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Internet-delivered cognitive behavioural therapy for children with anxiety disorders: A randomised controlled trial.

Background: Cognitive behaviour therapy (CBT) has been shown to be an effective treatment for anxiety disorders in children, but few affected seek or receive treatment. Internet-delivered CBT (ICBT) could be a way to increase the availability of empirically supported treatments. Aims: A randomised controlled trial was conducted to evaluate ICBT for children with anxiety disorders. Method: Families (N = 93) with a child aged 8-12 years with a principal diagnosis of generalised anxiety disorder, panic disorder, separation anxiety, social phobia or specific phobia were recruited through media advertisement. Participants were randomised to 10 weeks of ICBT with therapist support, or to a waitlist control condition. The primary outcome measure was the Clinician Severity Rating (CSR) and secondary measures included child- and parent-reported anxiety. Assessments were made at pre-treatment, post-treatment and at three-month follow-up. Results: At post-treatment, there were significant reductions on CSR in the treatment group, with a large between-group effect size (Cohen's d = 1.66). Twenty per cent of children in the treatment group no longer met criteria for their principal diagnosis at post-treatment and at follow-up this number had increased to 50%. Parent-reported child anxiety was significantly lower in the treatment group than in the waitlist group at post-treatment, with a small between-group effect size (Cohen's d = 0.45). There were no significant differences between the groups regarding child-ratings of anxiety at post-treatment. Improvements were maintained at three-month follow-up, although this should be interpreted cautiously due to missing data. Conclusions: Within the limitations of this study, results suggest that ICBT with therapist support for children with anxiety disorders can reduce clinician- and parent-rated anxiety symptoms. Trial registration: Clinicaltrials.gov: NCT01533402.

Behaviour research and therapy · randomised controlled trial · 87 citationsread the source →

Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974.

Background: Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life. Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity. This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a randomized trial. Methods: Employees with moderate to severe anxiety of longer than 6 weeks duration were randomized based on age and gender to receive naturopathic care (NC) (n = 41) or standardized psychotherapy intervention (PT) (n = 40) over a period of 12 weeks. Blinding of investigators and participants during randomization and allocation was maintained. Participants in the NC group received dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera) (300 mg b.i.d. standardized to 1.5% with anolides, prepared from root). The PT intervention received psychotherapy, and matched deep breathing relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life respectively. Participants were blinded to the placebo-controlled intervention. Results: Seventy-five participants (93%) were followed for 8 or more weeks on the trial. Final BAI scores decreased by 56.5% (p<0.0001) in the NC group and 30.5% (p<0.0001) in the PT group. BAI group scores were significantly decreased in the NC group compared to PT group (p = 0.003). Significant differences between groups were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life with the NC group exhibiting greater clinical benefit. No serious adverse reactions were observed in either group. Relevance: Many patients seek alternatives and/or complementary care to conventional anxiety treatments. To date, no study has evaluated the potential of a naturopathic treatment protocol to effectively treat anxiety. Knowledge of the efficacy, safety or risk of natural health products, and naturopathic treatments is important for physicians and the public in order to make informed decisions. Interpretation: Both NC and PT led to significant improvements in patients' anxiety. Group comparison demonstrated a significant decrease in anxiety levels in the NC group over the PT group. Significant improvements in secondary quality of life measures were also observed in the NC group as compared to PT. The whole system of naturopathic care for anxiety needs to be investigated further including a closer examination of the individual components within the context of their additive effect. Trial registration: Controlled-Trials.com ISRCTN78958974.

PloS one · randomised controlled trial · 50 citationsread the source →

Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: The mental disorders included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were depressive disorders, anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, eating disorders, idiopathic developmental intellectual disability, and a residual category of other mental disorders. We aimed to measure the global, regional, and national prevalence, disability-adjusted life-years (DALYS), years lived with disability (YLDs), and years of life lost (YLLs) for mental disorders from 1990 to 2019. Methods: In this study, we assessed prevalence and burden estimates from GBD 2019 for 12 mental disorders, males and females, 23 age groups, 204 countries and territories, between 1990 and 2019. DALYs were estimated as the sum of YLDs and YLLs to premature mortality. We systematically reviewed PsycINFO, Embase, PubMed, and the Global Health Data Exchange to obtain data on prevalence, incidence, remission, duration, severity, and excess mortality for each mental disorder. These data informed a Bayesian meta-regression analysis to estimate prevalence by disorder, age, sex, year, and location. Prevalence was multiplied by corresponding disability weights to estimate YLDs. Cause-specific deaths were compiled from mortality surveillance databases. The Cause of Death Ensemble modelling strategy was used to estimate death rate by age, sex, year, and location. The death rates were multiplied by the years of life expected to be remaining at death based on a normative life expectancy to estimate YLLs. Deaths and YLLs could be calculated only for anorexia nervosa and bulimia nervosa, since these were the only mental disorders identified as underlying causes of death in GBD 2019. Findings: Between 1990 and 2019, the global number of DALYs due to mental disorders increased from 80·8 million (95% uncertainty interval [UI] 59·5-105·9) to 125·3 million (93·0-163·2), and the proportion of global DALYs attributed to mental disorders increased from 3·1% (95% UI 2·4-3·9) to 4·9% (3·9-6·1). Age-standardised DALY rates remained largely consistent between 1990 (1581·2 DALYs [1170·9-2061·4] per 100 000 people) and 2019 (1566·2 DALYs [1160·1-2042·8] per 100 000 people). YLDs contributed to most of the mental disorder burden, with 125·3 million YLDs (95% UI 93·0-163·2; 14·6% [12·2-16·8] of global YLDs) in 2019 attributable to mental disorders. Eating disorders accounted for 17 361·5 YLLs (95% UI 15 518·5-21 459·8). Globally, the age-standardised DALY rate for mental disorders was 1426·5 (95% UI 1056·4-1869·5) per 100 000 population among males and 1703·3 (1261·5-2237·8) per 100 000 population among females. Age-standardised DALY rates were highest in Australasia, Tropical Latin America, and high-income North America. Interpretation: GBD 2019 showed that mental disorders remained among the top ten leading causes of burden worldwide, with no evidence of global reduction in the burden since 1990. The estimated YLLs for mental disorders were extremely low and do not reflect premature mortality in individuals with mental disorders. Research to establish causal pathways between mental disorders and other fatal health outcomes is recommended so that this may be addressed within the GBD study. To reduce the burden of mental disorders, coordinated delivery of effective prevention and treatment programmes by governments and the global health community is imperative. Funding: Bill & Melinda Gates Foundation, Australian National Health and Medical Research Council, Queensland Department of Health, Australia.

The lancet. Psychiatry · systematic review · 4002 citationsread the source →

Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil.

