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حَدَّثَنِي أَبُو الطَّاهِرِ، أَحْمَدُ بْنُ عَمْرِو بْنِ سَرْحٍ وَحَرْمَلَةُ بْنُ يَحْيَى التُّجِيبِيُّ - قَالَ أَبُو الطَّاهِرِ حَدَّثَنَا وَقَالَ، حَرْمَلَةُ أَخْبَرَنَا - ابْنُ وَهْبٍ، أَخْبَرَنِي يُونُسُ، عَنِ ابْنِ شِهَابٍ، أَخْبَرَنِي عُرْوَةُ بْنُ الزُّبَيْرِ، أَنَّهُ سَأَلَ عَائِشَةَ عَنْ قَوْلِ اللَّهِ، ‏{‏ وَإِنْ خِفْتُمْ أَنْ لاَ، تُقْسِطُوا فِي الْيَتَامَى فَانْكِحُوا مَا طَابَ لَكُمْ مِنَ النِّسَاءِ مَثْنَى وَثُلاَثَ وَرُبَاعَ‏}‏ قَالَتْ يَا ابْنَ أُخْتِي هِيَ الْيَتِيمَةُ تَكُونُ فِي حَجْرِ وَلِيِّهَا تُشَارِكُهُ فِي مَالِهِ فَيُعْجِبُهُ مَالُهَا وَجَمَالُهَا فَيُرِيدُ وَلِيُّهَا أَنْ يَتَزَوَّجَهَا بِغَيْرِ أَنْ يُقْسِطَ فِي صَدَاقِهَا فَيُعْطِيَهَا مِثْلَ مَا يُعْطِيهَا غَيْرُهُ فَنُهُوا أَنْ يَنْكِحُوهُنَّ إِلاَّ أَنْ يُقْسِطُوا لَهُنَّ وَيَبْلُغُوا بِهِنَّ أَعْلَى سُنَّتِهِنَّ مِنَ الصَّدَاقِ وَأُمِرُوا أَنْ يَنْكِحُوا مَا طَابَ لَهُمْ مِنَ النِّسَاءِ سِوَاهُنَّ ‏.‏ قَالَ عُرْوَةُ قَالَتْ عَائِشَةُ ثُمَّ إِنَّ النَّاسَ اسْتَفْتَوْا رَسُولَ اللَّهِ صلى الله عليه وسلم بَعْدَ هَذِهِ الآيَةِ فِيهِنَّ فَأَنْزَلَ اللَّهُ عَزَّ وَجَلَّ ‏{‏ وَيَسْتَفْتُونَكَ فِي النِّسَاءِ قُلِ اللَّهُ يُفْتِيكُمْ فِيهِنَّ وَمَا يُتْلَى عَلَيْكُمْ فِي الْكِتَابِ فِي يَتَامَى النِّسَاءِ اللاَّتِي لاَ تُؤْتُونَهُنَّ مَا كُتِبَ لَهُنَّ وَتَرْغَبُونَ أَنْ تَنْكِحُوهُنَّ‏}‏ ‏.‏ قَالَتْ وَالَّذِي ذَكَرَ اللَّهُ تَعَالَى أَنَّهُ يُتْلَى عَلَيْكُمْ فِي الْكِتَابِ الآيَةُ الأُولَى الَّتِي قَالَ اللَّهُ فِيهَا ‏{‏ وَإِنْ خِفْتُمْ أَنْ لاَ تُقْسِطُوا فِي الْيَتَامَى فَانْكِحُوا مَا طَابَ لَكُمْ مِنَ النِّسَاءِ‏}‏ ‏.‏ قَالَتْ عَائِشَةُ وَقَوْلُ اللَّهِ فِي الآيَةِ الأُخْرَى ‏{‏ وَتَرْغَبُونَ أَنْ تَنْكِحُوهُنَّ‏}‏ رَغْبَةَ أَحَدِكُمْ عَنِ الْيَتِيمَةِ الَّتِي تَكُونُ فِي حَجْرِهِ حِينَ تَكُونُ قَلِيلَةَ الْمَالِ وَالْجَمَالِ فَنُهُوا أَنْ يَنْكِحُوا مَا رَغِبُوا فِي مَالِهَا وَجَمَالِهَا مِنْ يَتَامَى النِّسَاءِ إِلاَّ بِالْقِسْطِ مِنْ أَجْلِ رَغْبَتِهِمْ عَنْهُنَّ ‏.‏

Urwa b. Zubair reported that he asked 'A'isha about the words of Allah:" If you fear that you will not be able to maintain equity amongst the orphan girls, then marry (those) you like from amongst the women two, three or four." She said: O, the son of my sister, the orphan girl is one who is under the patronage of her guardian and she shares with him in his property and her property and beauty fascinate him and her guardian makes up his mind to marry her without giving her due share of the wedding money and is not prepared (to pay so much amount) which anyone else is prepared to pay and so Allah has forbidden to marry these girls but in case when equity is observed as regards the wedding money and they are prepared to pay them the full amount of the wedding money and Allah commanded to marry other women besides them according to the liking of their heart. 'Urwa reported that 'A'isha said that people began to seek verdict from Allah's Messenger (ﷺ) after the revelation of this verse about them (orphan girls) and Allah, the Exalted and Glorious, revealed this verse:" They asked thee verdict about women; say: Allah gives verdict to you in regard to them and what is recited to you in the Book about orphan woman, whom you give not what is ordained for them while you like to marry them" (iv. 126). She said: The wording of Allah" what is recited to you" in the Book means the first verse, i. e." if you fear that you may not be able to observe equity in case of an orphan woman, marry what you like in case of woman" (iv. 3). 'A'isha said: (And as for this verse [iv. 126], i. e. and you intend" to marry one of them from amongst the orphan girls" it pertains to one who is in charge (of orphans) having small amount of wealth and less beauty and they have been forbidden that they should marry what they like of her wealth and beauty out of the orphan girls, but with equity, because of their disliking for them

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Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial.

Background: New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M1 and M4-preferring muscarinic receptor agonist that does not block D2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline-trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. Methods: EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18-65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3-7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at week 5, along with the 95% CI and two-sided p values were calculated for the primary and secondary continuous efficacy endpoints. Safety analyses included all participants receiving at least one trial medication dose and used descriptive statistics. This trial is registered with ClinicalTrials.gov (NCT04659161). Findings: From Dec 16, 2020, to April 13, 2022, of 407 people who were screened, 252 participants meeting enrolment criteria were randomly assigned to the KarXT (n=126) or placebo (n=126). Baseline PANSS total scores were 98·3 (KarXT; n=126) and 97·9 (placebo; n=125). The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (-21·2 points, SE 1·7) versus placebo (-11·6 points, 1·6; least squares mean difference -9·6; 95% CI -13·9 to -5·2; p<0·0001, Cohen's d effect size=0·61). All secondary endpoints were also met, and favoured KarXT versus placebo (p<0·05). The most common adverse events with KarXT versus placebo were constipation (27 [21%] vs 13 [10%]), dyspepsia (24 [19%] vs 10 [8%]), headache (17 [14%] vs 15 [12%]), nausea (24 [19%] vs seven [6%]), vomiting (18 [14%] vs one [1%]), hypertension (12 [10%] vs one [1%]), dizziness (11 [9%] vs four [3%]), gastro-oesophageal reflux disease (eight [6%] vs zero [0%]), and diarrhoea (seven [6%] vs four [3%]). Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]). Interpretation: In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential for KarXT to represent a new class of effective and well tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications. Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia. Funding: Karuna Therapeutics.

Lancet (London, England) · randomised controlled trial · 144 citationsread the source →

Physical therapy for the critically ill in the ICU: a systematic review and meta-analysis.

Objective: The purpose of this systematic review was to review the evidence base for exercise in critically ill patients. Data sources and study selection: Using keywords critical care and physical therapy and related synonyms, randomized controlled trials, meta-analyses, and systematic reviews were identified through electronic database searches and citation tracking. Clinical trials with outcomes of mortality, length of hospital and ICU stay, physical function and quality of life, muscle strength, and ventilator-free days were included. Data extraction and synthesis: Two reviewers abstracted data and assessed quality independently. Effect sizes and 95% confidence intervals were calculated. From 3,126 screened abstracts, 10 randomized controlled trials and five reviews were found. The mean Physiotherapy Evidence Database score was 5.4. Overall there was a significant positive effect favoring physical therapy for the critically ill to improve the quality of life (g = 0.40, 95% confidence interval 0.08, 0.71), physical function (g = 0.46, 95% confidence interval 0.13, 0.78), peripheral muscle strength (g = 0.27, 95% confidence interval 0.02, 0.52), and respiratory muscle strength (g = 0.51, 95% confidence interval 0.12, 0.89). Length of hospital (g = -0.34, 95% confidence interval -0.53, -0.15) and ICU stay (g = -0.34, 95% confidence interval -0.51, -0.18) significantly decreased and ventilator-free days increased (g = 0.38, 95% confidence interval 0.16, 0.59) following physical therapy in the ICU. There was no effect on mortality. Conclusion: Physical therapy in the ICU appears to confer significant benefit in improving quality of life, physical function, peripheral and respiratory muscle strength, increasing ventilator-free days, and decreasing hospital and ICU stay. However, further controlled trials of better quality and larger sample sizes are required to verify the strength of these tentative associations.

Critical care medicine · meta-analysis · 302 citationsread the source →

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.

Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3-6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58-81%) in the 74 Gy group vs 59% (95% CI 45-70%) in the 64 Gy group. There were 23 failures in the 74 Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38-1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53-77% vs 63%, 95% CI 50-74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50-1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent > or =Grade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P=0.006), and increases in both acute bowel side effects during treatment (P=0.05) and acute bladder sequelae (P=0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOG> or =2) were seen more commonly in the 74 Gy and 1.5 cm margin groups (P=0.02 and P=0.05, respectively) in the first 2 years after randomisation. Similar results were found using the LENT SOM assessments. No significant differences in late bladder side effects were seen between the randomised groups using the RTOG scoring system. Using the LENT SOM instrument, a higher proportion of men treated in the 74 Gy group had Grade > or =3 urinary frequency at 6 and 12 months. Compared to baseline scores, bladder symptoms improved after 6 months or more follow-up in all groups. Sexual function deteriorated after treatment with the number of men reporting some sexual dysfunction (Grade> or =1) increasing from 38% at baseline to 66% at 6 months and 1 year and 81% by year 5. However, no consistent differences were seen between the randomised groups. In conclusion, dose escalation from 64 to 74 Gy using conformal radiotherapy may improve long-term PSA control, but a treatment margin of 1.5 cm is unnecessary and is associated with increased acute bowel and bladder reactions and more late rectal side effects. Data from this randomised pilot study informed the Data Monitoring Committee of the Medical Research Council RT 01 Trial and the two studies will be combined in subsequent meta-analysis.

British journal of cancer · randomised controlled trial · 155 citationsread the source →

Safety of Tirofiban in acute Ischemic Stroke: the SaTIS trial.

Background and purpose: Tirofiban is a highly selective, fast-acting nonpeptide glycoprotein IIb/IIIa platelet receptor antagonist with a short half-life time. Glycoprotein IIb/IIIa antagonists are effective for the treatment of acute coronary syndromes proven in large clinical trials. Safety and efficacy in patients with ischemic stroke are uncertain. This was addressed in the Safety of Tirofiban in acute Ischemic Stroke (SaTIS) trial. Methods: Two hundred sixty patients with acute ischemic stroke were randomized in a placebo-controlled, prospective, open-label treatment, blinded outcome reading multicenter trial. Subjects with a National Institutes of Health Stroke Scale between 4 and 18 received intravenously either tirofiban or placebo within 3 to 22 hours after symptom onset for 48 hours. The primary end point was the rate of cerebral bleeding as measured in follow-up CT scans 2 to 7 days after inclusion. The secondary end point was clinical efficacy within 1 week (National Institutes of Health Stroke Scale, modified Rankin Scale) and after 5 months (Barthel Index, modified Rankin Scale). Results: The rate of cerebral hemorrhagic transformation (I/II) and parenchymal hemorrhage (I/II) did not differ between both groups (tirofiban 36 of 120; placebo 33 of 124: OR, 1.18; 95% CI, 0.66 to 2.06). Mortality after 5 months was significantly lower in patients treated with tirofiban (3 of 130 [2.3%] versus 11 of 126 [8.7%]; OR, 4.05; 95% CI, 1.1 to 14.9). No difference in neurological/functional outcome was found after 1 week and after 5 months. Conclusions: We conclude that tirofiban might be safe in acute moderate ischemic stroke even when administered within a large time window after symptom onset and might save lives in the late outcome. Clinical Trial Registration- URL: www.strokecenter.org/trials/. Trial name: SaTIS. Enrollment began before July 1, 2005.

Stroke · randomised controlled trial · 134 citationsread the source →

Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status.

Background/objective: Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort. Methods: Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m-2), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l-1), breastfeeding duration <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models. Results: Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity. Conclusions: Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.

International journal of obesity (2005) · 47 citationsread the source →

Sexual victimisation, peer victimisation, and mental health outcomes among adolescents in Burkina Faso: a prospective cohort study.

