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A multidomain lifestyle intervention to maintain optimal cognitive functioning in Dutch older adults-study design and baseline characteristics of the FINGER-NL randomized controlled trial.

Background: Evidence on the effectiveness of multidomain lifestyle interventions to prevent cognitive decline in older people without dementia is mixed. Embedded in the World-Wide FINGERS initiative, FINGER-NL aims to investigate the effectiveness of a 2-year multidomain lifestyle intervention on cognitive functioning in older Dutch at risk individuals. Methods: Multi-center, randomized, controlled, multidomain lifestyle intervention trial with a duration of 24 months. 1210 adults between 60-79 years old with presence of ≥ 2 modifiable risk factors and ≥ 1 non-modifiable risk factor for cognitive decline were recruited between January 2022 and May 2023 via the Dutch Brain Research Registry and across five study sites in the Netherlands. Participants were randomized to either a high-intensity or a low-intensity intervention group. The multidomain intervention comprises a combination of 7 lifestyle components (physical activity, cognitive training, cardiovascular risk factor management, nutritional counseling, sleep counseling, stress management, and social activities) and 1 nutritional product (Souvenaid®) that could help maintain cognitive functioning. The high-intensity intervention group receives a personalized, supervised and hybrid intervention consisting of group meetings (on-site and online) and individual sessions guided by a trained lifestyle coach, and access to a digital intervention platform that provides custom-made training materials and selected lifestyle apps. The low-intensity intervention group receives bi-monthly online lifestyle-related health advice via the digital intervention platform. Primary outcome is 2-year change on a cognitive composite score covering processing speed, executive function, and memory. Results: Within 17 months, participant recruitment has been successfully completed (N = 1210; mean age: 67.7 years (SD: 4.6); 64% female). Modifiable risk factors commonly present at baseline were physical inactivity (89%), low mental/cognitive activity (50%), low social engagement (39%), hypertension (39%) and high alcohol consumption (39%). The mean body mass index of participants was 28.3 (SD: 4.2) and the total serum cholesterol was 5.4 mmol/L (SD: 1.2). Conclusions: Baseline lifestyle and clinical measurements showed successful recruitment of participants with sufficient potential for prevention. Results of FINGER-NL will provide further insight into the efficacy of a multidomain lifestyle intervention to prevent cognitive decline in older adults. Trial registration: ClinicalTrials.gov (ID: NCT05256199)/2022-01-11.

Alzheimer's research & therapy · randomised controlled trial · 24 citationsread the source →

Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study.

Background: Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety. Methods: In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in eight countries and enrolled within 16 h of presentation. Patients were randomly assigned, in a double-blind manner via a telephone-based interactive voice response system, to standard care plus 48-h intravenous infusion of placebo (n=62) or relaxin 10 microg/kg (n=40), 30 microg/kg (n=43), 100 microg/kg (n=39), or 250 microg/kg (n=50) per day. Several clinical endpoints were explored to assess whether intravenous relaxin should be pursued in larger studies of acute heart failure, to identify an optimum dose, and to help to assess endpoint selection and power calculations. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00520806. Findings: In the modified intention-to-treat population, 61 patients were assessed in the placebo group, 40 in the relaxin 10 microg/kg per day group, 42 in the relaxin 30 microg/kg per day group, 37 in the relaxin 100 microg/kg per day group, and 49 in the relaxin 250 microg/kg per day group. Dyspnoea improved with relaxin 30 microg/kg compared with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0.044) and visual analogue scale through day 14 (8214 mm x h [SD 8712] vs 4622 mm x h [9003]; p=0.053). Length of stay was 10.2 days (SD 6.1) for relaxin-treated patients versus 12.0 days (7.3) for those given placebo, and days alive out of hospital were 47.9 (10.1) versus 44.2 (14.2). Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced with relaxin (2.6% [95% CI 0.4-16.8] vs 17.2% [9.6-29.6]; p=0.053). The number of serious adverse events was similar between groups. Interpretation: When given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favourable relief of dyspnoea and other clinical outcomes, with acceptable safety.

Lancet (London, England) · randomised controlled trial · 314 citationsread the source →

Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis.

Objective: To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. Study selection: Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. Data extraction: Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months after hospital discharge, and beyond 6 months after discharge. Data synthesis: Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months after discharge were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 15–45%); and reduced exercise capacity (mean 6-min walking distance 461 m, CI 450–473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 31–47%), depression (33%, 95% CI 20–50%) and anxiety (30%, 95% CI 10–61) beyond 6 months after discharge were considerable. Low scores on Short-Form 36 were identified beyond 6 months after discharge. Conclusion: Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.

Journal of rehabilitation medicine · meta-analysis · 418 citationsread the source →

Group trauma-focused cognitive-behavioural therapy with former child soldiers and other war-affected boys in the DR Congo: a randomised controlled trial.

Background: The Democratic Republic of Congo (DRC) has been home to the world's deadliest conflict since World War II and is reported to have the largest number of child soldiers in the world. Despite evidence of the debilitating impact of war, no group-based mental health or psychosocial intervention has been evaluated in a randomised controlled trial for psychologically distressed former child soldiers. Method: A randomised controlled trial involving 50 boys, aged 13-17, including former child soldiers (n = 39) and other war-affected boys (n = 11). They were randomly assigned to an intervention group, or wait-list control group. The intervention group received a 15-session, group-based, culturally adapted Trauma-Focused Cognitive-Behavioural Therapy (TF-CBT) intervention. Assessment interviews were completed at baseline, postintervention and 3-month follow-up (intervention group). Results: Analysis of Covariance (ANCOVA) demonstrated that, in comparison to the wait-list control group, the TF-CBT intervention group had highly significant reductions in posttraumatic stress symptoms, overall psychosocial distress, depression or anxiety-like symptoms, conduct problems and a significant increase in prosocial behaviour (p < .001 for all). Effect sizes were higher when former child soldier scores were separated for sub-analysis. Three-month follow-up of the intervention group found that treatment gains were maintained. Conclusions: A culturally modified, group-based TF-CBT intervention was effective in reducing posttraumatic stress and psychosocial distress in former child soldiers and other war-affected boys.

Journal of child psychology and psychiatry, and allied disciplines · randomised controlled trial · 105 citationsread the source →

The Impact of Long COVID-19 on Mental Health: Observational 6-Month Follow-Up Study.

Background: The psychological impact of COVID-19 can be substantial. However, knowledge about long-term psychological outcomes in patients with COVID-19 is scarce. Objective: In this longitudinal, observational study, we aimed to reveal symptoms of posttraumatic stress disorder (PTSD) and symptoms of anxiety and depression up to 6 months after the onset of COVID-19-related symptoms in patients with confirmed COVID-19 and persistent complaints. To demonstrate the impact in nonhospitalized patients, we further aimed to compare these outcomes between nonhospitalized and hospitalized patients. Methods: Demographics, symptoms of PTSD (Trauma Screening Questionnaire [TSQ] ≥6 points) and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS] ≥8 points) were assessed at 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID-19 peer support groups. Results: Data from 239 patients with confirmed COVID-19 (198/239, 82.8% female; median age: 50 [IQR 39-56] years) were analyzed. At the 3-month follow-up, 37.2% (89/239) of the patients had symptoms of PTSD, 35.6% (85/239) had symptoms of anxiety, and 46.9% (112/239) had symptoms of depression, which remained high at the 6-month follow-up (64/239, 26.8%, P=.001; 83/239, 34.7%, P=.90; 97/239, 40.6%, P=.08, respectively; versus the 3-month follow-up). TSQ scores and HADS anxiety and depression scores were strongly correlated at the 3- and 6-month follow-ups (r=0.63-0.71, P<.001). Symptoms of PTSD, anxiety, and depression were comparable between hospitalized (n=62) and nonhospitalized (n=177) patients. Conclusions: A substantial percentage of patients with confirmed COVID-19 and persistent complaints reported symptoms of PTSD, anxiety, or depression 3 and 6 months after the onset of COVID-19-related symptoms. The prevalence rates of symptoms of PTSD, anxiety, and depression were comparable between hospitalized and nonhospitalized patients and merely improved over time. Health care professionals need to be aware of these psychological complications and intervene on time in post-COVID-19 patients with persistent complaints. Trial registration: Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705.

JMIR mental health · 98 citationsread the source →

Empowerment in adolescents and young adults with cancer: Relationship with health-related quality of life.

Background: The difficulties adolescents and young adults (AYAs) encounter during a cancer experience may result in a reduction in or absence of empowerment. The aims of the current study were to assess levels of empowerment and associated (demographic, clinical, or psychological) factors and examine the association between empowerment and health-related quality of life (HRQOL) among AYA patients with cancer. Methods: Patients aged 18 to 35 years at time of cancer diagnosis and who were seen by 1 of the members of the specialized multidisciplinary AYA team of the Radboud University Medical Center were invited to complete questionnaires regarding empowerment; HRQOL; and sociodemographic, clinical, and psychological characteristics (autonomy, coping, unmet social support needs, and psychological distress). Results: A total of 83 AYA patients completed the questionnaires. The mean age of the participants at the time of diagnosis was 27.5 years. The vast majority had been treated with chemotherapy (86%), had a more advanced stage of disease, and had completed treatment at the time of participation (74%). The mean empowerment level was 154.1 (standard deviation, 17.8) with a range of 114 to 200. Multivariate analysis demonstrated that the autonomy subscales of self-awareness (β = .35), capacity for managing new situations (β = .19), and social support (β = .35) were found to be positively associated with empowerment. Coping difficulties (β = -.19) were found to be negatively associated with empowerment. Empowerment was independently associated with physical (β = .31), psychological (β = .50), social (β = .39), religious (β = .33), and total HRQOL (β = .52; all P<.01). Conclusions: Low levels of empowerment were associated with low levels of autonomy and social support, female sex, and coping difficulties among AYA patients with cancer. Recognizing these patients as candidates for empowerment interventions ultimately could help to improve HRQOL in late adolescence and young adulthood. Cancer 2017;123:4039-47. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cancer · 42 citationsread the source →

Comparison of Racial, Ethnic, and Geographic Location Diversity of Participants Enrolled in Clinic-Based vs 2 Remote COVID-19 Clinical Trials.

Importance: Racial and ethnic diversity among study participants is associated with improved generalizability of clinical trial results and may address inequities in evidence that informs public health strategies. Novel strategies are needed for equitable access and recruitment of diverse clinical trial populations. Objective: To investigate demographic and geographical location data for participants in 2 remote COVID-19 clinical trials with online recruitment and compare with those of a contemporaneous clinic-based COVID-19 study. Design, setting, and participants: This cohort study was conducted using data from 3 completed, prospective randomized clinical trials conducted at the same time: 2 remotely conducted studies (the Early Treatment Study and Hydroxychloroquine COVID-19 Postexposure Prophylaxis [PEP] Study) and 1 clinic-based study of convalescent plasma (the Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study). Data were collected from March to August 2020 with 1 to 28 days of participant follow-up. All studies had clinical sites in Seattle, Washington; the 2 remote trials also had collaborating sites in New York, New York; Syracuse, New York; Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; New Orleans, Louisiana; and Los Angeles, California. Two remote trials with inclusive social media strategies enrolled 929 participants with recent SARS-CoV-2 exposure (Hydroxychloroquine COVID-19 PEP Trial) and 231 participants with COVID-19 infection (Early Treatment Study); the clinic-based Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study enrolled 250 participants with recent COVID-19 infection. Data were analyzed from April to August 2021. Interventions: Remote trials used inclusive social media strategies and clinician referral for recruitment and telehealth, courier deliveries, and self-collected nasal swabs for remotely conducted study visits. For the clinic-based study, participants were recruited via clinician referral and attended in-person visits. Main outcomes and measures: Google Analytics data were used to measure online participant engagement and recruitment. Participant demographics and geographical location data from remote trials were pooled and compared with those of the clinic-based study. Statistical comparison of demographic data was limited to participants with COVID infections (ie, those in the remotely conducted Early Treatment Study vs those in the clinic-based study) to improve accuracy of comparison given that the Hydroxychloroquine COVID-19 PEP Trial enrolled participants with COVID-19 exposures and thus had different enrollment criteria. Results: A total of 1410 participants were included. Among 1160 participants in remote trials and 250 participants in the clinic-based trial, the mean (range) age of participants was 39 (18-80) years vs 50 (19-79) years and 676 individuals (58.3%) vs 131 individuals (52.4%) reported female sex. The Early Treatment Study with inclusive social media strategies enrolled 231 participants in 41 US states with increased rates of racial, ethnic, and geographic diversity compared with participants in the clinic-based study. Among 228 participants in the remotely conducted Early Treatment Study with race data vs participants in the clinic-based study, 39 individuals (17.1%) vs 1 individual (0.4%) identified as Alaska Native or American Indian, 11 individuals (4.8%) vs 22 individuals (8.8%) identified as Asian, 26 individuals (11.4%) vs 4 individuals (1.6%) identified as Black, 3 individuals (1.3%) vs 1 individual identified as Native Hawaiian or Pacific Islander, 117 individuals (51.3%) vs 214 individuals (85.6%) identified as White, and 32 individuals (14.0%) vs 8 individuals (3.2%) identified as other race (P < .001). Among 230 individuals in the Early Treatment Study vs 236 individuals in the clinic-based trial with ethnicity data, 71 individuals (30.9%) vs 11 individuals (4.7%) identified as Hispanic or Latinx (P<.001). There were 29 individuals in the Early Treatment Study with nonurban residences (ie, rural, small town, or peri-urban; 12.6%) vs 6 of 248 individuals in the clinic-based trial with residence data (2.4%) (P < .001). In remote trial online recruitment, the highest engagement was with advertisements on social media platforms; among 125 147 unique users with age demographics who clicked on online recruitment advertisements, 84 188 individuals (67.3%) engaged via Facebook. Conclusions and relevance: These findings suggest that remote clinical trials with online advertising may be considered as a strategy to improve diversity among clinical trial participants.

JAMA network open · 48 citationsread the source →

Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden.

Background: Severe obesity in adolescents has a profound impact on current and future health. Metabolic and bariatric surgery (MBS) is increasingly used in adolescents internationally. However, to our knowledge, there are no randomised trials examining the currently most used surgical techniques. Our aim was to evaluate changes in BMI and secondary health and safety outcomes after MBS. Methods: The Adolescent Morbid Obesity Surgery 2 (AMOS2) study is a randomised, open-label, multicentre trial done at three university hospitals in Sweden (located in Stockholm, Gothenburg, and Malmö). Adolescents aged 13-16 years with a BMI of at least 35 kg/m2, who had attended treatment for obesity for at least 1 year, passed assessments from a paediatric psychologist and a paediatrician, and had a Tanner pubertal stage of at least 3, were randomly assigned (1:1) to MBS or intensive non-surgical treatment. Exclusion criteria included monogenic or syndromic obesity, major psychiatric illness, and regular self-induced vomiting. Computerised randomisation was stratified for sex and recruitment site. Allocation was concealed for both staff and participants until the end of the inclusion day, and then all participants were unmasked to treatment intervention. One group underwent MBS (primarily gastric bypass), while the other group received intensive non-surgical treatment starting with 8 weeks of low-calorie diet. The primary outcome was 2-year change in BMI, analysed as intention-to-treat. The trial is registered at ClinicalTrials.gov, NCT02378259. Findings: 500 people were assessed for eligibility between Aug 27, 2014, and June 7, 2017. 450 participants were excluded (397 did not meet inclusion criteria, 39 declined to participate, and 14 were excluded for various other reasons). Of the 50 remaining participants, 25 (19 females and six males) were randomly assigned to receive MBS and 25 (18 females and seven males) were assigned to intensive non-surgical treatment. Three participants (6%; one in the MBS group and two in the intensive non-surgical treatment group) did not participate in the 2-year follow-up, and in total 47 (94%) participants were assessed for the primary endpoint. Mean age of participants was 15·8 years (SD 0·9) and mean BMI at baseline was 42·6 kg/m2 (SD 5·2). After 2 years, BMI change was -12·6 kg/m2 (-35·9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0·2 kg/m2 (0·4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12·4 kg/m2 [95% CI -15·5 to -9·3]; p<0·0001). Five (20%) patients in the intensive non-surgical group crossed over to MBS during the second year. Adverse events (n=4) after MBS were mild but included one cholecystectomy. Regarding safety outcomes, surgical patients had a reduction in bone mineral density, while controls were unchanged after 2 years (z-score change mean difference -0·9 [95% CI -1·2 to -0·6]). There were no significant differences between the groups in vitamin and mineral levels, gastrointestinal symptoms (except less reflux in the surgical group), or in mental health at the 2-year follow-up. Interpretation: MBS is an effective and well tolerated treatment for adolescents with severe obesity resulting in substantial weight loss and improvements in several aspects of metabolic health and physical quality of life over 2 years, and should be considered in adolescents with severe obesity. Funding: Sweden's Innovation Agency, Swedish Research Council Health.

The Lancet. Child & adolescent health · randomised controlled trial · 45 citationsread the source →

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

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

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

Transcutaneous electrical nerve stimulation (TENS) for fibromyalgia in adults.