Background: Breastfeeding has clear short-term benefits, but its long-term consequences on human capital are yet to be established. We aimed to assess whether breastfeeding duration was associated with intelligence quotient (IQ), years of schooling, and income at the age of 30 years, in a setting where no strong social patterning of breastfeeding exists. Methods: A prospective, population-based birth cohort study of neonates was launched in 1982 in Pelotas, Brazil. Information about breastfeeding was recorded in early childhood. At 30 years of age, we studied the IQ (Wechsler Adult Intelligence Scale, 3rd version), educational attainment, and income of the participants. For the analyses, we used multiple linear regression with adjustment for ten confounding variables and the G-formula. Findings: From June 4, 2012, to Feb 28, 2013, of the 5914 neonates enrolled, information about IQ and breastfeeding duration was available for 3493 participants. In the crude and adjusted analyses, the durations of total breastfeeding and predominant breastfeeding (breastfeeding as the main form of nutrition with some other foods) were positively associated with IQ, educational attainment, and income. We identified dose-response associations with breastfeeding duration for IQ and educational attainment. In the confounder-adjusted analysis, participants who were breastfed for 12 months or more had higher IQ scores (difference of 3·76 points, 95% CI 2·20-5·33), more years of education (0·91 years, 0·42-1·40), and higher monthly incomes (341·0 Brazilian reals, 93·8-588·3) than did those who were breastfed for less than 1 month. The results of our mediation analysis suggested that IQ was responsible for 72% of the effect on income. Interpretation: Breastfeeding is associated with improved performance in intelligence tests 30 years later, and might have an important effect in real life, by increasing educational attainment and income in adulthood. Funding: Wellcome Trust, International Development Research Center (Canada), CNPq, FAPERGS, and the Brazilian Ministry of Health.

The Lancet. Global health · 382 citationsread the source →

The contribution of spirituality and religiousness to the quality of life of cancer patients treated with radiotherapy in Ghana: a cross-sectional study.

Cancer is one of the leading causes of morbidity and mortality globally. A significant proportion of all patients with cancer require radiotherapy as part of their treatment. Cancer can be very terrifying for patients undergoing radiotherapy, especially when it undermines their ability to hope or cope. In Ghana, where religious and spiritual beliefs play a significant role in many individuals' lives, understanding how these factors affect patients' well-being during cancer treatment is crucial. This study examined the contribution of spirituality and religiousness to the quality of life (QoL) of cancer patients undergoing radiotherapy in Accra, Ghana. Pre-validated questionnaires were used to collect data that were analysed using the Statistical Package for the Social Sciences software (version 20). Patient interviews were also conducted and analysed thematically. Most of the respondents were female (n = 58, 65%), whereas 32 (35%) were male. The mean age of the respondents was 45.8 years (SD 12.9). All the participants of the study were religious and considered themselves to be either Christian (n = 82, 91.1%) or Muslim (n = 8, 8.9%). Approximately 93% of the participants relied on their spiritual beliefs to cope with cancer. Many patients reported that spirituality and religious coping are important aspects of their experience, potentially influencing their perceived QoL during radiotherapy. Most patients considered attention to spiritual concerns an important part of cancer care by doctors (88%) and nurses (85%). Five themes were identified from the analysis of the qualitative data. These themes indicated nuanced insights into how spirituality and religiousness influence the experiences of cancer patients. The findings of this study demonstrate the need to cater not only to bodily but also to emotional, social and spiritual needs that arise in the lives of cancer patients.

Ecancermedicalscience · 3 citationsread the source →

Association of Irritability and Anxiety With the Neural Mechanisms of Implicit Face Emotion Processing in Youths With Psychopathology.

Importance: Psychiatric comorbidity complicates clinical care and confounds efforts to elucidate the pathophysiology of commonly occurring symptoms in youths. To our knowledge, few studies have simultaneously assessed the effect of 2 continuously distributed traits on brain-behavior relationships in children with psychopathology. Objective: To determine shared and unique effects of 2 major dimensions of child psychopathology, irritability and anxiety, on neural responses to facial emotions during functional magnetic resonance imaging. Design, setting, and participants: Cross-sectional functional magnetic resonance imaging study in a large, well-characterized clinical sample at a research clinic at the National Institute of Mental Health. The referred sample included youths ages 8 to 17 years, 93 youths with anxiety, disruptive mood dysregulation, and/or attention-deficit/hyperactivity disorders and 22 healthy youths. Main outcomes and measures: The child's irritability and anxiety were rated by both parent and child on the Affective Reactivity Index and Screen for Child Anxiety Related Disorders, respectively. Using functional magnetic resonance imaging, neural response was measured across the brain during gender labeling of varying intensities of angry, happy, or fearful face emotions. In mixed-effects analyses, the shared and unique effects of irritability and anxiety were tested on amygdala functional connectivity and activation to face emotions. Results: The mean (SD) age of participants was 13.2 (2.6) years; of the 115 included, 64 were male. Irritability and/or anxiety influenced amygdala connectivity to the prefrontal and temporal cortex. Specifically, irritability and anxiety jointly influenced left amygdala to left medial prefrontal cortex connectivity during face emotion viewing (F4,888 = 9.20; P < .001 for mixed model term). During viewing of intensely angry faces, decreased connectivity was associated with high levels of both anxiety and irritability, whereas increased connectivity was associated with high levels of anxiety but low levels of irritability (Wald χ21 = 21.3; P < .001 for contrast). Irritability was associated with differences in neural response to face emotions in several areas (F2, 888 ≥ 13.45; all P < .001). This primarily occurred in the ventral visual areas, with a positive association to angry and happy faces relative to fearful faces. Conclusions and relevance: These data extend prior work conducted in youths with irritability or anxiety alone and suggest that research may miss important findings if the pathophysiology of irritability and anxiety are studied in isolation. Decreased amygdala-medial prefrontal cortex connectivity may mediate emotion dysregulation when very anxious and irritable youth process threat-related faces. Activation in the ventral visual circuitry suggests a mechanism through which signals of social approach (ie, happy and angry expressions) may capture attention in irritable youth.

JAMA psychiatry · 80 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 →

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 →

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

Background: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted. Objectives: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets. Search methods: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies. Selection criteria: We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD. Data collection and analysis: We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible. Main results: We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence). Authors' conclusions: There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.

The Cochrane database of systematic reviews · meta-analysis · 192 citationsread the source →

How to reduce parental provision of unhealthy foods to 3- to 8-year-old children in the home environment? A systematic review utilizing the Behaviour Change Wheel framework.

Background and objective: The effectiveness of obesity prevention interventions to improve children's diet can be enhanced. Deconstructing past interventions can identify components with potential to change behaviour. This systematic review using the Behaviour Change Wheel aimed to examine the behaviour change content of interventions supporting parents of 3- to 8-year olds to reduce provision of unhealthy foods to children. Methods: Ebscohost, Ovid, Scopus and Web of Science were searched. Eligible studies included controlled interventions with active parent involvement, at least one intervention strategy and outcome measure for unhealthy foods ≥3 months from baseline. Seventeen interventions were included describing 18 intervention arms. Results: Interventions frequently targeted parents' reflective motivation (n = 17) and psychological capability (n = 15), through education (n = 15) or enablement (n = 15) intervention functions and service provision (n = 18) policy category. Only 24 of the 93 behaviour change techniques were used with an average of five techniques used per intervention. Conclusions: Existing interventions achieving small reductions in unhealthy food intake are homogenous in approach. There is potential to utilize untapped behaviour change techniques, through comprehensive intervention design and behavioural analysis guided by the Behaviour Change Wheel. Interventions targeting opportunity through persuasion, modelling or environmental restructuring, and using different policy categories are urgently needed to provide an evidence base to inform policy and practice.

