient (e.g., the of treatment to that stressors symptoms might to an diagnosis of major depression. The of the consequences of the stressor in symptoms is in the DSM-IV definition of adjustment disorder. on the of adjustment disorder are by DSM-IV and ICD-10 The are broadly similar in the two classifications from adjustment disorder with they have The is the most common in adults, while the with of or of and are more diagnosed among children and The between adjustment disorder and a normal stress response is based on the severity of symptoms and the impact on functioning into account the nature of the stressor; the personal and context in which it has cultural with to such responses. PTSD and acute stress disorder the presence of a stressor of a that would be for almost and the symptom is also although both of these have been 40. not to such events by developing PTSD and the that other disorders follow to be considered. For those not the PTSD diagnostic but with significant symptoms and/or functional adjustment disorder should be considered a possible may to be an adjustment disorder, because of the sub-threshold of the symptoms or the of functional might be an axis I disorder in that only as a a period of the of an diagnosis of adjustment disorder may be at especially if there are symptoms in of of the stressor. studies have the disorders that are with adjustment disorder, an that is by the fact that the criteria for this disorder axis I Yet, a recent study 19 found that almost of patients with major depression or and adjustment disorder were not significantly The between and adjustment disorder is also of since it may the instability of the adjustment disorder diagnosis. may be for of symptoms such as anxiety and depression, which are in adjustment disorder. such as are and may with mood changes to This may in one study 6 patients with an diagnosis of adjustment disorder were on as having a primary diagnosis of The evidence for the treatment of adjustment disorder is due to the of A further problem is that these are so that of may fail to any due to In are as being the most with the exception that, when stressors are measures may be However, there is a for children and adolescents diagnosed with adjustment disorder, since there is evidence that a of adolescents major mental disorders. measures may be to the person in the stressful A person being at work might to an system or may the of the A person in an might a A person on too much work may from family such as social or in a or may distress. or in groups, the range including and symptoms of the of and and the that the stressor has for the might also symptoms. In who engage in self-harm, in that do not may be of and to behaviour has the evidence was found to be of in older patients a including and was in patients with adjustment disorder to was when to patients with adjustment disorder who stress and among with adjustment disorder In a study of cancer patients similar were found in those with adjustment disorder and other psychiatric Some of these have been in specific medically ill groups, such as those with or in coping have been it is if adjustment disorder, were studies (e.g., and and of life than symptoms were the measures in (e.g., The of adjustment disorder of treatment of anxiety and The use of to these is common are by especially if there has been no from there is evidence to Nevertheless, those with and anxiety may have a when are such as in those with a of There are to the treatment of adjustment disorder and these are on with the anxiety A study a with a found that the of were although more to the including from and other and a on symptoms. A study found that and were while a study of cancer patients with and mood found to a study in primary the response of patients with major depression and with adjustment disorder to using reported changes in functional disability based on Overall, the adjustment disorder was as likely to to However, as this was a the of the is study compared and in with adjustment disorder assigned to an a or and found that all significantly Overall, these studies for the of and arguably for any specific in the of adjustment disorder, but further studies are Adjustment disorders are common mental disorders, especially in consultation-liaison prevalence seems to be in children and in they are with significant morbidity and a than in Suicidal behaviour is common in both adolescents and adults with these disorders, and adjustment disorder is the diagnosis in up to one third of young people who die by There are major problems with the diagnostic criteria for adjustment disorder in both ICD-10 and The most of these is the as This has in being the subject of Furthermore, current classifications fail to on these disorders from normal adaptive reactions to and the diagnosis of major depression in people with reactions to for adjustment disorders are although are likely to be the

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