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Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies.

Objective: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). Design: Umbrella review. Data sources: PubMed, PsychInfo, Embase, up to 9 February 2022. Eligibility criteria for selecting studies: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. Results: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). Conclusions: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events. Study registration: PROSPERO CRD42018093045. Funding: None.

BMJ (Clinical research ed.) · systematic review · 159 citationsread the source →

Effect of a Novel Online Group-Coaching Program to Reduce Burnout in Female Resident Physicians: A Randomized Clinical Trial.

Importance: Female resident physicians are disproportionately affected by burnout, which can have serious consequences for their well-being and career trajectory. Growing evidence supports the use of professional coaching to reduce burnout in resident physicians, yet individual coaching is resource intensive and infeasible for many training programs. Objective: To assess whether a structured professional group-coaching program for female resident physicians would lead to decreased burnout. Design, setting, and participants: This pilot randomized clinical trial was conducted from January 1 to June 30, 2021, among 101 female resident physicians in graduate medical education at the University of Colorado who voluntarily enrolled in the trial after a recruitment period. Surveys were administered to participants before and after the intervention. Intervention: With the use of a computer-generated 1:1 algorithm, 50 participants were randomly assigned to the intervention group and 51 participants were randomly assigned to the control group. The intervention group was offered a 6-month, web-based group-coaching program, Better Together Physician Coaching, developed and facilitated by trained life coaches and physicians. The control group received residency training as usual, with no coaching during the study. The control group was offered the 6-month coaching program after study completion. Main outcomes and measures: The primary outcome of burnout was measured using the Maslach Burnout Inventory, defined by 3 Likert-type 7-point subscales: emotional exhaustion, depersonalization, and professional accomplishment. Higher scores on the emotional exhaustion and depersonalization subscales and lower scores on the professional accomplishment subscale indicate higher burnout. Secondary outcomes of impostor syndrome, self-compassion, and moral injury were assessed using the Young Impostor Syndrome Scale, Neff's Self-Compassion Scale-Short Form, and the Moral Injury Symptom Scale-Healthcare Professionals, respectively. An intention-to-treat analysis was performed. Results: Among the 101 female residents in the study, the mean (SD) age was 29.4 (2.3) years, 96 (95.0%) identified as heterosexual, and 81 (80.2%) identified as White. There were 19 residents (18.8%) from surgical subspecialties, with a range of training levels represented. After 6 months of professional coaching, emotional exhaustion decreased in the intervention group by a mean (SE) of 3.26 (1.25) points compared with a mean (SE) increase of 1.07 (1.12) points in the control group by the end of the study (P = .01). The intervention group experienced a significant reduction in presence of impostor syndrome compared with controls (mean [SE], -1.16 [0.31] vs 0.11 [0.27] points; P = .003). Self-compassion scores increased in the intervention group by a mean (SE) of 5.55 (0.89) points compared with a mean (SE) reduction of 1.32 (0.80) points in the control group (P < .001). No statistically significant differences in depersonalization, professional accomplishment, or moral injury scores were observed. Owing to the differential follow-up response rates in the treatment groups (88.2% in the control group [45 of 51]; 68.0% in the intervention group [34 of 50]), a sensitivity analysis was performed to account for the missing outcomes, with similar findings. Conclusions and relevance: In this randomized clinical trial, professional coaching reduced emotional exhaustion and impostor syndrome scores and increased self-compassion scores among female resident physicians. Trial registration: ClinicalTrials.gov Identifier: NCT05280964.

JAMA network open · randomised controlled trial · 97 citationsread the source →

Parent training in non-violent resistance for children with attention deficit hyperactivity disorder: a controlled outcome study.

Current forms of parent training for childhood attention deficit hyperactivity disorder (ADHD) are often insufficient. Many families drop out of the training, and treatment gains are often not maintained. Nonviolent resistance parent training (NVR) focuses on helping parents resist the child's negative behaviors without escalating the problem. NVR helps parents to fulfill an anchoring function, supporting the child through presence, self-regulation, structure, and support network. This study is a randomized controlled trial designed to assess the efficacy of NVR in the treatment of childhood ADHD. Participants were Israeli parents of children with primary ADHD diagnosis (N = 101; 5-13 years old; 79% male participants) randomly assigned to either 12-session NVR (N = 50) or waiting list (N = 51). Measures were administered before and after treatment and at a 4-month follow-up. ADHD outcomes included the Conners and Child Behavior Checklist. Parenting outcomes included parental helplessness, emotional regulation, anchoring function, and family chaos. Participants in the NVR condition reported significant improvements in the child's internalizing, externalizing, and ADHD symptoms, as well as improvement in paternal and maternal helplessness and anchoring. Participants in the control condition did not report changes in the child's symptoms or the parents' condition. The results at follow-up revealed maintenance of change in the child's externalizing and internalizing symptoms, but failure to maintain gains in ADHD core symptoms. Maternal helplessness and anchoring, as well as family chaos continued to improve at follow-up. Dropout rates in the treatment group were low (5%), and fathers' engagement was close to 100%. NVR is an efficient treatment for childhood ADHD, with benefits extending beyond the child's symptoms to the entire family. NVR's special focus on parental distress may have contributed to low dropout, high paternal engagement, and maintenance of change.

European child & adolescent psychiatry · randomised controlled trial · 4 citationsread the source →

Randomized, controlled trial of topical exit-site application of honey (Medihoney) versus mupirocin for the prevention of catheter-associated infections in hemodialysis patients.

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Journal of the American Society of Nephrology : JASN · randomised controlled trial · 91 citationsread the source →

Favourable prognosis of trigeminal neuralgia when enrolled in a multidisciplinary management program - a two-year prospective real-life study.

Background: Prognosis of medically treated trigeminal neuralgia patients is assumed to be poor, but the evidence is lacking. Thus, prospective real-life studies of medical management of trigeminal neuralgia are warranted. Methods: This was an observational study. Patients were consecutively enrolled in a structured management program at a specialist centre for facial pain. Optimisation of medical treatment, physiotherapy, psychotherapy, and advice from trained nurses, were parts of the program. Medically intractable patients were referred for neurosurgery. Data-collection was prospective using standardised schemes and patient surveys. The aim was to describe the two-year outcome of medical treatment at the specialist centre. The primary outcome was a 50% reduction in the overall burden of pain according to a Numerical Rating Scale (NRS) after two years. Results: A total of 186 primary TN patients were enrolled in the program of which 103 patients remained medically managed and completed the two-year follow-up. Fifty patients were treated surgically within the first two years of follow-up. Half of the medically managed patients (53 (51%)), had more than a 50% reduction in the overall burden of pain over the two-year period. The overall burden of pain on NRS decreased from mean 5.34 to 3.00, p < 0.01. There was no significant association between primary outcome and sex, depression and/or anxiety, concomitant persistent pain, or neurovascular contact with morphological changes of the trigeminal nerve. Conclusions: Patients with trigeminal neuralgia improve over a two-year period when enrolled in a structured medical management program. Optimisation of drug treatment, continuous advice and education and support by the multidisciplinary team, referral of the medically intractable patients for surgery or the natural history of the disease, can be some of the reasons for the improvement. The favourable prognosis provides hope and optimism for medically managed TN patients. Trial registration: Current study was observational, and patients were offered standard clinical care and laboratory workups according to current American Academy of Neurology and European Federation of Neurological Societies treatment guidelines. The study has been registered at ClincalTrials.gov. ID: NCT03838393 .

The journal of headache and pain · cohort or longitudinal · 30 citationsread the source →

Promoting social cohesion, compassion and forgiveness among Rwandan survivors and perpetrators through community resiliency model training: a longitudinal randomized comparison study.

Introduction: The 1994 genocide against the Tutsi severely broke Rwandan society, leaving deep family and societal scars. Efforts to restore resilience and social cohesion hold promise but continue to face significant challenges. This study aimed to investigate whether the Community Resiliency Model (CRM) intervention was able to promote social cohesion, forgiveness, and compassion while strengthening personal resilience among survivors and released genocide perpetrators in post-genocide, Rwanda. We set out to address a methodological gap by exploring whether participants who experienced the Rwandan genocide do better in mixed groups versus homogeneous groups on key social function outcomes. Methods: A longitudinal randomized comparison group study design was employed to evaluate the impact of CRM on social cohesion, compassion, resilience, and forgiveness in a convenience sample of three comparison groups to which participants were randomly assigned: one with genocide survivors (N = 51), one with genocide perpetrators (N = 51), and one with a combination of both (N = 50). In August 2023, participants completed a consecutive three-day Community Resiliency Model (CRM) training in community settings. Data were collected using standardized tools at baseline, immediately after the intervention, and at six-month follow-up, between August 2023 and March 2024. ANOVA was conducted to identify significant differences among outcome variables. Results: The results showed that social cohesion (F(1) = 36.1, p < .001), compassion (F(1) = 131, p < .001), forgiveness (F(1) = 19.8, p < .001), and resilience (F(1) = 8.10, p = .005) significantly improved across all groups. Participants in the mixed group showed slightly more improvement than other groups, but the difference was not statistically significant. Conclusion: The results are promising, suggesting that CRM could serve as an effective intervention to address the challenges of rebuilding cohesive and resilient communities by improving social functioning in societies that have experienced fragmentation due to societal traumas.

European journal of psychotraumatology · randomised controlled trialread the source →

The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses.

Schizophrenia is the eighth leading cause of disability worldwide in people aged 15-44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42-0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [⩾20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (⩾50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3-6 months' duration; trough clozapine level ⩾350-400 μg/L) with a response rate (⩾20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade.

Therapeutic advances in psychopharmacology · review · 154 citationsread the source →

Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain: A Randomized Clinical Trial.

Importance: Chronic back pain (CBP) is a leading cause of disability, and treatment is often ineffective. Approximately 85% of cases are primary CBP, for which peripheral etiology cannot be identified, and maintenance factors include fear, avoidance, and beliefs that pain indicates injury. Objective: To test whether a psychological treatment (pain reprocessing therapy [PRT]) aiming to shift patients' beliefs about the causes and threat value of pain provides substantial and durable pain relief from primary CBP and to investigate treatment mechanisms. Design, setting, and participants: This randomized clinical trial with longitudinal functional magnetic resonance imaging (fMRI) and 1-year follow-up assessment was conducted in a university research setting from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Clinical and fMRI data were analyzed from January 2019 to August 2020. The study compared PRT with an open-label placebo treatment and with usual care in a community sample. Interventions: Participants randomized to PRT participated in 1 telehealth session with a physician and 8 psychological treatment sessions over 4 weeks. Treatment aimed to help patients reconceptualize their pain as due to nondangerous brain activity rather than peripheral tissue injury, using a combination of cognitive, somatic, and exposure-based techniques. Participants randomized to placebo received an open-label subcutaneous saline injection in the back; participants randomized to usual care continued their routine, ongoing care. Main outcomes and measures: One-week mean back pain intensity score (0 to 10) at posttreatment, pain beliefs, and fMRI measures of evoked pain and resting connectivity. Results: At baseline, 151 adults (54% female; mean [SD] age, 41.1 [15.6] years) reported mean (SD) pain of low to moderate severity (mean [SD] pain intensity, 4.10 [1.26] of 10; mean [SD] disability, 23.34 [10.12] of 100) and mean (SD) pain duration of 10.0 (8.9) years. Large group differences in pain were observed at posttreatment, with a mean (SD) pain score of 1.18 (1.24) in the PRT group, 2.84 (1.64) in the placebo group, and 3.13 (1.45) in the usual care group. Hedges g was -1.14 for PRT vs placebo and -1.74 for PRT vs usual care (P < .001). Of 151 total participants, 33 of 50 participants (66%) randomized to PRT were pain-free or nearly pain-free at posttreatment (reporting a pain intensity score of 0 or 1 of 10), compared with 10 of 51 participants (20%) randomized to placebo and 5 of 50 participants (10%) randomized to usual care. Treatment effects were maintained at 1-year follow-up, with a mean (SD) pain score of 1.51 (1.59) in the PRT group, 2.79 (1.78) in the placebo group, and 3.00 (1.77) in the usual care group. Hedges g was -0.70 for PRT vs placebo (P = .001) and -1.05 for PRT vs usual care (P < .001) at 1-year follow-up. Longitudinal fMRI showed (1) reduced responses to evoked back pain in the anterior midcingulate and the anterior prefrontal cortex for PRT vs placebo; (2) reduced responses in the anterior insula for PRT vs usual care; (3) increased resting connectivity from the anterior prefrontal cortex and the anterior insula to the primary somatosensory cortex for PRT vs both control groups; and (4) increased connectivity from the anterior midcingulate to the precuneus for PRT vs usual care. Conclusions and relevance: Psychological treatment centered on changing patients' beliefs about the causes and threat value of pain may provide substantial and durable pain relief for people with CBP. Trial registration: ClinicalTrials.gov Identifier: NCT03294148.

JAMA psychiatry · randomised controlled trial · 223 citationsread the source →

Caregivers' role in breaking bad news: patients, doctors, and nurses' points of view.

The aim of the research was to identify the caregivers' response patterns when breaking bad news at the first time of cancer diagnosis and their affect on the patient. These issues were examined from 3 points of view: patients, doctors, and nurses. A total of 152 Israelis subjects participated in the research: 51 patients with cancer, 51 nurses, and 50 doctors. They filled out a questionnaire developed for the research that included 35 items. Support patterns identified as effective were as follows: allowing for the expression of emotions, empathetic silence, support through touch, and the use of participatory, commendation, and encouragement statements. The research findings indicate the crucial need in the involvement of a family member and a nurse in the process and in supplying written information for the receiver of the news. Significant differences (P < .05) between patients and caregivers were found in the type of information given, in the timing and quantity, and in the support and communication patterns. The principal emotions professional caregivers experienced were identification and helplessness. Most of them were not trained in this field. The research findings could bridge the gap between what patients want and what caregivers do and would benefit in designing guidelines for breaking bad news and formulating a workshop program for furthering the team skills.

Cancer nursing · 33 citationsread the source →

Effect of leukocyte telomere length on total and regional brain volumes in a large population-based cohort.

Importance: Telomere length has been associated with dementia and psychological stress, but its relationship with human brain size is unknown. Objective: To determine if peripheral blood telomere length is associated with brain volume. Design, setting, and participants: Peripheral blood leukocyte telomere length and brain volumes were measured for 1960 individuals in the Dallas Heart Study, a population-based, probability sample of Dallas County, Texas, residents, with a median (25th-75th percentile) age of 50 (42-58) years. Global and 48 regional brain volumes were assessed from the automated analysis of magnetic resonance imaging. Main outcomes and measures: Telomere length and global and regional brain volumes. Results: Leukocyte telomere length was associated with total cerebral volume (β [SE], 0.06 [0.01], P <.001) including white and cortical gray matter volume (β [SE], 0.04 [0.01], P = .002; β [SE], 0.07 [0.02], P <.001, respectively), independent of age, sex, ethnicity, and total intracranial volume. While age was associated with the size of most subsegmental regions of the cerebral cortex, telomere length was associated with certain subsegmental regions. Compared with age, telomere length (TL) explained a sizeable proportion of the variance in volume of the hippocampus, amygdala, and inferior temporal region (hippocampus: βTL [SE], 0.08 [0.02], R2, 0.91% vs βage [SE], -0.16 [0.02], R2, 3.80%; amygdala: βTL [SE], 0.08 [0.02], R2, 0.78% vs βage [SE],-0.19 [0.02], R2,4.63%; inferior temporal: βTL [SE], 0.07 [0.02], R2, 0.92% vs βage [SE], -0.14 [0.02], R2, 3.98%) (P <.001 for all). The association of telomere length and the size of the inferior and superior parietal, hippocampus, and fusiform regions was stronger in individuals older than 50 years than younger individuals (inferior parietal: β>50 [SE], 0.13 [0.03], P <.001 vs β≤50 [SE], 0.02 [0.02], P = .51, P for interaction = .001; superior parietal: β>50 [SE], 0.11 [0.03], P <.001 vs β≤50 [SE], 0.01 [0.02], P = .71, P for interaction = .004; hippocampus: β>50 [SE], 0.10 [0.03], P = .004 vs β≤50 [SE], 0.05 [0.02], P = .07, P for interaction = .04; fusiform: β>50 [SE], 0.09 [0.03], P = .002, β≤50 [SE], 0.03 [0.02], P = .31, P for interaction = .03). The volume of the hippocampus, amygdala, superior and inferior temporal, precuneus, lateral orbitofrontal, posterior cingulate, thalamus and ventral diencephalon were independently associated with telomere length after adjustment for all covariates (age, gender, ethnicity, total intracranial volume, body mass index, blood pressure, diabetes, smoking status, and APOE genotype). Conclusions and relevance: To our knowledge, this is the first population-based study to date to evaluate telomere length as an independent predictor of global and regional brain size. Future studies are needed to determine how telomere length and anatomic structural changes are related to cognitive function, dementia, and psychological disease.