Obesity reviews : an official journal of the International Association for the Study of Obesity · systematic review · 32 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 →

Reducing the psychological distress of family caregivers of home based palliative care patients: longer term effects from a randomised controlled trial.

Background: Palliative care incorporates comprehensive support of family caregivers because many of them experience burden and distress. However, evidence-based support initiatives are few. Purpose: We evaluated a one-to-one psychoeducational intervention aimed at mitigating the distress of caregivers of patients with advanced cancer receiving home-based palliative care. We hypothesised that caregivers would report decreased distress as assessed by the General Health Questionnaire (GHQ). Method: A randomised controlled trial comparing two versions of the delivery of the intervention (one face-to-face home visit plus telephone calls versus two visits) plus standard care to a control group (standard care only) across four sites in Australia. Results: Recruitment to the one visit condition was 57, the two visit condition 93, and the control 148. We previously reported non-significant changes in distress between times 1 (baseline) and 2 (1-week post-intervention) but significant gains in competence and preparedness. We report here changes in distress between times 1 and 3 (8-week post-death). There was significantly less worsening in distress between times 1 and 3 in the one visit intervention group than in the control group; however, no significant difference was found between the two visit intervention and the control group. Conclusions: These results are consistent with the aim of the intervention, and they support existing evidence demonstrating that relatively short psychoeducational interventions can help family caregivers who are supporting a dying relative. The sustained benefit during the bereavement period may also have positive resource implications, which should be the subject of future inquiry.

Psycho-oncology · randomised controlled trial · 66 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 →

Coached Mobile App Platform for the Treatment of Depression and Anxiety Among Primary Care Patients: A Randomized Clinical Trial.

Importance: Depression and anxiety are common and disabling. Primary care is the de facto site for treating these mental health problems but is typically underresourced to meet the burden of these demands. Objective: To evaluate the efficacy of a mobile intervention platform, IntelliCare, for addressing depression and anxiety among primary care patients. Design, setting, and participants: Two-arm randomized clinical trial at internal medicine clinics at the University of Arkansas for Medical Sciences. Adult primary care patients (N = 146) who screened positive for depression on the Patient Health Questionnaire-8 (PHQ; score  ≥ 10) or anxiety on the Generalized Anxiety Disorder-7 (GAD-7; score ≥ 8) were recruited between July 17, 2018, and December 14, 2018. Interventions: The coach-supported platform composed of a suite of apps, was delivered over 8 weeks. Wait list control participants received treatment as usual for 8 weeks, then the mobile platform. Main outcomes and measures: Primary outcomes were changes in depression (PHQ-9) and anxiety (GAD-7) during the intervention period. Secondary outcomes were differences in the proportion of patients who achieved recovery (PHQ-9/GAD-7 <5 or 50% improvement from baseline), sustainment of intervention effects during 2-month follow-up, and app use during the intervention period. Results: One hundred forty-six patients were included (119 of 146 were women [81.5%]; mean [SD] age, 42.3 [13.8] years). Of the 146 patients, 122 (83.6%) were diagnosed as having depression and 131 (89.7%) were diagnosed as having anxiety. A greater proportion of intervention vs wait list control participants achieved recovery from depression (n = 38 of 64 [59%] vs n = 18 of 58 [31%]; odds ratio, 3.25; 95% CI, 1.54-6.86) and anxiety (n = 37 of 65 [57%] vs n = 25 of 66 [38%]; odds ratio, 2.17; 95% CI, 1.08-4.36). Sustained effects were observed for depression (slope, 0.01; 95% CI, -0.09 to 0.10; P = .92) and anxiety scores (slope, 0.02; 95% CI, -0.08 to 0.12; P = .67) during follow-up. App use was high, with a median of 93 and 98 sessions among participants with depression and anxiety, respectively. Conclusions and relevance: In this trial, a mobile intervention app was effective for depression and anxiety among primary care patients. Findings also support designing digital mental health interventions as platforms containing simple, brief apps that can be bundled by users to meet their needs. Trial registration: ClinicalTrials.gov Identifier: NCT03500536.

JAMA psychiatry · randomised controlled trial · 122 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 →

A randomised trial comparing weight loss with aerobic exercise in overweight individuals with coronary artery disease: The CUT-IT trial.

Background: We aimed to compare the effect of aerobic interval training (AIT) versus a low energy diet (LED) on physical fitness, body composition, cardiovascular risk factors and symptoms in overweight individuals with coronary artery disease (CAD). Methods and design: Seventy non-diabetic participants with CAD, a BMI>28 kg/m(2) and aged 45 to 75 years were randomised to 12 weeks' AIT at 90% peak heart rate three times a week or LED (800-1000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight maintenance diet. Results: Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. VO2peak (mL/kg fat free mass(0.67)/min) increased by 10.4% (p = 0.002) following AIT, whereas no change was observed after LED (-3.0%, p = 0.095). The LED group lost 10.6% body weight and 26.6% body fat mass (p < 0.001) compared to 1.6% (p = 0.002) and 5.5% (p < 0.001) following AIT. Waist circumference and visceral abdominal fat were reduced by both interventions but were most pronounced following LED (between-group, p < 0.001). Total cholesterol, non-HDL-C and triglycerides decreased significantly in both groups whereas HDL-C and blood pressure were unchanged. Six participants had their antihypertensive treatment reduced following LED (between-group, p = 0.032). Canadian Cardiovascular Society (CCS), New York Heart Association (NYHA) and anxiety scores were improved, while depressive symptoms remained unchanged. Intention-to-treat analyses including 65 participants (93%) were similar to per protocol analysis. Conclusion: Both interventions were feasible and effective in achieving the desired effects. LED was superior in improving body composition and blood pressure, whereas effects on lipids and symptoms were similar in the two groups. Thus, both AIT and LED improve the cardiovascular risk profile in overweight individuals with contemporarily treated CAD.

European journal of preventive cardiology · randomised controlled trial · 30 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 →

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 →

Neurofeedback, sham neurofeedback, and cognitive-behavioural group therapy in adults with attention-deficit hyperactivity disorder: a triple-blind, randomised, controlled trial.