Background: Sexual victimisation and peer victimisation are pervasive and increase risk for mental illness. Longitudinal studies that compare their unique and cumulative effects are scarce and have been done predominantly in high-income countries. The aims of this study were to examine the prevalence, prospective associations, and gender differences in sexual and peer victimisation and mental health in a low-income, African setting. Methods: In this prospective cohort study, data were obtained from the 2017 ARISE Adolescent Health Study, a population-representative, two-wave, prospective study of adolescents (aged 12-20 years) from Burkina Faso. A random sample of adolescents was drawn from ten villages, selected to capture the five main ethnic groups, and from one of the seven sectors of Nouna town, Burkina Faso, at two timepoints: Nov 12 to Dec 27, 2017, and Nov 15 to Dec 20, 2018. Standardised interviews were conducted in French or a local language by trained researchers. We measured victimisation exposure as sexual victimisation, peer victimisation, and polyvictimisation, using lifetime frequency of exposure, and we measured mental health symptoms and disorders using the Kutcher Adolescent Depression Scale, the Primary Care Post-Traumatic Stress Disorder screen IV and 5, and a question on lifetime self-harm and number of incidents in the past year. We calculated prevalence of victimisation and mental health symptoms and disorders at the two timepoints, and we used lifetime victimisation at the first timepoint to predict mental health at the second timepoint using logistic and negative binomial regressions. Gender differences were examined using interaction terms. Findings: Of 2544 eligible adolescents, 1644 participated at time 1 and 1291 participated at time 2. The final sample with data at both timepoints included 1160 adolescents aged 12-20 years (mean 15·1, SE 0·2), of whom 469 (40·4%) were girls and 691 (59·6%) were boys. The majority ethnic group was Dafin (626 [39·1%]), followed by Bwaba (327 [20·5%]), Mossi (289 [16·0%]), Samo (206 [13·0%]), Peulh (166 [9·7%]), and other (30 [1·6%]). After survey weight adjustment, sexual victimisation (weighted percentages, time 1, 256 [13·8%] of 1620; time 2, 93 [7·2%] of 1264) and peer victimisation (weighted percentages, time 1, 453 [29·9%] of 1620; time 2, 272 [21·9%] of 1264) were common, whereas polyvictimisation was more rare (weighted percentages, time 1, 116 [6·6%] of 1620; time 2, 76 [5·7%] of 1264). Longitudinally, sexual victimisation was associated with probable clinical disorder (adjusted odds ratio 2·59, 95% CI 1·15-5·84), depressive symptoms (adjusted incidence rate ratio [aIRR] 1·39, 95% CI 1·12-1·72), and symptoms of post-traumatic stress disorder (aIRR 2·34, 1·31-4·16). Peer victimisation was associated with symptoms of post-traumatic stress disorder (aIRR 1·89, 1·13-3·17) and polyvictimisation was associated with depressive symptoms (aIRR 1·34, 1·01-1·77). Girls reported more sexual victimisation (weighted percentages, 130 [17·3%] of 681 vs 126 [11·4%] of 939), boys reported more peer victimisation (weighted percentages, 290 [33·1%] of 939 vs 163 [25·2%] of 681), and there was a significant interaction between lifetime victimisation and gender for probable clinical disorder (F [degrees of freedom 7, sample 376] 2·16; p=0·030). Interpretation: Sexual and peer victimisation were common in the study setting and increased risk for mental health problems. Adolescent girls who have been sexually victimised are especially at risk of mental health problems. Interventions targeting sexual and peer violence in low-income settings are needed. Funding: Alexander von Humboldt Foundation, the Wellcome Trust, Fondation Botnar, and Harvard TH Chan School of Public Health.

The lancet. Psychiatry · 9 citationsread the source →

Interventions for the treatment of metastatic extradural spinal cord compression in adults.

Background: Metastatic extradural spinal cord compression (MESCC) is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects. This is an updated version of the original Cochrane review published in theCochrane Database of Systematic Reviews (Issue 4, 2008). Objectives: To determine the efficacy and safety of radiotherapy, surgery and corticosteroids in MESCC. Search methods: In March 2015, we updated previous searches (July 2008 and December 2013) of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS, CANCERLIT, clinical trials registries, conference proceedings, and references, without language restrictions. We also contacted experts for relevant published, unpublished and ongoing trials. Selection criteria: Randomised controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC. Data collection and analysis: Three authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. Where possible, we pooled relative risks with their 95% confidence intervals, using a random effects model if heterogeneity was significant. We assessed overall evidence-quality using the GRADE approach. Main results: This update includes seven trials involving 876 (723 evaluable) adult participants (19 to 87 years) in high-income countries. Most were free of the risk of bias. Different radiotherapy doses and schedulesTwo equivalence trials in people with MESCC and a poor prognosis evaluated different radiotherapy doses and schedules. In one, a single dose (8 Gray (Gy)) of radiotherapy (RT) was as effective as short-course RT (16 Gy in two fractions over one week) in enhancing ambulation in the short term (65% versus 69%; risk ratio (RR) was 0.93, (95% confidence interval (CI) 0.82 to 1.04); 303 participants; moderate quality evidence). The regimens were also equally effective in reducing analgesic and narcotic use (34% versus 40%; RR 0.85, 95% CI 0.62 to 1.16; 271 participants), and in maintaining urinary continence (90% versus 87%; RR 1.03, 95% CI 0.96 to 1.1; 303 participants) in the short term (moderate quality evidence). In the other trial, split-course RT (30 Gy in eight fractions over two weeks) was no different from short-course RT in enhancing ambulation (70% versus 68%; RR 1.02, 95% CI 0.9 to 1.15; 276 participants); reducing analgesic and narcotic use (49% versus 38%; RR 1.27, 95% CI 0.96 to 1.67; 262 participants); and in maintaining urinary continence (87% versus 90%; RR 0.97, 0.93 to 1.02; 275 participants) in the short term (moderate quality evidence). Median survival was similar with the three RT regimens (four months). Local tumour recurrence may be more common with single-dose compared to short-course RT (6% versus 3%; RR 2.21, 95% CI 0.69 to 7.01; 303 participants) and with short-course compared to split-course RT (4% versus 0%; RR 0.1, 95% CI 0.01 to 1.72; 276 participants), but these differences were not statistically significant (low quality evidence). Gastrointestinal adverse effects were infrequent with the three RT regimens (moderate quality evidence), and serious adverse events or post-radiotherapy myelopathy were not noted. We did not find trials comparing radiotherapy schedules in people with MESCC and a good prognosis. Surgery plus radiotherapy compared to radiotherapyLaminectomy plus RT offered no advantage over RT in one small trial with 29 participants (very low quality evidence). In another trial that was stopped early for apparent benefit, decompressive surgery plus RT resulted in better ambulatory rates (84% versus 57%; RR 1.48, 95% CI 1.16 to 1.90; 101 participants, low quality evidence). Narcotic use may also be lower, and bladder control may also be maintained longer than with than RT in selected patients (low quality evidence). Median survival was longer after surgery (126 days versus 100 days), but the proportions surviving at one month (94% versus 86%; RR 1.09, 95% CI 0.96 to 1.24; 101 participants) did not differ significantly (low quality evidence). Serious adverse events were not noted. Significant benefits with surgery occurred only in people younger than 65 years. High dose corticosteroids compared to moderate dose or no corticosteroidsData from three small trials suggest that high-dose steroids may not differ from moderate-dose or no corticosteroids in enhancing ambulation (60% versus 55%; RR 1.08, 95% CI 0.81 to 1.45; 3 RCTs, 105 participants); survival over two years (11% versus 10%; RR 1.11, 95% CI 0.24 to 5.05; 1 RCT, 57 participants); pain reduction (78% versus 91%; RR 0.86, 95% CI 0.62 to 1.20; 1 RCT, 25 participants); or urinary continence (63% versus 53%; RR 1.18, 95% CI 0.66 to 2.13; 1 RCT, 34 participants; low quality evidence). Serious adverse effects were more frequent with high-dose corticosteroids (17% versus 0%; RR 8.02, 95% CI 1.03 to 62.37; 2 RCTs, 77 participants; moderate quality evidence).None of the trials reported satisfaction with care or quality of life in participants. Authors' conclusions: Based on current evidence, ambulant adults with MESCC with stable spines and predicted survival of less than six months will probably benefit as much from one dose of radiation (8 Gy) as from two doses (16 Gy) or eight doses (30 Gy). We are unsure if a single dose is as effective as two or more doses in preventing local tumour recurrence. Laminectomy preceding radiotherapy may offer no benefits over radiotherapy alone. Decompressive surgery followed by radiotherapy may benefit ambulant and non-ambulant adults younger than 65 years of age, with poor prognostic factors for radiotherapy, a single area of compression, paraplegia for less than 48 hours, and a predicted survival of more than six months. We are uncertain whether high doses of corticosteroids offer any benefits over moderate doses or indeed no corticosteroids; but high-dose steroids probably significantly increases the risk of serious adverse effects. Early detection; and treatment based on neurological status, age and estimated survival, are crucial with all treatment modalities. Most of the evidence was of low quality. High-quality evidence from more trials is needed to clarify current uncertainties, and some studies are in progress.

The Cochrane database of systematic reviews · meta-analysis · 39 citationsread the source →

Interventions for self-harm in children and adolescents.

Background: Self-harm (SH; intentional self-poisoning or self-injury) is common in children and adolescents, often repeated, and strongly associated with suicide. This is an update of a broader Cochrane review on psychosocial and pharmacological treatments for deliberate SH first published in 1998 and previously updated in 1999. We have now divided the review into three separate reviews; this review is focused on psychosocial and pharmacological interventions for SH in children and adolescents. Objectives: To identify all randomised controlled trials of psychosocial interventions, pharmacological agents, or natural products for SH in children and adolescents, and to conduct meta-analyses (where possible) to compare the effects of specific treatments with comparison types of treatment (e.g., treatment as usual (TAU), placebo, or alternative pharmacological treatment) for children and adolescents who SH. Search methods: For this update the Cochrane Depression, Anxiety and Neurosis Group (CCDAN) Trials Search Co-ordinator searched the CCDAN Specialised Register (30 January 2015). Selection criteria: We included randomised controlled trials comparing psychosocial or pharmacological treatments with treatment as usual, alternative treatments, or placebo or alternative pharmacological treatment in children and adolescents (up to 18 years of age) with a recent (within six months) episode of SH resulting in presentation to clinical services. Data collection and analysis: Two reviewers independently selected trials, extracted data, and appraised study quality, with consensus. For binary outcomes, we calculated odds ratios (OR) and their 95% confidence intervals (CI). For continuous outcomes measured using the same scale we calculated the mean difference (MD) and 95% CI; for those measured using different scales we calculated the standard mean difference (SMD) and 95% CI. Meta-analysis was only possible for two interventions: dialectical behaviour therapy for adolescents and group-based psychotherapy. For these analyses, we pooled data using a random-effects model. Main results: We included 11 trials, with a total of 1,126 participants. The majority of participants were female (mean = 80.6% in 10 trials reporting gender). All trials were of psychosocial interventions; there were none of pharmacological treatments. With the exception of dialectical behaviour therapy for adolescents (DBT-A) and group-based therapy, assessments of specific interventions were based on single trials. We downgraded the quality of evidence owing to risk of bias or imprecision for many outcomes. Therapeutic assessment appeared to increase adherence with subsequent treatment compared with TAU (i.e., standard assessment; n = 70; k = 1; OR = 5.12, 95% CI 1.70 to 15.39), but this had no apparent impact on repetition of SH at either 12 (n = 69; k = 1; OR 0.75, 95% CI 0.18 to 3.06; GRADE: low quality) or 24 months (n = 69; k = 1; OR = 0.69, 05% CI 0.23 to 2.14; GRADE: low quality evidence). These results are based on a single cluster randomised trial, which may overestimate the effectiveness of the intervention. For patients with multiple episodes of SH or emerging personality problems, mentalisation therapy was associated with fewer adolescents scoring above the cut-off for repetition of SH based on the Risk-Taking and Self-Harm Inventory 12 months post-intervention (n = 71; k = 1; OR = 0.26, 95% CI 0.09 to 0.78; GRADE: moderate quality). DBT-A was not associated with a reduction in the proportion of adolescents repeating SH when compared to either TAU or enhanced usual care (n = 104; k = 2; OR 0.72, 95% CI 0.12 to 4.40; GRADE: low quality). In the latter trial, however, the authors reported a significantly greater reduction over time in frequency of repeated SH in adolescents in the DBT condition, in whom there were also significantly greater reductions in depression, hopelessness, and suicidal ideation. We found no significant treatment effects for group-based therapy on repetition of SH for individuals with multiple episodes of SH at either the six (n = 430; k = 2; OR 1.72, 95% CI 0.56 to 5.24; GRADE: low quality) or 12 month (n = 490; k = 3; OR 0.80, 95% CI 0.22 to 2.97; GRADE: low quality) assessments, although considerable heterogeneity was associated with both (I(2) = 65% and 77% respectively). We also found no significant differences between the following treatments and TAU in terms of reduced repetition of SH: compliance enhancement (three month follow-up assessment: n = 63; k = 1; OR = 0.67, 95% CI 0.15 to 3.08; GRADE: very low quality), CBT-based psychotherapy (six month follow-up assessment: n = 39; k = 1; OR = 1.88, 95% CI 0.30 to 11.73; GRADE: very low quality), home-based family intervention (six month follow-up assessment: n = 149; k = 1; OR = 1.02, 95% CI 0.41 to 2.51; GRADE: low quality), and provision of an emergency card (12 month follow-up assessment: n = 105, k = 1; OR = 0.50, 95% CI 0.12 to 2.04; GRADE: very low quality). No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported. Authors' conclusions: There are relatively few trials of interventions for children and adolescents who have engaged in SH, and only single trials contributed to all but two comparisons in this review. The quality of evidence according to GRADE criteria was mostly very low. There is little support for the effectiveness of group-based psychotherapy for adolescents with multiple episodes of SH based on the results of three trials, the evidence from which was of very low quality according to GRADE criteria. Results for therapeutic assessment, mentalisation, and dialectical behaviour therapy indicated that these approaches warrant further evaluation. Despite the scale of the problem of SH in children and adolescents there is a paucity of evidence of effective interventions. Further large-scale trials, with a range of outcome measures including adverse events, and investigation of therapeutic mechanisms underpinning these interventions, are required. It is increasingly apparent that development of new interventions should be done in collaboration with patients to ensure that these are likely to meet their needs. Use of an agreed set of outcome measures would assist evaluation and both comparison and meta-analysis of trials.

The Cochrane database of systematic reviews · meta-analysis · 114 citationsread the source →

Intrinsic, identified, and controlled types of motivation for school subjects in young elementary school children

BACKGROUND: There are two approaches to the differential examination of school motivation. The first is to examine motivation towards specific school subjects (between school subject differentiation). The second is to examine school motivation as a multidimensional concept that varies in terms of not only intensity but also quality (within school subject differentiation). These two differential approaches have led to important discoveries and provided a better understanding of student motivational dynamics. However, little research has combined these two approaches. AIMS: This study examines young elementary students' motivations across school subjects (writing, reading, and maths) from the stance of self-determination theory. First, we tested whether children self-report different levels of intrinsic, identified, and controlled motivation towards specific school subjects. Second, we verified whether children self-report differentiated types of motivation across school subjects. SAMPLE: Participants were 425 French-Canadian children (225 girls, 200 boys) from three elementary schools. Children were in Grades 1 (N=121), 2 (N=126), and 3 (N=178). RESULTS: Results show that, for a given school subject, young elementary students self-report different levels of intrinsic, identified, and controlled motivation. Results also indicate that children self-report different levels of motivation types across school subjects. Our findings also show that most differentiation effects increase across grades. Some gender effects were also observed. CONCLUSION: These results highlight the importance of distinguishing among types of school motivation towards specific school subjects in the early elementary years.

British Journal of Educational Psychology · 554 citationsread the source →

Older Adults' Social Relationships and Health Care Utilization: A Systematic Review.

