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Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial.

Background: The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China. Methods: In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 1010 viral particles, 1·6 × 1011 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively. Findings: Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 1010 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90 peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC90 titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group. Interpretation: The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease. Funding: Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.

The Lancet. Global health · randomised controlled trial · 76 citationsread the source →

Meaning and Purpose (MaP) therapy in advanced cancer patients: a randomised controlled trial.

Purpose: We aimed to examine the efficacy of Meaning and Purpose (MaP) Therapy in promoting posttraumatic growth and meaningful life attitudes (choices and goal seeking) in people living with advanced cancer. Methods: Patients with a prognosis ≥ 1 year were stratified across two sites and randomised to receive MaP therapy and regular oncology/palliative care (Intervention) or usual care (Control). They completed measures at baseline (t0), post-intervention (12 weeks, t1) and 12 weeks later (t2). Our primary outcome was posttraumatic growth (PTGI); secondary outcome measures included life attitudes (LAPR), spiritual wellbeing (FACIT-Sp), anxiety, demoralization and depression. Trial registration number: ACTRN12618001751268, 7 January 2019. Results: We consented 107 from 404 eligible patients (26.5%) and randomised 55 to MaP Invention (35 completing t1, 25 t2) and 52 to Control (32 completing t1, 25 t2). Fidelity of the intervention was sustained. PTGI mean scores were significantly higher post-intervention on analysis by covariance (Cohen's d = 0.7 at t1 & d = 0.5 at t2). Secondary measures were significant, including LAPR (d = 0.4) and FACIT-Sp (meaning subscale d = 0.4; total d = 0.4). Participants completing six sessions achieved more noteworthy effect sizes. Conclusion: This brief, structured individual intervention shows promise for sustaining sense of coherence, meaning and choices in life despite living with advanced cancer.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · randomised controlled trial · 9 citationsread the source →

The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.

Background: The problems of adherence to energy restriction in humans are well known. Objective: To compare the feasibility and effectiveness of intermittent continuous energy (IER) with continuous energy restriction (CER) for weight loss, insulin sensitivity and other metabolic disease risk markers. Design: Randomized comparison of a 25% energy restriction as IER (∼ 2710 kJ/day for 2 days/week) or CER (∼ 6276 kJ/day for 7 days/week) in 107 overweight or obese (mean (± s.d.) body mass index 30.6 (± 5.1) kg m(-2)) premenopausal women observed over a period of 6 months. Weight, anthropometry, biomarkers for breast cancer, diabetes, cardiovascular disease and dementia risk; insulin resistance (HOMA), oxidative stress markers, leptin, adiponectin, insulin-like growth factor (IGF)-1 and IGF binding proteins 1 and 2, androgens, prolactin, inflammatory markers (high sensitivity C-reactive protein and sialic acid), lipids, blood pressure and brain-derived neurotrophic factor were assessed at baseline and after 1, 3 and 6 months. Results: Last observation carried forward analysis showed that IER and CER are equally effective for weight loss: mean (95% confidence interval ) weight change for IER was -6.4 (-7.9 to -4.8) kg vs -5.6 (-6.9 to -4.4) kg for CER (P-value for difference between groups = 0.4). Both groups experienced comparable reductions in leptin, free androgen index, high-sensitivity C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure and increases in sex hormone binding globulin, IGF binding proteins 1 and 2. Reductions in fasting insulin and insulin resistance were modest in both groups, but greater with IER than with CER; difference between groups for fasting insulin was -1.2 (-1.4 to -1.0) μU ml(-1) and for insulin resistance was -1.2 (-1.5 to -1.0) μU mmol(-1) l(-1) (both P = 0.04). Conclusion: IER is as effective as CER with regard to weight loss, insulin sensitivity and other health biomarkers, and may be offered as an alternative equivalent to CER for weight loss and reducing disease risk.

International journal of obesity (2005) · randomised controlled trial · 548 citationsread the source →

A pilot randomized trial of community-based parent training for immigrant Latina mothers.

