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A double-blind, randomized clinical trial comparing soybean oil-based versus olive oil-based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition.

Objective: Parenteral nutrition has been associated with metabolic and infectious complications in intensive care unit patients. The underlying mechanism for the high risk of complications is not known but may relate to the proinflammatory effects of soybean oil-based lipid emulsions, the only Food and Drug Administration-approved lipid formulation for clinical use. Design: Prospective, double-blind, randomized, controlled trial. Setting: Medical-surgical intensive care units from a major urban teaching hospital and a tertiary referral university hospital. Patients: Adult medical-surgical intensive care unit patients. Intervention: Parenteral nutrition containing soybean oil-based (Intralipid) or olive oil-based (ClinOleic) lipid emulsions. Measurements: Differences in hospital clinical outcomes (nosocomial infections and noninfectious complications), hospital length of stay, glycemic control, inflammatory and oxidative stress markers, and granulocyte and monocyte functions between study groups. Results: A total of 100 patients were randomized to either soybean oil-based parenteral nutrition or olive oil-based parenteral nutrition for up to 28 days. A total of 49 patients received soybean oil-based parenteral nutrition (age 51 ± 15 yrs, body mass index 27 ± 6 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.5 ± 7 [±SD]), and a total of 51 patients received olive oil-based lipid emulsion in parenteral nutrition (age 46 ± 19 yrs, body mass index 27 ± 8 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.1 ± 6 [±SD]) for a mean duration of 12.9 ± 8 days. The mean hospital blood glucose concentration during parenteral nutrition was 129 ± 14 mg/dL, without differences between groups. Patients treated with soybean oil-based and olive oil-based parenteral nutrition had a similar length of stay (47 ± 47 days and 41 ± 36 days, p = .49), mortality (16.3% and 9.8%, p = .38), nosocomial infections (43% vs. 57%, p = .16), and acute renal failure (26% vs. 18%, p = .34). In addition, there were no differences in inflammatory and oxidative stress markers or in granulocyte and monocyte functions between groups. Conclusion: The administration of parenteral nutrition containing soybean oil-based and olive oil-based lipid emulsion resulted in similar rates of infectious and noninfectious complications and no differences in glycemic control, inflammatory and oxidative stress markers, and immune function in critically ill adults.

Critical care medicine · randomised controlled trial · 43 citationsread the source →

Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort.

Background: Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. Methods: We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. Findings: We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. Interpretation: The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted. Funding: National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.

The Lancet. Oncology · cohort or longitudinal · 102 citationsread the source →

Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention.

Background: Early life may be a "critical period" when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects. Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey). Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m(2)) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry-assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003. Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001). Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.

The American journal of clinical nutrition · 85 citationsread the source →

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut-brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs. Findings: Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3-36·0) in 58 studies (I2=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0-28·5) in 75 studies (I2=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn's disease and ulcerative colitis within the same study population, patients with Crohn's disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1-1·4) and depression symptoms (1·2, 1·1-1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5-41·5] for women vs 22·8% [18·7-27·2] for men; OR 1·7 [95% CI 1·2-2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4-27·6] for women vs 16·2% [12·6-20·3] for men; OR 1·3 [95% CI 1·0-1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6-75·4]) or depression (38·9% [26·2-52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9-45·7] for anxiety symptoms and 24·2% [14·7-35·3] for depression symptoms; ORs 2·5 [95% CI 1·5-4·1] for anxiety and 3·1 [1·9-4·9] for depression). Interpretation: There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD. Funding: None.

The lancet. Gastroenterology & hepatology · meta-analysis · 514 citationsread the source →

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

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

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

Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.

Background: Excessive alcohol use contributes significantly to physical and psychological illness, injury and death, and a wide array of social harm in all age groups. A proven strategy for reducing excessive alcohol consumption levels is to offer a brief conversation-based intervention in primary care settings, but more recent technological innovations have enabled people to interact directly via computer, mobile device or smartphone with digital interventions designed to address problem alcohol consumption. Objectives: To assess the effectiveness and cost-effectiveness of digital interventions for reducing hazardous and harmful alcohol consumption, alcohol-related problems, or both, in people living in the community, specifically: (i) Are digital interventions more effective and cost-effective than no intervention (or minimal input) controls? (ii) Are digital interventions at least equally effective as face-to-face brief alcohol interventions? (iii) What are the effective component behaviour change techniques (BCTs) of such interventions and their mechanisms of action? (iv) What theories or models have been used in the development and/or evaluation of the intervention? Secondary objectives were (i) to assess whether outcomes differ between trials where the digital intervention targets participants attending health, social care, education or other community-based settings and those where it is offered remotely via the internet or mobile phone platforms; (ii) to specify interventions according to their mode of delivery (e.g. functionality features) and assess the impact of mode of delivery on outcomes. Search methods: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, ERIC, HTA and Web of Knowledge databases; ClinicalTrials.com and WHO ICTRP trials registers and relevant websites to April 2017. We also checked the reference lists of included trials and relevant systematic reviews. Selection criteria: We included randomised controlled trials (RCTs) that evaluated the effectiveness of digital interventions compared with no intervention or with face-to-face interventions for reducing hazardous or harmful alcohol consumption in people living in the community and reported a measure of alcohol consumption. Data collection and analysis: We used standard methodological procedures expected by The Cochrane Collaboration. Main results: We included 57 studies which randomised a total of 34,390 participants. The main sources of bias were from attrition and participant blinding (36% and 21% of studies respectively, high risk of bias). Forty one studies (42 comparisons, 19,241 participants) provided data for the primary meta-analysis, which demonstrated that participants using a digital intervention drank approximately 23 g alcohol weekly (95% CI 15 to 30) (about 3 UK units) less than participants who received no or minimal interventions at end of follow up (moderate-quality evidence).Fifteen studies (16 comparisons, 10,862 participants) demonstrated that participants who engaged with digital interventions had less than one drinking day per month fewer than no intervention controls (moderate-quality evidence), 15 studies (3587 participants) showed about one binge drinking session less per month in the intervention group compared to no intervention controls (moderate-quality evidence), and in 15 studies (9791 participants) intervention participants drank one unit per occasion less than no intervention control participants (moderate-quality evidence).Only five small studies (390 participants) compared digital and face-to-face interventions. There was no difference in alcohol consumption at end of follow up (MD 0.52 g/week, 95% CI -24.59 to 25.63; low-quality evidence). Thus, digital alcohol interventions produced broadly similar outcomes in these studies. No studies reported whether any adverse effects resulted from the interventions.A median of nine BCTs were used in experimental arms (range = 1 to 22). 'B' is an estimate of effect (MD in quantity of drinking, expressed in g/week) per unit increase in the BCT, and is a way to report whether individual BCTs are linked to the effect of the intervention. The BCTs of goal setting (B -43.94, 95% CI -78.59 to -9.30), problem solving (B -48.03, 95% CI -77.79 to -18.27), information about antecedents (B -74.20, 95% CI -117.72 to -30.68), behaviour substitution (B -123.71, 95% CI -184.63 to -62.80) and credible source (B -39.89, 95% CI -72.66 to -7.11) were significantly associated with reduced alcohol consumption in unadjusted models. In a multivariable model that included BCTs with B > 23 in the unadjusted model, the BCTs of behaviour substitution (B -95.12, 95% CI -162.90 to -27.34), problem solving (B -45.92, 95% CI -90.97 to -0.87), and credible source (B -32.09, 95% CI -60.64 to -3.55) were associated with reduced alcohol consumption. The most frequently mentioned theories or models in the included studies were Motivational Interviewing Theory (7/20), Transtheoretical Model (6/20) and Social Norms Theory (6/20). Over half of the interventions (n = 21, 51%) made no mention of theory. Only two studies used theory to select participants or tailor the intervention. There was no evidence of an association between reporting theory use and intervention effectiveness. Authors' conclusions: There is moderate-quality evidence that digital interventions may lower alcohol consumption, with an average reduction of up to three (UK) standard drinks per week compared to control participants. Substantial heterogeneity and risk of performance and publication bias may mean the reduction was lower. Low-quality evidence from fewer studies suggested there may be little or no difference in impact on alcohol consumption between digital and face-to-face interventions. The BCTs of behaviour substitution, problem solving and credible source were associated with the effectiveness of digital interventions to reduce alcohol consumption and warrant further investigation in an experimental context. Reporting of theory use was very limited and often unclear when present. Over half of the interventions made no reference to any theories. Limited reporting of theory use was unrelated to heterogeneity in intervention effectiveness.

The Cochrane database of systematic reviews · meta-analysis · 210 citationsread the source →

Comparison of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation before and during the COVID-19 pandemic: a systematic review and meta-analysis.

Background: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897. Findings: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05). Interpretation: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents. Funding: None.

The lancet. Psychiatry · meta-analysis · 164 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 →

Pharmacotherapy for anxiety and comorbid alcohol use disorders.

Background: Anxiety disorders are a potentially disabling group of disorders that frequently co-occur with alcohol use disorders. Comorbid anxiety and alcohol use disorders are associated with poorer outcomes, and are difficult to treat with standard psychosocial interventions. In addition, improved understanding of the biological basis of the conditions has contributed to a growing interest in the use of medications for the treatment of people with both diagnoses. Objectives: To assess the effects of pharmacotherapy for treating anxiety in people with comorbid alcohol use disorders, specifically: to provide an estimate of the overall effects of medication in improving treatment response and reducing symptom severity in the treatment of anxiety disorders in people with comorbid alcohol use disorders; to determine whether specific medications are more effective and tolerable than other medications in the treatment of particular anxiety disorders; and to identify which factors (clinical, methodological) predict response to pharmacotherapy for anxiety disorders. Search methods: Review authors searched the specialized registers of The Cochrane Collaboration Depression, Anxiety and Neurosis Review Group (CCDANCTR, to January 2014) and the Cochrane Drugs and Alcohol Group (CDAG, to March 2013) for eligible trials. These registers contain reports of relevant randomized controlled trials (RCT) from: the Cochrane Central Register of Controlled Trials (CENTRAL, all years), MEDLINE (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to date). Review authors ran complementary searches on EMBASE, PubMed, PsycINFO and the Alcohol and Alcohol Problems Science Database (ETOH) (to August 2013). We located unpublished trials through the National Institutes of Health (NIH) RePORTER service and the World Health Organization (WHO) International Clinical Trials Registry Platform (to August 2013). We screened reference lists of retrieved articles for additional studies. Selection criteria: All true RCTs of pharmacotherapy for treating anxiety disorders with comorbid alcohol use disorders. Trials assessing drugs administered for the treatment of drinking behaviour, such as naltrexone, disulfiram and acomprosate were not eligible for inclusion in this systematic review. Data collection and analysis: A systematic review is a standardised evaluation of all research studies that address a particular clinical issue. Two review authors independently assessed RCTs for inclusion in the review, collated trial data and assessed trial quality. We contacted investigators to obtain missing data. We calculated categorical and continuous treatment effect estimates and their 95% confidence intervals (CI) for treatment using a random-effects model with effect-size variability expressed using Chi(2) and I(2) heterogeneity statistics. Main results: We included five placebo-controlled pharmacotherapy RCTs (with 290 participants) in the review. Most of the trials provided little information on how randomization was performed or on whether both participants and study personnel were blinded to the intervention. Two of the three trials reporting superiority of medication compared with placebo on anxiety symptom outcomes were industry funded. We regarded one trial as being at high risk of bias due to selective reporting. Study participants had Diagnostic and Statistical Manual (DSM) III- and DSM IV-diagnosed alcohol use disorders and post-traumatic stress disorder (two studies), social anxiety disorder (SAD; two studies) or generalized anxiety disorder (GAD; one study). Four trials assessed the efficacy of the selective serotonin re-uptake inhibitors (SSRIs: sertraline, paroxetine); one RCT investigated the efficacy of buspirone, a 5-hydroxytryptamine (5-HT) partial agonist. Treatment duration lasted between eight and 24 weeks. Overall, 70% of participants included in the review were male. There was very low quality evidence for an effect of paroxetine on global clinical response to treatment, as assessed by the Clinical Global Impressions - Improvement scale (CGI-I). Global clinical response was observed in more than twice as many participants with paroxetine than with placebo (57.7% with paroxetine versus 25.8% with placebo; risk ratio (RR) 2.23, 95% CI 1.13 to 4.41; 2 trials, 57 participants). However, there was substantial uncertainty regarding the size of the effect of paroxetine due to the small number of studies providing data on clinically diverse patient samples. The second primary outcome measure was reduction of anxiety symptom severity. Although study investigators reported that buspirone (one trial) was superior to placebo in reducing the severity of anxiety symptoms over 12 weeks, no evidence of efficacy was observed for paroxetine (mean difference (MD) -14.70, 95% CI -33.00 to 3.60, 2 trials, 44 participants) and sertraline (one trial). Paroxetine appeared to be equally effective in reducing the severity of post-traumatic stress disorder (PTSD) symptoms as the tricyclic antidepressant desipramine in one RCT. The maximal reduction in anxiety disorder symptom severity was achieved after six weeks with paroxetine (two RCTs) and 12 weeks with buspirone (one RCT), with maintenance of medication efficacy extending to 16 with paroxetine and 24 weeks with buspirone. There was no evidence of an effect for any of the medications tested on abstinence from alcohol use or depression symptoms. There was very low quality evidence that paroxetine was well tolerated, based on drop-out due to treatment-emergent adverse effects. Nevertheless, levels of treatment discontinuation were high, with 43.1% of the participants in the studies withdrawing from medication treatment. Certain adverse effects, such as sexual problems, were commonly reported after treatment with paroxetine and sertraline. Authors' conclusions: The evidence-base for the effectiveness of medication in treating anxiety disorders and comorbid alcohol use disorders is currently inconclusive. There was a small amount of evidence for the efficacy of medication, but this was limited and of very low quality. The majority of the data for the efficacy and tolerability of medication were for SSRIs; there were insufficient data to establish differences in treatment efficacy between medication classes or patient subgroups. There was a small amount of very low quality evidence that medication was well tolerated. There was no evidence that alcohol use was responsive to medication. Large, rigorously conducted RCTs would help supplement the small evidence-base for the efficacy and tolerability of pharmacotherapy for anxiety and comorbid alcohol use disorders. Further research on patient subgroups who may benefit from pharmacological treatment, as well as novel pharmacological interventions, is warranted.