Background: Many studies suggest that electroencephalographic (EEG) neurofeedback might be beneficial in the treatment of attention-deficit hyperactivity disorder (ADHD). However, numbers of well controlled studies are low and neurofeedback techniques are regarded as highly controversial. The present trial examined the efficacy (compared with sham neurofeedback) and efficiency (compared with meta-cognitive therapy) of a standard EEG neurofeedback protocol in adults with ADHD. Methods: We did a concurrent, triple-blind, randomised, controlled trial using authorised deception in adults with ADHD from one centre (University of Tübingen) in Tübingen, Germany. Participants were eligible if they fulfilled the DSM-IV-TR criteria for ADHD, were aged between 18 years and 60 years, and had no or stable use of medication for at least 2 months with no intention to change. We excluded participants who had comorbid schizophrenia or schizoaffective disorder, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury; substance abuse or dependence; or current or planned other psychological treatment. Those eligible were randomly assigned to three groups: a neurofeedback group which received 30 verum θ-to-β neurofeedback sessions over 15 weeks, a sham neurofeedback group which received 15 sham followed by 15 verum θ-to-β neurofeedback sessions over 15 weeks, or a meta-cognitive group therapy group which received 12 sessions over 12 weeks. Participants were assigned equally to one of the three interventions through a computerised minimisation randomisation procedure stratified by sex, age, and baseline symptom severity of ADHD. Participants were masked as to whether they were receiving neurofeedback or sham neurofeedback, but those receiving meta-cognitive therapy were aware of their treatment. Clinical assessors (ie, those assessing outcomes) and research staff who did the neurofeedback training were masked to participants' randomisation status only for neurofeedback and sham neurofeedback. The primary outcome was symptom score on the Conners' adult ADHD rating scale, assessed before treatment, at midtreatment (after 8 weeks), after treatment (after 16 weeks), and 6 months later. All individuals with at least one observation after randomisation were included in the analyses. This trial is registered with ClinicalTrials.gov, number NCT01883765. Findings: Between Feb 1, 2013, and Dec 1, 2015, 761 people were assessed for eligibility. 656 (86%) were excluded and 118 (15%) were eligible for participation in this study. Eligible participants were randomly assigned to neurofeedback (38 [32%]), sham neurofeedback (39 [33%]), or meta-cognitive therapy (41 [35%]). 37 (97%) individuals for neurofeedback, 38 (97%) for sham neurofeedback, and 38 (93%) for meta-cognitive therapy were included in analyses. Self-reported ADHD symptoms decreased substantially for all treatment groups (B=-2·58 [95% CI -3·48 to -1·68]; p<0·0001) between pretreatment and the end of 6 month follow-up, independent of treatment condition (neurofeedback vs sham neurofeedback B=-0·89 [95% CI -2·14 to 0·37], p=0·168; neurofeedback vs meta-cognitive therapy -0·30 [-1·55 to 0·95], p=0·639). No treatment-related or trial-related serious adverse events were reported. Interpretation: Our findings suggest that neurofeedback training is not superior to a sham condition or group psychotherapy. All three treatments were equivalently effective in reducing ADHD symptoms. This first randomised, sham-controlled trial did not show any specific effects of neurofeedback on ADHD symptoms in adults. Funding: German Research Foundation.

The lancet. Psychiatry · randomised controlled trial · 91 citationsread the source →

Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial.

Background: Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial. Objective: To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. Methods: This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months. Results: Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p < 0.001). Leukocyte TL was significantly higher, while serum 8-OXO-dG, OGG1mRNA, and P16INK4amRNA revealed greater decreases in the vitamin D group over the placebo group (p < 0.001). According to mixed-model repeated-measures ANOVA analysis, vitamin D group showed a significant enhancement in the FSIQ score for 12 months compared with the control (estimate value = 5.132, p < 0.001). Conclusion: Vitamin D supplementation for 12 months appears to improve cognitive function through reducing oxidative stress regulated by increased TL in order adults with MCI. Vitamin D may be a promising public health strategy to prevent cognitive decline.

Journal of Alzheimer's disease : JAD · randomised controlled trial · 85 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 →

Computer-assisted delivery of cognitive-behavioral therapy: efficacy and durability of CBT4CBT among cocaine-dependent individuals maintained on methadone.

Objective: A previous pilot trial evaluating computer-based training for cognitive-behavioral therapy (CBT4CBT) in 77 heterogeneous substance users (alcohol, marijuana, cocaine, and opioids) demonstrated preliminary support for its efficacy in the context of a community-based outpatient clinic. The authors conducted a more definitive trial in a larger, more homogeneous sample. Method: In this randomized clinical trial, 101 cocaine-dependent individuals maintained on methadone were randomly assigned to standard methadone maintenance or methadone maintenance with weekly access to CBT4CBT, with seven modules delivered within an 8-week trial. Results: Treatment retention and data availability were high and comparable across the treatment conditions. Participants assigned to the CBT4CBT condition were significantly more likely to attain 3 or more consecutive weeks of abstinence from cocaine (36% compared with 17%; p<0.05, odds ratio=0.36). The group assigned to CBT4CBT also had better outcomes on most dimensions, including urine specimens negative for all drugs, but these reached statistical significance only for individuals completing the 8-week trial (N=69). Follow-up data collected 6 months after treatment termination were available for 93% of the randomized sample; these data indicate continued improvement for those assigned to the CBT4CBT group, replicating previous findings regarding its durability. Conclusions: This trial replicates earlier findings indicating that CBT4CBT is an effective adjunct to addiction treatment with durable effects. CBT4CBT is an easily disseminable strategy for broadening the availability of CBT, even in challenging populations such as cocaine-dependent individuals enrolled in methadone maintenance programs.

The American journal of psychiatry · randomised controlled trial · 129 citationsread the source →

Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial).

Objectives: To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. Design: A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Setting: Four UK study centres from the original trial. Participants: 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8-15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received. Main outcome measures: Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance. Results: There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%). Conclusions: Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37-38 weeks of gestation. Trial registration: : Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662.

Archives of disease in childhood. Fetal and neonatal edition · randomised controlled trial · 105 citationsread the source →

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial.

Background: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available. Objective: To determine the safety and feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response. Design, setting, and participants: In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo. Intervention: A single fraction of 20-Gy SABR to each lesion. Results and limitations: Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91-100) and 93% (95% CI: 84-100), and DPFS was 58% (95% CI: 43-77) and 39% (95% CI: 25-60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm. Conclusions: A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy. Patient summary: This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.

European urology · clinical trial · 222 citationsread the source →

Mindfulness-based cognitive therapy for preventing relapse in recurrent depression: a randomized dismantling trial.

Objective: We compared mindfulness-based cognitive therapy (MBCT) with both cognitive psychological education (CPE) and treatment as usual (TAU) in preventing relapse to major depressive disorder (MDD) in people currently in remission following at least 3 previous episodes. Method: A randomized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU, CPE plus TAU, and TAU alone, and data were analyzed for the 255 (93%; MBCT = 99, CPE = 103, TAU = 53) retained to follow-up. MBCT was delivered in accordance with its published manual, modified to address suicidal cognitions; CPE was modeled on MBCT, but without training in meditation. Both treatments were delivered through 8 weekly classes. Results: Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up, hazard ratio for MBCT vs. CPE = 0.88, 95% CI [0.58, 1.35]; for MBCT vs. TAU = 0.69, 95% CI [0.42, 1.12]. However, severity of childhood trauma affected relapse, hazard ratio for increase of 1 standard deviation = 1.26 (95% CI [1.05, 1.50]), and significantly interacted with allocated treatment. Among participants above median severity, the hazard ratio was 0.61, 95% CI [0.34, 1.09], for MBCT vs. CPE, and 0.43, 95% CI [0.22, 0.87], for MBCT vs. TAU. For those below median severity, there were no such differences between treatment groups. Conclusion: MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma, but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression.