This paper reports on the development and piloting of the Madres a Madres (Mothers to Mothers) program, a new, community-based parent training program designed for immigrant Latina mothers and their children. Promotoras, or female community health workers of Latina background, delivered the program in a home visitation format. A total of 194 mothers and 194 focal children (87 male, 107 female) ages 7-12 were randomized to the intervention (113 mother-child dyads) or wait-list control condition (81 mother-child dyads) over the study period. Outcomes of interest were mother-reported parenting skills, broad family functioning, and child externalizing and internalizing behaviors. Data collection occurred at pretest, 3-month posttest, and 9-month follow-up periods. Multilevel growth models revealed increases in intervention mothers' reported parenting skills, family support, and family organization, and reductions in child internalizing behavior from pretest to follow-up, relative to the control condition. Outcomes did not vary by focal child age, gender, nativity status, or mother acculturative status (years in the United States). Findings are discussed in the context of future directions for research on the Madres a Madres program and on the implementation and dissemination of empirically-supported parent training practices to culturally diverse families.

American journal of community psychology · randomised controlled trial · 24 citationsread the source →

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

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

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

Stratified Care vs Stepped Care for Depression: A Cluster Randomized Clinical Trial.

Importance: Depression is a major cause of disability worldwide. Although empirically supported treatments are available, there is scarce evidence on how to effectively personalize psychological treatment selection. Objective: To compare the clinical effectiveness and cost-effectiveness of 2 treatment selection strategies: stepped care and stratified care. Design, setting, and participants: This multisite, cluster randomized clinical trial recruited participants from the English National Health Service from July 5, 2018, to February 1, 2019. Thirty clinicians working across 4 psychological therapy services were randomly assigned to provide stratified (n = 15) or stepped (n = 15) care. In stepped care, patients sequentially access low-intensity guided self-help followed by high-intensity psychotherapy. In stratified care, patients are matched with either low- or high-intensity treatments at initial assessment. Data were analyzed from May 18, 2020, to October 13, 2021, using intention-to-treat principles. Interventions: All clinicians used the same interview schedule to conduct initial assessments with patients seeking psychological treatment for common mental disorders, but those in the stratified care group received a personalized treatment recommendation for each patient generated by a machine learning algorithm. Eligible patients received either stratified or stepped care (ie, treatment as usual). Main outcomes and measures: The preregistered outcome was posttreatment reliable and clinically significant improvement (RCSI) of depression symptoms (measured using the 9-item Patient Health Questionnaire). The RCSI outcome was compared between groups using logistic regression adjusted for baseline severity. Cost-effectiveness analyses compared incremental costs and health outcomes of the 2 treatment pathways. Results: A total of 951 patients were included (618 women among 950 with data available [65.1%]; mean [SD] age, 38.27 [14.53] years). The proportion of cases of RCSI was significantly higher in the stratified care arm compared with the stepped care arm (264 of 505 [52.3%] vs 134 of 297 [45.1%]; odds ratio, 1.40 [95% CI, 1.04-1.87]; P = .03). Stratified care was associated with a higher mean additional cost per patient (£104.5 [95% CI, £67.5-£141.6] [$139.83 (95% CI, $90.32-$189.48)]; P < .001) because more patients accessed high-intensity treatments (332 of 583 [56.9%] vs 107 of 368 [29.1%]; χ2 = 70.51; P < .001), but this additional cost resulted in an approximately 7% increase in the probability of RCSI. Conclusions and relevance: In this cluster randomized clinical trial of adults with common mental disorders, stratified care was efficacious and cost-effective for the treatment of depression symptoms compared with stepped care. Stratified care can improve depression treatment outcomes at a modest additional cost. Trial registration: isrctn.org Identifier: ISRCTN11106183.

JAMA psychiatry · randomised controlled trial · 118 citationsread the source →

International consensus on a standard set of outcome measures for child and youth anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder.