JAMA neurology · 74 citationsread the source →

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

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

Frontiers in Psychology · 12 citationsread the source →

Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure.

Background: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. Methods: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. Results: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). Conclusions: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120.

Circulation · randomised controlled trial · 88 citationsread the source →

Racial discrimination and psychological distress: the impact of ethnic identity and age among immigrant and United States-born Asian adults.

The association between racial and ethnic discrimination and psychological distress was examined among 2,047 Asians (18 to 75 years of age) in the National Latino and Asian American Study, the first-ever nationally representative study of mental health among Asians living in the United States. Stratifying the sample by age in years (i.e., 18 to 30, 31 to 40, 41 to 50, 51 to 75) and nativity status (i.e., immigrant vs. U.S.-born), ethnic identity was tested as either a protective or exacerbating factor. Analyses showed that ethnic identity buffered the association between discrimination and mental health for U.S.-born individuals 41 to 50 years of age. For U.S.-born individuals 31 to 40 years of age and 51 to 75 years of age, ethnic identity exacerbated the negative effects of discrimination on mental health. The importance of age and immigrant status for the association between ethnic identity, discrimination, and well-being among Asians in the United States is discussed.

Developmental psychology · 177 citationsread the source →

A Validation of Six Wearable Devices for Estimating Sleep, Heart Rate and Heart Rate Variability in Healthy Adults.

The primary aim of this study was to examine the validity of six commonly used wearable devices, i.e., Apple Watch S6, Garmin Forerunner 245 Music, Polar Vantage V, Oura Ring Generation 2, WHOOP 3.0 and Somfit, for assessing sleep. The secondary aim was to examine the validity of the six devices for assessing heart rate and heart rate variability during, or just prior to, night-time sleep. Fifty-three adults (26 F, 27 M, aged 25.4 ± 5.9 years) spent a single night in a sleep laboratory with 9 h in bed (23:00-08:00 h). Participants were fitted with all six wearable devices-and with polysomnography and electrocardiography for gold-standard assessment of sleep and heart rate, respectively. Compared with polysomnography, agreement (and Cohen's kappa) for two-state categorisation of sleep periods (as sleep or wake) was 88% (κ = 0.30) for Apple Watch; 89% (κ = 0.35) for Garmin; 87% (κ = 0.44) for Polar; 89% (κ = 0.51) for Oura; 86% (κ = 0.44) for WHOOP and 87% (κ = 0.48) for Somfit. Compared with polysomnography, agreement (and Cohen's kappa) for multi-state categorisation of sleep periods (as a specific sleep stage or wake) was 53% (κ = 0.20) for Apple Watch; 50% (κ = 0.25) for Garmin; 51% (κ = 0.28) for Polar; 61% (κ = 0.43) for Oura; 60% (κ = 0.44) for WHOOP and 65% (κ = 0.52) for Somfit. Analyses regarding the two-state categorisation of sleep indicate that all six devices are valid for the field-based assessment of the timing and duration of sleep. However, analyses regarding the multi-state categorisation of sleep indicate that all six devices require improvement for the assessment of specific sleep stages. As the use of wearable devices that are valid for the assessment of sleep increases in the general community, so too does the potential to answer research questions that were previously impractical or impossible to address-in some way, we could consider that the whole world is becoming a sleep laboratory.

Sensors (Basel, Switzerland) · 188 citationsread the source →

Targeting Behavioral Symptoms and Functional Decline in Dementia: A Randomized Clinical Trial.

Background/objectives: Dementia-related behavioral symptoms and functional dependence result in poor quality of life for persons with dementia and their caregivers. The goal was to determine whether a home-based activity program (Tailored Activity Program; TAP-VA) would reduce behavioral symptoms and functional dependence of veterans with dementia and caregiver burden. Design: Single-blind (interviewer), parallel, randomized, controlled trial (Clinicaltrials.gov: NCT01357564). Setting: Veteran's homes. Participants: Veterans with dementia and their family caregivers (N = 160 dyads). Intervention: Dyads in TAP-VA underwent 8 sessions with occupational therapists to customize activities to the interests and abilities of the veterans and educate their caregivers about dementia and use of customized activity. Caregivers assigned to attention control received up to 8 telephone-based dementia education sessions with a research team member. Measurements: Primary outcomes included number of behaviors and frequency of their occurrence multiplied by severity of occurrence; secondary outcomes were functional dependence, pain, emotional well-being, caregiver burden (time spent caregiving, upset with behaviors) and affect at 4 (primary endpoint) and 8 months. Results: Of 160 dyads (n = 76 TAP-VA; n = 84 control), 111 completed 4-month interviews (n = 51 TAP-VA; n = 60 control), and 103 completed 8-month interviews (n = 50 TAP-VA; n = 53 control). At 4 months, compared to controls, the TAP-VA group showed reductions in number (difference in mean change from baseline = -0.68, 95% CI = -1.23 to -0.13) and frequency by severity (-24.3, 95% CI = -45.6 to -3.1) of behavioral symptoms, number of activities needing assistance with (-0.80, 95% CI = -1.41 to -0.20), functional dependence level (4.09, 95% CI = 1.06, 7.13), and pain (-1.18, 95% CI = -2.10 to -0.26). Caregivers of veterans in TAP-VA reported less behavior-related distress. Benefits did not extend to 8 months. Conclusion: TAP-VA had positive immediate effects and no adverse events. Because TAP-VA reduces behavioral symptoms, slows functional dependence, and alleviates pain and caregiver distress, it is a viable treatment option for families.

Journal of the American Geriatrics Society · randomised controlled trial · 70 citationsread the source →

Non-pharmacological interventions for assisting the induction of anaesthesia in children.

Background: Induction of general anaesthesia can be distressing for children. Non-pharmacological methods for reducing anxiety and improving co-operation may avoid the adverse effects of preoperative sedation. Objectives: To assess the effects of non-pharmacological interventions in assisting induction of anaesthesia in children by reducing their anxiety, distress or increasing their co-operation. Search methods: In this updated review we searched CENTRAL (the Cochrane Library 2012, Issue 12) and searched the following databases from inception to 15 January 2013: MEDLINE, EMBASE, PsycINFO and Web of Science. We reran the search in August 2014. We will deal with the single study found to be of interest when we next update the review. Selection criteria: We included randomized controlled trials of a non-pharmacological intervention implemented on the day of surgery or anaesthesia. Data collection and analysis: At least two review authors independently extracted data and assessed risk of bias in trials. Main results: We included 28 trials (2681 children) investigating 17 interventions of interest; all trials were conducted in high-income countries. Overall we judged the trials to be at high risk of bias. Except for parental acupuncture (graded low), all other GRADE assessments of the primary outcomes of comparisons were very low, indicating a high degree of uncertainty about the overall findings. Parental presence: In five trials (557 children), parental presence at induction of anaesthesia did not reduce child anxiety compared with not having a parent present (standardized mean difference (SMD) 0.03, 95% confidence interval (CI) -0.14 to 0.20). In a further three trials (267 children) where we were unable to pool results, we found no clear differences in child anxiety, whether a parent was present or not. In a single trial, child anxiety showed no significant difference whether one or two parents were present, although parental anxiety was significantly reduced when both parents were present at the induction. Parental presence was significantly less effective than sedative premedication in reducing children's anxiety at induction in three trials with 254 children (we could not pool results). Child interventions (passive): When a video of the child's choice was played during induction, children were significantly less anxious than controls (median difference modified Yale Preoperative Anxiety Scale (mYPAS) 31.2, 95% CI 27.1 to 33.3) in a trial of 91 children. In another trial of 120 children, co-operation at induction did not differ significantly when a video fairytale was played before induction. Children exposed to low sensory stimulation were significantly less anxious than control children on introduction of the anaesthesia mask and more likely to be co-operative during induction in one trial of 70 children. Music therapy did not show a significant effect on children's anxiety in another trial of 51 children. Child interventions (mask introduction): We found no significant differences between a mask exposure intervention and control in a single trial of 103 children for child anxiety (risk ratio (RR) 0.59, 95% CI 0.31 to 1.11) although children did demonstrate significantly better co-operation in the mask exposure group (RR 1.27, 95% CI 1.06 to 1.51). Child interventions (interactive): In a three-arm trial of 168 children, preparation with interactive computer packages (in addition to parental presence) was more effective than verbal preparation, although differences between computer and cartoon preparation were not significant, and neither was cartoon preparation when compared with verbal preparation. Children given video games before induction were significantly less anxious at induction than those in the control group (mYPAS mean difference (MD) -9.80, 95% CI -19.42 to -0.18) and also when compared with children who were sedated with midazolam (mYPAS MD -12.20, 95% CI -21.82 to -2.58) in a trial of 112 children. When compared with parental presence only, clowns or clown doctors significantly lessened children's anxiety in the operating/induction room (mYPAS MD -24.41, 95% CI -38.43 to -10.48; random-effects, I² 75%) in three trials with a total of 133 children. However, we saw no significant differences in child anxiety in the operating room between clowns/clown doctors and sedative premedication (mYPAS MD -9.67, 95% CI -21.14 to 1.80, random-effects, I² 66%; 2 trials of 93 children). In a trial of hypnotherapy versus sedative premedication in 50 children, there were no significant differences in children's anxiety at induction (RR 0.59, 95% CI 0.33 to 1.04). Parental interventions: Children of parents having acupuncture compared with parental sham acupuncture were less anxious during induction (mYPAS MD -17, 95% CI -30.51 to -3.49) and were more co-operative (RR 1.59, 95% CI 1.01 to 2.53) in a single trial of 67 children. Two trials with 191 parents assessed the effects of parental video viewing but did not report any of the review's prespecified primary outcomes. Authors' conclusions: This review shows that the presence of parents during induction of general anaesthesia does not diminish their child's anxiety. Potentially promising non-pharmacological interventions such as parental acupuncture; clowns/clown doctors; playing videos of the child's choice during induction; low sensory stimulation; and hand-held video games need further investigation in larger studies.

The Cochrane database of systematic reviews · meta-analysis · 100 citationsread the source →

Psychological therapies for women who experience intimate partner violence.

Background: Intimate partner violence (IPV) against women is prevalent and strongly associated with mental health problems. Women experiencing IPV attend health services frequently for mental health problems. The World Health Organization recommends that women who have experienced IPV and have a mental health diagnosis should receive evidence-based mental health treatments. However, it is not known if psychological therapies work for women in the context of IPV and whether they cause harm. Objectives: To assess the effectiveness of psychological therapies for women who experience IPV on the primary outcomes of depression, self-efficacy and an indicator of harm (dropouts) at six- to 12-months' follow-up, and on secondary outcomes of other mental health symptoms, anxiety, quality of life, re-exposure to IPV, safety planning and behaviours, use of healthcare and IPV services, and social support. Search methods: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR), CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, and three other databases, to the end of October 2019. We also searched international trials registries to identify unpublished or ongoing trials and handsearched selected journals, reference lists of included trials and grey literature. Selection criteria: We included randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and cross-over trials of psychological therapies with women aged 16 years and older who self-reported recent or lifetime experience of IPV. We included trials if women also experienced co-existing mental health diagnoses or substance abuse issues, or both. Psychological therapies included a wide range of interventions that targeted cognition, motivation and behaviour compared with usual care, no treatment, delayed or minimal interventions. We classified psychological therapies according to Cochrane Common Mental Disorders's psychological therapies list. Data collection and analysis: Two review authors extracted data and undertook 'Risk of Bias' assessment. Treatment effects were compared between experimental and comparator interventions at short-term (up to six months post-baseline), medium-term (six to under 12 months, primary outcome time point), and long-term follow-up (12 months and above). We used standardised mean difference (SMD) for continuous and odds ratio (OR) for dichotomous outcomes, and used random-effects meta-analysis, due to high heterogeneity across trials. Main results: We included 33 psychological trials involving 5517 women randomly assigned to experimental (2798 women, 51%) and comparator interventions (2719 women, 49%). Psychological therapies included 11 integrative therapies, nine humanistic therapies, six cognitive behavioural therapy, four third-wave cognitive behavioural therapies and three other psychologically-orientated interventions. There were no trials classified as psychodynamic therapies. Most trials were from high-income countries (19 in USA, three in Iran, two each in Australia and Greece, and one trial each in China, India, Kenya, Nigeria, Pakistan, Spain and UK), among women recruited from healthcare, community, shelter or refuge settings, or a combination of any or all of these. Psychological therapies were mostly delivered face-to-face (28 trials), but varied by length of treatment (two to 50 sessions) and staff delivering therapies (social workers, nurses, psychologists, community health workers, family doctors, researchers). The average sample size was 82 women (14 to 479), aged 37 years on average, and 66% were unemployed. Half of the women were married or living with a partner and just over half of the participants had experienced IPV in the last 12 months (17 trials), 6% in the past two years (two trials) and 42% during their lifetime (14 trials). Whilst 20 trials (61%) described reliable low-risk random-sampling strategies, only 12 trials (36%) described reliable procedures to conceal the allocation of participant status. While 19 trials measured women's depression, only four trials measured depression as a continuous outcome at medium-term follow-up. These showed a probable beneficial effect of psychological therapies in reducing depression (SMD -0.24, 95% CI -0.47 to -0.01; four trials, 600 women; moderate-certainty evidence). However, for self-efficacy, there may be no evidence of a difference between groups (SMD -0.12, 95% CI -0.33 to 0.09; one trial with medium-term follow-up data, 346 women; low-certainty evidence). Further, there may be no difference between the number of women who dropped out from the experimental or comparator intervention groups, an indicator of no harm (OR 1.04, 95% CI 0.75 to 1.44; five trials with medium-term follow-up data, 840 women; low-certainty evidence). Although no trials reported adverse events from psychological therapies or participation in the trial, only one trial measured harm outcomes using a validated scale. For secondary outcomes, trials measured anxiety only at short-term follow-up, showing that psychological therapies may reduce anxiety symptoms (SMD -0.96, 95% CI -1.29 to -0.63; four trials, 158 women; low-certainty evidence). However, within medium-term follow-up, low-certainty evidence revealed that there may be no evidence between groups for the outcomes safety planning (SMD 0.04, 95% CI -0.18 to 0.25; one trial, 337 women), post-traumatic stress disorder (SMD -0.24, 95% CI -0.54 to 0.06; four trials, 484 women) or re-exposure to any form of IPV (SMD 0.03, 95% CI -0.14 to 0.2; two trials, 547 women). Authors' conclusions: There is evidence that for women who experience IPV, psychological therapies probably reduce depression and may reduce anxiety. However, we are uncertain whether psychological therapies improve other outcomes (self-efficacy, post-traumatic stress disorder, re-exposure to IPV, safety planning) and there are limited data on harm. Thus, while psychological therapies probably improve emotional health, it is unclear if women's ongoing needs for safety, support and holistic healing from complex trauma are addressed by this approach. There is a need for more interventions focused on trauma approaches and more rigorous trials (with consistent outcomes at similar follow-up time points), as we were unable to synthesise much of the research.

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

Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis.

Background: Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents. Methods: We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841. Findings: From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (-0·78, 95% CrI -1·55 to -0·01) and psychodynamic therapy (-1·14, -2·20 to -0·08), but not more effective than fluoxetine alone (-0·22, -0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from -1·73 to -0·51); and only interpersonal therapy was more effective than all psychological controls (-1·37 to -0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as "low" to "very low" in terms of confidence of evidence according to Confidence In Network Meta-Analysis. Interpretation: Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. Funding: National Key Research and Development Program of China.

The lancet. Psychiatry · systematic review · 248 citationsread the source →

Prediction and prevention of schizophrenia: what has been achieved and where to go next?

