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Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial.

Background: Fatigue is one of the most disabling symptoms reported by people with multiple sclerosis. Although behavioural and pharmacological interventions might be partly beneficial, their combined effects have not been evaluated for multiple sclerosis fatigue, or examined with sufficient consideration of characteristics that might affect treatment response. In this comparative effectiveness research trial, we compared the effectiveness of cognitive behavioural therapy (CBT), modafinil, and their combination for treating multiple sclerosis fatigue. Methods: This randomised, analyst-blinded, parallel-arm, comparative effectiveness trial was done at two universities in the USA. Adults (aged ≥18 years) with multiple sclerosis and problematic fatigue (Fatigue Severity Scale [FSS] score ≥4) were randomly assigned (1:1:1), using a web-based treatment assignment system with minimisation, to receive CBT, modafinil, or both for 12 weeks. Statisticians were masked to group assignment, but participants, study neurologists, CBT interventionalists, and coordinators were not masked to treatment assignment. The primary outcome was the change in Modified Fatigue Impact Scale (MFIS) from baseline to 12 weeks, assessed using multiple linear regression, adjusted for age, sex, study site, anxiety, pain, baselines MFIS score, and physical activity. Analyses were done by intent to treat. The trial was registered with clinicaltrials.gov, NCT03621761, and is completed. Findings: Between Nov 15, 2018, and June 2, 2021, 336 participants were randomly assigned treatment (114 assigned to CBT, 114 assigned to modafinil, and 108 assigned to combination therapy). At 12 weeks, CBT (n=103), modafinil (n=107), and combination therapy (n=102) were associated with clinically meaningful within-group MFIS reductions of 15·20 (SD 11·90), 16·90 (15·90), and 17·30 (16·20) points, respectively. Change in MFIS scores from baseline to 12 weeks did not differ between groups: relative to combination therapy, the adjusted total mean difference in MFIS change score was 1·88 (95% CI -2·21 to 5·96) for CBT and 1·20 (-2·83 to 5·23) for modafinil. Most common adverse events for modafinil-containing treatment groups included insomnia (eight [7%] for modafinil and eight [7%] for combination therapy) and anxiety (three [3%] for modafinil and nine [8%] for combination therapy). Interpretation: Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks. Combination therapy was not associated with augmented improvement compared with the individual interventions. Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness. No serious adverse events related to the study drug were encountered. Funding: Patient-Centered Outcomes Research Institute and National Multiple Sclerosis Society.

The Lancet. Neurology · randomised controlled trial · 6 citationsread the source →

Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial.

Background: Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. Methods: In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged ≥58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Findings: Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in the telemedicine group and 104 (86%) in the same-room group. Treatment response according to GDS did not differ significantly between the telemedicine (22 [22·45%, 90% CI 15·52-29·38] patients) and same-room (21 [20·39%, 90% CI 13·86-26·92]) groups, with an absolute difference of 2·06% (90% CI -7·46 to 11·58). Response according to BDI also did not differ significantly (telemedicine 19 [24·05%, 90% CI 16·14-31·96] patients; same room 19 [23·17%, 90% CI 15·51-30·83]), with an absolute difference of 0·88% (90% CI -10·13 to 11·89). Response on the Structured Clinical Interview for DSM-IV, clinician version, also did not differ significantly (39 [43·33%, 90% CI 34·74-51·93] patients in the telemedicine group and 46 [48·42%, 90% CI 39·99-56·85] in the same-room group), with a difference of -5·09% (-17·13 to 6·95; p=0·487). Results from the intention-to-treat population were similar. MEM analyses showed that no significant differences existed between treatment trajectories over time for BDI and GDS. The criteria for non-inferiority were met. We did not note any adverse events. Interpretation: Telemedicine-delivered psychotherapy for older adults with major depression is not inferior to same-room treatment. This finding shows that evidence-based psychotherapy can be delivered, without modification, via home-based telemedicine, and that this method can be used to overcome barriers to care associated with distance from and difficulty with attendance at in-person sessions in older adults. Funding: US Department of Veterans Affairs.

The lancet. Psychiatry · randomised controlled trial · 123 citationsread the source →

Well-being app to support young people during the COVID-19 pandemic: randomised controlled trial.

Objectives: To evaluate the efficacy and acceptability of 'Whitu: seven ways in seven days', a well-being application (app) for young people. Design: Prospective randomised controlled trial of Whitu against waitlist control, with 45 participants in each arm. Participants: 90 New Zealand young people aged 16-30 recruited via a social media advertising campaign. Setting: Participants' homes. Interventions: Developed during the COVID-19 pandemic, and refined from a prototype version that was evaluated during a smaller qualitative study, 'Whitu: seven ways in seven days' is a well-being app that, as its name suggests, contains seven modules to help young people (1) recognise and rate emotions, (2) learn relaxation and mindfulness, (3) practice self-compassion and (4) gratitude, (5) connect with others, (6) care for their physical health and (7) engage in goal-setting. It can be completed within a week or as desired. Main outcome measures: Primary outcomes were changes in well-being on the WHO 5-item Well-Being Index and Short Warwick-Edinburgh Mental Well-Being Scale. Secondary outcomes were changes in depression on the Centre for Epidemiological Studies Depression Scale, anxiety on the Generalised Anxiety Disorder 7-item Scale, self-compassion on the Self Compassion Scale-Short Form, stress on the 10-item Perceived Stress Scale, sleep on the single-item Sleep Quality Scale and user engagement on the end-user version of the Mobile Application Rating Scale and via qualitative feedback during an online survey. Outcomes were evaluated at baseline, 4 weeks (primary study endpoint) and 3 months, and analysed using linear mixed models with group, time and a group-time interaction. Results: At 4 weeks, participants in the Whitu group experienced significantly higher emotional (Mean difference (md) 13.19 (3.96 to 22.42); p=0.005) and mental (md 2.44 (0.27 to 4.61); p=0.027) well-being, self-compassion (md 0.56 (0.28 to 0.83); p<0.001) and sleep (md 1.13 (0.24 to 2.02); p=0.018), and significantly lower stress (md -4.69 (-7.61 to -1.76); p=0.002) and depression (md -5.34 (-10.14 to -0.53); p=0.030), compared with the waitlist controls. Group differences remained statistically significant at 3 months for all outcomes. Symptoms of anxiety were also lower in the intervention group at 4 weeks (p=0.096), with statistically significant differences at 3 months (md -2.31 (-4.54 to -0.08); p=0.042). Usability of Whitu was high (subjective ratings of 4.45 (0.72) and 4.38 (0.79) out of 5 at 4 weeks and 3 months, respectively) and qualitative feedback indicated individual and cultural acceptability of the app. Conclusions: Given the evolving psychological burden of the COVID-19 pandemic, Whitu could provide a clinically effective and scalable means of improving the well-being, mental health and resilience of young people. Replication of current findings with younger individuals and in other settings is planned. Trial registration number: Australian New Zealand Clinical Trials Registry (ACTRN12620000516987).

BMJ open · randomised controlled trial · 20 citationsread the source →

Randomized controlled trial of maintaining quality of life during radiotherapy for advanced cancer.

Background: Psychosocial interventions often address only 1 domain of quality of life (QOL), are offered to patients with early-stage cancer, do not include the caregiver, and are delivered after cancer treatment has been completed. Methods: In the current randomized controlled trial, 131 patients with advanced cancer who received radiotherapy and their caregivers were randomly assigned to either a 6-session, structured, multidisciplinary intervention arm or a standard care arm. The average age of the patients was 58 years, the majority were male (63%), and tumor types varied (gastrointestinal [37%], brain [22%], head and neck [16%], lung [13%], and other [12%]). The six 90-minute sessions addressed the 5 domains of QOL: cognitive, physical, emotional, social, and spiritual. The in-person intervention was followed by 10 brief telephone counseling sessions that took place over the next 6 months. Results: Of the 117 patients who completed the study, overall QOL (assessed by Functional Assessment of Cancer Therapy-General [FACT-G]) at week 4 was significantly higher in the intervention group (n = 54) compared with the standard arm control group (n = 63) (75.2 vs 68.7; P = .02). The 10 brief telephone contacts did not appear to impact QOL because at week 27 the groups had identical QOL (means of 77.6 and 77.7, respectively). There was no effect of the intervention noted on caregiver QOL. Conclusions: Participating in a 6-session multidisciplinary intervention was found to be effective in maintaining the QOL of patients with advanced cancer who were actively receiving radiotherapy. The QOL and symptom burden of this population is striking, making it important to identify effective QOL strategies to implement in conjunction with cancer care.

Cancer · randomised controlled trial · 91 citationsread the source →

Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson's disease.

The progressive nature of Parkinson's disease, its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge. Clinicians have limited face-to-face consultation time with Parkinson's disease patients, making it difficult to comprehensively address non-adherence. Here we share the results from a multi-centre (seven centres) randomised controlled trial conducted in England and Scotland to assess the impact of using a smartphone-based Parkinson's tracker app to promote patient self-management, enhance treatment adherence and quality of clinical consultation. Eligible Parkinson's disease patients were randomised using a 1:1 ratio according to a computer-generated random sequence, stratified by centre and using blocks of variable size, to intervention Parkinson's Tracker App or control (Treatment as Usual). Primary outcome was the self-reported score of adherence to treatment (Morisky medication adherence scale -8) at 16 weeks. Secondary outcomes were Quality of Life (Parkinson's disease questionnaire -39), quality of consultation for Parkinson's disease patients (Patient-centred questionnaire for Parkinson's disease), impact on non-motor symptoms (Non-motor symptoms questionnaire), depression and anxiety (Hospital anxiety and depression scale) and beliefs about medication (Beliefs about Medication Questionnaire) at 16 weeks. Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate. 158 patients completed the study (Parkinson's tracker app = 68 and TAU = 90). At 16 weeks Parkinson's tracker app significantly improved adherence, compared to treatment as usual (mean difference: 0.39, 95%CI 0.04-0.74; p = 0.0304) with no confounding effects of gender, number of comorbidities and age. Among secondary outcomes, Parkinson's tracker app significantly improved patients' perception of quality of consultation (0.15, 95% CI 0.03 to 0.27; p = 0.0110). The change in non-motor symptoms was -0.82 (95% CI -1.75 to 0.10; p = 0.0822). 72% of participants in the Parkinson's tracker app group continued to use and engage with the application throughout the 16-week trial period. The Parkinson's tracker app can be an effective and novel way of enhancing self-reported medication adherence and quality of clinical consultation by supporting self-management in Parkinson's disease in patients owning smartphones. Further work is recommended to determine whether the benefits of the intervention are maintained beyond the 16 week study period.

NPJ Parkinson's disease · 60 citationsread the source →

Online group-based internal family systems treatment for posttraumatic stress disorder: Feasibility and acceptability of the program for alleviating and resolving trauma and stress.

Objective: Demand for trauma-focused therapy continues to increase, especially in community mental health care settings where group treatment models can be cost-effective and increase access to care. The Internal Family Systems (IFS) model for posttraumatic stress disorder (PTSD) may offer an effective therapeutic approach. The purpose of this proof-of-concept study was to evaluate the feasibility and acceptability of a novel, trauma-focused, group-based treatment approach and investigate potential mechanisms of action. Method: Study participants completed the Program for Alleviating and Resolving Trauma and Stress (PARTS), an online-delivered program including 16 weeks of 90-min IFS-based groups with eight 50-min individual IFS counseling sessions. Participants completed assessments including clinician-administered and self-report measures of PTSD, common comorbid conditions (e.g., complex PTSD [disturbances in self-organization], depression, anxiety, and suicidality), and potential mechanisms (e.g., decentering, self-compassion, and emotion regulation). Results: Most participants (n = 11/15; 73%) attended 12+ group sessions, with 92% (12/13 responders) reporting they would recommend PARTS to a friend. All respondents reported the program was helpful (13/13; 100%). PTSD symptom severity was reduced from baseline to Weeks 16 (d = -0.7, p = .005) and 24 (d = -0.9, p < .001). A clinically meaningful response (i.e., 10+ point reduction on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders [5th ed.]) was demonstrated in 53% of participants (8/15) by Week 24. Decentering, self-compassion, and emotion regulation all improved (p < .05). Conclusions: PARTS was feasible and acceptable as a group-based, online intervention in an urban, public community health care system. While PARTS showed promise in reducing overall PTSD symptom severity, well-controlled efficacy research is needed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psychological trauma : theory, research, practice and policy · 2 citationsread the source →

Effect of the Goals of Care Intervention for Advanced Dementia: A Randomized Clinical Trial.

Importance: In advanced dementia, goals of care decisions are challenging and medical care is often more intensive than desired. Objective: To test a goals of care (GOC) decision aid intervention to improve quality of communication and palliative care for nursing home residents with advanced dementia. Design, setting, and participants: A single-blind cluster randomized clinical trial, including 302 residents with advanced dementia and their family decision makers in 22 nursing homes. Interventions: A GOC video decision aid plus a structured discussion with nursing home health care providers; attention control with an informational video and usual care planning. Main outcomes and measures: Primary outcomes at 3 months were quality of communication (QOC, questionnaire scored 0-10 with higher ratings indicating better quality), family report of concordance with clinicians on the primary goal of care (endorsing same goal as the "best goal to guide care and medical treatment," and clinicians' "top priority for care and medical treatment"), and treatment consistent with preferences (Advance Care Planning Problem score). Secondary outcomes at 9 months were family ratings of symptom management and care, palliative care domains in care plans, Medical Orders for Scope of Treatment (MOST) completion, and hospital transfers. Resident-family dyads were the primary unit of analysis, and all analyses used intention-to-treat assignment. Results: Residents' mean age was 86.5 years, 39 (12.9%) were African American, and 246 (81.5%) were women. With the GOC intervention, family decision makers reported better quality of communication (QOC, 6.0 vs 5.6; P = .05) and better end-of-life communication (QOC end-of-life subscale, 3.7 vs 3.0; P = .02). Goal concordance did not differ at 3 months, but family decision makers with the intervention reported greater concordance by 9 months or death (133 [88.4%] vs 108 [71.2%], P = .001). Family ratings of treatment consistent with preferences, symptom management, and quality of care did not differ. Residents in the intervention group had more palliative care content in treatment plans (5.6 vs 4.7, P = .02), MOST order sets (35% vs 16%, P = .05), and half as many hospital transfers (0.078 vs 0.163 per 90 person-days; RR, 0.47; 95% CI, 0.26-0.88). Survival at 9 months was unaffected (adjusted hazard ratio [aHR], 0.76; 95% CI, 0.54-1.08; P = .13). Conclusions and relevance: The GOC decision aid intervention is effective to improve end-of-life communication for nursing home residents with advanced dementia and enhance palliative care plans while reducing hospital transfers. Trial registration: clinicaltrials.gov Identifier: NCT01565642.

JAMA internal medicine · randomised controlled trial · 193 citationsread the source →

To Nap or Not to Nap? A Systematic Review Evaluating Napping Behavior in Athletes and the Impact on Various Measures of Athletic Performance.

Purpose: The objective of this systematic review was to 1) determine how studies evaluated napping behavior in athletes (frequency, duration, timing and measurement); 2) explore how napping impacted physical performance, cognitive performance, perceptual measures (eg, fatigue, muscle soreness, sleepiness and alertness), psychological state and night-time sleep in athletes. Methods: Five bibliographic databases were searched from database inception to 11 August 2020. Observational and experimental studies comprising able-bodied athletes (mean age ≥12 years), published in English, in peer-reviewed journal papers were included. The Downs and Black Quality Assessment Checklist was used for quality appraisal. Results: Thirty-seven studies were identified of moderate quality. Most studies did not include consistent information regarding nap frequency, duration, and timing. Napping may be beneficial for a range of outcomes that benefit athletes (eg, physical and cognitive performance, perceptual measures, psychological state and night-time sleep). In addition, napping presents athletes with the opportunity to supplement their night-time sleep without compromising sleep quality. Conclusion: Athletes may consider napping between 20 to 90 min in duration and between 13:00 and 16:00 hours. Finally, athletes should allow 30 min to reduce sleep inertia prior to training or competition to obtain better performance outcomes. Future studies should include comprehensive recordings of nap duration and quality, and consider using sleep over a 24 hour period (daytime naps and night-time sleep period), specifically using objective methods of sleep assessment (eg, polysomnography/actigraphy).

Nature and science of sleep · review · 86 citationsread the source →

The effectiveness of third wave cognitive behavioural therapies for children and adolescents: A systematic review and meta-analysis.

Objectives: Third wave cognitive behavioural therapies are increasingly used with children and adolescents. This meta-analysis aimed to determine the effectiveness of four third-wave interventions (acceptance and commitment therapy, compassion focused therapy, mindfulness-based cognitive therapy, and metacognitive therapy) for youth. Methods: Four electronic databases were used to identify randomized controlled trials, which tested effects related to health, well-being and functioning. Sensitivity analyses considering study quality were conducted and moderators were explored. Results: The results based on 50 RCTs meeting inclusion criteria indicated emotional symptoms/internalizing problems (g = -.68, 95% CI -.98 to -.37, k = 43, N = 3265), behavioural difficulties/externalizing problems (g = -.62, 95% CI -1.01 to -.22, k = 23, N = 1659), interference from difficulties (g = -.46, 95% CI -.87 to -.05, k = 21, N = 1786), third wave processes (g = .39, 95% CI .17 to .62, k = 22, N = 1900), wellbeing/flourishing (g = .76, 95% CI .35 to 1.17, k = 21, N = 1303) and physical health/pain (g = .72, 95% CI .01 to 1.44, k = 9, N = 1171) yielded significant effects. Effect for quality of life (g = .62, 95% CI -.08 to 1.31, k = 12, N = 1271) was non-significant. When analysing only those studies rated moderate-high quality, third wave interventions yielded significant superiority effects compared to controls for emotional symptoms/internalizing problems (g = -.55, 95% CI -.82 to -.27, k = 28, N = 2110), interference from difficulties (g = -.48, 95% CI -.90 to -.05, k = 21, N = 1605), third wave processes (g = .27, 95% CI .11 to .43, k = 18, N = 1692), well-being/flourishing (g = .50, 95% CI .18 to .81, k = 16, N = 1063), and quality of life (g = .32, 95% CI .04 to .60, k = 10, N = 1212). Behavioural difficulties/externalizing problems (g = -.38, 95% CI -.86 to .10, k = 15, N = 1351) and physical health/pain (g = .52, 95% CI -.14 to 1.17, k = 8, N = 1139) ceased to be significant. Widespread heterogeneity raised concerns about generalizability and follow-up data was relatively sparse. Conclusions: This meta-analysis finds promising results for use of third wave CBT with youth, though the review has limitations.

The British journal of clinical psychology · meta-analysis · 19 citationsread the source →

Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus.