A major barrier to improving care effectiveness for mental health is a lack of consensus on outcomes measurement. The International Consortium for Health Outcomes Measurement (ICHOM) has already developed a consensus-based standard set of outcomes for anxiety and depression in adults (including the Patient Health Questionnaire-9, the Generalised Anxiety Disorder 7-item Scale, and the WHO Disability Schedule). This Position Paper reports on recommendations specifically for anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder in children and young people aged between 6 and 24 years. An international ICHOM working group of 27 clinical, research, and lived experience experts formed a consensus through teleconferences, an exercise using an adapted Delphi technique (a method for reaching group consensus), and iterative anonymous voting, supported by sequential research inputs. A systematic scoping review identified 70 possible outcomes and 107 relevant measurement instruments. Measures were appraised for their feasibility in routine practice (ie, brevity, free availability, validation in children and young people, and language translation) and psychometric performance (ie, validity, reliability, and sensitivity to change). The final standard set recommends tracking symptoms, suicidal thoughts and behaviour, and functioning as a minimum through seven primarily patient-reported outcome measures: the Revised Children's Anxiety and Depression Scale, the Obsessive Compulsive Inventory for Children, the Children's Revised Impact of Events Scale, the Columbia Suicide Severity Rating Scale, the KIDSCREEN-10, the Children's Global Assessment Scale, and the Child Anxiety Life Interference Scale. The set's recommendations were validated through a feedback survey involving 487 participants across 45 countries. The set should be used alongside the anxiety and depression standard set for adults with clinicians selecting age-appropriate measures.

The lancet. Psychiatry · systematic review · 117 citationsread the source →

Exercise as an intervention for first-episode psychosis: a feasibility study.

Aim: Exercise can improve psychiatric symptoms, neurocognitive functioning and physical health in schizophrenia. However, the effects in early psychosis have not been explored. This study aimed to assess the feasibility of an exercise intervention for early psychosis and to determine if it was associated with changes in physical and mental health. Methods: Thirty-one patients with first-episode psychosis (FEP) were recruited from early intervention services to a 10-week exercise intervention. The intervention group received individualized training programmes, aiming to achieve ≥90 min of moderate-to-vigorous activity each week, using exercise programmes tailored to individual preferences and needs. A comparison FEP sample from the same services (n = 7) received treatment as usual. Results: Rates of consent and retention in the exercise group were 94% and 81%, respectively. Participants achieved an average of 107 min of moderate-to-vigorous exercise per week. Positive and Negative Syndrome Scale total scores reduced by 13.3 points after 10 weeks of exercise, which was significantly greater than the treatment as usual comparison group (P = 0.010). The greatest differences were observed in negative symptoms, which reduced by 33% in the intervention group (P = 0.013). Significant improvements were also observed in psychosocial functioning and verbal short-term memory. Increases in cardiovascular fitness and processing speed were positively associated with the amounts of exercise achieved by participants. Conclusion: Individualized exercise training could provide a feasible treatment option for improving symptomatic, neurocognitive and metabolic outcomes in FEP.

Early intervention in psychiatry · randomised controlled trial · 76 citationsread the source →

Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial.

Background: Graded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help. Methods: In this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026. Findings: Between May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference -4·2 points, 95% CI -6·1 to -2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data. Interpretation: GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings. Funding: UK National Institute for Health Research Research for Patient Benefit Programme and the Sue Estermann Fund.

Lancet (London, England) · randomised controlled trial · 44 citationsread the source →

A community-based, multi-level, multi-setting, multi-component intervention to reduce weight gain among low socioeconomic status Latinx children with overweight or obesity: The Stanford GOALS randomised controlled trial.