Journal of consulting and clinical psychology · randomised controlled trial · 215 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 →

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

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

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

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 →

The Tailored Activity Program to reduce behavioral symptoms in individuals with dementia: feasibility, acceptability, and replication potential.

Purpose: The Tailored Activity Program (TAP) is a home-based occupational therapy intervention shown to reduce behavioral symptoms and caregiver burden in a randomized trial. This article describes TAP, its assessments, acceptability, and replication potential. Design and methods: TAP involves 8 sessions for a period of 4 months. Interventionists identify preserved capabilities, previous roles, habits, and interests of individuals with dementia; develop activities customized to individual profiles; and train families in activity use. Interventionists documented time spent and ease conducting assessments, and observed receptivity of TAP. For each implemented prescribed activity, caregivers reported the amount of time their relative spent in activity and perceived benefits. Results: The TAP assessment, a combination of neuropsychological tests, standardized performance-based observations, and clinical interviewing, yielded information on capabilities from which to identify and tailor activities. Assessments were easy to administer, taking an average of two 1-hr sessions. Of 170 prescribed activities, 81.5% were used, for an average of 4 times for 23 min by families between treatment sessions for a period of months. Caregivers reported high confidence in using activities, being less upset with behavioral symptoms (86%), and enhanced skills (93%) and personal control (95%). Interventionists observed enhanced engagement (100%) and pleasure (98%) in individuals with dementia during sessions. Implications: TAP offers families knowledge of their relative's capabilities and easy-to-use activities. The program was well received by caregivers. Prescribed activities appeared to be pleasurable and engaging to individuals with dementia. TAP merits further evaluation to establish efficacy with larger more diverse populations and consideration as a nonpharmacological approach to manage behavioral symptoms.

The Gerontologist · randomised controlled trial · 116 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 →

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 →

Dementia and Alzheimer's disease in community-dwelling elders taking vitamin C and/or vitamin E.

Background: Since increased oxidative stress may impair cognition and be a risk factor for dementia, there has been interest in determining whether use of antioxidants could protect against such events. Objective: To determine whether supplement use of vitamins C and/or E in a community-based sample of older African American and white individuals delayed incident dementia or Alzheimer's disease (AD). Methods: We selected a subgroup from the Duke Established Populations for Epidemiologic Studies of the Elderly, a longitudinal study of community-representative persons aged 65-105 years living in 5 adjacent counties in North Carolina, and followed them for dementia (1986-1987 through June 2000). Information gathered during in-home interviews included sociodemographic characteristics, health status, health service use, and vitamin use. Diagnosis of dementia and AD was based on evaluations using the clinical and neuropsychological batteries of the Consortium to Establish a Registry for Alzheimer's Disease, with final determination by consensus agreement of specialists using Diagnostic and Statistical Manual of Mental Disorders, third revision, and National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. Results: Of 616 persons initially dementia-free (mean age 73 y; 62% female; 62% African American), 141 developed dementia, of whom 93 developed AD. Increased age and mobility problems were risk factors for dementia (only age for AD), while an increased number of outpatient visits reduced the likelihood of developing dementia. Neither use of any vitamins C and/or E (used by 8% of subjects at baseline) nor high-dose use reduced the time to dementia or AD. Conclusions: In this community in the southeastern US where vitamin supplement use is low, use of vitamins C and/or E did not delay the incidence of dementia or AD.

The Annals of pharmacotherapy · clinical trial · 70 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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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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Annals of Internal Medicine · review · 370 citationsread the source →

Knowledge, attitudes, and planned practice of HIV-positive to HIV-positive transplantation in US transplant centers.

Background: HIV+ donor organs can now be transplanted into HIV+ recipients (HIV D+/R+) following the HIV Organ Policy Equity (HOPE) Act. Implementation of the HOPE Act requires transplant center awareness and support of HIV D+/R+ transplants. Methods: To assess center-level barriers to implementation, we surveyed 209 transplant centers on knowledge, attitudes, and planned HIV D+/R+ protocols. Results: Responding centers (n = 114; 56%) represented all UNOS regions. Fifty centers (93 organ programs) planned HIV D+/R+ protocols (kidney n = 48, liver n = 34, pancreas n = 8, heart n = 2, lung = 1), primarily in the eastern United States (28/50). Most (91.2%) were aware that HIV D+/R+ transplantation is legal; 21.4% were unaware of research restrictions. Respondents generally agreed with HOPE research criteria except the required experience with ≥5 HIV+ transplants by organ type. Centers planning HIV D+/R+ protocols had higher transplant volume, HIV+ recipient volume, increased infectious risk donor utilization, and local HIV prevalence (P < 0.01). Centers not planning HIV D+/R+ protocols were more likely to believe their HIV+ candidates would not accept HIV+ donor organs (P < 0.001). Most centers (83.2%) supported HIV+ living donation. Conclusions: Although many programs plan HIV D+/R+ transplantation, center-level barriers remain including geographic clustering of kidney/liver programs and concerns about HIV+ candidate willingness to accept HIV+ donor organs.

Clinical transplantation · 26 citationsread the source →

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

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

The Lancet. Public health · 239 citationsread the source →

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 →

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 →

Outcomes of community-based suicide prevention program in primary health care of Iran.

Background: Suicidal management and prevention in communities, especially in its first stages, is an effective intervention for the health systems. However, in numerous societies most cases go undetected. Primary Health Care (PHC) is an effective place for the management of Suicide Prevention Programs (SPP). In Malekan County, a health community assessment found suicide as the most important health problem. A regional SPP was performed for suicide prevention during 2014-2017. Methods: This study was carried out in six steps: (1) Establishing a research team, (2) Improving a registry for suicidal behaviors (SBs), (3) Identifying local determinants of SBs, (4) Training healthcare providers, (5) Follow-up and monitoring of SBs, and (6) Public awareness campaigns. Our ultimate goal was to lower the rates of suicide, and suicide attempt (SA) by 15 and 20 %, respectively. Multiple logistic regression was used to estimate the adjusted odds ratios and the 95% confidence intervals. Results: A total of 821 SAs and 32 suicides were identified. The gender distribution for suicides was 70% males whereas SAs were 64% among females. The majority of suicides occurred in spring 18 (56.25%) while summer was the most common season among SAs 288 (35.8%). Almost 62 and 75% of suicides and SAs have used hanging and poisoning methods, respectively. Hanging increased suicide risk significantly (OR: 8.5, 95% CI 2.9-76.99). During the study, 93 life-skill and parenting education sessions were held. The incidence rates of suicide and SA decreased from 11.22, and 203 per 100,000 in 2013 to 2.63, and 157 in 2017, respectively. Similarly, the re-attempt to SAs ratio decreased from 12% to 2013 to 6.7% in 2017. Moreover, more than 8% of SBs were collected from adjacent Counties. Conclusions: At the study end, suicide, SA, and re-attempt were lowered by 75%, 22%, and 42%, respectively. The practical framework that achieved in this study could be used as a basis for developing future SPPs and suicide researches in the Iranian context. Furthermore, the various socio-economic and socio-cultural challenges highlight the need to consider a wide range of contextual factors when developing an SPP.