Background: Hepatitis is a viral infection of the liver. It is mainly transmitted between people through contact with infected blood, frequently from mother to baby in-utero. Hepatitis B poses significant risk to the fetus and up to 85% of infants infected by their mothers at birth develop chronic hepatitis B virus (HBV) infection. Hepatitis B immunoglobulin (HBIG) is a purified solution of human immunoglobulin that could be administered to the mother, newborn, or both. HBIG offers protection against HBV infection when administered to pregnant women who test positive for hepatitis B envelope antigen (HBeAg) or hepatitis B surface antigen (HBsAg), or both. When HBIG is administered to pregnant women, the antibodies passively diffuse across the placenta to the child. This materno-fetal diffusion is maximal during the third trimester of pregnancy. Up to 1% to 9% infants born to HBV-carrying mothers still have HBV infection despite the newborn receiving HBIG plus active HBV vaccine in the immediate neonatal period. This suggests that additional intervention such as HBIG administration to the mother during the antenatal period could be beneficial to reduce the transmission rate in utero. Objectives: To determine the benefits and harms of hepatitis B immunoglobulin (HBIG) administration to pregnant women during their third trimester of pregnancy for the prevention of mother-to-child transmission of hepatitis B virus infection. Search methods: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), SCOPUS, African Journals OnLine, and INDEX MEDICUS up to June 2016. We searched ClinicalTrials.gov and portal of the WHO International Clinical Trials Registry Platform (ICTRP) in December 2016. Selection criteria: We included randomised clinical trials comparing HBIG versus placebo or no intervention in pregnant women with HBV. Data collection and analysis: Two authors extracted data independently. We analysed dichotomous outcome data using risk ratio (RR) and continuous outcome data using mean difference (MD) with 95% confidence intervals (CI). For meta-analyses, we used a fixed-effect model and a random-effects model, along with an assessment of heterogeneity. If there were statistically significant discrepancies in the results, we reported the more conservative point estimate. If the two estimates were equal, we used the estimate with the widest CI as our main result. We assessed bias control using the Cochrane Hepato-Biliary Group suggested bias risk domains and risk of random errors using Trial Sequential Analysis (TSA). We assessed the quality of the evidence using GRADE. Main results: All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo. Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. Authors' conclusions: Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.

The Cochrane database of systematic reviews · meta-analysis · 42 citationsread the source →

Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for adults with swallowing disturbances.

Background: A number of conditions compromise the passage of food along the digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven technique, although its prolonged use can lead to complications such as lesions to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG), is generally used when there is a need for enteral nutrition for a longer time period. There is a high demand for PEG in patients with swallowing disorders, although there is no consistent evidence about its effectiveness and safety as compared to NGT. Objectives: To evaluate the effectiveness and safety of PEG compared with NGT for adults with swallowing disturbances. Search methods: We searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to January 2014, and contacted the main authors in the subject area. There was no language restriction in the search. Selection criteria: We planned to include randomised controlled trials comparing PEG versus NGT for adults with swallowing disturbances or dysphagia and indications for nutritional support, with any underlying diseases. The primary outcome was intervention failure (e.g. feeding interruption, blocking or leakage of the tube, no adherence to treatment). Data collection and analysis: We used standard methodological procedures expected by The Cochrane Collaboration. For dichotomous and continuous variables, we used risk ratio (RR) and mean difference (MD), respectively with the random-effects statistical model and 95% confidence interval (CI). We assumed statistical heterogeneity when I² > 50%. Main results: We included 11 randomised controlled studies with 735 participants which produced 16 meta-analyses of outcome data. Meta-analysis indicated that the primary outcome of intervention failure, occurred in lower proportion of participants with PEG compared to NGT (RR 0.18, 95% CI 0.05 to 0.59, eight studies, 408 participants, low quality evidence) and this difference was statistically significant. For this outcome, we also subgrouped the studies by endoscopic gastrostomy technique into pull, and push and not reported. We observed a significant difference favouring PEG in the pull subgroup (RR 0.07, 95% CI 0.01 to 0.35, three studies, 90 participants). Thepush subgroup contained only one clinical trial and the result favoured PEG (RR 0.05, 95% CI 0.00 to 0.74, one study, 33 participants) techniques. We found no statistically significant difference in cases where the technique was not reported (RR 0.43, 95% CI 0.13 to 1.44, four studies, 285 participants).There was no statistically significant difference between the groups for meta-analyses of the secondary outcomes of mortality (RR 0.86, 95% CI 0.58 to 1.28, 644 participants, nine studies, very low quality evidence), overall reports of any adverse event at any follow-up time point (ITT analysis, RR 0.83, 95% CI 0.51 to 1.34), 597 participants, 6 studies, moderate quality evidence), specific adverse events including pneumonia (aspiration) (RR 0.70, 95% CI 0.46 to 1.06, 645 participants, seven studies, low quality evidence), or for the meta- analyses of the secondary outcome of nutritional status including weight change from baseline, and mid-arm circumference at endpoint, although there was evidence in favour of PEG for meta-analyses of mid-arm circumference change from baseline (MD 1.16, 95% CI 1.01 to 1.31, 115 participants, two studies), and levels of serum albumin were higher in the PEG group (MD 6.03, 95% CI 2.31 to 9.74, 107 participants).For meta-analyses of the secondary outcomes of time on enteral nutrition, there was no statistically significant difference (MD 14.48, 95% CI -2.74 to 31.71; 119 participants, two studies). For meta-analyses of quality of life measures (EuroQol) outcomes in two studies with 133 participants, for inconvenience (RR 0.03, 95% CI 0.00 to 0.29), discomfort (RR 0.03, 95% CI 0.00 to 0.29), altered body image (RR 0.01, 95% CI 0.00 to 0.18; P = 0.001) and social activities (RR 0.01, 95% CI 0.00 to 0.18) the intervention favoured PEG, that is, fewer participants found the intervention of PEG to be inconvenient, uncomfortable or interfered with social activities. However, there were no significant differences between the groups for pain, ease of learning to use, or the secondary outcome of length of hospital stay (two studies, 381 participants). Authors' conclusions: PEG was associated with a lower probability of intervention failure, suggesting the endoscopic procedure may be more effective and safe compared with NGT. There is no significant difference in mortality rates between comparison groups, or in adverse events, including pneumonia related to aspiration. Future studies should include details of participant demographics including underlying disease, age and gender, and the gastrostomy technique.

The Cochrane database of systematic reviews · meta-analysis · 101 citationsread the source →

Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms.

In 2 meta-analyses on gender differences in depression in nationally representative samples, we advance previous work by including studies of depression diagnoses and symptoms to (a) estimate the magnitude of the gender difference in depression across a wide array of nations and ages; (b) use a developmental perspective to elucidate patterns of gender differences across the life span; and (c) incorporate additional theory-driven moderators (e.g., gender equity). For major depression diagnoses and depression symptoms, respectively, we meta-analyzed data from 65 and 95 articles and their corresponding national data sets, representing data from 1,716,195 and 1,922,064 people in over 90 different nations. Overall, odds ratio (OR) = 1.95, 95% confidence interval (CI) [1.88, 2.03], and d = 0.27 [0.26, 0.29]. Age was the strongest predictor of effect size. The gender difference for diagnoses emerged earlier than previously thought, with OR = 2.37 at age 12. For both meta-analyses, the gender difference peaked in adolescence (OR = 3.02 for ages 13-15, and d = 0.47 for age 16) but then declined and remained stable in adulthood. Cross-national analyses indicated that larger gender differences were found in nations with greater gender equity, for major depression, but not depression symptoms. The gender difference in depression represents a health disparity, especially in adolescence, yet the magnitude of the difference indicates that depression in men should not be overlooked. (PsycINFO Database Record

Psychological bulletin · meta-analysis · 1630 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 →

Effect of high-docosahexaenoic acid omega-3 supplementation in low-risk pregnant women on maternal and neonatal health outcomes in Southeast Brazil: a randomized clinical trial.

Despite well-documented benefits of omega-3 for maternal and child health, evidence on high-docosahexaenoic acid (DHA) supplementation in low-risk pregnant women is limited. A randomized, double-blind, placebo-controlled trial was conducted among low-risk pregnant women aged 20-40 years at 22-24 weeks of gestation to evaluate the effects of high-DHA omega-3 supplementation on maternal and neonatal health outcomes. The control group (CG, n = 30) received oral olive oil supplementation, and the intervention group (IG, n = 30) received omega-3 [1700 mg, 260 mg of eicosapentaenoic acid (EPA), and 1440 mg of DHA] for ∼16 weeks or until delivery. Maternal and neonatal health outcomes were collected by telephone 15 days after delivery. Forty-five pregnant women completed the study (IG: 20; CG: 25). Adherence to supplementation was above 90% and did not differ between groups (P > .05). There were no differences between groups in mean gestational age (CG: 39.3 ± 1.6; IG: 39.2 ± 1.6; P = .877), adequate gestational weight gain (CG: 24.0%; IG: 50.0%; P = .088), adequate gestational BMI before delivery (CG: 33.3%; IG: 27.8%; P = .261), vaginal delivery (CG: 72.0%; IG: 60.0%; P = .396), full-term birth (CG: 92%; IG: 90%; P = .815), adequate weight (CG: 91.3%; IG: 94.7%; P = .237), and adequate length for gestational age (CG: 82.6%; IG: 100%; P = .056). Omega-3 supplementation with a higher concentration of DHA had no effect on the maternal and neonatal health outcomes investigated in a Brazilian sample of low-risk pregnant women. Further studies are needed to evaluate this effect in pregnant women at higher nutritional risk and with low dietary intake of omega-3.

Journal of tropical pediatrics · randomised controlled trialread the source →

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

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

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

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial.

Importance: Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance. Objective: To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms. Design, setting, and participants: This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment. Interventions: Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each). Main outcomes and measures: The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms. Results: Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy. Conclusions and relevance: These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy. Trial registration: ClinicalTrials.gov Identifier: NCT02349477.

JAMA internal medicine · randomised controlled trial · 119 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 →

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. Limitations: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. Conclusions: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. Future work: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). Trial registration: This trial is registered as ISRCTN99559262. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

Health technology assessment (Winchester, England) · randomised controlled trial · 24 citationsread the source →

Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster randomised trial.

Background: Parenting interventions have been implemented to improve the compromised developmental potential among 39% of children younger than 5 years living in low-income and middle-income countries. Maternal wellbeing is important for child development, especially in children younger than 3 years who are vulnerable and dependent on their mothers for nutrition and stimulation. We assessed an integrated, community-based parenting intervention that targeted both child development and maternal wellbeing in rural Uganda. Methods: In this community-based, cluster randomised trial, we assessed the effectiveness of a manualised, parenting intervention in Lira, Uganda. We selected and randomly assigned 12 parishes (1:1) to either parenting intervention or control (inclusion on a waitlist with a brief message on nutrition) groups using a computer-generated list of random numbers. Within each parish, we selected two to three eligible communities that had a parish office or a primary school in which a preschool could be established, more than 75 households with children younger than 6 years, and at least 15 socially disadvantaged families (ie, maternal education of primary school level or lower) with at least one child younger than 36 months. Participants within communities were mother-child dyads, where the child was 12-36 months of age at enrollment, and the mother had low maternal education. In the parenting intervention group, participants attended 12 fortnightly peer-led group sessions focusing on child care and maternal wellbeing. The primary outcomes were cognitive and receptive language development, as measured with the Bayley Scales of Infant Development, 3rd edn. Secondary outcomes included self-reported maternal depressive symptoms, using the Center for Epidemiologic Studies Depression Scale, and child growth. Theoretically-relevant parenting practices, including the Home Observation for Measurement of the Environment inventory, and mother-care variables, such as perceived spousal support, were also assessed as potential mediators. Baseline assessments were done in January, 2013, and endline assessments were done in November, 2013, 3 months after completion of the programme. Ethics approval was received from Mbarara and McGill universities. This trial is registered with ClinicalTrials.gov, NCT01906606. Findings: Between December, 2012, and January, 2013, 13 communities (194 dyads) were randomly assigned to receive intervention, and 12 communities (154 dyads) were assigned to a waitlist control. 319 dyads completed baseline measures (171 in the intervention group and 148 in the control group), and 291 dyads completed endline measures (160 in the intervention group and 131 in the control group). At endline, children in the intervention group had significantly higher cognitive scores (58·90 vs 55·65, effect size 0·36, 95% CI 0·12-0·59) and receptive language scores (23·86 vs 22·40, 0·27, 0·03-0·50) than did children in the control group. Mothers in the intervention group reported significantly fewer depressive symptoms (15·36 vs 18·61, -0·391, 95% CI -0·62 to -0·16) than did mothers in the control group. However, no differences were found in child growth between groups. Interpretation: The 12 session integrated parenting intervention delivered by non-professional community members improved child development and maternal wellbeing in rural Uganda. Because this intervention was largely managed and implemented by a local organisation, using local community members and minimal resources, such a programme has the potential to be replicated and scaled up in other low-resource, village-based settings. Funding: Plan Uganda via Plan Finland (Ministry of Foreign Affairs) and Plan Australia (Australian Aid).

The Lancet. Global health · randomised controlled trial · 208 citationsread the source →

The impact of a multilevel childhood obesity prevention intervention on healthful food acquisition, preparation, and fruit and vegetable consumption on African-American adult caregivers.

Objective: To evaluate the secondary impact of a multilevel, child-focused, obesity intervention on food-related behaviours (acquisition, preparation, fruit and vegetable (FV) consumption) on youths' primary caregivers. Design: B'More Healthy Communities for Kids (BHCK) group-randomized controlled trial promoted access to healthy foods and food-related behaviours through wholesaler and small store strategies, peer mentor-led nutrition education aimed at youths, and social media and text messaging targeting their adult caregivers. Measures included caregivers' (n 516) self-reported household food acquisition frequency for FV, snacks and grocery items over 30 d, and usual FV consumption in a sub-sample of 226 caregivers via the NCI FV Screener. Hierarchical models assessed average treatment effects (ATE). Treatment-on-the-treated-effect (TTE) analyses evaluated correlation between behavioural change and exposure to BHCK. Exposure scores at post-assessment were based on self-reported viewing of BHCK materials and participating in activities. Setting: Thirty Baltimore City low-income neighbourhoods, USA.ParticipantsAdult caregivers of youths aged 9-15 years. Results: Of caregivers, 90·89 % were female; mean age 39·31 (sd 9·31) years. Baseline mean (sd) intake (servings/d) was 1·30 (1·69) fruits and 1·35 (1·05) vegetables. In ATE, no significant intervention effect was found on caregivers' food-related behaviours. In TTE, each point increase in BHCK exposure score (range: 0-6·9) increased caregivers' daily fruit consumption by 0·2 servings (0·24 (se 0·11); 95 % CI 0·04, 0·47). Caregivers reporting greater social media exposure tripled their daily fruit intake (3·16 (se 0·92); 95 % CI 1·33, 4·99) and increased their frequency of unhealthy food purchasing v. baseline. Conclusions: Child-focused community-based nutrition interventions may also benefit family members' fruit intake. Child-focused interventions should involve adult caregivers and intervention effects on family members should be assessed. Future multilevel studies should consider using social media to improve reach and engage caregiver participants.

Public health nutrition · randomised controlled trial · 20 citationsread the source →

Face-to-Face and Internet-Based Mindfulness-Based Cognitive Therapy Compared With Treatment as Usual in Reducing Psychological Distress in Patients With Cancer: A Multicenter Randomized Controlled Trial.

Purpose Mindfulness-based cognitive therapy (MBCT) has been shown to alleviate psychological distress in patients with cancer. However, patients experience barriers to participating in face-to-face MBCT. Individual Internet-based MBCT (eMBCT) could be an alternative. The study aim was to compare MBCT and eMBCT with treatment as usual (TAU) for psychological distress in patients with cancer. Patients and Methods We obtained ethical and safety approval to include 245 patients with cancer with psychological distress (≥ 11 on the Hospital Anxiety and Depression Scale) in the study. They were randomly allocated to MBCT (n = 77), eMBCT (n = 90), or TAU (n = 78). Patients completed baseline (T0) and postintervention (T1) assessments. The primary outcome was psychological distress on the Hospital Anxiety and Depression Scale. Secondary outcomes were psychiatric diagnosis, fear of cancer recurrence, rumination, health-related quality of life, mindfulness skills, and positive mental health. Continuous outcomes were analyzed using linear mixed modeling on the intention-to-treat sample. Because both interventions were compared with TAU, the type I error rate was set at P < .025. Results Compared with TAU, patients reported significantly less psychological distress after both MBCT (Cohen's d, .45; P < .001) and eMBCT (Cohen's d, .71; P < .001) . In addition, post-treatment prevalence of psychiatric diagnosis was lower with both MBCT (33% improvement; P = .030) and eMBCT (29% improvement; P = .076) in comparison with TAU (16%), but these changes were not statistically significant. Both interventions reduced fear of cancer recurrence and rumination, and increased mental health-related quality of life, mindfulness skills, and positive mental health compared with TAU (all Ps < .025). Physical health-related quality of life did not improve ( P = .343). Conclusion Compared with TAU, MBCT and eMBCT were similarly effective in reducing psychological distress in a sample of distressed heterogeneous patients with cancer.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 165 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 →

Smoking cessation for people with severe mental illness (SCIMITAR+): a pragmatic randomised controlled trial.

Background: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness. Methods: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete. Findings: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13). Interpretation: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting. Funding: National Institute for Health Research Health Technology Assessment Programme.

The lancet. Psychiatry · randomised controlled trial · 134 citationsread the source →

Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 Randomized Clinical Trial.

Importance: Atopic dermatitis is associated with substantial patient and caregiver burden. Currently available treatments for atopic dermatitis are inadequate or contraindicated for some patients. Abrocitinib (PF-04965842) is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of atopic dermatitis. Objective: To investigate the efficacy and safety of abrocitinib for patients with moderate to severe atopic dermatitis. Design, setting, and participants: A phase 2b, randomized, double-blinded, placebo-controlled, parallel-group trial was conducted from April 15, 2016, to April 4, 2017, at 58 centers in Australia, Canada, Germany, Hungary, and the United States among 267 patients 18 to 75 years of age with a clinical diagnosis of moderate to severe atopic dermatitis for 1 year or more and inadequate response or contraindication to topical medications for 4 weeks or more within 12 months. Efficacy was assessed in the full analysis set, which was a modified intention-to-treat population that included all patients who received 1 dose or more of the study drug except for 4 patients from 1 site. Interventions: Participants were randomly assigned 1:1:1:1:1 to receive abrocitinib (200 mg, 100 mg, 30 mg, or 10 mg) or placebo once daily for 12 weeks. Main outcomes and measures: The primary outcome was the proportion of patients achieving an Investigator's Global Assessment of clear (0) or almost clear (1) with an improvement from baseline of 2 grades or more at week 12. The secondary outcome was the percentage change from baseline in the Eczema Area and Severity Index at week 12. Results: Of the 267 participants, 144 were women (mean [SD] age, 40.8 [16.1] years). At week 12, 21 of 48 patients receiving 200 mg of abrocitinib (43.8%; P < .001, 2-sided), 16 of 54 patients receiving 100 mg of abrocitinib (29.6%; P < .001), and 3 of 52 patients receiving placebo (5.8%) achieved grades of clear or almost clear on the Investigator's Global Assessment scale with improvement of 2 grades or more; these rates correspond to maximum effect model-based estimates of 44.5% (95% CI, 26.7%-62.3%) for those receiving 200 mg of abrocitinib, 27.8% (95% CI, 14.8%-40.9%) for those receiving 100 mg of abrocitinib, and 6.3% (95% CI, -0.2% to 12.9%) for those receiving placebo. Reductions in the Eczema Area and Severity Index were 82.6% (90% CI, 72.4%-92.8%; P < .001) for those receiving 200 mg of abrocitinib, 59.0% (90% CI, 48.8%-69.3%; P = .009) for those receiving 100 mg of abrocitinib, and 35.2% (90% CI, 24.4%-46.1%) for those receiving placebo. Adverse events were observed in 184 of 267 patients (68.9%); the most frequently reported adverse events (in ≥3 patients in any group) were dermatitis atopic, upper respiratory tract infection, headache, nausea, and diarrhea. Dose-dependent decreases in platelet count were observed but trended upward toward baseline levels after week 4. Conclusions and relevance: Once-daily oral abrocitinib was effective and well tolerated for short-term use in adults with moderate to severe atopic dermatitis. Additional trials are necessary to evaluate long-term efficacy and safety. Trial registration: ClinicalTrials.gov identifier: NCT02780167.