Background: Deficiencies in older people's social relationships (including loneliness, social isolation, and low social support) have been implicated as a cause of premature mortality and increased morbidity. Whether they affect service use is unclear. Objectives: To determine whether social relationships are associated with older adults' use of health services, independently of health-related needs. Search methods: We searched 8 electronic databases (MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus, the Cochrane Library, and the Centre for Reviews and Dissemination) for data published between 1983 and 2016. We also identified relevant sources from scanning the reference lists of included studies and review articles, contacting authors to identify additional studies, and searching the tables of contents of key journals. Selection criteria: Studies met inclusion criteria if more than 50% of participants were older than 60 years or mean age was older than 60 years; they included a measure of social networks, received social support, or perceived support; and they reported quantitative data on the association between social relationships and older adults' health service utilization. Data collection and analysis: Two researchers independently screened studies for inclusion. They extracted data and appraised study quality by using standardized forms. In a narrative synthesis, we grouped the studies according to the outcome of interest (physician visits, hospital admissions, hospital readmissions, emergency department use, hospital length of stay, utilization of home- and community-based services, contact with general health services, and mental health service use) and the domain of social relationships covered (social networks, received social support, or perceived support). For each service type and social relationship domain, we assessed the strength of the evidence across studies according to the quantity and quality of studies and consistency of findings. Main results: The literature search retrieved 26 077 citations, 126 of which met inclusion criteria. Data were reported across 226 678 participants from 19 countries. We identified strong evidence of an association between weaker social relationships and increased rates of readmission to hospital (75% of high-quality studies reported evidence of an association in the same direction). In evidence of moderate strength, according to 2 high-quality and 3 medium-quality studies, smaller social networks were associated with longer hospital stays. When we considered received and perceived social support separately, they were not linked to health care use. Overall, the evidence did not indicate that older patients with weaker social relationships place greater demands on ambulatory care (including physician visits and community- or home-based services) than warranted by their needs. Authors' conclusions: Current evidence does not support the view that, independently of health status, older patients with lower levels of social support place greater demands on ambulatory care. Future research on social relationships would benefit from a consensus on clinically relevant concepts to measure. Public Health Implications. Our findings are important for public health because they challenge the notion that lonely older adults are a burden on all health and social care services. In high-income countries, interventions aimed at reducing social isolation and loneliness are promoted as a means of preventing inappropriate service use. Our review cautions against assuming that reductions in care utilization can be achieved by intervening to strengthen social relationships.

American journal of public health · systematic review · 128 citationsread the source →

TELEMEDICINE VERSUS IN-PERSON DELIVERY OF COGNITIVE PROCESSING THERAPY FOR WOMEN WITH POSTTRAUMATIC STRESS DISORDER: A RANDOMIZED NONINFERIORITY TRIAL

BACKGROUND: This study examined the effectiveness of telemedicine to provide psychotherapy to women with posttraumatic stress disorder (PTSD) who might be unable to access treatment. Objectives were to compare clinical and process outcomes of PTSD treatment delivered via videoteleconferencing (VTC) and in-person (NP) in an ethnically diverse sample of veteran and civilian women with PTSD. METHODS: A randomized controlled trial of Cognitive Processing Therapy, an evidence-based intervention for PTSD, was conducted through a noninferiority design to compare delivery modalities on difference in posttreatment PTSD symptoms. Women with PTSD, including 21 veterans and 105 civilians, were assigned to receive psychotherapy delivered via VTC or NP. Primary treatment outcomes were changes in PTSD symptoms in the completer sample. RESULTS: Improvements in PTSD symptoms in the VTC condition (n = 63) were noninferior to outcomes in the NP condition (n = 63). Clinical outcomes obtained when both conditions were pooled together (N = 126) demonstrated that PTSD symptoms declined substantially posttreatment (mean = -20.5, 95% CI -29.6 to -11.4) and gains were maintained at 3- (mean = -20.8, 95% CI -30.1 to -11.5) and 6-month followup (mean = -22.0, 95% CI -33.1 to -10.9. Veterans demonstrated smaller symptom reductions posttreatment (mean = -9.4, 95% CI -22.5 to 3.7) than civilian women (mean = -22.7, 95% CI -29.9 to -15.5. CONCLUSIONS: Providing psychotherapy to women with PTSD via VTC produced outcomes comparable to NP treatment. VTC can increase access to specialty mental health care for women in rural or remote areas.

Depression and Anxiety · randomised controlled trial · 179 citationsread the source →

Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, setting, and participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main outcomes and measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial registration: ClinicalTrials.gov Identifier: NCT02933970.

JAMA · randomised controlled trial · 49 citationsread the source →

Effect of Family Navigation on Diagnostic Ascertainment Among Children at Risk for Autism: A Randomized Clinical Trial From DBPNet.

Importance: Early identification of autism spectrum disorder (ASD) is associated with improved cognitive and behavioral outcomes. Targeted strategies are needed to support equitable access to diagnostic services to ensure that children from low-income and racial/ethnic minority families receive the benefits of early ASD identification and treatment. Objective: To test the efficacy of family navigation (FN), an individually tailored, culturally informed care management strategy, to increase the likelihood of achieving diagnostic ascertainment among young children at risk for ASD. Design, setting, and participants: This randomized clinical trial of 249 families of children aged 15 to 27 months who had positive screening results for possible ASD was conducted in 11 urban primary care sites in 3 cities. Data collection occurred from February 24, 2015, through November 5, 2018. Statistical analysis was performed on an intent-to-treat basis from November 5, 2018, to July 27, 2020. Interventions: Families were randomized to FN or conventional care management (CCM). Families receiving FN were assigned a navigator who conducted community-based outreach to families to address structural barriers to care and support engagement in recommended services. Families receiving CCM were assigned to a care manager, who did limited telephone outreach. Families received FN or CCM after positive initial screening results and for 100 days after diagnostic ascertainment. Main outcomes and measures: The primary outcome, diagnostic ascertainment, was measured as the number of days from randomization to completion of the child's clinical developmental evaluation, when a diagnosis of ASD or other developmental disorder was determined. Results: Among 250 families randomized, 249 were included in the primary analysis (174 boys [69.9%]; mean [SD] age, 22.0 [3.5] months; 205 [82.3%] publicly insured; 233 [93.6%] non-White). Children who received FN had a greater likelihood of reaching diagnostic ascertainment over the course of 1 year (FN, 108 of 126 [85.7%]; CCM, 94 of 123 [76.4%]; unadjusted hazard ratio [HR], 1.39 [95% CI, 1.05-1.84]). Site (Boston, New Haven, and Philadelphia) and ethnicity (Hispanic vs non-Hispanic) moderated the effect of FN (treatment × site interaction; P = .03; Boston: HR, 2.07 [95% CI, 1.31-3.26]; New Haven: HR, 1.91 [95% CI, 0.94-3.89]; and Philadelphia: HR, 0.91 [95% CI, 0.60-1.37]) (treatment × ethnicity interaction; P < .001; Hispanic families: HR, 2.81 [95% CI, 2.23-3.54] vs non-Hispanic families: HR, 1.49 [95% CI, 1.45-1.53]). The magnitude of FN's effect was significantly greater among Hispanic families than among non-Hispanic families (diagnostic ascertainment among Hispanic families: FN, 90.9% [30 of 33], and CCM, 53.3% [16 of 30]; vs non-Hispanic families: FN, 89.7% [35 of 39], and CCM, 77.5% [31 of 40]). Conclusions and relevance: Family navigation improved the likelihood of diagnostic ascertainment among children from racial/ethnic minority, low-income families who were detected as at risk for ASD in primary care. Results suggest differential effects of FN by site and ethnicity. Trial registration: ClinicalTrials.gov Identifier: NCT02359084.

JAMA pediatrics · randomised controlled trial · 46 citationsread the source →

Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial.

Background: Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65-70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies on maintenance of reduced depression symptoms 12 months after treatment. Methods: We did this multicentre, pragmatic, observer-blind, randomised controlled superiority trial (IMPACT) at 15 National Health Service child and adolescent mental health service (CAMHS) clinics in three regions in England. Adolescent patients (aged 11-17 years) with a diagnosis of DSM IV major depressive disorder were randomly assigned (1:1:1), via a web-based randomisation service, to receive cognitive behavioural therapy (CBT) or short-term psychoanalytical therapy versus a reference brief psychological intervention. Randomisation was stochastically minimised by age, sex, self-reported depression sum score, and region. Patients and clinicians were aware of group allocation, but allocation was concealed from outcome assessors. Patients were followed up and reassessed at weeks 6, 12, 36, 52, and 86 post-randomisation. The primary outcome was self-reported depression symptoms at weeks 36, 52, and 86, as measured with the self-reported Mood and Feelings Questionnaire (MFQ). Because our aim was to compare the two psychological therapies with the brief psychosocial intervention, we first established whether CBT was inferior to short-term psychoanalytical psychotherapy for the same outcome. Primary analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN83033550. Findings: Between June 29, 2010, and Jan 17, 2013, we randomly assigned 470 patients to receive the brief psychosocial intervention (n=158), CBT (n=155), or short-term psychoanalytical therapy (n=157); 465 patients comprised the intention-to-treat population. 392 (84%) patients had available data for primary analysis by the end of follow-up. Treatment fidelity and differentiation were established between the three interventions. The median number of treatment sessions differed significantly between patients in the brief psychosocial intervention group (n=6 [IQR 4-11]), CBT group (n=9 [5-14]), and short-term psychoanalytical therapy group (n=11 [5-23]; p<0·0001), but there was no difference between groups in the average duration of treatment (27·5 [SD 21·5], 24·9 [17·7], 27·9 [16·8] weeks, respectively; Kruskal-Wallis p=0·238). Self-reported depression symptoms did not differ significantly between patients given CBT and those given short-term psychoanalytical therapy at weeks 36 (treatment effect 0·179, 95% CI -3·731 to 4·088; p=0·929), 52 (0·307, -3·161 to 3·774; p=0·862), or 86 (0·578, -2·948 to 4·104; p=0·748). These two psychological treatments had no superiority effect compared with brief psychosocial intervention at weeks 36 (treatment effect -3·234, 95% CI -6·611 to 0·143; p=0·061), 52 (-2·806, -5·790 to 0·177; p=0·065), or 86 (-1·898, -4·922 to 1·126; p=0·219). Physical adverse events (self-reported breathing problems, sleep disturbances, drowsiness or tiredness, nausea, sweating, and being restless or overactive) did not differ between the groups. Total costs of the trial interventions did not differ significantly between treatment groups. Interpretation: We found no evidence for the superiority of CBT or short-term psychoanalytical therapy compared with a brief psychosocial intervention in maintenance of reduced depression symptoms 12 months after treatment. Short-term psychoanalytical therapy was as effective as CBT and, together with brief psychosocial intervention, offers additional patient choice for psychological therapy, alongside CBT, for adolescents with moderate to severe depression who are attending routine specialist CAMHS clinics. Funding: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health.

The lancet. Psychiatry · randomised controlled trial · 149 citationsread the source →

Towards universal voluntary HIV testing and counselling: a systematic review and meta-analysis of community-based approaches.

Background: Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC. Methods and findings: PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's "risk of bias" tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates. 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27-18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06-1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16-1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37-0.96), relative to facility-based approaches. 80% (95% CI 75%-85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%-85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2-US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52-14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73-1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested. Conclusions: Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment. Review registration: International Prospective Register of Systematic Reviews CRD42012002554 Please see later in the article for the Editors' Summary.

PLoS medicine · meta-analysis · 313 citationsread the source →

A home-based training program improves caregivers' skills and dementia patients' aggressive behaviors: a randomized controlled trial.

Objective: To investigate the effects of an individualized, home-based caregiver-training program for caregivers of elderly patients with dementia and behavioral problems. Methods: Using a randomized clinical trial in the neurologic clinics of two hospitals and a community care management center in northern Taiwan, we tested an individualized home-based caregiver-training program for managing behavioral problems, with referrals to community services and telephone consultation. Participants were patients with dementia and their caregivers (N = 129): 63 in the intervention group and 66 in the control group. The control group received only written instructions and social telephone follow-ups. Behavioral problems of elderly dementia patients were assessed by the Chinese version of the Cohen-Mansfield Agitation Inventory, community form. Family caregivers' outcomes were measured by the Agitation Management Self-efficacy Scale and the Preparedness and Competence Scales. These instruments were administered before the program and 2 weeks, 3 months, and 6 months afterward. Results: Family caregivers who received the individualized home-based training program had better preparedness (t = 2.72, df = 127, p <0.01), competence (t = 4.77, df = 126, p <0.001), and overall self-efficacy (t = 3.81, df = 127, p <0.001) at 3 months than those in the control group. Moreover, the growth rate by treatment interaction effect was significant for caregiver competence (t = 2.25, df = 127, p <0.05) and overall self-efficacy for managing behavioral problems (t = 2.16, df = 127, p <0.05). The probability of physically aggressive behavior for patients in the intervention group decreased from 0.27 to 0.12. Conclusion: Our individualized home-based caregiver-training program improved caregivers' preparedness, competence, and self-efficacy for managing problematic behaviors and decreased physical aggressiveness of elderly patients with dementia.

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · randomised controlled trial · 49 citationsread the source →

Healthy feeding habits: efficacy results from a cluster-randomized, controlled exploratory trial of a novel, habit-based intervention with parents.

Background: As dietary gatekeepers for young children, parents are often the proximal target of family-based dietary interventions. Habit theory offers a novel approach to modifying parental feeding, based on "context-dependent repetition" to promote automatic responding and to reduce decisional conflict. Objective: This exploratory trial evaluated an intervention promoting habit formation for 3 parental feeding behaviors: serving fruit/vegetables, serving healthy snacks, and serving nonsweetened drinks. The primary outcome was parental habit strength for each behavior. The secondary outcome was children's food intake. Design: Parents of children aged 2-6 y (n = 126) were recruited from 6 children's centers in London and cluster-randomized to intervention (n = 3) or no-treatment control (n = 3) conditions. Parents in the intervention group (n = 58) received training on habit formation for 3 feeding behaviors; control participants (n = 68) were asked only to complete the measures. At baseline and after treatment, parents completed validated measures of subjective "automaticity" for feeding behaviors and a brief child food-frequency measure. Parents in the intervention group were interviewed about the program. The change between groups, after clustering was controlled for, was analyzed. Results: For all parental feeding behaviors, automaticity increased more in the intervention group than in the control group (P < 0.01 for all). Significant intervention effects on children's intake of vegetables (P = 0.003), healthy snacks (P = 0.009), and water (P = 0.032) were observed. Changes in children's food intake correlated with changes in parental automaticity of feeding behaviors, and program acceptability was high. Conclusions: A habit-based intervention successfully modified parental feeding behaviors, affected children's diets positively, and was well received by parents. Habit theory provides a promising new tool to support family-based obesity prevention. This trial was registered as ISRCTN09910187.

The American journal of clinical nutrition · randomised controlled trial · 67 citationsread the source →

Randomized controlled trial of a clinic-based survivorship intervention following adjuvant therapy in breast cancer survivors.