Background: Fibromyalgia is characterised by persistent, widespread pain; sleep problems; and fatigue. Transcutaneous electrical nerve stimulation (TENS) is the delivery of pulsed electrical currents across the intact surface of the skin to stimulate peripheral nerves and is used extensively to manage painful conditions. TENS is inexpensive, safe, and can be self-administered. TENS reduces pain during movement in some people so it may be a useful adjunct to assist participation in exercise and activities of daily living. To date, there has been only one systematic review in 2012 which included TENS, amongst other treatments, for fibromyalgia, and the authors concluded that TENS was not effective. Objectives: To assess the analgesic efficacy and adverse events of TENS alone or added to usual care (including exercise) compared with placebo (sham) TENS; no treatment; exercise alone; or other treatment including medication, electroacupuncture, warmth therapy, or hydrotherapy for fibromyalgia in adults. Search methods: We searched the following electronic databases up to 18 January 2017: CENTRAL (CRSO); MEDLINE (Ovid); Embase (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS; PEDRO; Web of Science (ISI); AMED (Ovid); and SPORTDiscus (EBSCO). We also searched three trial registries. There were no language restrictions. Selection criteria: We included randomised controlled trials (RCTs) or quasi-randomised trials of TENS treatment for pain associated with fibromyalgia in adults. We included cross-over and parallel-group trial designs. We included studies that evaluated TENS administered using non-invasive techniques at intensities that produced perceptible TENS sensations during stimulation at either the site of pain or over nerve bundles proximal (or near) to the site of pain. We included TENS administered as a sole treatment or TENS in combination with other treatments, and TENS given as a single treatment or as a course of treatments. Data collection and analysis: Two review authors independently determined study eligibility by assessing each record and reaching agreement by discussion. A third review author acted as arbiter. We did not anonymise the records of studies before assessment. Two review authors independently extracted data and assessed risk of bias of included studies before entering information into a 'Characteristics of included studies' table. Primary outcomes were participant-reported pain relief from baseline of 30% or greater or 50% or greater, and Patient Global Impression of Change (PGIC). We assessed the evidence using GRADE and added 'Summary of findings' tables. Main results: We included eight studies (seven RCTs, one quasi-RCT, 315 adults (299 women), aged 18 to 75 years): six used a parallel-group design and two used a cross-over design. Sample sizes of intervention arms were five to 43 participants. Two studies, one of which was a cross-over design, compared TENS with placebo TENS (82 participants), one study compared TENS with no treatment (43 participants), and four studies compared TENS with other treatments (medication (two studies, 74 participants), electroacupuncture (one study, 44 participants), superficial warmth (one cross-over study, 32 participants), and hydrotherapy (one study, 10 participants)). Two studies compared TENS plus exercise with exercise alone (98 participants, 49 per treatment arm). None of the studies measured participant-reported pain relief of 50% or greater or PGIC. Overall, the studies were at unclear or high risk of bias, and in particular all were at high risk of bias for sample size. Only one study (14 participants) measured the primary outcome participant-reported pain relief of 30% or greater. Thirty percent achieved 30% or greater reduction in pain with TENS and exercise compared with 13% with exercise alone. One study found 10/28 participants reported pain relief of 25% or greater with TENS compared with 10/24 participants using superficial warmth (42 °C). We judged that statistical pooling was not possible because there were insufficient data and outcomes were not homogeneous. There were no data for the primary outcomes participant-reported pain relief from baseline of 50% or greater and PGIC.There was a paucity of data for secondary outcomes. One pilot cross-over study of 43 participants found that the mean (95% confidence intervals (CI)) decrease in pain intensity on movement (100-mm visual analogue scale (VAS)) during one 30-minute treatment was 11.1 mm (95% CI 5.9 to 16.3) for TENS and 2.3 mm (95% CI 2.4 to 7.7) for placebo TENS. There were no significant differences between TENS and placebo for pain at rest. One parallel group study of 39 participants found that mean ± standard deviation (SD) pain intensity (100-mm VAS) decreased from 85 ± 20 mm at baseline to 43 ± 20 mm after one week of dual-site TENS; decreased from 85 ± 10 mm at baseline to 60 ± 10 mm after single-site TENS; and decreased from 82 ± 20 mm at baseline to 80 ± 20 mm after one week of placebo TENS. The authors of seven studies concluded that TENS relieved pain but the findings of single small studies are unlikely to be correct. One study found clinically important improvements in Fibromyalgia Impact Questionnaire (FIQ) subscales for work performance, fatigue, stiffness, anxiety, and depression for TENS with exercise compared with exercise alone. One study found no additional improvements in FIQ scores when TENS was added to the first three weeks of a 12-week supervised exercise programme. No serious adverse events were reported in any of the studies although there were reports of TENS causing minor discomfort in a total of 3 participants. The quality of evidence was very low. We downgraded the GRADE rating mostly due to a lack of data; therefore, we have little confidence in the effect estimates where available. Authors' conclusions: There was insufficient high-quality evidence to support or refute the use of TENS for fibromyalgia. We found a small number of inadequately powered studies with incomplete reporting of methodologies and treatment interventions.

The Cochrane database of systematic reviews · meta-analysis · 48 citationsread the source →

Cannabis-based medicines for chronic neuropathic pain in adults.

Background: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. Objectives: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. Search methods: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. Selection criteria: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. Data collection and analysis: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table. Main results: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate. Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed. Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence). Authors' conclusions: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.

The Cochrane database of systematic reviews · meta-analysis · 288 citationsread the source →

Rates of abstinence following psychological or behavioral treatments for binge-eating disorder: Meta-analysis.

Objective: Standardized effect sizes reported in previous meta-analyses of binge-eating disorder (BED) treatment are sometimes difficult to interpret and are criticized for not being a useful indicator of the clinical importance of a treatment. Abstinence from binge eating is a clinically relevant component of a definition of a successful treatment outcome. This meta-analysis estimated the prevalence of patients with BED who achieved binge eating abstinence following psychological or behavioral treatments. Method: This meta-analysis included 39 randomized controlled trials, with 65 treatment conditions and 2,349 patients. Most conditions comprised cognitive-behavioral therapy (n = 40). Pooled event rates were calculated at posttreatment and follow-up using random effects models. Results: The total weighted percentage of treatment-completers who achieved abstinence at posttreatment was 50.9% (95% CI = 43.9, 57.8); this estimate was almost identical at follow-up (50.3%; 95% CI = 43.6, 56.9). The total weighted percentage of patients who achieved abstinence at posttreatment in the intention-to-treat analysis (all randomized patients) was 45.1% (95% CI =40.7, 49.5), and at follow-up it was 42.3% (95% CI =37.5, 47.2). Interpersonal psychotherapy (IPT) produced the highest abstinence rates. Clinician-led group treatments produced significantly higher posttreatment (but not follow-up) abstinence estimates than guided self-help treatments. Neither timeframe for achieving abstinence, assessment type (interview/questionnaire), number of treatment sessions, patient demographics, nor trial quality, moderated the abstinence estimates. Discussion: The present findings demonstrate that 50% of patients with BED do not fully respond to treatment. Continued efforts toward improving eating disorder treatments are needed.

The International journal of eating disorders · meta-analysis · 126 citationsread the source →

Urinary fistulae after partial nephrectomy.

Objective: To report the risk factors and natural history of urinary fistula (UF) after partial nephrectomy (PN), as their incidence has been reported to be 3-6% in large series of PN but there are few reports of the risk factors associated with the development of UF after PN, and the natural history of UF in a large group of patients. Patients and methods: This was a retrospective review of 1118 PN at one tertiary-care institution. Most patients had a drain placed in the perinephric space after surgery. Fifty-two patients were identified as having a UF if they had persistent flank drainage for >14 days after surgery, or presented with evidence of a UF after the drain had been removed. Risk factors for development and the course of the UF are reported. Results: Fifty-two patients developed a UF after PN (4.4%, 95% confidence interval, CI, 3.5-6.1%) The rate of a persistent urine leak (defined as drain fluid consistent with urine for >2 weeks after surgery) was 4.0 (95% CI 2.9-5.3)%. The overall rate of delayed UF presentation was only 0.4 (0.09-0.9)%. Patients who developed a UF had larger tumours (3.5 vs 2.6  cm, P= 0.03), a higher estimated blood loss (400 vs 300  mL, P < 0.001), and longer ischaemia time (50 vs 39  min, P < 0.001) than patients who did not develop a UF. Differences in tumour histology, laterality, multifocality, type of surgery (laparoscopic vs open), and intraoperative collecting system entry were not statistically different in patients who did or did not develop a UF. Patients with tumours of >2.5  cm were twice as likely to develop a UF than patients with tumours of <2.5  cm (P= 0.02). Most patients were managed conservatively with a percutaneous drain until the UF resolved, if they were asymptomatic. Overall, in 36 patients (69%) the fistula resolved with no intervention, while 16 (31%) required intervention. Stenting was the commonest intervention (15%). No patient required re-operative open surgery. Conclusion: The rate of development of UF after PN is low. Tumour size, blood loss and ischaemia time were all associated with the development of a UF. In most patients with a urine leak immediately after surgery the UF will resolve with no intervention, and can be managed conservatively with patience, in the absence of clinical symptoms.

BJU international · 37 citationsread the source →

Establishing Clinically Relevant Severity Levels for the Central Sensitization Inventory.

Objectives: The aim of this study was to create and validate severity levels for the central sensitization inventory (CSI), a valid and reliable patient-reported outcome instrument designed to identify patients whose presenting symptoms may be related to a central sensitivity syndrome (CSS; eg, fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome), with a proposed common etiology of central sensitization (CS). Methods: Based on CSI score means and standard deviations from previously published subject samples, the following CSI severity levels were established: subclinical = 0 to 29; mild = 30 to 39; moderate = 40 to 49; severe = 50 to 59; and extreme = 60 to 100. The concurrent validity of the CSI severity levels was then confirmed in a separate chronic pain patient sample (58% with a CSS diagnosis and 42% without) by demonstrating associations between CSI scores and (1) the number of physician-diagnosed CSSs; (2) CSI score distributions in both CSS and non-CSS patient samples; (3) patient-reported history of CSSs; and (4) patient-reported psychosocial measures, which are known to be associated with CSSs. Results: Compared to the non-CSS patient subsample, the score distribution of the CSS patient subsample was skewed toward the higher severity ranges. CSI mean scores moved into higher severity levels as the number of individual CSS diagnoses increased. Patients who scored in the extreme CSI severity level were more likely to report previous diagnoses of fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, tension/migraine headaches, and anxiety or panic attacks (P < 0.01). CSI severity levels were also associated with patient-reported depressive symptoms, perceived disability, sleep disturbance, and pain intensity (P ≤ 0.02). Conclusion: This study provides support for these CSI severity levels as a guideline for healthcare providers and researchers in interpreting CSI scores and evaluating treatment responsiveness.

Pain practice : the official journal of World Institute of Pain · 199 citationsread the source →

Couple Interventions for Chronic Pain: A Systematic Review.

Objective: Couple interventions for chronic pain have been shown to more effectively reduce pain intensity for individuals with chronic pain (ICPs) than individual behavioral interventions or usual care. This systematic review identified randomized controlled trials of couple interventions to highlight strategies that could be incorporated into psychotherapy with ICPs and their romantic partners. Methods: The authors identified articles reporting randomized controlled trials of couple interventions for chronic pain. Three databases were searched (ie, PubMed, Embase, and PsycInfo), resulting in 18 studies and 22 articles. Results: Couple interventions resulted in statistically significant improvements in pain intensity compared with other conditions in 8% to 40% of the studies depending on the comparator group (i.e., control, individual intervention, another couple intervention), and in statistically significant improvements on a pain-related outcome compared with other conditions in 31% to 50% of the studies depending on the comparator group (ie, control, individual intervention, another couple intervention). Educating couples about pain was the most common strategy (83%). Jointly administered relaxation or meditation skills were included in nearly half of the interventions (48%). Many interventions taught cognitive-behavioral skills jointly to couples (39%) or to the ICP with partner encouragement (30%). Teaching couples how to request and provide assistance (30%), and encouraging partners to avoid reinforcing pain behaviors (39%), occurred frequently. ICPs and their partners were often asked to set goals (30%). Discussion: This review outlined strategies included in couple interventions for chronic pain that are derived from the cognitive-behavioral therapy, acceptance and commitment therapy, and operant behavioral traditions, but delivered relationally. Therapists working with ICPs and their partners may integrate these strategies into their practice to help couples who are managing chronic pain.

The Clinical journal of pain · systematic review · 12 citationsread 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 →

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis.

Background: Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices. Methods: A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106. Findings: Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias. Interpretation: To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of network analysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy. Funding: No funding was received for this research.

Lancet (London, England) · systematic review · 217 citationsread the source →

Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial.

Background: Functional gastrointestinal disorders are common and costly to the health-care system. Most specialist care is provided by a gastroenterologist, but only a minority of patients have improvement in symptoms. Although they have proven to be effective, psychological, behavioural, and dietary therapies are not provided routinely. We aimed to compare the outcome of gastroenterologist-only standard care with multidisciplinary care. Methods: In an open-label, single-centre, pragmatic trial, consecutive new referrals of eligible patients aged 18-80 years with Rome IV criteria-defined functional gastrointestinal disorders were randomly assigned (1:2) to receive gastroenterologist-only standard care or multidisciplinary clinic care. The multidisciplinary clinic included gastroenterologists, dietitians, gut-focused hypnotherapists, psychiatrists, and behavioural (biofeedback) physiotherapists. Randomisation was stratified by Rome IV disorder and whether referred from gastroenterology or colorectal clinic. Outcomes were assessed at clinic discharge or 9 months after the initial visit. The primary outcome was a score of 4 (slightly better) or 5 (much better) on a 5-point Likert scale assessing global symptom improvement. Modified intention-to-treat analysis included all patients who attended at least one clinic visit and who had answered the primary outcome question. This study is registered with ClinicalTrials.gov, NCT03078634. Findings: Between March 16, 2017, and May 10, 2018, 1632 patients referred to the hospital gastrointestinal clinics were screened, of whom 442 were eligible for a screening telephone call and 188 were randomly assigned to receive either standard care (n=65) or multidisciplinary care (n=123). 144 patients formed the modified intention-to-treat analysis (n=46 in the standard-care group and n=98 in the multidisciplinary-care group), 90 (63%) of whom were women. 61 (62%) of 98 patients in the multidisciplinary-care group patients saw allied clinicians. 26 (57%) patients in the standard-care group and 82 (84%) patients in the multidisciplinary-care group had global symptom improvement (risk ratio 1·50 [95% CI 1·13-1·93]; p=0·00045). 29 (63%) patients in the standard-care group and 81 (83%) patients in the multidisciplinary-care group had adequate relief of symptoms in the past 7 days (p=0·010). Patients in the multidisciplinary-care group were more likely to experience a 50% or higher reduction in all Gastrointestinal Symptom Severity Index symptom clusters than were patients in the standard-care group. Of the patients with irritable bowel syndrome, a 50-point or higher reduction in IBS-SSS occurred in 10 (38%) of 26 patients in the standard care group compared with 39 (66%) of 59 patients in the multidisciplinary-care group (p=0·017). Of the patients with functional dyspepsia, a 50% reduction in the Nepean Dyspepsia Index was noted in three (11%) of 11 patients in the standard-care group and in 13 (46%) of 28 in the multidisciplinary-care group (p=0·47). After treatment, the median HADS scores were higher in the standard-care group than in the multidisciplinary-care group (13 [8-20] vs 10 [6-16]; p=0·096) and the median EQ-5D-5L quality of life visual analogue scale was lower in the standard-care group compared with the multidisciplinary-care group (70 [IQR 50-80] vs 75 [65-85]; p=0·0087). The eight SF-36 scales did not differ between the groups at discharge. After treatment, median Somatic Symptom Scale-8 score was higher in the standard-care group than in the multidisciplinary-care group (10 [IQR 7-7] vs 9 [5-13]; p=0·082). Cost per successful outcome was higher in the standard-care group than the multidisciplinary-care group. Interpretation: Integrated multidisciplinary clinical care appears to be superior to gastroenterologist-only care in relation to symptoms, specific functional disorders, psychological state, quality of life, and cost of care for the treatment of functional gastrointestinal disorders. Consideration should be given to providing multidisciplinary care for patients with a functional gastrointestinal disorder. Funding: None.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 89 citationsread the source →

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 →

Compensatory mechanisms activated with intermittent energy restriction: A randomized control trial.

Background & aims: Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL. Methods: 35 adults (age: 39 ± 9 y) with obesity (BMI: 36 ± 4 kg/m2) were randomized to lose a similar weight with an IER (N = 18) or a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall energy restriction (33% reduction) were similar between groups. Body weight/composition, RMR, fasting respiratory quotient (RQ), ExEff (10, 25, and 50 W), subjective appetite ratings (hunger, fullness, desire to eat, and prospective food consumption (PFC)), and appetite-regulating hormones (active ghrelin (AG), cholecystokinin (CCK), total peptide YY (PYY), active glucagon-like peptide-1 (GLP-1), and insulin) were measured before and after WL. Results: Changes in body weight (≈12.5% WL) and composition were similar in both groups. Fasting RQ and ExEff at 10 W increased in both groups. Losing weight, either by IER or CER dieting, did not induce significant changes in subjective appetite ratings. RMR decreased and ExEff at 25 and 50 W increased (P < 0.001 for all) in IER group only. Basal and postprandial AG increased (P < 0.05) in IER group, whereas basal active GLP-1 decreased (P = 0.033) in CER group only. Postprandial CCK decreased in both groups (P = 0.0012 and P = 0.009 for IER and CER groups, respectively). No between group differences were apparent for any of the outcomes. Conclusions: The technique used to achieve energy restriction, whether it is continuous or intermittent, does not appear to modulate the compensatory mechanisms activated by weight loss. Clinical trial registration number: NCT02169778 (the study was registered in clinicaltrial.gov).

Clinical nutrition (Edinburgh, Scotland) · randomised controlled trial · 77 citationsread the source →

Efficacy of Internet-Based Cognitive Behavioral Therapy in Improving Sexual Functioning of Breast Cancer Survivors: Results of a Randomized Controlled Trial.

