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Exercise on prescription for women aged 40-74 recruited through primary care: two year randomised controlled trial.

Objective: To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period. Design: Randomised controlled trial. Setting: 17 primary care practices in Wellington, New Zealand Participants: 1089 women aged 40-74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention: Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months. Main outcome measure: Physical activity assessed at baseline and 12 and 24 months. Secondary outcomes were quality of life (SF-36), weight, waist circumference, blood pressure, concentrations of fasting serum lipids, glycated haemoglobin (HbA(1c)), glucose, insulin, and physical fitness. Results: Mean age was 58.9 (SD 7) years. Trial retention rates were 93% and 89% at 12 and 24 months, respectively. At baseline, 10% of intervention participants and 11% of control participants were achieving 150 minutes of at least moderate intensity physical activity a week. At 12 months rates increased to 43% and 30% and at 24 months to 39.3% and 32.8% (P<0.001), respectively. SF-36 physical functioning (P=0.03) and mental health (P<0.05) scores improved more in intervention compared with control participants, but role physical scores were significantly lower (P<0.01). There were no significant differences in clinical outcomes. More falls (P<0.001) and injuries (P=0.03) were recorded in the intervention group. Conclusions: This programme of exercise on prescription increased physical activity and quality of life over two years, although falls and injuries also increased. This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ANZCTRN012605000490673.

BMJ (Clinical research ed.) · randomised controlled trial · 108 citationsread the source →

A Community Health Worker-Led Positive Psychology Intervention for African American Older Adults With Chronic Pain.

Background and objectives: Experiencing structural racism over the life course contributes to disproportionate pain-related disability among African American older adults. Positive STEPS, delivered by community health workers, is a culturally congruent chronic pain self-management intervention that incorporates positive psychology principles and gives attention to social determinants of pain and pain management. Research design and methods: We conducted a randomized pilot trial among older adults with chronic musculoskeletal pain in an underserved, primarily African American community (Detroit, Michigan). The 7-week intervention included weekly telephone sessions with a community health worker; web-based videos teaching pain self-management skills; positive activities (e.g., Life Review, Gratitude Jar); and use of wearable activity trackers. Outcomes were measured at baseline and 8-week follow-up. We assessed participant retention, engagement, and satisfaction. Results: Study completers (n = 46; 90% retention) were 93% African American, 89% female, mean 72 years, and completed 5.7 of 7 sessions. Intervention participants versus controls showed greater improvement in PROMIS Pain Interference (4.3-point T-score decrease vs. 0.4-point increase; p = .01) and the Pain Self-Efficacy Questionnaire (p = .007). Furthermore, compared with controls, significantly more intervention participants reported "better" or "much better" global functioning (86% vs. 25%; p = .000) and pain (67% vs. 21%; p = .003) since baseline. Improvements in physical functioning, social participation, and resilience were noted, but differences were not significant. Participant feedback on the intervention was overwhelmingly positive. Discussion and implications: A community health worker-led chronic pain self-management intervention combining positive activities with self-management skills training demonstrated the potential to enhance pain-related functioning among a vulnerable group of older adults. Clinical trial number: NCT04321239.

The Gerontologist · randomised controlled trial · 16 citationsread the source →

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

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

The lancet. Psychiatry · 9 citationsread the source →

Cost and cost-effectiveness of a universal HIV testing and treatment intervention in Zambia and South Africa: evidence and projections from the HPTN 071 (PopART) trial.

Background: The HPTN 071 (PopART) trial showed that a combination HIV prevention package including universal HIV testing and treatment (UTT) reduced population-level incidence of HIV compared with standard care. However, evidence is scarce on the costs and cost-effectiveness of such an intervention. Methods: Using an individual-based model, we simulated the PopART intervention and standard care with antiretroviral therapy (ART) provided according to national guidelines for the 21 trial communities in Zambia and South Africa (for all individuals aged >14 years), with model parameters and primary cost data collected during the PopART trial and from published sources. Two intervention scenarios were modelled: annual rounds of PopART from 2014 to 2030 (PopART 2014-30; as the UNAIDS Fast-Track target year) and three rounds of PopART throughout the trial intervention period (PopART 2014-17). For each country, we calculated incremental cost-effectiveness ratios (ICERs) as the cost per disability-adjusted life-year (DALY) and cost per HIV infection averted. Cost-effectiveness acceptability curves were used to indicate the probability of PopART being cost-effective compared with standard care at different thresholds of cost per DALY averted. We also assessed budget impact by projecting undiscounted costs of the intervention compared with standard care up to 2030. Findings: During 2014-17, the mean cost per person per year of delivering home-based HIV counselling and testing, linkage to care, promotion of ART adherence, and voluntary medical male circumcision via community HIV care providers for the simulated population was US$6·53 (SD 0·29) in Zambia and US$7·93 (0·16) in South Africa. In the PopART 2014-30 scenario, median ICERs for PopART delivered annually until 2030 were $2111 (95% credible interval [CrI] 1827-2462) per HIV infection averted in Zambia and $3248 (2472-3963) per HIV infection averted in South Africa; and $593 (95% CrI 526-674) per DALY averted in Zambia and $645 (538-757) per DALY averted in South Africa. In the PopART 2014-17 scenario, PopART averted one infection at a cost of $1318 (1098-1591) in Zambia and $2236 (1601-2916) in South Africa, and averted one DALY at $258 (225-298) in Zambia and $326 (266-391) in South Africa, when outcomes were projected until 2030. The intervention had almost 100% probability of being cost-effective at thresholds greater than $700 per DALY averted in Zambia, and greater than $800 per DALY averted in South Africa, in the PopART 2014-30 scenario. Incremental programme costs for annual rounds until 2030 were $46·12 million (for a mean of 341 323 people) in Zambia and $30·24 million (for a mean of 165 852 people) in South Africa. Interpretation: Combination prevention with universal home-based testing can be delivered at low annual cost per person but accumulates to a considerable amount when scaled for a growing population. Combination prevention including UTT is cost-effective at thresholds greater than $800 per DALY averted and can be an efficient strategy to reduce HIV incidence in high-prevalence settings. Funding: US National Institutes of Health, President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation.

The Lancet. Global health · 24 citationsread the source →

Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease.

Background: Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease. Exacerbation action plans are considered to be a key component of COPD self-management interventions. Studies assessing these interventions show contradictory results. In this Cochrane Review, we compared the effectiveness of COPD self-management interventions that include action plans for acute exacerbations of COPD (AECOPD) with usual care. Objectives: To evaluate the efficacy of COPD-specific self-management interventions that include an action plan for exacerbations of COPD compared with usual care in terms of health-related quality of life, respiratory-related hospital admissions and other health outcomes. Search methods: We searched the Cochrane Airways Group Specialised Register of trials, trials registries, and the reference lists of included studies to May 2016. Selection criteria: We included randomised controlled trials evaluating a self-management intervention for people with COPD published since 1995. To be eligible for inclusion, the self-management intervention included a written action plan for AECOPD and an iterative process between participant and healthcare provider(s) in which feedback was provided. We excluded disease management programmes classified as pulmonary rehabilitation or exercise classes offered in a hospital, at a rehabilitation centre, or in a community-based setting to avoid overlap with pulmonary rehabilitation as much as possible. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. Study authors were contacted to obtain additional information and missing outcome data where possible. When appropriate, study results were pooled using a random-effects modelling meta-analysis. The primary outcomes of the review were health-related quality of life (HRQoL) and number of respiratory-related hospital admissions. Main results: We included 22 studies that involved 3,854 participants with COPD. The studies compared the effectiveness of COPD self-management interventions that included an action plan for AECOPD with usual care. The follow-up time ranged from two to 24 months and the content of the interventions was diverse. Over 12 months, there was a statistically significant beneficial effect of self-management interventions with action plans on HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score, where a lower score represents better HRQoL. We found a mean difference from usual care of -2.69 points (95% CI -4.49 to -0.90; 1,582 participants; 10 studies; high-quality evidence). Intervention participants were at a statistically significant lower risk for at least one respiratory-related hospital admission compared with participants who received usual care (OR 0.69, 95% CI 0.51 to 0.94; 3,157 participants; 14 studies; moderate-quality evidence). The number needed to treat to prevent one respiratory-related hospital admission over one year was 12 (95% CI 7 to 69) for participants with high baseline risk and 17 (95% CI 11 to 93) for participants with low baseline risk (based on the seven studies with the highest and lowest baseline risk respectively).There was no statistically significant difference in the probability of at least one all-cause hospital admission in the self-management intervention group compared to the usual care group (OR 0.74, 95% CI 0.54 to 1.03; 2467 participants; 14 studies; moderate-quality evidence). Furthermore, we observed no statistically significant difference in the number of all-cause hospitalisation days, emergency department visits, General Practitioner visits, and dyspnoea scores as measured by the (modified) Medical Research Council questionnaire for self-management intervention participants compared to usual care participants. There was no statistically significant effect observed from self-management on the number of COPD exacerbations and no difference in all-cause mortality observed (RD 0.0019, 95% CI -0.0225 to 0.0263; 3296 participants; 16 studies; moderate-quality evidence). Exploratory analysis showed a very small, but significantly higher respiratory-related mortality rate in the self-management intervention group compared to the usual care group (RD 0.028, 95% CI 0.0049 to 0.0511; 1219 participants; 7 studies; very low-quality evidence).Subgroup analyses showed significant improvements in HRQoL in self-management interventions with a smoking cessation programme (MD -4.98, 95% CI -7.17 to -2.78) compared to studies without a smoking cessation programme (MD -1.33, 95% CI -2.94 to 0.27, test for subgroup differences: Chi² = 6.89, df = 1, P = 0.009, I² = 85.5%). The number of behavioural change techniques clusters integrated in the self-management intervention, the duration of the intervention and adaptation of maintenance medication as part of the action plan did not affect HRQoL. Subgroup analyses did not detect any potential variables to explain differences in respiratory-related hospital admissions among studies. Authors' conclusions: Self-management interventions that include a COPD exacerbation action plan are associated with improvements in HRQoL, as measured with the SGRQ, and lower probability of respiratory-related hospital admissions. No excess all-cause mortality risk was observed, but exploratory analysis showed a small, but significantly higher respiratory-related mortality rate for self-management compared to usual care. For future studies, we would like to urge only using action plans together with self-management interventions that meet the requirements of the most recent COPD self-management intervention definition. To increase transparency, future study authors should provide more detailed information regarding interventions provided. This would help inform further subgroup analyses and increase the ability to provide stronger recommendations regarding effective self-management interventions that include action plans for AECOPD. For safety reasons, COPD self-management action plans should take into account comorbidities when used in the wider population of people with COPD who have comorbidities. Although we were unable to evaluate this strategy in this review, it can be expected to further increase the safety of self-management interventions. We also advise to involve Data and Safety Monitoring Boards for future COPD self-management studies.