In 2006, the IOM released a report citing the importance of "survivorship plans" to improve quality of life and care coordination for cancer survivors, but little has been done to evaluate their efficacy. Women with early-stage breast cancer were randomized within 6 weeks of completing adjuvant therapy to a survivorship intervention group (SI) or control group (CG). All subjects were given the NCI publication, "Facing Forward: Life after Cancer Treatment." The SI also met with a nurse/nutritionist to receive a treatment summary, surveillance, and lifestyle recommendations. Both groups completed questionnaires on the impact of cancer (IOC), patient satisfaction (FACIT-TS-PS), and assessment of survivor concerns (ASC) at baseline, 3 and 6 months. Within and between group t tests and linear regression analyses were performed. Among 126 women (60 CG, 66 SI), mean age was 54 years, 48 % were Hispanic, and the groups were well-balanced by baseline characteristics. No significant differences between the CG and SI on the FACIT-TS-PS or IOC at 3 and 6 months were seen. The ASC health worry subscale was lower (less worry) in the SI compared to CG (p = 0.02). At all time-points, Hispanic women had higher (worse) health worry (p = 0.0008), social-life interference (p = 0.009), and meaning of cancer scales (p = 0.0004), and more trust in medical professionals (p = 0.03) compared to non-Hispanic women. While the SI did not lead to significant improvements in most patient-reported outcomes, it was associated with decreased health worry. Future interventions should determine the most efficient and effective method for delivering survivorship care plans.

Breast cancer research and treatment · randomised controlled trial · 95 citationsread the source →

Acceptance and commitment therapy as guided self-help for psychological distress and positive mental health: a randomized controlled trial.

Background: In order to reduce the high prevalence of depression, early interventions for people at risk of depression are warranted. This study evaluated the effectiveness of an early guided self-help programme based on acceptance and commitment therapy (ACT) for reducing depressive symptomatology. Method: Participants with mild to moderate depressive symptomatology were recruited from the general population and randomized to the self-help programme with extensive email support (n=125), the self-help programme with minimal email support (n=125) or to a waiting list control group (n=126). Participants completed measures before and after the intervention to assess depression, anxiety, fatigue, experiential avoidance, positive mental health and mindfulness. Participants in the experimental conditions also completed these measures at a 3-month follow-up. Results: In the experimental conditions significant reductions in depression, anxiety, fatigue, experiential avoidance and improvements in positive mental health and mindfulness were found, compared with the waiting list condition (effect sizes Cohen's d=0.51-1.00). These effects were sustained at the 3-month follow-up. There were no significant differences between the experimental conditions on the outcome measures. Conclusions: The ACT-based self-help programme with minimal email support is effective for people with mild to moderate depressive symptomatology.

Psychological medicine · randomised controlled trial · 103 citationsread the source →

An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline.

Objective: Major depressive disorder has been linked with inflammatory processes, but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial. The authors tested the hypothesis that C-reactive protein (CRP), a commonly available marker of systemic inflammation, predicts differential response to escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor). Method: The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter open-label randomized clinical trial. CRP was measured with a high-sensitivity method in serum samples from 241 adult men and women with major depressive disorder randomly allocated to 12-week treatment with escitalopram (N=115) or nortriptyline (N=126). The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale (MADRS), administered weekly. Results: CRP level at baseline differentially predicted treatment outcome with the two antidepressants (CRP-drug interaction: β=3.27, 95% CI=1.65, 4.89). For patients with low levels of CRP (<1 mg/L), improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline. For patients with higher CRP levels, improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram. CRP and its interaction with medication explained more than 10% of individual-level variance in treatment outcome. Conclusions: An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.

The American journal of psychiatry · randomised controlled trial · 303 citationsread the source →

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial.

Objectives: Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression. Study design: We enrolled 126 pregnant women at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a history of depression) in early pregnancy and randomly assigned them to receive EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment, 26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were analyzed at entry and at 34-36 weeks' gestation. Results: One hundred eighteen women completed the trial. There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation. The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively. Serum DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late pregnancy. Conclusion: EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum.

American journal of obstetrics and gynecology · randomised controlled trial · 63 citationsread the source →

Development and validation of two measures of emotional contrast avoidance: The contrast avoidance questionnaires.

The Contrast Avoidance (CA) model (Newman & Llera, 2011) proposed that individuals with generalized anxiety disorder (GAD) fear sharp emotional shifts (or contrasts), such as the shift from a pleasant or neutral state to one of sudden distress following a negative event. Further, the model suggests that chronic worry is employed by those with GAD to sustain negative emotionality as a means to avoid sudden shifts into negativity. The model has received empirical support; however, no validated measure exists to assess CA tendencies. In this paper we developed and tested two measures of CA: one focusing on worry, and another examining broader mechanisms of CA that could be used test whether CA is applicable to other disorders. In Study 1, Part 1, we used 3 samples of participants (each N=410) to perform item reduction, exploratory factor analysis, and confirmatory factor analysis. In Study 1, Part 2, we performed tests of construct validity. In Study 2, we used a new sample (N=126) to determine test-retest reliability. All data point to the strong psychometric properties of the CA questionnaires and their relationship to GAD. Both measures distinguished between participants reporting clinical levels of GAD symptoms and nonanxious controls, demonstrating their utility as complementary measures of CA tendencies.

Journal of anxiety disorders · cohort or longitudinal · 44 citationsread the source →

Delayed emergency healthcare seeking behaviour by Dutch emergency department visitors during the first COVID-19 wave: a mixed methods retrospective observational study.

Background: Emergency department (ED) visits due to non-coronavirus disease 2019 (COVID-19) conditions have drastically decreased since the outbreak of the COVID-19 pandemic. This study aimed to identify the magnitude, characteristics and underlying motivations of ED visitors with delayed healthcare seeking behaviour during the first wave of the pandemic. Methods: Between March 9 and July 92,020, adults visiting the ED of an academic hospital in the East of the Netherlands received an online questionnaire to collect self-reported data on delay in seeking emergency care and subsequent motivations for this delay. Telephone interviews were held with a subsample of respondents to better understand the motivations for delay as described in the questionnaire. Quantitative data were analysed using descriptive statistics. Qualitative data were thematically analysed. Results: One thousand three hundred thirty-eight questionnaires were returned (34.0% response). One in five respondents reported a delay in seeking emergency care. Almost half of these respondents (n = 126; 45.4%) reported that the pandemic influenced the delay. Respondents reporting delay were mainly older adults (mean 61.6; ±13.1 years), referred to the ED by the general practitioner (GP; 35.1%) or a medical specialist (34.7%), visiting the ED with cardiac problems (39.7%). The estimated median time of delay in receiving ED care was 3 days (inter quartile range  8 days). Respectively 46 (16.5%) and 26 (9.4%) respondents reported that their complaints would be either less severe or preventable if they had sought for emergency care earlier. Delayed care seeking behaviour was frequently motivated by: fear of contamination, not wanting to burden professionals, perceiving own complaints less urgent relative to COVID-19 patients, limited access to services, and by stay home instructions from referring professionals. Conclusions: A relatively large proportion of ED visitors reported delay in seeking emergency care during the first wave. Delay was often driven by misperceptions of the accessibility of services and the legitimacy for seeking emergency care. Public messaging and close collaboration between the ED and referring professionals could help reduce delayed care for acute needs during future COVID-19 infection waves.

BMC emergency medicine · cohort or longitudinal · 54 citationsread the source →

The Surgeon as the Second Victim? Results of the Boston Intraoperative Adverse Events Surgeons' Attitude (BISA) Study.

Background: An intraoperative adverse event (iAE) is often directly attributable to the surgeon's technical error and/or suboptimal intraoperative judgment. We aimed to examine the psychological impact of iAEs on surgeons as well as the surgeons' attitude about iAE reporting. Study design: We conducted a web-based cross-sectional survey of all surgeons at 3 major teaching hospitals of the same university. The 29-item questionnaire was developed using a systematic closed and open approach focused on assessing the surgeons' personal account of iAE incidence, emotional response to iAEs, available support systems, and perspective about the barriers to iAE reporting. Results: The response rate was 44.8% (n = 126). Mean age of respondents was 49 years, 77% were male, and 83% performed >150 procedures/year. During the last year, 32% recalled 1 iAE, 39% recalled 2 to 5 iAEs, and 9% recalled >6 iAEs. The emotional toll of iAEs was significant, with 84% of respondents reporting a combination of anxiety (66%), guilt (60%), sadness (52%), shame/embarrassment (42%), and anger (29%). Colleagues constituted the most helpful support system (42%) rather than friends or family; a few surgeons needed psychological therapy/counseling. As for reporting, 26% preferred not to see their individual iAE rates, and 38% wanted it reported in comparison with their aggregate colleagues' rate. The most common barriers to reporting iAEs were fear of litigation (50%), lack of a standardized reporting system (49%), and absence of a clear iAE definition (48%). Conclusions: Intraoperative AEs occur often, have a significant negative impact on surgeons' well-being, and barriers to transparency are fear of litigation and absence of a well-defined reporting system. Efforts should be made to support surgeons and standardize reporting when iAEs occur.

Journal of the American College of Surgeons · cohort or longitudinal · 110 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 →