Purpose We evaluated the effect of Internet-based cognitive behavioral therapy (CBT) on sexual functioning and relationship intimacy (primary outcomes) and body image, menopausal symptoms, marital functioning, psychological distress, and health-related quality of life (secondary outcomes) in breast cancer survivors (BCSs) with a DSM-IV diagnosis of a sexual dysfunction. Patients and Methods We randomly assigned 169 BCSs to either Internet-based CBT or a waiting-list control group. The CBT consisted of weekly therapist-guided sessions, with a maximum duration of 24 weeks. Self-report questionnaires were completed by the intervention group at baseline (T0), midtherapy (T1), and post-therapy (T2) and at equivalent times by the control group. We used a mixed-effect modeling approach to compare the groups over time. Results Compared with the control group, the intervention group showed a significant improvement over time in overall sexual functioning (effect size for T2 [EST2] = .43; P = .031), which was reflected in an increase in sexual desire (EST1 = .48 and EST2 = .72; P < .001), sexual arousal (EST2 = .50; P = .008), and vaginal lubrication (EST2 = .46; P = .013). The intervention group reported more improvement over time in sexual pleasure (EST1 = .32 and EST2 = .62; P = .001), less discomfort during sex (EST1 = .49 and EST2 = .66; P = .001), and less sexual distress (EST2 = .59; P = .002) compared with the control group. The intervention group reported greater improvement in body image (EST2 = .45; P = .009) and fewer menopausal symptoms (EST1 = .39; P = .007) than the control group. No significant effects were observed for orgasmic function, sexual satisfaction, intercourse frequency, relationship intimacy, marital functioning, psychological distress, or health-related quality of life. Conclusion Internet-based CBT has salutary effects on sexual functioning, body image, and menopausal symptoms in BCSs with a sexual dysfunction.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 108 citationsread the source →

Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02).

Background: Various brain stimulation techniques are in use to treat epilepsy. These methods usually require surgical implantation procedures. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive technique to stimulate the left auricular branch of the vagus nerve at the ear conch. Objective: We performed a randomized, double-blind controlled trial (cMPsE02) to assess efficacy and safety of tVNS vs. control stimulation in patients with drug-resistant epilepsy. Methods: Primary objective was to demonstrate superiority of add-on therapy with tVNS (stimulation frequency 25 Hz, n = 39) versus active control (1 Hz, n = 37) in reducing seizure frequency over 20 weeks. Secondary objectives comprised reduction in seizure frequency from baseline to end of treatment, subgroup analyses and safety evaluation. Results: Treatment adherence was 84% in the 1 Hz group and 88% in the 25 Hz group, respectively. Stimulation intensity significantly differed between the 1 Hz group (1.02 ± 0.83 mA) and the 25 Hz group (0.50 ± 0.47 mA; p = 0.006). Mean seizure reduction per 28 days at end of treatment was -2.9% in the 1 Hz group and 23.4% in the 25 Hz group (p = 0.146). In contrast to controls, we found a significant reduction in seizure frequency in patients of the 25 Hz group who completed the full treatment period (20 weeks; n = 26, 34.2%, p = 0.034). Responder rates (25%, 50%) were similar in both groups. Subgroup analyses for seizure type and baseline seizure frequency revealed no significant differences. Adverse events were usually mild or moderate and comprised headache, ear pain, application site erythema, vertigo, fatigue, and nausea. Four serious adverse events were reported including one sudden unexplained death in epilepsy patients (SUDEP) in the 1 Hz group which was assessed as not treatment-related. Conclusions: tVNS had a high treatment adherence and was well tolerated. Superiority of 25 Hz tVNS over 1 Hz tVNS could not be proven in this relatively small study, which might be attributed to the higher stimulation intensity in the control group. Efficacy data revealed results that justify further trials with larger patient numbers and longer observation periods.

Brain stimulation · randomised controlled trial · 206 citationsread the source →

Coaching for primary care physician well-being: A randomized trial and follow-up analysis.

Primary Care Physicians (PCPs) are integral to the health of all people in the U.S. Many PCPs experience burnout, and declines in well-being. We conducted a randomized controlled trial of a six-session positive psychology-based coaching intervention to improve PCP personal and work-related well-being and decrease stress and burnout. Fifty-nine U.S.-based PCPs were randomized into a primary (n = 29) or a waitlisted control group (n = 30). Outcome measures were assessed preintervention, postintervention, and at three and six months post-intervention. Hypotheses 1a-1h were for a randomized controlled trial test of coaching on PCP burnout (a), stress (b), turnover intentions (c), work engagement (d), psychological capital (e), compassion (f), job self-efficacy (g), and job satisfaction (h). Results from 50 PCPs who completed coaching and follow-up assessments indicated significantly decreased burnout (H1a) and increased work engagement (H1d), psychological capital (H1e), and job satisfaction (H1h) for the primary group from pre- to postcoaching, compared to changes between comparable time points for the waitlisted group. Hypotheses 2a-2h were for stability of positive effects and were tested using follow-up data from participants in the primary and waitlisted groups combined. Results from 39 PCPs who completed the intervention and the six-month follow-up indicated that positive changes observed for H1a, H1d, H1e, and H1h were sustained during a six-month follow-up (supporting H2a, H2d, H2e, and H2h). Results indicate that coaching is a viable and effective intervention for PCPs in alleviating burnout and improving well-being. We recommend that employers implement coaching for PCPs alongside systemic changes to work factors driving PCP burnout. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Journal of occupational health psychology · randomised controlled trial · 54 citationsread the source →

Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.

Background: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown. Methods: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months. Results: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups. Conclusions: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).

The New England journal of medicine · randomised controlled trial · 207 citationsread the source →

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

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

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

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.

Background: Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population. Methods: We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100-125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour. This study is registered with ClinicalTrials.gov, number NCT01211405. Findings: Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of -58·3 [SD 9·8] and -44·3 [28·7]; p=0·001) than the 30 mg group (-11·4 [12·7]). Compared with the 30 mg group, Cohen's d effect sizes were large: 2·8 (95% CI 1·19-4·39) for the 75 mg group and 1·1 (0·04-2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100-125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment. Interpretation: Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well tolerated in reducing PTSD symptoms in veterans and first responders. Funding: Multidisciplinary Association for Psychedelic Studies.

The lancet. Psychiatry · randomised controlled trial · 258 citationsread the source →

Neural predictors of treatment response to brain stimulation and psychological therapy in depression: a double-blind randomized controlled trial.

Standard depression treatments, including antidepressant medication and cognitive behavioural therapy (CBT), are ineffective for many patients. Prefrontal transcranial direct current stimulation (tDCS) has been proposed as an alternative treatment, but has shown inconsistent efficacy for depression, and its mechanisms are poorly understood. We recruited unmedicated patients with major depressive disorder (N = 71 approached; N = 39 randomised) for a mechanistic, double-blind, randomized controlled trial consisting of eight weekly sessions of prefrontal tDCS administered to the left prefrontal cortex prior to CBT. We probed (1) whether tDCS improved the efficacy of CBT relative to sham stimulation; and (2) whether neural measures predicted clinical response. We found a modest and non-significant effect of tDCS on clinical outcome over and above CBT (active: 50%; sham: 31.6%; odds ratio: 2.16, 95% CI = 0.59-7.99), but a strong relationship, predicted a priori, between baseline activation during a working memory task in the stimulated prefrontal region and symptom improvement. Repeating our analyses of symptom outcome splitting the sample according to this biomarker revealed that tDCS was significantly superior to sham in individuals with high left prefrontal cortex activation at baseline; we also show 86% accuracy in predicting clinical response using this measure. Exploratory analyses revealed several other regions where activation at baseline was associated with subsequent response to CBT, irrespective of tDCS. This mechanistic trial revealed variable, but predictable, clinical effects of prefrontal tDCS combined with CBT for depression. We have discovered a potential explanation for this variability: individual differences in baseline activation of the region stimulated. Such a biomarker could potentially be used to pre-select patients for trials and, eventually, in the clinic.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · randomised controlled trial · 62 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 →

Impact of lockdown and school closure on children's health and well-being during the first wave of COVID-19: a narrative review.

Background: In the context of containment measures against the COVID-19 pandemic, the aims were to examine the impact of lockdown and school closures on childs' and adolescents' health and well-being and social inequalities in health. Methods: Literature review by searching five databases until November 2020. We included quantitative peer-reviewed studies reporting health and well-being outcomes in children (0-18 years) related to closure measures' impact due to COVID-19. A pair of authors assessed the risk of bias of included studies. A descriptive and narrative synthesis was carried out. Findings: Twenty-two studies, including high-income, middle-income and low-income countries, fulfilled our search criteria and were judged not to have an increased risk of bias. Studies from Australia, Spain and China showed an increase in depressive symptoms and decrease in life satisfaction. A decrease in physical activity and increase in unhealthy food consumption were shown in studies from two countries. There was a decrease in the number of visits to the emergency department in four countries, an increase in child mortality in Cameroon and a decrease by over 50% of immunisations administered in Pakistan. A significant drop of 39% in child protection medical examination referrals during 2020 compared with the previous years was found in the UK, a decrease in allegations of child abuse and neglect by almost one-third due to school closures in Florida, and an increase in the number of children with physical child abuse trauma was found in one centre in the USA. Interpretation: From available reports, pandemic school closure and lockdown have adverse effects on child health and well-being in the short and probably long term. We urge governments to take the negative public health consequences into account before adopting restrictive measures in childhood.

BMJ paediatrics open · review · 94 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Social epidemiology is defined as the study of the distribution of health outcomes and their social determinants (1). It builds on the classic epidemiologic triangle of host, agent, and environment to focus explicitly on the role of social determinants in infectious disease transmission and progression. These determinants are the “features of and pathways by which societal conditions affect health” (2, p. 697). Early studies of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) focused on individual characteristics and behaviors in determining HIV risk, an approach that Fee and Krieger (3) refer to as “biomedical individualism.” Biomedical individualism is the basis of risk factor epidemiology; by contrast, the social epidemiology perspective emphasizes social conditions as fundamental causes of disease (4) (table 1). Social epidemiologists examine how persons become exposed to risk or protective factors and under what social conditions individual risk factors are related to disease. Social factors are thus the focus of analysis and are not simply adjusted for as potentially confounding factors or used as proxies for unavailable individual-level data. Social factors are indeed critical to understanding nonuniform infectious disease patterns that emerge as a result of the dependent nature of disease transmission or the idea that an outcome in one person is dependent upon outcomes and exposures in others (5, 6). Contact patterns that enhance HIV/AIDS vulnerability may be conceptualized at multiple levels. Figure 1 distinguishes determinants of HIV/AIDS at three levels: individual, social, and structural. Individual factors include biologic, demographic, and behavioral risk factors that may influence the risk of HIV acquisition and disease progression. Social-level factors include critical pathways by which community and network structures link persons to society. These structures are central to understanding the diffusion and differential distribution of HIV/AIDS in population subgroups. Structural-level factors include social and economic factors, as well as laws and policies. These factors, in turn, affect HIV transmission dynamics and the differential distribution of HIV/AIDS. Infectious disease epidemiology provides models of the mechanisms through which social determinants affect HIV transmission (7). For example, the basic reproductive number of an infectious disease, R0 (8), describes secondary infections that arise from a primary infection. In the equation R0 = βCD, β is the probability of infection per contact, C is the number of contacts, and D is the duration of infectivity. The goal of intervention efforts is to reduce the empirical value of these terms by modifying the social conditions under which individual risk factors lead to disease. Examples of factors that affect the component terms of R0 in HIV epidemiology are presented in table 2. In this review, we present existing evidence linking social and structural determinants to HIV/AIDS. In addition, we discuss the implications of these findings for future social epidemiology research on HIV/AIDS as well as the design of more effective HIV/AIDS interventions. We searched the published literature to identify conceptual and empirical research reports on the social epidemiology of HIV/AIDS. Five databases were searched: PsycINFO (American Psychological Association, Washington, DC), PubMed (MEDLINE; National Institutes of Health, Bethesda, Maryland), Social Science Citation Index (Web of Science; Thomson ISI, Stamford, Connecticut), Sociological Abstracts (CSA, Bethesda, Maryland), and Digital Dissertations (ProQuest; UMI, Ann Arbor, Michigan). Searches were designed to include the factors we specified in our framework as social or structural factors (figure 1). Searches were limited to published articles in the English language for the period 1981–2003. The following keywords were included in each search: AIDS/acquired immunodeficiency syndrome, HIV, and epidemiol*. Additional searches were conducted by using combinations of keywords listed in Appendix table 1 corresponding with our framework. We identified four categories of social-level factors of importance to HIV/AIDS epidemiology: cultural context, social networks, neighborhood effects, and social capital. Each uses different conceptual and methodological approaches to examine the effects of social forces on population HIV/AIDS vulnerability. Anthropologist Edward Tylor defined culture as “that complex whole which includes knowledge, belief, art, law, morals, custom, and any other capabilities and habits acquired by man as a member of society” (9, p. 1). Anthropologic and epidemiologic approaches may be integrated in a variety of ways to identify features of the social environment that affect HIV/AIDS risk. One way to explore how the social environment affects HIV/AIDS epidemiology is through the use of mixed research methods. Mixed-methods study designs integrate qualitative and quantitative research methods either sequentially or concurrently (10). In sequential study designs, qualitative methods may be used to explore a topic under study or to explain quantitative epidemiologic findings. Concurrent study designs are meant to confirm, cross-validate, or corroborate findings within a single study. A common type of concurrent mixed methods study is “triangulation,” and this approach has been used extensively in rapid assessments of illicit drug use and HIV/AIDS (11–13). Mixed methods approaches are particularly well suited to the investigation of the often hidden and stigmatizing behavioral and social factors underlying HIV epidemics. One exemplary study combining qualitative methods with quantitative methods was conducted by Beyrer et al. (14) to examine the role of overland heroin trafficking routes in shaping explosive HIV/AIDS epidemics among injection drug users in Southeast Asia. Piecing together data from a variety of sources, including existing epidemiologic data, key informant interviews, and laboratory data, this study revealed that distinct HIV subtypes emerged and recombined along drug trafficking routes originating in Myanmar, one of the world’s largest heroin producers. Along these trafficking routes, communities of injection drug users formed, facilitating the spread of HIV into local communities in Laos, Thailand, Vietnam, India, and China (refer, for example, to Panda et al. (15)). This illustration highlights the broader understanding of HIV/AIDS epidemiology that can be achieved by examining the interplay between contextual factors and social and behavioral factors. Investigation of social networks in HIV/AIDS began with the mapping of relationships between one of the first identified AIDS cases, an airline steward, and a large number of his male sex partners in the early 1980s (16). Social network analysis generates measures of the quality, density, position, and structure of relationships between persons, including dyads (partnerships), personal networks (“egocentric” networks), and larger communities (“sociometric” networks) (17, 18). Social networks can influence health outcomes in direct and indirect ways, including 1) social influence, 2) social engagement and participation, 3) prevalence of infectious disease and network member mixing, 4) access to material goods and informational resources, and 5) social support (19). Researchers have demonstrated that patterns in the structure of relationships—rather than differences in individual risk behaviors alone—explain observed HIV patterns (20, 21). The theoretical foundation for examining social networks in HIV research is closely tied to advances in sexually transmitted disease (STD) epidemiology. A key concept from STD epidemiology is the notion of the “core group,” a small group of disease transmitters responsible for a large proportion of cases (22). Friedman et al. (23) found that individuals’ locations within sociometric risk networks were associated with HIV risk among a group of injection drug users in New York City. Other concepts from STD epidemiology, such as partner concurrency, bridging, and mixing patterns, are also important in understanding HIV risk (24–29). Specific network characteristics that have been associated with HIV/AIDS include the size of subgroups and their distribution in a network (23), the centrality of HIV-positive persons within networks (30), partner selection patterns (24, 31–33), and concurrent sexual partnerships (28). Inclusion of these variables has been shown to improve transmission estimates in mathematical modeling (34, 35). Social and normative influences have also been associated with individual HIV risks (36, 37). Network-related social and normative influences are predictive of illicit drug use (38) and condom use behavior (37, 39), highlighting the importance of network-based interventions for HIV prevention (18). Kelly et al. (40, 41) developed a popular opinion leader model that has been effective in reducing HIV risk in several populations, including men who have sex with men and women in low-income housing (42). The success of this model has led to its adaption for international use by the National Institute of Mental Health Collaborative HIV/STD Prevention Trial in China, India, Peru, Russia, and Zimbabwe. Neighborhoods represent the intersection of social networks and physical spatial locations, a confluence Wallace (43) has called the “sociogeographic networks” through which infectious diseases spread. Early interest in the role of neighborhood social environment in disease transmission was sparked by a study in Colorado Springs, Colorado, in which researchers found that gonorrhea was highly focused geographically in core residential neighborhoods (44). Both direct and indirect mechanisms may determine how neighborhood-level factors shape population HIV/AIDS patterns. Direct mechanisms are those that increase the likelihood of a person coming into contact with someone who is HIV positive, for example, through residential segregation and the social isolation of marginalized populations. Indirect mechanisms include those that increase population vulnerability to HIV/AIDS, such as exposure to poor socioeconomic conditions, high unemployment, or the proliferation of illicit drug markets. A range of neighborhood-level factors have been examined in relation to infectious disease, including poverty and income (45, 46), residential segregation (47), and neighborhood physical environment (48, 49). Current research in neighborhood and area effects on health emphasizes the importance of moving beyond documentation of associations to analyze the social and epidemiologic mechanisms through which neighborhood effects might operate (50–54). Increasing concentrations of affluence and poverty are contributing to what demographer Douglas Massey has called “a radical change in the geographic basis of human society” (55, p. 395). Powerful social and economic forces in US cities are increasing neighborhood segregation by class and race/ethnicity (56, 57). Resulting social disorganization and loss of resources and services in poor neighborhoods are in turn shaping HIV/AIDS patterns at the neighborhood level. In a number of studies in New York City, for example, Wallace (58–63) has examined the complex interplay of public policies such as “planned shrinkage” with HIV epidemic dynamics in the Bronx, documenting the “synergy of plagues” that has accompanied rapid social change and the destruction of essential protective networks in poor communities. Using AIDS surveillance data, ecologic studies conducted in various US cities have also consistently found significant associations between income and poverty measures and neighborhood-level AIDS incidence and prevalence rates, and these findings have been consistent across census block groups (46), census tracts (64), and zip codes (65, 66). 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Epidemiologic Reviews · meta-analysis · 394 citationsread the source →

Children's intake of fruit and selected energy-dense nutrient-poor foods is associated with fathers' intake.