JAMA dermatology · randomised controlled trial · 197 citationsread the source →

Test-Retest Reliability for Physical Function Measures in Patients with Chronic Kidney Disease.

Background: It is important to determine relative and absolute reliability values in outcome measures that are used in clinical practice so as to discriminate between true changes following exercise interventions for patients with chronic kidney disease (CKD). Objective: The study aimed to assess test-retest reliability of the incremental shuttle walk test (ISWT), sit-to-stand transfers in 60 seconds (STS-60), timed up and go (TUAG), Duke's activity status index (DASI) and hospital anxiety and depression scale (HAD) in patients with CKD. Study design: This study was a pragmatic non-randomised controlled trial. Methods: Forty people attended two study visits within a 16-day window involving the ISWT, STS-60, TUAG, DASI and HAD tests. Relative reliability was assessed using intraclass correlation coefficient (ICC) and absolute reliability using the standard error of measurement (SEM) and minimal detectable change (MDC). Results: Good test-retest reliability was found for the entire sample size across all outcome measures, with TUAG having the highest (ICC = 0.96) and HAD the lowest (ICC = 0.71). The MDC scores at 90% confidence interval (CI) were: 79.6 m for the ISWT, 2.9 seconds for the TUAG, 7.0 repetitions for the STS-60, 8.4 for the DASI, 3.8 for the anxiety HAD subscale and 4.4 for the depression HAD subscale. Conclusions: This study demonstrated good test-retest reliability for all outcome measures across the CKD trajectory but caution needs to be taken when interpreting the findings for each CKD sub-group separately. The MDC scores at 90% CI can support therapists in determining a true improvement in CKD patients' physical or mental performance.

Journal of renal care · randomised controlled trial · 10 citationsread the source →

A pilot study examining the initial effectiveness of a brief acceptance-based behavior therapy for modifying diet and physical activity among cardiac patients.

Approximately 90% of cardiac events are attributable to a small number of modifiable behavioral risk factors that, if changed, can greatly decrease morbidity and mortality. However, few at-risk individuals make recommended behavioral changes, including those who receive formal interventions designed to facilitate healthy behavior. Given evidence for the potential of specific psychological factors inherent in acceptance-based behavior therapy (ABBT; that is, intolerance of discomfort, mindfulness, and values clarity) to impact health behavior change, the authors evaluated the feasibility and initial effectiveness of an ABBT pilot program designed to increase adherence to behavioral recommendations among cardiac patients. Participants (N = 16) were enrolled in four, 90-min group sessions focused on developing mindfulness and distress tolerance skills, and strengthening commitment to health-related behavior change. Participants reported high treatment satisfaction and comprehension and made positive changes in diet and physical activity. This was the first evaluation of an ABBT program aimed at increasing heart-healthy behaviors among cardiac patients.

Behavior modification · 41 citationsread the source →

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking.

Deep brain stimulation (DBS) modulates the neuronal activity in specific brain circuits and has been recently considered as a promising intervention for refractory addiction. The insula cortex is the hub of interoception and is known to be involved in different aspects of substance use disorder. In the present study, we investigate the effects of continuous high frequency DBS in the anterior insula (AI) on drug-seeking behaviors and examined the molecular mechanisms of DBS action in morphine-addicted rats. Sprague-Dawley rats were trained to the morphine-conditioned place preference (CPP, day 1-8) followed by bilaterally implanted with DBS electrodes in the AI (Day 10) and recovery (Day 10-15). Continuous high-frequency (HF) -DBS (130 Hz, 150 μA, 90 μs) was applied during withdrawal (Day 16-30) or extinction sessions. CPP tests were conducted on days 16, 30, 40 during withdrawal session and several rats were used for proteomic analysis on day 30. Following the complete extinction, morphine-CPP was reinstated by a priming dose of morphine infusion (2 mg/kg). The open field and novel objective recognition tests were also performed to evaluate the DBS side effect on the locomotion and recognition memory. Continuous HF-DBS in the AI attenuated the expression of morphine-CPP post-withdrawal (Day 30), but morphine addictive behavior relapsed 10 days after the cessation of DBS (Day 40). Continuous HF-DBS reduced the period to full extinction of morphine-CPP and blocked morphine priming-induced recurrence of morphine addiction. HF-DBS in the AI had no obvious effect on the locomotor activity and novel objective recognition and did not cause anxiety-like behavior. In addition, our proteomic analysis identified eight morphine-regulated proteins in the AI and their expression levels were reversely changed by HF-DBS. Continuous HF-DBS in the bilateral anterior insula prevents the relapse of morphine place preference after withdrawal, facilitates its extinction, blocks the reinstatement induced by morphine priming and reverses the expression of morphine-regulated proteins. Our findings suggest that manipulation of insular activity by DBS could be a potential intervention to treat substance use disorder, although future research is warranted.

Frontiers in psychiatry · 17 citationsread the source →

Use of electronic clinical documentation: time spent and team interactions.

Objective: To measure the time spent authoring and viewing documentation and to study patterns of usage in healthcare practice. Design: Audit logs for an electronic health record were used to calculate rates, and social network analysis was applied to ascertain usage patterns. Subjects comprised all care providers at an urban academic medical center who authored or viewed electronic documentation. Measurement: Rate and time of authoring and viewing clinical documentation, and associations among users were measured. Results: Users spent 20-103 min per day authoring notes and 7-56 min per day viewing notes, with physicians spending less than 90 min per day total. About 16% of attendings' notes, 8% of residents' notes, and 38% of nurses' notes went unread by other users, and, overall, 16% of notes were never read by anyone. Viewing of notes dropped quickly with the age of the note, but notes were read at a low but measurable rate, even after 2 years. Most healthcare teams (77%) included a nurse, an attending, and a resident, and those three users' groups were the first to write notes during an admission. Limitations The limitations were restriction to a single academic medical center and use of log files without direct observation. Conclusions: Care providers spend a significant amount of time viewing and authoring notes. Many notes are never read, and rates of usage vary significantly by author and viewer. While the rate of viewing a note drops quickly with its age, even after 2 years inpatient notes are still viewed.

Journal of the American Medical Informatics Association : JAMIA · 119 citationsread the source →

A comparison of contingency management and cognitive-behavioral approaches for stimulant-dependent individuals.

Aims: Previous research has reported that both contingency management (CM) and cognitive-behavioral therapy (CBT) are efficacious interventions for the treatment of stimulant abusers. The present study sought to directly compare the effectiveness of (CM) and (CBT) alone and in combination in reducing stimulant use. Design: Randomized clinical trial. Participants: Stimulant-dependent individuals (n = 171). Intervention: CM, CBT or combined CM and CBT, 16-week treatment conditions. CM condition participants received vouchers for stimulant-free urine samples. CBT condition participants attended three 90-minute group sessions each week. Measurements: Participants were interviewed at baseline and weeks 17, 26 and 52. Measures included psychiatric disorders and alcohol and drug use and concomitant social problems. Findings: CM procedures produced better retention and lower rates of stimulant use during the study period. Self-reported stimulant use was reduced from baseline levels at all follow-up points for all groups and urinalysis data did not differ between groups at follow-up. While CM produced robust evidence of efficacy during treatment application, CBT produced comparable longer-term outcomes. There was no evidence of an additive effect when the two treatments were combined. Conclusions: This study suggests that CM is an efficacious treatment for reducing stimulant use and is superior during treatment to a CBT approach. CM is useful in engaging substance abusers, retaining them in treatment and helping them achieve abstinence from stimulant use. CBT also reduces drug use from baseline levels and produces comparable outcomes on all measures at follow-up.

Addiction (Abingdon, England) · randomised controlled trial · 159 citationsread the source →

Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR).

Objectives: To determine the comparative effectiveness and cost-effectiveness of conventional ventilatory support versus extracorporeal membrane oxygenation (ECMO) for severe adult respiratory failure. Design: A multicentre, randomised controlled trial with two arms. Setting: The ECMO centre at Glenfield Hospital, Leicester, and approved conventional treatment centres and referring hospitals throughout the UK. Participants: Patients aged 18-65 years with severe, but potentially reversible, respiratory failure, defined as a Murray lung injury score > or = 3.0, or uncompensated hypercapnoea with a pH < 7.20 despite optimal conventional treatment. Interventions: Participants were randomised to conventional management (CM) or to consideration of ECMO. Main outcome measures: The primary outcome measure was death or severe disability at 6 months. Secondary outcomes included a range of hospital indices: duration of ventilation, use of high frequency/oscillation/jet ventilation, use of nitric oxide, prone positioning, use of steroids, length of intensive care unit stay, and length of hospital stay - and (for ECMO patients only) mode (venovenous/veno-arterial), duration of ECMO, blood flow and sweep flow. Results: A total of 180 patients (90 in each arm) were randomised from 68 centres. Three patients in the conventional arm did not give permission to be followed up. Of the 90 patients randomised to the ECMO arm, 68 received that treatment. ECMO was not given to three patients who died prior to transfer, two who died in transit, 16 who improved with conventional treatment given by the ECMO team and one who required amputation and could not therefore be heparinised. Ninety patients entered the CM (control) arm, three patients later withdrew and refused follow-up (meaning that they were alive), leaving 87 patients for whom primary outcome measures were available. CM consisted of any treatment deemed appropriate by the patient's intensivist with the exception of extracorporeal gas exchange. No CM patients received ECMO, although one received a form of experimental extracorporeal arteriovenous carbon dioxide removal support (a clear protocol violation). Fewer patients in the ECMO arm than in the CM arm had died or were severely disabled 6 months after randomisation, [33/90 (36.7%) versus 46/87 (52.9%) respectively]. This equated to one extra survivor for every six patients treated. Only one patient (in the CM arm) was known to be severely disabled at 6 months. Patients allocated to ECMO incurred average total costs of 73,979 pounds compared with 33,435 pounds for those undergoing CM (UK prices, 2005). A lifetime model predicted the cost per quality-adjusted life-year (QALY) of ECMO to be 19,252 pounds (95% confidence interval 7622 pounds to 59,200 pounds) at a discount rate of 3.5%. Lifetime QALYs gained were 10.75 for the ECMO group compared with 7.31 for the conventional group. Costs to patients and their relatives, including out of pocket and time costs, were higher for patients allocated to ECMO. Conclusions: Compared with CM, transferring adult patients with severe but potentially reversible respiratory failure to a single centre specialising in the treatment of severe respiratory failure for consideration of ECMO significantly increased survival without severe disability. Use of ECMO in this way is likely to be cost-effective when compared with other technologies currently competing for health resources. Trial registration: Current Controlled Trials ISRCTN47279827.

Health technology assessment (Winchester, England) · randomised controlled trial · 113 citationsread the source →

An evaluation of a brief motivational intervention among young ecstasy and cocaine users: no effect on substance and alcohol use outcomes.

Aims: To investigate whether a stimulant- and alcohol-focused brief motivational intervention induces positive behaviour change among young, regular users of MDMA ('ecstasy'), cocaine powder and crack cocaine. Design and measurements: A randomized trial of the intervention versus a control group who received written health risk information materials only. All participants completed a baseline self-assessment questionnaire before randomization. Outcome measures were self-reported period prevalence abstinence from ecstasy, cocaine powder and crack cocaine and the frequency and amount of stimulant and alcohol use in the previous 90 days, recorded at 6-month follow-up via self-completion questionnaire and personal interview. Participants and setting: A total of 342 adolescent and young adult stimulant users (aged 16-22 years) were recruited and 87% were followed-up. The intervention was delivered by a team of 12 agency youth drug workers and two researchers at five locations in Greater London and south-east England. Findings: There were no significant differences in abstinence for ecstasy, cocaine powder or crack cocaine use between the experimental and control groups. Contrasting follow-up with baseline self-reports, there were no between-group effects for changes in the frequency or amount of stimulant or alcohol use. Participant follow-up data suggested that the baseline assessment was a contributing factor in within-group behaviour change among experimental and control condition participants. Conclusions: Our brief motivational intervention was no more effective at inducing behaviour change than the provision of information alone. We hypothesize that research recruitment, baseline self-assessment and contact with study personnel are influences that induce positive reactive effects on stimulant use.

Addiction (Abingdon, England) · randomised controlled trial · 54 citationsread the source →

The effectiveness of a stress coping program based on mindfulness meditation on the stress, anxiety, and depression experienced by nursing students in Korea.

This study examined the effectiveness of a stress coping program based on mindfulness meditation on the stress, anxiety, and depression experienced by nursing students in Korea. A nonequivalent, control group, pre-posttest design was used. A convenience sample of 41 nursing students were randomly assigned to experimental (n=21) and control groups (n=20). Stress was measured with the PWI-SF (5-point) developed by Chang. Anxiety was measured with Spieberger's state anxiety inventory. Depression was measured with the Beck depression inventory. The experimental group attended 90-min sessions for eight weeks. No intervention was administered to the control group. Nine participants were excluded from the analysis because they did not complete the study due to personal circumstances, resulting in 16 participants in each group for the final analysis. Results for the two groups showed (1) a significant difference in stress scores (F=6.145, p=0.020), (2) a significant difference in anxiety scores (F=6.985, p=0.013), and (3) no significant difference in depression scores (t=1.986, p=0.056). A stress coping program based on mindfulness meditation was an effective intervention for nursing students to decrease their stress and anxiety, and could be used to manage stress in student nurses. In the future, long-term studies should be pursued to standardize and detail the program, with particular emphasis on studies to confirm the effects of the program in patients with diseases, such as cancer.

Nurse education today · randomised controlled trial · 108 citationsread the source →

Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report.

Background: Many patients with major depressive disorder (MDD) who experience full symptomatic remission after antidepressant treatment still have residual depressive symptoms. We describe the types and frequency of residual depressive symptoms and their relationship to subsequent depressive relapse after treatment with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: Participants in primary (n=18) and psychiatric (n=23) practice settings were openly treated with citalopram using measurement-based care for up to 14 weeks and follow-up for up to 1 year. We assessed 943 (32.8% of 2876) participants who met criteria for remission to determine the proportions with individual residual symptoms and any of the nine DSM-IV criterion symptom domains to define a major depressive episode. At each visit, the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16) and the self-report Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale were used to assessed depressive symptoms and side-effects respectively. Results: More than 90% of remitters had at least one residual depressive symptom (median=3). The most common were weight increase (71.3%) and mid-nocturnal insomnia (54.9%). The most common residual symptom domains were sleep disturbance (71.7%) and appetite/weight disturbance (35.9%). Those who remitted before 6 weeks had fewer residual symptoms at study exit than did later remitters. Residual sleep disturbance did not predict relapse during follow-up. Having a greater number of residual symptom domains was associated with a higher probability of relapse. Conclusions: Patients with remission of MDD after treatment with citalopram continue to experience selected residual depressive symptoms, which increase the risk of relapse.

Psychological medicine · randomised controlled trial · 339 citationsread the source →

The cost-effectiveness of smoking cessation support delivered by mobile phone text messaging: Txt2stop.

Background: The txt2stop trial has shown that mobile-phone-based smoking cessation support doubles biochemically validated quitting at 6 months. This study examines the cost-effectiveness of smoking cessation support delivered by mobile phone text messaging. Methods: The lifetime incremental costs and benefits of adding text-based support to current practice are estimated from a UK NHS perspective using a Markov model. The cost-effectiveness was measured in terms of cost per quitter, cost per life year gained and cost per QALY gained. As in previous studies, smokers are assumed to face a higher risk of experiencing the following five diseases: lung cancer, stroke, myocardial infarction, chronic obstructive pulmonary disease, and coronary heart disease (i.e. the main fatal or disabling, but by no means the only, adverse effects of prolonged smoking). The treatment costs and health state values associated with these diseases were identified from the literature. The analysis was based on the age and gender distribution observed in the txt2stop trial. Effectiveness and cost parameters were varied in deterministic sensitivity analyses, and a probabilistic sensitivity analysis was also performed. Findings: The cost of text-based support per 1,000 enrolled smokers is £16,120, which, given an estimated 58 additional quitters at 6 months, equates to £278 per quitter. However, when the future NHS costs saved (as a result of reduced smoking) are included, text-based support would be cost saving. It is estimated that 18 LYs are gained per 1,000 smokers (0.3 LYs per quitter) receiving text-based support, and 29 QALYs are gained (0.5 QALYs per quitter). The deterministic sensitivity analysis indicated that changes in individual model parameters did not alter the conclusion that this is a cost-effective intervention. Similarly, the probabilistic sensitivity analysis indicated a >90 % chance that the intervention will be cost saving. Interpretation: This study shows that under a wide variety of conditions, personalised smoking cessation advice and support by mobile phone message is both beneficial for health and cost saving to a health system.

The European journal of health economics : HEPAC : health economics in prevention and care · randomised controlled trial · 116 citationsread the source →

A brief dyadic group based psychoeducation program improves relapse rates in recently remitted bipolar disorder: a pilot randomised controlled trial.

Background: Various adjunctive psychotherapies assist in decreasing relapse and improving outcomes for people with bipolar disorder (BD). Psychoeducation programs involving patient-only or caregiver-only groups have demonstrated some efficacy. We tested in recently remitted BD if a combined group based psychoeducation program involving patient-companion dyads decreased relapse. Method: 58 recently remitted BD out-patients were randomised to receive either treatment as usual (TAU, n=31) or 12 x 90 minute psychoeducation sessions delivered weekly in a group program to the patient and companion (SIMSEP, n=27). After 12 weeks SIMSEP patients reverted to TAU and all patients were followed until week 60 or relapse. The primary outcome measure was relapse requiring hospital or intensive community intervention. Results: 45 patients completed the study. 29 patients remained well at week 60 (SIMSEP n=17, TAU n=12), whilst 16 had relapsed (SIMSEP n=3, TAU n=13). The SIMSEP group were less likely to relapse (Fisher's exact test p=0.013; OR=0.16; 95% CI 0.04-0.70) and had an 11 week longer time to relapse compared to the TAU group (chi-square (1)=8.48, p<0.01). At study completion SIMSEP compared to TAU patients had lower Young Mania Rating Scale scores (Mann-Whitney U=255, p<0.01). Limitations: The study was limited by a small sample size. Conclusion: A brief group psychoeducation program with recently remitted BD patients and their companions resulted in a decreased relapse rate, longer time to relapse, decreased manic symptoms and improved medication adherence suggesting utility in the adjunctive psychotherapeutic treatment of BD.

Journal of affective disorders · randomised controlled trial · 44 citationsread the source →

Sustained care intervention and postdischarge smoking cessation among hospitalized adults: a randomized clinical trial.