Since the traditional clinical paradigm has been replaced by the modern molecular one, medicine set off into new directions. “Prediction”, “prevention” and “personalization” are the programmatic key words of this new approach. Like other medical disciplines, psychiatry has broadened its focus from diagnosis and treatment to the detection and estimation of the risk of disease development, the prediction of its onset and strategies to avoid its manifestation 1,2,3,4. Although treatment of schizophrenia has greatly advanced over the last decades, a significant number of patients continue to take an unfavorable chronic course 5,6. This makes schizophrenia the leading cause for permanent occupational disability among people under 40 years of age in Germany 7, and the 8th most common cause for disability adjusted life years (DALYs) lost among the 15 to 34-year olds worldwide 8, despite its low prevalence. Moreover, schizophrenia involves tremendous direct and indirect societal costs 9 and a huge burden on patients and their families 8,10. It is becoming increasingly clear that schizophrenia is a complex disorder with polygenic heredity and that its pathogenesis is greatly influenced by interactions between different genes and between genes and environment. Associations to variants of the genes for dysbindin and neuregulin-1, the genetic locus G72 and the DAOA (D-amino acid oxidase activator) gene have now been repeatedly confirmed. As with all other complex diseases, research is focusing now on characterizing the polygenetic predisposition and clarifying its influence on the development of the phenotype 11. Research methods range from molecular genetics via proteome research to cell biology, neurophysiology, brain structural and functional imaging and neuropsychology. With all these methods, several indicators for an increased risk of schizophrenia have been identified. However, the currently recognized neurobiological risk factors are not sufficiently predictive to allow the development and application of “selective” prevention measures targeting asymptomatic persons at risk. For neuro-psychological risk factors, this has just become evident in the large-scale attempt of the North American Prodrome Longitudinal Study (NAPLS) group to improve their multivariate model by integrating the examined neurocognitive variables 12. There are also established environmental risk factors for schizophrenia, such as pregnancy or birth complications, growing up in a large city, IQ low but normal and drug consumption. However, with odds ratios around 2, each of these factors appears to increase the lifetime risk of the disease only slightly 13. Thus, the currently known risk factors, either alone or taken together, cannot be used for prediction and prevention without knowledge of the complete predispositional basis and the gene-gene and gene-environment interactions, which are probably numerous. In view of this situation, it may be argued that the current efforts towards prediction and prevention are still premature and that further progress of etiological research is needed. However, a different perspective has emerged from the work of the centers for early recognition and prevention, established first in Melbourne, Australia and in Cologne, Germany in the mid 1990s, and later on in many other places around the world. This resulted from retrospective research of the early course of psychosis, in which the pathophysiologically active disturbances in brain development extend beyond early abnormalities in behavior into psychopathologically definable early risk and ultra high risk (UHR) symptoms, depending on the individual combination of stressors and resilience factors. First episode psychosis (FEP) research has shown that the outbreak of the disease is preceded in about 70% to nearly 100% of cases by an initial prodrome, which lasts for an average of five to six years. Even in highly developed health care systems, an average of one year thereafter elapses from the first manifestation of psychotic positive symptoms to the initiation of adequate treatment 14,15. The period over which the FEP remains untreated (duration of untreated psychosis, DUP) correlates with: delayed and incomplete remission of the symptoms; necessity of more protracted treatment and greater risk of relapse; lower compliance, greater burden on the family, and a higher level of “expressed emotion”; increased risk of depression and suicide; greater impact on the individual's employment or education; increased drug abuse and delinquent behavior; markedly increased costs of treatment 16. These correlations have recently been confirmed by a meta-analysis 17, with coefficients ranging from 0.285 to 0.434 (95% CI). This does not only provide strong arguments in favor of treating the FEP as early as possible, but has also led to a systematic effort to decrease the incidence of psychosis through indicated prevention. Two important studies concerning the early stage prior to the conversion to FEP have demonstrated that the earliest and most common symptoms, which generally dominate during the prodrome, are unspecific and cannot be distinguished from impairment in mood, drive, contact, and concentration of depressive episodes. These are the Age-Beginning-Course (ABC) study of schizophrenia, a retrospective study with optimized methods 14, and the Cologne Early Recognition (CER) Study, a long-term prospective study with an average follow-up period just below 10 years 18. These studies also found striking cognitive impairments in the form of self-experienced disturbances in thought, speech, and perception processes. This subgroup of so-called basic symptoms, which were found in more than a quarter of patients, had high specificity and a high positive predictive power, accompanied by only low rates of false positive predictions 19,20,21. Basic symptoms were first operationalized in the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Shorter versions of the scale for adults and for children and adolescents — the Schizophrenia Proneness Instrument, Adult version (SPI-A) and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY) — were later developed from dimensional analyses 22,23,24. While the BSABS only allows an assessment of the current state, the SPI-A and the SPI-CY also allow severity ratings according to the maximum frequency of occurrence within the past 3 months. In the CER study, 385 patients who were presumably in the prodromal phase of schizophrenia were followed up for an average of 9.6 (±7.6) years past baseline. Twenty percent of the initial criterion-positive cases (1 of 66 basic symptoms) who agreed to be followed up developed schizophrenia after 12 months, a further 17% after 24 months, a further 13% after 36 months, and finally a total of 70% after an average of 4.5 years. Thus, only 30% did not convert to schizophrenia. The overall presence/absence of at least one basic symptom correctly predicted presence/absence of a subsequent transition to schizophrenia in 78.1% of cases. From further analyses, two partially overlapping basic symptom criteria for defining at risk mental states (ARMS) for psychosis, primarily schizophrenia, were developed (Table 1). The first criterion, which consists of ten cognitive-perceptive basic symptoms and is abbreviated as COPER, was based on findings concerning the predictive accuracy of individual basic symptoms 18,25. The second was based on a methodological re-analysis of the same data set, in which a cluster of nine cognitive basic symptoms had repeatedly been selected as the most predictive. This cluster was called “cognitive disturbances” (COGDIS). In terms of general predictive accuracy, the two criteria slightly differed in the CER study, as COGDIS tended to be more conservative than COPER, i.e. to perform better in ruling in subsequent schizophrenia at the cost of performing worse in ruling it out. The transition rate throughout the average follow-up period of roughly 10 years was 65% for COPER and 79% for COGDIS, with the majority of transitions occurring within the first 3 years past baseline. In a second prospective study 26, conducted with the SPI-A and with a systematic follow-up of 24 months, 38% of the initially included 146 at-risk subjects developed a frank psychosis, mainly schizophrenia, within 12.3 (±10.4) months on average (1–48; median=9) according to COPER. Thus, the positive results of the CER study were confirmed. Again, COGDIS appeared to be more specific but less sensitive than COPER. As a consequence of these findings, predictive basic symptoms have been established as a set of criteria for risk assessment in international research on the early recognition of psychosis. In particular, the German Research Network on Schizophrenia used these symptoms, together with a combined criterion of functional deterioration and biological risk, in defining an “early at-risk of psychosis state” (ERPS), thereby suggesting a clinical risk staging model (Figure 1). Early and late initial prodromal state: a clinical staging approach The positive symptoms typical of schizophrenia — such as delusions, hallucinations or formal thought disorders — often first appear in an attenuated or transient form during the initial prodromal phase. These symptoms provide a valid prediction of conversion into FEP, particularly in the short term. Warning signs of this sort have been used as ultra-high risk (UHR) criteria 27,28. Notwithstanding their differences across studies, these criteria are generally composed of three alternative elements: attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), or a combination of one or more risk factors (always including genetic risk) and functional decline within a certain recent period. For the ascertainment of the UHR criteria, the Melbourne group gradually developed a specific instrument, the Comprehensive Assessment of At Risk Mental States (CAARMS) 29. Based on the Australian definition of the UHR criteria, the Structured Interview for Prodromal Syndromes (SIPS), the Scale for Prodromal Syndromes (SOPS) and, subsequently, the Criteria of Prodromal Syndromes (COPS) were developed 30,31. Different UHR-related approaches to an early detection of FEP, particularly schizophrenia, were developed by the Hillside Recognition and Prevention (RAP) program in New York 32 and the Basel Früherkennung von Psychosen (FEPSY) study 33. There have been at least 15 prediction studies using UHR criteria, some of which with large samples 34,35,36,37,38,39,40,41. The 12-month rates of transition into FEP published so far range between approximately 13% and 50%. A substantial variance is even observed with comparable observation periods in the same center 34,35. Yet, as the annual incidence for all forms of psychosis in the general population is only about 0.034% 42, even the lowest conversion rates still indicate a dramatic increase in the relative risk of illness, at least in the help-seeking samples of specialized centers. Table 2 depicts the predictive accuracy measures published so far, with the last five listed studies representing secondary predictor analyses of samples meeting at risk criteria. As a result, in the German Research Network on Schizophrenia, the UHR approach was combined with the basic symptom approach and applied in a slightly modified form for the definition of “late at-risk of psychosis state” (LRPS) (Figure 1). This clinical staging model, which suggests a syndromal sequence for the development of FEP progressing from unspecific prodromal symptoms to predictive basic symptoms, and then to APS, to BLIPS and to full-blown psychotic symptoms, was recently strongly supported 15. Universal or selective prevention measures target healthy population groups or clinically still healthy risk carriers, respectively 43. Indicated prevention, instead, targets individuals with basic symptoms and UHR symptoms. Even at the early stages when these individuals seek advice and help at the early recognition and prevention centers, they must be regarded as ill and in need of treatment. Furthermore, the impending deterioration of psychosocial performance in schizophrenia often already occurs in the initial prodromal phase, even prior to the conversion into FEP 14,15. These clinical and psychosocial impairments justify defining the interventions in EPRS and LPRS as indicated prevention, pursuing the following three objectives: a) improvement in the current burden of prodromal symptoms; b) avoidance or perhaps delay in the development of psychosocial handicap; c) prevention of or at least delay or attenuation of psychosis. Five international intervention studies have attempted to find out whether or to what extent these three objectives can be reached 44,45,46,47,48,49,50,51 (Table 3). The preventive measures used were either cognitive behavioral therapy (CBT), adapted to the requirements of the persons at risk, or atypical antipsychotics (risperidone, olanzapine, and amisulpride). These were randomized controlled studies, but there were problems with the blinding condition in the two CBT interventions. This and other methodological shortcomings currently limit conclusions and have encouraged the research groups working in this area to set up new, optimized intervention studies. For example, the protocol of the ongoing parallel group PREVENT study includes careful comparative analyses and superiority and inferiority tests of the psychological and pharmacological treatments 52. A staging of risk, thereby implying a temporal dimension, was considered for the first time in the two intervention studies of the German Research Network on Schizophrenia. One of these studies covered ERPS and only offered CBT as a preventive measure 49,50. The other study was designed for LRPS and used only preventive treatment with amisul-pride 51. When the symptom development in the initial prodromal state follows the sequence shown in Figure 1, it would be beneficial for scientific and especially ethical reasons to focus on psychological interventions in ERPS, which are well tolerated and highly accepted. As soon as the first attenuated or transient psychotic symptoms occur, it seems justifiable to apply well tolerated antipsychotics with few side effects. This differential prevention strategy is now pursued in all German early recognition centers and is also increasingly gaining support in other countries. Another pharmacological option is aripiprazole, tested in a pilot study in UHR states 53. Its possible preventive effects are currently being analyzed in the PREVENT study. Antidepressants were used in a naturalistic, non-randomized observational study of an adolescent sample employing only the APS criterion for inclusion, but, for methodological reasons, this study does not allow any conclusion about differential preventive effects of these medications 54. A critical evaluation of the achievements over the past 15 years through continuous efforts to enhance prediction and prevention of psychoses, particularly of schizophrenia, reveals quite impressive results. However, the results achieved thus far need to be evaluated in the light of the ambitious, initially mentioned objectives of modern predictive and preventive medicine. Once predictive basic symptoms and UHR symptoms have occurred, the underlying pathophysiological process might have already progressed. For such a complex disease with a long-term course and a pre-dispositional basis, this kind of risk identification and risk-oriented prevention may possibly come too late. A more substantial reduction in incidence could be reached with selective and universal prevention measures. Therefore, symptom-based prediction and prevention need to be further developed into the direction of selective prevention for symptom-free risk carriers. In the future, it is necessary to strive for: a) an improvement of risk enrichment with the inclusion of biological risk factors; b) a stronger individualization of the risk estimation by stratification; c) the inclusion of sub-psychotic mental states, as cross-sectionally by current at risk criteria, in the the application of prevention strategies more with the of the the initial prodromal phase for as as then most of the follow-up periods shown in Table 2 are not to the transition A significant number of later may be as and, the predictive of the risk may be 12. Therefore, the first and most important is to out new, optimized large-scale studies with follow-up periods the of the initial prodromal phase, as in the CER study 18. The risk enrichment can also be advanced through the inclusion of following the of recent research on the prediction of through the cognitive impairment This condition a risk for with a conversion rate comparable to the risk for the patients certain imaging and the predictive risk enrichment may be possible for using brain but also impairments of and which are with the psychosis risk and are more and in cases with a later transition to schizophrenia and other new large-scale studies with sufficiently observation periods could whether the risk enrichment can be achieved by of such The of this strategy is on the progress of research on biological and environmental risk factors and their interactions, as is currently attempted in the Network of schizophrenia study In other medical disciplines, such as or a risk which does not in a of is using for multivariate clinical staging by risk In the of study, this approach was into psychosis prediction research for the first time A clinical model was developed based on a including six variables positive disturbances Assessment of in the past and years of Based on the individual a multivariate for further the risk of transition to psychosis into risk was each a increased relative risk to the general with each This model was argued to improve the prediction of psychosis by a of the individual risk in terms of and a more risk estimation or clinical staging of risk, in studies, could the development of risk adapted inclusion criteria for randomized preventive In the first application of this approach in the only clinical and variables were It remains to be whether a model including or environmental variables would increase the predictive accuracy even In studies have to whether such can also be applied to the prediction of psychosis within different time The currently ongoing of the has a about the inclusion of a risk for psychosis in to prevention initially argued this and to the that the application of as criteria could that the high rate of predictions in would be to increase up to in general This is and prior to whether to the in the of the The on the predictive of at risk criteria, thereby the persons meeting at risk criteria already from mental and functional for which they seek Moreover, they psychological and cognitive with and functional the majority of help-seeking at risk persons general criteria for mental disorder a clinically significant behavioral or psychological with disability and have to be considered as i.e. as people with the need and to be these in there are reasons for the inclusion of a clinical in the as by current at risk criteria, not as a prodromal risk for first psychosis, but as an to medical the of such an diagnosis would have the of the by the current mental state to a and Although an increased risk of psychosis would continue to be a of such a the psychological and medical focus would be from an to and At this current state of the criteria would be the for the inclusion of this A for the and of a new of international and studies would be with this inclusion in and later on also in A new prevention approach is by the of and studies a of the onset of psychosis the with the first results are for and The transition rate was lower in an group of UHR adolescents than in a group and this was at a an was evaluated in 10 patients in an pilot and a significant improvement in different was In an study, time was in an UHR group with as with a group suggesting a of This was the first study imaging data on effects in individuals at risk. The preventive of is currently in the process of in the Australian Prodrome study With the of schizophrenia is the first mental disorder to which the prediction and prevention program of modern medicine has been The results are and justify the that in the years to come it be possible to provide preventive strategies to the individual risk of of each In to a reduction in risk assessment has to be by neurobiological and psychosocial risk factors, and indicated prevention has to be further developed towards selective prevention. This a new of large sample studies for prediction as well as prevention, with observation In these studies, of risk selected to predictive must be psychological and pharmacological interventions need to be on a long-term basis, more prevention strategies have to be In to be to and such studies, it would be to mental states, as by the currently used risk symptoms, in the of the

World Psychiatry · 127 citationsread the source →

Acute Finnish sauna heat exposure induces stronger immune cell than cytokine responses.

Regular exposure to Finnish sauna bathing (FSB) has been associated with reduced morbidity and mortality. This study aimed to examine the acute effects of FSB on immune cell mobilization, circulating cytokines, and their associations with changes in body temperature. A total of 51 adults - 27 women (mean age 50 ± 9 years, body mass index (BMI) 27 ± 5 kg/m2) and 24 men (mean age 50 ± 10 years, BMI 27 ± 3 kg/m2) - were exposed to a 30-minute session of acute FSB at a temperature of + 73°C. Venous blood samples were collected at baseline, immediately after and 30 minutes after the FSB and analyzed for immune cells and 37 cytokines. Subjects were allowed to drink water throughout. FSB increased body temperature from 36.4 ± 0.5°C to 38.4 ± 0.7°C, without altering plasma volume. Total white blood cell (WBC) count rose significantly and remained slightly elevated 30 minutes post-sauna in women. Neutrophil and lymphocyte counts increased immediately after the FSB but returned to baseline after 30 minutes, whereas MXD cells (monocytes, eosinophils, basophils) remained elevated. The levels of only two cytokines changed significantly. Although only a few correlations were observed between changes in immune cells and cytokines, 18 significant associations were identified between changes in body temperature and circulating cytokines - particularly immediately post-sauna - but not with WBC changes. Thus, a 30-minute session of acute FSB induces immune cell mobilization. The observed associations between changes in body temperature and circulating cytokines suggest that sauna-induced heat stress, along with immune activation, may partly mediate the health benefits of FSB.

Temperature (Austin, Tex.)read the source →

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis.

Background: Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects. Objectives: • To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification). Selection criteria: Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded. Data collection and analysis: A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo. Main results: We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353. Authors' conclusions: We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).