The Cochrane database of systematic reviews · meta-analysis · 187 citationsread the source →

Mindfulness-based interventions for binge eating: a systematic review and meta-analysis.

Mindfulness-based interventions are increasingly used to treat binge eating. The effects of these interventions have not been reviewed comprehensively. This systematic review and meta-analysis sought to summarize the literature on mindfulness-based interventions and determine their impact on binge eating behavior. PubMED, Web of Science, and PsycINFO were searched using keywords binge eating, overeating, objective bulimic episodes, acceptance and commitment therapy, dialectical behavior therapy, mindfulness, meditation, mindful eating. Of 151 records screened, 19 studies met inclusion criteria. Most studies showed effects of large magnitude. Results of random effects meta-analyses supported large or medium-large effects of these interventions on binge eating (within-group random effects mean Hedge's g = -1.12, 95 % CI -1.67, -0.80, k = 18; between-group mean Hedge's g = -0.70, 95 % CI -1.16, -0.24, k = 7). However, there was high statistical heterogeneity among the studies (within-group I(2) = 93 %; between-group I(2) = 90 %). Limitations and future research directions are discussed.

Journal of behavioral medicine · meta-analysis · 119 citationsread the source →

Not to be overshadowed or overlooked: functional impairments associated with comorbid anxiety disorders in youth with ASD.

This study's objective was to examine associations between comorbid anxiety disorders and difficulties commonly attributed to both anxiety and ASD (autism spectrum disorder) including self-injury, depressive symptoms, functional communication, social skill deficits and parent stress, in a well-characterized sample of youth with ASD. Fifty-nine verbally fluent participants (7-17 years; 93% Caucasian) diagnosed with ASD and their parents completed semistructured diagnostic interviews to confirm ASD diagnosis and assess for anxiety disorders. Parents completed questionnaires on child behavior and social skill as well as parental stress. Co-occurring anxiety disorders were associated with more parent-reported self-injurious behavior, depressive symptoms, and parental stress in youth with ASD, after controlling for other influential variables (e.g., ASD severity, cognitive ability, medication status). In contrast, youth with co-occurring anxiety disorders appeared to have significantly stronger parent-reported functional communication than youth with ASD alone as well as a comparable ability, according to parents, to initiate social interaction and develop relationships. Findings support a profile of challenges and relative strengths associated with the presence of anxiety disorders in youth with ASD. Though more research is needed to determine the direction of these associations, results provide further rationale for improving recognition and targeted treatment of this comorbidity in clinical practice.

Behavior therapy · 116 citationsread the source →

Interventions for fatigue in people with kidney failure requiring dialysis.

Background: Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD). Objectives: We aimed to evaluate the effects of pharmacological and non-pharmacological interventions on fatigue in people with kidney failure receiving dialysis, including HD and peritoneal dialysis (PD), including any setting and frequency of the dialysis treatment. Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 18 October 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: Studies evaluating pharmacological and non-pharmacological interventions affecting levels of fatigue or fatigue-related outcomes in people receiving dialysis were included. Studies were eligible if fatigue or fatigue-related outcomes were reported as a primary or secondary outcome. Any mode, frequency, prescription, and duration of therapy were considered. Data collection and analysis: Three authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI) or standardised MD (SMD) if different scales were used. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results: Ninety-four studies involving 8191 randomised participants were eligible. Pharmacological and non-pharmacological interventions were compared either to placebo or control, or to another pharmacological or non-pharmacological intervention. In the majority of domains, risks of bias in the included studies were unclear or high. In low certainty evidence, when compared to control, exercise may improve fatigue (4 studies, 217 participants (Iowa Fatigue Scale, Modified Fatigue Impact Scale, Piper Fatigue Scale (PFS), or Haemodialysis-Related Fatigue scale score): SMD -1.18, 95% CI -2.04 to -0.31; I2 = 87%) in HD. In low certainty evidence, when compared to placebo or standard care, aromatherapy may improve fatigue (7 studies, 542 participants (Fatigue Severity Scale (FSS), Rhoten Fatigue Scale (RFS), PFS or Brief Fatigue Inventory score): SMD -1.23, 95% CI -1.96 to -0.50; I2 = 93%) in HD. In low certainty evidence, when compared to no intervention, massage may improve fatigue (7 studies, 657 participants (FSS, RFS, PFS or Visual Analogue Scale (VAS) score): SMD -1.06, 95% CI -1.47, -0.65; I2 = 81%) and increase energy (2 studies, 152 participants (VAS score): MD 4.87, 95% CI 1.69 to 8.06, I2 = 59%) in HD. In low certainty evidence, when compared to placebo or control, acupressure may reduce fatigue (6 studies, 459 participants (PFS score, revised PFS, or Fatigue Index): SMD -0.64, 95% CI -1.03 to -0.25; I2 = 75%) in HD. A wide range of heterogenous interventions and fatigue-related outcomes were reported for exercise, aromatherapy, massage and acupressure, preventing our capability to pool and analyse the data. Due to the paucity of studies, the effects of pharmacological and other non-pharmacological interventions on fatigue or fatigue-related outcomes, including non-physiological neutral amino acid, relaxation with or without music therapy, meditation, exercise with nandrolone, nutritional supplementation, cognitive-behavioural therapy, ESAs, frequent HD sections, home blood pressure monitoring, blood flow rate reduction, serotonin reuptake inhibitor, beta-blockers, anabolic steroids, glucose-enriched dialysate, or light therapy, were very uncertain. The effects of pharmacological and non-pharmacological treatments on death, cardiovascular diseases, vascular access, QoL, depression, anxiety, hypertension or diabetes were sparse. No studies assessed tiredness, exhaustion or asthenia. Adverse events were rarely and inconsistently reported. Authors' conclusions: Exercise, aromatherapy, massage and acupressure may improve fatigue compared to placebo, standard care or no intervention. Pharmacological and other non-pharmacological interventions had uncertain effects on fatigue or fatigue-related outcomes in people receiving dialysis. Future adequately powered, high-quality studies are likely to change the estimated effects of interventions for fatigue and fatigue-related outcomes in people receiving dialysis.

The Cochrane database of systematic reviews · meta-analysis · 16 citationsread the source →

Adherence to Once-daily and Twice-daily Direct-acting Antiviral Therapy for Hepatitis C Infection Among People With Recent Injection Drug Use or Current Opioid Agonist Therapy.

Background: This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. Methods: SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. Results: Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28-4.82]), unstable housing (OR, 2.18 [95% CI, 1.01-4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47-5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897). Conclusions: This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 59 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 →

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

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

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

Sexual dysfunction related to psychiatric disorders: a systematic review.