Importance: Health care systems need effective models to manage chronic diseases like tobacco dependence across transitions in care. Hospitalizations provide opportunities for smokers to quit, but research suggests that hospital-delivered interventions are effective only if treatment continues after discharge. Objective: To determine whether an intervention to sustain tobacco treatment after hospital discharge increases smoking cessation rates compared with standard care. Design, setting, and participants: A randomized clinical trial compared sustained care (a postdischarge tobacco cessation intervention) with standard care among 397 hospitalized daily smokers (mean age, 53 years; 48% were males; 81% were non-Hispanic whites) who wanted to quit smoking after discharge and received a tobacco dependence intervention in the hospital; 92% of eligible patients and 44% of screened patients enrolled. The study was conducted from August 2010 through November 2012 at Massachusetts General Hospital. Interventions: Sustained care participants received automated interactive voice response telephone calls and their choice of free smoking cessation medication (any type approved by the US Food and Drug Administration) for up to 90 days. The automated telephone calls promoted cessation, provided medication management, and triaged smokers for additional counseling. Standard care participants received recommendations for postdischarge pharmacotherapy and counseling. Main outcomes and measures: The primary outcome was biochemically confirmed past 7-day tobacco abstinence at 6-month follow-up after discharge from the hospital; secondary outcomes included self-reported tobacco abstinence. Results: Smokers randomly assigned to sustained care (n = 198) used more counseling and more pharmacotherapy at each follow-up assessment than those assigned to standard care (n = 199). Biochemically validated 7-day tobacco abstinence at 6 months was higher with sustained care (26%) than with standard care (15%) (relative risk [RR], 1.71 [95% CI, 1.14-2.56], P = .009; number needed to treat, 9.4 [95% CI, 5.4-35.5]). Using multiple imputation for missing outcomes, the RR for 7-day tobacco abstinence was 1.55 (95% CI, 1.03-2.21; P = .04). Sustained care also resulted in higher self-reported continuous abstinence rates for 6 months after discharge (27% vs 16% for standard care; RR, 1.70 [95% CI, 1.15-2.51]; P = .007). Conclusions and relevance: Among hospitalized adult smokers who wanted to quit smoking, a postdischarge intervention providing automated telephone calls and free medication resulted in higher rates of smoking cessation at 6 months compared with a standard recommendation to use counseling and medication after discharge. These findings, if replicated, suggest an approach to help achieve sustained smoking cessation after a hospital stay. Trial registration: clinicaltrials.gov Identifier: NCT01177176.

JAMA · randomised controlled trial · 110 citationsread the source →

High-intensity exercise prescription guided by heart rate variability in breast cancer patients: a study protocol for a randomized controlled trial.

Background: Breast cancer is a chronic disease with a large growth in its treatments, prognosis, improvements, side effects and rehabilitation therapies research. These advances have also highlighted the need to use physical exercise as a countermeasure to reduce the cardiotoxicity of pharmacological treatments, increase patients' strength and quality of life and improve body composition, physical condition and mental health. However, new investigations show the need for a closed exercise individualisation to produce higher physiological, physical and psychological benefits in remote exercise programs. To this end, the present study will use, in a novel way in this population, heart rate variability (HRV) as a measure for prescribing high-intensity training. Thus, the primary objective of this randomised clinical trial is to analyse the effects of a high-intensity exercise program daily guided by HRV, a preplanned moderate to high-intensity exercise intervention and a usual care group, in breast cancer patients after chemotherapy and radiotherapy treatments. Methods: For this purpose, a 16-week intervention will be carried out with 90 breast cancer patients distributed in 3 groups (a control group, a moderate to high-intensity preplanned exercise group and a high-intensity exercise group guided by HRV). Both physical exercise interventions will be developed remotely and supervised including strength and cardiovascular exercises. Physiological variables, such as cardiotoxicity, biomarkers, lipid profile, glucose, heart rate and blood pressure; physical measures like cardiorespiratory capacity, strength, flexibility, agility, balance and body composition; and psychosocial variables, as health-related quality of life, fatigue, functionality, self-esteem, movement fear, physical exercise level, anxiety and depression will be measure before, after the intervention and 3 and 6 months follow up. Discussion: Personalized high-intensity exercise could be a promising exercise intervention in contrast to moderate-intensity or usual care in breast cancer patients to reach higher clinical, physical and mental effects. In addition, the novelty of controlling HRV measures daily may reflect exercise effects and patients' adaptation in the preplanned exercise group and a new opportunity to adjust intensity. Moreover, findings may support the effectiveness and security of physical exercise remotely supervised, although with high-intensity exercise, to reach cardiotoxicity improvements and increase physical and psychosocial variables after breast cancer treatments. Trial registration ClinicalTrials.gov nº NCT05040867 ( https://clinicaltrials.gov/ct2/show/record/NCT05040867 ).

BMC sports science, medicine & rehabilitation · 10 citationsread the source →

Use of traditional complementary and alternative medicine for HIV patients in KwaZulu-Natal, South Africa.

Background: Traditional medicine use has been reported is common among individuals with moderate and advanced HIV disease. The aim of this cross-sectional study was to assess the use of Traditional Complementary and Alternative Medicine (TCAM) for HIV patients prior to initiating antiretroviral therapy in three public hospitals in KwaZulu-Natal, South Africa. Methods: Using systematic sampling, 618 HIV-positive patients were selected from outpatient departments from three hospitals and interviewed with a questionnaire. Results: TCAM was commonly used for HIV in the past six months by study participants (317, 51.3%) and herbal therapies alone (183, 29.6%). The use of micronutrients (42.9%) was excluded from TCAM since mostly vitamins were provided by the health facility. Herbal therapies were the most expensive, costing on average 128 Rand (US$16) per patient per month. Most participants (90%) indicated that their health care provider was not aware that they were taking herbal therapies for HIV (90%). Herbal therapies were mainly used for pain relief (87.1%) and spiritual practices or prayer for stress relief (77.6%). Multivariate logistic regression with use of herbs for HIV as the dependent variable identified being on a disability grant and fewer clinic visits to be associated with use of herbs, and TCAM use for HIV identified being on a disability grant, number of HIV symptoms and family members not contributing to main source of household income to be associated with TCAM use. Conclusion: Traditional herbal therapies and TCAM are commonly used by HIV treatment naïve outpatients of public health facilities in South Africa. Health care providers should routinely screen patients on TCAM use when initiating ART and also during follow-up and monitoring keeping in mind that these patients may not fully disclose other therapies.

BMC public health · 94 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 →

Long-term trends in child maltreatment in England and Wales, 1858-2016: an observational, time-series analysis.

Background: It is unclear whether child maltreatment is increasing or decreasing in England and Wales. More evidence is needed, from multiple sources and over longer periods of time, to explore trends in child maltreatment. We investigated whether the annual incidence of child maltreatment has changed over time, using official record data and time-series methods to establish long-term trends. Methods: In this observational time-series analysis, we used six data sources (Government records for child mortality, police-recorded child homicides, crimes against children, child protection, and children in care; and NSPCC data) to estimate the incidence of child maltreatment in England and Wales and examine long-term trends. We included nationally representative data that could estimate the incidence of child maltreatment for more than 25 years. Our primary outcomes were the number of victims (age <20 years) or perpetrators (age >16 years) of child maltreatment per 12-month period in England, including or excluding Wales. We fitted Poisson regression models with year as the exposure and the number of victims or perpetrators of child maltreatment as the outcome (adjusted for population age-structure and size). When a linear trend was not appropriate, we fitted generalised additive models with penalised splines to visualise trends. Findings: The incidence of child mortality by homicide or assault decreased by 90% (2·7 per 100 000 children) between 1858 and 2016 and the incidence of people guilty of child cruelty or neglect decreased by 83% (6·7 per 100 000 adults) between 1893 and 2016, whereas child protection registrations increased by 182% (328·7 per 100 000 children) between 1988 and 2016. Crimes against children and children entering care increased between 2000 and 2016. In 2016, 40 children died by homicide, with twice as many adolescent (15-19 years) deaths than infant (age <1 year) deaths. In 2016, 67 700 children were placed on the child protection register and neglect and emotional abuse were the most common reasons. Interpretation: Although long-term trends have decreased, child maltreatment remains a major public health problem in England and Wales. Further research is needed to establish whether adolescents are a particularly vulnerable age group and whether neglect and emotional abuse are increasing. Future child protection policies and practices should respond to these areas of growing need. Funding: Andrew W Mellon Foundation and Clarendon through The Oxford Research Centre in the Humanities, Oxford.

The Lancet. Public health · cohort or longitudinal · 22 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 →

Does child maltreatment predict alcohol use disorders in young adulthood? A cohort study of linked notifications and survey data.

Background and aims: Most studies of the association between child maltreatment and subsequent problem alcohol use are retrospective. We studied the association of prospectively substantiated child maltreatment with problem alcohol use in adulthood. Design: We used a prospective cohort record linkage correlational design using data from a statutory child protection agency of prospectively substantiated child maltreatment linked to a birth cohort from a major metropolitan maternity hospital. Setting: The Mater-University of Queensland Study of Pregnancy in Brisbane, Australia. Participants: Of the 3762 young people at the 21-year follow-up, 169 (4.5%) had a history of substantiated maltreatment by 16 years. This was most commonly emotional abuse (n = 90). Measurements: The main outcome was heavy alcohol use at the 21-year follow-up, defined as four or more standard drinks per day. Secondary outcomes were life-time and 12-month diagnoses of alcohol use disorders in  2531 participants who completed the Composite International Diagnostic Interview-auto (CIDI-auto) version. Predictor variables were physical, sexual and emotional abuse, as well as neglect. Findings: At follow-up, 407 of the 3762 participants reported heavy alcohol use (10.8%). On adjusted analyses, participants who had experienced emotional abuse were significantly more likely to report heavy alcohol use at the time of interview (adjusted odds ratio = 1.856; 95% confidence interval = 1.038-3.319; P = 0.037). Neglect was associated with a life-time CIDI diagnosis of an alcohol use disorder. Other types of child maltreatment were not significantly associated with any of the outcomes. Conclusions: Prospectively identified experience of childhood emotional abuse and neglect appears to be positively associated with problem alcohol use at age 21.

Addiction (Abingdon, England) · 27 citationsread the source →

Gender and ethnic differences in arterial compliance in patients with intermittent claudication.

Objective: To assess the gender and ethnic differences in arterial compliance in patients with intermittent claudication. Methods: A total of 114 patients participated, including 38 Caucasian men, 32 Caucasian women, 16 African American men, and 28 African American women. Patients were assessed on large artery elasticity index (LAEI), small artery elasticity index (SAEI), age, weight, body mass index, ankle-brachial index (ABI), smoking status, and metabolic syndrome components. Results: Group differences were found for LAEI (P = .042), SAEI (P = .019), body mass index (P = .020), prevalence of elevated fasting glucose (P = .001), and prevalence of abdominal obesity (P = .025). Significant covariates for LAEI included age (P = .0002) and elevated triglycerides (P = .0719). LAEI (units = 10 mL x mm Hg) adjusted for age and triglycerides was 39% lower (P = .0005) in African Americans (11.4 +/- .90; mean +/- SE) than in Caucasians (15.8 +/- 0.72), whereas no significant difference (P = .7904) existed between men (13.8 +/- 0.81) and women (13.5 +/- 0.79). Significant covariates for SAEI included age (P = .0001), abdominal obesity (P = .0030), and elevated blood pressure (P = .0067). SAEI (units = 100 mL x mm Hg) adjusted for age, abdominal obesity, and elevated blood pressure was 32% lower (P = .0007) in African-Americans (2.8 +/- 0.3) than in Caucasians 4.1 +/- 0.2), and was 18% lower (P = .0442) in women (3.1 +/- 0.2) than in men (3.8 +/- 0.2). Conclusion: African American patients with intermittent claudication have more impaired macrovascular and microvascular function than Caucasian patients, and women have more impaired microvascular function than men. These ethnic and gender differences in arterial compliance are evident even though ABI was similar among groups, suggesting that arterial compliance provides unique information to quantify vascular impairment in patients with intermittent claudication.

Journal of vascular surgery · cohort or longitudinal · 34 citationsread the source →

Sleep duration and health in young adults.

Background: Both long and short sleep durations have been associated with negative health outcomes in middle-aged and older adults. This study assessed the relationship between sleep duration and self-rated health in young adults. Methods: Using anonymous questionnaires, data were collected from 17 465 university students aged 17 to 30 years who were taking non-health-related courses at 27 universities in 24 countries. The response rate was greater than 90%. Sleep duration was measured by self-report; the health outcome was self-rated health; and age, sex, socioeconomic background, smoking, alcohol consumption, body mass index, physical activity, depression (Beck Depression Inventory), recent use of health services, and country of origin were included as covariates. Results: Sixty-three percent of respondents slept for 7 to 8 hours; 21% were short sleepers (6%, <6 hours; 15%, 6-7 hours); and 16% were long sleepers (10%, 8-10 hours; 6%, >10 hours). Compared with the reference category (7-8 hours), the adjusted odds ratio of poor health was 1.56 (95% confidence interval [CI], 1.22-1.99) for respondents sleeping 6 to 7 hours and 1.99 (95% CI, 1.31-3.03) for those sleeping less than 6 hours. The same significant pattern was seen when the results were analyzed separately by sex. When respondents from Japan, Korea, and Thailand (characterized by relatively short sleep durations) were excluded, the adjusted odds ratios were 1.33 (95% CI 1.03-1.73) and 1.62 (95% CI, 1.06-2.48) for those sleeping 6 to 7 hours and less than 6 hours, respectively. There were no significant associations between self-rated health and long sleep duration. Conclusion: Our data suggest that short sleep may be more of a concern than long sleep in young adults.

Archives of internal medicine · cohort or longitudinal · 255 citationsread the source →

Perceptions and attitudes toward sexual norms: key insights from the International Society of Sexual Medicine Young Researchers Committee survey.

Background: Sexuality is a complex aspect of human life, and the perception of sexual normality may vary across genders, religious beliefs, and other aspects. Aim: To report preliminary findings of a pilot survey on sexual attitudes, behaviors, and individual perception of sexual normality in a contemporary cross-cultural scenario. Methods: A 48-item survey was developed by the Young Researchers Committee (YRC) on behalf of the International Society for Sexual Medicine (ISSM) to collect data on cross-cultural perceptions and attitudes toward sexual norms. The survey consisted of questions related to sexual attraction, behavior, identity, orientation, and subjective perception of sexual normality. Data were collected via five translated versions across five countries (Italy, United States, Brazil, Spain, and Japan) and analyzed to investigate how cultural norms, personal experiences, and social expectations shape individuals' views on sexual normality. Outcomes: The primary outcome was to assess gender-based differences in sexual behaviors, satisfaction, religious beliefs' impact, pornography use, and anatomical perceptions. Results: This pilot study included 3423 respondents [63.5% female, 36.2% male; median (IQR) age 39 (30.00, 50.00) years]. Of all, active sexual life was reported by 83.3% participants, with 58.8% expressing satisfaction with their sex life. Heterosexual orientation was predominant (90%), with significant differences in distribution between genders in terms of sexual orientation (P < .001). Religious influence on sexual activity was reported by 18.6% of respondents, more commonly among females (20.2% vs 15.8%, P < .001). Median ages of first sexual intercourse and pornography exposure were 18 (16.00, 19.00) and 14 (12.00, 16.00) years, respectively, with females reporting older ages for both experiences (P < .001). Regarding perceptions of normality, most respondents (55.6%) believed first sexual intercourse typically occurs between 16 and 19 years. The perception of normal erect penile length differed between genders, with men more likely to report greater values (>16.1 cm: 13.1% vs 6.2%, P < .01). Gender differences were also observed in orgasm frequency, with fewer females reporting orgasm during >80% of sexual encounters (38.2% vs 66.5%, P < .001). Clinical implications: Our findings shape the development of sexual education, fostering inclusivity, equity, and sexual health for overall satisfaction. Strengths and limitations: Possible biases associated with different modalities throughout data collections and with different linguistic and cultural weights given the cross-sectional nature of the pilot survey. Conclusion: Current preliminary findings from the pilot survey developed by the ISSM YRC start shedding lights on perceptions and attitudes toward sexual norms, and gender differences in sexual behaviors and satisfaction.

Sexual medicine · reviewread the source →

Nature-based outdoor activities for mental and physical health: Systematic review and meta-analysis.

Mental health problems are associated with lower quality of life, increased unscheduled care, high economic and social cost, and increased mortality. Nature-based interventions (NBIs) that support people to engage with nature in a structured way are asset-based solutions to improve mental health for community based adults. However, it is unclear which NBIs are most effective, or what format and dose is most efficacious. We systematically reviewed the controlled and uncontrolled evidence for outdoor NBIs. The protocol was registered at PROSPERO (CRD42020163103). Studies that included adults (aged ≥18 years) in community-based settings with or without mental and/or physical health problems were eligible for inclusion. Eligible interventions were structured outdoor activities in green and/or blue space for health and wellbeing. We searched ASSIA, CENTRAL, Embase, Greenfile, MEDLINE, PsycINFO, and Web of Science in October 2019; the search was updated in September 2020. We screened 14,321 records and included 50 studies. Sixteen studies were randomised controlled trials (RCTs); 18 were controlled studies; and 16 were uncontrolled before and after studies. Risk of bias for RCTs was low to moderate; and moderate to high for controlled and uncontrolled studies. Random effects meta-analysis of RCTs showed that NBIs were effective for improving depressive mood -0.64 (95% CI: 1.05 to -0.23), reducing anxiety -0.94 (95% CI: 0.94 to -0.01), improving positive affect 0.95 (95% CI: 0.59 to 1.31), and reducing negative affect -0.52 (95% CI: 0.77 to -0.26). Results from controlled and uncontrolled studies largely reflected findings from RCTs. There was less evidence that NBIs improved physical health. The most effective interventions were offered for between 8 and 12 weeks, and the optimal dose ranged from 20 to 90 min. NBIs, specifically gardening, green exercise and nature-based therapy, are effective for improving mental health outcomes in adults, including those with pre-existing mental health problems.

SSM - population health · review · 193 citationsread the source →

First trimester preeclampsia screening and prediction.

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. Early-onset disease requiring preterm delivery is associated with a higher risk of complications in both mothers and babies. Evidence suggests that the administration of low-dose aspirin initiated before 16 weeks' gestation significantly reduces the rate of preterm preeclampsia. Therefore, it is important to identify pregnant women at risk of developing preeclampsia during the first trimester of pregnancy, thus allowing timely therapeutic intervention. Several professional organizations such as the American College of Obstetricians and Gynecologists (ACOG) and National Institute for Health and Care Excellence (NICE) have proposed screening for preeclampsia based on maternal risk factors. The approach recommended by ACOG and NICE essentially treats each risk factor as a separate screening test with additive detection rate and screen-positive rate. Evidence has shown that preeclampsia screening based on the NICE and ACOG approach has suboptimal performance, as the NICE recommendation only achieves detection rates of 41% and 34%, with a 10% false-positive rate, for preterm and term preeclampsia, respectively. Screening based on the 2013 ACOG recommendation can only achieve detection rates of 5% and 2% for preterm and term preeclampsia, respectively, with a 0.2% false-positive rate. Various first trimester prediction models have been developed. Most of them have not undergone or failed external validation. However, it is worthy of note that the Fetal Medicine Foundation (FMF) first trimester prediction model (namely the triple test), which consists of a combination of maternal factors and measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has undergone successful internal and external validation. The FMF triple test has detection rates of 90% and 75% for the prediction of early and preterm preeclampsia, respectively, with a 10% false-positive rate. Such performance of screening is superior to that of the traditional method by maternal risk factors alone. The use of the FMF prediction model, followed by the administration of low-dose aspirin, has been shown to reduce the rate of preterm preeclampsia by 62%. The number needed to screen to prevent 1 case of preterm preeclampsia by the FMF triple test is 250. The key to maintaining optimal screening performance is to establish standardized protocols for biomarker measurements and regular biomarker quality assessment, as inaccurate measurement can affect screening performance. Tools frequently used to assess quality control include the cumulative sum and target plot. Cumulative sum is a sensitive method to detect small shifts over time, and point of shift can be easily identified. Target plot is a tool to evaluate deviation from the expected multiple of median and the expected median of standard deviation. Target plot is easy to interpret and visualize. However, it is insensitive to detecting small deviations. Adherence to well-defined protocols for the measurements of mean arterial pressure, uterine artery pulsatility index, and placental growth factor is required. This article summarizes the existing literature on the different methods, recommendations by professional organizations, quality assessment of different components of risk assessment, and clinical implementation of the first trimester screening for preeclampsia.