The Cochrane database of systematic reviews · systematic review · 127 citationsread the source →

Mobile Apps for Bipolar Disorder: A Systematic Review of Features and Content Quality.

Background: With continued increases in smartphone ownership, researchers and clinicians are investigating the use of this technology to enhance the management of chronic illnesses such as bipolar disorder (BD). Smartphones can be used to deliver interventions and psychoeducation, supplement treatment, and enhance therapeutic reach in BD, as apps are cost-effective, accessible, anonymous, and convenient. While the evidence-based development of BD apps is in its infancy, there has been an explosion of publicly available apps. However, the opportunity for mHealth to assist in the self-management of BD is only feasible if apps are of appropriate quality. Objective: Our aim was to identify the types of apps currently available for BD in the Google Play and iOS stores and to assess their features and the quality of their content. Methods: A systematic review framework was applied to the search, screening, and assessment of apps. We searched the Australian Google Play and iOS stores for English-language apps developed for people with BD. The comprehensiveness and quality of information was assessed against core psychoeducation principles and current BD treatment guidelines. Management tools were evaluated with reference to the best-practice resources for the specific area. General app features, and privacy and security were also assessed. Results: Of the 571 apps identified, 82 were included in the review. Of these, 32 apps provided information and the remaining 50 were management tools including screening and assessment (n=10), symptom monitoring (n=35), community support (n=4), and treatment (n=1). Not even a quarter of apps (18/82, 22%) addressed privacy and security by providing a privacy policy. Overall, apps providing information covered a third (4/11, 36%) of the core psychoeducation principles and even fewer (2/13, 15%) best-practice guidelines. Only a third (10/32, 31%) cited their information source. Neither comprehensiveness of psychoeducation information (r=-.11, P=.80) nor adherence to best-practice guidelines (r=-.02, P=.96) were significantly correlated with average user ratings. Symptom monitoring apps generally failed to monitor critical information such as medication (20/35, 57%) and sleep (18/35, 51%), and the majority of self-assessment apps did not use validated screening measures (6/10, 60%). Conclusions: In general, the content of currently available apps for BD is not in line with practice guidelines or established self-management principles. Apps also fail to provide important information to help users assess their quality, with most lacking source citation and a privacy policy. Therefore, both consumers and clinicians should exercise caution with app selection. While mHealth offers great opportunities for the development of quality evidence-based mobile interventions, new frameworks for mobile mental health research are needed to ensure the timely availability of evidence-based apps to the public.

Journal of medical Internet research · systematic review · 249 citationsread the source →

Humor as a character strength among the elderly: empirical findings on age-related changes and its contribution to satisfaction with life.

Background: Positive psychology studies what is best in people. In their classification of strengths and virtues, Peterson and Seligman [11] assign humor to the virtue of transcendence. Thus far, there is no specific study that deals with age-related changes in humor (as a strength of character) across a lifespan and its relation to well-being in the elderly. Participants and methods: A total of n=42,964 participants completed an online questionnaire on humor as a strength of character. Participants also completed the Satisfaction with Life Scale and the Orientations to Happiness Scale. Results: In a cross-sectional design, the scores for humor decreased until the age of 50. Men between 51 and 62 years had higher scores; there was a trend for women older than 70 to score higher (but this was not statistically significant). Humor was robustly positively correlated with life satisfaction, as well with a pleasurable and an engaged life, but was lowest with a meaningful life. The oldest participants had the lowest (yet still meaningful) correlation coefficients (with the exception of a meaningful life). Conclusion: The study contributes to the understanding of humor across the lifespan and underlines the importance of studies among the elderly within a framework of positive psychology.

Zeitschrift fur Gerontologie und Geriatrie · 15 citationsread the source →

Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response.

Vagus nerve stimulation (VNS) was approved by the US FDA in 1997 as an adjunctive treatment for medically refractory epilepsy. It is considered for use in patients who are poor candidates for resection or those in whom resection has failed. However, disagreement regarding the utility of VNS in epilepsy continues because of the variability in benefit reported across clinical studies. Moreover, although VNS was approved only for adults and adolescents with partial epilepsy, its efficacy in children and in patients with generalized epilepsy remains unclear. The authors performed the first meta-analysis of VNS efficacy in epilepsy, identifying 74 clinical studies with 3321 patients suffering from intractable epilepsy. These studies included 3 blinded, randomized controlled trials (Class I evidence); 2 nonblinded, randomized controlled trials (Class II evidence); 10 prospective studies (Class III evidence); and numerous retrospective studies. After VNS, seizure frequency was reduced by an average of 45%, with a 36% reduction in seizures at 3-12 months after surgery and a 51% reduction after > 1 year of therapy. At the last follow-up, seizures were reduced by 50% or more in approximately 50% of the patients, and VNS predicted a ≥ 50% reduction in seizures with a main effects OR of 1.83 (95% CI 1.80-1.86). Patients with generalized epilepsy and children benefited significantly from VNS despite their exclusion from initial approval of the device. Furthermore, posttraumatic epilepsy and tuberous sclerosis were positive predictors of a favorable outcome. In conclusion, VNS is an effective and relatively safe adjunctive therapy in patients with medically refractory epilepsy not amenable to resection. However, it is important to recognize that complete seizure freedom is rarely achieved using VNS and that a quarter of patients do not receive any benefit from therapy.

Journal of neurosurgery · meta-analysis · 333 citationsread the source →

The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial.

Background: Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings. Methods: In this randomised controlled trial, we recruited participants aged 18-65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997. Findings: Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference -7·57 [95% CI -10·27 to -4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34-1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference -2·73 [-4·39 to -1·06]; p=0·001), days out of work (-2·29 [-3·84 to -0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29-0·96]; p=0·04), behavioural activation (2·17 [1·34-3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45-0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $9333 (95% CI 3862-28 169; 2015 international dollars), with an 87% chance of being cost-effective in the study setting. Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group; p=1·00). Interpretation: HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India. HAP was readily accepted by this previously untreated population and was cost-effective in this setting. HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide. Funding: Wellcome Trust.

Lancet (London, England) · randomised controlled trial · 295 citationsread the source →

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

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

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

Acceptance and Commitment Therapy for Symptom Interference in Advanced Lung Cancer and Caregiver Distress: A Pilot Randomized Trial.

Context: Advanced lung cancer patients typically have a poor prognosis and many symptoms that interfere with functioning, contributing to high rates of emotional distress in both patients and family caregivers. There remains a need for evidence-based interventions to improve functional outcomes and distress in this population. Objectives: This pilot trial examined the feasibility and preliminary efficacy of telephone-based Acceptance and Commitment Therapy (ACT) for symptomatic, advanced lung cancer patients and their distressed family caregivers. Primary outcomes were patient symptom interference with functioning and patient and caregiver distress. Methods: Symptomatic, advanced lung cancer patients and distressed caregivers (n = 50 dyads) were randomly assigned to six sessions of ACT or an education/support condition. Patients completed measures of symptom interference and measures assessing the severity of fatigue, pain, sleep disturbance, and breathlessness. Patients and caregivers completed measures of distress and illness acceptance and struggle. Results: The eligibility screening rate (51%) and retention rate (76% at six weeks postintervention) demonstrated feasibility. No group differences were found with respect to patient and caregiver outcomes. Both groups showed a small, significant decrease in struggle with the illness over the study period, but did not show meaningful change in other outcomes. Conclusion: Findings suggest that telephone-based ACT is feasible for many advanced lung cancer patients and caregivers, but may not substantially reduce symptom interference and distress. Low baseline levels of certain symptoms may have contributed to null findings. Next steps include applying ACT to specific, clinically meaningful symptom interference and varying intervention dose and modality.

Journal of pain and symptom management · randomised controlled trial · 69 citationsread the source →

Underlying mechanisms and efficacy of a suicide-focused psychological intervention for psychosis, the Cognitive Approaches to Combatting Suicidality (CARMS): a multicentre, assessor-masked, randomised controlled trial in the UK.

Background: There is a need for theoretically grounded and testable suicide-focused psychological therapies, especially in people with severe mental health problems, specifically non-affective psychosis. We aimed to test both the underlying mechanisms and efficacy of a suicide-focused therapy, cognitive behavioural suicide prevention for psychosis (CBSPp). Methods: We did a multicentre, assessor-masked, randomised controlled trial conducted at four UK National Health Service (NHS) sites. Participants were eligible for enrolment if they were 18 years or older; met ICD-10 criteria for non-affective psychosis (F20-F29); had self-reported suicidal experiences in the 3 months before recruitment; were under the care of an NHS mental health services team; were not receiving a psychological therapy as part of a similar trial; had sufficient competency in the English language not to need an interpreter to participate; and were able to give informed consent. After screening for eligibility and completion of baseline assessments, participants were randomly allocated in a 1:1 ratio to either the treatment as usual group (control) or CBSPp therapy plus standard treatment group (treatment), with stratification by use of antidepressant medication and NHS site. Randomisation took place using an online Sealed Envelope randomisation procedure conducted and overseen by the Manchester Academic Health Sciences Centre Clinical Trials Unit (MCTU). This system was accessed only by specially allocated staff (eg, the CARMS Trial Manager or the MCTU Trial manager). When the system randomly allocated a participant, an unmasked email confirmation was sent to the unmasked coprincipal investigator and the CARMS Trial Manager (also unmasked). Assessors, the trial statistician, and one coprincipal investigator were masked to allocation group. Participants were informed of their randomised allocation group by an unmasked CARMS staff member. Experts-by-experience were involved in all stages of the research. For those in the treatment group, approximately 24 one-to-one therapy sessions were offered, usually weekly, for around 50 min per session. Assessments were conducted at baseline, month 6, and month 12. The primary outcome was suicide ideation severity measured by the 25-item Adult Suicide Ideation Questionnaire (ASIQ), assessed at month 6 relative to baseline. Outcome analyses used mixed models in the intention-to-treat population. Planned mediation indirect linear regression models examined appraisals of poor social support, emotional difficulties, interpersonal problem-solving difficulties, defeat, entrapment, and hopelessness as mediators at 6 months with allocation condition (treatment vs control) as the predictor variable and suicidal ideation severity (ASIQ) at 6 months as the outcome variable, whilst controlling for baseline levels of the mediator and outcome variables. The trial was registered before recruitment at ClinicalTrials.gov (NCT03114917) and ISRCTN (ISRCTN17776666) and is complete. Findings: We recruited participants from four NHS sites from June 21, 2017, to Nov 25, 2020, with the final 12-month assessment completed on Jan 10, 2022. 479 participants were screened for eligibility, and of these 329 (69%) provided consent and were enrolled. After 69 participants were lost to follow-up, 292 participants were randomly allocated to the treatment and control groups (149 [51%] and 143 [49%], respectively). At baseline, 161 (55%) participants were male and 130 (45%) were female; one participant (<1%) in the treatment group was missing gender data. Mean age was 35·1 years (SD 13·2; range 18-69), and 247 (85%) were White or Caucasian. Severity of suicidal ideation was not statistically different between the treatment (n=136) and the control groups (n=116) at 6 months (p=0·07; Cohen's d -0·20 [95% CI -0·42 to 0·02]). A significant indirect mediation effect (-2·85, -7·00 to -0·23) showed that therapy strengthened social support appraisals which, in turn, reduced suicidal ideation severity at 6 months more in the treatment group than in the control group. Suicide attempts were the most frequent severe adverse event (132 attempts in 26 participants in the treatment group vs 91 attempts in 30 participants in the control group). There were four deaths in the CARMS study, none of which were by suicide or considered related to treatment. Interpretation: CBSPp had no effect on suicidal ideation at 6 months, but it did have a significant indirect effect via improving appraisals of social support. It is important to explore how suicide-focused therapies can be developed and implemented in mental health services so that they maximally enhance appraisals of social support and social connection in ways that endure. Funding: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health and Care Research partnership (reference number: 13/161/25).

The lancet. Psychiatry · randomised controlled trial · 4 citationsread the source →

Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial.

Background: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. Methods: In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. Results: A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93-3.82 m/s]; aortic valve calcium score, 1152 AU [655-2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18-0.33 µg/L] to 0.11 µg/L [0.08-0.17 µg/L]) and alendronic acid (0.20 [0.14-0.28 µg/L] to 0.09 µg/L [0.08-0.13 µg/L]) but was unchanged with placebo (0.23 [0.17-0.30 µg/L] to 0.26 µg/L [0.16-0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198-804 AU] versus 354 AU [76-675 AU]; P=0.41) or alendronic acid and placebo (326 [138-813 AU] versus 354 AU [76-675 AU]; P=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake. Conclusions: Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Circulation · randomised controlled trial · 126 citationsread the source →

A Multicomponent Exercise Intervention that Reverses Frailty and Improves Cognition, Emotion, and Social Networking in the Community-Dwelling Frail Elderly: A Randomized Clinical Trial.

Background: Frailty can be an important clinical target to reduce rates of disability. Objective: To ascertain if a supervised-facility multicomponent exercise program (MEP) when performed by frail older persons can reverse frailty and improve functionality; cognitive, emotional, and social networking; as well as biological biomarkers of frailty, when compared with a controlled population that received no training. Design: This is an interventional, controlled, simple randomized study. Researchers responsible for data gathering were blinded for this study. Setting: Participants from 2 primary rural care centers (Sollana and Carcaixent) of the same health department in Spain were enrolled in the study between December 2013 and September 2014. Patients: We randomized a volunteer sample of 100 men and women who were sedentary, with a gait speed lower than 0.8 meters per second and frail (met at least 3 of the frailty phenotype criteria). Interventions: Participants were randomized to a supervised-facility MEP (n = 51, age = 79.5, SD 3.9) that included proprioception, aerobic, strength, and stretching exercises for 65 minutes, 5 days per week, 24 weeks, or to a control group (n = 49, age = 80.3, SD 3.7). The intervention was performed by 8 experienced physiotherapists or nurses. Protein-calorie and vitamin D supplementation were controlled in both groups. Results: Our MEP reverses frailty (number needed to treat to recover robustness in subjects with attendance to ≥50% of the training sessions was 3.2) and improves functional measurements: Barthel (trained group 91.6 SD 8.0 vs 82.0 SD 11.0 control group), Lawton and Brody (trained group 6.9 SD 0.9 vs 5.7 SD 2.0 control group), Tinetti (trained group 24.5 SD 4.4 vs 21.7 SD 4.5 control group), Short Physical Performance Battery (trained group 9.5 SD 1.8 vs 7.1 SD 2.8 control group), and physical performance test (trained group 23.5 SD 5.9 vs 16.5 SD 5.1 control group) as well as cognitive, emotional, and social networking determinations: Mini-Mental State Examination (trained group 28.9 SD 3.9 vs 25.9 SD 7.3 control group), geriatric depression scale from Yesavage (trained group 2.3 SD 2.2 vs 3.2 SD 2.0 control group), EuroQol quality-of-life scale (trained group 8.2 SD 1.6 vs 7.6 SD 1.3 control group), and Duke social support (trained group 48.5 SD 9.3 vs 41.2 SD 8.5 control group). This program is unique in that it leads to a decrease in the number of visits to primary care physician (trained group 1.3 SD 1.4 vs 2.4 SD 2.9 control group) and to a significant improvement in frailty biomarkers. Conclusions: We have designed a multicomponent exercise intervention that reverses frailty and improves cognition, emotional, and social networking in a controlled population of community-dwelling frail older adults. Trial registration: ClinicalTrials.gov. Identifier: NCT02331459.

Journal of the American Medical Directors Association · randomised controlled trial · 400 citationsread the source →

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

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

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

Fall rates in hospital rehabilitation units after individualised patient and staff education programmes: a pragmatic, stepped-wedge, cluster-randomised controlled trial.

Background: Falls are the most frequent adverse events that are reported in hospitals. We examined the effectiveness of individualised falls-prevention education for patients, supported by training and feedback for staff, delivered as a ward-level programme. Methods: Eight rehabilitation units in general hospitals in Australia participated in this stepped-wedge, cluster-randomised study, undertaken during a 50 week period. Units were randomly assigned to intervention or control groups by use of computer-generated, random allocation sequences. We included patients admitted to the unit during the study with a Mini-Mental State Examination (MMSE) score of more than 23/30 to receive individualised education that was based on principles of changes in health behaviour from a trained health professional, in addition to usual care. We provided information about patients' goals, feedback about the ward environment, and perceived barriers to engagement in falls-prevention strategies to staff who were trained to support the uptake of strategies by patients. The coprimary outcome measures were patient rate of falls per 1000 patient-days and the proportion of patients who were fallers. All analyses were by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials registry, number ACTRN12612000877886). Findings: Between Jan 13, and Dec 27, 2013, 3606 patients were admitted to the eight units (n=1983 control period; n=1623 intervention period). There were fewer falls (n=196, 7·80/1000 patient-days vs n=380, 13·78/1000 patient-days, adjusted rate ratio 0·60 [robust 95% CI 0·42-0·94], p=0·003), injurious falls (n=66, 2·63/1000 patient-days vs 131, 4·75/1000 patient-days, 0·65 [robust 95% CI 0·42-0·88], p=0·006), and fallers (n=136 [8·38%] vs n=248 [12·51%] adjusted odds ratio 0·55 [robust 95% CI 0·38 to 0·81], p=0·003) in the intervention compared with the control group. There was no significant difference in length of stay (intervention median 11 days [IQR 7-19], control 10 days [6-18]). Interpretation: Individualised patient education programmes combined with training and feedback to staff added to usual care reduces the rates of falls and injurious falls in older patients in rehabilitation hospital-units. Funding: State Health Research Advisory Council, Department of Health, Government of Western Australia.