Background: Sexual dysfunction is thought to be highly prevalent in patients with psychiatric disorders. Factors such as the use of psychotropic substances (ie, psychopharmaceuticals and drugs), age, or somatic diseases may contribute to sexual problems, but the extent to which psychopathology itself affects sexual functioning is not well understood. Aim: The study sought to provide an overview of the literature on the prevalence of sexual dysfunction in psychotropic-free and somatic disease-free psychiatric patients. Method: A systematic review (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) was conducted by 2 authors (TH and AWMP) independently, with the review process being monitored by a third author. Relevant articles on the relationship between sexual dysfunctions and psychopathology were searched in PubMed, Web of Science, and PsycINFO from inception until June 16, 2022. The study methods were entered in the international register of systematic reviews PROSPERO (2021, CRD42021223410). Outcomes: The main outcome measures were sexual dysfunction and sexual satisfaction. Results: Twenty-four studies were identified, including a total of 1199 patients. These studies focused on depressive disorders (n = 9 studies), anxiety disorders (n = 7), obsessive- compulsive disorder (OCD) (n = 5), schizophrenia (n = 4), and posttraumatic stress disorder (n = 2). No studies on bipolar disorder were found. Reported prevalence rates of sexual dysfunction in psychiatric disorders were 45% to 93% for depressive disorders, 33% to 75% for anxiety disorders, 25% to 81% for OCD, and 25% for schizophrenia. The most affected phase of the sexual response cycle was sexual desire, in both men and women with depressive disorders, posttraumatic stress disorder, and schizophrenia. Patients with OCD and anxiety disorders most frequently reported dysfunction in the orgasm phase, 24% to 44% and 7% to 48%, respectively. Clinical implications: The high prevalence of sexual dysfunction requires more clinical attention by means of psychoeducation, clinical guidance, sexual anamnesis, and additional sexological treatment. Strengths and limitations: This is the first systematic review on sexual dysfunction in psychotropic-free and somatic disease-free psychiatric patients. Limitations include the small number of studies, small sample sizes, the use of multiple questionnaires (some not validated), which may contribute to bias. Conclusion: A limited number of studies identified a high prevalence of sexual dysfunction in patients with a psychiatric disorder, with substantial variation between patient groups in frequency and phase of reported sexual dysfunction.

The journal of sexual medicine · systematic review · 33 citationsread the source →

Effect of an early perinatal depression intervention on long-term child development outcomes: follow-up of the Thinking Healthy Programme randomised controlled trial.

Background: Perinatal depression has been linked with deleterious child development outcomes, yet maternal depression interventions have not been shown to have lasting effects on child development, and evidence is not available from countries of low or middle income. In the Thinking Healthy Programme cluster-randomised controlled trial, a perinatal depression intervention was assessed in Pakistan in 2006-07. The intervention significantly reduced depression levels 12 months post partum compared with a control. We aimed to assess the effect of this same intervention on the cognitive, socioemotional, and physical development of children at around age 7 years. Methods: Mother-child dyads who participated in the Thinking Healthy Programme cluster-randomised controlled trial were interviewed when the index child was about 7 years old. A reference group of 300 mothers who did not have prenatal depression and, therefore, did not receive the original intervention, was enrolled with their children at the same time. The primary cognitive outcome was the score on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV); primary socioemotional outcomes included scores on the Strengths and Difficulties Questionnaire (SDQ) and the Spence Children's Anxiety Scale (SCAS); and primary physical outcomes were height-for-age, weight-for-age, and body-mass index (BMI)-for-age Z scores. Generalised linear modelling with random effects to account for clustering was the main method of analysis. Analyses were by intention to treat. The Thinking Healthy Programme cluster-randomised trial was registered at ISRCTN.com, number ISRCTN65316374. Findings: Of 705 participating mother-child dyads interviewed at the end of the Thinking Healthy Programme randomised controlled trial, 584 (83%) dyads were enrolled. 289 mothers had received the intervention and 295 had received a control consisting of enhanced usual care. The mean age of the children was 7·6 years (SD 0·1). Overall, cognitive, socioemotional, or physical development outcomes did not differ between children in the intervention or control groups whose mothers had prenatal depression. When compared with the reference group of children whose mothers did not have prenatal depression, the Thinking Healthy Programme trial children had worse socioemotional outcomes; mean scores were significantly higher on the SDQ for total difficulty (11·34 vs 10·35; mean difference 0·78, 95% CI 0·09-1·47; p=0·03) and on the SCAS for anxiety (21·33 vs 17·57; mean difference 2·93, 1·15-4·71; p=0·0013). Cognitive and physical outcomes did not differ. Interpretation: Our findings show that cognitive, socioemotional, and physical developmental outcomes of children at age 7 years whose mother had prenatal depression did not differ between those who received the Thinking Healthy Programme intervention and those who received the control. Further investigation is needed to understand what types of complex interventions or approaches are needed for long-term gains in maternal and child wellbeing. Prolonged, detailed, and frequent follow-up is warranted for all interventions. Funding: Grand Challenges Canada (Government of Canada), Saving Brains programme.

The lancet. Psychiatry · randomised controlled trial · 76 citationsread the source →

Differences in attitudes and beliefs toward end-of-life care between hematologic and solid tumor oncology specialists.

Background: Patients with hematologic malignancies often receive aggressive care at the end-of-life. To better understand the end-of-life decision-making process among oncology specialists, we compared the cancer treatment recommendations, and attitudes and beliefs toward palliative care between hematologic and solid tumor specialists. Patients and methods: We randomly surveyed 120 hematologic and 120 solid tumor oncology specialists at our institution. Respondents completed a survey examining various aspects of end-of-life care, including palliative systemic therapy using standardized case vignettes and palliative care proficiency. Results: Of 240 clinicians, 182 (76%) clinicians responded. Compared with solid tumor specialists, hematologic specialists were more likely to favor prescribing systemic therapy with moderate toxicity and no survival benefit for patients with Eastern Cooperative Oncology Group (ECOG) performance status 4 and an expected survival of 1 month (median preference 4 versus 1, in which 1 = strong against treatment and 7 = strongly recommend treatment, P < 0.0001). This decision was highly polarized. Hematologic specialists felt less comfortable discussing death and dying (72% versus 88%, P = 0.007) and hospice referrals (81% versus 93%, P = 0.02), and were more likely to feel a sense of failure with disease progression (46% versus 31%, P = 0.04). On multivariate analysis, hematologic specialty [odds ratio (OR) 2.77, P = 0.002] and comfort level with prescribing treatment to ECOG 4 patients (OR 3.79, P = 0.02) were associated with the decision to treat in the last month of life. Conclusions: We found significant differences in attitudes and beliefs toward end-of-life care between hematologic and solid tumor specialists, and identified opportunities to standardize end-of-life care.

Annals of oncology : official journal of the European Society for Medical Oncology · randomised controlled trial · 97 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 →

A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial.

Background: Attention-deficit hyperactivity disorder (ADHD) is a common paediatric neurodevelopmental disorder with substantial effect on families and society. Alternatives to traditional care, including novel digital therapeutics, have shown promise to remediate cognitive deficits associated with this disorder and may address barriers to standard therapies, such as pharmacological interventions and behavioural therapy. AKL-T01 is an investigational digital therapeutic designed to target attention and cognitive control delivered through a video game-like interface via at-home play for 25 min per day, 5 days per week for 4 weeks. This study aimed to assess whether AKL-T01 improved attentional performance in paediatric patients with ADHD. Methods: The Software Treatment for Actively Reducing Severity of ADHD (STARS-ADHD) was a randomised, double-blind, parallel-group, controlled trial of paediatric patients (aged 8-12 years, without disorder-related medications) with confirmed ADHD and Test of Variables of Attention (TOVA) Attention Performance Index (API) scores of -1·8 and below done by 20 research institutions in the USA. Patients were randomly assigned 1:1 to AKL-T01 or a digital control intervention. The primary outcome was mean change in TOVA API from pre-intervention to post-intervention. Safety, tolerability, and compliance were also assessed. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02674633 and is completed. Findings: Between July 15, 2016, and Nov 30, 2017, 857 patients were evaluated and 348 were randomly assigned to receive AKL-T01 or control. Among patients who received AKL-T01 (n=180 [52%]; mean [SD] age, 9·7 [1·3] years) or control (n=168 [48%]; mean [SD] age, 9·6 [1·3] years), the non-parametric estimate of the population median change from baseline TOVA API was 0·88 (95% CI 0·24-1·49; p=0·0060). The mean (SD) change from baseline on the TOVA API was 0·93 (3·15) in the AKL-T01 group and 0·03 (3·16) in the control group. There were no serious adverse events or discontinuations. Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180). Patient compliance was a mean of 83 (83%) of 100 expected sessions played (SD, 29·2 sessions). Interpretation: Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events. Funding: Sponsored by Akili Interactive Labs.

The Lancet. Digital health · randomised controlled trial · 215 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 →

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study.

Background: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 103 citationsread the source →

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

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

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

Association of behaviour change techniques with effectiveness of dietary interventions among adults of retirement age: a systematic review and meta-analysis of randomised controlled trials.