American journal of obstetrics and gynecology · review · 212 citationsread the source →

Psychological distress, depression, anxiety, and life satisfaction following COVID-19 infection: evidence from 11 UK longitudinal population studies.

Background: Evidence on associations between COVID-19 illness and mental health is mixed. We aimed to examine whether COVID-19 is associated with deterioration in mental health while considering pre-pandemic mental health, time since infection, subgroup differences, and confirmation of infection via self-reported test and serology data. Methods: We obtained data from 11 UK longitudinal studies with repeated measures of mental health (psychological distress, depression, anxiety, and life satisfaction; mental health scales were standardised within each study across time) and COVID-19 status between April, 2020, and April, 2021. We included participants with information available on at least one mental health outcome measure and self-reported COVID-19 status (suspected or test-confirmed) during the pandemic, and a subset with serology-confirmed COVID-19. Furthermore, only participants who had available data on a minimum set of covariates, including age, sex, and pre-pandemic mental health were included. We investigated associations between having ever had COVID-19 and mental health outcomes using generalised estimating equations. We examined whether associations varied by age, sex, ethnicity, education, and pre-pandemic mental health, whether the strength of the association varied according to time since infection, and whether associations differed between self-reported versus confirmed (by test or serology) infection. Findings: Between 21 Dec, 2021, and July 11, 2022, we analysed data from 54 442 participants (ranging from a minimum age of 16 years in one study to a maximum category of 90 years and older in another; including 33 200 [61·0%] women and 21 242 [39·0%] men) from 11 longitudinal UK studies. Of 40 819 participants with available ethnicity data, 36 802 (90·2%) were White. Pooled estimates of standardised differences in outcomes suggested associations between COVID-19 and subsequent psychological distress (0·10 [95% CI 0·06 to 0·13], I2=42·8%), depression (0·08 [0·05 to 0·10], I2=20·8%), anxiety (0·08 [0·05 to 0·10], I2=0·0%), and lower life satisfaction (-0·06 [-0·08 to -0·04], I2=29·2%). We found no evidence of interactions between COVID-19 and sex, education, ethnicity, or pre-pandemic mental health. Associations did not vary substantially between time since infection of less than 4 weeks, 4-12 weeks, and more than 12 weeks, and were present in all age groups, with some evidence of stronger effects in those aged 50 years and older. Participants who self-reported COVID-19 but had negative serology had worse mental health outcomes for all measures than those without COVID-19 based on serology and self-report. Participants who had positive serology but did not self-report COVID-19 did not show association with mental health outcomes. Interpretation: Self-reporting COVID-19 was longitudinally associated with deterioration in mental health and life satisfaction. Our findings emphasise the need for greater post-infection mental health service provision, given the substantial prevalence of COVID-19 in the UK and worldwide. Funding: UK Medical Research Council and UK National Institute for Health and Care Research.

The lancet. Psychiatry · 52 citationsread the source →

Understanding patterns of food insecurity and family well-being amid the COVID-19 pandemic using daily surveys.

This paper investigates economic and psychological hardship during the COVID-19 pandemic among a diverse sample (61% Latinx; 16% White; 9% Black; 14% mixed/other race) of socioeconomically disadvantaged parents (90% mothers; mean age = 35 years) and their elementary school-aged children (ages 4-11; 49% female) in rural Pennsylvania (N = 272). Families participating in a local food assistance program reported on food insecurity (FI) and parent and child mood and behavior daily from January to May 2020. Longitudinal models revealed that FI, negative parent and child mood, and child misbehavior significantly increased when schools closed; only FI and parent depression later decreased. FI decreased most among those who received the local food assistance program; Supplemental Nutrition Assistance Program receipt uniquely predicted decreases in child FI.

Child development · 26 citationsread the source →

How Do Corticosteroids Work in Asthma?

Reviews2 September 2003How Do Corticosteroids Work in Asthma?Peter J. Barnes, DM, DSc and Ian M. Adcock, PhDPeter J. Barnes, DM, DScFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this author and Ian M. Adcock, PhDFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-5_Part_1-200309020-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAsthma is the most common chronic disease in westernized countries. Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants. This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness. Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms. Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular ...References1. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62. [PMID: 11172168] CrossrefMedlineGoogle Scholar2. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515-96. [PMID: 9860804] MedlineGoogle Scholar3. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J. 1998;12:221-34. [PMID: 9701442] CrossrefMedlineGoogle Scholar4. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-B, in asthma. 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A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654-9. [PMID: 8805670] MedlineGoogle Scholar57. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109:649-57. [PMID: 11941315] CrossrefMedlineGoogle Scholar58. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, . Increased glucocorticoid receptor in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600-4. [PMID: 10228133] CrossrefMedlineGoogle Scholar59. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, . Glucocorticoid receptor and in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7-13. [PMID: 10903212] CrossrefMedlineGoogle Scholar60. 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Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155:542-8. [PMID: 9032192] CrossrefMedlineGoogle Scholar64. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635-9. [PMID: 10556133] CrossrefMedlineGoogle Scholar65. Nightingale JA, Rogers DF, Fan Chung K, Barnes PJ. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med. 2000;161:479-86. [PMID: 10673189] CrossrefMedlineGoogle Scholar66. Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, . Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:24-31. [PMID: 12406856] CrossrefMedlineGoogle Scholar67. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15:1110-2. [PMID: 11292684] CrossrefMedlineGoogle Scholar68. Ito K, Watanabe S, Kharitonov S, Hanazawa T, Adcock IM, Barnes PJ. Histone deacetylase activity and gene expression in COPD patients [Abstract]. Eur Respir J. 2001;18:316S. MedlineGoogle Scholar69. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175-7. [PMID: 10988150] CrossrefMedlineGoogle Scholar70. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157:S1-53. [PMID: 9520807] CrossrefMedlineGoogle Scholar71. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, . A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J. 1994;13:4087-95. [PMID: 8076604] CrossrefMedlineGoogle Scholar72. Adcock IM, Nasuhara Y, Stevens DA, Barnes PJ. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-B and lack of I-B involvement. Br J Pharmacol. 1999;127:1003-11. [PMID: 10433509] CrossrefMedlineGoogle Scholar73. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, . Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245-55. [PMID: 9259316] CrossrefMedlineGoogle Scholar74. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, . Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol. 2001;166:1975-82. [PMID: 11160246] CrossrefMedlineGoogle Scholar75. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93-105. [PMID: 12151000] CrossrefMedlineGoogle Scholar76. Barnes PJ. New treatments for COPD. Nat Rev Drug Discov. 2002;1:437-46. [PMID: 12119745] CrossrefMedlineGoogle Scholar77. Ito K, Lim S, Chung KF, Barnes PJ, Adcock IM. Theophylline enhances histone deacetylase activity and restores glucocorticoid function during oxidative stress [Abstract]. Am J Respir Crit Care Med. 2002;165:A625. Google Scholar Author, Article, and Disclosure InformationAffiliations: From National Heart and Lung Institute, Imperial College, London, United Kingdom. Disclosures:Grants received: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca); Grants pending: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca).Corresponding Author: P.J. Barnes, DM, DSc, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom; e-mail, p.j.[email protected]ac.uk. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseasesLipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in ToadsThe central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to interventionAsthma and COVID-19: Emphasis on Adequate of as of and as a Effect of the resistance in asthma: and molecular effects of on a of allergic between and and gene expression of glucocorticoid and receptors from the for of human respiratory with glucocorticoids in the treatment of asthma: of the oral corticosteroids and persistent in from the asthma to bronchial asthma as for A of of Melatonin and Glucocorticoid with in the a between Melatonin and of in Steroid Drug by of proteins during the Efficacy of to in a of corticosteroids in asthma: the between and the novel mode of action of the Association and 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of in obstructive lung disease through and airway and as novel for asthma and in resistance in inflammatory T cells control lung inflammation during by between and lung function in response to inhaled corticosteroid in patients with of HDAC2 in the of to in asthma: A rationale for corticosteroids as in as novel for Cell or and effect of and alone or in combination in primary human bronchial is a in a of pulmonary strategies for and corticosteroid the of airway smooth muscle in of chronic Glucocorticoid activity is increased in asthmatic airways by inhaled of the of in A of and receptor expression in of asthmatic and and of transcription of T cells in asthma: by allergic and oral and Clinical and Therapeutic and their receptors as for the treatment of expression asthma of of Increased and of corticosteroids on the of in steroids are associated with lung function in with asthma with for of the of in a and airways for of glucocorticoid to treatment and Effects of Corticosteroids in Corticosteroids in the of glucocorticoid actions in airway smooth muscle through allergic asthma in effects of in a of factor and glucocorticoid as an Inflammatory corticosteroids control role of MAPK in human cell and of in Glucocorticoid Steroid in The to on glucocorticoid action and of and Dexamethasone on Lung and Transcription Expression in of with Glucocorticoid and of transduction for the treatment of airway for of Histone in in and glucocorticoid receptor proteins in human by the and Effects of be steroids for of with in the of of smoking on the treatment response in patients with suppress transcriptional up-regulation of receptors in a in vitro of chronic airway protein and of airway of smoking on the treatment response in patients with between the of by a 1 and Regulation of Expression by An in Inflammatory Lung Regulation of Histone and of the Inflammatory for New of the of Effects of Corticosteroids in of the of for in Corticosteroids for of resistance in chronic 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Annals of Internal Medicine · review · 370 citationsread the source →

Consensus Statement on 21-Hydroxylase Deficiency from The Lawson Wilkins Pediatric Endocrine Society and The European Society for Paediatric Endocrinology

Despite over 50 yr of experience with steroid replacement therapy, the management of congenital adrenal hyperplasia (CAH) remains difficult, and clinical practice varies substantially throughout the world. To consider the evidence for best practice, to formulate management guidelines, and to consider innovative therapies, The Lawson Wilkins Pediatric Endocrine Society (LWPES) and The European Society for Pediatric Endocrinology (ESPE) convened a meeting in Gloucester, MA, March 14–17, 2002. The 40 participating physicians, psychologists, scientists, and surgeons from 12 countries on 4 continents agreed with the following consensus statement; this statement is concerned exclusively with CAH caused by 21-hydroxylase deficiency and does not address the other, rarer forms of CAH. The newborn female with CAH and ambiguous external genitalia requires urgent expert medical attention. The ambiguity is highly distressing to the family; therefore, immediate comprehensive evaluation is needed by referral to, or a visit by, a pediatric endocrinologist. An important goal is to ensure that the parents develop a positive relationship with their child. A well-organized multidisciplinary team (including specialists in pediatric endocrinology, psychosocial services, pediatric surgery/urology, and genetics) is essential for the diagnosis and management of the infant with ambiguous genitalia. It is important that the coordinator of the team has experience in the long-term care of the patient with CAH and provides a consistent message to the parents. Every newborn with ambiguous genitalia, a suspected diagnosis of CAH, or an abnormal result in a newborn screen for 17-hydroxyprogesterone (17OHP) should be evaluated by a pediatric endocrinologist. The evaluation of an infant with ambiguous genitalia includes a complete history, a physical examination, a reliable ultrasound investigation of the internal genitalia and adrenals, karyotype or fluorescence in situ hybridization for sex chromosome material, and a rapid, reliable plasma or serum measurement of 17OHP. Premature newborns may need serial measurements of 17OHP to differentiate false positive results from affected infants with CAH. Neonatal mass screening for 21-hydroxylase deficiency identifies both male and female affected infants, prevents incorrect sex assignment, and decreases mortality and morbidity (1–4). Therefore, newborn screening for CAH is beneficial and is recommended. Newborn screening is sufficiently specific and sensitive to detect almost all infants with classical CAH and some infants with nonclassical CAH (NCCAH). Sampling of blood spots should be performed, ideally between 48 and 72 h of age, and sent to the screening laboratory without delay. At present, direct binding assays for blood-spot 17OHP are the only practical method for screening. Each screening laboratory needs to establish validated cut-off levels related to gestational age and birth-weight, because 17OHP levels decline with increasing gestational age. Only laboratories with excellent internal and external quality control, demonstrated accuracy, and a rapid turn-around time on a large number of samples should be used. The laboratory should report immediately any abnormal result to the physician responsible for the patient. A reliable CAH screening program requires both clinical evaluation and laboratory investigation for diagnostic confirmation. A positive screening result needs to be confirmed either by a validated 17OHP measurement of a second serum/plasma sample, a urine sample for a steroid profile, or analysis of the CYP21 gene. Newborn screening, using 17OHP, may detect other forms of CAH. In uncertain cases, additional specific tests are required. Measurements of androstenedione, aldosterone, cortisol, and testosterone by direct immunoassays are of limited value for diagnosis in the newborn. Molecular genetic analysis is not essential for the diagnosis but may be helpful to confirm the basis of the defect, to aid in genetic counseling, and to establish the diagnosis in uncertain cases. Ten mutations account for 90–95% of the affected alleles, but molecular genetic analysis is complicated by multiple copies of the genes and the possibility of multiple mutations on one allele (5, 6). The clinical features may not correlate with the genetic mutation in a small percentage of cases. Parental DNA samples are essential to segregate alleles. Salt wasters may not be apparent in the first days, or even weeks, after birth by electrolyte measurements. Salt wasters may be differentiated from simple virilizers by serial serum/plasma and/or urine electrolytes, plasma renin activity (PRA) or direct renin, and the results of CYP21 molecular analysis. Prenatal treatment has been advocated for fetuses at risk for classic CAH but is not appropriate for nonclassic CAH. The appropriateness, ethics, and outcomes of the prenatal treatment of CAH with dexamethasone remain controversial (7, 8). However, based on more than 200 fetuses treated to term and more than 1000 partially treated fetuses, it is clear that very early institution of treatment ameliorates the genital virilization in all affected females and completely eliminates it in more than 85% (7, 9). Variations in outcome may be attributable to starting treatment late, interruption of treatment, and individual differences in dexamethasone metabolism and androgen sensitivity. No consistent untoward effects have been reported, and birth weight is not reduced. However, few treated fetuses have reached adulthood, and long-term prospective studies have not been done. Thus, all agree that the results to date are very good, but long-term safety has not yet been proven in patients treated to term or in the 7 of 8 fetuses in whom treatment is stopped because they are male or unaffected. Treated mothers experience greater weight gain, edema, and striae than untreated mothers, but present data do not show increased risk of hypertension or gestational diabetes (9). Feto/maternal glucocorticoid physiology and pharmacology are poorly understood. Available data indicate that human fetal cortisol levels are low, approximately 20 nm or 0.7 μg/dl (10); the administered dose of dexamethasone may result in fetal concentrations of glucocorticoid that greatly exceed normal levels. However, the data on serum cortisol values in the fetus are scanty, and fetal serum dexamethasone values have not been reported. Several recent reports have raised concerns about the use of short-term, very-high-dose glucocorticoids in late pregnancy or in premature infants (11). Animal studies have reported numerous complications from long-term, high-dose treatment of pregnant rodents and primates. Treatment of pregnant rats with 20 μg/kg·d dexamethasone was associated with decreased birth weight and adult hypertension, whereas similar treatment of pregnant sheep caused no apparent complications. However, the relevance of any of these studies to human physiology is not known. Components of a prenatal treatment program include prepregnancy genetic counseling and genotyping of the proband and parents, followed by diagnosis on fetal DNA obtained by chorionic villous biopsy. Fetal sex should be determined by Y chromosome PCR or karyotype. Allele-specific PCR should identify at least 90% of affected alleles. This number can be increased to nearly 100% with microsatellite analysis; Southern blotting; and, occasionally, DNA sequencing (5, 6). Competent core laboratories should study large numbers of samples. Inclusion criteria for prenatal treatment include: 1) a previously affected sibling or first-degree relative with known mutations causing classic CAH, proven by DNA analysis; 2) reasonable expectation that the father is the same as the proband’s; 3) availability of rapid, high-quality genetic analysis; 4) therapy started less than 9 wk after the last menstrual period; 5) no plans for therapeutic abortion; and 6) reasonable expectation of patient compliance. The optimal dosage and timing is 20 μg/kg maternal body weight·d, in three divided doses, starting as soon as pregnancy is confirmed, and no later than 9 wk after the last menstrual period. Treatment is continued to term in the affected female fetus and discontinued in all other fetuses. Maternal blood pressure (BP), weight, glycosuria, HbA1C plasma cortisol, dehydroepiandrosterone sulfate, and androstenedione should be measured initially and then every 2 months, adding plasma or urinary estriol after 15–20 wk of gestation. There is substantial difference of opinion concerning whether prenatal treatment of CAH is a research endeavor. However, all are agreed that this requires a team consisting of a pediatric endocrinologist, an expert in high-risk obstetrics, a genetic counselor, and a reliable molecular genetics laboratory. It is not the “standard of care” for obstetricians in the community. The treatment of 7 out of 8 fetuses who cannot be helped by prenatal treatment creates an ethical dilemma for which there is no clear answer, and parents should be aware of this. We believe that this specialized and demanding therapy should be undertaken by designated teams using nationally or multinationally approved protocols, subject to institutional review boards or ethics committees in recognized centers. Written informed consent must be obtained after the balanced review of the risks and benefits of treatment. Families and clinicians should be obliged to undertake prospective follow-up of prenatally treated children whether they have CAH or not. The data should be entered into a central database audited by an independent safety committee. Study protocols should consider all psychological/behavioral and somatic effects of excess prenatal glucocorticoids and androgens that have been observed in animal experiments or in human studies. Long-term follow-up into late adolescence is mandatory. Relevant control populations should be identified. These studies should also include the partially treated fetuses. Funding agencies, such as the National Institutes of Health or the European Commission, should be encouraged to support such long-term studies. The decision about surgery should be made by the parents, together with the clinical team, after complete disclosure of all relevant clinical information and all available options have been discussed and after informed consent has been obtained. The goals of surgery are: 1) genital appearance compatible with gender; 2) unobstructed urinary emptying without incontinence or infections; and 3) good adult sexual and reproductive function. Once a decision has been made to raise a newborn as female, surgery for those with virilized genitalia caused by CAH is recommended when the patient has a high proximal junction between the vagina and urethra (12, 13). Surgery on infants with ambiguous genitalia requires a high degree of expertise and should only be performed in centers with significant experience. Based on recent clinical experience, the recommended time for surgery is at age 2–6 months; although, at present, this is not universal practice. It is important to note that surgery at this stage is technically easier than at later stages. When the degree of virilization is less (minimal clitoromegaly and the junction between the vagina and urethra near the perineum), surgery may not be necessary. In such cases, the decision to operate should be based on appropriate contrast studies of the urinary tract and examination under anesthesia, with cystoscopy. Surgery to reduce clitoral size requires careful consideration. Total removal of the clitoris should never be performed. If clitoral reduction is elected, it is crucial to preserve the neurovascular bundle, the glans, and the preputial skin related to the glans (14, 15). The early operation should be a one-stage complete repair using the newest techniques of vaginoplasty, clitoral, and labial surgery (12–14, 16) and should be carried out at a center with experience of at least 3–4 cases/yr. Revision vaginoplasty is often required at adolescence, and the timing should be decided with the patient and family. Patients who wish to consider further procedures should be treated by a surgeon experienced in the current techniques. Surgery between the age of 12 months and adolescence is not recommended in the absence of complications causing medical problems. Vaginal dilatations are contraindicated at this stage, although this procedure is often useful in adolescence and in adulthood. Repeated genital examinations should be minimized. Genital photography should be discouraged and only be done with parental consent and, except in infancy, performed only under anesthesia. At each designated center, one surgical team should be responsible for all surgery involving ambiguous genitalia. There should be close cooperation between centers to broaden experience, to audit results, and to allow adequate evaluation of outcomes. We acknowledge that there are concerns about early surgery. However, surgical techniques have improved. We urge caution in judging outcome from outdated procedures. Systematic studies are needed to evaluate ultimate function for all girls undergoing surgery. It is recognized that 46,XX children with significant virilization may present at a later age. Consideration for sex reassignment must be undertaken only after thorough psychological evaluation of patient and family. Surgery appropriate to gender assignment should be undertaken after a period of endocrine treatment. Females with CAH show behavioral masculinization, most pronounced in gender role behavior, less so in sexual orientation, and rarely in gender identity (17–19). Even in females with psychosexual problems, general psychological adjustment seems to be similar to that of females without CAH. Currently, there is insufficient evidence to support rearing a 46,XX infant at Prader stage 5 as male. Whereas studies of women whose surgery was performed 20–30 yr ago indicate a range of psychosexual difficulties, there is reason for optimism that outcome will be better with current surgical and medical treatment. We recognize a need for greater availability of professional psychological services and support groups for patients and families. Decisions concerning sex assignment and associated genital surgery must consider the culture in which a child and her/his family are embedded. As the pace of societal change, including the flexibility of gender role, increases, more frequent review of management policies and long-term outcomes is important. Recognizing that treatment does not mimic physiologic secretion, the goal is to replace deficient steroids while minimizing adrenal sex hormone and glucocorticoid excess, preventing virilization, optimizing growth, and protecting potential fertility. Outcome is not always ideal. Consensus is based on clinical experience. During infancy, initial reduction of markedly elevated adrenal sex hormones may require up to 25 mg hydrocortisone (HC)/m2·d, but typical dosing is 10–15 mg/m2·d divided three times daily. HC oral suspension is not recommended (20); divided or of HC should be in requires to cortisol for HC is the of first doses, infancy, may and other Therefore, complete adrenal should be data to or Whereas HC is and glucocorticoids may be an at or near the of and need to be daily. may be because this is the The dose should be approximately one the dose of The dosage of dexamethasone is daily. of these more glucocorticoids should include in to weight, and other clinical and laboratory These steroids have with In children with age, such as in with CAH, of therapy may central treatment with a classic CAH patients should be treated with at diagnosis in the newborn period. in early range from whereas typical are on the therapy will reduce and levels and the dosage of glucocorticoid required. The need for should be based on and are often needed in infancy, at in The method of diagnosis a with However, a of 17OHP may also as a reliable screening Treatment is only recommended for patients those with an age with a with the family menstrual and the may be based on physical and of or steroid measurements may include serum/plasma electrolytes, serum 17OHP, androstenedione, and/or and or direct renin, every months and every months The time from the last glucocorticoid dose should be the of the adrenal should be into Patients adequate replacement therapy may have hormone levels the normal measurements include urinary or blood and laboratory data will indicate a need for dose physical growth, and indicate or Patients with CAH should medical and information concerning therapy for should have an of HC or glucocorticoid levels of cortisol patients should be increased of glucocorticoids when or when to oral after and surgery. in may also require steroid and such as does not require increased dosing should be times the glucocorticoid dose for patients to oral and patients and those to oral steroids require or concentrations should be and and replacement may be required. or patients may or When an may be followed by of for and dosage are as for children than yr of age, 25 mg followed by for children yr of age, 50 mg followed by and for and mg followed by CAH and should be by and and made available to other pediatric endocrine of useful as family include: and The practice of frequent genital examinations in females should be Therefore, there is clinical or laboratory evidence of control or one to the and size of the genital examinations should not be performed. In females or the of the use of or of sexual genital examination with to the of the may need to be performed. the patient and/or family should be of the for the examinations and support of the patient both classic and and family should be a of the comprehensive care and management of these and/or patients should be the of and counseling at the time of the initial sexual gender role, and related to with a should be the pediatric or for infants, and with CAH. In late adolescence or even early adulthood, care is to an internal in the same institution or clinical We that a team should also as a a and a with specific expertise and in the treatment of such should be that with treatment is important to normal and reduce the risk of a mass by may not be of clinical physical examinations and, as and of both to in the of such removal of a glucocorticoid may be in or The of the genital repair in and adult women needs to be and should be about and other sexual as as is useful with should be an increased risk of However, the risk is not available and may on the and degree of with The risk of women with CAH or an affected fetus is women with CAH should be and in a center and experienced to such that do not the such as HC and should be used. should be when in prenatal should be to maternal serum testosterone concentrations near the range of normal for pregnancy When surgery has been performed, to to the genital When is performed, of HC have to be increased and after A should be present to care of the newborn and to diagnostic procedures when an affected child is to the results of prenatal by is in adrenal androgens and the of It should be only in therapy is in of HC and is with institution of at the of The patient must be throughout for of adrenal The procedure should only be carried out long-term follow-up is and in the of approved clinical studies. The use of in CAH is on but of with Based on the of an in male sexual it was that the effects of elevated androgens on adult be by using an to androgen and/or an to of androgen to studies in CAH show control of and at glucocorticoid dosage Long-term safety data are not and reproductive effects are not known. function has to be Patients with CAH from of and of the adrenal as deficiency This may a role in to therapeutic are under genetic diagnosis for CAH is but further research is required to therapy is not in with this CAH patients on glucocorticoid treatment have levels. in adult patients with have beneficial effects of replacement but the relevance in CAH is have the potential for activity of glucocorticoids At present, there are no specific that are of or and clinical experience with is Therefore, the use of these cannot be at A of patients with CAH with an of Thus, an is by patients with CAH, and the adult is substantially less than However, some CAH patients to normal adult A small of CAH patients have been treated with for 2 either or in with a This and but adult data are not yet These are to all of the management of this in from diagnosis adulthood. The multidisciplinary of management is with the that such expert teams need appropriate and There remain important in about this and these have been therapeutic are as require evaluation into practice. In the should on early optimal medical and surgical treatment, and to compliance. The for support of the consensus meeting in The following convened in Gloucester, March 14–17, and to this The and The also the of and congenital adrenal European Society for Pediatric Lawson Wilkins Pediatric Endocrine nonclassical plasma renin