Parental dietary intake, lifestyle behavior, and parenting style influence a child's weight status. Few studies have examined associations between parent-child dietary intake, or specific father-child associations. This cross-sectional study examined associations between father-child dietary intakes of fruit, vegetables, and selected energy-dense nutrient-poor foods. The study population consisted of overweight fathers with 50 father-child dyads included in the analysis; median (interquartile range) age of fathers was 39±8.0 years; body mass index was 32.7±5.3; and their primary school-aged children (n=50) (54% boys aged 8.5±3.0 years, body mass index z score 0.6±1.6) who had been targeted to participate in the Healthy Dads, Healthy Kids pilot trial in the Hunter region, New South Wales, Australia in 2008. Dietary intakes of fathers and children were assessed using validated food frequency questionnaires, with mothers reporting their child's food intake. Descriptive statistics were reported and Spearman's rank order correlations used to test the strength of associations between father-child intakes. Fathers' median (interquartile range) daily fruit and vegetable intakes were 0.9 (1.5) and 2.2 (1.3) servings/day, respectively, whereas children consumed 2.1 (2.4) fruit and 2.9 (2.1) vegetable servings/day. Moderately-strong positive correlations were found between father-child fruit intakes (r=0.40, P<0.01), cookies (r=0.54, P<0.001), and potato chips (r=0.33, P<0.05). There were no associations between intakes of vegetables, ice cream, chocolate, or french fries (P>0.05). Children's intakes of fruit and some energy-dense nutrient-poor foods but not vegetables were related to their father's intakes. The targeting of fathers should be tested in experimental studies as a potential strategy to improve child and family eating habits.

Journal of the American Dietetic Association · randomised controlled trial · 57 citationsread the source →

Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials.

Background: Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals. We did a phase II study to establish efficacy and physiological mechanism, and a phase III study to confirm efficacy of the melatonin agonist tasimelteon (VEC-162) for treatment of transient insomnia associated with shifted sleep and wake time. Methods: We undertook phase II and phase III randomised, double-blind, placebo-controlled, parallel-group studies. In a phase II study, 39 healthy individuals from two US sites were randomly assigned to tasimelteon (10 [n=9], 20 [n=8], 50 [n=7], or 100 mg [n=7]) or placebo (n=8). We monitored individuals for 7 nights: 3 at baseline, 3 after a 5-h advance of sleep-wake schedule with treatment before sleep, and 1 after treatment; we measured plasma melatonin concentration for circadian phase assessment. In a phase III study, 411 healthy individuals from 19 US sites, who had transient insomnia induced in a sleep clinic by a 5-h advance of the sleep-wake schedule and a first-night effect in a sleep clinic, were given tasimelteon (20 [n=100], 50 [n=102], or 100 mg [n=106]) or placebo (n=103) 30 min before bedtime. Prespecified primary efficacy outcomes were polysomnographic sleep efficiency (phase II study), latency to persistent sleep (phase III study), and circadian phase shifting (phase II study). Analysis was by intention to treat. Safety was assessed in both studies. These trials are registered with ClinicalTrials.gov, numbers NCT00490945 and NCT00291187. Findings: In the phase II study, tasimelteon reduced sleep latency and increased sleep efficiency compared with placebo. The shift in plasma melatonin rhythm to an earlier hour was dose dependent. In the phase III study, tasimelteon improved sleep latency, sleep efficiency, and wake after sleep onset (ie, sleep maintenance). The frequency of adverse events was similar between tasimelteon and placebo. Interpretation: After an abrupt advance in sleep time, tasimelteon improved sleep initiation and maintenance concurrently with a shift in endogenous circadian rhythms. Tasimelteon may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders.

Lancet (London, England) · randomised controlled trial · 140 citationsread the source →

Effectiveness of group acceptance and commitment therapy for fibromyalgia: a 6-month randomized controlled trial (EFFIGACT study).

In the last decade, there has been burgeoning interest in the effectiveness of third-generation psychological therapies for managing fibromyalgia (FM) symptoms. The present study examined the effectiveness of acceptance and commitment therapy (ACT) on functional status as well as the role of pain acceptance as a mediator of treatment outcomes in FM patients. A total of 156 patients with FM were enrolled at primary health care centers in Zaragoza, Spain. The patients were randomly assigned to a group-based form of ACT (GACT), recommended pharmacological treatment (RPT; pregabalin + duloxetine), or wait list (WL). The primary end point was functional status (measured with the Fibromyalgia Impact Questionnaire, FIQ). Secondary end points included pain catastrophizing, pain acceptance, pain, anxiety, depression, and health-related quality of life. The differences between groups were calculated by linear mixed-effects (intention-to-treat approach) and mediational models through path analyses. Overall, GACT was statistically superior to both RPT and WL immediately after treatment, and improvements were maintained at 6months with medium effect sizes in most cases. Immediately after treatment, the number needed to treat for 20% improvement compared to RPT was 2 (95% confidence interval 1.2-2.0), for 50% improvement 46, and for achieving a status of no worse than mild impaired function (FIQ total score <39) also 46. Unexpectedly, 4 of the 5 tested path analyses did not show a mediation effect. Changes in pain acceptance only mediated the relationship between study condition and health-related quality of life. These findings are discussed in relation to previous psychological research on FM treatment.

Pain · randomised controlled trial · 100 citationsread the source →

Association of Early-Life Antibiotic Use and Protective Effects of Breastfeeding: Role of the Intestinal Microbiota.

Importance: Long duration of breastfeeding is known to reduce the frequency of infections and the risk of overweight, both of which are prevalent health problems among children, but the mechanisms are unclear. Objectives: To test whether early-life antibiotic use in children prevents the beneficial long-term effects of breastfeeding on weight development and lifetime antibiotic use, and to investigate whether the duration of breastfeeding is associated with long-term microbiota development. Design, setting, and participants: Retrospective cohort study, conducted from June 2015 to December 2015, of the association between the duration of breastfeeding and lifetime antibiotic use by children as well as body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) z score in a cohort of 226 healthy children aged 2 to 6 years attending day care at the study area in northern Finland and participating in a probiotic trial from October 1, 2009, through April 30, 2010. Fecal microbiota composition analysis was performed in a subcohort of 42 of these children. Exposures: Duration of breastfeeding and the number of different antibiotic courses purchased for the child. Main outcomes and measures: The BMI z score, lifetime antibiotic use after weaning, and fecal microbiota composition. Results: A total of 226 children (mean [SD] age, 55 [1.4] months; 54% male) were included in the study. Among the 113 children with no antibiotics before weaning, each month of breastfeeding decreased the mean number of postweaning antibiotic courses by 5% (95% CI, 2% to 8%; P = .001) and mean BMI z scores by 0.08 unit (95% CI, 0.04 to 0.11; P < .001). Among the 113 early-life antibiotic users, the effect of breastfeeding on postweaning antibiotic use was borderline significant (estimated 4% decrease per month; 95% CI, 0% to 7%; P = .04) and the effect on BMI z score disappeared (estimated 1% increase; 95% CI, -3% to 5%; P = .50). In the subcohort of 42 children with fecal microbiota composition analysis, the children with short breastfeeding duration (0-6 months) and no early-life antibiotic use or with long breastfeeding duration (8-16 months) and early-life use of antibiotics had a significantly lower abundance of Bifidobacterium (by 55%; 95% CI, 43% to 87%; P = .006; and 39%, 95% CI, 30% to 68%; P < .001, respectively) and Akkermansia (by 71%; 95% CI, 28% to 87%; P = .008; and 69%; 95% CI, 22% to 90%; P = .02, respectively) compared with those with long duration of breastfeeding and no early-life antibiotics. Conclusions and relevance: Antibiotic use in a child during breastfeeding may weaken the beneficial effects of long breastfeeding duration. The results suggest that particularly the long-term metabolic benefits of breastfeeding are conveyed by the intestinal microbiota.

JAMA pediatrics · clinical trial · 75 citationsread the source →

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

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

European urology · clinical trial · 222 citationsread the source →

Mindfulness meditation for younger breast cancer survivors: A randomized controlled trial

BACKGROUND: Premenopausal women diagnosed with breast cancer are at risk for psychological and behavioral disturbances after cancer treatment. Targeted interventions are needed to address the needs of this vulnerable group. METHODS: This randomized trial provided the first evaluation of a brief, mindfulness-based intervention for younger breast cancer survivors designed to reduce stress, depression, and inflammatory activity. Women diagnosed with early stage breast cancer at or before age 50 who had completed cancer treatment were randomly assigned to a 6-week Mindful Awareness Practices (MAPS) intervention group (n = 39) or to a wait-list control group (n = 32). Participants completed questionnaires before and after the intervention to assess stress and depressive symptoms (primary outcomes) as well as physical symptoms, cancer-related distress, and positive outcomes. Blood samples were collected to examine genomic and circulating markers of inflammation. Participants also completed questionnaires at a 3-month follow-up assessment. RESULTS: In linear mixed models, the MAPS intervention led to significant reductions in perceived stress (P = .004) and marginal reductions in depressive symptoms (P = .094), as well as significant reductions in proinflammatory gene expression (P = .009) and inflammatory signaling (P = .001) at postintervention. Improvements in secondary outcomes included reduced fatigue, sleep disturbance, and vasomotor symptoms and increased peace and meaning and positive affect (P < .05 for all). Intervention effects on psychological and behavioral measures were not maintained at the 3-month follow-up assessment, although reductions in cancer-related distress were observed at that assessment. CONCLUSIONS: A brief, mindfulness-based intervention demonstrated preliminary short-term efficacy in reducing stress, behavioral symptoms, and proinflammatory signaling in younger breast cancer survivors.

Cancer · randomised controlled trial · 395 citationsread the source →

Pharmacist intervention to improve medication adherence in heart failure: a randomized trial.

Background: Patients with heart failure who take several prescription medications sometimes have poor adherence to their treatment regimens. Few interventions designed to improve adherence to therapy have been rigorously tested. Objective: To determine whether a pharmacist intervention improves medication adherence and health outcomes compared with usual care for low-income patients with heart failure. Design: Randomized, controlled trial conducted from February 2001 to June 2004. Setting: University-affiliated, inner-city, ambulatory care practice. Patients: 314 low-income patients 50 years of age or older with heart failure confirmed by their primary care physician. Intervention: Patients were randomly assigned to intervention (39% [n = 122]) or usual care (61% [n = 192]) groups and were followed for 12 months. A pharmacist provided a 9-month multilevel intervention, with a 3-month poststudy phase. An interdisciplinary team of investigators designed the intervention to support medication management by patients who have low health literacy and limited resources. Measurements: Primary outcomes were adherence, as measured by using electronic prescription monitors, and exacerbations requiring emergency department care or hospital admission. Secondary outcomes included health-related quality of life, patient satisfaction with pharmacy services, and total direct costs. Results: During the 9-month intervention period, medication adherence was 67.9% and 78.8% in the usual care and intervention groups, respectively (difference, 10.9 percentage points [95% CI, 5.0 to 16.7 percentage points]). However, these salutary effects dissipated in the 3-month postintervention follow-up period, in which adherence was 66.7% and 70.6%, respectively (difference, 3.9 percentage points [CI, -5.9 to 6.5 percentage points]). Medications were taken on schedule 47.2% of the time in the usual care group and 53.1% of the time in the intervention group (difference, 5.9 percentage points [CI, 0.4 to 11.5 percentage points]), but this effect also dissipated at the end of the intervention (48.9% vs. 48.6%, respectively; difference, 0.3 percentage point [CI, -5.9 to 6.5 percentage points]). Emergency department visits and hospital admissions were 19.4% less (incidence rate ratio, 0.82 [CI, 0.73 to 0.93]) and annual direct health care costs were lower ($-2960 [CI, $-7603 to $1338]) in the intervention group. Limitations: Because electronic monitors were used to ascertain adherence, patients were not permitted to use medication container adherence aids. The intervention involved 1 pharmacist and a single study site that served a large, indigent, inner-city population of patients. Because the intervention had several components, intervention effects could not be attributed to a single component. Conclusions: A pharmacist intervention for outpatients with heart failure can improve adherence to cardiovascular medications and decrease health care use and costs, but the benefit probably requires constant intervention because the effect dissipates when the intervention ceases. ClinicalTrials.gov registration number: NCT00388622.

Annals of internal medicine · randomised controlled trial · 329 citationsread the source →

A prospective randomized controlled trial of dynamic versus static progressive elbow splinting for posttraumatic elbow stiffness.

Background: Both dynamic and static progressive (turnbuckle) splints are used to help stretch a contracted elbow capsule to regain motion after elbow trauma. There are advocates of each method, but no comparative data. This prospective randomized controlled trial tested the null hypothesis that there is no difference in improvement of motion and Disabilities of the Arm, Shoulder and Hand (DASH) scores between static progressive and dynamic splinting. Methods: Sixty-six patients with posttraumatic elbow stiffness were enrolled in a prospective randomized trial: thirty-five in the static progressive and thirty-one in the dynamic cohort. Elbow function was measured at enrollment and at three, six, and twelve months later. Patients completed the DASH questionnaire at enrollment and at the six and twelve-month evaluation. Three patients asked to be switched to static progressive splinting. The analysis was done according to intention-to-treat principles and with use of mean imputation for missing data. Results: There were no significant differences in flexion arc at any time point. Improvement in the arc of flexion (dynamic versus static) averaged 29° versus 28° at three months (p = 0.87), 40° versus 39° at six months (p = 0.72), and 47° versus 49° at twelve months after splinting was initiated (p = 0.71). The average DASH score (dynamic versus static) was 50 versus 45 points at enrollment (p = 0.52), 32 versus 25 points at six months (p < 0.05), and 28 versus 26 points at twelve months after enrollment (p = 0.61). Conclusions: Posttraumatic elbow stiffness can improve with exercises and dynamic or static splinting over a period of six to twelve months, and patience is warranted. There were no significant differences in improvement in motion between static progressive and dynamic splinting protocols, and the choice of splinting method can be determined by the patients and their physicians.

The Journal of bone and joint surgery. American volume · randomised controlled trial · 47 citationsread the source →

Effects of nurse home visitation on cigarette smoking, pregnancy outcomes and breastfeeding: a randomized controlled trial.

Objective: antenatal smoking is more prevalent among young women with low socio-economic status. The aim of our study is to assess whether the VoorZorg programme, compared to usual care, is effective in reducing cigarette smoking among young high risk pregnant women. Furthermore, the effect of VoorZorg on pregnancy outcomes and on breast feeding will be described. Design: a randomised controlled trial of VoorZorg, a nurse home visitation intervention, was undertaken over a 2½ year period from 2007 to 2009. Data were collected between 16 and 28 weeks gestation, 32 weeks gestation and at two months post partum on cigarette smoking status plus six months post partum for breastfeeding prevalence. Neonatal birth weight and gestation at birth were also collected. Setting: participants living in 20 municipalities in the Netherlands. Participants: 460 pregnant women were recruited by different professionals. Inclusion criteria were age <26 years, ≤28 weeks pregnancy with the first child, low educational level and some knowledge of the Dutch language. Interventions: women in the intervention group received, in addition to usual care, the VoorZorg programme which consisted of 40-60 home visits by specialised nurses from pregnancy until two years after birth. Findings: the percentage of smokers was significantly lower in the intervention group (40%) compared to the control group (48%) during pregnancy (p=0.03) and at two months post birth (49% and 62%; p=0.02). During pregnancy the number of daily cigarettes smoked was reduced in both groups. After birth, the intervention group smoked 50% less cigarettes compared to the control group (C: 8±10; I: 4±7 (mean±standard deviation (SD)), p=0.01). Furthermore, women in the intervention group did not smoke near the baby (C: 2±5; I: 0±0 (mean±SD) p=0.03). Birth weight and gestational age were similar in both groups (C: 3147g, 40 weeks; I: 3144g, 39 weeks (p=0.94, p=0.17)). Significantly more women in the intervention group were still breast feeding their baby at six months post -birth (C: 6%; I: 13%, p=0.04). Key conclusions: VoorZorg seemed to be effective in reducing cigarette smoking and in increasing breastfeeding duration. No effect was found on pregnancy outcomes.