The Cochrane database of systematic reviews · meta-analysis · 54 citationsread the source →

Unconditional cash transfers for reducing poverty and vulnerabilities: effect on use of health services and health outcomes in low- and middle-income countries.

Background: Unconditional cash transfers (UCTs; provided without obligation) for reducing poverty and vulnerabilities (e.g. orphanhood, old age or HIV infection) are a type of social protection intervention that addresses a key social determinant of health (income) in low- and middle-income countries (LMICs). The relative effectiveness of UCTs compared with conditional cash transfers (CCTs; provided so long as the recipient engages in prescribed behaviours such as using a health service or attending school) is unknown. Objectives: To assess the effects of UCTs for improving health services use and health outcomes in vulnerable children and adults in LMICs. Secondary objectives are to assess the effects of UCTs on social determinants of health and healthcare expenditure and to compare to effects of UCTs versus CCTs. Search methods: We searched 17 electronic academic databases, including the Cochrane Public Health Group Specialised Register, the Cochrane Database of Systematic Reviews (the Cochrane Library 2017, Issue 5), MEDLINE and Embase, in May 2017. We also searched six electronic grey literature databases and websites of key organisations, handsearched key journals and included records, and sought expert advice. Selection criteria: We included both parallel group and cluster-randomised controlled trials (RCTs), quasi-RCTs, cohort and controlled before-and-after (CBAs) studies, and interrupted time series studies of UCT interventions in children (0 to 17 years) and adults (18 years or older) in LMICs. Comparison groups received either no UCT or a smaller UCT. Our primary outcomes were any health services use or health outcome. Data collection and analysis: Two reviewers independently screened potentially relevant records for inclusion criteria, extracted data and assessed the risk of bias. We tried to obtain missing data from study authors if feasible. For cluster-RCTs, we generally calculated risk ratios for dichotomous outcomes from crude frequency measures in approximately correct analyses. Meta-analyses applied the inverse variance or Mantel-Haenszel method with random effects. We assessed the quality of evidence using the GRADE approach. Main results: We included 21 studies (16 cluster-RCTs, 4 CBAs and 1 cohort study) involving 1,092,877 participants (36,068 children and 1,056,809 adults) and 31,865 households in Africa, the Americas and South-East Asia in our meta-analyses and narrative synthesis. The 17 types of UCTs we identified, including one basic universal income intervention, were pilot or established government programmes or research experiments. The cash value was equivalent to 1.3% to 53.9% of the annualised gross domestic product per capita. All studies compared a UCT with no UCT, and three studies also compared a UCT with a CCT. Most studies carried an overall high risk of bias (i.e. often selection and/or performance bias). Most studies were funded by national governments and/or international organisations. Throughout the review, we use the words 'probably' to indicate moderate-quality evidence, 'may/maybe' for low-quality evidence, and 'uncertain' for very low-quality evidence. UCTs may not have impacted the likelihood of having used any health service in the previous 1 to 12 months, when participants were followed up between 12 and 24 months into the intervention (risk ratio (RR) 1.04, 95% confidence interval (CI) 1.00 to 1.09, P = 0.07, 5 cluster-RCTs, N = 4972, I² = 2%, low-quality evidence). At one to two years, UCTs probably led to a clinically meaningful, very large reduction in the likelihood of having had any illness in the previous two weeks to three months (odds ratio (OR) 0.73, 95% CI 0.57 to 0.93, 5 cluster-RCTs, N = 8446, I² = 57%, moderate-quality evidence). Evidence from five cluster-RCTs on food security was too inconsistent to be combined in a meta-analysis, but it suggested that at 13 to 24 months' follow-up, UCTs could increase the likelihood of having been food secure over the previous month (low-quality evidence). UCTs may have increased participants' level of dietary diversity over the previous week, when assessed with the Household Dietary Diversity Score and followed up 24 months into the intervention (mean difference (MD) 0.59 food categories, 95% CI 0.18 to 1.01, 4 cluster-RCTs, N = 9347, I² = 79%, low-quality evidence). Despite several studies providing relevant evidence, the effects of UCTs on the likelihood of being moderately stunted and on the level of depression remain uncertain. No evidence was available on the effect of a UCT on the likelihood of having died. UCTs probably led to a clinically meaningful, moderate increase in the likelihood of currently attending school, when assessed at 12 to 24 months into the intervention (RR 1.06, 95% CI 1.03 to 1.09, 6 cluster-RCTs, N = 4800, I² = 0%, moderate-quality evidence). The evidence was uncertain for whether UCTs impacted livestock ownership, extreme poverty, participation in child labour, adult employment or parenting quality. Evidence from six cluster-RCTs on healthcare expenditure was too inconsistent to be combined in a meta-analysis, but it suggested that UCTs may have increased the amount of money spent on health care at 7 to 24 months into the intervention (low-quality evidence). The effects of UCTs on health equity (or unfair and remedial health inequalities) were very uncertain. We did not identify any harms from UCTs. Three cluster-RCTs compared UCTs versus CCTs with regard to the likelihood of having used any health services, the likelihood of having had any illness or the level of dietary diversity, but evidence was limited to one study per outcome and was very uncertain for all three. Authors' conclusions: This body of evidence suggests that unconditional cash transfers (UCTs) may not impact a summary measure of health service use in children and adults in LMICs. However, UCTs probably or may improve some health outcomes (i.e. the likelihood of having had any illness, the likelihood of having been food secure, and the level of dietary diversity), one social determinant of health (i.e. the likelihood of attending school), and healthcare expenditure. The evidence on the relative effectiveness of UCTs and CCTs remains very uncertain.

The Cochrane database of systematic reviews · meta-analysis · 78 citationsread the source →

How Should Social Media Be Used in Transplantation? A Survey of the American Society of Transplant Surgeons.

Background: Social media platforms are increasingly used in surgery and have shown promise as effective tools to promote deceased donation and expand living donor transplantation. There is a growing need to understand how social media-driven communication is perceived by providers in the field of transplantation. Methods: We surveyed 299 members of the American Society of Transplant Surgeons about their use of, attitudes toward, and perceptions of social media and analyzed relationships between responses and participant characteristics. Results: Respondents used social media to communicate with: family and friends (76%), surgeons (59%), transplant professionals (57%), transplant recipients (21%), living donors (16%), and waitlisted candidates (15%). Most respondents (83%) reported using social media for at least 1 purpose. Although most (61%) supported sharing information with transplant recipients via social media, 42% believed it should not be used to facilitate living donor-recipient matching. Younger age (P = 0.02) and fewer years of experience in the field of transplantation (P = 0.03) were associated with stronger belief that social media can be influential in living organ donation. Respondents at transplant centers with higher reported use of social media had more favorable views about sharing information with transplant recipients (P < 0.01), increasing awareness about deceased organ donation (P < 0.01), and advertising for transplant centers (P < 0.01). Individual characteristics influence opinions about the role and clinical usefulness of social media. Conclusions: Transplant center involvement and support for social media may influence clinician perceptions and practices. Increasing use of social media among transplant professionals may provide an opportunity to deliver high-quality information to patients.

Transplantation · 28 citationsread the source →

Neuropsychiatric symptoms and caregiver's burden in Parkinson's disease.

Introduction: In Parkinson's disease (PD), neuropsychiatric symptoms (NPS) can be particularly burdensome for caregivers. The main goal of this study was to assess the impact of NPS, assessed by means of a new specific scale, on caregiver burden. Methods: A sample of 584 pairs of PD patients and their primary caregivers was studied. Patients' NPS were measured with the Scale for Evaluation of Neuropsychiatric Disorders in PD (SEND-PD), and the Zarit Caregiver Burden Inventory was used to quantify caregiver burden. Three linear regression models were built to check factors associated with caregiver burden, one for the total sample and two for subgroups stratified by the presence of dementia. Results: The most frequent NPS were depression (in 66% of the sample), anxiety (65%) and mental fatigue (57%). Patients with dementia (n = 94; 16% of sample) consistently presented more NPS than patients without dementia (p < 0.001). On linear regression models, the main determinants of caregiver burden (for the total sample and the sample of patients without dementia) were SEND-PD dimensions mood/apathy and psychosis, PD-related disability and disease duration. For patients with dementia, the only significant caregiver burden determinants were SEND-PD psychosis and mood/apathy subscale scores. Conclusions: NPS in PD are highly associated with and are determinants of caregiver burden, and are more prevalent and burdensome in patients with dementia. Detailed assessment and specific interventions aimed at NPS could alleviate caregiver burden.

Parkinsonism & related disorders · 158 citationsread the source →

Cognitive reappraisal self-efficacy mediates the effects of individual cognitive-behavioral therapy for social anxiety disorder.

OBJECTIVE: To examine whether changes in cognitive reappraisal self-efficacy (CR-SE) mediate the effects of individually administered cognitive-behavioral therapy (I-CBT) for social anxiety disorder (SAD) on severity of social anxiety symptoms. METHOD: A randomized controlled trial in which 75 adult patients (21-55 years of age; 53% male; 57% Caucasian) with a principal diagnosis of generalized SAD were randomly assigned to 16 sessions of I-CBT (n = 38) or a wait-list control (WL) group (n = 37). All patients completed self-report inventories measuring CR-SE and social anxiety symptoms at baseline and post-I-CBT/post-WL, and I-CBT completers were also assessed at 1-year posttreatment. RESULTS: Compared with WL, I-CBT resulted in greater increases in CR-SE and greater decreases in social anxiety. Increases in CR-SE during I-CBT mediated the effect of I-CBT on social anxiety. Gains achieved by patients receiving I-CBT were maintained 1-year posttreatment, and I-CBT-related increases in CR-SE were also associated with reduction in social anxiety at the 1-year follow-up. CONCLUSIONS: Increasing CR-SE may be an important mechanism by which I-CBT for SAD produces both immediate and long-term reductions in social anxiety.

Journal of Consulting and Clinical Psychology · randomised controlled trial · 325 citationsread the source →

Mental health care for unaccompanied young refugees in Germany through a stepped care approach versus enhanced usual care: a cluster-randomised hybrid effectiveness-implementation trial.

Background: Unaccompanied young refugees are a vulnerable group with high rates of post-traumatic stress symptoms (PTSS). Stepped care approaches are recommended as a potential treatment framework, but research on the effectiveness of these models remains scarce. We aimed to compare a stepped care approach for unaccompanied young refugees with enhanced usual care under real-world conditions. Methods: In this cluster-randomised controlled type I hybrid implementation-effectiveness trial, we compared two active conditions, BETTER CARE and enhanced usual care, for unaccompanied young refugees in child and youth welfare service (CYWS) facilities across seven states in Germany. Eligibility criteria included age 12-20 years; arrival in Germany as unaccompanied minors; asylum application or intention; in CYWS facility care at baseline; and at least one traumatic event reported. Masking of participants was not possible due to each CYWS facility being randomly assigned to a specific treatment arm. Additionally, although study personnel were not masked to the condition, all data were self-reported and study personnel remained masked to data entry. BETTER CARE was a stepped care approach consisting of screening, prevention (via the Mein Weg [My Way] group intervention), and trauma-focused cognitive behavioural therapy (TF-CBT). Enhanced usual care included screening and a corresponding treatment recommendation. Clusters comprised one CYWS facility and were stratified and randomly assigned (1:1) using permuted blocks. Self-report questionnaires were used to assess PTSS, depressive symptoms, anxiety symptoms, and quality of life at baseline, 6 months, and 12 months. The primary outcome was a reduction in PTSS, analysed with the Child and Adolescent Trauma Screen (CATS-2) score in the intention-to-treat sample (all randomly assigned participants). The study was preregistered in the German Clinical Trials Register (DRKS00017453). Findings: The study was conducted between Oct 14, 2019, and July 27, 2023. 58 (11%) of 525 eligible facilities, including 627 unaccompanied young refugees originating from 40 countries, decided to participate and were randomly assigned. The mean age of the participants was 16·7 years (SD 1·3), with 569 (91%) identifying as male, 53 (8%) as female, and five (1%) as gender diverse. Participants reported a mean of six traumatic events (SD 3·3). 270 (43%) unaccompanied young refugees had clinically elevated levels of PTSS, and 357 (57%) were below the clinical threshold for PTSS (based on CATS-2 scores). 12 months after random assignment, there was a significant between-groups change over time effect size for PTSS in favour of BETTER CARE in the intention-to-treat sample (d=-0·17 [95% CI -0·34 to -0·004]). The dropout rate at 12 months was 38% (n=124) in BETTER CARE and 43% (n=131) in enhanced usual care. Service use and retention were low within the 12-month study period. Interpretation: This study shows the effectiveness of a stepped care model including screening, prevention, and evidence-based interventions for unaccompanied young refugees in a high-income country. The potential benefit of screening and structured care recommendations was highlighted further by improvements in the enhanced usual care condition. Dropout rates were high but similar to those in previous studies with young refugees. Future studies should address demand-side barriers to improve service use and retention. Funding: German Federal Ministry of Education and Research.