The Journal of Clinical Endocrinology & Metabolism · review · 331 citationsread the source →

What is pain management, and what is its relevance to the rheumatologist?

A predominant symptom common to most rheumatological conditions is musculoskeletal pain, and providing excellence in the diagnosis and treatment of painful inflammatory joint and connective tissue diseases probably represented a major motivating factor behind many individuals’ decision to become rheumatologists. Despite such aspirations, many rheumatological referrals are in respect of patients whose musculoskeletal pain is not due to inflammatory disease. Furthermore, as ‘benign’ non-inflammatory musculoskeletal pain cannot usually be prioritized as urgent, most patients will have become chronic pain (i.e. >3 months) sufferers by the time of their first hospital appointment. How rheumatologists view the chronic pain aspects of individual patients may vary greatly. Most feel comfortable dealing with chronic pain where this has an inflammatory cause, for example in rheumatoid arthritis (RA) sufferers with whom they may feel great empathy. In contrast, many rheumatologists feel uncomfortable dealing with chronic pain where the cause is unclear, as in mechanical low back pain (LBP). Here, therapeutic responses are predictably disappointing, and rheumatologists may have difficulty empathizing with such patients, particularly as their problems may appear to be predominantly psychological. For their part, such patients not only expect that proposed treatments be effective, but that they are sympathetically delivered. These mutual misunderstandings may explain the difficulties often experienced by rheumatologists during these ‘heart sink’ patients’ clinic visits. Drawing on our experience of a multidisciplinary pain management centre, we elaborate here an argument for a change in how chronic, non-inflammatory musculoskeletal pain patients should be viewed, to effect better outcomes. We use chronic LBP as a vehicle to illustrate our arguments, but the principles discussed would apply to other musculoskeletal pain problems, such as fibromyalgia. The time-honoured processes of history taking, examination and investigation are undertaken in the belief that confirmation of diagnosis will secure best outcome, through diagnosis-specific treatment. This systematic approach is unsatisfactory in chronic mechanical LBP, and for a number of reasons. Appropriate investigations, including multiple and complex radiology, may be normal. Even if investigations pinpoint lesions thought capable of causing chronic symptoms, such as degenerative disc disease, pain manipulations through physical, pharmaceutical and alternative therapies have usually already been tried, and their usefulness limited by lack of efficacy or side-effects. Whether opiates should be used here is an unresolved debate, but dose escalation clearly represents a potential hazard. Chronic LBP patients thus have symptoms that are neither amenable to cure nor fully suppressible by analgesia, and although attending doctors’ heart sink emotions are understandable, they can also lead to nihilism and thereby increase the risks of iatrogenic distress induction (see later). To minimize such risks when dealing with these difficult patients a robust alternative strategy is required, and we commend here the pain management approach. In this and many other pain centres, the initial phase of pain management is the gathering of information prior to patients’ first visit, through self-report screening questionnaires regarding patients’ understanding of their symptomatology, together with standardized psychometric measures of depression, pain-related fear/anxiety, disability and general quality of life. This facilitates subsequent triage whereby the collated biomedical, functional and psychosocial indicators inform decisions regarding clinical priority and likely assessment pathway, such as physician only, physician with psychologist, etc. An important function of the first visit is to exclude a previously missed treatable cause for the pain, for example supposed radicular leg pain which is actually due to a previously unsuspected osteoarthritic hip. Such a finding would be treated accordingly. Although the biomedical process appears similar to routine medical practice, there is, from a pain management perspective, an appreciation that information provision itself is unlikely to change inappropriate beliefs or behaviours. Thus, from this juncture, the pain management approach diverges from routine clinical practice. This will typically include addressing any misunderstandings about the cause of patients’ pain and, if indicated, their suboptimal management of their life with pain. Assuming that no curable diagnosis is present, a more detailed assessment of biopsychosocial factors follows and, after a short interdisciplinary case conference, the patient is given feedback regarding the clinical formulation. Given that patients’ beliefs will influence decision-making and subsequent behaviour, it is important to check that they have not misunderstood any technical information provided, or focused selectively on only part of the relevant message before interdisciplinary intervention is planned. To be successful the pain management approach requires patients and their physicians to realize their respective predicaments. Thus, patients must understand and accept that their pain is not curable, while physicians including rheumatologists must deliver this unwelcome news to patients, but do so carefully and sensitively, and with a view to dispelling their misconceptions and providing guidance as to the way out of their impasse. Following such communication, patients should understand that the ‘bottom line’ of the pain management approach is not abolition of pain, but a retention or restoration of function, despite their pain. Before progress can be made, patients must also appreciate that activity-related pain does not equate to activity-related tissue damage, i.e. it is safe for them to reintroduce physical activity into their lives. Patients are often very fearful of inducing damage and pain, so they must start physical reactivation at very low intensities. Once commenced, however, activity can be incrementally increased to reinforce the message that pain does not mean harm, and some patients can make remarkable progress. Patients also need to understand that they have developed psychological features that are common and understandable secondary sequelae of living with chronic pain, but that these features must be tackled openly to facilitate behavioural changes likely to effect functional improvements. Significant disability is not inevitable with chronic benign pain; but the greater the number of obstacles present, the greater the potential for maladaptive secondary psychological responses [1]. Helping patients to understand the counterproductive influence of ineffectual coping responses is a necessary strategy in the therapeutic change process. Research confirms the potency of misplaced beliefs, attitudes and feared expectations as barriers to change, and as a strong motivational factor in avoidance behaviour [2, 3]. Amongst chronic pain patients, perhaps the most clinically important cognitive presentation is the tendency to become preoccupied with beliefs and expectations that are catastrophic in nature (e.g. rapid and progressive pathology, loss of independent living, vulnerability to structural damage, cancer, marital breakdown, suicide). The fact that patients’ families often share biomedical misattributions, and may act as advocates for caution, also inhibits adaptive behaviour [4]. Education and attitude change must therefore also address the concerns of influential family members. Ultimately, the promotion of a change towards adaptive health-care behaviour is the shared responsibility of patients, their families and medical practitioners. The ability to motivate change towards adaptive health-care behaviour thus appears an important component of rheumatological clinical excellence [1]. In order to become advocates of the pain management approach, clinicians including rheumatologists require an understanding of research upon which the approach has evolved. That inflammation and pain follow acute tissue injury is well accepted, but understanding pain report is fraught with conceptual difficulties. Report of pain is a communication of the perceptual experience of nociception resulting from the interaction of biomechanical, biochemical and neurophysiological factors. These are, in turn, influenced by cognitive and behavioural (i.e. psychological) factors, including prior experience, beliefs about pain and illness, coping style and strategies, peer dynamics and socio-economic factors. Even the ‘normal’ painful state is characterized by a prolonged experience of pain following brief stimulation, in the lowering of pain threshold (allodynia), the magnified response to noxious stimulation (hyperalgesia), and the spread of pain and hyperalgesia in non-dermatomal distributions and in uninjured tissue (referred pain and secondary hyperalgesia). Presentation at the acute stage is characterized by a reduction in physical activity in association with verbal and facial expressions of pain and medication-taking, which are considered normal and acceptable ramifications of acute suffering [5]. These behaviours normally reverse as tissue injury is rectified and inflammation and ‘normal’ pain settle. Chronic nociceptive pain could arise through chronic tissue inflammation, as in RA, while chronic neuropathic pain could arise through chronic nerve damage, as in diabetic peripheral neuropathy. However, persistent pain, following an injury that has healed, is not explainable by peripheral biochemical or neurological activations. Research reviews on pain mechanisms note that chronic inflammatory pain sensitizes central nervous system (CNS) pathways, leading to stimulation of chemical, functional and structural changes that ‘prime the pain processing system’ [6]. This is achieved by lowering the thresholds of pain-sensing neurons, and a concomitant release of growth factors and neurotransmitters, which reinforce the genesis and transmission of pain messages. Increasing effort has been made to understand the potential contribution of such central neural plasticity in the maintenance of pain responses. Examples include referred pain and secondary hyperalgesia at the site of previous injuries (leading to hypothesized ‘neural pain memory’), phantom pain and the spread of CNS receptive fields following limb amputation (as reviewed by Coderre et al. [7]). It is only quite recently that medical education has abandoned the Cartesian model of pain, which implies that if no organic cause is found for pain, it must be psychogenic. The layperson cannot be blamed for medical ignorance, but medical practitioners acting on this belief may contribute to patients’ distress, by inadvertently giving the impression of disbelieving the sincerity and/or severity of patients’ symptoms, and thus implying that their pain is not real. Understanding the mechanisms underlying the development of chronic pain from acute pain is vital if the potentially harmful effects of assigning the ‘psychogenic’ label are to be avoided. Recent research has shown that ongoing pain is explainable in the absence of ongoing inflammation. The normal intervertebral disc has little innervation, thus making it an unlikely culprit for causing chronic mechanical LBP. It has now been shown, however, that neovascularization into the disc occurs as part of the degenerative process, and this is accompanied by in-growth of nociceptive neural structures [8]. This finding may explain how a previously insensitive structure could become capable of giving rise to pain. Individuals suffering chronic degenerative LBP would, unless otherwise instructed, follow their evolutionary instincts to rest. If no resolution of LBP occurs despite continued or even intensified rest, it is easy to see how previously normal, sensible individuals could become embroiled in this vicious circle, and thus develop chronic LBP and associated disability. It is not clear, however, why only some individuals with degenerative LBP are thus affected. It has been estimated that 90% of ‘first time’ LBP cases remit naturally within around 4 weeks [9]. More recent research suggests, however, that a greater proportion of LBP patients have mild ongoing, or recurrent acute, symptoms [10], and those developing chronic symptoms have undergone closer scrutiny. Of 117 LBP patients followed from onset to 6 months, 40% continued to suffer pain at 6 months [11]. This 40% rated their acute LBP as more intense and of a more averse sensory and affective quality, they scored higher on depression and anxiety questionnaires, they were more avoidant of activity and suffered greater consequences. The primary feature that usually distinguishes acute from chronic pain patients is that, in the latter, the ongoing pain problem cannot be causally related to an active inflammatory or structurally damaging process. Following acute injury, and guided by the prescription of ‘common sense’ advice to ‘take it easy’ or to ‘let pain be your guide’, patients may fail to mobilize normally. Burdened by fear that increased pain signifies increased tissue damage and bodily harm, such individuals become increasingly activity-avoidant, and progressive physical deconditioning inevitably follows, in concert with increasing social and psychological dysfunction. If this process does not resolve, a history of repeat specialist consultations and unhelpful medical or surgical interventions may unfold. Patients’ growing dissatisfaction with health-care professionals may culminate in conflict and hostility with each ‘failed’ treatment or communication. Further attempts to control pain by escalating the amount and/or potency of analgesics are usually ineffectual. At best, initially helpful analgesics become unhelpful over time, and give rise to central side-effects including sedation and mood change. Patients become passive and helpless, and illness behaviour may be exaggerated in an effort to convince others of the reality of their pain. When family and friends lose patience, conflict may follow. Subsequent loss of social and occupational responsibilities and status, combined with social withdrawal, heralds profound demoralization and resentment, and occasionally clinical depression. The most badly affected patients are effectively ‘prisoners of pain’, and it is vital that rheumatologists appreciate the importance of their potential role in this downward spiral. When faced with a stressor as aversive as chronic pain, it is understandable that some patients become unable to maintain adaptive coping strategies, and that even robust individuals may eventually exhibit psychological distress. If patients perceive consultations to be unsympathetic or dismissive, they understandably become angry and frustrated with all health-care professionals with whom they come into contact. These latter considerations illustrate the iatrogenic component of patients’ overall psychological distress. If the iatrogenic component is to be avoided, the non-iatrogenic components of distress must be regarded as understandable, and secondary to the adverse situation in which patients find themselves. It is also important to understand that once psychological distress has developed, it and the associated physical deconditioning conspire to maintain a vicious circle that lowers pain thresholds and thus amplifies the level of perceived pain (see Fig. 1). The theoretical vicious ‘circle’ leading to the development of chronic LBP-associated disability. This figure can be used during patient education, and to facilitate understanding during discussions, we often break the circle down into physical and psychological components, although clearly these are interactive. Any potential concurrent psychological stressor, including the iatrogenic component, will exert its effects in concert with pain-related distress. In recognition of the importance of psychological aspects in the development of chronic pain from acute pain, a series of recent articles [12–15] has highlighted a number of relevant factors, including fear of pain (and consequent activity avoidance), maladaptive coping strategies (e.g. catastrophizing), somatic anxiety and depression, the impact of acute pain on disability in terms of health-care utilization, and the physical, social and occupational consequences of the pain. These considerations highlight the need for psychological assessment and intervention. Indeed the New Zealand government now require GPs to screen LBP patients for psychosocial ‘yellow flags’ at the earliest opportunity (i.e. from around 4 weeks post-onset) to identify individuals at high risk for developing pain-related disability following back injury [16]. In the UK, the Clinical Standards and Advisory Group [17] and The Royal College of General Practitioners [18], have made similar recommendations. Much of the advice on appropriate early self-management of LBP is contained in a patient booklet called ‘The back book’ [19]. These guidelines, and issues relating to their implementation, are reviewed in Waddell [20]. The busy clinician, struggling to manage an already demanding caseload may, understandably, be reluctant to spend more time with patients in identifying and dealing with medically related psychosocial issues. Indeed there are political and economic sanctions in place for not meeting government targets and patients’ expectations. The adoption of preventative health-care strategies is pertinent to clinicians and managers at all levels of the health-care service and extends beyond a ‘quantity versus quality’ issue. Therefore, the argument against expediency and in favour of facilitating doctor–patient communication can, in our experience, reduce return visits and improve medication compliance and appropriate use of health-care services generally. For highly and patients, to a multidisciplinary pain may be indicated, the ability of any individual to effect change may be The of these patients will accept interdisciplinary pain on an individual and/or that upon a self-management approach. The and mechanisms of pain management are in in function and together with of (e.g. catastrophic and passive coping are about by This usually on education about and increasing and of of relevant for maladaptive behaviours and unhelpful and beliefs, problem and the role of the family in adaptive behaviours. of following multidisciplinary interventions that, with there is a reduction in medication use health-care use and pain behaviour an increased proportion of return to and physical function A more recent of of confirms the efficacy of these considered in of these have not for LBP patients, but also for those with RA, and pain. pain has shown that neither medical nor factors site of pain, cause of pain, number of for pain, history of pain-related or previous or psychological treatment for influenced treatment to following is an important of pain management intervention. to Waddell the that the of to return to following for LBP from at to at 6 months, and to at experience of only a pain management intervention for a of chronic LBP sufferers been out of for a mean of a return to on the in about of When with patients whose pain is more chronic and GPs and hospital physicians must the risks of maladaptive psychosocial factors, and their potential for inducing distress. Chronic symptoms cause, or where the cause is not amenable to a approach, is the the in chronic LBP. even in inflammatory diseases such as RA, the of disability may be to the of damage or When medical and investigations are normal, or for chronic pain, it should not be that the sufferers are their symptoms or psychological distress is and could be by and early communication. patients’ about pain, and addressing misplaced of activity-related tissue damage, is a necessary first in the therapeutic process. In this the pain management approach, used early on in a pain could potentially the development of chronic pain-related disability. However, this has to be management is not the as pain although the latter may an of the rheumatological are used pain for example in LBP patients develop An understanding of the mechanisms leading to chronic pain, and an of pain management would rheumatologists to with chronic, benign musculoskeletal pain patients in a more and and increased through in heart sink more rapid and health-care may concerns about the in initial interdisciplinary will be for the more complex which so health-care and