Midwifery · randomised controlled trial · 57 citationsread the source →

Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Despite increasing public health concerns regarding obesity, few safe and effective drug treatments are available. Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants. Methods: Men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA. Participants were prescribed mild hypocaloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB16), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation. Randomisation was done by use of a centralised, computer-generated, web-based system and was stratified by study centre. Co-primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more. The primary analysis included all randomised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug (last observation carried forward). This study is registered with ClinicalTrials.gov, number NCT00532779. Findings: 1742 participants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453 (83%) were included in the primary analysis (n=471; n=471; n=511). Mean change in bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone 32 mg plus bupropion group (p<0.0001 vs placebo) and -5.0% (0.3) in the naltrexone 16 mg plus bupropion group (p<0.0001 vs placebo). 84 (16%) participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (p<0.0001 vs placebo) and 186 (39%) assigned to naltrexone 16 mg plus bupropion (p<0.0001 vs placebo). The most frequent adverse event in participants assigned to combination treatment was nausea (naltrexone 32 mg plus bupropion, 171 participants [29.8%]; naltrexone 16 mg plus bupropion, 155 [27.2%]; placebo, 30 [5.3%]). Headache, constipation, dizziness, vomiting, and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group. A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups. Combination treatment was not associated with increased depression or suicidality events compared with placebo. Interpretation: A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity. Funding: Orexigen Therapeutics.

Lancet (London, England) · randomised controlled trial · 622 citationsread the source →

Index to predict 5-year mortality of community-dwelling adults aged 65 and older using data from the National Health Interview Survey.

Background: Prognostic information is becoming increasingly important for clinical decision-making. Objective: To develop and validate an index to predict 5-year mortality among community-dwelling older adults. Design and participants: A total of 24,115 individuals aged >65 who responded to the 1997-2000 National Health Interview Survey (NHIS) with follow-up through 31 December 2002 from the National Death Index; 16,077 were randomly selected for the development cohort and 8,038 for the validation cohort. Measurements: 39 risk factors (functional measures, illnesses, behaviors, demographics) were included in a multivariable Cox proportional hazards model to determine factors independently associated with mortality. Risk scores were calculated for participants using points derived from the final model's beta coefficients. To evaluate external validity, we compared survival by quintile of risk between the development and validation cohorts. Results: Seventeen percent of participants had died by the end of the study. The final model included 11 variables: age (1 point for 70-74 up to 7 points for >85); male: 3 points; BMI <25: 2 points; perceived health (good: 1 point, fair/poor: 2 points); emphysema: 2 points; cancer: 2 points; diabetes: 2 points; dependent in instrumental activities of daily living: 2 points; difficulty walking: 3 points; smoker-former: 1 point, smoker-current: 3 points; past year hospitalizations-one: 1 point, >2: 3 points. We observed close agreement between 5-year mortality in the two cohorts; which ranged from 5% in the lowest risk quintile to 50% in the highest risk quintile in the validation cohort. Conclusions: This validated mortality index can be used to account for participant life expectancy in analyses using NHIS data.

Journal of general internal medicine · randomised controlled trial · 166 citationsread the source →

Healthy lifestyle and life expectancy at age 30 years in the Chinese population: an observational study.

Background: The improvement of life expectancy is one of the aims of the Healthy China 2030 blueprint. We aimed to investigate the extent to which healthy lifestyles are associated with life expectancy in Chinese adults. Methods: We used the prospective China Kadoorie Biobank (CKB) study to examine the relative risk of mortality associated with individual and combined lifestyle factors (never smoking or quitting not for illness, no excessive alcohol use, being physically active, healthy eating habits, and healthy body shape). Participants with coronary heart disease, stroke, cancer, or missing values for body-mass index were excluded. For analysis of chronic respiratory diseases, participants with chronic obstructive pulmonary disease or asthma were excluded. We estimated the national prevalence of lifestyle factors using data from the China Nutrition and Health Surveillance (CNHS; 2015) and derived mortality rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (2015). All three data sources were combined to estimate the life expectancy of individuals at age 30 years following different levels of lifestyle factors by using the life table method. The cause-specific decomposition of the life expectancy differences was analysed using Arriaga's method. Findings: After the exclusion of CKB participants with coronary heart disease, stroke, cancer, or missing BMI data at baseline, 487 209 were included in the primary analysis. Participants with COPD or asthma at baseline were additionally excluded for chronic respiratory disease-related analysis, leaving 451 233 participants with data available for analysis. Data from 171 127 adults aged 30-84 years from the CNHS 2015 were used to estimate the sex-specific and age-specific prevalence of lifestyle-related factors. There were 42 496 deaths documented over a median follow-up of 11·1 years (IQR 10·2-12·1) in CKB. The adjusted hazard ratios (aHRs) of participants adopting five versus 0-1 low-risk factors was 0·38 (95% CI 0·34-0·43) for all-cause mortality, aHR 0·37 (0·30-0·46) for cardiovascular disease mortality, aHR 0·47 (0·39-0·56) for cancer mortality, and aHR 0·30 (0·14-0·64) for chronic respiratory disease mortality. The life expectancy at age 30 years for individuals with 0-1 low-risk factors was on average 41·7 years (95% CI 41·5-42·0) for men and 47·3 years (46·6-48·0) for women. For individuals with all five low-risk factors, the life expectancy at age 30 was 50·5 years (95% CI 48·5-52·4) for men and 55·4 years (53·5-57·4) for women; meaning a difference of 8·8 years (95% CI 6·8-10·7) for men and 8·1 years (6·5-9·9) for women. The estimated extended life expectancy for men and women was mainly attributable to reduced death from cardiovascular disease (2·4 years [27% of the total extended life expectancy] for men and 3·7 years [46%] for women), cancer (2·6 years [30%] for men and 0·9 years [11%] for women), and chronic respiratory disease (0·6 years [7%] for men and 1·2 years [15%] for women). Interpretation: Our findings suggest that increasing the adoption of these five healthy lifestyle factors through public health interventions could be associated with substantial gains in life expectancy in the Chinese population. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust.

The Lancet. Public health · cohort or longitudinal · 129 citationsread the source →

The Surgeon as the Second Victim? Results of the Boston Intraoperative Adverse Events Surgeons' Attitude (BISA) Study.

Background: An intraoperative adverse event (iAE) is often directly attributable to the surgeon's technical error and/or suboptimal intraoperative judgment. We aimed to examine the psychological impact of iAEs on surgeons as well as the surgeons' attitude about iAE reporting. Study design: We conducted a web-based cross-sectional survey of all surgeons at 3 major teaching hospitals of the same university. The 29-item questionnaire was developed using a systematic closed and open approach focused on assessing the surgeons' personal account of iAE incidence, emotional response to iAEs, available support systems, and perspective about the barriers to iAE reporting. Results: The response rate was 44.8% (n = 126). Mean age of respondents was 49 years, 77% were male, and 83% performed >150 procedures/year. During the last year, 32% recalled 1 iAE, 39% recalled 2 to 5 iAEs, and 9% recalled >6 iAEs. The emotional toll of iAEs was significant, with 84% of respondents reporting a combination of anxiety (66%), guilt (60%), sadness (52%), shame/embarrassment (42%), and anger (29%). Colleagues constituted the most helpful support system (42%) rather than friends or family; a few surgeons needed psychological therapy/counseling. As for reporting, 26% preferred not to see their individual iAE rates, and 38% wanted it reported in comparison with their aggregate colleagues' rate. The most common barriers to reporting iAEs were fear of litigation (50%), lack of a standardized reporting system (49%), and absence of a clear iAE definition (48%). Conclusions: Intraoperative AEs occur often, have a significant negative impact on surgeons' well-being, and barriers to transparency are fear of litigation and absence of a well-defined reporting system. Efforts should be made to support surgeons and standardize reporting when iAEs occur.

Journal of the American College of Surgeons · cohort or longitudinal · 110 citationsread the source →

Prevalence, determinants, and effect on quality of life of freezing of gait in Parkinson disease.

Importance: Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). Objective: To determine the prevalence of FOG in a large group of PD patients, assess its relationship with quality of life and clinical and pharmacological factors, and explore its changes from the off to on conditions in patients with motor fluctuations. Design, setting, and participants: Cross-sectional survey of 683 patients with idiopathic PD. Scores for FOG were missing in 11 patients who were not included in the analysis. Patients were recruited from referral centers and general neurology clinics in public or private institutions in France. Exposure: Patients with FOG were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson's Disease Rating Scale (UPDRS) in the on condition. Item 14 scores for FOG in the off condition were also collected in patients with fluctuating motor symptoms. Main outcomes and measures: Quality of life (measured by the 39-item Parkinson's Disease Questionnaire and 36-Item Short Form Health Survey), anxiety and depression (Hospital Anxiety and Depression Scale), clinical features (UPDRS), and drug consumption. Results: Of 672 PD patients, 257 reported FOG during the onstate (38.2%), which was significantly related to lower quality of life scores (P < .01). Freezing of gait was also correlated with longer PD duration (odds ratio, 1.92 [95% CI, 1.28-2.86]), higher UPDRS parts II and III scores (4.67 [3.21-6.78]), the presence of apathy (UPDRS item 4) (1.94 [1.33-2.82]), a higher levodopa equivalent daily dose (1.63 [1.09-2.43]), and more frequent exposure to antimuscarinics (3.07 [1.35-6.97]) (logistic regression). The FOG score improved from the off to on states in 148 of 174 patients with motor fluctuations (85.1%) and showed no change in 13.8%. The FOG score improved by more than 50% in 43.7% of patients. Greater improvement in the on state was observed in younger patients (r = -0.25; P < .01) with lower UPDRS II and III scores (r = -0.50; P < .01) and no antimuscarinic use (r = -0.21; P < .01). Conclusions and relevance: Freezing of gait in PD patients correlates with poor quality of life, disease severity, apathy, and exposure to antimuscarinics. Dopaminergic therapy improved FOG in most patients with motor fluctuations, especially younger ones with less severe disease and no antimuscarinic use. This finding suggests that quality of life is impaired in PD patients with FOG and that optimizing dopaminergic therapy and avoiding antimuscarinics should be considered.

JAMA neurology · cohort or longitudinal · 254 citationsread the source →

Child's symptom burden and depressive symptoms among caregivers of children with cancers: an argument for early integration of pediatric palliative care.

Background: Childhood cancers evoke various emotional reactions in caregivers which can impair their well-being and roles. Little is known about caregiving and which cancer-associated factors are related to caregiver's depression in resource-restricted settings. We sought to investigate if child's symptom burden is related to depressive symptoms in caregivers. Methods: Seventy-two caregivers and children with cancers were administered questionnaires to elicit socio-demographic and disease-related data. Subsequently, the child's symptoms were profiled with Memorial Symptom Assessment Scale (MSAS 7-12); while screening for depressive symptoms in caregivers was done using the Center for Epidemiologic Studies Depression Scale-Revised (CES-DR). Results: All the caregivers were parents, and largely mothers (83.7%). The mean ages of caregivers and children were 39±2 and 10±2 years respectively. Majority of caregivers (90.3%) were either ignorant or attributed spiritual causation to the cancers. The common symptoms with prevalence >50% in the children included pain, nausea, worry, and lack of energy (LE); symptoms' prevalence ranged from LE (68%) to itching (32%). Approximately, one-third each of the children reported hair and weight loss which were considered 'unusual' in the design of MSAS 7-12. The symptoms showed variability in distress, frequency and intensity. In particular, pain, lack of appetite (LA) and feeling sad (FS) were reported as most burdensome in >50% of the children. More than one-third of caregivers (38.2%) screened positive for significant depressive symptoms. The global symptom burden (r=0.58) and individual symptom correlated positively with depressive symptoms in caregivers (P<0.05). Conclusions: Our findings suggest the need for improved awareness creation on childhood cancers to obviate late presentations and poor access to care. Again, early integration of pediatric palliative care in childhood cancer care to ensure symptom management as well as its extended benefits on caregivers' wellbeing is desirable. The pattern of certain "unusual" symptoms in children with cancer in our work suggests the need to put into consideration 'novel' symptoms which were not captured in existing instruments. Future research on supportive care in pediatric cancers is indicated.

Annals of palliative medicine · review · 63 citationsread the source →

A scoping review of therapies used to treat psychological trauma post perinatal bereavement.

Background: Up to 39% of women who experience perinatal bereavement proceed to develop Post-Traumatic-Stress-Disorder (PTSD), with this large proportion meriting treatment. Before setting-up a treatment service for postnatal women who are experiencing psychological trauma, it is important to identify what therapies have been used in-the-past to address this problem. Aim: To scope for research that has implemented therapies to treat psychological trauma post perinatal bereavement, for potential inclusion in a flexible treatment package. Method: A scoping review mapped coverage, range, and type of research that has reported on prior therapies used to treat psychological trauma post perinatal bereavement. Findings: Due to the dearth of papers that directly addressed perinatal bereavement, we widened the scope of the review to view what treatments had been used to treat psychological trauma post-childbirth. Out of 23 studies that report on effectiveness of therapies used to treat psychological trauma post-childbirth, only 4-focused upon treating PTSD post perinatal bereavement (3 effective/1 ineffective). Successful treatments were reported by Kersting et al. (2013), who found CBT effective at reducing PTSD symptoms post-miscarriage, termination for medical reasons, and stillbirth (n = 33 & n = 115), and Navidian et al. (2s017)) found that 4-sessions of grief-counselling reduced trauma symptoms post-stillbirth in (n = 50) women. One study by Huberty et al. (2020found on-line yoga to be ineffective at reducing PTSD symptoms post-stillbirth. Conclusions: A dearth of research has explored effectiveness of therapies for treating psychological trauma post perinatal bereavement and post-childbirth, with need to develop and test a research informed flexible counselling package.

Journal of reproductive and infant psychology · review · 9 citationsread the source →

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. Am J Physiol Regul Integr Comp Physiol 281: R591-R595, 2001.Link | ISI | Google Scholar3 Aoyagi N, Ohashi K, and Yamamoto Y. Frequency characteristics of long-term heart rate variability during constant-routine protocol. Am J Physiol Regul Integr Comp Physiol 285: R171-R176, 2003.Link | ISI | Google Scholar4 Arora RC, Hirsch GM, Johnson Hirsch K, Hancock Friesen C, and Armour JA. Function of human intrinsic cardiac neurons in situ. Am J Physiol Regul Integr Comp Physiol 280: R1736-R1740, 2001.Link | ISI | Google Scholar5 Barbieri R, Triedman JK, and Saul JP. Heart rate control and mechanical cardiopulmonary coupling to assess central volume: a systems analysis. Am J Physiol Regul Integr Comp Physiol 283: R1210-R1220, 2002.Link | ISI | Google Scholar6 Barrett CJ, Navakatikyan MA, and Malpas SC. Long-term control of renal blood flow: what is the role of the renal nerves? Am J Physiol Regul Integr Comp Physiol 280: R1534-R1545, 2001.Link | ISI | Google Scholar7 Blumberg MS, Knoot TG, and Kirby RF. Neural and hormonal control of arterial pressure during cold exposure in un-anesthetized week-old rats. Am J Physiol Regul Integr Comp Physiol 281: R1514-R1521, 2001.Link | ISI | Google Scholar8 Boyett MR, Kodama I, Honjo H, Arai A, Suzuki R, and Toyama J. Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node. Cardiovasc Res 29: 867-878, 1995.Crossref | PubMed | ISI | Google Scholar9 Braga and of on fluctuations and changes in blood pressure. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and elicited of heart rate variability. 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. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and in heart rate variability. J Physiol | ISI | Google and function and cardiovascular interactions and Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and interval variability in isolated working rat hearts at various conditions and Res | PubMed | Google A, A, and and autonomic of in patients with mild Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Malpas SC. Neural on cardiovascular and Am J Physiol Heart Physiol 2002.Link | ISI | Google and thermoregulation in and rats in a Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and effects on reflex responses to mental stress in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and reflex during orthostatic in Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and and responses to and are in rats. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and and in a by cycle. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of humoral heart rate regulation in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Armour and within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol 285: 2003.Link | ISI | Google Rentero N, A, and McAllen of cardiac vagal motoneurons in rat nucleus ambiguus. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and modulate control of heart rate in conscious rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and central actions of angiotensin to increase arterial pressure. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulate control of renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulation of cardiovascular and autonomic function in role of Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Inhibition of sympathetic responses at birth in by of the paraventricular Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and JP. pattern of during acute and chronic in conscious adult rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Armour and of chronic cardiac on of canine intracardiac neurons in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and levels and circadian rhythm of activity in the a model of Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve response of suprachiasmatic nucleus and Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

Executive functioning deficits in preschool children with Fetal Alcohol Spectrum Disorders.

Executive function (EF) deficit is a hallmark of Fetal Alcohol Spectrum Disorders (FASD), but the vast majority of available evidence comes from school-age children and adolescents. Very little is known about EF during the critical developmental period prior to 6 years of age in FASD. We evaluated EF in 39 children with FASD (3.0-5.5 years) and a comparison group of 50 age-matched, nonexposed controls. Measures included the EF Scale for Early Childhood and a Delay of Gratification task. Compared to age-matched controls, preschool children with FASD had impairments on the EF Scale and showed more impulsivity on the Delay of Gratification task. To confirm the EF Scale finding, FASD group performance was compared to a separate normative dataset (N = 1,400). Those with FASD performed below normal (M = -0.57, SD = 0.92). Within the FASD group, IQ was correlated with the EF Scale (partial r = .60, p = .001) and Delay of Gratification (partial r = .58, p = .005). EF Scale performance did not differ significantly across levels of FASD severity (fetal alcohol syndrome [FAS], partial FAS, or alcohol-related neurobehavioral disorder [ARND]). However, compared to normative data, those with FAS had the largest deficits (M = -0.91 SD from the mean, SE = 0.23), followed by partial FAS (M = -0.66 SD from the mean, SE = 0.26), then ARND (M = -0.36 SD from the mean, SE = 0.20). These novel data show that EF deficits manifest well before the age of 6 years in children with FASD, that they occur across the spectrum, and that EF may be most impaired in children with more severe forms of FASD and/or lower IQs.

Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence · 44 citationsread the source →

Policy vs. Ethics.

Editor's Note: As Catholic ethics increasingly diverge from those of other religious traditions and from secular principles, it is important to explore how-if at all-Catholic physicians and institutions can work with those whose view of life and faith are very different. This article presents not only an historical vision of how the Ethical and Religious Directives came to be, it raises questions about just how Catholics go about moral reasoning when there are competing interests and principles at play. The author of the article, Warren T. Reich, was, at the time it was written, a Senior Research Scholar in Medical Ethics at the Kennedy Center for Bioethics, Georgetown University. He went on to be a founding member of the Kennedy Institute of Ethics. He was also founder and director of the Project for the History of Care, and is Distinguished Research Professor of Religion and Ethics in the Georgetown University Theology Department and Professor Emeritus of Bioethics in the Georgetown University School of Medicine. This article was prepared for delivery at the Annual Meeting of the National Federation of Catholic Physicians' Guilds, New Orleans, November 27. 1971. The issues he raises and the conflicts he perceives are as relevant now as they were 50 years ago. Reich, Warren T. (1972) "Policy vs. Ethics, "The Linacre Quarterly: Vol. 39: No. 1, Article 8. Available at: http://epublications.marquette.edu/lnq/vol39/iss1/8.

The Linacre quarterlyread the source →

Measuring education in the context of health inequalities

Socio-economic inequalities in a wide range of health outcomes are pervasive and enduring.1 Most often, the association between socio-economic indicators and health is inversely graded (commonly known as social gradients in health) so that the higher the socio-economic position (SEP), the lower is the rate of morbidity and mortality. SEP is a broad concept capturing resource- and prestige-based measures.2 To date, educational level/attainment has been commonly used as an indicator of SEP in health inequalities research due to general acceptance that education is easy to measure and unlikely to be affected by diseases that begin in adult life.3 Of note, early-life health gradients in education (i.e. health selection hypothesis or reverse causality) might also exist and needs to be considered.4 Education is less prone to non-response error compared with income or wealth as SEP indicators.3 In most nations, education shapes the future occupational position and earning potential of individuals. However, it is important to keep in mind that in this context, education is only a ‘proxy’ or a probabilistic indicator of social class, status or income.3 Despite perceptions of education as a straightforward measure for social epidemiological purposes, the relationship between education and health is complex, as are the underlying mechanisms, including psychosocial, material and behavioural mechanisms and pathways (Figure 1).3 The psychosocial pathway emphasizes the way in which education provides a means to alleviate the direct and indirect effects of stress related to being lower on the socio-economic hierarchy through psychological and social buffering. The material pathway emphasizes that highly educated adults are more likely to be employed and earn more money, which improves access to tangible material conditions, services and amenities, and assets. The behavioural pathway emphasizes that education can increase health-related knowledge through health literacy, but also provides increased personal control, which in turn can lead to the adoption of healthy behaviours. These pathways are not mutually exclusive. The material resources of daily life across the life course have psychosocial meaning attached to them, one’s experience of psychosocial stress may be associated with health behaviours, etc. Whereas newer advanced epidemiological techniques and wider data availability increase the potential to improve understanding of the association between education and health and its underlying mechanisms, current practices regarding the measurement and operationalization of education as a core indicator of SEP lack the ability to consistently capture and compare the diversity of individual participants’ educational experiences over time. Pathways between education and health Evidence is emerging that traditional education measures (educational qualification or years of schooling) are insufficient to fully understand the relationship between education and health. These traditional measures only focus on quantity and/or credentials and do not capture other facets of education, including the type and quality of education, school environment and dissonant/consonant relationships between family, and school and educational expectations. Traditional measures, mainly assessing early-childhood/adulthood educational experiences, typically neglect the importance of educational experiences throughout the life course based on assuming that education is unlikely to alter after early adulthood. Moreover, the justification for a specific conceptualization of education is often not adequately described. Of note, the choice of education as an SEP indicator and its operationalization often reflect the availability of data rather than any explicit theorization of the possible effect of different measures or categorizations. To further discussion regarding some of the problems with the current approaches to educational measurement in social inequality studies,5–7 our paper takes a different approach by both highlighting the methodological issues and emphasizing the importance of commonly neglected aspects of education in these studies. A widely used measure of education is based on attainment of a qualification or completion of a phase of education, such as primary or high school. Statistically, attainment measures can be dichotomized as having achieved a particular level or not or compared across categories of educational attainment. Some studies convert attainment measures into duration measures by allocating a number of years to each attainment level (e.g. finishing high school is commonly considered to be the equivalent of 12 years of education). Another frequently used education measure is the duration, usually elicited as the number of years and sometimes as the age of leaving school. Years of education has the advantage of being easy to obtain and also offers flexibility for statistical manipulation. It is handled most elegantly and parsimoniously as a continuous variable but additionally lends itself to dichotomous and categorical operationalizations.8 Both attainment and duration measures can be relatively straightforward to acquire in narrow contexts with well-defined educational structures; however, they become more complex when there is ambiguity in educational pathways, especially when comparing across countries.9,10 Literacy measures, which reflect skills obtained through education, are also used depending on the context.11 Literacy can be self-reported or assessed directly.11 Other less commonly used educational measures include latent variable models—using multiple variables to evaluate a construct that cannot be measured directly (e.g. quality of education, academic achievement).12Table 1 summarizes different educational measures. Different educational measures Different educational measures With many continuous variables, we can expect each unit to be of relatively equal worth, even if there is a cumulative effect. This is not the case with education.13 A year of education at age 5 years cannot be expected to be comparable with a year of education at age 15 years. Similarly, a year of education in 1950 likely differs from a year of education in 2020,14 as does a year of education in Syria compared with a year in Sweden. A year of education in a classroom of 50 students is unlikely to be equivalent to a year of education in a classroom of 5. Moreover, using simple counts of years of education as a measure treats all types of education and educational institutions equally. Educational content varies across different subjects, thus a year in an art college is not equal to a year in an engineering school or a year in military academies.14–16 These are all relatively innocuous examples, but we must also consider that these inequalities in a year of education are likely to mirror existing inequalities in society in terms of gender, race/ethnicity, socio-economic and other (dis)advantages.17 A continuous measure of years of education assumes that every year of education contributes equally to a person’s acquired SEP and that time spent in education is more important than educational achievements.13 Due to differences in the structure and organization of courses across educational institutions and countries, it is possible that qualifications with very different levels of complexity require a similar amount of time in education.15 Consequently, measurement of the number of years of education of an individual is not necessarily a good proxy for educational attainment.15 In most cohort studies and surveys educational level is measured using a self-completed questionnaire.7,18 Although few studies have focused on the accuracy of reported education, there is some evidence of inconsistency in reporting educational attainment.14,18 Limited evidence also shows that respondents tend to exaggerate the amount of schooling they have obtained.14 Consistency in measuring and modelling education allows researchers to compare the results from different studies and pool different data sources for within-country or cross-national comparative analysis.19 However, systematic reviews in the field highlight substantial heterogeneity in measuring and operationalizing education.20,21 Educational level does not have universal definitions. One important example in this regard is the definition of low education where researchers use different cut-offs for years of education to define low education, ranging from zero to 12.20 Importantly, results from studies that use different definitions are not comparable. Comparability is particularly essential for cross-national studies.10 For cross-national comparison, educational data need to be harmonized using an internationally comparable education variable.19 Although attempts have been made to implement standardized comparative measures (e.g. harmonization using the International Standard Classification of Education), different studies have used either different standards or implemented them in different ways.8,10,19 Consistency is also important within the same context over time given the potential demographic changes and alterations in the educational system.10 Another important issue that makes comparability generally more difficult is the absence of explicit information about measurement of education and its operationalization. Information on how educational attainment was obtained (self-report, proxy, records), how the number of years were obtained (self-report, extrapolated), how categorization was determined (related to attainment, to years or to literacy) and what was the basis of cut-offs (educational system, population mean, literature, arbitrary) should all be reported but rarely are in practice.20 Measurement of education as an SEP indicator is believed to capture the knowledge-related assets of an individual.13 Educational attainment also captures aspects of social opportunities for education and individual life chances.19 Moreover, educational attainment is strongly associated with attitudes, beliefs, values and behaviours as well as parents’ choices and constraints over how they can influence their children’s SEP.19,22 These highlight that education is a proxy for cultural capital, also captured by other variables such as the number of books in a child’s home.22,23 Some researchers argue that educational level is a proxy for intelligence that further affects health and health inequality24 despite findings from several studies that differences in educational achievements reflect the level of cultural capital and not intelligence.25,26 When interpreting results, it is important to distinguish between these two underlying hypothesized constructs. Education systems change and evolve in most nations over time. Thus, the meaning of educational levels and implications of educational achievements vary among different birth cohorts.13 For instance, comparing educational levels of participants who attended school before or during the First World War with those who attended school after the Second World War is complicated as they have been educated under different circumstances with varying access to educational opportunities beyond compulsory education.15 Moreover, most of today’s older adults in Europe and the UK left school at the minimum age with no academic qualifications; thus, older cohorts will be over-represented among those classified as having low education.27 When using duration measures, researchers should consider changes to the length of compulsory education over time.27 Therefore, studies that include participants from several birth cohorts should consider specific birth cohort effects to avoid bias in their results. From 1970 onwards, gender/sex differences in educational attainment levels, favouring male over female, have declined sharply in nearly all high-income countries (HICs) and, in some, have been eliminated or even reversed.28 However, the socio-economic impact of education on health is still gender-related; the education–occupation–wage relationship continues to favour men, with the economic returns for a given level of education higher for men than for women.2 Nevertheless, based on the resource substitution theory, educational level may have a greater impact on the health of women than men.5,29 This theory highlights that the less there is of one resource (e.g. earnings, power), the more important another will be (e.g. education), or the presence of one resource makes the absence of another less harmful.29 This impact on health has been observed with differences in mortality by educational level across age groups that are more pronounced in men than in women.30 Of note, it is important to highlight that maternal and paternal education might have different impacts on their offspring health. For instance, a 2021 global systematic review and meta-analysis highlighted that maternal education is a stronger predictor of child mortality than paternal education.31 The interactions between race, ethnicity and SEP should always be considered in interpreting the underlying mechanisms involved in education inequalities in health for several reasons. First, it has been shown that educational attainment is generally lower among ethnic minority populations.32 Apart from a lack of English-language proficiency, another important reason why ethnic minorities may have lower attendance or completion rates could be a lack of cultural competence in dominant educational paradigms (e.g. imposing cultural values and ignoring ancestral knowledge). Moreover, ethnic minority populations tend to receive a different amount of education than privileged population groups in a society and the quality of education received may also differ. Additionally, racial segregation in schools along with residential racial segregation or disproportional allocation of ethnic minority students into low-ability or non-college preparatory classes are primary mechanisms underlying socio-economic differences for many ethnic minority groups.32 It has been shown that sometimes attainment or duration measures are less appropriate than other measures for specific ethnic groups, likely due to differences in the quality of educational offerings. For instance, studies suggest that the quality of education is a more important consideration among minoritized people rather than years spent in education.33,34 Moreover, in some lower- and middle-income countries (LMICs) where compulsory education is either non-existent or not binding, just the fact of an adolescent attending school (or not) might be more relevant. Third, ethnic minorities do not experience the same returns (e.g. economic returns) from education as dominant groups (the diminishing returns hypothesis).18 These differences are not only due to variations in educational quality, but also due to structural inequalities in society.35 Thus, weaker educational gradients among ethnic minorities, particularly women, could be due to smaller economic returns from education among these groups than privileged population groups.5 Finally, the extent to which education reflects socio-economic wellbeing may depend on the proportions of immigrants in different ethnic communities and whether they obtained their education outside or inside their host country, as the value attached to qualifications is often country-specific.13,36 Most SEP measures in common usage, including education, are developed by researchers from HICs.13,18 It is therefore important to question the appropriateness of imposing educational measures from HIC, with their accompanying cultural and values systems, on LMICs. Educational systems, with their idiosyncratic institutions and certificates and differential funding between public and private schools, differ substantially across countries, so common measures of education and their operationalization might not be appropriate in different contexts.19 This highlights the importance of using nation/country-specific educational measures in health inequality studies. Not paying attention to these important contextual details prevents us from capturing health inequalities by educational level. However, there is a conflict between the need for standardization for comparability and country-level appropriateness of educational measures. Researchers need to decide which is more appropriate for their research question and perhaps sacrifice one or the other, accepting and acknowledging the limitations in order to interpret their findings in this context. Researchers also need to account for characteristics specific to different populations. For example, reverse causality can be a factor, with the limiting effect of ill health in childhood on educational attainment a possible important consideration in LMIC.11 Of note, cohort effects and gender differences are likely to be of particular importance in LMIC compared with HICs. Currently, little is known about specific elements of education that might influence health. Measuring the number of years of education or levels of attainment captures no information about the quality of the education and/or school (e.g. pupil-to-teacher ratio, teacher salary, highly skilled teachers). For instance, school quality at critical time points in life (e.g. during adolescence) may influence long-term health trajectories.37 Dissonant/consonant relationships between family and school can be also an important factor in understanding the effects of education on health. In several studies, parental interest in their child’s education has been reported as an upstream determinant of education having lasting effects on health.38,39 Moreover, the socio-economic mix of schools and the educational expectations within schools may influence social class differences in educational achievement.40 Thus, apart from studies focusing on education at individual or interpersonal levels, further research focusing on education at system/organization or community levels is needed. Of note, due to the mandatory minimum age requirements for leaving school and greater availability of higher education, the range in the amount of education obtained within some populations is narrowing.18 In HICs at least, with the exception of older cohorts, it is rare to find adults with low or very low education, so shifting the focus towards looking at educational quality and type along with level is needed. As different education elements may be differentially associated with health outcomes, using conventional measures of education may violate the consistency assumption.6 The consistency assumption entails that the exposure (e.g. education) needs to be detailed with enough specificity that any variation within the exposure specification would not result in a different outcome. For instance, literacy may have a different impact on health than the number of years of education and may ultimately lead to different policy recommendations.6 Thus, considering several indicators of education allows a better understanding of the context. Formal education measures do not capture informal and non-accredited education, including on-the-job training and other career investments made by individuals with similar levels of formal schooling.41 This neglects the concept of life-long learning, which is a dynamic, ever-evolving accumulation of knowledge, skills and capacities. Measures of formal education neglect education at later adulthood and older ages, as formal education is normally completed in young adulthood. To date, the informal component of education is rarely considered.27 This may be due to the complexity of the task of eliciting, coding, classifying and interpreting a wide range of formal and informal educational experiences. Moreover, reverse causality is an issue to be considered when using educational measures that include post-school qualification and training at work rather than measures based on school qualifications.27 In Figure 2, we summarize recommendations regarding how to appropriately select the best available educational measure(s) with regard to a research question, considering birth cohorts, social groups and contexts that capture and compare the diversity of participants’ educational experiences over time in health inequality studies. We also recommend considering the quality of education as well as the quantity along with formal and informal education throughout the life course. To do this, cohort studies, public health research and surveillance need to collect data on quality and informal education routinely. Recommendations for appropriately selecting and operationalizing educational measures in health inequality studies We have presented conceptual arguments to illustrate major methodological issues and challenges associated with current approaches regarding educational measures in health inequality studies. Consequently, we suggested strategies and recommendations for improving approaches towards selection and operationalization of educational measure(s). We also highlighted the potential future direction of health inequality studies towards including other facets of education and considering the impact of informal education on health. Education plays a potentially important and multifaceted role in redressing health inequalities and by enhancing our research assumptions and methods about hypothesized mechanisms, we may come closer to understanding this in more depth. Not applicable. Not applicable. S.K.S. conceived of the idea for the manuscript. S.K.S. drafted the manuscript. to to and the and the before S.K.S. is by the of in number received funding from the the funding from the under the research and The no role in of the and to

International Journal of Epidemiology · editorial or comment · 58 citationsread the source →

Benefits of pulmonary rehabilitation in COVID-19: a prospective observational cohort study.

Background: Coronavirus disease 2019 (COVID-19) can result in a large variety of chronic health issues such as impaired lung function, reduced exercise performance and diminished quality of life. Our study aimed to investigate the efficacy, feasibility and safety of pulmonary rehabilitation in COVID-19 patients and to compare outcomes between patients with a mild/moderate and a severe/critical course of the disease. Methods: Patients in the post-acute phase of a mild to critical course of COVID-19 admitted to a comprehensive 3-week inpatient pulmonary rehabilitation programme were included in this prospective, observational cohort study. Several measures of exercise performance (6-min walk distance (6MWD)), lung function (forced vital capacity (FVC)) and quality of life (36-question short-form health survey (SF-36)) were assessed before and after pulmonary rehabilitation. Results: 50 patients were included in the study (24 with mild/moderate and 26 with severe/critical COVID-19). On admission, patients had a reduced 6MWD (mild: median 509 m, interquartile range (IQR) 426-539 m; severe: 344 m, 244-392 m), an impaired FVC (mild: 80%, 59-91%; severe: 75%, 60-91%) and a low SF-36 mental health score (mild: 49 points, 37-54 points; severe: 39 points, 30-53 points). Patients attended a median (IQR) 100% (94-100%) of all provided pulmonary rehabilitation sessions. At discharge, patients in both subgroups improved in 6MWD (mild/moderate: +48 m, 35-113 m; severe/critical: +124 m, 75-145 m; both p<0.001), FVC (mild/moderate: +7.7%, 1.0-17.8%, p=0.002; severe/critical: +11.3%, 1.0-16.9%, p<0.001) and SF-36 mental component (mild/moderate: +5.6 points, 1.4-9.2 points, p=0.071; severe/critical: +14.4 points, -0.6-24.5, p<0.001). No adverse event was observed. Conclusion: Our study shows that pulmonary rehabilitation is a feasible, safe and effective therapeutic option in COVID-19 patients independent of disease severity.