The Lancet. Global health · randomised controlled trial · 1 citationsread the source →

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

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

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

Effects of incorporating multidomain interventions into integrated primary care on quality of life: a randomised controlled trial.

Background: Integrating primary prevention into care pathways for older adults is a core strategy of healthy ageing, but evidence remains limited. We aimed to determine whether incorporating a multidomain intervention into primary health care could improve standard value-based health outcomes and quality of life. Methods: For this Taiwan Integrated Geriatric Care (TIGER) study, a pragmatic randomised controlled trial, we recruited community-dwelling outpatients aged 65 years or older with at least three chronic medical conditions. We excluded people with malignancies undergoing chemotherapy, people with a life expectancy of less than 12 months, or people who were insufficiently able to communicate with study staff. Participants were randomly assigned (1:1) to usual care or to the integrated multidomain intervention using block randomisation. The integrated multidomain intervention entailed 16 2-h sessions per year, comprising communal physical exercise, cognitive training, nutrition and disease education, plus individualised treatment by specialists in integrated geriatric care. The primary outcome was changes from baseline quality of life, based on 36-item Short Form Health Survey (SF-36) scores, at 3, 6, 9, and 12 months. Intervention effects were analysed per protocol using a generalised linear mixed model. This trial is registered with ClinicalTrials.gov, NCT03528005. Findings: Between June 25, 2018, and Feb 15, 2019, 628 participants were screened, of whom 398 were assigned to the integrated multidomain intervention (n=199) or to usual care (n=199). 335 (84%) participants completed the 12-month follow-up. Compared with the usual care group, the integrated multidomain intervention group had significantly higher mean SF-36 physical component scores across all timepoints (overall difference 0·8, 95% CI 0·2-1·5; p=0·010), but differences at 3, 6, 9, and 12 months did not reach statistical significance. The SF-36 mental component scores did not differ significantly overall, but were significantly higher in the integrated multidomain intervention group at the 12-month follow-up (55·3 [SD 7·6] vs 57·2 [7·0]; p=0·019). No serious adverse events occurred. Interpretation: Incorporating multidomain interventions into integrated health care improved quality of life. Our standardised protocol is amenable to inclusion in policies to promote value-based care and healthy ageing. Funding: National Health Research Institutes, Taiwan, and Ministry of Science and Technology, Taiwan.

The lancet. Healthy longevity · randomised controlled trial · 63 citationsread the source →

Improving patient experiences of mental health inpatient care: a randomised controlled trial.

Background: Poorer patient views of mental health inpatient treatment predict both further admissions and, for those admitted involuntarily, longer admissions. As advocated in the UK Francis report, we investigated the hypothesis that improving staff training improves patients' views of ward care. Method: Cluster randomised trial with stepped wedge design in 16 acute mental health wards randomised (using the ralloc procedure in Stata) by an independent statistician in three waves to staff training. A psychologist trained ward staff on evidence-based group interventions and then supported their introduction to each ward. The main outcome was blind self-report of perceptions of care (VOICE) before or up to 2 years after staff training between November 2008 and January 2013. Results: In total, 1108 inpatients took part (616 admitted involuntarily under the English Mental Health Act). On average 51.6 staff training sessions were provided per ward. Involuntary patient's perceptions of, and satisfaction with, mental health wards improved after staff training (N582, standardised effect -0·35, 95% CI -0·57 to -0·12, p = 0·002; interaction p value 0·006) but no benefit to those admitted voluntarily (N469, -0.01, 95% CI -0.23 to 0.22, p = 0.955) and no strong evidence of an overall effect (N1058, standardised effect -0.18 s.d., 95% CI -0.38 to 0.01, p = 0.062). The training costs around £10 per patient per week. Resource allocation changed towards patient perceived meaningful contacts by an average of £12 (95% CI -£76 to £98, p = 0.774). Conclusion: Staff training improved the perceptions of the therapeutic environment in those least likely to want an inpatient admission, those formally detained. This change might enhance future engagement with all mental health services and prevent the more costly admissions.

Psychological medicine · randomised controlled trial · 34 citationsread the source →

Psychosocial Effect of Newborn Genomic Sequencing on Families in the BabySeq Project: A Randomized Clinical Trial.

Importance: Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families. Objective: To assess the psychosocial effect of nGS on families from the BabySeq Project, a randomized clinical trial evaluating the effect of nGS on the clinical care of newborns from well-baby nurseries and intensive care units. Design, setting, and participants: In this randomized clinical trial conducted from May 14, 2015, to May 21, 2019, at well-baby nurseries and intensive care units at 3 Boston, Massachusetts, area hospitals, 519 parents of 325 infants completed surveys at enrollment, immediately after disclosure of nGS results, and 3 and 10 months after results disclosure. Statistical analysis was performed on a per-protocol basis from January 16, 2019, to December 1, 2019. Intervention: Newborns were randomized to receive either standard newborn screening and a family history report (control group) or the same plus an nGS report of childhood-onset conditions and highly actionable adult-onset conditions (nGS group). Main outcomes and measures: Mean responses were compared between groups and, within the nGS group, between parents of children who received a monogenic disease risk finding and those who did not in 3 domains of psychosocial impact: parent-child relationship (Mother-to-Infant Bonding Scale), parents' relationship (Kansas Marital Satisfaction Scale), and parents' psychological distress (Edinburgh Postnatal Depression Scale anxiety subscale). Results: A total of 519 parents (275 women [53.0%]; mean [SD] age, 35.1 [4.5] years) were included in this study. Although mean scores differed for some outcomes at singular time points, generalized estimating equations models did not show meaningful differences in parent-child relationship (between-group difference in adjusted mean [SE] Mother-to-Infant Bonding Scale scores: postdisclosure, 0.04 [0.15]; 3 months, -0.18 [0.18]; 10 months, -0.07 [0.20]; joint P = .57) or parents' psychological distress (between-group ratio of adjusted mean [SE] Edinburgh Postnatal Depression Scale anxiety subscale scores: postdisclosure, 1.04 [0.08]; 3 months, 1.07 [0.11]; joint P = .80) response patterns between study groups over time for any measures analyzed in these 2 domains. Response patterns on one parents' relationship measure differed between groups over time (between-group difference in adjusted mean [SE] Kansas Marital Satisfaction Scale scores: postdisclosure, -0.19 [0.07]; 3 months, -0.04 [0.07]; and 10 months, -0.01 [0.08]; joint P = .02), but the effect decreased over time and no difference was observed on the conflict measure responses over time. We found no evidence of persistent negative psychosocial effect in any domain. Conclusions and relevance: In this randomized clinical trial of nGS, there was no persistent negative psychosocial effect on families among those who received nGS nor among those who received a monogenic disease risk finding for their infant. Trial registration: ClinicalTrials.gov Identifier: NCT02422511.

JAMA pediatrics · randomised controlled trial · 70 citationsread the source →

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, settings, and participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main outcomes and measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial registration: clinicaltrials.gov Identifier: NCT01685840.

JAMA · randomised controlled trial · 395 citationsread the source →

Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial.

Background: Functional gastrointestinal disorders are common and costly to the health-care system. Most specialist care is provided by a gastroenterologist, but only a minority of patients have improvement in symptoms. Although they have proven to be effective, psychological, behavioural, and dietary therapies are not provided routinely. We aimed to compare the outcome of gastroenterologist-only standard care with multidisciplinary care. Methods: In an open-label, single-centre, pragmatic trial, consecutive new referrals of eligible patients aged 18-80 years with Rome IV criteria-defined functional gastrointestinal disorders were randomly assigned (1:2) to receive gastroenterologist-only standard care or multidisciplinary clinic care. The multidisciplinary clinic included gastroenterologists, dietitians, gut-focused hypnotherapists, psychiatrists, and behavioural (biofeedback) physiotherapists. Randomisation was stratified by Rome IV disorder and whether referred from gastroenterology or colorectal clinic. Outcomes were assessed at clinic discharge or 9 months after the initial visit. The primary outcome was a score of 4 (slightly better) or 5 (much better) on a 5-point Likert scale assessing global symptom improvement. Modified intention-to-treat analysis included all patients who attended at least one clinic visit and who had answered the primary outcome question. This study is registered with ClinicalTrials.gov, NCT03078634. Findings: Between March 16, 2017, and May 10, 2018, 1632 patients referred to the hospital gastrointestinal clinics were screened, of whom 442 were eligible for a screening telephone call and 188 were randomly assigned to receive either standard care (n=65) or multidisciplinary care (n=123). 144 patients formed the modified intention-to-treat analysis (n=46 in the standard-care group and n=98 in the multidisciplinary-care group), 90 (63%) of whom were women. 61 (62%) of 98 patients in the multidisciplinary-care group patients saw allied clinicians. 26 (57%) patients in the standard-care group and 82 (84%) patients in the multidisciplinary-care group had global symptom improvement (risk ratio 1·50 [95% CI 1·13-1·93]; p=0·00045). 29 (63%) patients in the standard-care group and 81 (83%) patients in the multidisciplinary-care group had adequate relief of symptoms in the past 7 days (p=0·010). Patients in the multidisciplinary-care group were more likely to experience a 50% or higher reduction in all Gastrointestinal Symptom Severity Index symptom clusters than were patients in the standard-care group. Of the patients with irritable bowel syndrome, a 50-point or higher reduction in IBS-SSS occurred in 10 (38%) of 26 patients in the standard care group compared with 39 (66%) of 59 patients in the multidisciplinary-care group (p=0·017). Of the patients with functional dyspepsia, a 50% reduction in the Nepean Dyspepsia Index was noted in three (11%) of 11 patients in the standard-care group and in 13 (46%) of 28 in the multidisciplinary-care group (p=0·47). After treatment, the median HADS scores were higher in the standard-care group than in the multidisciplinary-care group (13 [8-20] vs 10 [6-16]; p=0·096) and the median EQ-5D-5L quality of life visual analogue scale was lower in the standard-care group compared with the multidisciplinary-care group (70 [IQR 50-80] vs 75 [65-85]; p=0·0087). The eight SF-36 scales did not differ between the groups at discharge. After treatment, median Somatic Symptom Scale-8 score was higher in the standard-care group than in the multidisciplinary-care group (10 [IQR 7-7] vs 9 [5-13]; p=0·082). Cost per successful outcome was higher in the standard-care group than the multidisciplinary-care group. Interpretation: Integrated multidisciplinary clinical care appears to be superior to gastroenterologist-only care in relation to symptoms, specific functional disorders, psychological state, quality of life, and cost of care for the treatment of functional gastrointestinal disorders. Consideration should be given to providing multidisciplinary care for patients with a functional gastrointestinal disorder. Funding: None.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 89 citationsread the source →

Imaginator: A Proof-of-Concept Feasibility Trial of a Brief Imagery-Based Psychological Intervention for Young People Who Self-Harm.

Objectives: The Imaginator study tested the feasibility of a short mental imagery-based psychological intervention for young people who self-harm and used a stepped-wedge design to investigate effects on self-harm frequency reduction at 3 and 6 months. Method: A total of 38 participants aged 16-25 were recruited via community self-referral and mental health services. Participants were randomized to immediate delivery of Functional Imagery Training (FIT) or usual care followed by delayed delivery after 3 months. FIT comprised two face-to-face sessions, five phone sessions, and use of a smartphone app. Outcomes' assessment was blind to allocation. Results: Three quarters of those who began treatment completed face-to-face sessions, and 57% completed five or more sessions in total. Self-harm frequency data were obtained on 76% of the sample at 3 months (primary outcome) and 63% at 6 months. FIT produced moderate reductions in self-harm frequency at 3 months after immediate (d = 0.65) and delayed delivery (d = 0.75). The Immediate FIT group maintained improvements from 3 to 6 months (d = 0.05). Participants receiving usual care also reduced self-harm (d = 0.47). Conclusions: A brief mental imagery-based psychological intervention targeting self-harm in young people is feasible and may comprise a novel transdiagnostic treatment for self-harm.

Suicide & life-threatening behavior · randomised controlled trial · 34 citationsread the source →

Uptake of antiretroviral therapy and male circumcision after community-based HIV testing and strategies for linkage to care versus standard clinic referral: a multisite, open-label, randomised controlled trial in South Africa and Uganda.