Inflammation and Schizophrenia

An association between inflammatory abnormalities and schizophrenia has been found repeatedly. The purposes of this special feature are to clarify the key findings on inflammation in schizophrenia, identify major gaps in the literature, and suggest priorities for research in this area. Inflammation is one of the body’s first lines of defense in response to injury or infection, and increased inflammation is found in many diseases. Acute inflammation is a nonspecific response characterized by warmth, pain, and swelling. Leukocytes migrate to the area of injury and become activated, the blood supply to the area increases, and blood vessels become more permeable, allowing cells and molecules to leave blood vessels and enter the injured tissue. The inflammatory response also involves the complement system, a group of proteins that, when activated, combine to form a complex molecular structure that kills cells, usually bacteria and parasites. Cytokines are key molecules that regulate inflammation; they also have important roles in the immune system. They are produced by a wide variety of immune cells and cells outside of the immune system. The term cytokine derives from their ability to influence the movement of inflammatory cells, but they also have other functions. Chronic inflammation is usually a lower grade response, lacks the grossly visible signs of acute inflammation, and may be systemic rather than localized. Chronic inflammation plays a role in the pathophysiology of many chronic diseases, including cardiovascular and cerebrovascular disease, diabetes, Alzheimer’s disease, and some cancers. The characteristics of chronic inflammation differ somewhat in the brain from what occurs in other tissues. An important component of neuroinflammation is the microglial activation. The brain contains relatively few of the inflammatory cells that are found outside the brain. Microglia, which are related to the peripheral inflammatory cells, serve some of the protective functions such cells play in the rest of the body. Microglia are involved in other brain functions, including the pruning and maintenance of synapses, trafficking of neurotransmitters, and devouring—phagocytosis—of cell fragments and damaged cells. Activated microglia produce inflammatory cytokines and the phagocytose cells or proteins that provoke the inflammatory response. Microglial activation and subsequent proinflammatory cytokine production may disrupt the blood-brain barrier (BBB). An intact BBB usually tightly controls the entry of cytokines and leukocytes into brain tissue. Damage to the BBB impairs its ability to control which inflammatory cells and molecules enter the brain; other substances leak into brain tissue, and the brain is unable to function normally. A discussion of prenatal inflammation as a risk factor for schizophrenia is beyond the scope of the present special feature, and the reader is referred to previous reviews of human1,2 and animal studies.3–6 Numerous studies have found that people with schizophrenia have increased blood concentrations of inflammatory cytokines.7 Two important themes emerge from these studies. First, inflammatory abnormalities are present in subjects with first-episode, drug-naive psychosis (FEP) compared with controls, suggesting an association that may be independent of the effects of antipsychotic medications. Second, the concentrations of some inflammatory molecules may vary with the clinical status of patients: ie, there appear to be separate groups of state and trait markers. The state-related markers include interleukin (IL) 1-beta, IL-6, and transforming growth factor-beta. People with schizophrenia have higher concentrations of these cytokines than controls during an exacerbation of symptoms, but there is no difference during periods of clinical stability. IL-12, interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) appear to be trait markers. Concentrations of these cytokines are higher in patients with FEP than in controls, and in patients with chronic illness, during both periods of symptomatic worsening, than in controls. C-reactive protein (CRP), another proinflammatory molecule, also appears to be a state marker,8 and specific lymphocyte populations may also segregate into state and trait markers.9 Additional evidence for potential state-related markers in schizophrenia has been reviewed elsewhere.10 Two studies suggest that inflammatory molecules may predict subsequent relapse.11,12 Other studies have found abnormal levels of inflammatory parameters in the central nervous system (CNS) in schizophrenia, including cerebrospinal fluid (CSF) cytokine11 and leukocyte levels,13,14 CNS microglia and lymphocytes,15–19 CSF and CNS oxidative stress,20,21 and anti-N-methyl-D-aspartate receptor autoantibodies.22 There is also evidence suggesting that infections may be associated with illness relapse.23 Within schizophrenia, blood cytokine abnormalities have been associated with poorer cognitive function and measures of regional brain volume24–26 and negative symptoms.27–30 There are several randomized clinical trials of the nonsteroidal anti-inflammatory drugs (NSAIDs) celecoxib and aspirin as adjuncts to antipsychotics.31 Interpretation of this evidence is complex, as these studies have not consistently distinguished relapsed from clinically stable patients. Furthermore, if inflammation plays a role in psychotic relapse, the efficacy of anti-inflammatory treatments may “disappear” in a lengthy trial because the treatment would not have any effect once patients have returned to their clinical baseline. However, an adjunctive agent that accelerates a patient’s antipsychotic response would be valuable. Agents other than NSAIDs that have anti-inflammatory properties, used in adjunct to antipsychotics, have been found to be superior to placebo. There have been two trials of minocycline,32,33 a second-generation tetracycline with anti-inflammatory and antimicrobial effects, that were superior to placebo. The efficacy of minocycline may have “disappeared” over the course of one trial,33 raising the possibility of an effect restricted to relapsed patient and not in those at a stable baseline. Adenosine is a purine nucleoside that modulates many physiological processes and has anti-inflammatory effects. A meta-analysis found that adjunctive treatment with adenosine-modulating drugs is superior to the effects of placebo.34 These drugs were associated with significant symptomatic improvement in inpatients, but not in outpatients, supporting the concept that state/trait differences may be an important predictor of antipsychotic response to adjunctive agents. Oxidative stress refers to an increase in free radicals, highly reactive molecules generated from metabolism and environmental exposures that can damage cell membranes. Inflammation and oxidative stress strongly influence each other.35 Antioxidant drugs decrease oxidative stress. One trial found that adjunctive treatment with the antioxidant N-acetylcysteine significantly reduced psychopathology in schizophrenia.36 A trial of fish oil, which also has significant anti-inflammatory effects, was conducted in adolescents and young adults with subthreshold psychotic symptoms,37 ie, “prodromal” patients. Patients receiving fish oil were significantly less likely to progress to a psychotic disorder than subjects receiving a placebo. Interestingly, fish oil was prescribed for 12 weeks, but the protective benefits with regards to transition to psychosis remained significant for 40 weeks after cessation of treatment. Inflammation may be a common mediator of diverse prenatal risk factors for schizophrenia, including preterm labor; preeclampsia (pregnancy-induced hypertension); neonatal birth asphyxia; and maternal gestational diabetes, stress, and depression.2 Maternal serum concentrations of the cytokines IL-838 and TNF-alpha39 during pregnancy were associated with an increased risk of schizophrenia in the offspring. Animal studies suggest that inflammation during critical periods of neurodevelopment may permanently alter the “set-point” of the inflammatory system, with increased inflammation in adult offspring.40–45 Meta-analyses have confirmed the presence of other abnormalities in schizophrenia that are associated with inflammation: increased autoantibodies,22 oxidative stress,46 CRP,8 and circulating lymphocytes.9 Antibodies are crucial “weapons” the immune system uses against foreign proteins. Autoantibodies, antibodies against a person’s own proteins, are associated with cytokine abnormalities.47 Lymphocytes, a group of white blood cells that combat infections, produce antibodies, and are an important source of cytokines, are increased in schizophrenia.9 Some subsets of lymphocytes may be state markers for acute psychosis, whereas others may be trait markers.9 CRP is a protein synthesized by the liver in response to inflammation, particularly IL-6 and other cytokines. Inflammation and oxidative stress may contribute to the decreased blood and CNS membrane levels of polyunsaturated fatty acids observed in schizophrenia.48 There are other disorders outside of schizophrenia in which peripheral inflammation appears to impact brain function. Inflammation is a risk factor for Alzheimer’s disease and mild cognitive impairment,49 rheumatoid arthritis is a risk factor for dementia,50 and “sickness behavior” is induced by peripheral cytokines.51,52 Depression is also associated with increased inflammation.53 The effects in depressed patients of an antibody against the cytokine TNF-alpha54 support the concept that brain function is impacted by peripheral cytokines. There are other mechanisms by which peripheral inflammation might cause or reflect brain dysfunction in schizophrenia. Cytokines may directly modulate dopaminergic neurotransmission55–57 or indirectly modulate glutamatergic neurotransmission through tryptophan metabolism.58–61 There is also some movement of peripheral leukocytes into the brain parenchyma, and the interaction of cytokines with the vagus nerve influences brain function.62 Blood cytokines induce cytokine production in the cells that form the BBB, and cytokines may move into the brain via the circumventricular organs, which lack a BBB.62 Inflammation may also disrupt the BBB, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. Some have suggested that the increase in blood concentrations of the protein S100-beta in schizophrenia63 is consistent with abnormal function of the BBB in people with schizophrenia, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. However, circulating S100-beta has sources other than the brain.64,65 Several potentially confounding variables are important to consider in studies of inflammation. Antipsychotics increase the risk of weight gain and diabetes, which are associated with inflammation. However, there is evidence from meta-analyses of abnormal inflammatory parameters in FEP,8,9,22,46 suggesting that the association between schizophrenia and inflammation is not solely due to antipsychotics. Antipsychotic-naïve relatives of people with schizophrenia also have increased inflammation compared with controls.66–68 Other potentially confounding variables include body mass index, age, gender, smoking, alcohol and illicit drug use, and whether patients are fasting at the time of sampling.69 The proportion of studies that either matched patients and controls, or statistically controlled for many of these potential confounders, has been low.8,9,22,46 Inflammation is comorbid with other physiological abnormalities, including hypertension, impaired glucose tolerance (fasting blood glucose [FBG] 100–126mg/dl), diabetes (FBG > 126, or a random blood glucose >200mg/dl), and increased oxidative stress. The associations with these other conditions also support the plausibility of increased inflammation in schizophrenia. However, the comorbidity of these physiological measures in schizophrenia complicates the interpretation of adjunctive treatment trials: what is the best therapeutic target? Another complicating issue is the relationship of inflammation to neurotropic viruses. One study found that treatment of patients with antibodies to herpes simplex 1 virus with a herpes-specific antiviral drug improved cognition with impressive effect sizes, suggesting the presence of an ongoing problem related to the virus.70 The association of other infectious agents with schizophrenia also raises the question of what relationship might exist between inflammation and either chronic infections or the expression of genes derived from an infectious agent and integrated into human DNA. The background presented above can be used to guide future research. Attempts to replicate current findings in well-matched patients and controls would be helpful. Cytokine levels in subjects with prodromal psychosis have not been investigated. We would hypothesize that these subjects should have abnormal trait markers compared with controls; within prodromal subjects, those who develop clinical psychosis should have abnormal state markers compared with high-risk subjects who do not. The effects of fish oil in preventing conversion to psychosis in high-risk subjects should be investigated in relationship to its effects on inflammation. The therapeutic anti-inflammatory agents that have been studied to date, such as aspirin, celecoxib, and fish oil, have multiple actions. Specific antibodies against individual cytokines are used in the treatment of rheumatoid arthritis and have been studied in depression.54 A change in symptoms or cognition in response to these antibodies would directly implicate inflammation in the pathophysiology of schizophrenia. More longitudinal studies with serial measurement of inflammatory parameters across the clinical course of illness are needed. It would be useful to test the hypothesis that patients with treatment-resistant schizophrenia have a different inflammatory profile than other patients with schizophrenia.7 Although it seems likely that there is increased inflammation in the brain when there are cytokine increases in the peripheral blood, the response might not be exactly the same in these two compartments. For instance, the inflammatory cytokines with altered levels in the brain might not be the same as those that change in the blood. More studies of markers of inflammation in the CNS—including CSF, postmortem analyses, and imaging studies—are needed. Two strategies may increase the signal-to-noise ratio for adjunctive trials of anti-inflammatory agents. First, inflammation may play a role in some patients with schizophrenia but not others. Patients with evidence of inflammation in the peripheral blood may be more likely to respond to an anti-inflammatory treatment strategy than those without inflammation and should be the ones included in treatment studies. Second, acutely ill and stable patients should be studied in separate trials and considered separately in meta-analyses. Furthermore, baseline-to-end-point analyses may not appropriate for studies of relapsed patients because there may be faster improvement with the use of adjunctive anti-inflammatories but not a greater total improvement by the end of the study. Studies of inflammation in schizophrenia should assess possible relationships of inflammatory cells and molecules to symptoms and cognition. To date, few studies have considered these measures.8,9,22,46 The comorbidity of inflammation, oxidative stress, hypertension, and abnormal glucose concentrations raise the issue what is the most appropriate treatment target in schizophrenia. As a first step in understanding this issue, it would be helpful to investigate relationships between inflammation, oxidative stress, hypertension, and glucose intolerance on the one hand, and clinical variables on the other. Several studies found that first-degree relatives of people with schizophrenia have increased inflammation and oxidative stress.66–68 It would advance the field to test the hypothesis that relatives have abnormal concentrations of the trait markers for schizophrenia but not of the state markers associated with relapse. Inflammatory molecules do not work in isolation but have complex interactions among themselves and with other systems. Most previous studies have measured only a small number of molecules. Concurrent measurement of cytokines, leukocytes, oxidative stress, and related parameters would increase the ability to make broader inferences regarding inflammation. Furthermore, if groups or clusters of covarying molecules—ie, molecules that change simultaneously—could be defined within schizophrenia, investigation of these groups is likely to yield better signal-to-noise ratios than individual molecules and should have more biological validity. Does increased inflammation due to infections or physical trauma increase the risk of relapse? If so, do preventive measures (eg, antibiotic prophylaxis for recurrent urinary tract infections)23 decrease that risk? What is the relationship between inflammation and the presence of antibodies to herpes viruses, toxoplasmosis, etc? Although the evidence on inflammation in schizophrenia is provocative, the number of studies in some areas is small, and increased methodological rigor is needed. Nonetheless, the evidence from FEP and first-degree relatives of patients with schizophrenia supports the idea that increased inflammation is truly associated with schizophrenia. This research raises the possibility that further study of inflammation will lead to greater understanding of the etiology and pathophysiology of schizophrenia. Dr B.K. is a member of Advisory Boards for Genentech and Roche. In the past 3 years, Dr B.J.M has received grant support from the National Institute of Mental Health (K23MH098014), the Georgia Regents University (GRU) Intramural Scientist Training Program, the GRU Brain & Behavior and Immunotherapy Discovery Institutes, the University of Oulu (Finland), the Thule Institute of the University of Oulu, and Oy H. Lundbeck Ab; research support from the National Institutes of Health Clinical Loan Repayment Program; consultancy fees for surveys from Medefied Europe and Plaza Research, on behalf of Genetech/Roche; speaker fees for grand rounds lectures from the Maryland Psychiatric Research Center and the Texas A&M University and Scott and White Hospital Department of Psychiatry; and payment for a survey from e-Rewards Medical Market Research.

Schizophrenia Bulletin · review · 315 citationsread the source →

Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies.

Background: In the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs. We did three substudies to assess the mechanisms underlying this superiority and the pathogenesis of resistant hypertension. Methods: PATHWAY-2 was a randomised, double-blind crossover trial done at 14 UK primary and secondary care sites in 314 patients with resistant hypertension. Patients were given 12 weeks of once daily treatment with each of placebo, spironolactone 25-50 mg, bisoprolol 5-10 mg, and doxazosin 4-8 mg and the change in home systolic blood pressure was assessed as the primary outcome. In our three substudies, we assessed plasma aldosterone, renin, and aldosterone-to-renin ratio (ARR) as predictors of home systolic blood pressure, and estimated prevalence of primary aldosteronism (substudy 1); assessed the effects of each drug in terms of thoracic fluid index, cardiac index, stroke index, and systemic vascular resistance at seven sites with haemodynamic monitoring facilities (substudy 2); and assessed the effect of amiloride 10-20 mg once daily on clinic systolic blood pressure during an optional 6-12 week open-label runout phase (substudy 3). The PATHWAY-2 trial is registered with EudraCT, number 2008-007149-30, and ClinicalTrials.gov, number NCT02369081. Findings: Of the 314 patients in PATHWAY-2, 269 participated in one or more of the three substudies: 126 in substudy 1, 226 in substudy 2, and 146 in substudy 3. Home systolic blood pressure reduction by spironolactone was predicted by ARR (r2=0·13, p<0·0001) and plasma renin (r2=0·11, p=0·00024). 42 patients had low renin concentrations (predefined as the lowest tertile of plasma renin), of which 31 had a plasma aldosterone concentration greater than the mean value for all 126 patients (250 pmol/L). Thus, 31 (25% [95% CI 17-33]) of 126 patients were deemed to have inappropriately high aldosterone concentrations. Thoracic fluid content was reduced by 6·8% from baseline (95% CI 4·0 to 8·8; p<0·0001) with spironolactone, but not other treatments. Amiloride (10 mg once daily) reduced clinic systolic blood pressure by 20·4 mm Hg (95% CI 18·3-22·5), compared with a reduction of 18·3 mm Hg (16·2-20·5) with spironolactone (25 mg once daily). No serious adverse events were recorded, and adverse symptoms were not systematically recorded after the end of the double-blind treatment. Mean plasma potassium concentrations increased from 4·02 mmol/L (95% CI 3·95-4·08) on placebo to 4·50 (4·44-4·57) on amiloride (p<0·0001). Interpretation: Our results suggest that resistant hypertension is commonly a salt-retaining state, most likely due to inappropriate aldosterone secretion. Mineralocorticoid receptor blockade by spironolactone overcomes the salt retention and resistance of hypertension to treatment. Amiloride seems to be as effective an antihypertensive as spironolactone, offering a substitute treatment for resistant hypertension. Funding: British Heart Foundation and UK National Institute for Health Research.

The lancet. Diabetes & endocrinology · 213 citationsread the source →

Provider Burnout and Fatigue During the COVID-19 Pandemic: Lessons Learned From a High-Volume Intensive Care Unit