Lancet (London, England) · randomised controlled trial · 143 citationsread the source →

Quality of life in long-term cervical cancer survivors.

Objectives: To describe the quality of life (QOL) and long-term psychosocial sequelae of women of childbearing age diagnosed with cervical cancer 5-10 years earlier. Methods: Utilizing a cross-sectional descriptive design, 51 cervical cancer survivors and 50 age-matched controls completed a comprehensive QOL interview. Results: Participants were predominantly married, non-Hispanic White, with a mean age at diagnosis of 37 years and a mean age at interview of 45 years. This disease-free sample enjoys a good QOL, with physical, social, and emotional functioning comparable to or better than comparative norms. However, certain psychological survivorship sequelae and reproductive concerns persist. Participants reporting good QOL were less likely to report ongoing coping efforts related to having had this illness and were more likely to report greater social support, greater sexual pleasure, and less cervical cancer-specific distress. In a multiple-regression model, cancer-specific distress, spiritual well-being, maladaptive coping, and reproductive concerns accounted for 72% of the variance in QOL scores. Fifty-nine percent of respondents expressed that they would likely participate in a counseling program today to discuss psychosocial issues raised by having had cervical cancer, and 69% stated that they would have attended a support group program during the initial treatment if it had been offered. Conclusions: This information provides insight into the complex survivorship relationships between QOL and sequelae of cervical cancer for women diagnosed during childbearing years. Therefore, it is important for health care professionals to recognize that aspects of cancer survivorship continue to require attention and possible follow-up care.

Gynecologic oncology · 166 citationsread the source →

A preliminary study of luteal phase versus symptom-onset dosing with escitalopram for premenstrual dysphoric disorder.

Objective: This preliminary study compared the efficacy and tolerability of escitalopram administered at symptom onset or throughout the luteal phase in premenstrual dysphoric disorder (PMDD). Method: Twenty-seven women meeting DSM-IV criteria for PMDD were randomly assigned in a double-blind manner to luteal phase (N = 13) or symptom-onset (N = 14) dosing of escitalopram (10-20 mg/day) for 3 consecutive menstrual cycles. Participants were enrolled from November 2002 to July 2003, and data collection was completed in December 2003. Symptoms were assessed using the 17-item Penn Daily Symptom Report (DSR), the Clinical Global Impressions-Improvement scale, the Hamilton Rating Scale for Depression, and the Sheehan Disability Scale. Scores were compared using repeated measures analysis of covariance and t statistics. Results: Luteal phase and symptom-onset groups received escitalopram for a mean of 13.5 and 6.0 days, respectively (mean +/- SD dose = 15.2 +/- 5.1 mg/day at the third treatment cycle). Total premenstrual DSR scores significantly improved from baseline (p = .003), with a 57% decrease in the luteal phase group and a 51% decrease in the symptom-onset group. Clinical improvement (DSR score decrease > or = 50% from baseline) was reported by 11 of 13 patients in the luteal phase group and 9 of 14 patients in the symptom-onset group. Symptom severity differentiated the response in the symptom-onset group, with those having more severe symptoms less likely to respond. Symptom severity did not differentiate treatment response to luteal phase dosing. Escitalopram was well tolerated. Adverse events were mild and transient, with only 2 patients discontinuing due to adverse events related to the medication. Conclusion: Premenstrual dysphoric disorder improved significantly with either luteal phase or symptom-onset dosing of escitalopram. Women with more severe PMDD may respond better to luteal phase dosing than symptom-onset dosing.

The Journal of clinical psychiatry · randomised controlled trial · 38 citationsread the source →

Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis.

Background: Cancer survival has improved in the past 20 years, affecting the long-term risk of mood disorders. We assessed whether depression and anxiety are more common in long-term survivors of cancer compared with their spouses and with healthy controls. Methods: We systematically searched Medline, PsycINFO, Embase, Science Direct, Ingenta Select, Ovid, and Wiley Interscience for reports about the prevalence of mood disorders in patients diagnosed with cancer at least 2 years previously. We also searched the records of the International Psycho-oncology Society and for reports that cited relevant references. Three investigators independently extracted primary data. We did a random-effects meta-analysis of the prevalences of depression and anxiety in cancer patients compared with spouses and healthy controls. Findings: Our search returned 144 results, 43 were included in the main analysis: for comparisons with healthy controls, 16 assessed depression and ten assessed anxiety; of the comparisons with spouses, 12 assessed depression and five assessed anxiety. The prevalence of depression was 11·6% (95% CI 7·7-16·2) in the pooled sample of 51 381 cancer survivors and 10·2% (8·0-12·6) in 217 630 healthy controls (pooled relative risk [RR] 1·11, 95% CI 0·96-1·27; p=0·17). The prevalence of anxiety was 17·9% (95% CI 12·8-23·6) in 48 964 cancer survivors and 13·9% (9·8-18·5) in 226 467 healthy controls (RR 1·27, 95% CI 1·08-1·50; p=0·0039). Neither the prevalence of depression (26·7% vs 26·3%; RR 1·01, 95% CI 0·86-1·20; p=0·88) nor the prevalence of anxiety (28·0% vs 40·1%; RR 0·71, 95% CI 0·44-1·14; p=0·16) differed significantly between cancer patients and their spouses. Interpretation: Our findings suggest that anxiety, rather than depression, is most likely to be a problem in long-term cancer survivors and spouses compared with healthy controls. Efforts should be made to improve recognition and treatment of anxiety in long-term cancer survivors and their spouses. Funding: None.

The Lancet. Oncology · meta-analysis · 536 citationsread the source →

Stepped care vs. matched care for mood and anxiety disorders: a randomized trial in routine practice.

Objective: The effectiveness of two versions of stepped care [with either brief therapy (BT) or cognitive behavioural therapy (CBT) as a first step] is studied in comparison with the traditional matched care approach (CAU) for patients with mood and anxiety disorders. Method: A randomized trial was performed in routine mental health care in 12 settings, including 702 patients. Patients were interviewed once in 3 months for 18-24 months (response rate 69%). Results: Overall, patients' health improved significantly over time: 51% had achieved recovery from the DSM-IV disorder(s) after 1 year and 66% at the end of the study. Respectively, 50% and 60% had 'normal' SCL90 and SF36 scores. Cognitive behavioural therapy and BT patients achieved recovery more often than CAU patients (ORs between 1.26 and 1.48), although these results were not statistically significant. Conclusion: Stepped care, with BT or CBT as a first step, is at least as effective as matched care.

Acta psychiatrica Scandinavica · randomised controlled trial · 39 citationsread the source →

Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial.

Background: In current international guidelines the recommendation for intra-aortic balloon pump (IABP) use has been downgraded in cardiogenic shock complicating acute myocardial infarction on the basis of registry data. In the largest randomised trial (IABP-SHOCK II), IABP support did not reduce 30 day mortality compared with control. However, previous trials in cardiogenic shock showed a mortality benefit only at extended follow-up. The present analysis therefore reports 6 and 12 month results. Methods: The IABP-SHOCK II trial was a randomised, open-label, multicentre trial. Patients with cardiogenic shock complicating acute myocardial infarction who were undergoing early revascularisation and optimum medical therapy were randomly assigned (1:1) to IABP versus control via a central web-based system. The primary efficacy endpoint was 30 day all-cause mortality, but 6 and 12 month follow-up was done in addition to quality-of-life assessment for all survivors with the Euroqol-5D questionnaire. A masked central committee adjudicated clinical outcomes. Patients and investigators were not masked to treatment allocation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00491036. Findings: Between June 16, 2009, and March 3, 2012, 600 patients were assigned to IABP (n=301) or control (n=299). Of 595 patients completing 12 month follow-up, 155 (52%) of 299 patients in the IABP group and 152 (51%) of 296 patients in the control group had died (relative risk [RR] 1·01, 95% CI 0·86-1·18, p=0·91). There were no significant differences in reinfarction (RR 2·60, 95% CI 0·95-7·10, p=0·05), recurrent revascularisation (0·91, 0·58-1·41, p=0·77), or stroke (1·50, 0·25-8·84, p=1·00). For survivors, quality-of-life measures including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression did not differ significantly between study groups. Interpretation: In patients undergoing early revascularisation for myocardial infarction complicated by cardiogenic shock, IABP did not reduce 12 month all-cause mortality. Funding: German Research Foundation; German Heart Research Foundation; German Cardiac Society; Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte; University of Leipzig--Heart Centre; Maquet Cardiopulmonary; Teleflex Medical.

Lancet (London, England) · randomised controlled trial · 641 citationsread the source →

Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial.

Purpose: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. Methods: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. Results: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. Conclusions: Training in meditation or exercise may be effective in reducing ARI illness burden.

Annals of family medicine · randomised controlled trial · 91 citationsread the source →

Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy.

Four weeks after bilateral nerve-sparing radical retropubic prostatectomy, men with normal erectile function before surgery were randomized to double-blind sildenafil (50 or 100 mg) or placebo nightly for 36 weeks, followed by an 8-week drug-free period before assessment of erectile function. Enrollment was prematurely ceased and only 76 men completed because, assuming a placebo response rate similar to the published literature (for example, 34% in meta-analysis), the 25% response at blinded interim review suggested a lack of treatment effect. On the contrary, spontaneous erectile function (a combined score of >or=8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to 'Were erections good enough for satisfactory sexual activity?') occurred in only 4% of the placebo group (n=1 of 25) versus 27% (n=14 of 51, P=0.0156, Fisher's exact test) of the sildenafil group. Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections.

International journal of impotence research · randomised controlled trial · 204 citationsread the source →

Recreational drug use, polydrug use, and sexual behaviour in HIV-diagnosed men who have sex with men in the UK: results from the cross-sectional ASTRA study.

Background: Recreational drug use in men who have sex with men (MSM) is of concern because it might be linked to the transmission of HIV and other sexually transmitted infections. Evidence about drug use in HIV-diagnosed MSM in the UK is limited by representativeness of the study populations. We describe patterns of drug use and associations with sexual behaviours in HIV-diagnosed MSM in the UK. Methods: We used data from the cross-sectional ASTRA study, which recruited participants aged 18 years or older with HIV from eight HIV outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012. We examined data for MSM, assessing the prevalence of recreational drug use and polydrug use in the previous 3 months and associations with sociodemographic and HIV-related factors. We examined the association of polydrug use with measures of condomless sex in the previous 3 months and with other sexual behaviours. Findings: Our analysis included data for 2248 MSM: 2136 (95%) were gay, 1973 (89%) were white, 1904 (85%) were on antiretroviral treatment (ART), and 1682 (76%) had a viral load of 50 copies per mL or lower. 1138 (51%) used recreational drugs in the previous 3 months; 608 (27%) used nitrites, 477 (21%) used cannabis, 460 (21%) used erectile dysfunction drugs, 453 (20%) used cocaine, 280 (13%) used ketamine, 258 (12%) used 3,4-methylenedioxy-N-methylamphetamine (MDMA), 221 (10%) used gamma-hydroxybutyrate or gamma-butyrolactone, 175 (8%) used methamphetamine, and 162 (7%) used mephedrone. In the 1138 individuals who used drugs, 529 (47%) used three or more drugs and 241 (21%) used five or more. Prevalence of injection drug use was 3% (n = 68). Drug use was independently associated with younger age (p < 0·0001), not being religious (p = 0·001), having an HIV-positive stable partner (p = 0·0008), HIV-serostatus disclosure (p = 0·009), smoking (p < 0·0001), evidence of harmful alcohol drinking (p = 0·0001), and ART non-adherence (p < 0·0001). Increasing polydrug use was associated with increasing prevalence of condomless sex (prevalence range from no drug use to use of five or more drugs was 24% to 78%), condomless sex with HIV-seroconcordant partners (17% to 69%), condomless sex with HIV-serodiscordant partners (10% to 25%), and higher-HIV-risk condomless sex after taking viral load into account (4% to 16%; p ≤ 0·005 for all). Associations were similar after adjustment for sociodemographic and HIV-related factors. Methamphetamine was more strongly associated with higher-HIV-risk condomless sex than were other commonly used drugs. Interpretation: Polydrug use is prevalent in HIV-diagnosed MSM and is strongly associated with condomless sex. Specialist support services for MSM with HIV who use recreational drugs might be beneficial in the reduction of harm and prevention of ongoing transmission of HIV and other sexually transmitted infections. Funding: National Institute for Health Research.

The lancet. HIV · 226 citationsread the source →

Health-related quality of life and associated factors in people with HIV: an Irish cohort study.

Background: Considering the chronic and debilitating nature of HIV infection, health-related quality of life (HRQoL) is an important patient-reported clinical outcome to better understand the effects of this infection and its treatment on patients' lives. The purpose of this study was to assess the HRQoL and its association with sociodemographic, behavioural, clinical, nutrition-related factors and social support in an Irish HIV cohort. Methods: A cross-sectional, prospective study using the Medical Outcomes Study HIV Health survey assessed the 10 dimensions of HRQoL and summarised as Physical Health Summary (PHS) and Mental Health Summary (MHS) scores. Participants were categorised as having good or poor PHS and MHS using the standardised mean score of 50. The variables independently associated with PHS and MHS were identified using multivariable logistic regression models. Results: Overall, 521 participants completed the HRQoL questionnaire. The median (IQR) PHS and MHS scores were 56 (47-60) and 51 (41-58) respectively. All the covariate groups had lower MHS than PHS. Participants with symptoms of HIV reported the lowest median (IQR) PHS score 44.7 (32.-54.5) and MHS score 36.1 (28.6-48.4). Of the 10 dimensions of HRQoL, the lowest scores were for the energy level and general health. Symptoms of HIV, co-morbidities, social support, employment and ethnicity had independent association with both PHS and MHS. Gender, education, alcohol intake and HIV-complications were associated with PHS. Age, illicit drugs, BMI and malnutrition were associated with MHS. However, CD4 count and viral load were not independently associated with PHS and MHS in multivariable regression models. Conclusion: Overall, HIV-infected people in this cohort had an average level of HRQoL. However, it is impaired in people with symptoms and co-morbidities, and not independently associated with CD4 and viral load. Alleviating HIV symptoms and preventing co-morbidities are important in managing HIV. Providing psychosocial supports for behaviour modification and return to work or exploring new opportunities will help to improve HRQoL. Healthcare providers and policy makers need to plan and implement programs to routinely assess the HRQoL in a systematic method to facilitate a holistic management of HIV.

Health and quality of life outcomes · cohort or longitudinal · 64 citationsread the source →

Dose-dependent and joint associations between screen time, physical activity, and mental wellbeing in adolescents: an international observational study.

Background: Mental wellbeing in adolescents has declined considerably during past decades, making the identification of modifiable risk factors important. Prolonged screen time and insufficient physical activity appear to operate independently and synergistically to increase the risk of poor mental wellbeing in school-aged children. We aimed to examine the gender-stratified dose-dependent and joint associations of screen time and physical activity with mental wellbeing in adolescents. Methods: We used data from three rounds of Health Behaviour in School-aged Children cross-sectional surveys (2006, 2010, and 2014) from 42 European and North American countries. Survey participants, aged 11 years, 13 years, and 15 years, provided self-reported information by completing an anonymous questionnaire that included items on health indicators and related behaviours. We used the self-reported variables of life satisfaction and psychosomatic complaints as indicators of adolescents' mental wellbeing, combining these with the self-reported discretionary use of screens and engagement in physical activity. We used generalised additive models and multilevel regression modelling to examine the gender-stratified relationships between mental wellbeing and screen time and physical activity. Findings: Our sample included 577 475 adolescents (mean age 13·60 years, SD 1·64), with 296 542 (51·35%) girls and 280 933 (48·64%) boys. The mean reported life satisfaction score (on a scale of 0-10) was 7·70 (95% CI 7·69-7·71) in boys and 7·48 (7·46-7·50) in girls. Psychosomatic complaints were more common among girls (mean 9·26, 95% CI 9·23-9·28) than boys (6·89, 6·87-6·91). Generalised additive model analyses showed slightly non-linear associations of screen time and physical activity with life satisfaction and psychosomatic complaints for girls and boys. Detrimental associations between screen time and mental wellbeing started when screen time exceeded 1 h per day, whereas increases in physical activity levels were beneficially and monotonically associated with wellbeing. Multilevel modelling showed that screen time levels were negatively associated with life satisfaction and positively associated with psychosomatic complaints in a dose-dependent manner. Physical activity levels were positively associated with life satisfaction and negatively associated with psychosomatic complaints in a dose-dependent manner. Joint associations of screen time-physical activity with mental wellbeing showed that, compared with the least active participants with more than 8 h per day of screen time and no physical activity, most of the other screen time-physical activity groups had considerably higher life satisfaction and lower psychosomatic complaints. Interpretation: Higher levels of screen time and lower levels of physical activity were associated with lower life satisfaction and higher psychosomatic complaints among adolescents from high-income countries. Public health strategies to promote adolescents' mental wellbeing should aim to decrease screen time and increase physical activity simultaneously. Funding: None.