International journal of mental health systems · 22 citationsread the source →

Ambient greenness, access to local green spaces, and subsequent mental health: a 10-year longitudinal dynamic panel study of 2·3 million adults in Wales.

Background: Living in greener areas, or close to green and blue spaces (GBS; eg, parks, lakes, or beaches), is associated with better mental health, but longitudinal evidence when GBS exposures precede outcomes is less available. We aimed to analyse the effect of living in or moving to areas with more green space or better access to GBS on subsequent adult mental health over time, while explicitly considering health inequalities. Methods: A cohort of the people in Wales, UK (≥16 years; n=2 341 591) was constructed from electronic health record data sources from Jan 1, 2008 to Oct 31, 2019, comprising 19 141 896 person-years of follow-up. Household ambient greenness (Enhanced Vegetation Index [EVI]), access to GBS (counts, distance to nearest), and common mental health disorders (CMD, based on a validated algorithm combining current diagnoses or symptoms of anxiety or depression [treated or untreated in the preceding 1-year period], or treatment of historical diagnoses from before the current cohort [up to 8 years previously, to 2000], where diagnosis preceded treatment) were record-linked. Cumulative exposure values were created for each adult, censoring for CMD, migration out of Wales, death, or end of cohort. Exposure and CMD associations were evaluated using multivariate logistic regression, stratified by area-level deprivation. Findings: After adjustment, exposure to greater ambient greenness over time (+0·1 increased EVI on a 0-1 scale) was associated with lower odds of subsequent CMD (adjusted odds ratio 0·80, 95% CI 0·80-0·81), where CMD was based on a combination of current diagnoses or symptoms (treated or untreated in the preceding 1-year period), or treatments. Ten percentile points more access to GBS was associated with lower odds of a later CMD (0·93, 0·93-0·93). Every additional 360 m to the nearest GBS was associated with higher odds of CMD (1·05, 1·04-1·05). We found that positive effects of GBS on mental health appeared to be greater in more deprived quintiles. Interpretation: Ambient exposure is associated with the greatest reduced risk of CMD, particularly for those who live in deprived communities. These findings support authorities responsible for GBS, who are attempting to engage planners and policy makers, to ensure GBS meets residents' needs. Funding: National Institute for Health and Care Research Public Health Research programme.

The Lancet. Planetary health · 35 citationsread the source →

Carbohydrate ingestion attenuates cognitive dysfunction following long-duration exercise in the heat in humans.

Introduction: To determine if electrolyte or carbohydrate supplementation vs. water would limit the magnitude of dehydration and decline in cognitive function in humans following long-duration hyperthermic-exercise. Methods: 24 subjects performed 3 visits of 2 h walking (3mph/7% grade) in an environmental chamber (33 °C/10% relative humidity). In random order, subjects consumed water (W), electrolytes (Gatorade Zero; E), or electrolytes+carbohydrates (Gatorade; E+C). Throughout exercise (EX), subjects carried a 23 kg pack and drank ad-libitum. Pre-and post-EX, body mass (BM) and plasma osmolality (pOsm) were measured. Physiological Strain Index (PSI) and core temperature (TC) were recorded every 15 min. Plasma glucose (GLU) was measured every 30 min. Cognitive processing (SCWT) was measured post-EX and compared to baseline (BL). A subset of 8 subjects performed a normothermic (N) protocol (21 °C/ambient humidity) to ascertain how the exercise stimulus influenced hydration status and cognition without heat. Results: There were no significant differences between fluid conditions (W, E, E+C) for BM loss (Δ2.5 ± 0.2, 2.5 ± 0.2, 2.3 ± 0.2 kg), fluid consumption (1.9 ± 0.2, 1.9 ± 0.2, 1.8 ± 0.2L), pOsm (Δ1.5 ± 2.7, 2.2 ± 2.4, 2.0 ± 1.5 mmol/L), peak-PSI (7.5 ± 0.4, 7.0 ± 0.6, 7.9 ± 0.5), and peak-TC (38.7 ± 0.1, 38.6 ± 0.2, 38.8 ± 0.2 °C). GLU decreased significantly in W and E, whereas it increased above BL in E+C at 60, 90, and 120 min (P < 0.05). Compared to BL values (43.6 ± 26 ms), SCWT performance significantly decreased in all conditions (463 ± 93, 422 ± 83, 140 ± 52 ms, P < 0.05). Importantly, compared to W and E, the impairment in SCWT was significantly attenuated in E+C (P < 0.05). As expected, when compared to the heat-stress protocol (W, E, E+C), N resulted in lower BM loss, fluid consumption, and peak-PSI (1.1 ± 0.1 kg, 1.2 ± 0.7L, 4.8, respectively), and improved SCWT performance. Conclusions: These data are the first to suggest that, independent of supplementation variety, cognitive processing significantly decreases immediately following long-duration exercise in the heat in healthy humans. Compared to water and fluids supplemented with only electrolytes, fluids supplemented with carbohydrates significantly blunts this decrease in cognitive function.

Journal of thermal biology · 6 citationsread the source →

Cost-Effectiveness of Noninvasive Screening for Alcohol-Related Liver Fibrosis.

Background and aims: Alcohol-related liver disease is often undetected until irreversible late-stage decompensated disease manifests. Consequently, there is an unmet need for effective and economically reasonable pathways to screen for advanced alcohol-related fibrosis. Approach and results: We used real-world data from a large biopsy-controlled study of excessive drinkers recruited from primary and secondary care, to evaluate the cost-effectiveness of four primary care initiated strategies: (1) routine liver function tests with follow-up ultrasonography for test-positives, (2) the enhanced liver fibrosis (ELF) test with hospital liver stiffness measurement (LSM) for positives, (3) a three-tier strategy using the Forns Index to control before strategy 2, and (4) direct referral of all to LSM. We used linked decision trees and Markov models to evaluate outcomes short term (cost-per-accurate diagnosis) and long term (quality-adjusted life-years [QALYs]). For low-prevalence populations, ELF with LSM follow-up was most cost-effective, both short term (accuracy 96%, $196 per patient) and long term (incremental cost-effectiveness ratio [ICER] $5,387-$8,430/QALY), depending on whether diagnostic testing had lasting or temporary effects on abstinence rates. Adding Forns Index decreased costs to $72 per patient and accuracy to 95%. The strategy resulted in fewer QALYs due to more false negatives but an ICER of $3,012, making this strategy suited for areas with restricted access to ELF and transient elastography or lower willingness-to-pay. For high-prevalence populations, direct referral to LSM was highly cost-effective (accuracy 93%, $297 per patient), with ICERs between $490 and $1,037/QALY. Conclusions: Noninvasive screening for advanced alcohol-related fibrosis is a cost-effective intervention when different referral pathways are used according to the prevalence of advanced fibrosis. Patients in the primary health care sector should be tested with the ELF test followed by LSM if the test was positive, whereas direct referral to LSM is highly cost-effective in high-prevalence cohorts.