Background: There is a need for development of more effective interventions to achieve healthy eating, enhance healthy ageing, and to reduce the risk of age-related diseases. The aim of this study was to identify the behaviour change techniques (BCTs) used in complex dietary behaviour change interventions and to explore the association between BCTs utilised and intervention effectiveness. Methods: We undertook a secondary analysis of data from a previous systematic review with meta-analysis of the effectiveness of dietary interventions among people of retirement age. BCTs were identified using the reliable CALO-RE taxonomy in studies reporting fruit and vegetable (F and V) consumption as outcomes. The mean difference in F and V intake between active and control arms was compared between studies in which the BCTs were identified versus those not using the BCTs. Random-effects meta-regression models were used to assess the association of interventions BCTs with F and V intakes. Results: Twenty-eight of the 40 BCTs listed in the CALO-RE taxonomy were identified in the 22 papers reviewed. Studies using the techniques 'barrier identification/problem solving' (93 g, 95% confidence interval (CI) 48 to 137 greater F and V intake), 'plan social support/social change' (78 g, 95%CI 24 to 132 greater F and V intake), 'goal setting (outcome)' (55 g 95%CI 7 to 103 greater F and V intake), 'use of follow-up prompts' (66 g, 95%CI 10 to 123 greater F and V intake) and 'provide feedback on performance' (39 g, 95%CI -2 to 81 greater F and V intake) were associated with greater effects of interventions on F and V consumption compared with studies not using these BCTs. The number of BCTs per study ranged from 2 to 16 (median = 6). Meta-regression showed that one additional BCT led to 8.3 g (95%CI 0.006 to 16.6 g) increase in F and V intake. Conclusions: Overall, this study has identified BCTs associated with effectiveness suggesting that these might be active ingredients of dietary interventions which will be effective in increasing F and V intake in older adults. For interventions targeting those in the peri-retirement age group, 'barrier identification/problem solving' and 'plan for social support/social change' may be particularly useful in increasing the effectiveness of dietary interventions.

BMC medicine · meta-analysis · 78 citationsread the source →

Development and Feasibility Testing of Internet-Delivered Acceptance and Commitment Therapy for Severe Health Anxiety: Pilot Study.

Background: Severe health anxiety (hypochondriasis), or illness anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, is characterized by preoccupation with fear of suffering from a serious illness in spite of medical reassurance. It is a debilitating, prevalent disorder associated with increased health care utilization. Still, there is a lack of easily accessible specialized treatment for severe health anxiety. Objective: The aims of this paper were to (1) describe the development and setup of a new internet-delivered acceptance and commitment therapy (iACT) program for patients with severe health anxiety using self-referral and a video-based assessment; and (2) examine the feasibility and potential clinical efficacy of iACT for severe health anxiety. Methods: Self-referred patients (N=15) with severe health anxiety were diagnostically assessed by a video-based interview. They received 7 sessions of clinician-supported iACT comprising self-help texts, video clips, audio files, and worksheets over 12 weeks. Self-report questionnaires were obtained at baseline, post-treatment, and at 3-month follow-up. The primary outcome was Whiteley-7 Index (WI-7) measuring health anxiety severity. Depressive symptoms, health-related quality of life (HRQoL), life satisfaction, and psychological flexibility were also assessed. A within-group design was employed. Means, standard deviations, and effect sizes using the standardized response mean (SRM) were estimated. Post-treatment interviews were conducted to evaluate the patient experience of the usability and acceptability of the treatment setup and program. Results: The self-referral and video-based assessments were well received. Most patients (12/15, 80%) completed the treatment, and only 1 (1/15, 7%) dropped out. Post-treatment (14/15, 93%) and 3-month follow-up (12/15, 80%) data were available for almost all patients. Paired t tests showed significant improvements on all outcome measures both at post-treatment and 3-month follow-up, except on one physical component subscale of HRQoL. Health anxiety symptoms decreased with 33.9 points at 3-month follow-up (95% CI 13.6-54.3, t11= 3.66, P=.004) with a large within-group effect size of 1.06 as measured by the SRM. Conclusions: Treatment adherence and potential efficacy suggest that iACT may be a feasible treatment for health anxiety. The uncontrolled design and small sample size of the study limited the robustness of the findings. Therefore, the findings should be replicated in a randomized controlled trial. Potentially, iACT may increase availability and accessibility of specialized treatment for health anxiety. Trial registration: Danish Data Protection Agency, Central Denmark Region: 1-16-02-427-14; https://www.rm.dk/sundhed/faginfo/forskning/datatilsynet/ (Archived by Webcite at http://www.webcitation.org/6yDA7WovM).

JMIR mental health · 18 citationsread the source →

Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II).

Objectives: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. Trial design: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. Participants: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. Inclusion criteria: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the "informed consent form" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. Intervention and comparator: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x107 human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. Main outcomes: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. Abbreviations: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h ± 30min, 24h ± 30min after the injection) and follow-up period D90 ± 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h ± 30min, 24h ± 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 ± 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 ± 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 β, IL-2, TNF-a, ITN-γ), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood β-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 ± 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h ± 30min after the injection and not detected after discharge). Randomization: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. Blinding (masking): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. Numbers to be randomized (sample size): Twenty participants will be randomized to the experimental and control groups (10 per group). Trial status: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16th April and an estimated date of the recruitment of the final participants will be around end of July. . Trial registration: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials · clinical trial · 31 citationsread the source →

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.

Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding: Vivus.

Lancet (London, England) · randomised controlled trial · 667 citationsread the source →

Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.

Background: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.

The Lancet. Oncology · randomised controlled trial · 277 citationsread the source →

Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.

Background: Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status. Methods: We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519. Findings: We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively). Interpretation: StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support. Funding: National Prevention Research Initiative.

The Lancet. Respiratory medicine · randomised controlled trial · 99 citationsread the source →

Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial.

Background: Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB). Methods: Patients (≥50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day) according to a computer-generated list. Patients and all physicians who had contact with them were masked to treatment assignment. No primary endpoint was defined. Safety analyses were done for all patients who took at least one dose of memantine or placebo, and efficacy analyses were done for all patients who had at least one valid postbaseline assessment. This trial is registered with ClinicalTrials.gov, number NCT00855686. Findings: Of the 199 patients randomly assigned to treatment, 34 with DLB and 62 with PDD were given memantine, and 41 with DLB and 58 with PDD were given placebo. 159 (80%) patients completed the study: 80 in the memantine group and 79 in the placebo group. 93 patients treated with memantine and 97 patients treated with placebo were included in the efficacy analysis. At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo (mean change from baseline 3·3 vs 3·9, respectively, difference -0·6 [95% CI -1·2 to -0·1]; p=0·023). No significant differences were noted between the two treatments in patients with PDD (3·6 with memantine vs 3·8 with placebo, -0·1 [-0·6 to 0·3]; p=0·576) or in the total population (3·5 with memantine vs 3·8 with placebo, -0·3 [-0·7 to 0·1]; p=0·120). Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group (-4·3 vs 1·7, respectively, -5·9 [-11·6 to -0·2]; p=0·041) in patients with DLB, but not in those with PDD (-1·6 vs -0·1, respectively, -1·4 [-5·9 to 3·0]; p=0·522) or in the total patient population (-2·6 vs 0·4, respectively, -2·9 [-6·3 to 0·5]; p=0·092). In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations. The incidence of adverse events and number of discontinuations due to adverse events were similar in the two groups. The most common serious adverse events were stroke (n=3 in memantine group), falls (n=2 in memantine group; n=1 in placebo group), and worsening of dementia (n=2 in memantine group). Interpretation: Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients. Funding: Lundbeck.

The Lancet. Neurology · randomised controlled trial · 262 citationsread the source →

Creating Opportunities for Parent Empowerment: Program Effects on the Mental Health/Coping Outcomes of Critically Ill Young Children and Their Mothers