The Lancet. Child & adolescent health · cohort or longitudinal · 63 citationsread the source →

Predictors of primary health care pharmaceutical expenditure by districts in Uganda and implications for budget setting and allocation.

Background: There is need for the Uganda Ministry of Health to understand predictors of primary health care pharmaceutical expenditure among districts in order to guide budget setting and to improve efficiency in allocation of the set budget among districts. Methods: Cross sectional, retrospective observational study using secondary data. The value of pharmaceuticals procured by primary health care facilities in 87 randomly selected districts for the Financial Year 2011/2012 was collected. Various specifications of the dependent variable (pharmaceutical expenditure) were used: total pharmaceutical expenditure, Per capita district pharmaceutical expenditure, pharmaceutical expenditure per district health facility and pharmaceutical expenditure per outpatient department visit. Andersen's behaviour model of health services utilisation was used as conceptual framework to identify independent variables likely to influence health care utilisation and hence pharmaceutical expenditure. Econometric analysis was conducted to estimate parameters of various regression models. Results: All models were significant overall (P < 0.01), with explanatory power ranging from 51 to 82%. The log linear model for total pharmaceutical expenditure explained about 80% of the observed variation in total pharmaceutical expenditure (Adjusted R(2) = 0.797) and contained the following variables: Immunisation coverage, Total outpatient department attendance, Urbanisation, Total number of government health facilities and total number of Health Centre IIs. The model based on Per capita Pharmaceutical expenditure explained about 50% of the observed variation in per capita pharmaceutical expenditure (Adjusted R(2) = 0.513) and was more balanced with the following variables: Outpatient per capita attendance, percentage of rural population below poverty line 2005, Male Literacy rate, Whether a district is characterised by MOH as difficult to reach or not and the Human poverty index. Conclusions: The log-linear model based on total pharmaceutical expenditure works acceptably well and can be considered useful for predicting future total pharmaceutical expenditure following observed trends. It can be used as a simple tool for rough estimation of the potential overall national primary health pharmaceutical expenditure to guide budget setting. The model based on pharmaceutical expenditure per capita is a more balanced model containing both need and enabling factor variables. These variables would be useful in allocating any set budget to districts.

BMC health services research · cohort or longitudinal · 9 citationsread the source →

Does microvolt T-wave alternans testing predict ventricular tachyarrhythmias in patients with ischemic cardiomyopathy and prophylactic defibrillators? The MASTER (Microvolt T Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients) trial.

Objectives: The purpose of this trial was to determine whether microvolt T-wave alternans (MTWA) predicts ventricular tachyarrhythmic events (VTEs) in post-myocardial infarction patients with left ventricular ejection fraction (LVEF) < or =30%. Background: Previous studies have established MTWA as a predictor for total and arrhythmic mortality, but its ability to identify prophylactic implantable cardioverter-defibrillator (ICD) recipients most likely to experience VTEs remains uncertain. Methods: This prospective trial was conducted at 50 U.S. centers. Patients were eligible if they met MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II) indications for device implant. All patients underwent MTWA testing followed by ICD implantation, with pre-specified programming to minimize the likelihood of therapies for non-life-threatening VTE. Minimum follow-up was 2 years with annual MTWA testing. Initially indeterminate MTWA tests were repeated. Results: Analyses were conducted on 575 patients (84% male; average age +/- SD = 65 +/- 11 years; average LVEF +/- SD = 0.24 +/- 0.05). The final distribution of MTWA results were: MTWA positive in 293 (51%), MTWA negative in 214 (37%), and indeterminate in 68 patients (12%). Over an average follow-up of 2.1 +/- 0.9 years, there were 70 VTEs. A VTE occurred in 48 of 361 (13%, 6.3%/year) MTWA non-negative and 22 of 214 (10%, 5.0%/year) MTWA negative patients. A non-negative MTWA test result was not associated with VTE (hazard ratio: 1.26; 95% confidence interval: 0.76 to 2.09; p = 0.37), although total mortality was significantly increased (hazard ratio: 2.04; 95% confidence interval: 1.10 to 3.78; p = 0.02). Conclusions: In MADIT-II-indicated ICD-treated patients, the risk of VTE does not differ according to MTWA classification, despite differences in total mortality. (MASTER I-Microvolt T Wave Alternans Testing for Risk Stratification of Post MI Patients; NCT00305240).

Journal of the American College of Cardiology · cohort or longitudinal · 134 citationsread the source →

Is cyberchondria specific to hypochondriasis?

Cyberchondria (i.e., excessive health-related Internet search linked to psychological distress) is usually associated with health anxiety, but relationships with other psychopathological symptoms were also found. However, studies are lacking in patients with hypochondriasis, and it remains unclear whether cyberchondria and its subfacets are specific to hypochondriasis (i.e., higher levels in hypochondriasis compared to other mental disorders). Patients with hypochondriasis (N = 50), a clinical (N = 70), and a healthy comparison group (N = 51) completed two questionnaires on cyberchondria whose combined 17 subscales were reduced to three relevant cyberchondria subfacets by second-order factor analysis. The cyberchondria subfacet emotional distress/negative consequences linked to health-related Internet searches showed significantly higher scores in patients with hypochondriasis than in the two comparison groups (d ≥ 1.7) and was the only predictor of dimensional health anxiety (β = .58, p ≤ .001). The two subfacets type/extent of health-related Internet searches and characteristics of the Internet (e.g., attitude toward unreliability, vast amounts of information) were less specifically associated with hypochondriasis. The results are consistent with models of cyberchondria and hypochondriasis, particularly on the anxiety-reinforcing vicious circle and maintaining factors. Based on the findings, practical implications are discussed.

Journal of anxiety disorders · 5 citationsread the source →

Frequency of illness anxiety (hypochondriasis) by proxy encountered by doctors in parents towards their children.

Background: Illness anxiety disorder is a condition of having a persistent fear of having a serious or life-threatening illness despite few or no symptoms. Current classification systems assume that illness anxiety is experienced relative to one's own health, and not towards others ("by proxy"), yet it has been observed to occur in parents towards their children. This study was designed to survey doctors about how commonly they encounter illness anxiety by proxy (IAP). Methods: We conducted a qualitative survey of 149 physicians who work with children (pediatricians, psychiatrists, and general practitioners) from the United Arab Emirates (UAE) and Egypt. The survey was administered via email and a paper-based form. In the UAE, 108 physicians were emailed the survey; 55 (50.1%) responded. For the email survey we used items from the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). An additional 100 physicians were surveyed in person; 94 (94%) responded. Results: Nearly all respondents (98.7%) reported having encountered IAP in parents. Of these, 51 (34.2%) reported frequently encountering these types of health anxieties, and 50 (33.6%) reported that the parents' concern that their child had a serious disease persisted despite reassurance and appropriate medical evaluation. Seventy-eight (52.3%) respondents reported that exaggeration of actual existing symptoms was the most common reason for parents' fears; 72 (48.3%) reported that the concerned parent was more likely to be the mother; and 36 (24.2%) reported that most parents were not 100% certain of their own beliefs. Conclusions: IAP is frequently encountered by pediatricians, psychiatrists, and general practitioners. Practitioners who work with children and their parents need to be aware of this phenomenon to provide appropriate support and treatment. More research is needed to screen for the extent and severity of this phenomenon.

Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists · 1 citationsread the source →

The Pediatric Role in the Care of Children in Foster and Kinship Care

In September 2010, 408,425 children and adolescents resided in foster care. Recent legislation highlights an increasing focus on involving pediatricians in supporting children in foster care and defines specific requirements relevant to the role of pediatricians. After completing this article, readers should be able to: Foster care is intended to provide a temporary haven for children during a time of family crisis when children are at imminent risk for harm. The goals of foster care are to promote child health, safety, permanency, and well-being. Foster care also has the mission of building on family strengths and providing birth parents with the services they need to reconnect (reunify) with their children. Because children fare best in stable and nurturing families, there has been an increased emphasis in the past decade on shortening the time to permanency through reunification, placement with relatives, and adoption. Foster care also has the obligation to prepare youth for independent living when none of these permanency options is possible. In some states, more than one third of children in foster care are in court-ordered (formal) kinship placements, arrangements in which the related (kin) caregiver may or may not be a certified foster parent. Even outside the child welfare system, somewhere between 4% and 8% of children reside with members of their extended family, neighbors, or friends for a variety of reasons. During the past decade, several studies were published reporting that children experience greater placement stability in kinship care than in nonrelative foster care, and that kin caregivers report fewer child behavior problems. Other data indicate that children in kinship care have as many issues as children in foster care, and that kinship caregivers are older, are less healthy, and have less access to services than nonrelative foster parents. However, recognizing that maintaining a child’s ties to his or her family of origin holds advantages for the child, relatively more children are being placed in kinship care as a result of child protective investigation. Other children are spending brief amounts of time in foster care while child welfare attempts to identify and investigate kinship resources. The definition of kin has expanded to include nonrelatives, such as family friends, acquaintances, and neighbors. There is little information about the outcomes of reunification with parents or kinship care, including child health and mental health outcomes and the percentage of kinship homes that undergo disruption. The vast majority of kinship placements are without oversight or subsidy, although recent federal legislation was intended to improve financial support for this group of caregivers. Children in foster care are classified as children who have special health-care needs by the American Academy of Pediatrics (AAP) because of their high prevalence of medical, emotional, behavioral, developmental, educational, and dental health-care problems. Most pediatric practitioners will encounter children and adolescents in foster or kinship care in their practices. It is important that pediatricians be familiar with the effects of childhood trauma and adversity, separation from family, and ongoing uncertainty on child behavior, mental health, and development. Pediatricians are in a unique position to identify problems, make appropriate referrals, and offer support and advice to caregivers. Foster care ideally should be developmentally appropriate and child-centered, and pediatricians can play a crucial role in offering developmentally sound advice and emotional support to caregivers about parenting traumatized children and children who have significant behavior problems. Pediatricians also should suggest ways to promote placement stability and successful permanency. Most maltreated children are not removed from their birth parents, but they appear to have the same health issues as children in foster and kinship care. The knowledge and skills that pediatricians bring to the care of children in foster and kinship care also apply to the larger population of children whose families are involved with child welfare agencies. Of 3.3 million child abuse and neglect reports in 2010, 436,321 (22%) were substantiated, and 254,000 children were removed to foster care. Over the past decade, the increasing trend toward keeping children with their birth parents or with kin caregivers after child protective investigation has reduced the total number of children in foster care. In the United States, on September 30, 2010, 408,425 children and adolescents resided in foster care, 26% in a relative (kinship) foster home, 48% in a nonrelative foster home, and 9% in either a group home or residential care setting. Of the remainder, 4% lived with a preadoptive family, 5% were on a trial discharge with their parents, and 2% were listed as “run-away.”Estimates suggest that more than 700,000 individual children have spent some time in foster care during the preceding 12 months. Census data indicate that approximately four to eight times as many children and teenagers live in informal, unregulated kinship care without child welfare involvement. Approximately 40% of those in foster care are teenagers, whereas 30% are children under age 5 years. Children in foster care range in age from birth to 21 years, although 47 states still emancipate adolescents at age 18 years. Minorities are represented prominently in foster care. In 2010, 29% of children were of African American heritage, 21% Hispanic, 41% white, and 5% of two or more races. Significant concern exists that the overrepresentation of minority children reflects bias in child protective referrals, investigation, and removal, as well as a lower likelihood of reunification after removal. Discrete subpopulations in foster care that present with unique health needs include children who have multiple handicaps, teenagers involved with juvenile justice, pregnant and parenting teenagers, and unaccompanied refugee minors from countries ravaged by war or severe internal strife. The average length of stay in foster care in 2010 was 25 months, with a median of 14.5 months. The lower median is attributed to more intensive permanency planning, resulting in shorter times to reunification or placement with extended family. However, the higher mean is affected by the 25% of children who remain in care for years. Length of stay is affected by several factors: the biological family’s cooperation with the individualized case plan for their family; the availability of appropriate extended family to care for the child; diligence in permanency planning by child welfare; and the challenges of finding adoptive resources for older children, minority children, large sibling groups, and children who have significant behavioral and developmental problems. Longer stays in foster care are associated with a reduced likelihood of reunification and an increased number of placements. Approximately 50% of children and teenagers will experience more than one foster care placement, with approximately 25% having three or more placements. In 2010, of the 254,114 children who exited foster care, 51% returned to their parents and 14% went to a relative or guardian, whereas 21% were adopted and 11% aged out of foster care. The vast majority of the 27,854 individuals who aged out were emancipated at age 18 years. Because the long-term benefit of foster care placement is uncertain, admission to foster care is and should be difficult. Almost all children entering foster care are placed involuntarily by court order after child protective investigation. Child neglect, including lack of supervision or neglect of basic nutritional, educational, and medical needs, is the most commonly cited reason for placement. Overall, approximately 70% of admissions are for maltreatment. Teenagers tend to be placed for disruptive behaviors through either the juvenile justice system or as persons in need of supervision. Voluntary placements constitute less than 1% of admissions and often are made by families as a means of accessing treatment services for a child or teenager who has complex mental health or medical problems. Families whose children reside in foster care come from all walks of life, but financial poverty remains a pervasive common factor underlying foster care placement (>50% of children live with impoverished families before foster care). Poverty, however, extends beyond the financial to the lack of the normal, predictable, nurturing environment that promotes good developmental and emotional health. Most children have experienced childhood adversities beyond maltreatment, including exposure to significant violence in their homes (84%) or communities placement, report that of caregivers have parenting with mental health abuse or often lack have and high and are one third of birth parents to being or as children, and about the same percentage spent time in foster care. Children often have multiple caregivers before placement in foster care. of a child often with child welfare with the after have been when the child’s health and are at imminent that childhood trauma or multiple childhood and are associated with and long-term mental health, developmental, and health exposure and in the of protective the of the in a those of the involved in emotional and children entering foster care with their and adversities are children who have emotional, developmental, and health on and are but data indicate that stability in a nurturing and family promotes after childhood foster care is with and for children. high of family from the family of origin and all that is familiar is experience for many children, for children, placement in foster care may be the time they have stable placement in a foster home can promote the ongoing and to foster care may a child’s of highlights an increasing focus on involving pediatricians in supporting children in foster care. The to and of foster care to identify kinship resources at to foster care, promote and support kinship care, children in their of support American in keeping children foster care and resources for with a of independent for pediatric health states to health for children in foster care, pediatricians in the of such health improve health-care promote the of medical and health foster care system is in of providing children with nurturing families, but also complex in legislation of and but for the of foster care with which in to or child welfare by the foster care system remains by birth parents who have multiple problems, and and that appear to be in with child welfare is for and for is a complex multiple skills with Most however, more than of in many case for the biological family, parents the care of their children while to with or resources are mental health, parenting medical care, and and to promote also educational, developmental, medical, and mental health services for children, and support the foster parents in their care. birth parents are or to the for reunification, have the of supporting through the of permanency also are to children and a of to a family than their family of also and foster parents. have a with the system in their family court and the juvenile justice of a child from a family, the prepare a court the for the child or in foster care, the to court at to provide ongoing for the of placement and to their on of parents and children toward child in foster care is represented in court by a who may or may not be an on the In some states, in the court also may a special on of the who are not special many to the child’s for to the oversight with the court have the of on information to in a child remains in placement after or services for biological and at the case for a child in care to placement or an permanency is the court the permanency with the that such a is on the from all child welfare mental health and and the youth who is of age and developmental to on his or her for the child and childhood trauma remains parents are the and of the foster care system, and foster parenting is the Foster parents come from all walks of life, on tend to be be of lower have at a high be and have children of their have and most are by a to for children. foster parents with the of percentage of foster parents are and are to that can foster and 5% of foster families undergo to as resources for or children. However, most foster parents little about parenting children who have significant trauma and There are some studies that specific and for foster parents and birth parents as Foster and parenting for foster improve outcomes for children, but these have not for foster parenting are a for child in their care that is by individual The is by the child’s health needs, and the of the parenting The is to needs, and most and recent that approximately two of the of parenting a child in foster and of foster families are some of the most child welfare are in the foster care system in of and Foster families the of the for children and teenagers, but are to the system, and the birth family for the child’s care. remains with the birth a child is for but the foster care is for that a child’s needs are and the child is well of youth in foster care, reside in residential or group home placements, which can of child health services are but is The outcomes of group care have not been well and there to be in the of such of a child with his or her biological is the best for reunification, may be for the parents and The of the is Children who have been or by their parents may not in a setting. parents may not the need to focus on the child during and focus on their issues or with child parents may to the of the child with the and may which is and for children, and and the the with separation that may be for and through with by in a setting. to a or the home, the is before placement may for more with the birth but kin caregivers also may unique challenges they toward the birth are about or have to court-ordered to which the and is for of in which a mental health parents identify their child’s their child’s developmental parenting skills in parenting and to their child in an appropriate such as or still are not because such are and and is in which prepare birth parents for the stay on during the and with to the challenges associated with children may encounter adversities in foster care. in foster care placement, in or child care placement, separation from the of children entering or their foster home, by birth parents, a with their foster being or and court are but some of the children may an child, one can be to is as the of a child to foster care after reunification, placement with extended family or guardian, or adoption. on the to 30% of children to foster care, as a result of a of reunification with their birth parents. but percentage of undergo during an parents of their children in the care and of the or of can be as of a in which the the child’s the child either the age of majority or is parents to their children for more of involuntarily after at reunification have The can years, during which time but at reunification and permanency planning by federal legislation in states to a child has been in foster care for of the past and when there is reason not to the and in the with which they this federal child as a result of the of studies on childhood and placement has toward a to foster care, the is not to permanency on the of the out of foster care several Over of children adopted out of care are adopted by their foster parents, and 30% are adopted by kinship caregivers. to the most recent there were children out of foster care in 2010, of were for and resided in preadoptive children without an adoptive tend to be older, minority children, to be of large sibling groups, or to have significant emotional and behavioral problems, that to be to parents most often child welfare as an their and the reason for the of their family. some parents with child welfare either to remain with a or in that the child for the removal, whereas the of their family and for the resources that child welfare birth parents have trauma and their that have and lack the most basic of parenting and of their children may their of and welfare may children in a an foster home, or the home of a the of the court after child protective investigation. with kin caregivers is to be less the child has a with The in foster care may be with a of from child protective to health and members of the foster to foster care often are for the several a by most child welfare as a time of emotional for the and Children who have severe trauma may to behaviors that were in their but in the setting. The majority of children are by they not and or in in foster care often about they are in foster care, and children may for the of their about the of their parents and and their they will be in care, or when their parents will come for or when a will out of or parents may make they not or Other children about being in foster care, to their and of children and to foster parents and may their less birth as a in parenting or between for children and Children may not be for discharge from foster care or to a in foster care placement are for children, that a that of and for placements but include child behavior problems, foster between birth and foster parents, and a foster home may be or neglect a child’s needs, resulting in foster care is because the care is and nurturing foster a of and for the child, the child to the of family and to the The foster care placement is stable during the child’s time in care. The foster and birth and on of the The birth for at and of the services by child Child welfare the birth identify and on the family’s and the crisis that to the family’s is Children appropriate mental health and their parents in those services as the foster care experience not this in foster care are a have in foster care, whereas foster care through the juvenile justice system or are placed by a to their behaviors or to access appropriate mental health-care tend to have the placement they experience a variety of foster care time family group residential or and between foster care, home, juvenile percentage of teenagers are and have significant behavior teenagers may lack the to in or parenting teenagers are group who may be living with their children or placed from they have significant mental health issues or constitute a risk to their teenagers foster care as unaccompanied refugee having to the United from a variety of countries after or the of their majority of adolescents in foster care reside in their are is and they mental health services and adolescents in foster care have experienced childhood including maltreatment, as children in foster care. have and but their including and may be that the underlying remain in foster care are less to permanency, either through reunification or adoption. to parents or relatives, but many age out at age 18 years, or are to or placement care or group home care). to and for independent living is resources are Foster or kin families who remain in youth are their best and youth who identify and remain to foster parents, or appear to fare is about the outcomes of youth who have aged out is a of most youth have spent at one and many have an who are a decade removed from foster care are have with in and have high of mental health problems, including and studies indicate that with a of foster care are the and is the time during which the individual is to a stable in a of in and a larger of and in to in foster care, minority lack of and a lack of are outcomes of the of multiple and a of is from living in the of foster abuse and neglect, with separation and and a lack of role for result in a high prevalence of who are and to well are those foster youth who are and a multiple childhood health issues of children in foster care are in their of neglect, and and multiple childhood and childhood with the lack of protective the health of children in foster care. The defines children in foster care as children with special health-care needs because of their high prevalence of medical developmental dental problems, and behavioral, emotional, and mental health In of children in foster care have issues related to family about the health of the foster care population have to care, 30% to have at one medical and approximately have complex health problems. The for the high prevalence of health include medical neglect or lack of access to health services before foster of the to with child’s health needs, resulting in and the of childhood adversities on health. and developmental are and may be the result of the of and childhood or the result of studies report that the ongoing health of children in foster care are mental health and developmental problems. of children under age foster care with developmental in at one and to 70% of children age 5 have a mental health or behavioral are in the adversities and trauma children have experienced before foster care. that may have been in a or environment in a more setting. that significant behavioral of by developmental problems, to placement in emotional and mental health children foster care, their health not appear to improve The of the population the likelihood that they will to have access to information on admission foster care is foster parents have the of knowledge to as the health-care the foster system on to this complex most children in foster care have health in the of this also access to health-care because of in and of medical to in care may access to medical care, but mental health access for children in foster care. to support and foster parents about a child’s medical, developmental, and mental health needs and to appropriate treatment can to in placement when foster parents and requirements may and treatment and care can be is not However, has specific about who can for health-care on of a child in foster care. states, for of the guardian, who is the birth for including of In child welfare have in for and health-care should issues with their child welfare the health of the legislation states to health for children in foster care, is in in most with intensive care are because health-care the of care children children in foster care will their health-care as children who have special health-care needs in the of a pediatric medical The has a number of resources to pediatric but the of the medical home for the child in foster care are as The medical home should the health-care for children and teenagers in foster care by the on Foster from for Children and in Foster The are on the Foster was for by child mental health, and and youth in foster care. resources and may also be to pediatricians in with states and foster care for health brief of the health-care for children in foster care are listed in and should children and after to care, because often more health needs than one and they a between the and The admission health-care for all children, but for those with special health-care Children in foster care should have health-care and those for all children to all of their health developmental, educational, emotional and behavioral, and health-care encounter should include for child abuse and neglect in the placement. Foster that should be in to the children who have complex medical, developmental, or mental health problems, the may more health health is the most important health-care need of children in foster care. Children need and of mental health and to pediatric mental health of mental health-care basic should be in when and are two health needs of children in foster care. and may result in and multiple and are the most to be developmental for all children in foster care is not the pediatric should at a developmental to identify children in need of a some children developmental skills and in foster care, child who has behavioral or in should an It is that the with the child’s to that needs are and parents in most communities report that children in foster care have access to dental care, a high prevalence of significant dental are to with their health and dental to access issues for children in foster is a and in foster care. foster families have a of but the should not that they have in parenting children and teenagers who have past and ongoing In to the should issues specific to foster care, such as on the child’s parenting the of trauma on child supporting children through permanency planning, in placement, significant the need for and with birth parents to and and children should be about planning for their and with teenagers in foster care, have their to to a pediatric can foster parents the emotional while supporting an parenting for foster families and youth in foster care and can a foster care placement for a the also the birth and the child’s in these is the of the foster care with the as the case However, the pediatric medical home has an important role to play in that a child in foster care all health-care in a and that and youth in care all and in the health-care that health with child welfare to and information health-care are in are in a unique position to for in of care for children in foster care, in of the health in the can with their the and a and on in the of Children in Foster and the children and families for their and her at Pediatrics and the of for their and