Background: There are few long-term studies of interventions to reduce in low socioeconomic status children with overweight or obesity. The Stanford GOALS trial evaluated a 3-year, community-based, multi-level, multi-setting, multi-component (MMM) systems intervention, to reduce weight gain among low socioeconomic status, Latinx children with overweight or obesity. Methods: We did a two-arm, parallel group, randomised, open-label, active placebo-controlled trial with masked assessment over 3 years. Families from low-income, primarily Latinx communities in Northern California, CA, USA, with 7-11-year-old children with overweight or obesity were randomly assigned to a MMM intervention or a Health Education (HE) comparison intervention. The MMM intervention included home environment changes and behavioural counselling, community after school team sports, and reports to primary health-care providers. The primary outcome was child BMI trajectory over three years. Secondary outcomes included one- and two-year changes in BMI. This trial is registered with ClinicalTrials.govNCT01642836. Findings: Between July 13, 2012, and Oct 3, 2013, 241 families were recruited and randomly assigned to MMM (n=120) or HE (n=121). Children's mean age was 9·5 (SD 1·4) years, 134 (56%) were female and 107 (44%) were male, and 236 (98%) were Latinx. 238 (99%) children participated in year 1, 233 (97%) in year 2, and 227 (94%) in year 3 of follow-up assessments. In intention-to-treat analysis, over 3 years, the difference between intervention groups in BMI trajectory was not significant (mean adjusted difference -0·25 [95% CI -0·90 to 0·40] kg/m2; Cohen's d=0.10; p=0·45). Children in the MMM intervention group gained less BMI over 1 year than did children in the HE intervention group (-0·73 [-1·07 to -0·39] kg/m2, d=0.55); the same was true over 2 years (-0·63 [-1·13 to -0·14] kg/m2; d =0.33). No differential adverse events were observed. Interpretation: The MMM intervention did not reduce BMI gain versus HE over 3 years but the effects over 1 and 2 years in this rigorous trial show the promise of this systems intervention approach for reducing weight gain and cardiometabolic risk factors in low socioeconomic status communities. Funding: US National Institutes of Health.

The lancet. Diabetes & endocrinology · randomised controlled trial · 33 citationsread the source →

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

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

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

Rotavirus Infection, Illness, and Vaccine Performance in Malnourished Children: A Review of the Literature.

Live, oral rotavirus vaccines are more effective at preventing rotavirus disease in countries with low child mortality compared with high child mortality. Among several hypotheses, poorer protection in malnourished children, who are more prevalent in countries with high child mortality, may partially explain this difference. We conducted a literature search to identify articles with a laboratory-confirmed rotavirus endpoint that evaluated differences by malnutrition status in rotavirus vaccine effectiveness and vaccine efficacy (VE) or the prevalence of rotavirus infection or illness among children <5 years old. We identified 7 analyses from 11 countries published from 2007 to 2019 that stratified rotavirus VE by malnutrition status. Among well-nourished children, VE point estimates ranged from 71% to 84% in observational studies and 26% to 61% in clinical trials. Among malnourished children, they ranged from -28% to 45% in observational studies and -3% to 61% in clinical trials. The relative difference between VE in well-nourished and malnourished children by length-for-age ranged from 37% to 64%, by weight-for-age ranged from 0% to 107%, and by weight-for-height ranged from -65% to 137%. We identified 3 cohort and 6 cross-sectional studies of natural rotavirus infection and illness and none reported that malnourished children were more susceptible to rotavirus infection or illness than well-nourished children. Overall, rotavirus vaccines may offer less protection to children with malnutrition than well-nourished children. As malnourished children often have worse outcomes from diarrhea, high rotavirus vaccine coverage and a better understanding of the performance of oral rotavirus vaccines in this population is important, though our finding that malnourished children may be less susceptible to rotavirus provides important context and information for vaccine evaluation design.

The Pediatric infectious disease journal · review · 26 citationsread the source →

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation.

Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use of CPIs. Detailed discussions and prospective well-designed clinical trials are needed to explore this issue further.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · review · 134 citationsread the source →

Ethnic differences in perception of lung function: a factor in pediatric asthma disparities?