Hepatology (Baltimore, Md.) · 48 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 →

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 →

A Novel Multimodal Digital Service (Moderated Online Social Therapy+) for Help-Seeking Young People Experiencing Mental Ill-Health: Pilot Evaluation Within a National Youth E-Mental Health Service.

Background: Mental ill-health is the leading cause of disability worldwide. Moreover, 75% of mental health conditions emerge between the ages of 12 and 25 years. Unfortunately, due to lack of resources and limited engagement with services, a majority of young people affected by mental ill-health do not access evidence-based support. To address this gap, our team has developed a multimodal, scalable digital mental health service (Enhanced Moderated Online Social Therapy [MOST+]) merging real-time, clinician-delivered web chat counseling; interactive user-directed online therapy; expert and peer moderation; and peer-to-peer social networking. Objective: The primary aim of this study is to ascertain the feasibility, acceptability, and safety of MOST+. The secondary aims are to assess pre-post changes in clinical, psychosocial, and well-being outcomes and to explore the correlations between system use, perceived helpfulness, and secondary outcome variables. Methods: Overall, 157 young people seeking help from a national youth e-mental health service were recruited over 5 weeks. MOST+ was active for 9 weeks. All participants had access to interactive online therapy and integrated web chat counseling. Additional access to peer-to-peer social networking was granted to 73 participants (46.5%) for whom it was deemed safe. The intervention was evaluated via an uncontrolled single-group study. Results: Overall, 93 participants completed the follow-up assessment. Most participants had moderate (52/157, 33%) to severe (96/157, 61%) mental health conditions. All a priori feasibility, acceptability, and safety criteria were met. Participants provided mean scores of ≥3.5 (out of 5) on ease of use (mean 3.7, SD 1.1), relevancy (mean 3.9, SD 1.0), helpfulness (mean 3.5, SD 0.9), and overall experience (mean 3.9, SD 0.8). Moreover, 98% (91/93) of participants reported a positive experience using MOST+, 82% (70/93) reported that using MOST+ helped them feel better, 86% (76/93) felt more socially connected using it, and 92% (86/93) said they would recommend it to others. No serious adverse events or inappropriate use were detected, and 97% (90/93) of participants reported feeling safe. There were statistically significant improvements in 8 of the 11 secondary outcomes assessed: psychological distress (d=-0.39; P<.001), perceived stress (d=-0.44; P<.001), psychological well-being (d=0.51; P<.001), depression (d=-0.29; P<.001), loneliness (d=-0.23; P=.04), social support (d=0.30; P<.001), autonomy (d=0.36; P=.001), and self-competence (d=0.30; P<.001). There were significant correlations between system use, perceived helpfulness, and a number of secondary outcome variables. Conclusions: MOST+ is a feasible, acceptable, and safe online clinical service for young people with mental ill-health. The high level of perceived helpfulness, the significant improvements in secondary outcomes, and the correlations between indicators of system use and secondary outcome variables provide initial support for the therapeutic potential of MOST+. MOST+ is a promising and scalable platform to deliver standalone e-mental health services as well as enhance the growing international network of face-to-face youth mental health services.

Journal of medical Internet research · 74 citationsread the source →

Trajectories of Nicotine and Cannabis Vaping and Polyuse From Adolescence to Young Adulthood.

Importance: Little is known about cannabis vaping trajectories across adolescence and young adulthood or the co-occurrence with nicotine vaping. Objective: To evaluate nicotine vaping and cannabis vaping trajectories from late adolescence to young adulthood (≥18 years of age) and the extent of polysubstance vaping. Design, setting, and participants: In this prospective cohort study, 5 surveys (including information on substance vaped) were completed at 10 high schools in the Los Angeles, California, metro area. Students were surveyed at 6-month intervals from fall of 11th grade (October to December 2015; wave 5) through spring of 12th grade (March to June 2017; wave 8) and again approximately 1 to 2 years after high school (October 2018 to October 2019; wave 9). Exposures: Past 30-day nicotine and cannabis vaping frequency across 5 waves. Main outcomes and measures: Self-reported frequency of nicotine vaping and cannabis vaping within the past 30 days across 5 time points from late adolescence to young adulthood. Trajectories were measured with these past 30-day use frequencies at each wave. Parallel growth mixture modeling estimated conditional probabilities of polysubstance vaping. Results: The analytic sample included 3322 participants with at least 1 time point of data (mean [SD] age, 16.50 [0.42] years at baseline; 1777 [53.5%] female; 1573 [47.4%] Hispanic or Latino). Growth mixture modeling identified the 5-trajectory model as optimal for both nicotine vaping and cannabis vaping. Trajectories for nicotine and cannabis vaping were similar (nonusers: 2246 [67.6%] nicotine, 2157 [64.9%] cannabis; infrequent users: 566 [17.0%] nicotine, 608 [18.3%] cannabis; moderate users: 167 [5.0%] nicotine, 233 [7.0%] cannabis; young adult-onset frequent users: 213 [6.4%] nicotine, 190 [5.7%] cannabis; adolescent-onset escalating frequent users: 131 [3.9%] nicotine, 134 [4.0%] cannabis). Males had greater odds of belonging to the adolescent-onset escalating frequent users nicotine (adjusted odds ratio, 2.88; 95% CI, 1.58-5.23; P < .01) and cannabis (adjusted odds ratio, 1.95; 95% CI,1.03-3.66; P < .05) vaping trajectories compared with nonusers. Polysubstance vaping was common, with those in trajectories reflecting more frequent nicotine vaping (adolescent-onset escalating frequent users and young adult-onset frequent users) having a high probability of membership (85% and 93%, respectively) in a cannabis-use trajectory. Conclusions and relevance: In this cohort study, the prevalence and type of nicotine vaping and cannabis vaping developmental trajectories from late adolescence to young adulthood were similar. Polysubstance vaping was common from late adolescence to young adulthood, particularly among those reporting more frequent vaping use. The findings suggest that public health policy and clinical interventions should address polysubstance vaping in both adolescence and young adulthood.

JAMA network open · 35 citationsread the source →

Does perinatal exposure to exogenous oxytocin influence child behavioural problems and autistic-like behaviours to 20 years of age?