OBJECTIVE: Increasing numbers of children in the United States (ie, approximately 200 children per 100,000 population) require intensive care annually, because of advances in pediatric therapeutic techniques and a changing spectrum of pediatric disease. These children are especially vulnerable to a multitude of short- and long-term negative emotional, behavioral, and academic outcomes, including a higher risk of posttraumatic stress disorder (PTSD) and a greater need for psychiatric treatment, compared with matched hospitalized children who do not require intensive care. In addition, the parents of these children are at risk for the development of PTSD, as well as other negative emotional outcomes (eg, depression and anxiety disorders). There has been little research conducted to systematically determine the effects of interventions aimed at improving psychosocial outcomes for critically ill children and their parents, despite recognition of the adverse effects of critical care hospitalization on the nonphysiologic well-being of patients and their families. The purpose of this study was to evaluate the effects of a preventive educational-behavioral intervention program, the Creating Opportunities for Parent Empowerment (COPE) program, initiated early in the intensive care unit hospitalization on the mental health/psychosocial outcomes of critically ill young children and their mothers. DESIGN: A randomized, controlled trial with follow-up assessments 1, 3, 6, and 12 months after hospitalization was conducted with 174 mothers and their 2- to 7-year-old children who were unexpectedly hospitalized in the pediatric intensive care units (PICUs) of 2 children's hospitals. The final sample of 163 mothers ranged in age from 18 to 52 years, with a mean of 31.2 years. Among the mothers reporting race/ethnicity, the sample included 116 white (71.2%), 33 African American (20.3%), 3 Hispanic (1.8%), and 2 Indian (1.2%) mothers. The mean age of the hospitalized children was 50.3 months. Ninety-nine children (60.7%) were male and 64 (39.3%) were female. The major reasons for hospitalization were respiratory problems, accidental trauma, neurologic problems, and infections. Fifty-seven percent (n = 93) of the children had never been hospitalized overnight, and none had experienced a previous PICU hospitalization. INTERVENTIONS: Mothers in the experimental (COPE) group received a 3-phase educational-behavioral intervention program 1) 6 to 16 hours after PICU admission, 2) 2 to 16 hours after transfer to the general pediatric unit, and 3) 2 to 3 days after their children were discharged from the hospital. Control mothers received a structurally equivalent control program. The COPE intervention was based on self-regulation theory, control theory, and the emotional contagion hypothesis. The COPE program, which was delivered with audiotapes and matching written information, as well as a parent-child activity workbook that facilitated implementing the audiotaped information, focused on increasing 1) parents' knowledge and understanding of the range of behaviors and emotions that young children typically display during and after hospitalization and 2) direct parent participation in their children's emotional and physical care. The COPE workbook, which was provided to parents and children after transfer from the PICU to the general pediatric unit, contained 3 activities to be completed before discharge from the hospital, ie, 1) puppet play to encourage expression of emotions in a nonthreatening manner, 2) therapeutic medical play to assist children in obtaining some sense of mastery and control over the hospital experience, and 3) reading and discussing Jenny's Wish, a story about a young child who successfully copes with a stressful hospitalization. OUTCOME MEASURES: Primary outcomes included maternal anxiety, negative mood state, depression, maternal beliefs, parental stress, and parent participation in their children's care, as well as child adjustment, which was assessed with the Behavioral Assessment System for Children (parent form). RESn (parent form). RESULTS: COPE mothers reported significantly less parental stress and participated more in their children's physical and emotional care on the pediatric unit, compared with control mothers, as rated by nurses who were blinded with respect to study group. In comparison with control mothers, COPE mothers reported less negative mood state, less depression, and fewer PTSD symptoms at certain follow-up assessments after hospitalization. In addition, COPE mothers reported stronger beliefs regarding their children's likely responses to hospitalization and how they could enhance their children's adjustment, compared with control mothers. COPE children, in comparison with control children, exhibited significantly fewer withdrawal symptoms 6 months after discharge, as well as fewer negative behavioral symptoms and externalizing behaviors at 12 months. COPE mothers also reported less hyperactivity and greater adaptability among their children at 12 months, compared with control mothers. One year after discharge, a significantly higher percentage of control group children (25.9%) exhibited clinically significant behavioral symptoms, compared with COPE children (2.3%). In addition, 6 and 12 months after discharge, significantly higher percentages of control group children exhibited clinically significant externalizing symptoms (6 months, 14.3%; 12 months, 22.2%), compared with COPE children (6 months, 1.8%; 12 months, 4.5%). CONCLUSIONS: The findings of this study indicated that mothers who received the COPE program experienced improved maternal functional and emotional coping outcomes, which resulted in significantly fewer child adjustment problems, in comparison with the control group. With the increasing prevalence of attention-deficit/hyperactivity disorder and externalizing problems among children and the documented lack of mental health screening and early intervention services for children in this country, the COPE intervention could help protect this high-risk population of children from developing these troublesome problems. As a result, the mental health status of children after critical care hospitalization could be improved. With routine provision of the COPE program in PICUs throughout the country, family burdens and costs associated with the mental health treatment of these problems might be substantially reduced.

PEDIATRICS · randomised controlled trial · 401 citationsread the source →

Trajectories of anxiety and depressive symptoms during enforced isolation due to COVID-19 in England: a longitudinal observational study.

Background: There is major concern about the impact of the global COVID-19 outbreak on mental health. Several studies suggest that mental health deteriorated in many countries before and during enforced isolation (ie, lockdown), but it remains unknown how mental health has changed week by week over the course of the COVID-19 pandemic. This study aimed to explore the trajectories of anxiety and depression over the 20 weeks after lockdown was announced in England, and compare the growth trajectories by individual characteristics. Methods: In this prospective longitudinal observational study, we analysed data from the UCL COVID-19 Social Study, a panel study weighted to population proportions, which collects information on anxiety (using the Generalised Anxiety Disorder assessment) and depressive symptoms (using the Patient Health Questionnaire) weekly in the UK since March 21, 2020. We included data from adults living in England who had at least three repeated measures between March 23 and Aug 9, 2020. Analyses were done using latent growth models, which were fitted to account for sociodemographic and health covariates. Findings: Between March 23, and Aug 9, data from over 70 000 adults were collected in the UCL COVID-19 Social Study. When including participants living in England with three follow-up measures and no missing values, our analytic sample consisted of 36 520 participants. The average depression score was 6·6 (SD=6·0, range 0-27) and the average anxiety score 5·7 (SD=5·6, range 0-21) in week 1. Anxiety and depression levels both declined across the first 20 weeks following the introduction of lockdown in England (b=-1·93, SE=0·26, p<0·0001 for anxiety; b=-2·52, SE=0·28, p<0·0001 for depressive symptoms). The fastest decreases were seen across the strict lockdown period (between weeks 2 and 5), with symptoms plateauing as further lockdown easing measures were introduced (between weeks 16 and 20). Being a woman or younger, having lower educational attainment, lower income, or pre-existing mental health conditions, and living alone or with children were all risk factors for higher levels of anxiety and depression at the start of lockdown. Many of these inequalities in experiences were reduced as lockdown continued, but differences were still evident 20 weeks after the start of lockdown. Interpretation: These data suggest that the highest levels of depression and anxiety occurred in the early stages of lockdown but declined fairly rapidly, possibly because individuals adapted to circumstances. Our findings emphasise the importance of supporting individuals in the lead-up to future lockdowns to try to reduce distress, and highlight that groups already at risk for poor mental health before the pandemic have remained at risk throughout lockdown and its aftermath. Funding: Nuffield Foundation, UK Research and Innovation, Wellcome Trust.

The lancet. Psychiatry · cohort or longitudinal · 745 citationsread the source →

Cognitive-motor dissociation and time to functional recovery in patients with acute brain injury in the USA: a prospective observational cohort study.

Background: Recovery trajectories of clinically unresponsive patients with acute brain injury are largely uncertain. Brain activation in the absence of a behavioural response to spoken motor commands can be detected by EEG, also known as cognitive-motor dissociation. We aimed to explore the role of cognitive-motor dissociation in predicting time to recovery in patients with acute brain injury. Methods: In this observational cohort study, we prospectively studied two independent cohorts of clinically unresponsive patients (aged ≥18 years) with acute brain injury. Machine learning was applied to EEG recordings to diagnose cognitive-motor dissociation by detecting brain activation in response to verbal commands. Survival statistics and shift analyses were applied to the data to identify an association between cognitive-motor dissociation and time to and magnitude of recovery. The prediction accuracy of the model that was built using the derivation cohort was assessed using the validation cohort. Functional outcomes of all patients were assessed with the Glasgow Outcome Scale-Extended (GOS-E) at hospital discharge and at 3, 6, and 12 months after injury. Patients who underwent withdrawal of life-sustaining therapies were censored, and death was treated as a competing risk. Findings: Between July 1, 2014, and Sept 30, 2021, we screened 598 patients with acute brain injury and included 193 (32%) patients, of whom 100 were in the derivation cohort and 93 were in the validation cohort. At 12 months, 28 (15%) of 193 unresponsive patients had a GOS-E score of 4 or above. Cognitive-motor dissociation was seen in 27 (14%) patients and was an independent predictor of shorter time to good recovery (hazard ratio 5·6 [95% CI 2·5-12·5]), as was underlying traumatic brain injury or subdural haematoma (4·4 [1·4-14·0]), a Glasgow Coma Scale score on admission of greater than or equal to 8 (2·2 [1·0-4·7]), and younger age (1·0 [1·0-1·1]). Among patients discharged home or to a rehabilitation setting, those diagnosed with cognitive-motor dissociation consistently had higher scores on GOS-E indicating better functional recovery compared with those without cognitive-motor dissociation, which was seen as early as 3 months after the injury (odds ratio 4·5 [95% CI 2·0-33·6]). Interpretation: Recovery trajectories of clinically unresponsive patients diagnosed with cognitive-motor dissociation early after brain injury are distinctly different from those without cognitive-motor dissociation. A diagnosis of cognitive-motor dissociation could inform the counselling of families of clinically unresponsive patients, and it could help clinicians to identify patients who will benefit from rehabilitation. Funding: US National Institutes of Health.

The Lancet. Neurology · cohort or longitudinal · 115 citationsread the source →

Psychological Resources and Strategies to Cope with Stress at Work.

Introduction: the choice of strategies to cope with stress has differential effects on individual and organizational outcomes (e.g. well-being and performance at work). This study examined to what extent individuals differing in their positive psychological resources (optimism, hope, self-efficacy and resilience) implement different strategies to cope with stress in terms of change, acceptance, or withdrawal from a source of stress in an organizational setting. Method: A questionnaire was filled out by 554 employees from different organizations representing a wide range of jobs and positions. Results: Structural Equation Modeling (SEM; χ 2(7) = 27.64, ρ < .01, GFI = .99, NFI = .91, CFI = .93, RMSEA = .07). Conclusion: the results indicated that psychological resources (optimism, hope, self-efficacy and resilience) were positively related to coping by change and by acceptance and negatively related to withdrawal. The theoretical implications are discussed.