ERJ open research · editorial or comment · 146 citationsread the source →

Effects of exercise on fatigue and physical capacity in men with chronic widespread pain - a pilot study.

Background: There is very limited knowledge about the effects of exercise on men with Chronic Widespread Pain (CWP), especially regarding fatigue. We wanted to investigate the effects of resistance exercise compared with pool exercise on multidimensional fatigue, psychological distress and physical capacity in men with CWP. Methods: Thirty-four men with CWP, with a mean age of 49 (SD 8, range 26-59) years, were randomised to 12 weeks of standardised pool exercise (PE) or resistance exercise (RE). The primary outcome was the Multidimensional Fatigue Inventory (MFI-20). Depression, anxiety, isometric force, pain and health-related quality of life were also assessed. Results: No significant differences were found for changes in MFI-20 between the exercise groups. The RE group improved the isometric forces of right shoulder abduction (RE: ∆2.2 SD 1.5 N, PE: ∆0.6 SD 1.2 N, p = 0.009), right knee flexion (RE: ∆50, SD 50 N, PE: ∆-17, SD 71 N, p = 0.003) and left knee flexion (RE: ∆33 SD 39, PE: ∆-9 SD 52 N, p = 0.017) compared with the PE group. The drop-out rate was 29 % in the RE group and 18 % in the PE group. Conclusions: Both a resistance exercise programme and a pool exercise programme improved different dimensions of fatigue in men with CWP. There were no differences in the change in fatigue over time between the exercise groups. Resistance exercise improved isometric strength compared with pool exercise. Because different types of exercise appear to improve different aspects of health, the goals could guide the choice of treatment. Further exercise studies with larger groups are needed to gain more knowledge about the effect of exercise on fatigue in men with CWP. Trial registration: ClinicalTrials.gov Identifier NCT01278641. Registration date April 2008.

BMC sports science, medicine & rehabilitation · 8 citationsread the source →

Food pantry organizational features, nutrition environments, and partnerships: a community-engaged study in Southern California.

BACKGROUND: Charitable food organizations are critical community hubs for promoting food security and nutrition. Few studies have examined whether food pantry organizational features (e.g., setting and size) are associated with the use of health promotion strategies. METHODS: This cross-sectional study used a validated survey instrument (Nutrition Environment Food Pantry Assessment Tool+, NEFPAT+) in partnership with a southern California regional food bank to examine pantry consumer nutrition environments, including client choice models, marketing, and partnership/referral practices. Eligible pantries were: food bank partners, open at least 1/week for public distribution, and in high-poverty cities. We collected surveys from 27 of 35 eligible sites in 2024. We used descriptive statistics to summarize NEFPAT+ objective outcomes and conducted exploratory analyses to assess differences for specific objective results. Mann‒Whitney U tests and Kruskal‒Wallis tests were used to compare NEFPAT+ scores and objective results by pantry setting and size, respectively. RESULTS: Surveyed food pantries served a median of 450 households per month (range: 50 − 3,000). 52% were located in faith-based settings and 48% in other community settings. The median NEFPAT+ score was 39 out of 95 points (range: 8–61), indicating most pantries were classified as Silver (37%) or Gold (33%). Overall, 81% of pantries made nutritious foods easy to reach/identify, and 63% used client choice. Only 33% reported using certain marketing strategies. Few used local food sourcing or point-of-decision signage. Most pantries (78%) reported having external partnerships, and 74% referred clients to a local resource. Pantries located in other community settings used nutrition-focused strategies (i.e., client choice, healthy eating signage/recipes) and referred/partnered with community organizations (i.e., food, healthcare, employment assistance) at a significantly higher rate compared to pantries in faith-based settings. We did not find statistically significant differences by pantry size. CONCLUSIONS: This community-engaged study reveals how food pantries may function as multifaceted community health hubs for health promotion interventions. Results show both significant organizational strengths and targeted opportunities for improvement, with strategy use varying by food pantry setting type. Future research should evaluate whether pantries in faith-based settings need additional support, engagement, or technical assistance to promote community health in marginalized communities.

BMC public healthread the source →

Monofocal bone transport technique for bone defects greater than 5 cm in tibia: our experience in a case series of 24 patients.

Background: As the tibial bone defect increases in size, the problems in treatment also increase. The treatment may be problematic but different treatment approaches can be used. Among these approaches, distraction osteogenesis is a method an orthopedic surgeon with limited conditions can use although it has a longer treatment period. In our case series, we evaluated current treatment approaches. Method: Retrospective study based on patient records and radiographs. We evaluated our cases with tibial bone defects Type B and greater than 5 cm. Twenty four cases were operated between 1995 and 2013. Clinical follow-up consisted of physical examination, review of radiographs, and Association for the Study of the Method of Ilizarov (ASAMI) scoring system of bone and functional results. Results: The defects had an average lenght of 7.01 cm (SD:2.88) (range, 5-18). The mean follow-up time from removal of the apparatus to the time of the last clinic visit averaged 74.08 ±24.17 months (range: 39-122). The Ilizarov frame was placed for transport and until bone was solid, average of 275.5 ± 70.6 days (range: 190-437 days). The mean external fixator time (EFT) was 350.91 ± 89.22 days (range: 261-627 days). The mean external fixator index (EFI) was 52 days/cm (range: 34.8-62.8 days/cm). Bone union was obtained in 23/24 (95.8%) patients. Seven patients suffered from stiffness (2 knee, 5 ankle) from which 3 patients developed equinus deformity and required tenoplasty (Achilles tendon lengthening at the time of frame removal. After reaching docking site, 5 patients needed intramedullary nailing to speed up union. Twelve (50%) cases had excellent radiological results, 8 (33%) cases had good, 2 (8%) cases fair and 2 (8%) cases had poor results. Regarding the functional ASAMI scoring system 14 (58%) cases had excellent, 9 (38%) cases had good and one case (4%) had fair result. Conclusion: According to our experience, the Ilizarov bone transport technique remains a reliable method to repair bone defects. However, the treatment time is lengthy with a considerable risk of complications. We found closed intramedullary nailing as an effective and easy solution for cases without pin tract infections to manage the nonunion problem of the docking site and this option should be considered where the surgeon envisages difficulties of healing or the patient has lost patience with the frame. Careful selection of case and patient profile can optimize the outcomes.

Injury · 42 citationsread the source →

'Because it's the wife who has to look after the man': A descriptive qualitative study of older women and the intersection of gender and the provision of family caregiving at the end of life.

Background: Research indicates that women are the primary family caregivers for others at life's end and, because of ageing populations, will keep fulfilling this role as they age. Yet, little is known about how the gendered nature of caregiving contributes to older women's understandings of providing care. Aim: To explore how gender norms constructed older women's views about the appropriate roles of women and men in providing palliative and end-of-life care for family members. Design: Six focus groups were conducted with 39 community dwelling older adults (36 women and 3 men) using two vignettes to prompt discussion about experience of end of life caring and attitudes towards Advance Care Planning. This article reports on data gathered from female participants' reactions to Vignette 1 which prompted significant discussion regarding the intersection of gender and older women's caregiving experience. Setting/participants: A total of 36 women in the age ranges of '50-59 years' through to '90-99 years' from New Zealand. Results: Three themes regarding gender and caregiving were identified: the expectation women will care, women's duty to care and women's construction of men in relation to caregiving and illness. The women adhered to stereotypical gender norms that regard women as primary caregivers. There was little connection between the burden they associated with caregiving and this gender construction. Conclusion: The expectation that older women will provide end-of-life care even when experiencing considerable burden is an unacknowledged outcome of gender norms that construct women as caregivers.

Palliative medicine · 48 citationsread the source →

Pathophysiology of the risk factors associated with osteoporosis and their correlation to the T-score value in patients with osteopenia and osteoporosis in the United Arab Emirates

INTRODUCTION Osteoporosis is a bone disorder, characterized by loss of bone strength because of an imbalance between the bone resorption and the mechanisms of bone formation, leading to increased fragility and fractures. Pathophysiological mechanisms underlying this disorder include an inadequate formation response during the remodeling process of bone formation, which is an essential factor in osteoporosis pathogenesis. This inadequacy is due to the activation of large numbers of osteoclasts as a response to initiation of hematopoietic precursor cells with failure of normal interaction with the osteoblastic lineage. This will lead to excessive bone resorption that may result in complete loss of trabecular structure and loss of template for new bone formation. The time required for osteoblastic replacement is longer than the resorption phase of bone remodeling by osteoclasts. Therefore, any increase in bone remodeling will lead to damaged architecture and loss of bone mass.[1] Recently, it has been estimated that more than 200 million people worldwide have osteoporosis. On the basis of a statistics from the International Osteoporosis Foundation in 2017, one in five men and one in three women over the age of 50 years will experience fractures during their lifetime because of osteoporosis. Furthermore, it has been found that an osteoporotic fracture occurs every 3s, with the most common fractures occurring at the hip, spine, and wrist.[23] Osteoporotic fractures may be the first manifestation of the disease, which is why it is called a silent disease. Risk factors of osteoporosis, decreased bone mineral density (BMD), and increased fragility fractures may be modifiable or non-modifiable. Among the modifiable factors are low body mass index (BMI), vitamin D deficiency, low calcium intake, excessive caffeine and alcohol consumption, smoking, sedentary life and low physical activity, endocrine disorders (such as estrogen deficiency and insulin-dependent diabetes mellitus or hyperparathyroidism), some drugs (such as corticosteroids), and previous history of fragility fractures. The non-modifiable factors include female gender, family history, race, and early menopause.[45] According to the World Health Organization (WHO) diagnostic criteria, osteoporosis is diagnosed by BMD at the hip or spine, which is below the young normal mean reference population by 2.5 standard deviations (SDs) or more. This is called the T-score, and osteopenia is diagnosed by BMD less than or equal to 1 SD.[6] The guidelines for osteoporosis screening vary greatly in various publications. In general, most organizations recommend that all adults older than 50 years of age with a history of fracture must receive BMD screening.[7] Dual-energy X-ray absorptiometry (DXA) at the hip or spine is the best test for measuring central BMD. An association is present between the T-score values in DXA in patients with osteoporosis or osteopenia and the risk of fractures. A fracture risk assessment tool (FRAX) was designed. It is estimated that for every 1 SD decline in spine BMD, the risk of having a spine fracture increases 2.3 times and the risk of having a hip fracture increases 2.6 times.[89] As the most common bone disease in humans, the prevalence of osteoporosis is steadily increasing due to a growing elderly population, and thus represents a major public health concern with reduced bone strength and a higher risk of fractures.[68] The prevalence of osteoporosis is steadily escalating due to increased life expectancy as a result of developed health services. According to the 2016 WHO report, in the United Arab Emirates (UAE), life expectancy at birth for men was 76 years and for women it was 79 years.[10] The UAE population projection showed that in 2011, 7% of the population were 50 years of age or over and less than 1% were 70 years of age or over. By 2050, it is estimated that 12% of the population will be 50 years or over and 2% will be 70 years or over.[11] MATERIALS AND METHODS Study design The study was performed in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines. Ethical approval number UG-H-18-11-7-10 was obtained from the Research Ethics Committee of the college. The study was conducted on a population sample of national and nonnational people in the UAE. Both men and women were recruited in the study. Data were collected from the patients in six governmental and private hospitals. Research tools A total of 200 male and female participants between the age of 25 and 80 years were recruited in the study. Eighty percent of the sample were women and 20% were men. After obtaining the required consent, each participant was asked to fill a structured questionnaire consisting of 25 questions, which was used as the primary tool for data collection. The questions were formulated both in Arabic and English, it required 3–4min to be completed. BMD of the participants was assessed in the International Radiology Centre and correlated with their data in the questionnaires. DXA scan was used for the measurement of BMD. Data collection and data analysis After ensuring strict confidentiality, data were collected between March 20, 2016 and May 20, 2016. The following information was obtained: Demographic data (gender, age, race, BMI, and occupation) Family history of osteoporosis or osteoporotic fractures Social history and lifestyle, physical activity, and exposure to the sun Dietary habits such as calcium, caffeine, and soft drinks intake Medical history of diseases and medicines. For female participants, number of pregnancies, lactation, and age at menopause were included The following criteria were used to evaluate osteoporosis: Normal BMD: if T-score between +2.5 and –1 Osteopenia: if T-score between –1 and –2.5 Osteoporosis: if T-score below –2.5 The filled questionnaires were coded and data were analyzed statistically using the Statistical Package for the Social Sciences (SPSS) software (version 24; IBM Corporation, Newyork, USA). Spearman’s correlation test was carried out to assess the association between different variables in the study. A P value of less than 0.05 was considered significant. RESULTS Sociodemographic data The sociodemographic background of the study participants is listed in Table 1. A total of 200 participants were included in the study. The control group and the osteoporotic group consisted of 100 participants each, 20% of them were men, whereas 80% of the respondents were women. Table 1: Background demographic data of the respondentsBody mass index The patients with osteoporosis have significantly lower BMI than the control group (P < 0.05). Results showed that 72% of them have a BMI less than 25 kg/m2 (P < 0.05) [Table 2] [Figure 1].Table 2: Body mass index of the respondentsFigure 1: Body mass index (kg/m2) of the respondentsSmoking behavior Regarding smoking behavior, a significant value was evident between smoking and osteoporosis (P < 0.01) as 54% of the patients with osteoporosis were current smokers, whereas 72% of the controls had never smoked before [Table 3] [Figure 2].Table 3: Smoking behavior and intake of milk, coffee, and soft drinks by the respondentsFigure 2: Intake of milk and caffeine and smoking behavior by the respondentsDietary calcium intake The intake of milk and dairy products by the participants was used to assess the dietary calcium intake. The patients with osteoporosis have a significant low calcium intake (P < 0.01), whereas non-osteoporotic control significantly consume more milk and dairy products (P < 0.01). A positive correlation was found between the intake of milk and dairy products and the T-score value of the participants (P < 0.05) [Table 3] [Figures 2 and 3].Figure 3: Correlation between milk intake and T-score in patients with osteoporosisCaffeine consumption Caffeine intake was evaluated in this study by the amount of coffee, tea, or soft drinks consumed by the participants each day. The results showed that the patients with osteoporosis significantly consume more caffeine (P < 0.01). A negative correlation is present between the amount of caffeine intake and T-score value of the participants (P < 0.05) [Table 3] [Figures 2, 4, and 5].Figure 4: Correlation between tea/coffee intake and T-score in patients with osteoporosisFigure 5: Correlation between soft drinks intake and T-score in patients with osteoporosisExercise behavior and exposure to the sun Results showed a significant positive correlation between the duration of exercise and the T-score value of the participants (P < 0.05) [Table 4] [Figure 6].Table 4: Exercise behavior and exposure to sun of the respondentsFigure 6: Correlation between exercise duration and T-score in patients with osteoporosisRegarding the exposure to the sun, the results showed that 96% of the patients with osteoporosis were exposed to the sun for less than 15min, three to four times a week or not exposed at all, whereas most of the normal controls (72%) exposed their bodies to the sun for 16–30min/day, three to four times a week [Table 4] [Figure 7].Figure 7: Sun exposure behavior of the respondentsDiseases and medications Results of the study revealed that 46% of the patients with osteoporosis were diabetic, 42% of them were treated by antidiabetics, 18% had arthritis and 38% had been treated previously by corticosteroids [Table 5].Table 5: Distribution of patients with osteoporosis by their diseases and medicationsNumber of pregnancies and breastfeeding Female participants constituted 80% of the study sample, 75% of the females with osteoporosis were menopausal, 75% of them had three or more pregnancies, and 82.5% of them breastfed their children, whereas these values for the control group participants are 30%, 28%, and 33%, respectively. Results showed a significant positive correlation between the age at menopause and the T-score value of females with osteoporosis (P < 0.05) [Table 6] [Figure 8]. The distribution of patients according to the joint affected by Osteoporosis or Osteopenia is shown in [Figure 9] and [Table 7].Table 6: Distribution of female patients with osteoporosis by number of pregnancies and breastfeedingFigure 8: Correlation between age at menopause and T-score in female patients with osteoporosisFigure 9: Distribution of patients having osteopenia or osteoporosis in wrists, hips, or spineTable 7: Distribution of patients having osteoporosis and/or osteopenia in hips, wrists, and spineDISCUSSION To maintain normal bone structure, a remodeling process that consists of osteoclasts, removing old bone, and osteoblasts, synthesizing new bone, occurs. Hematopoietic progenitors produce osteoclasts, whereas mesenchymal stem cells called marrow stromal fibroblasts produce osteoblasts. This process is controlled by certain circulating hormones, growth factors, and locally produced cytokines through their effects on apoptosis of osteoblasts and osteoclasts. Estrogen deficiency or glucocorticoid excess leads to bone loss because of changes in the production of bone cells. This is caused by the prolongation of the life span of osteoclasts and the shortening of the life span of osteoblasts. On the contrary, drugs that aim to treat or prevent osteoporosis prevent apoptosis of osteoblasts and/or stimulate the apoptosis of osteoclasts.[12] The pathogenesis of osteoporosis is the consequence of various hormonal, genetic, dietary, lifestyle, and physical factors. Genetic factors mainly affect the BMD and bone formation, whereas low levels of estrogen increase parathyroid hormone, and local cytokines are mainly responsible for bone remodeling imbalance.[13] Age and gender In this study, 76% of the patients with osteoporosis were women at or above 50 years of age. Osteoporosis is usually considered a disease of the elderly with low BMD. In a recent study, most of the patients with osteoporosis were in the age groups of 45–49 and 50–54 years.[14] Previous studies showed that women were at an increased risk of developing osteoporosis because of their faulty behavior of physical inactivity, sun-avoidance behavior, low intake of dairy products, and poor diets.[151617] Body mass index The results of this study showed a significant number of patients of osteoporosis with BMI <25 kg/m2, where P < 0.05. Women that have low BMI are at a higher risk of developing osteoporosis. It is reported that one unit change in BMI has a larger effect on the risk of developing osteoporosis than most other modifiable risk factors. To help reduce the risk of osteoporosis, patients should be advised to maintain a weight within the normal range.[1516] The risk of osteoporotic fractures increases in adults who have low BMI of less than 20 kg/m2.[18] On the contrary, patients who are obese (BMI >30 kg/m2) are also at a high risk of developing osteoporosis and fractures because of the risk of repeated falls and the weakness of the skeletal muscles due to loss of its mass as a result of aging.[19] Exercise and physical activity The results of this study showed a significant correlation between the exercise time and the T-score value. Previous studies concluded that physical activity and exercises stimulate skeletal growth and bone strength.[45] Estrogen Estrogen deficiency has a critical effect on the pathogenesis of osteoporosis. The results of this study showed a significant positive correlation between the age at menopause and the T-score value of the female patients. Estrogen has a crucial role in bone formation and physiology. It stimulates the production of T cell cytokines, affects the osteoblastic cell by altering its production of receptor activator of nuclear factor-Kappa B ligand (RANKL) or Osteoprotegerin (OPG), inhibits the differentiation of osteoclasts by direct action, and stimulates the formation of bone performed by osteoblasts and osteocytes, which allows them to enhance their ability to respond to mechanical forces.[2021] Estrogen produces its effect through a specific cell surface receptor called the estrogen receptor alpha (ERα). This receptor binds and then transports estrogen into the nucleus of the cell where certain genes are then activated by the receptor–hormone complex. ERα receptors and estrogen receptor–related receptor alpha (ERRα) are found on the surface of osteoblasts. ERRα may play a supporting role in the regulation of bone cells.[22] Previous studies also suggest that sex hormone–binding globulin may play a significant role in regulating bone cells as well because it facilitates entry of estrogen into cells.[23] Because of the natural drop of estrogen level in postmenopausal women, they are at the highest risk of developing osteoporosis. A previous study showed that it is an increase in bone resorption that might be the driving force for bone loss during estrogen deficiency in postmenopausal women not impaired bone formation as was previously thought.[1] However, other studies indicated that both markers of bone resorption and formation also increased, leading to accelerated bone remodeling at menopause.[2425] Calcium intake and vitamin D Calcium and vitamin D are two pivotal contributors of bone formation and mineralization. The results of this study showed that the patients with osteoporosis have a significant low calcium intake, whereas controls significantly consume more milk and dairy products (P < 0.01). This significant result showed the importance of calcium intake. Results also established a positive correlation between calcium intake and the T-score value of the participants. Vitamin D plays an important role in maintaining calcium homeostasis and bone integrity as it is essential for intestinal calcium absorption.[26] It is estimated that over one billion people around the world have vitamin D deficiency.[2728] Sun exposure is considered as the source of vitamin D, the present results showed a significant value (P < 0.01) as 74% of the patients with osteoporosis exposed their bodies to the sun for 5min or less, three to four times per week, whereas 72% of controls exposed their bodies to the sun for 15–30min, 3 to 4 times a week. A previous study conducted in the UAE showed that 58.2% of the UAE nationals were vitamin D deficient compared to 45% of the patients from other nationalities.[29] In spite of living in sunny areas, such as UAE, Saudi Arabia, and India, young populations have a high prevalence of vitamin D deficiency because of insufficient knowledge and practice of vitamin D and its health implications.[3031] Decreased blood calcium level will lead to secondary hyperparathyroidism. This decrease may result from impaired intestinal calcium absorption due to vitamin D deficiency, aging, or other diseases. Calcitriol, the active form of vitamin D, stimulates the intestinal absorption of calcium and phosphorus. It has an inhibitory effect on the synthesis of parathyroid hormone as well. Therefore, calcitriol deficiency will lead to secondary hyperparathyroidism as well.[32] There is a clear evidence that the risk of having an osteoporotic fracture increases when vitamin D levels are below 50 nmol.[3334] However, a recent study showed that pathological macrophages produced by vitamin D receptor signaling play an important role in the development of myelofibrosis.[35] Smoking The results of this study showed that nicotine has a significant effect on the incidence of osteoporosis (P < 0.01). Smoking has been identified as a modifiable risk factor for low BMD and increased osteoporotic fracture risk.[3637] Smoking behavior should be evaluated when assessing the fracture risk and FRAX.[1638] The role of smoking in decreasing BMD is complicated; smoking is shown to be associated with other risk factors for osteoporosis such as decreased physical activity, low BMI, and poor diet.[38] Nicotine has both direct and indirect effects on BMD. The direct effect is on bone cell proliferation and is described to be biphasic, small doses have a stimulatory effect, whereas toxic large doses have an antiproliferative effect on the proliferation of osteoblasts.[39] This effect on osteoblasts is receptor mediated by the nicotinic acetylcholine receptors, where nicotine in low doses upregulates gene expression of alkaline phosphatase, type 1 collagen, and osteocalcin.[40] Nicotine produces an increased level of tumor necrosis factor α (TNFα) secretion that reduces bone formation by osteoblasts and increases bone resorption by osteoclasts. TNFα has a powerful osteoclastogenic effect through its stimulating effect on RANKL production and by intensifying osteoclasts production.[41] It is strongly supported that RANK/RANKL/OPG systems have a role in regulating bone resorption and the formation of osteoclasts.[42] The main predisposing factor for chronic obstructive pulmonary disease (COPD) has been found to be smoking. The most important factor in managing COPD continues to be the termination of smoking.[43] It has been shown in numerous studies that smokers with COPD have elevated levels of pro-inflammatory cytokines in the form of interleukin-6. In addition, TNFα levels are much higher in COPD smokers than in asymptomatic smokers. This indicates that COPD affects local and systemic inflammatory responses, which in turn affects bone remodeling.[4445] Nicotine has an indirect effect on BMD, which is caused by releasing calcitropic hormones and glucocorticoids, which leads to an increase in bone resorption.[43] Furthermore, smoking has been linked to an increase in the level of cortisol[4446] as well as a decrease in the level of estradiol.[47] Nicotine also harms intestinal calcium absorption, which might lessen the effectiveness of dietary calcium supplements.[48] Also, toxic carcinogenic metabolites of nicotine have also been found to increase osteoclast formation in rats.[49] Moreover, one hip fracture in eight postmenopausal women with osteoporosis is attributable to smoking. This correlation could not be explained by early menopause, low BMI, lower levels of exercise, or by the actions of nicotine on estrogen. This indicates that there is an independent negative effect of nicotine on BMD, which means that smokers lose bone at a faster rate than nonsmokers.[50] CONCLUSION Prevalence of osteoporosis is high in the UAE and is expected to grow due to increased life expectancy and faulty lifestyle of inadequate dietary habits, sun exposure, exercise behavior, and smoking. More intervention should be directed toward changing the modifiable risk factors in the patients with osteoporosis, and more studies should be directed toward osteoporosis in the UAE. Limitations of the study To make the study a polycentric research, it would require greater number of participants from all the emirates of the UAE. Financial support and sponsorship This work is self-funded by the authors. Conflicts of interest There are no conflicts of interest.