The novel coronavirus disease 2019 (COVID-19) pandemic has resulted in an overall surge in new cases of depression and anxiety and an exacerbation of existing mental health issues, with a particular emotional and physical toll on health care workers.1 Limited resources, longer shifts, disruptions to sleep and to work-life balance, and occupational hazards associated with exposure to COVID-19 have contributed to physical and mental fatigue, stress and anxiety, and burnout.2 Similar to most hospitals in the COVID-19–affected areas, the Houston Methodist Hospital (HMH) system has experienced an overwhelming impact of this pandemic on personnel. For example, we have observed an unprecedented number of staff requesting Americans with Disabilities Act exemptions. Physicians and nurses are worried about their families, and some hesitate to go home in fear of exposing family members to infection. It is common to see emotional exhaustion in the intensive care unit (ICU). We have observed front-line health care providers emotionally breaking down, mainly due to the added pressure to choose between family responsibilities and their inner sense of duty toward patients. At the same time, we have seen an overwhelming influx of support from medical leadership, public and private acknowledgments, community support (eg, food sent to care units), as well as additional services offered to staff, such as music therapy, counseling services, chaplain services, and accommodations in work schedules. Other organizational adaptations include allocation of more resources (eg, float nurses, physicians, patient care assistants, and new equipment). Moving forward, our institution has plans for marshaling resources from surgeons, anesthesiologists, other medical specialists across all disciplines, and, in extreme circumstances, anyone with medical training and background. In this article, we share the lessons learned collectively by an interdisciplinary team of ICU leadership and collaborating scientists at the Center for Outcomes Research at HMH about the experience of occupational fatigue and burnout of intensive care personnel as a result of responding to the COVID-19 pandemic. We propose specific policy recommendations and guidelines for organizational readiness, resilience, and disaster mitigation. BACKGROUND Houston Methodist Hospital HMH is the flagship hospital of an 8-hospital nonprofit health care system spanning the Greater Houston metropolitan area, including a wide range of urban, suburban, and rural settings. For more than 100 years, HMH has served the Houston and global community with the highest quality patient care in a spiritual environment―indeed ironically, beginning its existence amidst the 1918 influenza pandemic. HMH has 952 operating beds (2393 systemwide) and 8294 employees (25,543 systemwide). Each year, it has 45,511 emergency room visits, 381,585 outpatient visits, and 41,976 admissions (more than 1.3 million outpatient visits and more than 126,000 admissions systemwide).3US News & World Report has named HMH the no. 1 hospital in Texas for 8 consecutive years, with placement among its top 20 “Best Hospitals Honor Roll” 3 times. In addition, HMH is nationally ranked in 9 specialties,4 and has been named the no. 1 employer in Texas by Forbes.5 Of particular note regarding its critical care capacities during this pandemic, HMH has 5 ICU units (cardiovascular, medical, coronary, surgical, and neonatal—with a total of 130 ICU beds), with 311 ICU beds systemwide across the community hospitals. At the time of this writing, HMH is caring for about 120 patients who have tested positive for COVID-19. COVID-19 Pandemic The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in the same family as the causative agent for previous Middle East Respiratory Syndrome (MERS) and severe acute respiratory syndrome (SARS) outbreaks. COVID-19 arose most likely from animal-to-human transfer in Wuhan, China. Unlike previous coronavirus outbreaks, the current COVID-19 emergence was marked by high rates of person-to-person transmission, including from asymptomatic carriers, combined with high severity of illness in vulnerable populations, including those with very common preexisting chronic conditions like diabetes, heart disease, and lung disease.6 The dilemma posed to health care workers is 2-fold: first, the anticipated, and now experienced, overload on the health care system capacity to respond to this pandemic with a suitable flow of equipment; and second, the high risk posed to health care workers on the front lines and their family members as a result of constant exposure. The public has been repeatedly called on to “flatten the curve,” in reference to the social and behavioral changes that we as a society can undertake to slow the spread of disease. This strategy has been prominent in US Centers for Disease Control and Prevention (CDC) reports since 2007, with maintenance of the guidelines as recent as 2017.7,8 This strategy was even deftly memed by medical experts on social media.9 However, across several states, implementation of these preventive measures has fallen short of desired goals.1,2,10–14 LESSONS LEARNED Several factors may have exacerbated occupational fatigue and burnout in ICUs. Given our overarching roles across various facets of the health care system and our first-hand experiences with the response, the “lessons learned” documented here provide a holistic overview of major system-level problems exposed by the pandemic. In what follows, 4 major contributors to COVID-19–related occupational fatigue and burnout are discussed: (1) occupational hazards; (2) national versus locally scaled response; (3) process inefficiencies; and (4) financial instability. Occupational Hazards Given the highly contagious nature of SARS-CoV-2, the US CDC has published strict infection control and prevention guidelines for front-line health care workers, including limited administrative access, strict workplace hygiene requirements, and usage of personal protective equipment (PPE).15 The rapid spread of the COVID-19 pandemic revealed an overall lack of preparedness and insufficient training as well as limited supplies of PPE for ICU staff, including anesthesiologists, intensivists, pulmonologists, nurses, respiratory therapists, and other front-line providers in most affected areas. From the onset of the COVID-19 outbreak, it was apparent that testing for the virus, detecting its distribution through widespread surveillance, and subsequent contact tracing were major public health gaps. Most hospitals, including HMH, lacked the capacity to test significant portions of our patient population for novel infectious threats. This removed a highly effective infection control tool from our arsenal. Unfortunately, such unpreparedness, potentially resulting in poor patient outcomes, had a significant psychological burden on personnel. National Versus Locally Scaled Response The COVID-19 outbreak also exposed the inadequacy of the US Strategic National Stockpile (SNS) of PPE and ventilators during a pandemic affecting many states. In fact, to our knowledge, only 10%–25% of states’ requested PPE is being delivered, about 1 month into the pandemic. In addition, there are many uncertainties about when and how more PPE—and most important, ventilators—will become available. The process to access the US SNS should be as lean as possible, but it has proven slow and logistically cumbersome. While federal authorities are assembling practical guidelines to extend the life and use of PPE, such plans may void the warranty on PPE.16 Critical care personnel are well aware that the effectiveness of PPE deteriorates outside of recommended usage, and such awareness only worsens the psychological pressure on these personnel. Process Inefficiencies The COVID-19 pandemic has revealed several issues related to current processes and established practices. Most importantly, the lack of established policies for pandemic triage, equipment ordering, and emergency management has led to systemwide inefficiencies and has increased the burden on health care workers. While new protocols were put in place in response to the pandemic, these protocols were perceived as complex and, in some cases, premature. For example, anecdotal evidence suggests that most health care workers’ vulnerabilities and contamination were related to improper PPE doffing. While training videos on donning and doffing were shared with staff, such videos were not updated to reflect specific PPE used in our system, and instructions were not intuitive for less experienced personnel. Another important issue was related to policy overload coupled with mismatching policy from different levels or sources. For example, each subspecialty (eg, anesthesiology, critical care medicine, respiratory therapy, nursing, and others) follow guidelines provided by their respective professional societies for various procedures, in addition to new policies developed by the hospital. However, holistic efforts to align such guidelines were largely absent at the system level, resulting in teamwork issues, confusion, and frustration. At HMH, our physician executive and chief medical officer has addressed this issue via regular and timely update communications. Financial Instability At the time of this writing, COVID-19 has pushed the global economy to the brink of, or already into, a major recession. Modifications of population dispersion (social distancing) and quarantine protocols, and a complete halt to large portions of the US economy, have resulted in unprecedented overall societal stress and anxiety. Unfortunately, a disproportionate share of the sacrifice is borne by the portions of our population who are at greatest socioeconomic risk. While business is booming in health care, all indicators point to a likely sustained overall economic downturn. This undoubtedly contributes to health care workers’ stress and anxiety. In addition, anecdotal and news report evidence suggests that some private anesthesia groups in the country have experienced financial distress, resulting in furloughs and layoffs because they depend heavily on providing services for routine, elective surgeries, which have been canceled or delayed in a number of states.17 It is well documented that such uncertainty about future occupational stability (job security) is associated with a deterioration in mental well-being.18 ORGANIZATIONAL ADAPTATION AND OPPORTUNITIES Several traits of resilient performance and improvisation have been observed at HMH. The incident command team was rapidly assembled; leadership–employee communication was constant and responsive; and human resources (HR) adapted policies to employee needs. To long-standing employees, these adaptations were not surprising, because our leadership and teams have literally weathered storms before, including in recent history, Hurricane Ike and Hurricane Harvey. Hurricanes are not pandemics, but their local effects are similar in terms of financial and emotional strains on employees, as well as sudden geographical isolation of both employees and patients. In particular, the seamless way in which HMH executive leadership and HR adapted policies―including alternate paid time off options, advanced check dispersal with waived fees, telecommute policies, and waived copays for mental health services―was consistent with how the health system has previously assessed emerging disaster situations and responded with astute budget analyses to bolster employee bank accounts without breaking the hospital budget. Likewise, procedures for maintaining sensitive research areas such as our animal laboratories, clinical trials, and expedited institutional review board (IRB) approval mechanisms for disaster-critical research, much of which is now being implemented nationwide, are reminiscent of ride-out and recovery procedures already commonplace in a Texas Gulf Coast medical center. These proactive, positive responses corroborate that the best way to weather a storm is to look where storms have repeatedly been weathered. In a more direct way, we have seen this for the COVID pandemic in portions of Asia like Singapore and Hong Kong, which were previously affected most by SARS and novel influenza A (H1N1pdm09) virus of 2009 (H1N1) avian influenza and have likewise adapted comparatively faster to COVID-19.19 Digital communication tools have also shown promise in enabling remote work as well as intrainstitutional collaborative efforts. COVID-19 has brought health care professionals together across cities, states, and countries. For example, in the Greater Houston area alone, there have been more than 200 intensivists, extracorporeal membrane oxygenation (ECMO) specialists, and other specialized providers communicating through popular social media platforms (eg, WhatsApp) and learning from one another. In addition, this pandemic has opened the opportunity for innovations and adoption of alternative care delivery methods like telemedicine and virtual ICUs. HMH has been able to utilize these technologies for ECMO-treated COVID-19 patients and thus decreased traffic in and out of our ICU patient rooms. Resilience was also evident in the formation of interdisciplinary teams to design novel devices to help protect anesthesiologists in intubating COVID-19–positive patients or persons under investigation. DISCUSSION The COVID-19 pandemic exposed several gaps in our health care system, including the need for proactive investment to increase large-scale epidemic and pandemic preparedness. The following recommendations are made to prevent burnout and mitigate occupational stress, especially among intensive care providers during a pandemic. RECOMMENDATIONS AND POLICY IMPLICATIONS The national and regional disaster mitigation plans for future epidemics have to incorporate mechanisms to allow rapid and agile transformation of relevant industry to support massively increased demand for disinfectants, cleaning supplies, PPE, and other medical equipment for health care and community use. Although certain industries and corporations have exhibited a heightened sense of responsibility during the current COVID-19 pandemic, such efforts need to be preemptively planned, and specific industries should be earmarked, trained, and equipped for a rapid transformation. Industries willing to step up in times of crises and invest in disaster readiness may be incentivized by tax breaks or other mechanisms. Access to updated information about the availability of COVID-19 testing kits and PPE for health care workers may reduce the anxiety associated with uncertainty and reduce unproductive information seeking20 and emotional distress.21 Daily rounds and huddles, along with communication technologies, such as huddle boards, can be used to serve as reliable information sources. Structured training on large-scale disaster management and response must be provided. The Society of Critical Care Management offers a Fundamentals of Disaster Management course, which can build crucial mental models and support development of organization-specific structures for response management.22 In addition, the Federal Emergency Management Agency (FEMA) offers a variety of free courses and resources. Disasters necessitate innovation. With the rise of COVID-19, several innovative designs were proposed to protect the health care workers on the front lines from the rapidly and widely spreading virus.23 However, there is a dearth of manufacturing capacity and materials to produce many of these solutions. Systems of innovation that were developed and honed during other national emergencies when most resources were constrained (eg, the Functional Analysis Systems Technique [FAST] developed during the Manhattan Project)24 are being revisited to tackle the problem nationally and globally. We need these solutions to buy time for effective antiviral medications and a vaccine for COVID-19. Meanwhile, there is a need to provide technical oversight to ensure that new designs meet minimum safety requirements. For example, during this pandemic, an abundance of homemade masks and gowns were designed and adopted without proper attention to fit and leak protection, potentially leading to a false perception of protection among health care workers. The United States has a well-trained yet largely untapped resource of medical professionals in the form of internationally trained physicians, nurses, medical technicians, and other health care providers. Due to strict state licensing regulations, such individuals are barred from routine direct patient care. Though we do not propose a blanket relaxation in medical licensure requirements, we feel it is imperative that willing and able individuals be periodically trained to maintain a medical reserve corps at the regional, state, and national level. We opine that the notion of wartime-like preparedness has to be a serious and deliberate consideration, and maintaining a readily deployable human capital reserve is part and parcel of such preparedness. While studies emerged to investigate pandemic-related mental health issues,1 there is a need for feasible and practical methods to assess health care workers’ fatigue and burnout.25,26 Wearable sensors have shown promise27 by providing an opportunity to monitor fatigue, stress, and sleep biomarkers noninvasively and then communicating this information to clinical unit managers for timely intervention. In addition, mobile health (mHealth) tools have shown promise to facilitate mental health self-management. Simple methods such as breathing exercises, biofeedback, and mindfulness can be utilized to mitigate acute episodes of stress and anxiety, while telehealth services can be used to enable peer-support and occupational counseling. However, the integration of new technologies with current workflows may present additional burden and needs to be further examined. The lessons learned and documented here demonstrate that when confronted with seemingly inadequate federal-level logistics and response, it is perhaps time to recall the social virtues of local-level resilience and self-reliance. It is beyond the logistical capabilities of any government to provide what is needed to every citizen when the scope and of the disaster are beyond a (eg, large-scale and national capacity for It was local in many cases by private that all as one (eg, the during and response during We can the and efforts and resources to mitigate such and These efforts with and leadership that a sense of community and duty to the into the of our of this every 100 years, with more or less severe cases in the We have learned from each of but we have to of our public resources into providing supplies and to these This is to and it is our to The Center for Outcomes Houston Methodist review and of the for flow and This complete the and led the of the This and the This and the This and the This and the This was

Anesthesia & Analgesia · 388 citationsread the source →

Socioeconomic disparities in first stroke incidence, quality of care, and survival: a nationwide registry-based cohort study of 44 million adults in England.

Background: We aimed to estimate socioeconomic disparities in the incidence of hospitalisation for first-ever stroke, quality of care, and post-stroke survival for the adult population of England. Methods: In this cohort study, we obtained data collected by a nationwide register on patients aged 18 years or older hospitalised for first-ever acute ischaemic stroke or primary intracerebral haemorrhage in England from July 1, 2013, to March 31, 2016. We classified socioeconomic status at the level of Lower Super Output Areas using the Index of Multiple Deprivation, a neighbourhood measure of deprivation. Multivariable models were fitted to estimate the incidence of hospitalisation for first stroke (negative binomial), quality of care using 12 quality metrics (multilevel logistic), and all-cause 1 year case fatality (Cox proportional hazards). Findings: Of the 43·8 million adults in England, 145 324 were admitted to hospital with their first-ever stroke: 126 640 (87%) with ischaemic stroke, 17 233 (12%) with intracerebral haemorrhage, and 1451 (1%) with undetermined stroke type. We observed a socioeconomic gradient in the incidence of hospitalisation for ischaemic stroke (adjusted incidence rate ratio 2·0, 95% CI 1·7-2·3 for the most vs least deprived deciles) and intracerebral haemorrhage (1·6, 1·3-1·9). Patients from the lowest socioeconomic groups had first stroke a median of 7 years earlier than those from the highest (p<0·0001), and had a higher prevalence of pre-stroke disability and diabetes. Patients from lower socioeconomic groups were less likely to receive five of 12 care processes but were more likely to receive early supported discharge (adjusted odds ratio 1·14, 95% CI 1·07-1·22). Low socioeconomic status was associated with a 26% higher adjusted risk of 1-year mortality (adjusted hazard ratio 1·26, 95% CI 1·20-1·33, for highest vs lowest deprivation decile), but this gradient was largely attenuated after adjustment for the presence of pre-stroke diabetes, hypertension, and atrial fibrillation (1·11, 1·05-1·17). Interpretation: Wide socioeconomic disparities exist in the burden of ischaemic stroke and intracerebral haemorrhage in England, most notably in stroke hospitalisation risk and case fatality and, to a lesser extent, in the quality of health care. Reducing these disparities requires interventions to improve the quality of acute stroke care and address disparities in cardiovascular risk factors present before stroke. Funding: NHS England and the Welsh Government.

The Lancet. Public health · 104 citationsread the source →

Frailty increases the long-term risk for fall and fracture-related hospitalizations and all-cause mortality in community-dwelling older women.