International journal of psychological research · 14 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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Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. 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Glucocorticoids reverse IL-1-induced impairment of -adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases. Br J Pharmacol. 2002;135:987-96. [PMID: 11861327] CrossrefMedlineGoogle Scholar45. Eickelberg O, Roth M, Lorx R, Bruce V, Rudiger J, Johnson M, . Ligand-independent activation of the glucocorticoid receptor by 2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem. 1999;274:1005-10. [PMID: 9873044] CrossrefMedlineGoogle Scholar46. Pang L, Knox AJ. Regulation of TNF--induced eotaxin release from cultured human airway smooth muscle cells by 2-agonists and corticosteroids. FASEB J. 2001;15:261-269. [PMID: 11149914] CrossrefMedlineGoogle Scholar47. Korn SH, Wouters EF, Wesseling G, Arends JW, Thunnissen FB. Interaction between glucocorticoids and 2-agonists: and glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. Biochem Pharmacol. 1998;56:1561-9. [PMID: 9973176] CrossrefMedlineGoogle Scholar48. Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ. Glucocorticoid receptor activation following inhaled fluticasone and salmeterol [Abstract]. Am J Respir Crit Care Med. 2002;165:A616. Google Scholar49. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-8. [PMID: 12623857] CrossrefMedlineGoogle Scholar50. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, . A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99:8921-6. [PMID: 12070353] CrossrefMedlineGoogle Scholar51. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O'Connor BJ, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997;337:1412-8. [PMID: 9358138] CrossrefMedlineGoogle Scholar52. 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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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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 →

Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.

Background: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014. Methods: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years). Findings: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference -3·51 years, 95% CI -3·77 to -3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age. Interpretation: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled. Funding: British Heart Foundation and National Institute for Health Research.

Lancet (London, England) · 925 citationsread the source →

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders.

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, β-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, -1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD, depending on the disorder and parameter. Differences between cows without health disorders and those flagged by the AHMS for blood markers of metabolic and health status confirmed the observations of the CD and AHMS alerts. The overall sensitivity and timing of the AHMS alerts for cows with metabolic and digestive disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders.

Journal of dairy science · 106 citationsread the source →

Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study.

Background: Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups and younger people. We estimated the frequency of common disease combinations and identified non-random disease associations for all ages in a multiethnic population. Methods: In this population-based study, we examined multimorbidity and comorbidity patterns stratified by ethnicity or race, sex, and age for 308 health conditions using electronic health records from individuals included on the Clinical Practice Research Datalink linked with the Hospital Episode Statistics admitted patient care dataset in England. We included individuals who were older than 1 year and who had been registered for at least 1 year in a participating general practice during the study period (between April 1, 2010, and March 31, 2015). We identified the most common combinations of conditions and comorbidities for index conditions. We defined comorbidity as the accumulation of additional conditions to an index condition over an individual's lifetime. We used network analysis to identify conditions that co-occurred more often than expected by chance. We developed online interactive tools to explore multimorbidity and comorbidity patterns overall and by subgroup based on ethnicity, sex, and age. Findings: We collected data for 3 872 451 eligible patients, of whom 1 955 700 (50·5%) were women and girls, 1 916 751 (49·5%) were men and boys, 2 666 234 (68·9%) were White, 155 435 (4·0%) were south Asian, and 98 815 (2·6%) were Black. We found that a higher proportion of boys aged 1-9 years (132 506 [47·8%] of 277 158) had two or more diagnosed conditions than did girls in the same age group (106 982 [40·3%] of 265 179), but more women and girls were diagnosed with multimorbidity than were boys aged 10 years and older and men (1 361 232 [80·5%] of 1 690 521 vs 1 161 308 [70·8%] of 1 639 593). White individuals (2 097 536 [78·7%] of 2 666 234) were more likely to be diagnosed with two or more conditions than were Black (59 339 [60·1%] of 98 815) or south Asian individuals (93 617 [60·2%] of 155 435). Depression commonly co-occurred with anxiety, migraine, obesity, atopic conditions, deafness, soft-tissue disorders, and gastrointestinal disorders across all subgroups. Heart failure often co-occurred with hypertension, atrial fibrillation, osteoarthritis, stable angina, myocardial infarction, chronic kidney disease, type 2 diabetes, and chronic obstructive pulmonary disease. Spinal fractures were most strongly non-randomly associated with malignancy in Black individuals, but with osteoporosis in White individuals. Hypertension was most strongly associated with kidney disorders in those aged 20-29 years, but with dyslipidaemia, obesity, and type 2 diabetes in individuals aged 40 years and older. Breast cancer was associated with different comorbidities in individuals from different ethnic groups. Asthma was associated with different comorbidities between males and females. Bipolar disorder was associated with different comorbidities in younger age groups compared with older age groups. Interpretation: Our findings and interactive online tools are a resource for: patients and their clinicians, to prevent and detect comorbid conditions; research funders and policy makers, to redesign service provision, training priorities, and guideline development; and biomedical researchers and manufacturers of medicines, to provide leads for research into common or sequential pathways of disease and inform the design of clinical trials. Funding: UK Research and Innovation, Medical Research Council, National Institute for Health and Care Research, Department of Health and Social Care, Wellcome Trust, British Heart Foundation, and The Alan Turing Institute.

The Lancet. Digital health · 118 citationsread the source →

Repetitive negative thinking predicts depression and anxiety symptom improvement during brief cognitive behavioral therapy.

Repetitive negative thinking (RNT) is a common symptom across depression and anxiety disorders and preliminary evidence suggests that decreases in rumination and worry are related to improvement in depression and anxiety symptoms. However, despite its prevalence, relatively little is known about transdiagnostic RNT and its temporal associations with symptom improvement during treatment. The current study was designed to examine the influence of RNT on subsequent depression and anxiety symptoms during treatment. Participants (n = 131; 52% female; 93% White; M = 34.76 years) were patients presenting for treatment in a brief, cognitive behavior therapy based, partial hospitalization program. Participants completed multiple assessments of depression (Center for the Epidemiological Studies of Depression-10 scale), anxiety (the 7-item Generalized Anxiety Disorder Scale), and repetitive negative thinking (Perseverative Thinking Questionnaire) over the course of treatment. Results indicated statistically significant between and within person effects of RNT on depression and anxiety, even after controlling for the effect of time, previous symptom levels, referral source, and treatment length. RNT explained 22% of the unexplained variability in depression scores and 15% of the unexplained variability in anxiety scores beyond that explained by the control variables. RNT may be an important transdiagnostic treatment target for anxiety and depression.

Behaviour research and therapy · 53 citationsread the source →

Catastrophic health expenditure, social protection coverage, and financial coping strategies in adults with symptoms of chronic respiratory diseases in Kenya: a cross-sectional study.

Background: Despite the socioeconomic consequences of an increasing burden of chronic respiratory diseases, there is little evidence on the incidence and determinants of catastrophic health expenditure (CHE) in people with chronic respiratory disease symptoms in Kenya. We aimed to generate this evidence by collecting data on medical and non-medical costs, lost income, social protection coverage, and financial coping strategies for such people in Kenya. Methods: We conducted a cross-sectional survey of consecutively recruited adults seeking care for chronic respiratory disease symptoms at five public health-care facilities in Meru County, Kenya, between Sept 5, 2019, and Oct 1, 2020. Patient costs, National Health Insurance Fund (NHIF) coverage, financial coping strategies, and sociodemographic and clinical data were collected from surveys and medical records. The main study outcomes were the incidence of, and social and health factors associated with, CHE in this cohort. CHE incidence was calculated through the WHO threshold of direct out-of-pocket costs being greater than 10% of a household's monthly total expenditure. Multivariable logistic regression analyses generated adjusted odds ratios (aORs) with 95% CIs of health and social factors associated with CHE, including age, sex, education level, tobacco use, income, being accompanied, poverty level (with the first quintile being the richest to the fifth quintile being the poorest), NHIF usage, coping strategies, final diagnosis, and health system level at which they were seeking care. Findings: Of 319 eligible people invited, 296 (93%) consented to participate and completed surveys. Mean total cost was 1062 Kenyan shillings (KES; 95% CI 896-1228; US$9·1), of which 40·0% was due to direct non-medical costs (KES 425, 95% CI 361-489; $3·7), 36·7% to direct out-of-pocket medical costs (KES 390, 324-456; $3·1), and 23·3% to lost income (KES 247, 153-341, $2·1). 212 (72%) of 296 participants did not have NHIF, 282 (95%) of 296 used coping strategies during care-seeking, and 59 (20%) of 296 were accompanied by a carer during health-care seeking. 76 (26%) of 296 participants had CHE. CHE was associated with being aged 30-44 years old (aOR 2·6, 95% CI 1·3-5·3, p=0·010), being female (1·8, 1·3-2·7, p=0·0021), having higher than secondary school education (1·6, 1·1-2·3, p=0·0083), being accompanied during health-care-seeking visits (3·2, 1·7-5·9, p<0·0001), belonging to the second poverty quintile (2·0, 1·9-2·1, p<0·0001), and seeking care from subcounty hospitals (9·7, 9·6-9·8, p<0·0001) and county hospitals (25·1, 15·7-40·2, p<0·0001). Interpretation: These findings suggest a sizeable burden of CHE in people seeking care for chronic respiratory disease symptoms in Meru County in Kenya, driven by socioeconomic and sex inequalities and impaired access to health care and social protection. Funding: UK-Aid, UK National Institute for Health and Care Research, and UK Research and Innovation.