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Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. 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J Physiol | ISI | Google and modulation of sympathetic nerve activity to muscle in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and is not associated with of the exercise reflex in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google C, and Y. The effect of on the circadian control of human core body temperature is Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of adenosine receptors in the does not affect the in awake rats. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google JK, A, and circadian and during two Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and sympathetic nerve and heart rate spectral effects of lower body negative pressure. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Francis Johnson and of heart failure after myocardial in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google A, and of lower body pressure on muscle sympathetic nerve activity response to Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and Adenosine initial depression of in the rat in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google R, and and circadian phase in a diurnal the Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Johnson alterations and autonomic in an model of Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google MA, and The interaction of the Bainbridge and in the conscious Res | ISI | Google A, and handgrip exercise arterial control of sympathetic in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve regulation to is in rats. 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American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

Gender differences in perception of psychosocial distress and coping mechanisms among infertile men and women in Saudi Arabia.

The objective of the study was to evaluate the differences in psychosocial distress and coping mechanisms among infertile men and women in Saudi Arabia (SA). We performed a cross-sectional study of infertile patients (206 women and 200 men) attending infertility clinics in three referral hospitals in Riyadh, SA. A semi-structured questionnaire was developed to assess socio-demographic, clinical and psychosocial variables. Infertility-related psychosocial pressures were reported in 79 (39.7%) male and 97 (47.3%) female participants (p = 0.123). Males suffered more from intrusive questions and pressure to conceive, remarry or get divorced, while females were stressed more from psychological and emotional exhaustion, marital discord, attitudes of mothers-in-law or society, and persistent desire by the husband to have children. To cope with infertility, females engaged more in religious activities (p < 0.001) and spoke more to someone regarding their problems (p < 0.001). To solve their infertility problems, 50% tried to find solutions via the internet, and 38.5% of males and 51% of females reported using alternative medicines (p = 0.012). The patients with infertility in SA face multiple psychosocial stressors related to their infertility, and cope differently based on the gender and culture-specific knowledge of infertility. The female participants were significantly more affected from psychosocial stressors and the persistent desire by their spouse to have children.

Human fertility (Cambridge, England) · 15 citationsread the source →

Interoception and gender: What aspects should we pay attention to?

Interoception is involved in both somatic and mental disorders with different prevalence between genders; however, gender differences are often neglected. To examine the potential gender differences in interoceptive awareness, we recruited 376 healthy subjects (51% males, aged 17-30years), to fill in the Multidimensional Assessment of Interoceptive Awareness (MAIA). Of that sample, in a subgroup of 40 subjects (50% males), interoceptive accuracy was assessed by heartbeat counting task (HCT). The results on interroceptive awareness suggest that females tendto notice bodily sensations more often, better understand relations between bodily sensations and emotional states, worry or experience more emotional distress with sensations of pain or discomfort and see body as less safe. The results of interoceptive accuracy further suggest that females are less efficient in consciously detecting heartbeats. Therefore, gender should be considered when interoceptive evaluation is performed in disorders associated to bodily sensations and to the emotional/mood states.

Consciousness and cognition · 111 citationsread the source →

Assessing parental marital quality and divorce related to youth sexual experiences and adverse reproductive health outcomes among 50,000 Chinese college students.

Background: This study aimed to investigate the associations between parental marital quality, divorce, and sexual and reproductive health outcomes among Chinese young people. Methods: The study included 51,124 students from a large-scale cross-sectional study in China from 2019 to 2020. The exposures were parental marital quality and legal marital status reported by students. The dichotomous outcomes included sexual experiences, high-risk sexual behaviors, unintended health outcomes, and sexual abuse. Multivariate logistic regression models adjusting for socio-demographic factors were used to assess the relationship between parental marital quality, divorce, and sexual and reproductive health outcomes, stratified by sex. Results: A total of 10.72% of the surveyed students' parents had divorced. Participants from divorced family rated perceived parental marital quality less than half of the ratings on a 10-point scale of those from intact family (3.22 vs. 7.44). Parental divorce was associated with a higher likelihood of sexual abuse, high-risk sexual behaviors, and unintended health outcomes. A higher perceived parental marital quality was associated with a lower probability of adverse sexual and reproductive health experiences and outcomes, such as forced penetrative vaginal or anal intercourse (male: OR: 0.73, 95% CI: 0.64-0.83; female: OR:0.71, 95% CI: 0.65-0.77), casual sexual intercourse (male: OR: 0.78, 95% CI: 0.73-0.83; female: OR: 0.77, 95% CI: 0.72-0.83), and sexually transmitted infections (male: OR: 0.79, 95% CI: 0.70-0.89; female: OR: 0.82, 95% CI: 0.73-0.91). Conclusions: Parental marital quality and status are associated with poorer sexual and reproductive health outcomes among young adults, suggesting that specific intervention programs should be implemented for children from unharmonious families or divorced families to prevent adverse sexual and reproductive health outcomes.

Reproductive health · 2 citationsread the source →

Measuring connectedness to nature in preschool children in an urban setting and its relation to psychological functioning.

Background: The urban environment has been criticized for promoting 'nature-deficit' and 'child-nature disconnectedness'. Keeping in mind the importance of nature exposure and its extensive health benefits, many environmental programs around the world hope to (re)connect children with nature. To evaluate the effectiveness of such efforts, valid tools to measure Connectedness to Nature (CN) are needed but do not exist today, especially for use with pre-schoolers. Methods: The original CN Index was modified and tested among the Parents of Preschool Children (CNI-PPC) in an urban setting (Hong Kong) for its internal consistency (n = 299) and external validity (n = 194). The 'Strength and Difficulties Questionnaire' (SDQ) was chosen for divergent and convergent analysis. Conventional recommendations for test adaptation and translation were used. Results: Confirmatory factor analysis (CFA) revealed that the 16-item scale adequately captured four major dimensions: enjoyment of nature, empathy for nature, responsibility toward nature, and awareness of nature (Cronbach's α were respectively .86, .87, .75 and .80). When tested against the SDQ, a validated measure for child psychological functioning, and identification of children's problem behaviours, three CNI-PPC factors influenced the SDQ outcomes: (1) the more enjoyment of nature children displayed the less overall distress and impairment they exhibited (β = -.64); (2) greater responsibility toward nature in children was associated with less hyperactivity (β = -.50), fewer behavioural and peer difficulties (β = -.62 and β = -.65 respectively) and improved prosocial behaviour (β = .77); (3) the more aware children were of nature, the less emotional difficulties they exhibited (β = -.51). The variance explained was large (range R2 = .42 to .80). Conclusions: Thus, CNI-PPC factors have meaningful and substantive associations with the strengths and difficulties parents perceive in their children. This indicates that the CNI-PPC is a valid and reliable instrument to measure CN at an age when children cannot respond for themselves. Further, this simple tool can help researchers/practitioners to better understand how connectedness to nature affects child psychological functioning and wellbeing. Trial registration: ClinicalTrials.gov Identifier: NCT02715544. Registered 8 March 2016.

PloS one · 26 citationsread the source →

Perception of cancer in patients diagnosed with the most common gastrointestinal cancers.

Background: Gastrointestinal cancers, including colorectal cancer, stomach cancer and pancreatic cancer are among the most common cancers in Poland. Cancer patients usually assess their quality of life much worse than the general population, while negative emotions associated with the illness may affect the results of treatment. Methods: The study involved 378 patients with colorectal cancer, stomach cancer and pancreatic cancer, treated as outpatients at the Oncology Center - Maria Skłodowska-Curie Institute in Warsaw in 2013-2018. Standardized tools were used in the study: the Beliefs about Pain Control Questionnaire (BPCQ), the Pain Coping Strategies Questionnaire (CSQ), Approval Illness Scale (AIS), Mental Adjustment to Cancer (MiniMAC). The main goal of the study was to assess pain control, pain management strategies, illness acceptance and adaptation to cancer in patients with the most common gastrointestinal cancers. Results: Patients with gastrointestinal cancers ascribe the greatest role in controlling pain to internal factors (M = 16.84, SE = .34), and the highest score in this area was obtained by patients with colorectal cancer (M = 17.33, SE = .35). The most frequently chosen strategy is declaring coping (M = 20.95, SE = .57), although patients with pancreatic cancer obtained a high score also in the area of catastrophizing (M = 17.99, SE = 1.14). The average value of illness acceptance for patients with gastrointestinal cancers was M = 25.00 (SE = .50) and it was the lowest in the group of patients diagnosed with pancreatic cancer (M = 23.41, SE = 1.16), and the highest in a group of people with colorectal cancer (M = 27.76, SE = .51). Patients with gastrointestinal cancers obtained the highest values of the MiniMAC test in the area of the fighting spirit (M = 21.30, SE = .25), characteristic mainly for patients with colorectal cancer. Patients with pancreatic cancer were characterized by high anxiety and helplessness/hopelessness. Conclusions: Patients with gastrointestinal cancers use different methods of pain control and pain coping strategies, with active behaviors being preferred by patients with colorectal cancer and destructive - by patients with pancreatic cancer. The majority of socio-economic variables, as well as the treatment method, affect the patients' behaviors.