Rationale: Disparities in pediatric asthma exist in that Latino children have higher prevalence and greater morbidity from asthma than non-Latino white children. The factors behind these disparities are poorly understood, but ethnic-related variations in children's ability to accurately recognize and report their pulmonary functioning may be a contributing process. Objectives: To determine (1) if differences exist between Latino and non-Latino white children's perceptual accuracy and (2) whether these differences are related to asthma outcomes. Methods: Five hundred and twelve children, aged 7-16 years (290 island Puerto Ricans, 115 Rhode Island Latinos, and 107 Rhode Island non-Latino white children) participated in a 5-week home-based protocol in which twice daily they entered subjective estimates of their peak expiratory flow rate into a hand-held, programmable spirometer and then performed spirometry. Their accuracy was summarized as three perceptual accuracy scores. Demographic data, asthma severity, intelligence, emotional expression, and general symptom-reporting tendencies were assessed and covaried in analyses of the relationship of perceptual accuracy to asthma morbidity and health care use. Measurements and main results: Younger age, female sex, lower intelligence, and poverty were associated with lower pulmonary function perception scores. Island Puerto Rican children had the lowest accuracy and highest magnification scores, followed by Rhode Island Latinos; both differed significantly from non-Latino white children. Perceptual accuracy scores were associated with most indices of asthma morbidity. Conclusions: Controlling for other predictive variables, ethnicity was related to pulmonary function perception ability, as Latino children were less accurate than non-Latino white children. This difference in perceptual ability may contribute to recognized asthma disparities.

American journal of respiratory and critical care medicine · 54 citationsread the source →

Brief Digital Interventions to Support the Psychological Well-being of NHS Staff During the COVID-19 Pandemic: 3-Arm Pilot Randomized Controlled Trial.

Background: Health and social care staff are at high risk of experiencing adverse mental health (MH) outcomes during the COVID-19 pandemic. Hence, there is a need to prioritize and identify ways to effectively support their psychological well-being (PWB). Compared to traditional psychological interventions, digital psychological interventions are cost-effective treatment options that allow for large-scale dissemination and transcend social distancing, overcome rurality, and minimize clinician time. Objective: This study reports MH outcomes of a Consolidated Standards of Reporting Trials (CONSORT)-compliant parallel-arm pilot randomized controlled trial (RCT) examining the potential usefulness of an existing and a novel digital psychological intervention aimed at supporting psychological health among National Health Service (NHS) staff working through the COVID-19 pandemic. Methods: NHS Highland (NHSH) frontline staff volunteers (N=169) were randomly assigned to the newly developed NHSH Staff Wellbeing Project (NHSWBP), an established digital intervention (My Possible Self [MPS]), or a waitlist (WL) group for 4 weeks. Attempts were made to blind participants to which digital intervention they were allocated. The interventions were fully automated, without any human input or guidance. We measured 5 self-reported psychological outcomes over 3 time points: before (baseline), in the middle of (after 2 weeks), and after treatment (4 weeks). The primary outcomes were anxiety (7-item General Anxiety Disorder), depression (Patient Health Questionnaire), and mental well-being (Warwick-Edinburgh Mental Well-being Scale). The secondary outcomes included mental toughness (Mental Toughness Index) and gratitude (Gratitude Questionnaire-6). Results: Retention rates mid- and postintervention were 77% (n=130) and 63.3% (n=107), respectively. Postintervention, small differences were noted between the WL and the 2 treatment groups on anxiety (vs MPS: Cohen d=0.07, 95% CI -0.20 to 0.33; vs NHSWBP: Cohen d=0.06, 95% CI -0.19 to 0.31), depression (vs MPS: Cohen d=0.37, 95% CI 0.07-0.66; vs NHSWBP: Cohen d=0.18, 95% CI -0.11 to 0.46), and mental well-being (vs MPS: Cohen d=-0.04, 95% CI -0.62 to -0.08; vs NHSWBP: Cohen d=-0.15, 95% CI -0.41 to 0.10). A similar pattern of between-group differences was found for the secondary outcomes. The NHSWBP group generally had larger within-group effects than the other groups and displayed a greater rate of change compared to the other groups on all outcomes, except for gratitude, where the rate of change was greatest for the MPS group. Conclusions: Our analyses provided encouraging results for the use of brief digital psychological interventions in improving PWB among health and social care workers. Future multisite RCTs, with power to reliably detect differences, are needed to determine the efficacy of contextualized interventions relative to existing digital treatments. Trial registration: ISRCTN Registry (ISRCTN) ISRCTN18107122; https://www.isrctn.com/ISRCTN18107122.

JMIR mental health · 17 citationsread the source →

Risk and protective factors for childhood suicidality: a US population-based study.