The Lancet. Global health · 3 citationsread the source →

Delivering Cognitive Behavior Therapy to Young Adults With Symptoms of Depression and Anxiety Using a Fully Automated Conversational Agent (Woebot): A Randomized Controlled Trial

Background Web-based cognitive-behavioral therapeutic (CBT) apps have demonstrated efficacy but are characterized by poor adherence. Conversational agents may offer a convenient, engaging way of getting support at any time. Objective The objective of the study was to determine the feasibility, acceptability, and preliminary efficacy of a fully automated conversational agent to deliver a self-help program for college students who self-identify as having symptoms of anxiety and depression. Methods In an unblinded trial, 70 individuals age 18-28 years were recruited online from a university community social media site and were randomized to receive either 2 weeks (up to 20 sessions) of self-help content derived from CBT principles in a conversational format with a text-based conversational agent (Woebot) (n=34) or were directed to the National Institute of Mental Health ebook, “Depression in College Students,” as an information-only control group (n=36). All participants completed Web-based versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), and the Positive and Negative Affect Scale at baseline and 2-3 weeks later (T2). Results Participants were on average 22.2 years old (SD 2.33), 67% female (47/70), mostly non-Hispanic (93%, 54/58), and Caucasian (79%, 46/58). Participants in the Woebot group engaged with the conversational agent an average of 12.14 (SD 2.23) times over the study period. No significant differences existed between the groups at baseline, and 83% (58/70) of participants provided data at T2 (17% attrition). Intent-to-treat univariate analysis of covariance revealed a significant group difference on depression such that those in the Woebot group significantly reduced their symptoms of depression over the study period as measured by the PHQ-9 (F=6.47; P=.01) while those in the information control group did not. In an analysis of completers, participants in both groups significantly reduced anxiety as measured by the GAD-7 (F1,54= 9.24; P=.004). Participants’ comments suggest that process factors were more influential on their acceptability of the program than content factors mirroring traditional therapy. Conclusions Conversational agents appear to be a feasible, engaging, and effective way to deliver CBT.

JMIR Mental Health · 2643 citationsread the source →

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

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

The Lancet. Neurology · 5441 citationsread the source →

Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: a cross-sectional study of 91 105 participants from the UK Biobank.

Background: Disruption of sleep and circadian rhythmicity is a core feature of mood disorders and might be associated with increased susceptibility to such disorders. Previous studies in this area have used subjective reports of activity and sleep patterns, but the availability of accelerometer-based data from UK Biobank participants permits the derivation and analysis of new, objectively ascertained circadian rhythmicity parameters. We examined associations between objectively assessed circadian rhythmicity and mental health and wellbeing phenotypes, including lifetime history of mood disorder. Methods: UK residents aged 37-73 years were recruited into the UK Biobank general population cohort from 2006 to 2010. We used data from a subset of participants whose activity levels were recorded by wearing a wrist-worn accelerometer for 7 days. From these data, we derived a circadian relative amplitude variable, which is a measure of the extent to which circadian rhythmicity of rest-activity cycles is disrupted. In the same sample, we examined cross-sectional associations between low relative amplitude and mood disorder, wellbeing, and cognitive variables using a series of regression models. Our final model adjusted for age and season at the time that accelerometry started, sex, ethnic origin, Townsend deprivation score, smoking status, alcohol intake, educational attainment, overall mean acceleration recorded by accelerometry, body-mass index, and a binary measure of childhood trauma. Findings: We included 91 105 participants with accelerometery data collected between 2013 and 2015 in our analyses. A one-quintile reduction in relative amplitude was associated with increased risk of lifetime major depressive disorder (odds ratio [OR] 1·06, 95% CI 1·04-1·08) and lifetime bipolar disorder (1·11, 1·03-1·20), as well as with greater mood instability (1·02, 1·01-1·04), higher neuroticism scores (incident rate ratio 1·01, 1·01-1·02), more subjective loneliness (OR 1·09, 1·07-1·11), lower happiness (0·91, 0·90-0·93), lower health satisfaction (0·90, 0·89-0·91), and slower reaction times (linear regression coefficient 1·75, 1·05-2·45). These associations were independent of demographic, lifestyle, education, and overall activity confounders. Interpretation: Circadian disruption is reliably associated with various adverse mental health and wellbeing outcomes, including major depressive disorder and bipolar disorder. Lower relative amplitude might be linked to increased susceptibility to mood disorders. Funding: Lister Institute of Preventive Medicine.