Background: Male circumcision decreases HIV acquisition by 60%, and antiretroviral therapy (ART) almost eliminates HIV transmission from HIV-positive people who are virally suppressed; however, coverage of these interventions has lagged behind targets. We aimed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision. Methods: We did this multisite, open-label, randomised controlled trial in six research-naive communities in rural South Africa and Uganda. Eligible HIV-positive participants (aged ≥16 years) were randomly assigned (1:1:1) in a factorial design to receive lay counsellor clinic linkage facilitation, lay counsellor follow-up home visits, or standard-of-care clinic referral, and then (1:1) either point-of-care CD4 cell count testing or referral for CD4 testing. HIV-negative uncircumcised men (aged 16-49 years) who could receive secure mobile phone text messages were randomly assigned (1:1:1) to receive text message reminders, lay counsellor visits, or standard clinic referral. The study biostatistician generated the randomisation schedule via a computer-generated random number program with varying block sizes (multiples of six or three) stratified by country. Primary outcomes for HIV-positive people were obtaining a CD4 cell count, linkage to an HIV clinic, ART initiation, and viral suppression at 9 months, and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months. We assessed social harms as a safety outcome throughout the study. We did the primary analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02038582. Findings: Between June 6, 2013, and March 11, 2015, 15 332 participants were tested. 2339 (15%) participants tested HIV positive, of whom 1325 (57%) were randomly assigned to receive lay counsellor clinic linkage facilitation (n=437), lay counsellor follow-up home visits (n=449), or standard clinic referral (n=439), and then point-of-care CD4 cell testing (n=206, n=220, and n=213, respectively) or referral for CD4 testing (n=231, n=229, and n=226, respectively). 12 993 (85%) participants tested HIV negative, of whom 750 (6%) uncircumcised men were randomly assigned to receive clinic referral (n=230), text message reminders (n=288), or lay counsellor follow-up visits (n=232). 1218 (93%) of 1303 HIV-positive participants were linked to care, but only 488 (37%) participants initiated ART. Overall, 635 (50%) of 1272 HIV-positive individuals achieved viral suppression at 9 months: 219 (52%) of 419 participants in the clinic facilitation group, 202 (47%) of 431 participants in the lay counsellor follow-up group, and 214 (51%) of 422 participants in the clinic referral group, with no significant differences between groups (p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral). 523 (72%) of 734 HIV-negative men visited a circumcision facility, with no difference between groups. 62 (28%) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 (48%) of 284 men in the text message reminder group (relative risk 1·72, 95% CI 1·36-2·17; p<0·0001) and 106 (47%) of 226 men in the lay counsellor follow-up group (1·67, 1·29-2·14; p=0·0001). No cases of study-related social harm were reported, including probing about partnership separation, unintended disclosure, gender-based violence, and stigma. Interpretation: All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics, roughly a third of whom initiated ART, and of those more than 80% were virally suppressed at 9 months. Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received standard-of-care clinic referral. Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

The lancet. HIV · randomised controlled trial · 65 citationsread the source →

Neural correlates of psychotherapy in anxiety and depression: a meta-analysis.

Several studies have used neuroimaging methods to identify neural change in brain networks associated to emotion regulation after psychotherapy of depression and anxiety. In the present work we adopted a meta-analytic technique specific to neuroimaging data to evaluate the consistence of empirical findings and assess models of therapy that have been proposed in the literature. Meta-analyses were conducted with the Activation Likelihood Estimation technique, which evaluates the overlap between foci of activation across studies. The analysis included 16 studies found in Pubmed (200 foci of activation and 193 patients). Separate meta-analyses were conducted on studies of 1) depression, post-traumatic stress disorder and panic disorder investigated with rest state metabolism (6 studies, 70 patients); 2) depression, post-traumatic stress disorder and panic disorder investigated with task-related activation studies (5 studies, 65 patients); 3) the previous studies considered jointly; and 4) phobias investigated with studies on exposure-related activation (5 studies, 57 patients). Studies on anxiety and depression gave partially consistent results for changes in the dorsomedial prefrontal cortex and in the posterior cingulated gyrus/precuneus. Several areas of change in the temporal lobes were also observed. Studies on the therapy of phobia were consistent with a reduction of activity in medial temporal areas. The cluster of change in the prefrontal cortex may refer to increased recruitment of control processes, as hypothesized by influential models of emotion regulation changes due to psychotherapy. However, not all areas associated with controlled emotion regulation were detected in the meta-analysis, while involvement of midline structures suggested changes in self-related information processing. Changes in phobia were consistent with reduced reactivity to phobic stimuli.

PloS one · meta-analysis · 72 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

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

Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial.

Background: Chronic fatigue syndrome is characterised by persistent fatigue and severe disability. Cognitive behavioural therapy seems to be a promising treatment, but its availability is restricted. We developed Fatigue In Teenagers on the interNET (FITNET), the first dedicated internet-based therapeutic program for adolescents with this disorder, and compared its effectiveness with that of usual care. Methods: Adolescents aged 12-18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherlands by use of a computer-generated blocked randomisation allocation schedule. The study was open label. Primary outcomes were school attendance, fatigue severity, and physical functioning, and were assessed at 6 months with computerised questionnaires. Analysis was by intention to treat. Thereafter, all patients were offered FITNET if needed. This trial is registered, number ISRCTN59878666. Findings: 68 of 135 adolescents were assigned to FITNET and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months-full school attendance (50 [75%] vs 10 [16%], relative risk 4·8, 95% CI 2·7-8·9; p<0·0001), absence of severe fatigue (57 [85%] vs 17 [27%], 3·2, 2·1-4·9; p<0·0001), and normal physical functioning (52 [78%] vs 13 [20%], 3·8, 2·3-6·3; p<0·0001). No serious adverse events were reported. Interpretation: FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome. The results of this study justify implementation on a broader scale. Funding: Netherlands Organisation for Health Research and Development.

Lancet (London, England) · randomised controlled trial · 140 citationsread the source →

Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols.

Purpose: To determine the survival of infants and young children with non-metastatic medulloblastoma using intensive myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR). Methods: Twenty-one children less than 3 years old at diagnosis with non-metastatic medulloblastoma were enrolled on two identical serial studies, "Head Start" I and "Head Start" II. After surgery, patients received five cycles of induction chemotherapy consisting of vincristine, cisplatin, cyclophosphamide and etoposide. Following induction, all patients underwent myeloablative chemotherapy using carboplatin, thiotepa and etoposide with AuHCR. Irradiation was used only at relapse. Results: The 5-year event-free (EFS) and overall survival (OS) rates (+/-SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 +/- 11% and 70 +/- 10%, 64 +/- 13% and 79 +/- 11%, and 29 +/- 17% and 57 +/- 19%, respectively. The 5-year EFS and OS ( +/- SE) for patients with desmoplastic and classical medulloblastoma were 67 +/- 16% and 78 +/- 14%, and 42 +/- 14 and 67 +/- 14%, respectively. There were four treatment related deaths. The majority of survivors (71%) avoided irradiation completely. Mean intellectual functioning and quality of life (QoL) for children surviving without irradiation was within average range for a majority of survivors tested. Conclusion: This strategy of brief intensive chemotherapy for young children with non-metastatic medulloblastoma eliminated the need for craniospinal irradiation 52% of the patients, and may preserve QoL and intellectual functioning. The excellent survival rates are somewhat dampened by high toxic mortality.

Pediatric blood & cancer · randomised controlled trial · 155 citationsread the source →

The relationship between the therapeutic alliance and treatment outcome in two distinct psychotherapies for chronic depression.

Objective: This study tested whether the quality of the patient-rated working alliance, measured early in treatment, predicted subsequent symptom reduction in chronically depressed patients. Secondarily, the study assessed whether the relationship between early alliance and response to treatment differed between patients receiving cognitive behavioral analysis system of psychotherapy (CBASP) vs. brief supportive psychotherapy (BSP). Method: 395 adults (57% female; Mage = 46; 91% Caucasian) who met criteria for chronic depression and did not fully remit during a 12-week algorithm-based, open-label pharmacotherapy trial were randomized to receive either 16-20 sessions of CBASP or BSP in addition to continued, algorithm-based antidepressant medication. Of these, 224 patients completed the Working Alliance Inventory-Short Form at Weeks 2 or 4 of treatment. Blind raters assessed depressive symptoms at 2-week intervals across treatment using the Hamilton Rating Scale for Depression. Linear mixed models tested the association between early alliance and subsequent symptom ratings while accounting for early symptom change. Results: A more positive early working alliance was associated with lower subsequent symptom ratings in both the CBASP and BSP, F(1, 1236) = 62.48, p < .001. In addition, the interaction between alliance and psychotherapy type was significant, such that alliance quality was more strongly associated with symptom ratings among those in the CBASP treatment group, F(1, 1234) = 8.31, p = .004. Conclusions: The results support the role of the therapeutic alliance as a predictor of outcome across dissimilar treatments for chronic depression. Contrary to expectations, the therapeutic alliance was more strongly related to outcome in CBASP, the more directive of the 2 therapies.

Journal of consulting and clinical psychology · randomised controlled trial · 79 citationsread the source →

A randomized controlled trial of mindfulness meditation versus relaxation training: effects on distress, positive states of mind, rumination, and distraction.

Background: Although mindfulness meditation interventions have recently shown benefits for reducing stress in various populations, little is known about their relative efficacy compared with relaxation interventions. Purpose: This randomized controlled trial examines the effects of a 1-month mindfulness meditation versus somatic relaxation training as compared to a control group in 83 students (M age = 25; 16 men and 67 women) reporting distress. Method: Psychological distress, positive states of mind, distractive and ruminative thoughts and behaviors, and spiritual experience were measured, while controlling for social desirability. Results: Hierarchical linear modeling reveals that both meditation and relaxation groups experienced significant decreases in distress as well as increases in positive mood states over time, compared with the control group (p < .05 in all cases). There were no significant differences between meditation and relaxation on distress and positive mood states over time. Effect sizes for distress were large for both meditation and relaxation (Cohen's d = 1.36 and .91, respectively), whereas the meditation group showed a larger effect size for positive states of mind than relaxation (Cohen's d =.71 and .25, respectively). The meditation group also demonstrated significant pre-post decreases in both distractive and ruminative thoughts/behaviors compared with the control group (p < .04 in all cases; Cohen's d = .57 for rumination and .25 for distraction for the meditation group), with mediation models suggesting that mindfulness meditation's effects on reducing distress were partially mediated by reducing rumination. No significant effects were found for spiritual experience. Conclusions: The data suggest that compared with a no-treatment control, brief training in mindfulness meditation or somatic relaxation reduces distress and improves positive mood states. However, mindfulness meditation may be specific in its ability to reduce distractive and ruminative thoughts and behaviors, and this ability may provide a unique mechanism by which mindfulness meditation reduces distress.

Annals of behavioral medicine : a publication of the Society of Behavioral Medicine · randomised controlled trial · 507 citationsread the source →

A randomised controlled trial of cognitive behaviour therapy in adolescents with major depression treated by selective serotonin reuptake inhibitors. The ADAPT trial

OBJECTIVES: To determine if, in the short term, depressed adolescents attending routine NHS Child and Adolescent Mental Health Services (CAMHS), and receiving ongoing active clinical care, treatment with selective serotonin reuptake inhibitors (SSRIs) plus cognitive behaviour therapy (CBT) compared with SSRI alone, results in better healthcare outcomes. DESIGN: A pragmatic randomised controlled trial (RCT) was conducted on depressed adolescents attending CAMHS who had not responded to a psychosocial brief initial intervention (BII) prior to randomisation. SETTING: Six English CAMHS participated in the study. PARTICIPANTS: A total of 208 patients aged between 11 and 17 years were recruited and randomised. INTERVENTIONS: All participants received active routine clinical care in a CAMHS outpatient setting and an SSRI and half were offered CBT. MAIN OUTCOME MEASURES: The duration of the trial was a 12-week treatment phase, followed by a 16-week maintenance phase. Follow-up assessments were at 6, 12 and 28 weeks. The primary outcome measure was the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). Secondary outcome measures were self-report depressive symptoms, interviewer-rated depressive signs and symptoms, interviewer-rated psychosocial impairment and clinical global impression of response to treatment. Information on resource use was collected in interview at baseline and at the 12- and 28-week follow-up assessments using the Child and Adolescent Service Use Schedule (CA-SUS). RESULTS: Of the 208 patients randomised, 200 (96%) completed the trial to the primary end-point at 12 weeks. By the 28-week follow-up, 174 (84%) participants were re-evaluated. Overall, 193 (93%) participants had been assessed at one or more time points. Clinical characteristics indicated that the trial was conducted on a severely depressed group. There was significant recovery at all time points in both arms. The findings demonstrated no difference in treatment effectiveness for SSRI + CBT over SSRI only for the primary or secondary outcome measures at any time point. This lack of difference held when baseline and treatment characteristics where taken into account (age, sex, severity, co-morbid characteristics, quality and quantity of CBT treatment, number of clinic attendances). The SSRI + CBT group was somewhat more expensive over the 28 weeks than the SSRI-only group (p=0.057) and no more cost-effective. Over the trial period there was on average a decrease in suicidal thoughts and self-harm compared with levels recorded at baseline. There was no significant increase in disinhibition, irritability and violence compared with levels at baseline. Around 20% (n=40) of patients in the trial were non-responders. Of these, 17 (43%) showed no improvement by 28 weeks and 23 (57%) were considered minimally (n=10) or moderately to severely worse (n=13). CONCLUSIONS: For moderately to severely depressed adolescents who are non-responsive to a BII, the addition of CBT to fluoxetine plus routine clinical care does not improve outcome or confer protective effects against adverse events and is not cost-effective. SSRIs (mostly fluoxetine) are not likely to result in harmful adverse effects. The findings are broadly consistent with existing guidelines on the treatment of moderate to severe depression. Modification is advised for those presenting with moderate (6-8 symptoms) to severe depressions (>8 symptoms) and in those with either overt suicidal risk and/or high levels of personal impairment. In such cases, the time allowed for response to psychosocial interventions should be no more than 2-4 weeks, after which fluoxetine should be prescribed. Further research should focus on evaluating the efficacy of specific psychological treatments against brief psychological intervention, determining the characteristics of patients with severe depression who are non-responsive to fluoxetine, relapse prevention in severe depression and improving tools for determining treatment responders and non-responders.