Background: Childhood suicidal ideation and behaviours are poorly understood. We examined correlates of suicidality in a US population-based sample of children participating in the Adolescent Brain and Cognitive Development (ABCD) study. The ABCD study aims to examine trajectories of mental health from childhood to adulthood and collects information on multiple domains, including mental and physical wellbeing, brain imaging, behavioural and cognitive characteristics, and social and family environment. We sought to identify and rank risk and protective factors for childhood suicidal thoughts and behaviours across these multiple domains and evaluate their association with self-agreement and caregiver agreement in reporting suicidality. Methods: The ABCD sample comprises a cohort of 11 875 children aged 9-10 years. The sociodemographic factors on which the sample was recruited were age, sex, race, socioeconomic status, and urbanicity. Participants were enrolled at 22 sites, the catchment area of which encompassed over 20% of the entire US population in this age group. Multistage sampling was used to ensure both local randomisation and representativeness of sociodemographic variation of the ABCD sample. The data used in this study were accessed from the ABCD Study Curated Annual Release 2.0. Suicidal thoughts and behaviours (suicidality) in each child were evaluated through independent child and caregiver reports based on the computerized Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 (KSADS-5). We used bootstrapped logistic regression to quantify the association between suicidal ideation and behaviours, with measures of mental and physical wellbeing, behaviour, cognition, and social and family environment in participants from the ABCD study. Findings: Our study sample comprised 7994 unrelated children (mean age 9·9 years [SD 0·5]; 4234 [53%] male participants) with complete data on child-reported and caregiver-reported suicidal ideas and behaviours. Overall, 673 (8·4%) children reported any past or current suicidal ideation, 75 (0·9%) had any past or current suicidal plans, and 107 (1·3%) had any past or current suicidal attempts. According to caregivers, 650 (8·1%) of the children reported any past or current suicidal ideation, 46 (0·6%) reported any past or current suicidal plans, and 39 (0·5%) reported past or current suicidal attempts. However, inter-informant agreement was low (Cohen's κ range 0·0-0·2). Regardless of informant, child psychopathology (odds ratio [OR] 1·7-4·8, 95% CI 1·5-7·4) and child-reported family conflict (OR 1·4-1·8, 95% CI 1·1-2·5) were the most robust risk factors for suicidality. The risk of child-reported suicidality increased with higher weekend screen use time (OR 1·3, 95% CI 1·2-1·7) and reduced with greater parental supervision and positive school involvement (for both OR 0·8, 95% CI 0·7-0·9). Additionally, caregiver-reported suicidality was positively associated with caregiver educational level (OR 1·3, 95% CI 1·1-1·5) and male sex in children (1·5, 1·1-2·0), and inversely associated with the number of household cohabitants (0·8, 0·7-1·0). Interpretation: We identified risk and protective factors that show robust and generalisable associations with childhood suicidality. These factors provide actionable targets for optimising prevention and intervention strategies, support the need to identify and treat psychopathology in school-age children, and underscore the importance of school and family interventions for childhood suicidality. Funding: National Institutes of Health.

The lancet. Psychiatry · 158 citationsread the source →

Socioeconomic status and parenting in ethnic minority families: testing a minority family stress model.

According to the family stress model (Conger & Donnellan, 2007), low socioeconomic status (SES) predicts less-than-optimal parenting through family stress. Minority families generally come from lower SES backgrounds than majority families, and may experience additional stressors associated with their minority status, such as acculturation stress. The primary goal of this study was to test a minority family stress model with a general family stress pathway, as well as a pathway specific to ethnic minority families. The sample consisted of 107 Turkish-Dutch mothers and their 5- to 6-year-old children, and positive parenting was observed during a 7-min problem-solving task. In addition, mothers reported their daily hassles, psychological distress, and acculturation stress. The relation between SES and positive parenting was partially mediated by both general maternal psychological stress and maternal acculturation stress. Our study contributes to the argument that stressors specific to minority status should be considered in addition to more general demographic and family stressors in understanding parenting behavior in ethnic minority families.

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · 48 citationsread the source →

Contribution of infants' sleep and crying to marital relationship of first-time parent couples in the 1st year after childbirth.