Frailty is associated with declines in physiological capacity across sensory, neurological, and musculoskeletal systems. An underlying assumption is that the frailer an individual, the more likely they are to experience falls and fractures. We examined whether grades of frailty can assess the long-term risk of hospitalized falls, fractures, and all-cause mortality in 1261 community-dwelling older women (mean age [SD] of 75.1 [2.7] yr) over 14.5 yr. Frailty was operationalized using a frailty index (FI) of cumulative deficits from 33 variables across multiple health domains (physical, mental, comorbidities) at baseline. The total score across these variables was summed and divided by 33 to obtain the FI. Participants were graded as fit (FI ≤ 0.12), mildly frail (FI > 0.12-0.24), moderately frail (FI > 0.24-0.36), or severely frail (FI > 0.36). Fall-related (n = 498), any fracture-related (n = 347), and hip fracture-related hospitalizations (n = 137) and deaths (n = 482) were obtained from linked health records. Associations between FI grades and clinical outcomes were analyzed using multivariable-adjusted Cox-proportional hazard models including age, treatment (calcium/placebo), BMI, smoking history, socioeconomic status, plasma vitamin D (25OHD) status plus season obtained, physical activity, self-reported prevalent falls in the last 3 mo, and self-reported fractures since the age of 50 yr. At baseline, 713 (56.5%), 350 (27.8%), 163 (12.9%), and 35 (2.8%) of women were classified as fit, mildly frail, moderately frail, and severely frail, respectively. Women with mild, moderate, and severe frailty had significantly higher hazards (all P < .05) for a fall-related (46%, 104%, 168%), any fracture-related (88% for moderate, 193% for severe frailty), hip fracture-related hospitalizations (93%, 127%, 129%), and all-cause mortality (47%, 126%, 242%). The FI identified community-dwelling older women at risk for the most serious falls and fractures and may be incorporated into risk assessment tools to identify individuals with poorer clinical prognosis.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 52 citationsread the source →

Associations of sleep measures with neural activations accompanying fear conditioning and extinction learning and memory in trauma-exposed individuals.

Study objectives: Sleep disturbances increase risk of posttraumatic stress disorder (PTSD). Sleep effects on extinction may contribute to such risk. Neural activations to fear extinction were examined in trauma-exposed participants and associated with sleep variables. Methods: Individuals trauma-exposed within the past 2 years (N = 126, 63 PTSD) completed 2 weeks actigraphy and sleep diaries, three nights ambulatory polysomnography and a 2-day fMRI protocol with Fear-Conditioning, Extinction-Learning and, 24 h later, Extinction-Recall phases. Activations within the anterior cerebrum and regions of interest (ROI) were examined within the total, PTSD-diagnosed and trauma-exposed control (TEC) groups. Sleep variables were used to predict activations within groups and among total participants. Family wise error was controlled at p < 0.05 using nonparametric analysis with 5,000 permutations. Results: Initially, Fear Conditioning activated broad subcortical and cortical anterior-cerebral regions. Within-group analyses showed: (1) by end of Fear Conditioning activations decreased in TEC but not PTSD; (2) across Extinction Learning, TEC activated medial prefrontal areas associated with emotion regulation whereas PTSD did not; (3) beginning Extinction Recall, PTSD activated this emotion-regulatory region whereas TEC did not. However, the only between-group contrast reaching significance was greater activation of a hippocampal ROI in TEC at Extinction Recall. A greater number of sleep variables were associated with cortical activations in separate groups versus the entire sample and in PTSD versus TEC. Conclusions: PTSD nonsignificantly delayed extinction learning relative to TEC possibly increasing vulnerability to pathological anxiety. The influence of sleep integrity on brain responses to threat and extinction may be greater in more symptomatic individuals.

Sleep · 25 citationsread the source →

Cost-effectiveness of bariatric surgery and non-surgical weight management programmes for adults with severe obesity: a decision analysis model.

Objectives: To determine the most cost-effective weight management programmes (WMPs) for adults, in England with severe obesity (BMI ≥ 35 kg/m2), who are more at risk of obesity related diseases. Methods: An economic evaluation of five different WMPs: 1) low intensity (WMP1); 2) very low calorie diets (VLCD) added to WMP1; 3) moderate intensity (WMP2); 4) high intensity (Look AHEAD); and 5) Roux-en-Y gastric bypass (RYGB) surgery, all compared to a baseline scenario representing no WMP. We also compare a VLCD added to WMP1 vs. WMP1 alone. A microsimulation decision analysis model was used to extrapolate the impact of changes in BMI, obtained from a systematic review and meta-analysis of randomised controlled trials (RCTs) of WMPs and bariatric surgery, on long-term risks of obesity related disease, costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) measured as incremental cost per QALY gained over a 30-year time horizon from a UK National Health Service (NHS) perspective. Sensitivity analyses explored the impact of long-term weight regain assumptions on results. Results: RYGB was the most costly intervention but also generated the lowest incidence of obesity related disease and hence the highest QALY gains. Base case ICERs for WMP1, a VLCD added to WMP1, WMP2, Look AHEAD, and RYGB compared to no WMP were £557, £6628, £1540, £23,725 and £10,126 per QALY gained respectively. Adding a VLCD to WMP1 generated an ICER of over £121,000 per QALY compared to WMP1 alone. Sensitivity analysis found that all ICERs were sensitive to the modelled base case, five year post intervention cessation, weight regain assumption. Conclusions: RYGB surgery was the most effective and cost-effective use of scarce NHS funding resources. However, where fixed healthcare budgets or patient preferences exclude surgery as an option, a standard 12 week behavioural WMP (WMP1) was the next most cost-effective intervention.

International journal of obesity (2005) · 30 citationsread the source →

Bullying and Suicide: A Public Health Approach

Several recent studies have found an association between bullying and depression [[1]Wang J. Iannotti R.J. Luk J.W. Nansel T.R. Co-occurrence of victimization from five subtypes of bullying: Physical, verbal, social exclusion, spreading rumors, and cyber.J Pediatr Psychol. 2010; 35: 1103-1112Crossref PubMed Scopus (223) Google Scholar] or bullying and suicide-related behaviors [[2]Kim Y.S. Leventhal B. Suicide and bullying. A review. Int J Adolesc Med Health. 2008; 20: 133-154Crossref PubMed Scopus (324) Google Scholar], and one study found evidence consistent with a causal link, at least for girls [3Klomek A.B. Sourander A. Niemela S. et al. Childhood bullying behaviors as a risk for suicide attempts and completed suicides: A population-based birth cohort study.J Am Acad Child Adolesc Psychiatry. 2009; 48: 254-261Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar, 4Klomek A.B. Sourander A. Gould A. The association of suicide and bullying in childhood to young adulthood: A review of cross-sectional and longitudinal research findings. Can J Psychiatry. 2010; 55: 282-288PubMed Google Scholar]. These studies, in conjunction with extensive media coverage of the deaths by suicide of several young people who were victims of bullying, led the Centers for Disease Control and Prevention (CDC) to convene an expert panel focusing on the relationship between bullying involvement and suicide-related behaviors. The purpose of the panel, held in September 2010, was to synthesize the latest research about the relationship between youth involvement in bullying (youth who bully, youth who are bullied, and those who bully and are bullied) and suicide-related behaviors (attempts, fatalities, and risk factors associated with suicide, such as depression). Experts on the topics of bullying and suicide presented their research about the relationship between these two behaviors; their work is contained in this supplement. The panel and this special issue provide clarity around the complicated issues of bullying and suicide among youth. Three key themes emerged: (1) bullying among youth is a significant public health problem; it is prevalent and frequently has detrimental effects; (2) there is a strong association between bullying and suicide-related behaviors, but this relationship is often mediated by other factors, including depression and delinquency; and (3) there are public health strategies that can be applied to the prevention of bullying and suicide. Bullying is a significant public health problem because it is prevalent and harmful. Between 20% and 56% of young people are involved in bullying annually [5Centers for Disease Control and Prevention. Youth risk behavior surveillance—United States, 2011. MMWR, Surveillance Summaries 2012;61(no. SS-4). Available at: www.cdc.gov/mmwr/pdf/ss/ss6104.pdf. Google Scholar, 6Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 7Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Thus, in a classroom of 30 students, between 6 and 17 students are involved in bullying as a victim, perpetrator, or both (bully-victim). The specific rate of bullying victimization and perpetration varies according to age, type of bullying, time period over which bullying behaviors are assessed, and by subgroup. Younger (middle school-aged) children are more likely to be involved in bullying than high school-aged children [[8]Robers S. Zhang J. Truman J. Indicators of school crime and safety: 2011 (NCES 2012-002/NCJ 236021). National Center for Education Statistics, U.S. Department of Education, and Bureau of Justice Statistics, Office of Justice Programs, U.S. Department of Justice, Washington, DC2012Google Scholar]. Verbal bullying is generally more prevalent than physical or cyber-bullying and bullying is more likely to occur over a longer time period—“ever” or over the “past year” as opposed to “the past few months” [[9]David-Ferdon C. Hertz M.F. Electronic media and youth violence: A CDC issue brief for researchers. Centers for Disease Control, Atlanta, GA2009Google Scholar]. Specific subgroups are more likely to be victimized. For example, bullying victimization is more prevalent upon lesbian and gay youth—60% report victimization during the past 30 days prior to the survey compared with 28.8% of heterosexual youth [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. For young people involved in bullying in any capacity—youth who bully others, who are bullied, or who both bully and are bullied, this involvement is correlated with poor mental and physical health and engagement in other risk behaviors. Youth who are bullied are more likely to be depressed or anxious [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar], have lower academic achievement, report feeling like they do not belong at school [[12]Glew G.M. Fan M. Katon W. et al. Bullying, psychosocial adjustment, and academic performance in elementary school. Arch Pediatr Adolesc Med. 2005; 159: 1026-1031Crossref PubMed Scopus (384) Google Scholar], have poorer social and emotional adjustment, greater difficulty making friends, poorer relationships with classmates, and greater loneliness [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Bully-victims are more likely than those who bully, those who are bullied, or their uninvolved peers to report being physically hurt by a family member, to witness family violence, and exhibit suicide-related behaviors [[14]McKenna M. Hawk E. Mullen J. Hertz M. The association between bullying behavior and health risks among middle school and high school students in Massachusetts, 2009.Morbidity and Mortality Weekly Review. 2011; 60: 465-471PubMed Google Scholar]. Those who bully others are more likely to drink alcohol and use cigarettes, to have poorer academic achievement and poorer perceived school climate, but to also report greater ease of making friends [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Involvement in bullying can also have long-lasting, detrimental effects months or even years after the bullying occurs. Young people who are bullied are more likely than uninvolved youth to develop depression and anxiety and report abdominal pain and feeling tense over the course of a school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. One study examining the impact of bullying victimization of those who were between 9, 11, and 13 years of age when they were victimized found, that over a 7-year period, youth who were bullied were more likely to develop generalized anxiety and panic disorder as adults while bully-victims were more likely to subsequently suffer from depression, panic disorder, and suicidality [[15]Copeland W.E. Wolke D. Angold A. Costello E.J. Adult psychiatric outcomes of bullying and being bullied by peers in childhood and adolescence.JAMA Psychiatry. 2013; 70: 419-426Crossref PubMed Scopus (746) Google Scholar]. Another longitudinal study found that those who were perpetrators of bullying at age 14 were more likely to receive a diagnosis of antisocial personality disorder, to have low job status at age 18 years, and to use drugs at ages 27–32 years [[16]Farrington D.P. Ttofi M.M. Bullying as a predictor of offending, violence and later life outcomes. Crim Behav Ment Health. 2011; 21: 90-98Crossref PubMed Scopus (169) Google Scholar]. The articles in this special issue generally show a strong association between involvement in bullying behaviors and suicide-related behaviors. In Espelage and Holt's work with middle school students, suicidal ideation and attempts were significantly more prevalent among victims, bully-victims and perpetrators, with rates of ideation and attempts among those involved as a victim, perpetrator, or bully-victims three to five times higher than the rate of uninvolved youth [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar]. Likewise, in Borowsky's study of 6th, 9th, and 12th graders, 1.2% of uninvolved youth made a suicide attempt, compared with 5% for those who frequently bullied others verbally or socially; 6.5% for those who were frequent victims of verbal/social bullying; and 11.1% for those who were frequent bully-victims of verbal/social bullying [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. In Kowalski and Limber's paper, depression, anxiety, self-esteem, self-reported health problems, absences from school, leaving school because of illness, and grades were, with only one exception, significantly related to students' involvement in cyber-bullying others, being cyber-bullied, bullying others through traditional means, and being bullied through traditional means [[7]Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Those who witness bullying but are not directly involved are also at increased risk. Rivers and Noret [[18]Rivers I. Noret N. Potential suicide ideation and its association with observing bullying at school.J Adolesc Health. 2013; 53: S32-S36Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar] report that students who observed bullying behavior were significantly more likely than those uninvolved in bullying to report symptoms of interpersonal sensitivity (feelings of being hurt and feelings of inferiority) and greater helplessness. However, the papers in this issue also convey the complexity of the relationship between bullying and suicide-related behaviors. In Espelage and Holt's work [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar], after controlling for delinquency and depression there was no increased risk of suicide-related behaviors for perpetrators; the increased risk did remain for victims. Klomek's [[19]Klomek A.B. Kleinman M. Altschuler E. et al. Suicidal adolescents' experiences with bullying perpetration and victimization during high school as risk factors for later depression and suicidality.J Adolesc Health. 2013; 53: S37-S42Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar] comparison of young people with bullying involvement and psychiatric symptoms (depression, suicidality, or substance use) at an initial screen to those with psychiatric symptoms but no bullying involvement found, at 2-year follow-up, that only perpetrators of bullying were significantly more likely to be functionally impaired than bullying-uninvolved students. In King's study of hospitalized suicidal youth, those who reported perpetrating bullying were more likely than uninvolved youth to have severe suicidal thoughts and psychosocial impairment, and to abuse substances. However, at 12-month follow-up, only the difference in psychosocial impairment remained. Interestingly, over the course of 1-year treatment for the suicidality, the rate of bullying perpetration declined [[20]King C.A. Horwitz A. Berona J. Jiang Q. Acutely suicidal adolescents who engage in bullying behavior: 1-year trajectories.J Adolesc Health. 2013; 53: S43-S50Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. In Karch's analysis of suicide fatalities among youth, bullying involvement was one of a myriad of factors precipitating a death by suicide. A quarter of young suicide victims had school problems, but only 12.4% of these school problems were attributed to bullying [[21]Karch D.L. Logan J. McDaniel D.D. et al. Precipitating circumstances of suicide among youth aged 10–17 years by sex: Data from the National Violent Death Reporting System, 16 States, 2005–2008.J Adolesc Health. 2013; 53: S51-S53Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar]. Other salient circumstances included depressed mood and/or other current mental health problems (37%); intimate partner problems (25%); history of suicide attempts (18%); and substance abuse problems (16%). Suicide attempts and substance use were risk factors that co-occurred with suicide ideation in Borowsky et al. as well [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all groups (victims, perpetrators, and bully-victims) a history of self-harm within the prior year and greater emotional distress (feelings of sadness, hopelessness, worry, stress, or pressure) drastically increased risk for suicide. For victims and bully-victims, a history of sexual abuse, a mental health problem, or running away from home in the past year increased the likelihood of suicidal thinking or behavior [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. More than half of the youth who were bully-victims and who expressed suicidal ideation or reported making an attempt also witnessed family violence, had a history of physical abuse, smoked cigarettes, used marijuana, skipped school because of safety concerns, or carried a weapon at school. Youth who were involved in bullying and reported suicide-related thoughts or behaviors also had higher mean scores for distractibility/impulsivity and lower mean scores for parent connectedness, connectedness to other adults, perceived caring by teachers, perceived caring by friends, liking school, academic achievement, physical activity, perceived school safety, and perceived neighborhood safety [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all three bullying-involved groups, parent connectedness (feeling like you can talk to mom/dad about problems; that mom/dad care about you) was protective for suicidal ideation and attempts. Other protective factors for victims included stronger connections to nonparental adults, stronger perceived caring by friends, and liking school. For bully-victims, greater perceived caring by friends was also protective [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. That there is a relationship between bullying and depression and that this relationship may help to explain the relationship between bullying and suicide is fairly consistent across papers. However, the direction of this relationship is unclear. Do youth who are bullied become depressed or are depressed youth more likely to be bullied? A study from the Netherlands suggests the answer may be “both.” Researchers found that victims of bullying had significantly higher chances of developing new psychosomatic and psychosocial problems over the course of a school year compared with children who were not bullied. However, children with preexisting depressive symptoms or anxiety were also significantly more likely to be newly victimized over the course of the school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. Despite the complexity of the relationship between bullying and suicide, there is no doubt that bullying involvement can have detrimental effects and prevention of bullying could improve health and mental health outcomes for many youth. The findings in these articles underscore the complexity of the relationship between bullying and suicide. A critical difference distinguishes an association between bullying and suicide from a causal relationship, with significant implications for prevention. Conveying that bullying alone causes suicide at best minimizes, and at worst ignores, the other factors that may contribute to death by suicide. This neglect may result in too narrow a focus of preventive action. We echo the call made by others for an integrated approach to preventing suicide and youth violence by focusing on shared risk and protective factors including individual coping skills, family and school social support, and supportive school environments [[22]Lubell K.M. Vetter J.B. Suicide and youth violence prevention: The promise of an integrated approach. Aggression and Violent Behavior. 2006; 11: 167-175Crossref Scopus (71) Google Scholar]. Strengthening social connectedness and ensuring access to supportive adults may pay dividends in impacting both bullying and suicide behaviors. Supportive home and school environments where young people feel connected are just one overlapping protective factor. Borowksy's findings regarding connection to parents, other adults, school, and friends reflect the need for multiple strategies that focus on both the school and home environments and that move beyond the individual skill-building level to foster supportive environments [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. The case for a supportive environment on bullying and suicide prevention is supported by Hatzenbuehler's work. In the paper contained in this special issue, he reports findings that lesbian and gay youths living in counties with fewer school districts with antibullying policies that specifically mentioned sexual orientation as a protected group were nearly two times more likely to have attempted suicide in the past year compared with those living in counties where more districts had these policies [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. Williams and Guerra reported that youth who describe their school climate as being trusting, fair, and pleasant have lower involvement in verbal, physical, and Internet bullying perpetration [[23]Williams K.R. Guerra N.G. Prevalence and predictors of internet bullying.J Adolesc Health. 2007; 41: S14-S21Abstract Full Text Full Text PDF PubMed Scopus (669) Google Scholar]. As reflected in CDC's strategic direction on suicide [[24]Centers for Disease Control and Prevention (CDC). Connectedness as a strategic direction for the prevention of suicidal behavior. Available at: http://www.cdc.gov/violenceprevention/pdf/suicide_strategic_direction-one-pager-a.pdf. Google Scholar], approaches intended to build connections between youth and school and home environments, as well as communities, are essential to suicide prevention. Sources of Strength is a school-based suicide-prevention program that trains youth opinion leaders to change the norms and behaviors of their peers by conducting well-defined messaging activities with adult mentoring, as well as increasing perceptions of adult support for suicidal youths and the acceptability of seeking help M. et of the Sources of Strength suicide prevention program by leaders in high J Health. 2010; PubMed Scopus Google Scholar]. work also the of connections to support prevention. As an example, the youth suicide prevention found that who reported a stronger connection to youth in their program were as likely to suicidal youth. the research also that the bullying prevention are A of school bullying strategies that school approaches that included multiple and at of school more often reduced victimization and bullying than the that only included or social groups A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. there is about the prevention of bullying and suicide, there is also do not studies over the past two have the of bullying prevention However, studies have in the States, these have not A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. is evidence that youth violence prevention that for such as and also rates of bullying The impact of and on bullying and A Pediatr Adolesc Med. PubMed Scopus Google Scholar]. More work is to strategies that bullying from among youth in the In that depression is a significant risk for bullying and suicide as well as a of other behaviors. We need to to mental among young people and their and to do in and However, the and impact of bullying, it is to move while these strategies are being We can by and strategies that have at increasing protective factors and risk factors associated with both bullying and suicide. is not that bullying in is it that bullying occur in the in and health their focus beyond just to those who are involved in bullying or suicide-related behaviors, but also in strategies to bullying and suicidal behavior from in the