Health Technology Assessment · randomised controlled trial · 149 citationsread the source →

Sumatriptan-naproxen for acute treatment of migraine: a randomized trial.

Context: Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex, and multimechanism-targeted therapy may confer advantages over monotherapy. Objective: To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine. Design, setting, and participants: Two replicate, randomized, double-blind, single-attack, parallel-group studies conducted among 1461 (study 1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack. Interventions: Patients were randomized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan, 85 mg, and naproxen sodium, 500 mg; sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or placebo, to be used after onset of a migraine with moderate to severe pain. Main outcome measures: Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing, absence of photophobia, absence of phonophobia, and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo, and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy. Results: Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing (study 1, 65% vs 28%; P<.001 and study 2, 57% vs 29%; P<.001), absence of photophobia at 2 hours (58% vs 26%; P<.001 and 50% vs 32%; P<.001), and absence of phonophobia at 2 hours (61% vs 38%; P<.001 and 56% vs 34%; P<.001). The absence of nausea 2 hours after dosing was higher with sumatriptan-naproxen sodium than placebo in study 1 (71% vs 65%; P = .007), but in study 2 rates of absence of nausea did not differ between sumatriptan-naproxen sodium and placebo (65% vs 64%; P = .71). For 2- to 24-hour sustained pain-free response, sumatriptan-naproxen sodium was superior at P<.01 (25% and 23% in studies 1 and 2, respectively) to sumatriptan monotherapy (16% and 14% in studies 1 and 2), naproxen sodium monotherapy (10% and 10% in studies 1 and 2), and placebo (8% and 7% in studies 1 and 2). The incidence of adverse events was similar between sumatriptan-naproxen sodium and sumatriptan monotherapy. Conclusion: Sumatriptan, 85 mg, plus naproxen sodium, 500 mg, as a single tablet for acute treatment of migraine resulted in more favorable clinical benefits compared with either monotherapy, with an acceptable and well-tolerated adverse effect profile. Trial registration: clinicaltrials.gov Identifiers: NCT00434083 (study 1); NCT00433732 (study 2).

JAMA · randomised controlled trial · 181 citationsread the source →

Feasibility of a Mobile Phone App and Telephone Coaching Survivorship Care Planning Program Among Spanish-Speaking Breast Cancer Survivors.

Background: Spanish-speaking Latina breast cancer survivors experience disparities in knowledge of breast cancer survivorship care, psychosocial health, lifestyle risk factors, and symptoms compared with their white counterparts. Survivorship care planning programs (SCPPs) could help these women receive optimal follow-up care and manage their condition. Objective: This study aimed to evaluate the feasibility, acceptability, and preliminary efficacy of a culturally and linguistically suitable SCPP called the Nuevo Amanecer (New Dawn) Survivorship Care Planning Program for Spanish-speaking breast cancer patients in public hospital settings, approaching the end of active treatment. Methods: The 2-month intervention was delivered via a written bilingual survivorship care plan and booklet, Spanish-language mobile phone app with integrated activity tracker, and telephone coaching. This single-arm feasibility study used mixed methods to evaluate the intervention. Acceptability and feasibility were examined via tracking of implementation processes, debriefing interviews, and postintervention satisfaction surveys. Preliminary efficacy was assessed via baseline and 2-month interviews using structured surveys and pre- and postintervention average daily steps count based on activity tracker data. Primary outcomes were self-reported fatigue, health distress, knowledge of cancer survivorship care, and self-efficacy for managing cancer follow-up health care and self-care. Secondary outcomes were emotional well-being, depressive and somatic symptoms, and average daily steps. Results: All women (n=23) were foreign-born with limited English proficiency; 13 (57%) had an elementary school education or less, 16 (70%) were of Mexican origin, and all had public health insurance. Coaching calls lasted on average 15 min each (SD 3.4). A total of 19 of 23 participants (83%) completed all 5 coaching calls. The majority (n=17; 81%) rated the overall quality of the app as "very good" or "excellent" (all rated it as at least "good"). Women checked their daily steps graph on the app between 4.2 to 5.9 times per week. Compared with baseline, postintervention fatigue (B=-.26; P=.02; Cohen d=0.4) and health distress levels (B=-.36; P=.01; Cohen d=0.3) were significantly lower and knowledge of recommended follow-up care and resources (B=.41; P=.03; Cohen d=0.5) and emotional well-being improved significantly (B=1.42; P=.02; Cohen d=0.3); self-efficacy for managing cancer follow-up care did not change. Average daily steps increased significantly from 6157 to 7469 (B=1311.8; P=.02; Cohen d=0.5). Conclusions: We found preliminary evidence of program feasibility, acceptability, and efficacy, with significant 2-month improvements in fatigue, health distress, and emotional well-being and increased knowledge of recommended follow-up care and average daily steps. Tailored mobile phone and health coaching SCPPs could help to ensure equitable access to these services and improve symptoms and physical activity levels among Spanish-speaking Latina breast cancer survivors.

JMIR cancer · 44 citationsread the source →

What Are the Minimal and Substantial Improvements in the HOOS and KOOS and JR Versions After Total Joint Replacement?

Background: Patient-reported outcome measures (PROMs) are a gold standard for measuring therapeutic outcomes in research. Extending their use to inform clinical care decisions, determine the appropriateness of therapeutic choices, and assess healthcare quality is attractive but will require our professional community to establish valid estimates of minimal and substantial clinical improvements. Questions/purposes: The purposes of this study were (1) to assess the validity of estimates for the minimal clinically important difference (MCID) calculated using distribution- and anchor-based methods by determining whether they exceed the minimal detectable change (MDC) for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) domains, the HOOS, joint replacement (JR) and the KOOS, JR among patients who underwent THA or TKA; (2) to determine substantial clinical benefit thresholds for the HOOS and KOOS domains, the HOOS, JR, and the KOOS, JR among patients who underwent THA or TKA; and (3) to assess the proportions of patients who underwent THA or TKA who achieved an MCID for the HOOS and KOOS domains, HOOS, JR, and KOOS, JR based on distribution-based and anchor-based methods as well as the percentages of patients who achieved substantial clinical benefit using the anchor-based method. Methods: Medicare patients enrolled in our institutional joint replacement registry who subsequently underwent THA (n = 2323) or TKA (n = 2630) between 2007 and 2012 completed HOOS or KOOS preoperatively and 2 years postoperatively. Short-form joint replacement (JR) versions of each PROM were derived from the full PROMs. Of all eligible patients, 78% (3161 of 4080) of THAs and 74% of TKAs (3815 of 5156) consented to join the registry and completed a baseline survey, 88% (2796 of 3161) of THAs and 85% (3230 of 3815) of TKAs were eligible for followup survey administration, and 83% of THAs (2323 of 2796) and 81% (2630 of 3230) of TKAs returned 2-year surveys. For each HOOS domain, KOOS domain, HOOS, JR, and KOOS, JR, we calculated the calibration variation of the instrument (MDC) with confidence intervals (CIs) reflecting 80% (MDC80), 90% (MDC90), and 95% (MDC95) certainty; we calculated the smallest difference joint health patients might detect (MCID) using distribution- and anchor-based approaches and the difference that can be considered a large improvement in joint health (substantial clinical benefit) using an anchor-based approach. Results: Patients undergoing THA were 57% female with a mean (± SD) age of 73 ± 6 years, whereas patients undergoing TKA were 63% female with a mean age of 74 ± 6 years. Depending on the CI chosen for the MDC, values ranged from 7 to 16 for the HOOS and KOOS domains and the JRs. The MCIDs ranged from 6 to 9 for the distribution-based approach and 7 to 36 for the anchor-based approach. All HOOS and KOOS domains and all JR scores are scores from 0 (worst joint health) to 100 (best joint health). The MCIDs calculated using the distribution-based approach were not valid, because they were lower than the MDC for all HOOS/KOOS domains and both JRs at every confidence level. The anchor-based receiver operating characteristic approach, on the other hand, resulted in MCIDs exceeding MDC80 for seven of eight HOOS/KOOS domains and MDC95 for both JR scores. For all domains and JR versions, substantial clinical benefits ranged from 15 to 36, exceeding MDC95 in all domains and JR scores. Across HOOS and KOOS domains as well as the JR, the proportion of patients undergoing THA who achieved an MCID ranged from 77% to 95% with the distribution-based method and from 67% to 96% using the anchor-based method. The proportion achieving substantial clinical benefit ranged from 67% to 85%. Conclusions: The MDC and MCID differ greatly based on assumptions and methods used. The MCID anchor-based approach had superior construct and face validity compared with the MCID distribution-based approach, which never exceeded even small MDCs. Achieving consensus about standard definitions of meaningful improvement will be necessary to maximize utility of these PROMs to inform clinical care or performance measurement. Level of evidence: Level III, diagnostic study.

Clinical orthopaedics and related research · cohort or longitudinal · 400 citationsread the source →

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

Background: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events. Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Pain physician · guideline · 225 citationsread the source →

Right ventricular dysfunction after resuscitation predicts poor outcomes in cardiac arrest patients independent of left ventricular function.

Objective: Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction. Methods: A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012. Patients: 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous circulation (ROSC) and post-arrest echocardiograms. Measurements and main results: Of the 291 patients, 57% were male, with a mean age of 59 ± 16 years. 179 (63%) patients had LV dysfunction, 173 (59%) had RV dysfunction, and 124 (44%) had biventricular dysfunction on the initial post-arrest echocardiogram. Independent of LV function, RV dysfunction was predictive of worse survival (mild or moderate: OR 0.51, CI 0.26-0.99, p<0.05; severe: OR 0.19, CI 0.06-0.65, p=0.008) and neurologic outcome (mild or moderate: OR 0.33, CI 0.17-0.65, p=0.001; severe: OR 0.11, CI 0.02-0.50, p=0.005) compared to patients with normal RV function after cardiac arrest. Conclusions: Echocardiographic findings of post-arrest RV dysfunction were equally prevalent as LV dysfunction. RV dysfunction was significantly predictive of worse outcomes in post-arrest patients after accounting for LV dysfunction. Post-arrest RV dysfunction may be useful for risk stratification and management in this high-mortality population.

Resuscitation · 35 citationsread the source →

Interventions for Adolescent Mental Health: An Overview of Systematic Reviews.

Many mental health disorders emerge in late childhood and early adolescence and contribute to the burden of these disorders among young people and later in life. We systematically reviewed literature published up to December 2015 to identify systematic reviews on mental health interventions in adolescent population. A total of 38 systematic reviews were included. We classified the included reviews into the following categories for reporting the findings: school-based interventions (n = 12); community-based interventions (n = 6); digital platforms (n = 8); and individual-/family-based interventions (n = 12). Evidence from school-based interventions suggests that targeted group-based interventions and cognitive behavioral therapy are effective in reducing depressive symptoms (standard mean difference [SMD]: -.16; 95% confidence interval [CI]: -.26 to -.05) and anxiety (SMD: -.33; 95% CI: -.59 to -.06). School-based suicide prevention programs suggest that classroom-based didactic and experiential programs increase short-term knowledge of suicide (SMD: 1.51; 95% CI: .57-2.45) and knowledge of suicide prevention (SMD: .72; 95% CI: .36-1.07) with no evidence of an effect on suicide-related attitudes or behaviors. Community-based creative activities have some positive effect on behavioral changes, self-confidence, self-esteem, levels of knowledge, and physical activity. Evidence from digital platforms supports Internet-based prevention and treatment programs for anxiety and depression; however, more extensive and rigorous research is warranted to further establish the conditions. Among individual- and family-based interventions, interventions focusing on eating attitudes and behaviors show no impact on body mass index (SMD: -.10; 95% CI: -.45 to .25); Eating Attitude Test (SMD: .01; 95% CI: -.13 to .15); and bulimia (SMD: -.03; 95% CI: -.16 to .10). Exercise is found to be effective in improving self-esteem (SMD: .49; 95% CI: .16-.81) and reducing depression score (SMD: -.66; 95% CI: -1.25 to -.08) with no impact on anxiety scores. Cognitive behavioral therapy compared to waitlist is effective in reducing remission (odds ratio: 7.85; 95% CI: 5.31-11.6). Psychological therapy when compared to antidepressants have comparable effect on remission, dropouts, and depression symptoms. The studies evaluating mental health interventions among adolescents were reported to be very heterogeneous, statistically, in their populations, interventions, and outcomes; hence, meta-analysis could not be conducted in most of the included reviews. Future trials should also focus on standardized interventions and outcomes for synthesizing the exiting body of knowledge. There is a need to report differential effects for gender, age groups, socioeconomic status, and geographic settings since the impact of mental health interventions might vary according to various contextual factors.