British journal of rheumatology · review · 27 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 →

Hope for the Best, and Prepare for the Worst

Medical Writings4 March 2003Hope for the Best, and Prepare for the WorstAnthony L. Back, MD, Robert M. Arnold, MD, and Timothy E. Quill, MDAnthony L. Back, MDFrom Veterans Administration Puget Sound Health Care System, University of Washington, Seattle, Washington; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Rochester, Rochester, New York., Robert M. Arnold, MDFrom Veterans Administration Puget Sound Health Care System, University of Washington, Seattle, Washington; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Rochester, Rochester, New York., and Timothy E. Quill, MDFrom Veterans Administration Puget Sound Health Care System, University of Washington, Seattle, Washington; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Rochester, Rochester, New York. Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-138-5-200303040-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Mr. J., a 40-year-old father of two young children, has metastatic non–small-cell lung cancer that has not responded to two different chemotherapy regimens. His physician, Dr. B., explains that the cancer is progressing. Mr. J. says, Isn't there something you can do? Please don't give up on me. Dr. B. pauses and says, Well, there is an experimental protocol we could try. When faced with life-threatening illness, patients and physicians often feel that they must choose between hoping for disease remission and preparing for death. Mr. J. wants to fight the cancer in hope of living longer, and his physician ...References1. Delvecchio Good MJ, Good BJ, Schaffer C, Lind SE. American oncology and the discourse on hope. Cult Med Psychiatry. 1990;14:59-79. 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On Dying and Denying: A Psychiatric Study of Terminality. New York: Behavioral Publications; 1972. Google Scholar9. McCormick TR, Conley BJ. Patients' perspectives on dying and on the care of dying patients. West J Med. 1995;163:236-43. [PMID: 7571586] MedlineGoogle Scholar10. Barnard D, Boston P, Towers AM, Lambrinidou Y. Crossing over: Narratives of Palliative Care. New York: Oxford Univ Pr; 2000. Google Scholar11. Kuhl D. What Dying People Want: Practical Wisdom for the End of Life. New York: PublicAffairs; 2002. Google Scholar12. Herth K. Fostering hope in terminally-ill people. J Adv Nurs. 1990;15:1250-9. [PMID: 2269747] CrossrefMedlineGoogle Scholar13. Quill TE, Cassel CK. Nonabandonment: a central obligation for physicians. Ann Intern Med. 1995;122:368-74. [PMID: 7847649] LinkGoogle Scholar14. Crawshaw R, Rogers DE, Pellegrino ED, Bulger RJ, Lundberg GD, Bristow LR, . Patient-physician covenant. JAMA. 1995;273:1553. [PMID: 7739086] CrossrefMedlineGoogle Scholar15. Maguire P. Improving communication with cancer patients. Eur J Cancer. 1999;35:1415-22. [PMID: 10673972] CrossrefMedlineGoogle Scholar16. Steinhauser KE, Christakis NA, Clipp EC, McNeilly M, McIntyre L, Tulsky JA. Factors considered important at the end of life by patients, family, physicians, and other care providers. JAMA. 2000;284:2476-82. [PMID: 11074777] CrossrefMedlineGoogle Scholar17. Singer PA, Martin DK, Kelner M. Quality end-of-life care: patients' perspectives. JAMA. 1999;281:163-8. [PMID: 9917120] CrossrefMedlineGoogle Scholar18. Heaven CM, Maguire P. Disclosure of concerns by hospice patients and their identification by nurses. Palliat Med. 1997;11:283-90. [PMID: 9373579] CrossrefMedlineGoogle Scholar19. Quill TE. Recognizing and adjusting to barriers in doctor-patient communication. Ann Intern Med. 1989;111:51-7. [PMID: 2660647] LinkGoogle Scholar20. Quill TE, Brody H. Physician recommendations and patient autonomy: finding a balance between physician power and patient choice. Ann Intern Med. 1996;125:763-9. [PMID: 8929011] LinkGoogle Scholar21. Curtis JR, Wenrich MD, Carline JD, Shannon SE, Ambrozy DM, Ramsey PG. Understanding physicians' skills at providing end-of-life care perspectives of patients, families, and health care workers. J Gen Intern Med. 2001;16:41-9. [PMID: 11251749] MedlineGoogle Scholar22. Quill TE, Suchman AL. Uncertainty and control: learning to live with medicine's limitations. Humane Med. 1993;9:109-20. [PMID: 11656250] MedlineGoogle Scholar23. Meier DE, Back AL, Morrison RS. The inner life of physicians and care of the seriously ill. JAMA. 2001;286:3007-14. [PMID: 11743845] CrossrefMedlineGoogle Scholar24. Lamont EB, Christakis NA. Prognostic disclosure to patients with cancer near the end of life. Ann Intern Med. 2001;134:1096-105. [PMID: 11412049] LinkGoogle Scholar25. Weeks JC, Cook EF, O'Day SJ, Peterson LM, Wenger N, Reding D, . Relationship between cancer patients' predictions of prognosis and their treatment preferences. JAMA. 1998;279:1709-14. [PMID: 9624023] CrossrefMedlineGoogle Scholar26. Emanuel EJ, Young-Xu Y, Ash A, Gazelle G, Levinsky N, Moskowitz M. How much chemotherapy are cancer patients receiving at the end of life? [Abstract] Proceedings of the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA; 1215 May 2001. Abstract no. 953. Google Scholar27. Shapiro A. The Vigil. Chicago: Univ of Chicago Pr; 1997. Google Scholar28. Waisel DB. The hazards of hanging crepe or stating overly pessimistic prognoses. J Clin Ethics. 2000;11:171-4. [PMID: 11056876] MedlineGoogle Scholar29. Siegler M. Remarks on crepe hangingor ethics in everyday practice. Am Med News. 1977;20:22. [PMID: 11664719] MedlineGoogle Scholar30. Kagawa-Singer M, Blackhall LJ. Negotiating cross-cultural issues at the end of life: You got to go where he lives. JAMA. 2001;286:2993-3001. [PMID: 11743841] CrossrefMedlineGoogle Scholar31. Crawley L, Payne R, Bolden J, Payne T, Washington P, Williams S, . Palliative and end-of-life care in the African American community. JAMA. 2000;284:2518-21. [PMID: 11074786] CrossrefMedlineGoogle Scholar32. Quill TE, Williamson PR. Healthy approaches to physician stress. Arch Intern Med. 1990;150:1857-61. [PMID: 2393317] CrossrefMedlineGoogle Scholar33. Remen RN. Recapturing the soul of medicine: physicians need to reclaim meaning in their working lives. West J Med. 2001;174:4-5. [PMID: 11154646] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Veterans Administration Puget Sound Health Care System, University of Washington, Seattle, Washington; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Rochester, Rochester, New York. Acknowledgments: The authors thank Dr. Susan Block for her helpful suggestions about the role of ambivalence. Grant Support: Drs. Back and Arnold are Faculty Scholars of the Project on Death in America. Dr. Arnold was also supported by the Greenwall Foundation, Ladies Hospital Aid Society of Western Pennsylvania, and the LAS Trust Foundation. Corresponding Author: Anthony Back, MD, Veterans Administration Puget Sound Health Care System, 1660 South Columbian Way S111, Seattle, WA 98108; e-mail, [email protected]washington.edu. Current Author Addresses: Dr. Back: Veterans Administration Puget Sound Health Care System, 1660 South Columbian Way S111, Seattle, WA 98108.Dr. Arnold: Section of Palliative Care and Medical Ethics, MUH 200 Lothrop Street 932, Pittsburgh, PA 15213.Dr. Quill: Palliative Care Program, University of Rochester School of Medicine, Box 601, 601 Elmwood Avenue, Rochester, NY 14642. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHope for the Best, and Prepare for the Worst James D. 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M. MD, MD, and B. MD, of in and Benefits of Early Phase Cancer What Do What Do Patients About Conversations at the End of Life Is the illness in the of of patients who in the intensive care Regarding Palliative and End-of-Life Care in Severe Chronic Obstructive Pulmonary Disease or Advanced by and for end-of-life care in the intensive care A by the American of Care der pädiatrischen Palliativversorgung bei besonderen and Prognostic in a A for to the Care in Advanced of Palliative Care of communication skills for oncology advanced practice about Lung Transplantation: of Patients and about lung needs of patients and support and Discussing Death in the A of Physician care and end-of-life decision in and palliative care Understanding the of With Ill Patients and care for patients with chronic About Prognosis Between and of Children With Preferences and the Impact of Prognostic Care and Intensive Care Unit Care: Care and Intensive Care Unit Care: Intensive Care Unit Care care: evaluation in clinical at of with and with Families in Palliative Care: Not for a to improve palliative care: Advanced heart Clinical and On a of Palliative Care: A for and on and en de la of Chinese Cancer Patients of the and by Their about Palliative Care for Patients with Chronic Obstructive Pulmonary or Not to Is the Pain When Pain and are family members with palliative care A qualitative and hope when the future with cancer patients and their Prognostic Communication With Advanced Cancer the End of the Relationship with Patients Who Are L. Back, MD, Robert M. Arnold, MD, James A. MD, MD, and A. Perceptions of and the of About the Communication Issues and issues to end‐of‐life careA conceptual framework for end-of-life care: A of influencing the of the about the of treatment and transition to palliative Years Later: An Oncologist Reflects on palliative and supportive care in advanced heart and Bad A Patient's for the Best, and Prepare for the D. Communication and Hope: Communication in Palliative Issues for the and Cancer and End-of-Life advanced care planning and of dying for people with of palliative care March Issue care March Issue March & by American of

Annals of Internal Medicine · case report · 366 citationsread the source →

The Effectiveness of Self-Regulation Strategy Training on Academic Flourishing and Optimism in Students with Academic Procrastination Tendencies.

Background: Academic procrastination, a pervasive challenge among students, has been shown to significantly impede academic performance and overall well-being. This study investigated the efficacy of self-regulation strategy training in promoting academic flourishing and optimism among students exhibiting tendencies toward academic procrastination. Methods: This study used a quasi-experimental design with a control group. The study population consisted of male high school students exhibiting academic procrastination in Dezful, Iran during the 2022-2023 academic year. Thirty male high school students (aged 16-18), exhibiting procrastination tendencies (scores above 45 on a procrastination questionnaire), participated in this study. Using a convenience sampling method, the study participants were randomly allocated to either an experimental or a control group (n=15 per group). The experimental group underwent ten weekly 90-minute sessions of self-regulation strategy training. Academic flourishing and academic optimism were assessed using the Academic Flourishing Scale (AFS) and the Academic Optimism Questionnaire (AOQ), respectively, at three intervals: pre-intervention, post-intervention, and at a 45-day follow-up. Repeated measures ANOVA, using SPSS version 25, was employed for data analysis. Results: Academic flourishing increased significantly from the pre-test (21.01±7.72) to the post-test (34.40±8.09) and follow-up (32.53±7.22) in the experimental group (P<0.001), while remaining stable in the control group (21.13±7.32, Post-test: 20.93±7.12, Follow-up: 21.89±7.64). Similarly, academic optimism increased significantly from pre-test (68.87±13.88) to post-test (91.47±15.21) and follow-up (89.48±15.37) in the experimental group (P<0.001), while remaining relatively stable in the control group (Pre-test: 68.80±13.59, Post-test: 67.80±12.82, Follow-up: 66.87±14.54). The findings suggested that self-regulation strategy training can enhance academic flourishing and optimism among students with procrastination tendencies (P<0.001). Conclusions: The findings of this study provided evidence for the efficacy of self-regulation strategy training in promoting academic flourishing and optimism in students exhibiting procrastination tendencies. The significant improvement observed in the experimental group highlights the potential of this intervention to address procrastination and promote positive academic outcomes.

International journal of school healthread the source →

6-month multidisciplinary follow-up and outcomes of patients with paediatric inflammatory multisystem syndrome (PIMS-TS) at a UK tertiary paediatric hospital: a retrospective cohort study.

Background: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a new, rare, post-infectious complication of SARS-CoV-2 infection in children. We aimed to describe the 6-month outcomes of PIMS-TS. Methods: This retrospective cohort study comprised children (aged <18 years) who fulfilled the UK Royal College of Paediatrics and Child Health (RCPCH) diagnostic criteria for PIMS-TS and were admitted to Great Ormond Street Hospital (London, UK) between April 4 and Sept 1, 2020. Patients were followed up by a multidisciplinary team of specialists at 6 weeks and 6 months after admission. Biochemical and functional outcomes were analysed. Findings: 46 children were included in this study. The median age at presentation was 10·2 years (IQR 8·8-13·3), 30 (65%) patients were male and 16 (35%) were female, 37 (80%) were from minority ethnic groups, and eight (17%) had pre-existing comorbidities. All patients had elevated markers of systemic inflammation at baseline. None of the patients died. By 6 months, systemic inflammation was resolved in all but one patient. 38 (90%) of 42 patients who had positive SARS-CoV-2 IgG antibodies within 6 weeks of admission remained seropositive at 6 months. Echocardiograms were normal in 44 (96%) of 46 patients by 6 months, and gastrointestinal symptoms that were reported in 45 (98%) of 46 patients at onset were present in six (13%) of 46 patients at 6 months. Renal, haematological, and otolaryngological findings largely resolved by 6 months. Although minor abnormalities were identified on neurological examination in 24 (52%) of 46 patients at 6 weeks and in 18 (39%) of 46 at 6 months, we found minimal functional impairment at 6 months (median Expanded Disability Status Scale score 0 [IQR 0-1]). Median manual muscle test-8 scores improved from 53 (IQR 43-64) during hospital admission to 80 (IQR 68-80) at 6 months, but 18 (45%) of 40 patients showed 6-min walk test results below the third centile for their age or sex at 6 months. PedsQL responses revealed severe emotional difficulties at 6 months (seven [18%] of 38 by parental report and eight [22%] of 38 by self report). 45 (98%) of 46 patients were back in full-time education (virtually or face to face) by 6 months. Interpretation: Despite initial severe illness, few organ-specific sequelae were observed at 6 months. Ongoing concerns requiring physical re-conditioning and mental health support remained, and physiotherapy assessments revealed persisting poor exercise tolerance. Longer-term follow-up will help define the extended natural history of PIMS-TS. Funding: None.

The Lancet. Child & adolescent health · 151 citationsread the source →

Mental health resilience in the adolescent offspring of parents with depression: a prospective longitudinal study.

Background: Young people whose parents have depression have a greatly increased risk of developing a psychiatric disorder, but poor outcomes are not inevitable. Identification of the contributors to mental health resilience in young people at high familial risk is an internationally recognised priority. Our objectives were to identify protective factors that predict sustained good mental health in adolescents with a parent with depression and to test whether these contribute beyond what is explained by parent illness severity. Methods: The Early Prediction of Adolescent Depression study (EPAD) is a prospective longitudinal study of offspring of parents with recurrent depression. Parents with recurrent major depressive disorder, co-parents, and offspring (aged 9-17 years at baseline) were assessed three times over 4 years in a community setting. Offspring outcomes were operationalised as absence of mental health disorder, subthreshold symptoms, or suicidality on all three study occasions (sustained good mental health); and better than expected mental health (mood and behavioural symptoms at follow-up lower than predicted given severity of parental depression). Family, social, cognitive, and health behaviour predictor variables were assessed using interview and questionnaire measures. Findings: Between February and June, 2007, we screened 337 families at baseline, of which 331 were eligible. Of these, 262 completed the three assessments and were included in the data for sustained mental health. Adolescent mental health problems were common, but 53 (20%) of the 262 adolescents showed sustained good mental health. Index parent positive expressed emotion (odds ratio 1·91 [95% CI 1·31-2·79]; p=0·001), co-parent support (1·90 [1·38-2·62]; p<0·0001), good-quality social relationships (2·07 [1·35-3·18]; p=0·001), self-efficacy (1·49 [1·05-2·11]; p=0·03), and frequent exercise (2·96 [1·26-6·92]; p=0·01) were associated with sustained good mental health. Analyses accounting for parent depression severity were consistent, but frequent exercise only predicted better than expected mood-related mental health (β=-0·22; p=0·0004) not behavioural mental health, whereas index parents' expression of positive emotions predicted better than expected behavioural mental health (β=-0·16; p=0·01) not mood-related mental health. Multiple protective factors were required for offspring to be free of mental health problems (zero or one protective factor, 4% sustained good mental health; two protective factors, 10%; three protective factors, 13%, four protective factors, 38%; five protective factors, 48%). Interpretation: Adolescent mental health problems are common, but not inevitable, even when parental depression is severe and recurrent. These findings suggest that prevention programmes will need to enhance multiple protective factors across different domains of functioning. Funding: Sir Jules Thorn Charitable Trust, Economic and Social Research Council.