This study investigated the influence of infants' sleep and crying on marital relationship in first-time parent couples (N = 107) during the 1st year after birth. Control variables are parents' insomnia and parental self-efficacy in handling the baby. Questionnaires were administered to both parents before birth, at 2 and 7 weeks after birth, and at 1 year after birth. Results show that marital problem-solving ability did not change but that marital satisfaction diminished significantly over time. Crying was the main child variable that affected marital satisfaction. Fathers' self-efficacy contributed positively to marital problem solving and negatively to paternal insomnia. Both maternal and paternal insomnia affected spouses' insomnia. As infant sleep problems may worsen preexisting parental insomnia, it is recommended that first-time parents be informed about treatments of insomnia.

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · 55 citationsread the source →

Posttraumatic stress disorder and risk of dementia among US veterans.

Context: Posttraumatic stress disorder (PTSD) is highly prevalent among US veterans because of combat and may impair cognition. Objective: To determine whether PTSD is associated with the risk of developing dementia among older US veterans receiving treatment in the Department of Veterans Affairs medical centers. Design: A stratified, retrospective cohort study conducted using the Department of Veterans Affairs National Patient Care Database. Setting: Department of Veterans Affairs medical centers in the United States. Participants: A total of 181 093 veterans 55 years or older without dementia from fiscal years 1997 through 2000 (53 155 veterans with and 127 938 veterans without PTSD). Main outcome measures: During the follow-up period between October 1, 2000, and December 31, 2007, 31 107 (17.2%) veterans were ascertained to have newly diagnosed dementia according to International Classification of Diseases, Ninth Revision, Clinical Modification codes. Results: The mean baseline age of the veterans was 68.8 years, and 174 806 (96.5%) were men. Veterans with PTSD had a 7-year cumulative incident dementia rate of 10.6%, whereas those without had a rate of 6.6% (P < .001). With age as the time scale, Cox proportional hazards models indicated that patients with PTSD were more than twice as likely to develop incident dementia compared with those without PTSD (hazard ratio, 2.31; 95% confidence interval, 2.24-2.39). After multivariable adjustment, patients with PTSD were still more likely to develop dementia (hazard ratio, 1.77; 95% confidence interval, 1.70-1.85). Results were similar when we excluded those with a history of head injury, substance abuse, or clinical depression. Conclusions: In a predominantly male veteran cohort, those diagnosed as having PTSD were at a nearly 2-fold-higher risk of developing dementia compared with those without PTSD. Mechanisms linking these important disorders need to be identified with the hope of finding ways to reduce the increased risk of dementia associated with PTSD.

Archives of general psychiatry · 404 citationsread the source →

Using video images of dementia in advance care planning.

Background: Advance care planning is a process by which patients plan for future medical care under circumstances of impaired decision-making. Central to this process is the patient's understanding and ability to imagine future health states. Methods: A before and after oral survey was used to compare the effect of a video depiction with that of a verbal description of a patient with advanced dementia for individuals selecting level of medical care at 7 primary care clinics at 2 US medical centers. The study enrolled 120 adults, half of whom were nonwhite. Results: A total of 120 subjects completed the interview. Before watching the video, 60 (50.0%) subjects preferred comfort care, 25 (20.8%) desired life-prolonging care, 22 (18.3%) chose limited care, and 13 (10.8%) were unsure of their preferences. Subject preferences changed significantly after the video: 107 (89.2%) of the subjects chose comfort care, none desired life-prolonging care, 10 (8.3%) chose limited care, and 3 (2.5%) were unsure of their preferences (P < .001). Unadjusted analysis revealed a statistically significant difference regarding preferences, based on race/ethnicity, before watching the video: 40% of African Americans and 43% of Latinos chose comfort care, compared with 58% of whites (P = .04). Differences were also noted for educational level (P = .03). After the video, differences in preferences based on race/ethnicity and educational level disappeared. Conclusions: Watching the video significantly changed preferences for care, transcending apparent differences in preferences associated with race/ethnicity and educational level. This study suggests that using video in addition to improved verbal communication may lead to more informed advance care planning by enhancing the ability of patients to imagine a hypothetical health state.

Archives of internal medicine · 97 citationsread the source →