The Journal of adolescent health : official publication of the Society for Adolescent Medicine · review · 299 citationsread the source →

Evaluation of Parental Dental Fear and Anxiety (DFA) on Adolescent Dental Treatment

INTRODUCTION Dental anxiety is a negative state of mind of a dental patient, which is shown to be excessive and unreasonable.[1] Dental fear is a normal emotional response to particularly alarming stimuli in situations related to dental treatment.[1] Dental fear and anxiety (DFA) are often used together to describe different types of fear experienced in the dental environment.[2] American Academy of Pediatrics divides adolescents into three age groups: early 11–14 years, middle 15–17 years, and late 18–21 years.[3] Five specific pathways for DFA were seen in adolescent dental patients. One of which being the parental pathway plays an important role in the transmission of fear hindering their child’s dental treatment.[4] Parental DFA is usually an excessive perturbing of the things that could go wrong in child’s oral health and is an important factor that has an impact on adolescents receiving dental treatment and maintenance of their oral health. It is necessary to recognize and know how parental DFA affects the dental treatment of adolescents. Thus, this review aimed at evaluating the parental influence of DFA on dental treatment of adolescents. MATERIALS AND METHODS DATA EXTRACTION AND LITERATURE SEARCH STRATEGY A broad search of literature published between 2005 and 2021 from electronic databases through Scopus, PubMed, Google Scholar, and Web of Science was performed. These studies were conducted in different countries as mentioned in Table 1. This review article includes eight cross-sectional studies, three longitudinal studies, and one descriptive study. The age group of children included ranged from 10 to 19 years. Table 1: Summary study design, data collection, dental fear and anxiety assessment scales used analysis, and interpretation of reviewed articlesThe search was carried out using the following keywords: dental anxiety, parental dental anxiety, adolescent, and dental treatment. The terms used to formulate the search strategies were parent OR mother OR father AND dental fear OR dental anxiety AND adolescent AND dental treatment. Data extracted were independently reviewed and disagreements were solved by discussion. A flowchart representing the method of article selection for the review is shown in Figure 1.Figure 1: Flowchart representing the method of article selectionINCLUSION CRITERIA We included the studies in which parental dental anxiety was a major criterion affecting different dental health conditions. Articles referring to adolescents (10–19 years) facing different oral health problems were also included in the study. EXCLUSION CRITERIA Abstracts that were not giving relevant data, data from unpublished articles, parental dental anxiety in medically compromised and specially challenged adolescents, and articles that did not include the adolescent age group were excluded from the study. RESULTS Approximately 83 publications were found related. Screening identified 10 articles that fulfilled the criteria of inclusion; full-text versions were retrieved and their references were screened for further relevant articles. Checking the subreference list, another two relevant articles were found. Thus, 12 articles were considered for this review that met the final inclusion criteria. Of 12 articles reviewed, 8 studies[56789101112] used validated assessment scales as mentioned by authors for measuring parental DFA. The authors have not specified the validation of assessment scales used for the other four studies.[13141516] The various DFA assessment scales used in the reviewed articles are mentioned in Table 2. Summary study design, data collection, analysis, and interpretation of reviewed articles are mentioned in Table 1.Table 2: Tabular representation of dental fear and anxiety assessment scales usedDISCUSSION Dental anxiety being primarily a negative parental factor was found to affect children from assessing regular dental care. Among the reviewed articles based on the outcome, we found that three articles explained about a relationship between parental DFA and adolescent dental treatment,[67,13] and the remaining nine articles explained about the correlation between parental DFA scores with adolescent DFA scores.[6891011,13141516] No significant association was observed between parental DFA and adolescent DFA scores in two of the studies,[78] whereas two studies showed positive association only during early adolescence.[914] Other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety,[10111215,16] of which three studies also suggested fathers as mediating role in transmission of DFA to their children.[1011,15] RELATIONSHIP BETWEEN PARENTAL DENTAL FEAR AND ANXIETY AND ADOLESCENT DENTAL TREATMENT Adolescent dental treatment utilization mainly depends on parental/caretaker’s decision-making and their dental care obtaining habits. In childhood and even adolescence, this becomes very crucial for the development of good oral health behavior like regular visits to the dentist and preventive dental care.[17] Another postulated process is “social learning” wherein, media, friends, and relatives portray dentists in negative light or image leading to formation of DFA. These processes of information transmission and vicarious experience lead to negative portrayal of dentists and pessimistic expectations about the dentist’s role. All these predispose to DFA.[18] The absence of anxiety among parents would have a positive influence on a child.[19] Parental dental anxiety along with family income, economic stability, parental oral health literacy, and oral health practices is found to be a few factors that affect adolescent’s oral health-related quality of life (QOL).[202122] Dental anxiety being primarily a negative parental factor was found to affect children from accessing regular dental care, whereas parental self-dental utilization being a positive parental factor showed a positive impact on a child’s dental utilization.[23] Parents with higher anxiety levels were found to start brushing their children’s teeth at an earlier age; hence, a significant correlation was found between parent’s anxiety levels and the age at which the child starts to brush.[24] Dental health status of children was found to be better with more a positive attitude of parents toward dentistry.[25] Among the articles reviewed, two articles were found to have parental DFA during fixed orthodontic treatment of the adolescents which included the use of extraoral appliances. These two studies used different anxiety measurement scales for assessing parental DFA before and during the treatment procedures.[513] Poorer QOL is seen in families of adolescents with malocclusion as compared with the families of adolescents without any occlusal variation; the impact may have effects on parental or guardian’s emotions.[26] Both of the studies assessed state and trait dental anxiety of parents (STAI scale). State anxiety is transient, fluctuates, and varies in intensity. Trait anxiety is a personality trait; it is stable with time.[2728] The result showed that parent’s trait anxiety levels did not change during orthodontic treatment.[513] State anxiety was found to be within normal range and changed according to intensity of pressure.[13] There was an incidence of high levels of state anxiety and depression in both parents and patients under treatment with extra oral orthodontic appliances after 1 year of active treatment. Among patients waiting for orthodontic treatment and among their parents no statistically significant differences were noted in their trait anxiety levels.[5] The extra oral appliances had a negative effect on patient’s and parent’s anxiety levels which might indirectly affect the ongoing dental treatment. It was therefore recommended for clinicians to have alternate treatment modalities in mind to address this challenge.[5] Apart from orthodontic treatment, adolescents are also found commonly with traumatic dental injuries (TDIs) involving dentine/pulp or fracture of the root. A family’s QOL in such conditions was assessed using the family impact scale (FIS). This scale had four subscales, in which parental emotion was one of the subscales assessed. Parental emotion had a significant negative impact on the severity of TDI and severe untreated TDI of an adolescent can be a source of family distress.[629,30] EVIDENCE OF ASSOCIATION OF DENTAL FEAR AND ANXIETY BETWEEN PARENTS AND THEIR ADOLESCENTS Previous studies have shown that parents exhibit an influence on their children’s DFA through modeling and information.[31] The DFA experienced in childhood may lead into adulthood causing a predictor for dental treatment avoidance in adulthood.[3233] Among the reviewed articles, we found a correlation between the parental dental DFA scores with their adolescent’s DFA scores. Parent’s DFA and children’s DFA were assessed using the same dental anxiety measuring scale in nine of the studies,[6891011,13141516] and three studies[57,12] used different scales to measure anxiety levels in parents and children’s. Two of the studies showed no significant association between the anxiety level of adolescents and that of their parents.[78] One of the studies suggested that when a child reached adolescence, parental DFA does not directly contribute to child DFA. Other factors such as the presence of a sibling and family structure (single-parent family, nuclear) are found to play a significant role.[7] Lending support to the former findings, there was no relation between anxiety levels of adolescents (12–17 years) and that of their parents, whereas in the same study a positive association was found when the child is 8–11 years of age.[8] Two studies suggested a positive association in early adolescence.[914] In one of these two studies, mother’s and adolescents dental fear scores had a significant association at the age of 12 years and 18 years in given treatment scenarios such as “feeling about having their teeth scraped and polished, having teeth drilled and having an injection in gum,” whereas there was no significant association between dental fear scores of mother’s and adolescence at 15 years of age.[9] In another study reviewed, in early adolescence (11–12 years), there was a statistically significant association between parental and adolescent dental fear but in mid-adolescence (15–16 years) there was only an association with parental dental fear with their daughters.[14] It was found in the Finnish population, by eliminating dental fear among 30 years and elderly population, 41% of irregular attendees could become regular attenders.[34] In contrast, other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety.[10111215,16] Fearful parents of adolescents of age (11–16 years) assumed that their child had fear irrespective of whether the child had fear or not.[16] Three of these studies, where parental DFA was assessed in both the parents, suggested that the father also has a mediating role in the transmission of DFA to the children of age group 11–17 years,[10] 7–15 years,[11] and 7–12 years,[15] respectively. Father’s DFA is one of the best predictors of adolescence DFA[1035] and it is also found that child’s dental anxiety is best predicted by the parent’s fear of pain.[12] Previous studies have suggested that children experience fear and anxiety in their early life due to a lack of cognitive ability without having a clear perception of fearful situation and have been influenced by their parent’s fear and anxiety.[36] It is still unclear of the association of DFA between parents and late adolescents.[9] It was found that limited studies were found in the area of adolescent oral health. In the available literature, definite assessment methods were not used to assess the anxiety levels among parents. Furthermore, studies focused on late adolescence are indicated to establish the changes in oral health due to parental DFA. Adolescence is the transitional phase between childhood and adulthood and is a crucial period where they develop decision-making and independence; this has an impact on dental treatment-seeking behavior. The influence of parental dental anxiety might worsen the scenario. Parental DFA is seen to have a direct impact on the treatment itself.[56,20] Previously reviewed articles show a strong association of parental DFA and child’s DFA below 8 years of age.[37] In this study, we found parental DFA showed a positive association with their adolescent’s DFA, which thus hinders their dental treatment. There is a need to give attention to psychological parameters before and during the treatment of both parents and adolescents. Therefore, identifying parental dental anxiety prior to the treatment and intervention helps to reduce or eliminate DFA in children and further improves their dental treatment utilization. This study adds value in sensitizing dental professionals toward addressing parental concerns while treating adolescents and recommendations for appropriate implementations in teaching curricula and policies regarding the same. There is more potential to understand the background of parental DFA in single parents and in mother and father alone and also the factors that made them vulnerable. Parental education/counselling regarding various dental treatment procedures using appropriate methods such as focus group discussion will help to reduce DFA among the parental populations. ACKNOWLEDGEMENT We thank Health Sciences Library, Manipal Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India and Department of Psychiatry, Kasturba Medical College and Hospital, Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India. FINANCIAL SUPPORT AND SPONSORSHIP This study was self-funded. CONFLICTS OF INTEREST There are no conflicts of interest. AUTHORS CONTRIBUTIONS Idea and conceptualization: Ramprasad Vasthare. Literature search: Thrisha Hegde, Bhavyashri P. Manuscript writing: Thrisha Hegde, Bhavyashri P, Ramprasad Vasthare, Karthik M, Ravindra Munoli. Editing of the review: Ramprasad Vasthare, Thrisha Hegde, Bhavyashri P, Karthik M, Ravindra Munoli. Intellectual inputs: Ramprasad Vasthare, Ravindra Munoli, Karthik M. ETHICAL POLICY AND INSTITUTIONAL REVIEW BOARD STATEMENT Not applicable as this was a narrative review. PATIENT DECLARATION OF CONSENT Not applicable. DATA AVAILABILITY STATEMENT Data of literature search is available on appropriate request to the corresponding author.

Journal of International Society of Preventive and Community Dentistry · review · 16 citationsread the source →

When weak imagery is worse than none: Core aphantasia and hypophantasia relate differently to mental health, mediated by subjective interoception.

Aphantasia, characterized by absent or reduced visual mental imagery, has been associated with alexithymia and negative mental health outcomes. However, the underlying mechanisms remain unclear. Visual imagery has been proposed as part of an inwardly focused cognitive style that also encompasses interoceptive processing and emotion regulation, suggesting these constructs may be functionally linked. Since mental health is closely tied to interoception, we examined whether interoceptive processing mediates the relationship between imagery ability and mental health. We assessed self-reported imagery vividness (VVIQ), subjective interoceptive accuracy and attention, alexithymia, anxiety, and depression in individuals with aphantasia (n = 153, VVIQ = 16-32) and typical imagers (n = 680, VVIQ = 33-80). Within the aphantasia group, we distinguished core aphantasia (VVIQ 16-23, n = 96) from hypophantasia (VVIQ 24-32, n = 57). The results revealed that individuals with weak imagery (hypophantasia) showed greater alexithymia and worse mental health than those with almost no imagery (core aphantasia), with higher VVIQ predicting poorer outcomes within the aphantasia range. The opposite pattern emerged in typical imagers, where higher VVIQ predicted lower alexithymia and better mental health. Structural equation modeling revealed that these relationships were mediated by alexithymia and the ratio of subjective interoceptive accuracy to attention, with lower ratios (indicating effortful but unsuccessful interoceptive processing) associated with worse outcomes. These findings highlight critical heterogeneity within aphantasia, demonstrating that hypophantasia and core aphantasia have distinct interoceptive and mental health profiles, with implications for understanding the mechanisms linking imagery, bodily awareness, and emotional well-being.

Neuropsychologia · 4 citationsread the source →

Post-traumatic growth in mental health recovery: qualitative study of narratives.

Objectives: Post-traumatic growth, defined as positive psychological change experienced as a result of the struggle with challenging life circumstances, is under-researched in people with mental health problems. The aim of this study was to develop a conceptual framework for post-traumatic growth in the context of recovery for people with psychosis and other severe mental health problems. Design: Qualitative thematic analysis of cross-sectional semi-structured interviews about personal experiences of mental health recovery. Setting: England. Participants: Participants were adults aged over 18 and: (1) living with psychosis and not using mental health services (n=21); (2) using mental health services and from black and minority ethnic communities (n=21); (3) underserved, operationalised as lesbian, gay, bisexual and transgender community or complex needs or rural community (n=19); or (4) employed in peer roles using their lived experience with others (n=16). The 77 participants comprised 42 (55%) female and 44 (57%) white British. Results: Components of post-traumatic growth were present in 64 (83%) of recovery narratives. Six superordinate categories were identified, consistent with a view that post-traumatic growth involves learning about oneself (self-discovery) leading to a new sense of who one is (sense of self) and appreciation of life (life perspective). Observable positively valued changes comprise a greater focus on self-management (well-being) and more importance being attached to relationships (relationships) and spiritual or religious engagement (spirituality). Categories are non-ordered and individuals may start from any point in this process. Conclusions: Post-traumatic growth is often part of mental health recovery. Changes are compatible with research about growth following trauma, but with more emphasis on self-discovery, integration of illness-related experiences and active self-management of well-being. Trauma-related growth may be a preferable term for participants who identify as having experienced trauma. Trauma-informed mental healthcare could use the six identified categories as a basis for new approaches to supporting recovery. Trial registration number: ISRCTN11152837.