The lancet. Psychiatry · 265 citationsread the source →

Transitional Care Units: Greater Than the Sum of Their Parts

Introduction In 1981, alarmed at the trend of incident patients selecting in-center hemodialysis over home therapies, Northwest Kidney Centers (NWK) established the first “dialysis orientation unit” under the direction of Dr. Joel Eschbach (1). The orientation unit provided a 2-month stabilization program emphasizing modality and diet education, patient “rehabilitation,” and transitioning safely to home dialysis. What was the historically “low” rate of home hemodialysis uptake that spurred development of this program? 50%. Today, any dialysis organization would consider a 50% home therapy start rate a resounding success. In subsequent years, nephrologists learned hard lessons about the dangers posed to patients in the first year of dialysis, particularly those “crashing in.“ It is now understood that the first 90 days of dialysis remain a period of high cost, high hospitalization rates, and mortality (2). This finding is often attributed to a lack of or insufficient nephrology predialysis care (3). US Renal Data System information suggests nearly 40% of patients with ESKD initiate dialysis without adequate preparation (2). Despite efforts to improve these statistics, so-called “suboptimal starts,” patients initiating dialysis in a hospital or with a central venous catheter (CVC), predominate making up 80% of the incident dialysis cohort (2). A detailed review of the causes of this phenomenon is beyond the scope of this article; however, one underappreciated contributor to suboptimal starts is unexpected and rapid loss of GFR in established CKD immediately preceding dialysis initiation. This situation catches patient and physician unaware, precluding or abbreviating participation in pre-ESKD care. Estimates of the number of patients experiencing this scenario are hampered by a lack of predialysis kidney function data, but a recent retrospective study noted that approximately 50% of patients may enter dialysis this way (4). Another study of incident patients with ESKD followed previously in long-term CKD clinics compared those initiating dialysis with a CVC against patients with an existing fistula or graft. The CVC group experienced double the rate of GFR loss in the 6 months preceding dialysis compared with the fistula/graft group (5). These studies imply that a sizeable portion of patients, irrespective of predialysis nephrology care, may not have access to adequate preparation due to sudden rapid GFR decline. Such individuals require “rescue therapy” in their first weeks and months of dialysis to navigate what has been rightly described “the trauma of dialysis initiation” (6,7). Goals of Transitional Dialysis Care Transitional dialysis care, referring to the medical and psychosocial support provided during the peridialysis initiation period, may take many forms from simple programs where designated staff provide focused chairside education to physically separate dialysis units providing broad support services. Although terminology is still evolving, specialized units dedicated to the needs of incident patients may be termed “transitional care units” (TCUs). These units share many characteristics with existing home training programs, and therefore, many goals of a TCU will already be familiar to clinicians. Gentle medical stabilization of the patient who is new to dialysis In-depth education on modality, nutrition, and financial aspects of ESKD Provide emotional and psychologic support Provide a welcoming environment and education for caregivers/partners Provide “patient navigation” services to facilitate multiple appointments, such as access and transplant Provide a supportive, low-risk environment to sample home therapies Although patient-centered goals have been the primary driver for establishing TCUs, in the era of value-based care, these units may also represent a cost-effective quality improvement intervention. This is accomplished by adopting proven elements of existing programs, such as checklists, patient navigators, teaching methods, etc., and placing them under a single geographic and programmatic “roof.” In doing so, it is possible a TCU model can attain similar quality improvements, such as Decreased access placement latency times Improved transplant referral timing and volume Improved adoption of home therapies Decreased hospitalizations and mortality A typical transitional care program may last 4–8 weeks and involves all members of the interdisciplinary care team providing scheduled chairside teaching and enhanced educational activities. At program conclusion, patients should emerge with an understanding of all aspects of their disease, allowing for truly informed decisions in areas such as modality and transplant. Early support interventions have the potential to reduce disparities in home therapies and transplant by reducing provider modality bias in favor of patient choice. Historical Perspectives on Transitional Care The first documented example of a TCU (established as the “Dialysis Orientation Unit” at NWK) brought together distributed patient care activities and work flows. The goal was to “rehabilitate the patient,” promote self-care, and allow the patient to attain a quality of life as close as possible to their pre-ESKD self (1). The program featured a physically separate unit, high staff-to-patient ratio, and close collaboration with the home training group. Unit staff members were selected not only on the basis of clinical skill but also on the ability to empathize and educate. Primary nursing was a focus, with a now hard to imagine 1:2 nurse-to-patient ratio. All new patients began in the orientation unit—no cherry picking was allowed. In the first year, 93 patients completed the training curriculum and spent an average of 9 weeks in the program. Results were impressive: 62% of patients transitioned to the home dialysis training unit; 24% of patients, unable or unwilling to dialyze at home, transitioned to “limited care”—similar to today’s “in-center self-care,” and only 10% joined the general in-center population (1). Over the next decade, more medically complex patients began to enter dialysis, and the early results proved difficult to maintain. However, before its closing in the mid-1990s, this early TCU example attained a still impressive 25% uptake rate of home therapies (1). In the 2000s, large United States-based dialysis providers initiated dedicated quality improvement programs targeting incident patients. Although these programs included many elements of the dedicated TCU model, they did not use the separate physical plant component. Demonstrable improvements were observed in hard outcomes, such as access placement rates, hospitalizations, and mortality (8). Although modality education was a component of these programs, effects on home therapy uptake were not reported. In Canada, a number of hospital-based dialysis entities with a “home first” focus established TCUs with an emphasis on psychosocial support and meaningful modality education. One such example, Humber River Hospital’s TCU, reported results of 180 incident dialysis starts in a six-station dedicated unit. In their hands, home dialysis uptake rates more than doubled for participants in the TCU (56%) versus nonparticipants (21%) (9). More striking, patients with “unplanned” dialysis starts had a 50% home therapy uptake rate when funneled through the TCU. Today in the United States, TCUs are just beginning to take root, with only anecdotal outcome data available. One such program at Satellite Dialysis, termed “Optimal Transitions,” has described early results. Their TCU uses traditional education and psychosocial support program pillars but adds a new element—a 5-day per week dialysis schedule using home dialysis machines to provide a gentler break-in experience (10). The final weeks of the program conclude with a dedicated “self-care” phase, where patients are given hands-on training and time to experiment with home dialysis therapy. Conclusions Aside from transplantation, there is currently no single intervention in kidney disease that is as impactful as improving the transition from CKD to ESKD. Despite recent improvements in referral timing and the overall proportion of patients receiving pre-ESKD care, a substantial population of patients remains vulnerable to poor health outcomes and is deprived of meaningful modality choice at dialysis initiation due to lack of adequate support and education. A TCU provides the framework to both medically and emotionally support these patients. These units stitch together multiple proven interventions to provide a supportive medical home. Operationally, transitional units can scale as needed. A dialysis clinic with low-incident patient volumes may dedicate as few as one to two stations to transitional care and easily handle a year’s worth of incident patients. Although the intervention is intensive from the patient perspective, the program is limited to a unit’s new patients only. Staff and physicians are not overwhelmed by wholesale changes to dialysis operations, like those seen in more complex alternative payment models. The expected increased time commitment for the physician is akin to a couple of extra clinic visits per week. However promising early TCU results may be, clinical trials remain necessary to justify upfront investments in such units. Increases in home therapy adoption seem the most assured outcome; however, larger study populations are required to show improvements in hospitalization rates, mortality, and access placement. By bringing incident patients, providers, and proven interventions together in one location, the TCU model may prove greater than the sum of its parts. Disclosures Dr. Bowman is the principal investigator on a proposed multisite trial of the effect of the transitional care unit concept. NxStage Medical Inc. has agreed to provide data hosting for this trial. All other expenses are self-funded by the participating units.

Clinical Journal of the American Society of Nephrology · 27 citationsread the source →

Problematic internet use in adolescents and implementation of a social media hygiene protocol.

Purpose: This quality improvement project aimed to evaluate whether a social media hygiene education intervention designed for adolescents with problematic internet use (PIU) receiving treatment at a pediatric outpatient mental health clinic reduced PIU and/or improved mental health outcomes in adolescents. Methods: Participants were 28 adolescents (71.4% females, mean age = 14.2 years) with PIU seeking outpatient mental health treatment. The most common associated diagnoses were anxiety (42.9%) and attention-deficit activity disorder (28.6%). A within-adolescent pre-post design was used to evaluate changes in PIU severity measured by the Generalized Problematic Internet Use Scale-2 (GPIUS-2), depression and anxiety severity was assessed by the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS), and screen time defined as the average hours/day during past 7-days recorded of the adolescent's smartphone. The practice change was an ad hoc social media hygiene education intervention conducted by their provider over five, once-a-week, one-hour telehealth sessions. Results: A significant reduction in screen time (paired t = 10.14, df = 27, p < 0.001), severity of PIU (paired t = 12.07, df = 27, p < 0.001), and severity of depression and/or anxiety symptoms (paired t = 8.3, df = 27, p < 0.001) was demonstrated. Large effect sizes were observed (Cohen d = 1.6 to 2.3). Attendance for each session was 100% for Weeks 1, 2 and 5, 93% for Week 3 and 89% for Week 4. Conclusion: The findings suggest administration of a social-media hygiene protocol conducted via telehealth may reduce the severity of PIU and improve mental health outcomes in adolescents seeking outpatient mental health treatment.

Journal of pediatric nursing · 5 citationsread the source →

A Mindfulness Course Decreases Burnout and Improves Well-Being among Healthcare Providers

OBJECTIVE: Healthcare providers are under increasing stress and work-related burnout has become common. Mindfulness-based interventions have a potential role in decreasing stress and burnout. The purpose of this study was to determine if a continuing education course based on mindfulness-based stress reduction could decrease burnout and improve mental well-being among healthcare providers, from different professions. DESIGN: This was a pre-post observational study conducted in a university medical center. A total of 93 healthcare providers, including physicians from multiple specialties, nurses, psychologists, and social workers who practiced in both university and community settings, participated. The intervention was a continuing education course based on mindfulness-based stress reduction that met 2.5 hours a week for 8 weeks plus a 7-hour retreat. The classes included training in four types of formal mindfulness practices, including the body scan, mindful movement, walking meditation and sitting meditation, as well as discussion focusing on the application of mindfulness at work. The course was offered 11 times over 6 years. The main outcome measures were work-related burnout as measured by the Maslach Burnout Inventory and self-perceived mental and physical well-being as measured by the SF-12v2. RESULTS: Maslach Burnout Inventory scores improved significantly from before to after the course for both physicians and other healthcare providers for the Emotional Exhaustion (p < 0.03), Depersonalization (p < 0.04), and Personal Accomplishment (p < 0.001) scales. Mental well-being measured by the SF12v2 also improved significantly (p < 0.001). There were no significant changes in the SF12v2 physical health scores. CONCLUSION: A continuing education course based on mindfulness-based stress reduction was associated with significant improvements in burnout scores and mental well-being for a broad range of healthcare providers.

The International Journal of Psychiatry in Medicine · 457 citationsread the source →

Telephone-delivered Acceptance and Commitment Therapy for adult smoking cessation: a feasibility study.

Background: Quitline smoking cessation counseling results in a mere 12% success rate. Testing of new telephone-delivered cessation counseling approaches is needed. Objective: Determine the feasibility of the first telephone-delivered Acceptance and Commitment Therapy (ACT) intervention for smoking cessation. Design: Fourteen adults (57% racial/ethnic minority, 8/14) in a single-arm study. Counselor proactively delivered a 5-session (90-min total) ACT telephone intervention for smoking cessation. Hypothesized ACT processes were self-reported at baseline and posttreatment. Smoking status was self-reported at baseline, 20-day posttreatment (93% retention, 13/14), and 12-month posttreatment (93% retention, 13/14). Results: (a) Delivery length and duration: average of 3.5 calls and 81.9-min intervention duration. (b) Receptivity: 100% (14/14) felt respected by the counselor, 86% (12/14) said that intervention was a good fit, and 93% (13/14) said that intervention helped them quit. (c) ACT processes: (i) acceptance of physical cravings, emotions, and thoughts that cue smoking increased from baseline to posttreatment (p = .001, p = .038, and p = .085, respectively) and (ii) commitment to quitting increased from baseline to posttreatment (p = .01). (4) Intent-to-treat cessation outcomes: (i) at 20-day posttreatment, 43% (6/14) had not smoked the day of the survey and 29% (4/14) had not smoked in past 7 days and (ii) at 12-month posttreatment, 29% (4/14) had not smoked at all in past 12 months. These quit rates are over double the 12% quit rates of current standard telephone counseling. Conclusion: Telephone-delivered ACT shows promise for smoking cessation and warrants future testing in a well-powered randomized trial.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 47 citationsread the source →