BMC palliative care · 15 citationsread the source →

Characterization of Home Working Population during COVID-19 Emergency: A Cross-Sectional Analysis.

Evidence about the characterization of home workers in terms of both work-related outcomes and health issues is lacking. The purpose of this cross-sectional study was to examine the impact of home working on perceived job productivity and satisfaction, work-related stress, and musculoskeletal (MSK) issues. We included 51 mobile workers, collecting data about demographic characteristics, working experience, job productivity, and stress. Job satisfaction was assessed through the Utrecht Work Engagement Scale (UWES), while MSK pain was investigated by the Brief Pain Inventory (BPI) and Fear Avoidance Beliefs Questionnaire (FABQ). Moreover, a home workplace analysis had to be carried out according to current Italian regulations. Participants declared that they were less productive (39.2%) but less stressed (39.2%) and equally satisfied (51%) compared to the time of office working. Regarding MSK disorders, low back pain (LBP) was referred by 41.2% of home workers and neck pain by 23.5% of them. Neck pain worsened in 50% of home workers, while LBP did not exacerbate in 47.6% of cases. Home workers with MSK pain reported a lower job satisfaction. Depending on our data, the home environment seems to be not adequate in the mobile worker population, with an increased risk for mental health and MSK problems, particularly affecting the spine. Addressing these issues can significantly reduce risks for health, thus, improving job productivity and satisfaction and reducing cost.

International journal of environmental research and public health · 127 citationsread the source →

Cognitive decline in older adults in the UK during and after the COVID-19 pandemic: a longitudinal analysis of PROTECT study data.

Background: Although the long-term health effects of COVID-19 are increasingly recognised, the societal restrictions during the COVID-19 pandemic hold the potential for considerable detriment to cognitive and mental health, particularly because major dementia risk factors-such as those related to exercise and dietary habits-were affected during this period. We used longitudinal data from the PROTECT study to evaluate the effect of the pandemic on cognition in older adults in the UK. Methods: For this longitudinal analysis, we used computerised neuropsychology data from individuals aged 50 years and older participating in the PROTECT study in the UK. Data were collected from the same participants before the COVID-19 pandemic (March 1, 2019-Feb 29, 2020) and during its first (March 1, 2020-Feb 28, 2021) and second (March 1, 2021-Feb 28, 2022) years. We compared cognition across the three time periods using a linear mixed-effects model. Subgroup analyses were conducted in people with mild cognitive impairment and in people who reported a history of COVID-19, and an exploratory regression analysis identified factors associated with changes in cognitive trajectory. Findings: Pre-pandemic data were included for 3142 participants, of whom 1696 (54·0%) were women and 1446 (46·0%) were men, with a mean age of 67·5 years (SD 9·6, range 50-96). Significant worsening of executive function and working memory was observed in the first year of the pandemic across the whole cohort (effect size 0·15 [95% CI 0·12-0·17] for executive function and 0·51 [0·49-0·53] for working memory), in people with mild cognitive impairment (0·13 [0·07-0·20] and 0·40 [0·36-0·47]), and in people with a history of COVID-19 (0·24 [0·16-0·31] and 0·46 [0·39-0·53]). Worsening of working memory was sustained across the whole cohort in the second year of the pandemic (0·47; 0·44-0·49). Regression analysis indicated that cognitive decline was significantly associated with reduced exercise (p=0·0049; executive function) and increased alcohol use (p=0·049; working memory) across the whole cohort, as well as depression (p=0·011; working memory) in those with a history of COVID-19 and loneliness (p=0·0038; working memory) in those with mild cognitive impairment. In the second year of the pandemic, reduced exercise continued to affect executive function across the whole cohort, and associations were sustained between worsening working memory and increased alcohol use (p=0·0040), loneliness (p=0·042), and depression (p=0·014) in those with mild cognitive impairment, and reduced exercise (p=0·0029), loneliness (p=0·031) and depression (p=0·036) in those with a history of COVID-19. Interpretation: The COVID-19 pandemic resulted in a significant worsening of cognition in older adults, associated with changes in known dementia risk factors. The sustained decline in cognition highlights the need for public health interventions to mitigate the risk of dementia-particularly in people with mild cognitive impairment, in whom conversion to dementia within 5 years is a substantial risk. Long-term intervention for people with a history of COVID-19 should be considered to support cognitive health. Funding: National Institute for Health and Care Research.

The lancet. Healthy longevity · 43 citationsread the source →

Prevalence of burnout, depression, anxiety and stress in Australian midwives: a cross-sectional survey.

Background: The health and wellbeing of midwives are important considerations for workforce retention and quality care. The occurrence and relationships among mental health conditions such as burnout and depression have received little attention. We investigated the prevalence of burnout, depression, anxiety and stress in Australian midwives. Methods: An online survey was conducted in September 2014. Participants were recruited through the Australian College of Midwives and professional networks. The survey sought personal and professional details. Standard measures included the Copenhagen Burnout Inventory (CBI) (Personal, Work and Client subscales), and Depression, Anxiety, and Stress Scale (DASS). The sample was collapsed into two groups according to DASS clinical cut-offs (normal/mild versus moderate/severe/extreme). Effect size statistics were calculated and judged according to Cohen's guidelines. Results: One thousand thirty-seven surveys were received. Respondents were predominantly female (98%), with an average age of 46.43 years, and 16.51 years of practice. Using a CBI subscale cut-off score of 50 and above (moderate and higher), 64.9% (n = 643) reported personal burnout; 43.8% (n = 428) reported work-related burnout; and 10.4% (n = 102) reported client-related burnout. All burnout subscales were significantly correlated with depression, anxiety and stress, particularly personal and work-related burnout with Spearman's rho correlations ranging from .51 to .63 (p < .001). Around 20% of midwives reported moderate/ severe/ extreme levels of depression (17.3%); anxiety (20.4%), and stress (22.1%) symptoms. Mann-Whitney U tests revealed significant differences between groups with depression (r = .43), anxiety (r = .41) and stress (r = 48) having a medium size effect on burnout. Conclusion: Prevalence of personal and work-related burnout in Australian midwives was high. The physical and psychological exhaustion associated with the different types of burnout were reflected in symptoms of depression, anxiety and stress symptoms. Further research is needed to support the personal well-being of midwives and minimize workplace burnout by developing short and long term strategies.

BMC pregnancy and childbirth · 183 citationsread the source →

Association of Prepubertal and Postpubertal Exposure to Childhood Maltreatment With Adult Amygdala Function.

Importance: Abnormalities in amygdala response to threatening faces have been observed in anxiety disorders, autism, bipolar disorder, depression, posttraumatic stress disorder, and schizophrenia. Abnormally hyperactive and hypoactive responses have typically been associated with anxiety and inhibition vs risk taking and inappropriate social behaviors. Maltreatment is a major risk factor for most of these disorders and is associated with abnormal amygdala function. Objective: To identify the type and age of exposure to childhood maltreatment that are associated with hyperactive and hypoactive amygdala responses in young adulthood. Design, setting, and participants: Data collection for this retrospective cohort study took place from November 8, 2010, to August 23, 2012. Data analyses were conducted from September 20, 2012, to June 27, 2018. Participants were recruited from the urban and suburban Boston vicinity without diagnostic restrictions based on exposure history. Exposures: The Maltreatment and Abuse Chronology of Exposure (MACE) scale was used to retrospectively assess type and age of exposure to childhood maltreatment. Main outcomes and measures: Activation and pattern information functional magnetic resonance imaging were used to assess bilateral amygdala response to angry and fearful faces vs neutral faces or shapes, and sensitive exposure periods were identified using cross-validated artificial intelligence predictive analytics (50 averaged randomized iterations with training on 63.3% and testing on 36.7% of the sample). Results: Of the 202 participants (mean [SD] age, 23.2 [1.7] years; 118 [58.4%] female), 52 (25.7%) reported no exposure to maltreatment and 150 (74.3%) reported exposure to 1 or more maltreatment types. Eight participants (15.1%) with a MACE score of 0 and 51 (34.2%) with a MACE score of 1 or higher had a history of major depression (odds ratio, 2.40; 95% CI, 1.05-6.06; P = .03); 8 unexposed participants (15.1%) and 46 with MACE scores of 1 or higher (30.9%) had a history of 1 or more anxiety disorders (odds ratio, 2.45; 95% CI, 1.03-6.50; P = .03). Retrospective self-report of physical maltreatment between 3 and 6 years of age and peer emotional abuse at 13 and 15 years were associated with amygdala activation to emotional faces vs shapes. Early exposure was associated with blunted response (β = -0.17, P < .001), whereas later exposure was associated with augmented response (β = 0.16, P < .001). Prepubertal vs postpubertal maltreatment was associated with an opposite response on the voxelwise response pattern in clustering stimuli of the same type (eg, mean [SD] emotional ellipse areas for physical maltreatment at age 4 years vs nonverbal emotional abuse at 13 years: 1.41 [1.05] vs 0.25 [0.10], P < .001) and in distinguishing between stimuli of different types (eg, mean [SD] emotional vs neutral faces distance for peer emotional abuse at age 6 years vs 13 years: 1.89 [0.75] vs 0.80 [0.39], P < .001). Conclusions and relevance: The findings suggest that prepubertal vs postpubertal developmental differences in the association between maltreatment and amygdala response to threatening or salient stimuli exist. Understanding the role of adversity in different sensitive exposure periods and the potential adaptive significance of attenuated vs enhanced amygdala response may help explain why maltreatment may be a risk factor for many different disorders and foster creation of targeted interventions to preempt the emergence of psychopathology in at-risk youths.

JAMA psychiatry · 104 citationsread the source →

Mental health and psychosocial support for families of missing persons in Sri Lanka: A retrospective cohort study.

Background: The International Committee of the Red Cross (ICRC) has developed its 'Accompaniment model' to address the multi-faceted needs of relatives of people who go missing during armed conflict. In Sri Lanka an Accompaniment Programme was launched in 2015 for the relatives of the more than 16,000 missing persons who remain unaccounted for. Method: One thousand seven hundred eighty-three relatives who took part in the mental health and psychosocial support (MHPSS) component of the ICRC's Accompaniment Programme in Sri Lanka between April 2016 and August 2017 were offered eight peer-support group sessions, individual home visits, referrals to local services, and commemoration events to pay tribute to their missing relatives. Symptoms of anxiety and depression (using the HADS scale), somatic difficulties (using the BSI scale) and daily functioning (ICRC scale) were assessed before and after the MHPSS intervention. Results: Prior to receiving support, Tamil and Muslim ethnicity, ≥60 years of age and civilian status were predictors of severe symptoms of anxiety; Tamil ethnicity, ≥50 years of age and being the mother of a missing person were predictors of severe symptoms of depression; and ≥ 50 years of age and severe symptoms of anxiety and depression were predictors of severe somatic difficulties. After receiving support, the vast majority of the relatives of missing persons showed reduced levels of anxiety (81%), depression (79%) and somatic pain (77%), as well as increased functioning (75%). Predictors of improvement following support were severe levels of distress at baseline and Tamil and Muslim ethnicity. In addition, attending at least three group sessions was a predictor of decreased anxiety, age group 51-60 was a predictor of decreased depression, female gender was a predictor of decreased somatic difficulties, and referrals were a predictor of increased functioning. Conclusion: The MHPSS component of the ICRC's Accompaniment Programme is a relevant approach to helping families to cope with not knowing the fate and whereabouts of their missing relatives, to reduce distress, to break their social isolation and to resume more functional lives. However, further research is needed, possibly through a controlled trial, to better establish the effectiveness of this approach.

Conflict and health · 2 citationsread the source →

Assessing the Psychosocial Impact of Expressive Writing on Adults With Spinal Cord Injury: Qualitative Study.

Background: Spinal cord injury (SCI) results in significant physical, emotional, and social consequences, often leading to profound grief and unresolved emotional burdens. While expressive writing has shown potential in facilitating emotional processing and in aiding coping after trauma, loss, and health-related adversity, its impact on individuals who have suddenly lost physical abilities due to SCI remains underexplored. Objective: The study aimed to examine the experiences of adults with SCI who participated in a 10-week web-based coach-guided expressive writing program to understand its impact using a qualitative research design with a phenomenological approach. Methods: Participants were recruited through various outreach strategies based on a set of predefined criteria. A total of 50 individuals from 23 states expressed interest in the expressive writing program. Of those who met the eligibility criteria, 29 individuals completed the preprogram questionnaire. A total of 5 participants did not complete the postprogram assessments, including the exit interview. The program sessions were structured with reflective prompts designed to explore their emotions and life experiences related to their conditions. Qualitative data were collected through postprogram semistructured interviews and analyzed using thematic analysis to identify themes related to participants' experiences and program impact. The analysis was conducted without any preset theoretical framework of reference. Results: A total of 24 adults with SCI, aged between 34 and 76 years (average age 51, SD 12 years), participated in the expressive writing program and the exit interview. Of these, 19 participants were White, and 17 were female. In total, 18 participants had sustained a traumatic SCI; of these, 10 had quadriplegia, 12 had paraplegia, and 2 had monoplegia. Qualitative analysis revealed three overarching themes: (1) supportive environment: the program provided participants a space that encouraged open reflection on past events and personal struggles, and the guidance of patient and empathetic coaches offered a sense of comfort, direction, and motivation. (2) Cathartic experience: the program helped them process complex emotions, reframe their perspectives, and cultivate a more positive outlook on life and their injury. Many participants, new to guided expressive writing, found the process therapeutic and transformative. (3) Acceptance of life: the cumulative impact of the sessions fostered self-compassion, forgiveness, empowerment, and self-advocacy. Participants reported reduced feelings of loneliness, a greater sense of community, and profound positive changes, expressing the desire to continue writing beyond the program. Conclusions: The sudden onset of lifelong disability due to SCI leads to profound physical, mental, and social challenges. The coach-guided expressive writing program enhanced the emotional processing and articulation, coping mechanisms, and overall well-being of the participants. These results highlight the potential of expressive writing programs as accessible and valuable rehabilitative interventions for individuals with SCI.

JMIR formative research · 1 citationsread the source →

Trajectories of childhood adversity and mortality in early adulthood: a population-based cohort study.

Background: Childhood is a sensitive period with rapid brain development and physiological growth, and adverse events in childhood might interfere with these processes and have long-lasting effects on health. In this study, we aimed to describe trajectories of adverse childhood experiences and relate these to overall and cause-specific mortality in early adult life. Methods: For this population-based cohort study, we used unselected annually updated data from Danish nationwide registers covering more than 1 million children born between 1980 and 1998. We distinguished between three different dimensions of childhood adversities: poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics such as maternal separation. We used a group-based multi-trajectory clustering model to define the different trajectories of children aged between 0 and 16 years. We assessed the associations between these trajectories and mortality rates between 16 and 34 years of age using a Cox proportional hazards model and an Aalen hazards difference model. Findings: Between Jan 1, 1980 and Dec 31, 2015, 2 223 927 children were included in the Danish Life Course cohort. We excluded 1 064 864 children born after 1998, 50 274 children who emigrated before their 16th birthday, and 11 161 children who died before their 16th birthday, resulting in a final sample of 1 097 628 children. We identified five distinct trajectories of childhood adversities. Compared with children with a low adversity trajectory, those who had early-life material deprivation (hazard ratio 1·38, 95% CI 1·27-1·51), persistent deprivation (1·77, 1·62-1·93), or loss or threat of loss (1·80, 1·61-2·00) had a moderately higher risk of premature mortality. A small proportion of children (36 081 [3%]) had multiple adversities within all dimensions and throughout the entire childhood. This group had a 4·54 times higher all-cause mortality risk (95% CI 4·07-5·06) than that of children with a low adversity trajectory, corresponding to 10·30 (95% CI 9·03-11·60) additional deaths per 10 000 person-years. Accidents, suicides, and cancer were the most common causes of death in this high adversity population. Interpretation: Almost half of Danish children in our study experienced some degree of adversity, and this was associated with a moderately higher risk of mortality in adulthood. Among these, a small group of children had multiple adversities across social, health, and family-related dimensions. This group had a markedly higher mortality risk in early adulthood than that of other children, which requires public health attention. Funding: None.

Lancet (London, England) · 155 citationsread the source →