BMJ open · 51 citationsread the source →

Emotional responses and psychological health among young people amid climate change, Fukushima's radioactive water release, and wars in Ukraine and the Middle East, and the mediating roles of media exposure and nature connectedness: a cross-national analysis.

Background: New global crises are emerging, while existing global crises remain unabated. Coping with climate change, the radioactive water released into the Pacific Ocean subsequent to the Fukushima nuclear accident in Japan, and the wars in Ukraine and the Middle East (hereafter referred to as the wars) as individual crises can negatively affect the psychological health of young people, but little is known about the compounded impact of multiple crises. We aimed to examine: (1) the emotional responses of young people towards each individual crisis, (2) how aggregate levels of emotional engagement in global crises might pose different potential trajectories in psychological health, and (3) the protective or exacerbating role of media exposure and nature connectedness as mediators on psychological health outcomes of young people. Methods: We conducted a cross-national online survey among young people (aged 18-29 years) from China, Portugal, South Africa, the USA, and the UK. We adopted stratified purposive sampling and distributed the survey using online platforms (www.wenjuan.com and www.prolific.com). Individuals were eligible for inclusion in our analysis if they were literate in Chinese or English and had no mental disorders diagnosed within the past 12 months. Participants were asked questions on their demographic characteristics and time spent on social media, including proportion of time exposed to media pertaining to global crises of interest, and they completed surveys based on validated scales that measure depression, anxiety, stress, and wellbeing, as well as emotional responses to each global crisis and nature relatedness. We assessed the survey results using descriptive statistics, ANOVA tests, cluster analysis for individual emotional responses, and structural equation modelling for the aggregate measure of emotional engagement towards individual global crises. Findings: Between Oct 20 and Nov 3, 2023, 2579 individuals participated in the survey, of whom 400 participants from each country (200 male and 200 female participants) were included in our analysis (mean age 24·36 years [SD 2·86]). The mean emotional engagement varied between the global crises of interest (on a scale from 0 to 68, where 0 indicates no emotional response and 68 indicates strong emotional responses across 17 different emotions; wars: 32·42 [SD 14·57]; climate change: 28·79 [14·17]; radioactive water: 21·26 [16·08]), and emotional engagement also varied by country; for instance, for respondents from China, mean emotional engagement in radioactive water was relatively high (39·15 [10·72]) compared with the other countries, and for respondents from the USA, engagement with the wars was relatively low (29·45 [15·78]). We found significant variations in the level of emotional engagement between different crises, with distinct emotional profiles observed among individual countries. To assess the role of media exposure and nature connectedness on psychological outcomes, using structural equation modelling, we constructed a multi-country model comprising Portugal, South Africa, the USA, and the UK, and a standalone model for China. These models elucidated associations between emotional engagement and psychological distress and wellbeing, explaining substantial portions of the variance in both. Notably, while greater emotional engagement in the ecological crises (ie, climate change and radioactive water) generally predicted worse psychological health outcomes, we found the direction of effect for war crises to have positive outcomes for mental health in the standalone China model. Additionally, we found that media exposure mediated the negative effect of wars on psychological distress in the multi-country model, and positive psychological wellbeing in the standalone China model. Moreover, nature connectedness emerged as a potent mediator, effectively mitigating the adverse mental health effects of emotional engagement with some crises, such as radioactive water and climate change. Interpretation: Our findings offer valuable insights into the nuanced dynamics of emotional engagement in global crises and its implications for mental health outcomes among young people across diverse global contexts. Further research is needed to understand the contribution of ongoing and new global crises towards a compounded negative future outlook on young people's mental health to identify effective communication and intervention strategies that can mitigate the effect of this global challenge. Funding: Research Grants Council of Hong Kong, China.

The Lancet. Planetary health · 9 citationsread the source →

A comparison of mental health symptomatology and levels of social support in young treatment seeking transgender individuals who identify as binary and non-binary.

Background : Previous research has consistently reported high rates of mental health symptomatology and lower social support in young treatment seeking transgender individuals. However, these studies have failed to distinguish between transgender people who identify within the gender binary and those who identify as non-binary. Aims : This study aimed to compare levels of mental health symptomatology (anxiety, depression, and non-suicidal self-injury behavior) and social support of treatment seeking non-binary transgender young individuals with those self-identified as binary transgender young individuals. All participants attended a national transgender health service in the UK during a 2-year period. Measures : Age and gender identity descriptors were collected, as well as clinical measures of anxiety and depression (Hospital Anxiety and Depression Scale), self-esteem (The Rosenberg Self-Esteem Scale), non-suicidal self-injury (Non-Suicidal Self-Injury: Treatment Related), and social support (Multidimensional Scale of Perceived Social Support). Results : A total of 388 young people, aged 16-25 years, agreed participation; 331 (85.3%) identified as binary and 57 (14.7%) as non-binary. Analysis of the data showed the non-binary group experienced significantly more anxiety and depression and had significantly lower self-esteem than the binary group. There were no significant differences between groups in the likelihood of engaging in non-suicidal self-injury behavior or levels of social support. Conclusions : Non-binary identifying treatment seeking transgender youth are at increased risk of developing anxiety, depression, and low self-esteem compared to binary transgender youth. This may reflect the even greater barriers and feelings of discrimination that may be faced by those whose identity does not fit the notion of binary gender that is pervasive in how society views both cis- and transgender populations.

The international journal of transgenderism · 93 citationsread the source →

Heart rate variability

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

The psychiatric sequelae of the COVID-19 pandemic in adolescents, adults, and health care workers.

Background: The COVID-19 pandemic is the most serious global public health crisis since the 1918 influenza pandemic. This study is the first to assess its mental health impact across the lifespan in the United States in adolescents, adults, and health care workers. Methods: We recruited 4909 participants through an online survey advertising on Facebook and Instagram to assess exposure to COVID-19 and psychiatric symptoms from April 27 to July 13. We also recruited through the University of Pittsburgh, University of Pittsburgh Medical Center, and other health care systems around Pittsburgh. The primary outcomes were clinically significant depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms, suicidal ideation or behavior, and grief reactions since COVID-19. Results: Adolescents were significantly more likely to report moderate to severe symptoms of depression (55% vs. 29%; χ2  = 122, df = 1; p < .001), anxiety (48% vs. 29%; χ2  = 73; df = 1; p < .001), PTSD (45% vs. 33%; χ2  = 12; df = 1; p < .001), suicidal ideation or behavior (38% vs. 16%; χ2  = 117; df = 1; p < .001), and sleep problems (69% vs. 57%; χ2  = 26; df = 1; p < .001) compared to adults. The rates of intense grief reactions among those who lost someone to COVID-19 was 55%. Loneliness was the most common predictor across outcomes and higher number of hours spent on social media and exposure to media about COVID-19 predicted depression symptoms and suicidal ideation or behavior in adolescents. Conclusions: The COVID-19 pandemic is associated with increased rates of clinically significant psychiatric symptoms. Loneliness could put individuals at increased risk for the onset of psychiatric disorders.

Depression and anxiety · 157 citationsread the source →

Dynamic spread of happiness in a large social network: longitudinal analysis over 20 years in the Framingham Heart Study.

Objectives: To evaluate whether happiness can spread from person to person and whether niches of happiness form within social networks. Design: Longitudinal social network analysis. Setting: Framingham Heart Study social network. Participants: 4739 individuals followed from 1983 to 2003. Main outcome measures: Happiness measured with validated four item scale; broad array of attributes of social networks and diverse social ties. Results: Clusters of happy and unhappy people are visible in the network, and the relationship between people's happiness extends up to three degrees of separation (for example, to the friends of one's friends' friends). People who are surrounded by many happy people and those who are central in the network are more likely to become happy in the future. Longitudinal statistical models suggest that clusters of happiness result from the spread of happiness and not just a tendency for people to associate with similar individuals. A friend who lives within a mile (about 1.6 km) and who becomes happy increases the probability that a person is happy by 25% (95% confidence interval 1% to 57%). Similar effects are seen in coresident spouses (8%, 0.2% to 16%), siblings who live within a mile (14%, 1% to 28%), and next door neighbours (34%, 7% to 70%). Effects are not seen between coworkers. The effect decays with time and with geographical separation. Conclusions: People's happiness depends on the happiness of others with whom they are connected. This provides further justification for seeing happiness, like health, as a collective phenomenon.

BMJ (Clinical research ed.) · 517 citationsread the source →

Fecal Microbiota Changes in Patients With Postpartum Depressive Disorder.

Postpartum depressive disorder (PPD) is a unique subtype of major depressive disorder and a substantial contributor to maternal morbidity and mortality. However, the pathogenesis of PPD has still remained elusive, and it may associate with genetic and environmental factors. Gut microbiota has already been proved to be associated with depression; however, a limited number of studies have concentrated on PPD. The present study aimed to explore the potential correlations between gut microbiota and PPD. In this study, 57 participants were enrolled, in which fecal samples of 28 patients with PPD and 16 healthy controls (HCs) were collected and then analyzed by high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene. The results showed that diversity and composition of gut microbial communities were partly different between PPD patients and HCs. The relative abundance of Firmicutes phyla was lower in PPD patients. The levels of several predominant genera were significantly different between PPD patients and HCs. More importantly, the PPD patients experienced reduced levels of Faecalibacterium, Phascolarctobacterium, Butyricicoccus, and Lachnospiraceae, as well as increased levels of Enterobacteriaceae family. In addition, a correlation was observed between levels of Phascolarctobacterium, Lachnospiraceae, Faecalibacterium, and Tyzzerella.3 and the severity of depressive symptoms. Various kinds of bacteria, such as Lachnospiraceae and Faecalibacterium, were found to be associated with levels of sex hormones. This study indicated the correlation between gut microbiota and PPD, and gut microbiota-based biomarkers may be helpful for the diagnosis and treatment of PPD patients. However, further studies need to be conducted to clarify the cause-effect relationship between PPD patients and gut microbiota and to highlight the suitability of gut microbiome as a biomarker.

Frontiers in cellular and infection microbiology · 67 citationsread the source →

The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders.

The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.

Molecular psychiatry · editorial or comment · 299 citationsread the source →

Qualitative concept elicitation and cognitive debriefing interviews of symptoms, impacts and selected customized PROMIS® Short Forms: a study in patients with axial spondyloarthritis.

Background: Sleep disturbance, pain, and fatigue are key symptoms/impacts of axial spondyloarthritis (axSpA). Three customized Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Forms (Sleep Disturbance, Pain Interference, and Fatigue) have been proposed for use in axSpA to assess these key disease concepts. This study was designed to further understand the patient experience of axSpA and evaluate the content validity of the three customized PROMIS® Short Forms to support their use in axSpA clinical trials. Methods: Non-interventional, cross-sectional, qualitative (concept elicitation [CE] and cognitive debriefing [CD]) study. Participants took part in 90-min telephone interviews. The CE section used open-ended questions to elicit information about axSpA symptoms and impacts. The CD section involved a 'think-aloud' exercise where participants read out each instruction, item, and response option for the customized PROMIS® Short Forms and shared their feedback. Participants also discussed the relevance of the items, response options and recall period. Verbatim interview transcripts were subject to thematic and content analysis. Results: In total, there were 28 participants (non-radiographic axSpA, n = 12; ankylosing spondylitis, n = 16), from the US (n = 20) and Germany (n = 8). Mean age was 52.8 years, and 57% were male; mean time since diagnosis was 9.5 years. The CE section identified 12 distinct symptoms that characterized axSpA: pain, sleep problems, fatigue/tiredness, stiffness, swelling, vision/eye issues, restricted body movements, headache/migraine, spasms, change in posture/stature, balance/coordination problems, and numbness. Pain, sleep problems, and fatigue/tiredness were experienced by ≥ 90% of participants, occurring simultaneously and exacerbating one another. Participants reported axSpA impacted their lives across six domains of health-related quality of life (HRQoL): physical functioning (100%), emotional wellbeing (89%), work/volunteering (79%), social functioning (75%), activities of daily living (61%) and cognitive functioning (54%). Impacts were most frequently associated with pain, stiffness, and fatigue. CD showed the PROMIS® instruments were conceptually comprehensive and well understood, with all items relevant to ≥ 50% of participants. Conclusions: Pain, sleep problems and fatigue are pivotal symptoms of axSpA and associated with HRQoL impacts. These results were used to update a conceptual model of axSpA which was originally developed based on a targeted literature review. Interpretability and content validity of the customized PROMIS® Short Forms were confirmed, with each deemed to adequately assess key impacts associated with axSpA, making them suitable for use in axSpA clinical trials.

Journal of patient-reported outcomes · 5 citationsread the source →

Synergistic adversities and behavioral problems in traumatized children and adolescents.