Background: The neuropeptide and hormone oxytocin is known to have a significant impact on social cognition and behaviour in humans. There is growing concern regarding the influence of exogenous oxytocin (OT) administration in early life on later social and emotional development, including autism spectrum disorder (ASD). No study has examined offspring development in relation to the dose of exogenous oxytocin administered during labour. Methods: Between 1989 and 1992, 2,900 mothers were recruited prior to the 18th week of pregnancy, delivering 2,868 live offspring. The Child Behaviour Checklist was used to measure offspring behavioural difficulties at ages 5, 8, 10, 14 and 17 years. Autism spectrum disorder was formally diagnosed by consensus of a team of specialists. At 20 years, offspring completed a measure of autistic-like traits, the Autism Spectrum Quotient (AQ). Oxytocin exposure prior to birth was analysed using categorical and continuous approaches (maternal oxytocin dose) with univariate and multivariate statistical techniques. Results: Categorical analyses of oxytocin exposure prior to birth demonstrated no group differences in any measures of child behaviour. A small in magnitude dose-response association was observed for clinically significant total behaviour symptoms (adjusted odds ratio 1.03; 95% CI: 1.01-1.06, p < .01). Exogenous oxytocin administration prior to birth was not associated with ASD (OR: 0.64; 95% CI: 0.15-2.12, p = .46) or high levels of autistic-like traits (p = .93), as assessed by the AQ. Conclusions: This study is the first to investigate longitudinal mental health outcomes associated with the use of oxytocin-based medications during labour. The results do not provide evidence to support the theory that exogenous OT has a clinically significant negative impact on the long-term mental health of children.

Journal of child psychology and psychiatry, and allied disciplines · 24 citationsread the source →

Contribution of risk factors to excess mortality in isolated and lonely individuals: an analysis of data from the UK Biobank cohort study.

Background: The associations of social isolation and loneliness with premature mortality are well known, but the risk factors linking them remain unclear. We sought to identify risk factors that might explain the increased mortality in socially isolated and lonely individuals. Methods: We used prospective follow-up data from the UK Biobank cohort study to assess self-reported isolation (a three-item scale) and loneliness (two questions). The main outcomes were all-cause and cause-specific mortality. We calculated the percentage of excess risk mediated by risk factors to assess the extent to which the associations of social isolation and loneliness with mortality were attributable to differences between isolated and lonely individuals and others in biological (body-mass index, systolic and diastolic blood pressure, and handgrip strength), behavioural (smoking, alcohol consumption, and physical activity), socioeconomic (education, neighbourhood deprivation, and household income), and psychological (depressive symptoms and cognitive capacity) risk factors. Findings: 466 901 men and women (mean age at baseline 56·5 years [SD 8·1]) were included in the analyses, with a mean follow-up of 6·5 years (SD 0·8). The hazard ratio for all-cause mortality for social isolation compared with no social isolation was 1·73 (95% CI 1·65-1·82) after adjustment for age, sex, ethnic origin, and chronic disease (ie, minimally adjusted), and was 1·26 (95% CI 1·20-1·33) after further adjustment for socioeconomic factors, health-related behaviours, depressive symptoms, biological factors, cognitive performance, and self-rated health (ie, fully adjusted). The minimally adjusted hazard ratio for mortality risk related to loneliness was 1·38 (95% CI 1·30-1·47), which reduced to 0·99 (95% CI 0·93-1·06) after full adjustment for baseline risks. Interpretation: Isolated and lonely people are at increased risk of death. Health policies addressing risk factors such as adverse socioeconomic conditions, unhealthy lifestyle, and lower mental wellbeing might reduce excess mortality among the isolated and the lonely. Funding: Academy of Finland, NordForsk, and the UK Medical Research Council.

The Lancet. Public health · 295 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 →

Maternal postnatal depression and the development of depression in offspring up to 16 years of age.

Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702 mothers were screened, and probable cases interviewed. In all, 58 depressed mothers (95% of identified cases) and 42 nondepressed controls were recruited. A total of 93% were assessed through to 16-year follow-up. The main study outcome was offspring lifetime clinical depression (major depression episode and dysthymia) by 16 years, assessed via interview at 8, 13, and 16 years. It was analysed in relation to postnatal depression, repeated measures of child vulnerability (insecure infant attachment and lower childhood resilience), and family adversity. Results: Children of index mothers were more likely than controls to experience depression by 16 years (41.5% versus 12.5%; odds ratio = 4.99; 95% confidence interval = 1.68-14.70). Lower childhood resilience predicted adolescent depression, and insecure infant attachment influenced adolescent depression via lower resilience (model R(2) = 31%). Family adversity added further to offspring risk (expanded model R(2) = 43%). Conclusions: Offspring of postnatally depressed mothers are at increased risk for depression by 16 years of age. This may be partially explained by within child vulnerability established in infancy and the early years, and by exposure to family adversity. Routine screening for postnatal depression, and parenting support for postnatally depressed mothers, might reduce offspring developmental risks for clinical depression in childhood and adolescence.

Journal of the American Academy of Child and Adolescent Psychiatry · 272 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 →

Pediatric critical care nurses' perceptions, knowledge, and attitudes regarding organ donation after cardiac death.

Objective: Donation after cardiac death (DCD) is being implemented nationwide in the United States to increase the number of organ donors. Pediatric critical care nurses (PCRNs) are key facilitators in the organ donation process. This study assesses their perception, level of knowledge, and understanding of DCD and the effect of an educational intervention. Design: Anonymous questionnaire administered before and after an educational intervention. Setting: Children's hospital with 39 pediatric and cardiac/transplant intensive care unit beds. Subjects: PCRNs in these intensive care units. Interventions: DCD education. Measurements and main results: Response to the initial questionnaire was 93 of 123 (76%): 63% of PCRNs supported organ donation, 69% felt it gives meaning and worth to death, and 76% felt that it contributes positively to the donating family's grieving process. Ninety-five percent agreed that DCD patients have a right to pain medications, and 92% supported such medications even if they hasten death. However, 11% feared that the DCD donor feels pain and suffering. Fourteen percent felt that a 5-min observation period after asystole is insufficient to pronounce death, and 8% feared legal repercussions. PCRNs scored lower on questions assessing their knowledge (p < .01), their comfort answering family questions (p < .05), and their comfort in calling the organ procurement agency about DCD donors compared with similar questions about brain-dead donors. One month after 104 PCRNs attended the educational intervention, 64 (62%) completed a follow-up survey. Correct identification of the DCD process improved from 20% to 79%. Confidence with knowledge, comfort answering family questions, and comfort in calling the organ procurement agency about DCD donors improved by 41%, 25%, and 18%, respectively. Conclusions: PCRNs are generally supportive of organ donation but have a self-perceived and objectively identified knowledge deficit regarding DCD, resulting in their being unprepared to identify potential DCD donors or handle family questions. A simple educational intervention can improve PCRNs' knowledge of the DCD process and their confidence and comfort with this process. As DCD policies are implemented, specific interventions should target these key members of the intensive care unit team.

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 29 citationsread the source →