The lancet. Psychiatry · 120 citationsread the source →

Cohort Profile: The National Longitudinal Study of Adolescent to Adult Health (Add Health)

The National Longitudinal Study of Adolescent Health (Add Health) was developed in the 1990s in response to a mandate from the United States Congress to fund a study of adolescent health, and was designed by a team of multidisciplinary investigators from the social, behavioural and biomedical sciences. The original purpose of Add Health was to understand the causes of adolescent health and health behaviour, with special emphasis on the multiple contexts of adolescent life. To achieve this scientific goal, Add Health sampled the school and family environments in which young people live their lives, which included data on peer relationship dyads, parents, siblings, neighbourhoods and communities, and provides independent and direct measurement of these complex environments over time. As the cohort transitioned into adulthood, research objectives turned to understanding how adolescent experiences, behaviours and contexts are linked to health and achievement outcomes in adulthood, and the name of the study was officially changed to The National Longitudinal Study of Adolescent to Adult Health in 2014. Add Health is housed at the Carolina Population Center at the University of North Carolina (UNC) and has been led by two principal investigators and project directors: J Richard Udry from 1994–2004; and Kathleen Mullan Harris from 2004 to the present. Add Health is a nationally representative cohort study of more than 20 000 adolescents in grades 7–12 (aged 12–19) in the USA in 1994–95, who have been followed through adolescence and into adulthood with five in-home interviews in 1995 (Wave I), 1996 (Wave II), 2001–02 (Wave III), 2008–09 (Wave IV) and 2016–18 (Wave V).1Figure 1 displays the sampling design for selecting the original cohort. A school-based design selected 80 high schools and a paired feeder school from a list of all high schools in the USA in 1994. An in-school questionnaire was administered to more than 90 000 students in grades 7–12, who attended these schools during the 1994–95 school year, and school administrators also filled out a questionnaire about the school. Sampling structure. School rosters from the 1993–94 school year provided the sampling frame for a second level of sampling for a 90-min in-home interview with an adolescent and a 30-min interview with one parent. A grade- and gender-stratified core sample was selected from each school pair, representing a self-weighting nationally representative sample of 12 105 American adolescents in grades 7–12 in 1995. Based on responses to the in-school survey, specific subpopulations were oversampled for purposes of providing sufficient numbers for research on vulnerable and otherwise rare populations, including ethnic (Cuban, Puerto Rican and Chinese), genetic relatedness to siblings (identical/fraternal twins, full/half siblings and unrelated adolescents living in the same household), adoption status and disability samples. Black adolescents with highly educated parents were also oversampled. For two large schools and fourteen small schools, interviews with all enrolled students were attempted to create a special saturation sample. The core sample plus the special samples yield a total of 20 745 adolescents. This Wave I in-home sample represents the national cohort of adolescents in grades 7–12 in the USA in 1995, which is followed prospectively. Because school rosters from the year preceding sample selection were used as the sampling frame for the prospective cohort, high school dropouts over 2 years (e.g. 1993–94; 1994–95) were eligible for sample selection, resulting in little bias due to high school dropouts.2 For more details on design, see Harris 2010 and Harris et al., 2013.3,4 Figure 2 shows the longitudinal design of Add Health. The Wave I in-home adolescent cohort has been followed up with four subsequent waves spanning 20+ years. In 1996, all adolescents in grades 7 through 11 in Wave I (plus 12th graders who were part of the genetic and adopted sample) were re-interviewed for Wave II (n = 14 738); the decision not to follow up the seniors who were in grade 12 at Wave I was design-based. The Wave II sample were in grades 8 through 12. A follow-up school administrator interview measured change in school context from 1995 to 1996. Longitudinal design. The original cohort was followed through their transition to early adulthood with a Wave III in-home interview in 2001–02 when the sample was aged 18–26 years (n = 15 197). A sample of 1507 partners were randomly selected during the in-home interview and interviewed, filling quota samples of about 500 married, 500 cohabiting and 500 dating partners. Wave IV re-interviewed the original cohort as they settled into young adulthood in 2008–09 when the cohort was aged 24–32 years (n = 15 701). Wave V followed the cohort to the end of young adulthood when they were aged 32–42, with continuous interviewing using a mixed-mode protocol during 2016–18. Finally, the Add Health Parent Study completed a 20-year follow-up of a subset of the parents of Add Health respondents during 2015–17 (n = 3006). Add Health uses state-of-the-art methods and techniques for panel maintenance and tracing to locate and schedule an interview with all living eligible respondents, including those who may have been non-responsive in a preceding wave. Table 1 presents response rates for the eligible sample at each completed wave of interviews. Response rates have been quite high, highest when the interval between interview waves is short but remarkably high even when the interval is over 5 years at Waves III and IV. The transition from adolescence to early adulthood and the young adult period is an especially transient phase of the life course and it is difficult to track and locate young people. Add Health has done exceptionally well, with response rates of 77.4% and 80.3% at Waves III and IV. Response rates in Add Health for the eligible sample at each wave of in-home interviews By design, respondents who were in the 12th grade at Wave I and who were not part of the genetic sample were not interviewed at Wave II. Response rate at Wave III is based on 15 170 respondents who had data at Wave I. An additional 27 respondents without Wave I data were included at Wave III as part of the genetic subsample. Wave V response rates are not provided because data collection is ongoing, and only a subset of Wave V respondents completed in-home interviews. Response rates in Add Health for the eligible sample at each wave of in-home interviews By design, respondents who were in the 12th grade at Wave I and who were not part of the genetic sample were not interviewed at Wave II. Response rate at Wave III is based on 15 170 respondents who had data at Wave I. An additional 27 respondents without Wave I data were included at Wave III as part of the genetic subsample. Wave V response rates are not provided because data collection is ongoing, and only a subset of Wave V respondents completed in-home interviews. There has been differential attrition by gender, age, socioeconomic status, urban residence, immigrant status and race across time, with higher response rates for female, younger, higher socioeconomic status, urban, native-born and White respondents at Waves III and IV. These attrition patterns are consistent with most longitudinal cohort studies. Add Health response rates exceed other national studies with multiple year intervals between waves (e.g. National Survey of Families and Households 2001–03 wave had a 55% response rate; Midlife in the United States 2004–06 interview had a 75% retention rate).5,6 At each wave, Add Health analysed whether patterns of attrition pose any bias to estimates of survey outcomes.7–10 In general, non-response analyses compare respondents and non-respondents on a range of demographic, health, behavioural and attitudinal indicators measured at baseline, and estimate the extent to which differences between respondents and non-respondents introduce bias in study results. Results indicated that total and relative biases, remaining after study estimates were adjusted with final sampling weights, were minimal and that the sample at each wave adequately represented the same population as the Wave I sample. Analysis of bias due to attrition at Wave IV indicated low rates of bias that rarely exceeded 1%, which is small relative to the 20% to 80% prevalence rates for most of the baseline indicators. Despite common patterns of attrition over time, the design strategy to re-interview the original Wave I cohort at each follow-up wave minimizes non-response bias and continues to adequately represent the original cohort of 7-12th graders in US schools in 1995. Add Health contains unprecedented environmental, behavioural, psychosocial, biological and genetic data from early adolescence into adulthood on a large, nationally representative sample with extensive racial, ethnic, socioeconomic and geographical diversity.4 Longitudinal survey data on respondents’ social, economic, psychological and physical well-being is combined with contextual data on family, neighbourhood, community, school, friendships, peer groups and romantic relationships, providing unique opportunities to study how psychological characteristics, social environments and behaviours beginning in early adolescence are linked to health and well-being in adulthood. Extensive longitudinal life histories of health-related behaviour are available, including physical activity, risk behaviour, substance use, sexual behaviour, civic engagement, education and multiple longitudinal indicators of health status, such as general health, chronic illness, overweight status and obesity, mental health, disability, health promotion and sleep. Objective measures of health were collected across all waves, including anthropometrics, sexually transmitted infection (STI) test results [including human immunodeficiency virus (HIV)], DNA and an expanded set of biomarkers in adulthood (Waves IV and V) (including blood pressure and pulse, measures of glucose homeostasis, lipid metabolism, inflammation, immune and renal function and a medications inventory). Below we describe the innovative multilevel data that have provided unprecedented research opportunities for a multidisciplinary scientific community. The clustered design of Add Health makes possible unique contextual levels of measurement, shown in Table 2. School-context data come from school administrator reports on school policies, health services and other school characteristics and from the in-school interviews of students whose aggregated responses represent school census measures. From respondent reports of colleges attended, college context data have been linked to individual records. Family-context data come from parent questionnaires, adolescent in-school and in-home questionnaires and interviews with siblings and additional adolescents living in the same household. Contextual levels of measurement in Add Health W1 = adolescent in- school and in-home, parent and school administrator surveys, geocodes. W2 = adolescent in-home, school administrator and geocodes. W3 = young adult in-home and partner sample surveys, geocodes, biomarkers. W4 = young adult in-home, biomarkers, geocodes. W5 = adult survey, biomarkers, geocodes. Additional variables from administrative datasets (e.g. US Census, Centers for Disease Control and Prevention, National Center for Health Statistics, Federal Bureau of Investigation, National Council of Churches, Common Core of Data, Private School Survey). , variable available; o, planned variable construction. Contextual levels of measurement in Add Health W1 = adolescent in- school and in-home, parent and school administrator surveys, geocodes. W2 = adolescent in-home, school administrator and geocodes. W3 = young adult in-home and partner sample surveys, geocodes, biomarkers. W4 = young adult in-home, biomarkers, geocodes. W5 = adult survey, biomarkers, geocodes. Additional variables from administrative datasets (e.g. US Census, Centers for Disease Control and Prevention, National Center for Health Statistics, Federal Bureau of Investigation, National Council of Churches, Common Core of Data, Private School Survey). , variable available; o, planned variable construction. Adolescents were asked to nominate friends and sexual and romantic partners from the school rosters in the in-school and in-home surveys at Waves I and II. Peer networks characteristics can be constructed by linking friends’ data and constructing variables based on friends’ responses, and similar measures can be constructed for linked romantic and sexual partners. These peer- and dyad-context measures constitute the social network data, including information on friendship networks, sexual networks and friendship and relationship dyads. Respondents’ home residences have been geocoded at each interview wave, and contextual data on the neighbourhood, community and state have been merged to all individual records. Nearly 12 000 environmental data elements at multiple geographical levels are available across waves. This includes such information as race, ethnic, foreign-born and religious denomination composition, poverty rates, crime statistics, STI prevalence, divorce and child support laws, welfare policies, cigarette taxes, the proximity and number of parks, sidewalks, recreation centres, fast food restaurants, alcohol outlets and other physical and social characteristics of the environments in which young people live. Table 3 shows the array of survey and biological data in Add Health. The top panel lists the domains covered by the survey instruments at each wave, including individual-level data on household and family structure, personality, religiosity and spirituality, relationships, sexual behaviour, contraception, pregnancy, children and parenting, sleep patterns, physical activity, diet, substance use/abuse, violence, delinquency, involvement with the criminal justice system, education history, work experiences, military service, chronic and disabling conditions, injury, mental health, suicide and health service access and use. Even though respondents were first interviewed in early adolescence, there are data on infancy (birthweight) and childhood (e.g. maltreatment, chronic conditions, attention deficit hyperactivity disorder) and complete data on fertility outcomes (there were more than 14 500 births to Add Health respondents by Wave IV). Survey and biomarker domains across Waves I-V in Add Health Survey and biomarker domains across Waves I-V in Add Health The bottom panel of Table 3 shows the biological measures available across waves. The original study design included important features for understanding biological processes in health and developmental trajectories across the life course, including an embedded genetic sample with more than 3000 pairs of adolescents with varying biological resemblance (see Figure 1) and measurement of height and weight to track the obesity epidemic. At Wave III, urine and saliva samples were collected to test for STI and HIV,11,12 and buccal cell saliva was collected from twins and full siblings in the genetic subsample for DNA extraction.13 An expanded set of biological measures were collected at Wave IV, including biomarkers of cardiovascular health (blood pressure, pulse), metabolic processes (waist circumference, glycosylated haemoglobin, blood glucose, lipids), immune function (Epstein-Barr virus), inflammation (C-reactive protein) and a medications inventory. Repeat biomarker measures were collected at Wave V, including new markers of renal disease. Saliva DNA was collected from the full sample at Wave IV. Candidate loci in the dopamine and serotonin pathways have been genotyped and disseminated to the scientific community.14 Genome-wide genotyping was completed on 10 974 Wave IV respondents who consented to archive their specimens for further testing, and genome-wide association study (GWAS) data are available from the database of Genotypes and Phenotypes (dbGaP). Add Health maintains a biospecimen archive available for ancillary studies. Add Health has a large and multidisciplinary user base of more than 50 000 researchers around the world, who have published over 3500 peer-reviewed articles in more than 750 different disciplinary journals, and has been the data source for more than 800 master’s theses and dissertations. Publications are listed at [https://www.cpc.unc.edu/projects/addhealth/publications]. Early publications focused on the role of social context in the development of adolescent health, behaviour, expectations and attainment, finding important influences of family and school connectedness,15 peer influence,16–18 romantic relationships,19 and neighbourhoods.20–22 For example, adolescents with a greater number and higher quality of connections to their school and family had better physical and mental health and higher attainment than youth with Adolescents whose friendship networks included friends with highly parents were than those whose friends had parents to studies that romantic in adolescence can adolescent and is with higher rates of obesity and weight in publications an of chronic young including a prevalence of and prevalence of the longitudinal data, researchers have the developmental and health pathways to young adult Add Health data support longitudinal studies of partner substance and health during the early life course from adolescence into young Add Health has the obesity and outcomes for adolescents. In adolescence of the sample were in 2001–02 when the cohort was aged the to in of the cohort at 24–32 was on these longitudinal data, The and the of obesity early in that adolescents were more to obesity in young adulthood with overweight by a risk of to individual obesity trajectories from adolescence at Wave II to young adulthood at Wave III into not who were who during the transition to young adulthood, and who were adolescence and young adulthood, As shown in Figure greater to obesity during adolescence and young adulthood is with a higher of high and sleep in adulthood. from adolescence to young adulthood with multiple health outcomes in adulthood (n The unique design and of the sample possible health research on special including the adopted youth living with parents sexual and adopted adolescents are more to suicide than their adolescents are at higher health risk on a range of indicators with adolescents who only one and more and than There is a large and of research that the genetic data with the longitudinal environmental data to the of and in health and behavioural of genetic research articles have these on a range of including risk substance sexual and friendship and Genome-wide association study (GWAS) data were for the pairs and Wave IV archive the of a large number of These the new differences in the education and of school environments in the education association with and family and education role in social and cohort differences in the genetic relationship between education and In innovative new research is providing human of genetic in which the of individual behaviour, for and Figure for social genetic of and friends on attainment, and The the of school and of for attainment in the top in the second panel and height in the The is the baseline of on outcomes in a with other and the represent the adjusted for individual-level The results that the of an and friends the attainment, an height is with the height of Add Health has in for new including attainment, height and alcohol genetic Add Health research uses biomarker data to social and behavioural with measures of research has the between a childhood and STI social status and and and life course of social and life for The role of social and social context in pathways was for the first young the for in the early in life and biological are to family and urban young from social is with mental health but physical health for young with The of Add Health from contextual and national design. The adolescent social context and peer network data, in are unique because they not on to an of an national of people who live in all 50 and come from race, ethnic, geographical and socioeconomic and ethnic with sufficient numbers to of Puerto and and and vulnerable including with children and adopted and sexual genetic sample of over 3000 pairs of with varying biological and longitudinal data from respondents and their longitudinal social, behavioural and biological data beginning in early adolescence and into extensive longitudinal multilevel data beginning in early adolescence on life and social and physical including family, school, neighbourhood, community and social measures of health including blood pressure, glucose, virus circumference, and and DNA on 000 and genome-wide genotyping on the full sample at Wave and collection of DNA on twins and full data be available in the including and data (see Table a of the of survey data measurement of specific and a for survey and biomarker measures. are available to researchers in representing a subset of and high which are only to which can only be used in a data to Add Health data to other and high school data, which are available in data access the and of respondents data access to a range of including data access study and can be at data can be Add Health is an longitudinal study of a nationally representative US cohort of 20 745 adolescents in grades (aged in includes four in-home interviews in 1996, 2016–18. attrition has been with response rates from to across follow-up waves, and attrition bias has been The study unprecedented environmental, behavioural, psychosocial, biological and genetic data from early adolescence into adulthood with extensive racial, ethnic, socioeconomic and geographical Add Health has a large, multidisciplinary user base of over 50 000 researchers around the world, who have published over 3500 research the Add Health cohort at the of the obesity with for health and social genetic of and on health and Add Health datasets are to a data to the of information and in of the see Add Health is by the National of Health and with from other and The full list of can be at This research uses data from Add a project by Kathleen Mullan Harris and designed by J Richard and Kathleen Mullan at the University of North Carolina at and by from the National of Health and with from other and is due to and for in the original design. also to data from National of Health and to Kathleen Mullan Harris and to Kathleen Mullan and of

International Journal of Epidemiology · 531 citationsread the source →

Assessment of satisfaction of using socially marketed health consumables at government settings among beneficiaries in a rural area of Hooghly District, West Bengal.

Introduction: India is committed to achieving universal health care for all by 2030. The objective of social marketing is to promote public health and its goal is to improve health for all, but there are some challenges like irregular availability, quality issue, inadequacy of marketing causes under- utilization of the government supplied health consumables. Objectives: Present study aims to find out the usage pattern and assess the perceived satisfaction level of beneficiaries of using various socially marketed health consumables at government settings and explore the perception of healthcare personnel regarding barriers to its usage in a rural area of India. Materials and methods: A community-based, Mixed-Methods study (Convergent parallel design) was done in the service area of the Rural Health Unit and Training Centre (RHU&TC), Singur of Hooghly district, West Bengal, between January 2023 and December 2023, where the quantitative component was carried out by face-to-face interview among 150 beneficiary household respondents selected by two-stage cluster sampling; and qualitative component was done by 4 Key informant interviews (KII) among healthcare personnel (medical officer, public health nurse, pharmacist). Statistical data were analyzed by descriptive statistics using SPSS 16 version and Microsoft Excel for the quantitative part, and thematic analysis was done for the qualitative part. Institutional Ethics Committee clearance was obtained. Results: Ever use of government-supplied contraceptives like Chhaya (Ormeloxifene), Antara (Injectable contraceptive), emergency contraceptive pills, and intrauterine contraceptive devices (IUCD) was done by only 15.3%, 10.7%, 7.3%, 32% of eligible beneficiary households, respectively. The major reasons cited for irregular use were unawareness of availability of the products (Chhaya = 76.3%, Antara = 64.9%, EC pills = 46.7%), poor faith regarding quality (Male condom = 40%, Generic medicines = 70%), inadequate promotion (IUCD = 53.9%). The majority of users of male condoms (90%), IFA tablets (52.9%), ORS (51.1%), and generic medicines (55.7%) were not satisfied after using those products. Key informant interviews among healthcare personnel revealed avoidance of using modern contraceptive methods and frequent unavailability of some socially marketed health consumables were the predominant causes of reduced uptake of those products by beneficiaries. Conclusions: Proper social marketing strategies, adequate promotion, regular awareness campaigns, and tailored training of field healthcare workers are required to improve the acceptability, availability, and marketing of these health consumables.

Journal of family medicine and primary careread the source →