Journal of Adolescent Health · editorial or comment · 170 citationsread the source →

To belong is to matter: sense of belonging enhances meaning in life.

In four methodologically diverse studies (N = 644), we found correlational (Study 1), longitudinal (Study 2), and experimental (Studies 3 and 4) evidence that a sense of belonging predicts how meaningful life is perceived to be. In Study 1 (n = 126), we found a strong positive correlation between sense of belonging and meaningfulness. In Study 2 (n = 248), we found that initial levels of sense of belonging predicted perceived meaningfulness of life, obtained 3 weeks later. Furthermore, initial sense of belonging predicted independent evaluations of participants essays on meaning in life. In Studies 3 (n = 105) and 4 (n = 165), we primed participants with belongingness, social support, or social value and found that those primed with belongingness (Study 3) or who increased in belongingness (Study 4) reported the highest levels of perceived meaning. In Study 4, belonging mediated the relationship between experimental condition and meaning.

Personality & social psychology bulletin · 180 citationsread the source →

Comparative evaluation of oral hygiene practices and oral health status in autistic and normal individuals.

Aim: The present study attempts to explore the oral hygiene practices and oral health status in autistic patients as compared to nonaffected, same aged healthy individuals. Materials and methods: The oral hygiene practices, prevalence of caries and periodontal status were evaluated in 117 autistic patients and 126 healthy individuals. The test and control groups were divided into three categories, based on the type of dentition as Primary dentition (Category 1), Mixed dentition (Category 2) and Permanent dentition (Category 3). Plaque and gingival status was recorded by plaque index (Loe, 1967) and gingival index (Loe, 1967), periodontal status by community periodontal index of treatment needs and dental caries by DMFT/DEF index. Statistical analysis was done using descriptive statistics, independent sample t-test, contingency coefficient test and one-way ANOVA test by SPSS 14 software. Results: There was no statistically significant difference in the brushing habits between autistics and controls (P = 0.573); however, Autistics required assistance in brushing. Prevalence of caries was significantly lower in autistic patients (P = 0.000). Plaque and gingival scores were significantly higher in autistic patients (P = 0.000) and prevalence of periodontal disease was significantly higher in autistic patients (P = 0.000). Greater number of autistic patients required professional scaling and root planing (P = 0.000). Conclusion: The present study suggests that autistic patients have a higher rate of periodontal disease and lower caries compared to controls. Attempts should be made by parents, general dentists and periodontists to teach oral hygiene methods to these patients by constant repetition and patience, as autistic individuals can develop skills over a period of time and lead a more productive and independent life.

Journal of International Society of Preventive & Community Dentistry · 32 citationsread the source →

Physical and mental comorbidity of headache in a nationally representative sample of US adults.

Objective: To investigate the contribution of comorbidity to health utilization and negative health perception in a large-scale population-based study. Comorbidity of headache with physical and mental disorders has been reported frequently in clinical samples. Methods: This concern was addressed using combined 6-year data from the 1999 to 2004 National Health Examination and Nutrition Survey (n = 31,126 adults), nationally representative datasets of the US population. Measures of physical disorders were based on standardized interviews of chronic conditions, and mental disorders were assessed by the Composite International Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Results: The 3-month prevalence of severe headaches or migraine in the US general population was 22.73%, with females and young adults having greater rates than males and older adults. Adults with headache had increased odds for a variety of physical disorders (including asthma, rheumatoid arthritis, and stroke) and mental disorders (including depression, generalized anxiety disorder, and panic disorder). Adults with headache were more likely to rate their health as "fair or poor" (17.9% versus 6.1%), to seek health care four or more times in a year (43.3% versus 22.7%), and to endorse physical and mental limitations. Health utilization and negative health perception were more strongly influenced by comorbid mental disorders than physical disorders. Conclusions: The results from this nationally representative sample provide new information on the interrelationships of headache with mental and physical disorders. The greater impact of comorbid mental compared with physical disorders on healthcare utilization and health perception has important implications for the clinical evaluation and treatment of headache in the population.

Psychosomatic medicine · 62 citationsread the source →

Exploring the burden of the primary family caregivers of schizophrenia patients in Taiwan.

Aim: The purpose of the present study was to investigate the burden of the primary family caregivers of schizophrenia patients and the factors that affect caregiver burden. Methods: A total of 126 pairs of patients and their primary family caregivers were recruited from the day care and acute wards of two teaching general hospitals. Demographic information was collected. All patients went through an interview with a senior psychiatrist using the Brief Psychiatric Rating Scale (BPRS). The Caregiver Burden Inventory-Brief Version and the Chinese Health Questionnaire (CHQ) were used to assess the caregiver burden and the caregivers' health condition. One-way analysis of variance and Pearson correlation were used to analyze the relationship between demographic factors and caregiver burden. Multiple regression was used to analyze predictors of burden of caregivers. Statistical significance in this study was defined as P <or= 0.05. Results: The caregiver burden scores (25.9 +/- 10.7; range, 3-61) indicated a moderate burden level. Among the five dimensions of burden, caregiver anxiety (2.13 +/- 0.86) was the highest, followed by dependency of the patient (1.85 +/- 1.02), feeling shame and guilt (1.56 +/- 1.02), and family interference (1.43 +/- 0.83). The burden level of stigmata (1.32 +/- 1.24) was the lowest. The first three rankings of burden were 'I worry about his/her safety when he/she is alone' (2.26 +/- 1.15), 'I worry that she/he will become sick at any time' (2.23 +/- 1.10), and 'I feel he/she depends on me very much' (2.02 +/- 1.29). Patient satisfaction with medical staff support (P = 0.00), CHQ scores of the caregivers (P = 0.00), and the BPRS scores of the patients (P = 0.01) were significantly associated with the caregiver burden scores. Conclusions: The physical and mental health condition of the primary family caregiver of schizophrenia patients was the most important factor determining the caregiver burden level. Comprehensive multidisciplinary care of chronic schizophrenia patients is needed, care that supports the needs and improves the psychiatric symptoms of the patients, helps to decrease the caregiver burden level, and facilitates family participation in treatment.

Psychiatry and clinical neurosciences · 41 citationsread the source →

Death Anxiety in the Elderly: The Role of Spiritual Health and Perceived Social Support

Aging as one of the most important periods of life is associated with many challenges including death anxiety. Therefore, the aim of the current study was to investigate the role of spiritual health and perceived social support in predicting death anxiety in the elderly. The present study was a descriptive-correlational one. The study population consisted of the elderly living in Shahrekord in 2020, among whom 385 were selected using convenience sampling method and were assessed by the scales of Templer Death Anxiety, Zemen Perceived Social Support and Paloutzian & Ellison spiritual health. Data were analyzed using correlation coefficient and linear regression analysis in SPSS software version 22. The results indicated that there is a significant relationship between spiritual health (r=-0.51), perceived social support by family (r=-0.37), friends (r=-0.30) and significant other (r=-0.16) with death anxiety in the elderly. The results of linear regression analysis releaved that spiritual health (P=0.001, β=-0.46) and perceived social support by the family (P=0.001, β=-0.29) can predict negatively the death anxiety in the elderly and explain 26.7% of the variance of death anxiety in the elderly. Consequently, counselors and psychologists in the field of aging are suggested to reduce death anxiety in the elderly, using strategies to promote spiritual health and social support. ReferencesAbdel-Khalek, A. M. (2001). Death, anxiety, and depression in Kuwaiti undergraduates. OMEGA-Journal of Death and Dying, 42(4), 309-320.Abdel-Khalek, A. M. (2005). Death anxiety in clinical and non-clinical groups. Death Studies, 29(3), 251-259.Alipour, A., Aliakbari Dehkord, D. M., Amini, F., & Hashemi Jashni, J. A. (2016). Relationship between perceived social support and adherence of treatment in Diabetes Mellitus type 2: mediating role of resiliency and rope. Journal of Research in Psychological Health, 10(2), 53-67. 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Factors influencing death anxiety in community-dwelling elderly: based on the ecology theory. The Korean Journal of Hospice and Palliative Care, 22(1), 30-38.Krause, N., Pargament, K. I., & Ironson, G. (2018). In the shadow of death: Religious hope as a moderator of the effects of age on death anxiety. The Journals of Gerontology: Series B, 73(4), 696-703.Kübler-Ross, E. (2002). On death and dying; Questions and answers on death and dying; on life after death. Quality Paper Book Club. Kurtulan, M. H., & Karaırmak, Ö. (2016). Examination of the relationship among death anxiety, spirituality, religious orientation and existential anxiety. Spiritual Psychology and Counseling, 1(2), 206-217.Lehto, R. H., & Stein, K. F. (2009). Death anxiety: an analysis of an evolving concept. Research and theory for nursing practice, 23(1), 23–41.López‐Cerdá, E., Carmona‐Torres, J. M., & Rodríguez‐Borrego, M. A. (2019). Social support for elderly people over 65 years in Spain. 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The influence of social support and coping on quality of life among elderly with age-related hearing loss. American Journal of Audiology, 26(2), 170-179.Poordad, S., Momeni, K., & karami, J. (2019). Death anxiety and its relationship with social support and gratitude in older adults. Salmand: Iranian Journal of Ageing, 14(1), 26-39. [Persian].Rajabi, G.R., & Bahrani, M. (2001). Factor analysis of death anxiety scale questions. Journal of Psychology, 5 (4), 331-341. [Persian].Razavi, V. (2015). Relationship between social support and hope and death anxiety among the old people of Tehran Omid Cultural Center. International Journal of Life Sciences, 9(2), 65-70.Rocha, A. C. A. L. D., & Ciosak, S. I. (2014). Chronic disease in the elderly: spirituality and coping. Revista da Escola de Enfermagem da USP, 48(2), 87-93.Rostami, M., nosrati, K., Mahdinejad Gorji, G., kabiri, M. (2020). Death anxiety in the elderly: the role of psychological hardiness and practical commitment to prayer. 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Prayer and spiritual well-being in cancer patients. Health Monitor Journal of the Iranian Institute for Health Sciences Research, 5(4), 0-0. [Persian].Sharma, P., Asthana, H. S., Gambhir, I. S., & Ranjan, J. K. (2019). Death anxiety among elderly people: role of gender, spirituality and mental health

DOAJ (DOAJ: Directory of Open Access Journals) · 11 citationsread the source →