Objective: This study investigated synergy of commonly co-occurring pairs of childhood traumas/adversities to determine: 1) if synergistic pairings differ by gender and/or age grouping; and 2) if some traumas/adversities were more synergistically reactive. Methods: A sample of 10,355 clinic-referred youth (1.5-18 years) from the National Child Traumatic Stress Network Core Data Set was divided by gender and categorized into salient age groups (1.5-5 years, 6-12 years, and 13-18 years). Attributable Proportion (AP), a biomedically relevant metric, was calculated to assess additive synergy for behavior problems on the CBCL. Results: Overall, only four pairs of adversities were synergistic. Three involved sexual abuse with physical abuse, parental loss, and domestic violence. When the sample was analyzed by Gender X Age group, however, a more complicated picture emerges. Twelve of the twenty-one possible pairings (57 %) show additive synergy in one or more categories. The mean AP accounted for approximately 40 % of outcome variance. Males had more synergistic pairings (16) than females (7). The average synergistic effect was higher for males (42 % of variance) than females (36 % of variance). The vast majority of synergy occurs in the 6-12 and 13-18 age groups. Sexual abuse was the most synergistically reactive trauma, pairing most frequently (16) followed by physical abuse (10) or neglect (9). Conclusion: Sexual abuse was malignantly synergistic, frequently pairing with other adversities, followed by physical abuse, neglect, and domestic violence. The findings underscore that all ACEs are not equal in their contributions to commonly assessed outcomes. The findings also have considerable implications for prevention, intervention, and future research.

Child abuse & neglect · 27 citationsread the source →

Predictors of parental stress from admission to discharge in the neonatal special care unit.

Background: Exacerbated parental stress during a stay in the neonatal intensive care unit can negatively impact the development of the hospitalized infant, strain the dyadic relationship and put parents at risk for poor mental health. It is therefore important to identify risk factors of stress throughout the duration of a hospitalization. This longitudinal study aimed to investigate sources of stress for mothers and fathers who had a baby in the neonatal special care unit. Methods: Parents of 57 singletons and 11 twins (68 infants) admitted to a neonatal special care unit (46% for prematurity) were recruited. Sixty-four mothers and 20 fathers were assessed at admission, and 60 mothers and 16 fathers at discharge. Participants reported their satisfaction with hospital information and completed the Perceived Stress Scale, the Brief Illness Perception Questionnaire and the Dyadic Adjustment Scale. Results: Parents demonstrated similar stress trajectories, with stress on average declining over time. Higher maternal stress at admission was associated with a belief that the baby's illness would have a longer timeline, lower perceptions of treatment efficacy and lower satisfaction with the information received from medical staff. Younger age and lower levels of education predicted higher maternal stress at discharge. Fathers had higher stress at discharge when they were older, had a baby born at younger gestation and felt they had less control. At admission, information satisfaction was positively associated with parental beliefs about treatment efficacy and understanding the infant's condition. At discharge, information satisfaction was negatively associated with beliefs about illness severity and the likely time frame of the illness. Conclusion: The findings highlight that parents' perceptions of their baby's illness and treatment at admission and discharge have a significant association with stress. Clinical staff can use these factors to identify parents who are at risk of exhibiting a greater level of stress over the hospitalization period.

Child: care, health and development · 16 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 →

The immediate eff ect of the Same-Sex Marriage Prohibition Act on stigma, discrimination, and engagement on HIV prevention and treatment services in men who have sex with men in Nigeria: analysis of prospective data from the TRUST cohort.

Background: In January, 2014, the Same-Sex Marriage Prohibition Act was signed into law in Nigeria, further criminalising same-sex sexual relationships. We aimed to assess the immediate effect of this prohibition act on stigma, discrimination, and engagement in HIV prevention and treatment services in men who have sex with men (MSM) in Nigeria. Methods: The TRUST cohort study uses respondent-driven sampling to assess the feasibility and effectiveness of engagement of MSM in HIV prevention and treatment services at a clinical site located with a community-based organisation trusted by the MSM community. TRUST is a prospective implementation research cohort of MSM (≥16 years) in Abuja, Nigeria. We compared HIV clinical outcomes and stigma, including fear and avoidance of health care, across baseline and quarterly visits before and after implementation of the the Same-Sex Marriage Prohibition Act. Outcomes assessed were measures of stigma and discrimination, loss to follow-up, antiretroviral therapy status, and viral load. We compared outcomes before and after the legislation with χ2 statistics, and estimated incident stigma-related events and loss to follow-up with Poisson regression. Findings: Between March 19, 2013, and Aug 7, 2014, 707 MSM participated in baseline study procedures, contributing to 756 before legislation (prelaw) and 420 after legislation (postlaw) visits. Reported history of fear of seeking health care was significantly higher in postlaw visits than in prelaw visits (n=161 [38%] vs n=187 [25%]; p<0・0001), as was avoidance of health care (n=118 [28%] vs n=151 [20%]; p=0・001). In incidence analyses, of 192 MSM with follow-up data and no history of an event at baseline, reported fear of seeking health care was higher in the postlaw than the prelaw period (n=144; incidence rate ratio 2・57, 95% CI 1・29–5・10; p=0・007); loss to follow-up and incident healthcare avoidance were similar across periods. Of the 161 (89%) of 181 HIV-infected MSM with HIV viral loads available, those who had disclosed sexual behaviour with a health-care provider were more often virally suppressed at baseline than those with no previous disclosure (18 [29%] of 62 vs 13 [13%] of 99 men; p=0・013). Interpretation: These analyses represent individual-level, quantitative, real-time prospective data for the health-related effects resulting from the enactment of legislation further criminalising same-sex practices. The negative effects of HIV treatment and care in MSM reinforce the unintended consequences of such legislation on global goals of HIV eradication. Strategies to reach MSM less likely to engage in HIV testing and care in highly stigmatised environments are needed to reduce time to HIV diagnosis and treatment. Funding: National Institutes of Health.

The lancet. HIV · 161 citationsread the source →

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

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

Frontiers in Psychology · 12 citationsread the source →

Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding: Gates Foundation and Bloomberg Philanthropies.

Lancet (London, England) · 257 citationsread the source →

Using Online Screening in the General Population to Detect Participants at Clinical High-Risk for Psychosis.

Introduction: Identification of participants at clinical high-risk (CHR) for the development of psychosis is an important objective of current preventive efforts in mental health research. However, the utility of using web-based screening approaches to detect CHR participants at the population level has not been investigated. Methods: We tested a web-based screening approach to identify CHR individuals. Potential participants were invited to a website via e-mail invitations, flyers, and invitation letters involving both the general population and mental health services. Two thousand two hundred seventy-nine participants completed the 16-item version of the prodromal questionnaire (PQ-16) and a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms (BS) online. 52.3% of participants met a priori cut-off criteria for the PQ and 73.6% for PCA items online. One thousand seven hundred eighty-seven participants were invited for a clinical interview and n = 356 interviews were conducted (response rate: 19.9%) using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). n = 101 CHR participants and n = 8 first-episode psychosis (FEP) were detected. ROC curve analysis revealed good to moderate sensitivity and specificity for predicting CHR status based on online results for both UHR and BS criteria (sensitivity/specificity: PQ-16 = 82%/46%; PCA = 94%/12%). Selection of a subset of 10 items from both PQ-16 and PCA lead to an improved of specificity of 57% while only marginally affecting sensitivity (81%). CHR participants were characterized by similar levels of functioning and neurocognitive deficits as clinically identified CHR groups. Conclusion: These data provide evidence for the possibility to identify CHR participants through population-based web screening. This could be an important strategy for early intervention and diagnosis of psychotic disorders.

Schizophrenia bulletin · 80 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

Prevalence and nature of workplace bullying and harassment and associations with mental health conditions in England: a cross-sectional probability sample survey.

Background: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in WBH exposure, and quantify adjusted associations with mental health. Methods: Data were from the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional probability-sample survey of the household population in England, interviewed with verbal informed consent. Criteria for inclusion in the secondary analysis were being aged 16-70 years and in paid work in the past month (n=3838). Common mental disorders were assessed using the Clinical Interview Schedule-Revised and mental wellbeing using the Warwick-Edinburgh Mental Wellbeing Scale. Analyses were weighted. We examined associations between past-year WBH and current common mental disorders using multivariable regression modelling, adjusting for demographic and socioeconomic factors. Interaction terms tested for gender differences in associations. The study received ethics approval (ETH21220-299). Findings: One in ten employees (10·6% (weighted), n=444/3838) reported past-year experience of WBH, with rates higher in women (12·2%, n=284/2189); those of mixed, multiple, and other ethnicity (21·0%, n=15/92); and people in debt (15·2%, n=50/281) or living in cold homes (14·6%, n=42/234). Most commonly identified perpetrators of WBH were line managers (53·6%, n=244/444) or colleagues (42·8%, n=194/444). Excessive criticism (49·3%, n=212/444), verbal abuse (42·6%, n=187/444), and humiliation (31·4%, n=142/444) were the most common types. WBH was associated with all adverse mental health indicators, including common mental disorders (adjusted odds ratio [aOR] 2·65, 95% CI 2·02-3·49), and 11 of 14 mental wellbeing indicators, including lower levels of confidence (aOR 0·57, 0·46-0·72) and of closeness to others (aOR 0·57, 0·46-0·72). Patterns of association between WBH and mental health were similar in men and women. Interpretation: These findings reinforce a need for more cohesive UK legislation at the national level; guidance on recognition of bullying behaviours for employees, managers, and human resources at the organisational level, focusing on prevention and early intervention, and increased awareness of the impact of WBH on mental health among health-service practitioners. Study limitations include reliance on cross-sectional data collected before pandemic-related and other major changes in workplace practices. Longitudinal data are needed to improve evidence on causality and the longevity of mental health impacts. Funding: UK Prevention Research Partnership.

Lancet (London, England) · 1 citationsread the source →

Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study.

Background: With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status. Methods: We did an ambidirectional, longitudinal cohort study of individuals who had survived hospitalisation with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We measured health outcomes 6 months (June 16-Sept 3, 2020), 12 months (Dec 16, 2020-Feb 7, 2021), and 2 years (Nov 16, 2021-Jan 10, 2022) after symptom onset with a 6-min walking distance (6MWD) test, laboratory tests, and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and health-care use after discharge. A subset of COVID-19 survivors received pulmonary function tests and chest imaging at each visit. Age-matched, sex-matched, and comorbidities-matched participants without COVID-19 infection (controls) were introduced to determine the recovery status of COVID-19 survivors at 2 years. The primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnoea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnoea scale, and HRQoL were also assessed in controls. Findings: 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7 and May 29, 2020. 1192 COVID-19 survivors completed assessments at the three follow-up visits and were included in the final analysis, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57·0 years (48·0-65·0) and 551 (46%) were women. The median follow-up time after symptom onset was 185·0 days (IQR 175·0-197·0) for the visit at 6 months, 349·0 days (337·0-360·0) for the visit at 12 months, and 685·0 days (675·0-698·0) for the visit at 2 years. The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with fatigue or muscle weakness always being the most frequent. The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than the 288 (26%) of 1104 at 6 months (p<0·0001). HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) of 1105 at 6 months to 143 (12%) 1191 at 2 years (p<0·0001). The proportion of individuals with a 6MWD less than the lower limit of the normal range declined continuously in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original work at 2 years. Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormality, and increased health-care use after discharge than survivors without long COVID symptoms. COVID-19 survivors still had more prevalent symptoms and more problems in pain or discomfort, as well as anxiety or depression, at 2 years than did controls. Additionally, a significantly higher proportion of survivors who had received higher-level respiratory support during hospitalisation had lung diffusion impairment (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs 13 [20%], p<0·0001), and total lung capacity (26 [39%] vs four [6%], p<0·0001) than did controls. Interpretation: Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.

The Lancet. Respiratory medicine · 462 citationsread the source →

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

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

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

The IDEFICS cohort: design, characteristics and participation in the baseline survey.

Background: The European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study was set up to determine the aetiology of overweight, obesity and related disorders in children, and to develop and evaluate a tailored primary prevention programme. Objective: This paper focuses on the aetiological element of the multicentre study, the measures and examinations, sociodemographic characteristics of the study sample and proportions of participation. Design: Prospective cohort study with an embedded intervention study that started with a baseline survey in eight countries in 2007-2008. Subjects and measurements: Baseline participants of the prospective cohort study were 16,224 children aged 2-9 years. Parents reported sociodemographic, behavioural, medical, nutritional and other lifestyle data for their children and families. Examinations of children included anthropometry, blood pressure, fitness, accelerometry, DNA from saliva and physiological markers in blood and urine. The built environment, sensory taste perception and other mechanisms of children's food choices and consumer behaviour were studied in subgroups. Results: Between 1507 and 2567, children with a mean age of 6.0 years and an even sex distribution were recruited from each country. Of them, 82% lived in two-parent families. The distribution of standardised income levels differed by study sample, with low-income groups being strongly represented in Cyprus, Italy and Germany. At least one 24-h dietary recall was obtained for two-thirds of the children. Blood pressure and anthropometry were assessed in more than 90%. A 3-day accelerometry was performed in 46%, motor fitness was assessed in 41%, cardiorespiratory fitness in 35% and ∼11% participated in taste perception tests. The proportion of children donating venous blood, urine and saliva was 57, 86 and 88%, respectively. Conclusion: The IDEFICS cohort provides valuable data to investigate the interplay of social, environmental, genetic, physiological and behavioural factors in the development of major diet- and lifestyle-related disorders affecting children at present.

International journal of obesity (2005) · 267 citationsread the source →