Journal of Pharmacy And Bioallied Sciences · 11 citationsread the source →

Feasibility and pilot study of a brief self-compassion intervention addressing body image distress in breast cancer survivors.

Background: The majority of breast cancer survivors (BCSs) experience body image concerns following treatment. Body Image distress (BID) is associated with psychological distress and diminished quality of life. A web-based self-compassion focused writing activity (My Changed Body - MyCB) reduces BID in BCSs, yet limited research exists on participant characteristics associated with such intervention adherence. Self-compassion-based meditations are also efficacious in reducing BID in non-BCS populations. This parallel, double-blind pilot randomised controlled trial aimed to assess the feasibility and acceptability of MyCB, with and without an additional meditation component, on BID and related psychological outcomes in BCSs. The trial was registered with the Australian and New Zealand Clinical Trials Registry (#ACTRN12619001693112). Methods: BCSs were randomly allocated to MyCB (n = 39), MyCB + Meditation (MyCB + M) (n = 17) or an expressive writing (EW) active control arm (n = 23). The primary outcome was BID. Secondary outcomes were body appreciation, affect (positive and negative), psychological distress (depression, anxiety and stress) and self-compassion (state and trait). Assessments were completed online at baseline, post-intervention and 1-month. Results: Adherence to the MyCB writing (45%) and meditation (50%) was modest, and acceptability was high for both MyCB and MyCB + M. Intent to treat linear mixed model analyses indicated: Post-intervention - state self-compassion and positive affect increased for MyCB compared to EW; 1-month: BID scores decreased across all conditions; trait self-compassion increased and anxiety decreased for MyCB + M compared to MyCB and EW. Conclusion: These findings provide preliminary evidence for the efficacy and potential clinical use of the MyCB brief web-based self-compassion intervention alone and with the addition of meditation, to increase self-compassion and psychological wellbeing in BCSs.

Health psychology and behavioral medicine · 30 citationsread the source →

Psychosexual health in gynecological cancer

The literature surrounding psychosexual health and cancer patients has primarily considered the functional aspects of the disease and its treatment at the major expense of the emotional sequelae. Sexual health is defined by WHO as: "a state of physical, emotional, mental, and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination and violence" [1]. A principle goal of WHO is to assist its member states in achieving the highest attainable standard of health care for all, including sexual and reproductive health [2]. Global statistics show that the world's female population is carrying an overwhelming burden of need in this area. Over 200 million women cannot access modern contraception, and millions of women suffer rape, domestic violence, and sexual abuse, not only in the context of wars and criminal activities, but also in their own homes [2]. Although the physical sequelae of these disasters can be treated, such as treatment for sexually transmitted infections, the emotional impact can frequently be hidden, ignored, or may not reveal its impact until many years after the event. Any illness or traumatic life event, past or present, can lead to sexual problems in the lifetime of a woman, and gynecological cancer is no exception. It is the root cause or trigger for sexual difficulties in at least 50% of women affected [3]. In 2012, the estimated number of women living with gynecological cancers was over three million, which means that potentially 1.5 million gynecological cancer survivors could be affected by an associated sexual difficulty [4]. Within the context of gynecological cancer, many of these problems can be alleviated if recognized and acknowledged early in the cancer journey, therefore contributing dramatic improvements to a woman's overall well-being. It is now estimated that half of the population of either sex will develop cancer at some time in their life. Globally, 40% − 45% of women will have a sexual problem at some stage, with the prevalence increasing with age [5]. Between 10% and 90% of women with any cancer will have sexual problems [6] and over 50% of women with gynecological cancer will have either temporary or persistent sexual difficulties [3]. As diagnosis and treatments improve, the number of women surviving cancer will increase, and survivorship issues including quality of life have become increasingly important. Sexuality is a key component of most subjective measurable quality of life indicators [7]. Sexual function and enjoyment are important components of survivorship and should not be ignored. The most common sexual problems can be divided into two groups: problems of function and/or problems of desire. There is, however, a complex interplay of organic disorders with emotional and psychosocial issues, and these divisions are merely artificial. Formal definitions of female sexual dysfunction have been adopted, including the US classifications in the Diagnostic and Statistical Manual of Mental Disorders [8], although having a sexual difficulty does not constitute having a mental health disorder. Basson et al. [9] published a useful classification of the problems. Such classifications are useful for research purposes, but may often be less helpful when treating women. The predominant functional female sexual problem is pain on sexual intercourse, or dyspareunia. Deep dyspareunia describes intracoital pelvic pain, and superficial dyspareunia is pain on vaginal entry. Either could signify organic disease, and should be appropriately investigated. If no pathology is demonstrated, and the pain persists, then an emotional cause must be considered and pursued. Vaginismus, or involuntary spasm of the pubococcygeal and related musculature, can prevent sexual intercourse taking place. Good history taking can clarify whether there has been any penetration of the vagina, not only penile, but by fingers, sex toys, or tampons. If not, this is diagnostic of primary vaginismus, and apart from close inspection of the vulva and offer of gentle digital vaginal examination to determine the extent of the vaginismus, no further clinical investigation is warranted. Women with gynecological cancer are more likely to have secondary vaginismus caused by pain experienced from the disease or its treatment, and fear of the pain occurring during sex [10]. Loss of libido or loss of sexual interest on the other hand is a problem of desire. There are no physiological markers for loss of desire when its origins are psychogenic, with psychosocial contributions, past and present relationships, traumas, and emotional factors all inhibiting the woman's wish to be sexual. One of the key ways to determine the origins of the sexual difficulty is to ask about the sexual and emotional relationship between the woman and her partner before the cancer diagnosis. It should not be assumed that problems are all due to the cancer, as long-standing relationship problems may be disclosed, and need to be incorporated into any counselling. The exception to this is the woman who suddenly becomes menopausal following cancer treatment, who had no problems with sex or desire prior to her cancer therapy. Appropriate standard therapy for her menopausal symptoms should be considered; however, the impact of a cancer diagnosis will be life changing, and drug treatment of hormonal deprivation symptoms may not be sufficient without some psychological or counselling support, or may be contraindicated as in the case of breast and endometrial cancer [11]. A diagnosis of gynecological cancer is overwhelming. While the instinctive professional response from clinicians is to ensure long-term survival, sexual issues are important for quality of life and should be considered in the decision-making process [12]. Sexual dysfunction is one of the most common and distressing consequences of cancer treatment [13]. Many treatments are shown to have sexual impacts, both positive and negative, and should be discussed fully with the woman pre-treatment so that she can make an autonomous decision about her care. Early offer of discussion of sexual issues in the cancer journey can lead to better sexual outcomes. Cervical cancer is the most common gynecological cancer worldwide. Cervical cancer survivors are at risk of sexual pain disorders, no matter which modality of treatment is used. A small study of patients who underwent radical vaginal trachelectomy for early stage cervical cancer showed sexual dysfunction, including loss of libido, for up to one year following treatment; however, by 12 months, sexual activity had reached that of healthy women [14]. Following radical hysterectomy for locally advanced cervical cancer, there was no significant difference in sexual activity and enjoyment between women with benign or malignant disease; however, the cancer group had worse problems than healthy controls with body image and vaginal functioning [15]. In women with advanced cervical cancer given chemoradiotherapy, pain during intercourse was in fact reduced after treatment [16]. This may have been a result of the resolution of bleeding, discharge, and pelvic pain. However, the anxiety surrounding cancer remains for many women. Women surviving up to 15 years following cervical cancer treatment showed poorer quality of life than healthy controls, and those who had received radiotherapy were significantly more affected by sexual dysfunction than those who had surgery alone [17]. Despite this however, orgasm may be unimpaired following radiation [18]. Many additional needs were expressed by women with cervical cancer; however, sexuality and intimacy came to the fore as a predominant issue for survivorship [19]. It has been known for some time that the physical and emotional impact of ovarian cancer can be devastating, leading to sexual as well as global quality of life issues [20]. One study has shown a prevalence of 63% for sexual difficulties among women with a diagnosis of ovarian cancer [3]. The effects of chemotherapy and surgery, combined with the anxiety about survival can have a dramatic negative effect on the woman's libido, and even women who undertake risk-reducing salpingo-oophorectomy can suffer sexual dysfunction [21]. Many of these women are totally unprepared for the devastating effects of sudden menopause, with hot flushes, vaginal dryness, and loss of libido replacing a previously healthy sex life. This could be helped by more realistic counselling before the procedure, and increased postoperative emotional support. One study has shown that women who had surgery for endometrial cancer had no differences in their own sexual experience postoperatively, but compared with healthy controls, they had more sexual difficulties overall [22]. Women with Lynch syndrome who opt for preventive surgery tend to be happy overall with the surgery, but are often unprepared for the physical adverse effects of menopause [23]. In contrast, Moldovan et al. [24] has reported that, despite sometimes debilitating menopausal symptoms, there were no significant sexual difficulties associated with the procedure. Vulvectomy is a common treatment for vulvar malignancy. This is increasingly affecting younger women, who are HIV positive. Women with vulvar cancer can have many years of difficulties with sex due to often distressing vulvar symptoms and bleeding. Following treatment they still suffer severe dyspareunia and body image distortion due to the effects of treatment. Although a recent study showed no differences in psychosocial and sexual functioning before and after vulvectomy, it was acknowledged that women with vulvar malignancy have a high risk for sexual problems compared with healthy controls [25]. Factors associated with postoperative sexual difficulties are increased age, poor overall physical and mental health well-being, and extent of the surgical excision [25]. This often elderly group of patients is usually neglected from the psychosexual point of view. The majority of the literature related to sexuality and cancer stems from high-resource countries. Although most of these studies encompass all women, there is a lack of good published evidence on the treatment of the sexual sequelae of cancer in relation to ethnic minority groups, within a majority culture [26]. Furthermore, data from low- and middle-income countries are scant. Much of the literature focuses on sexual distress and activity in relation to HIV and AIDS which, of course, is a global priority; however, this focus on infection transmission should not take away from the emotional needs of the woman who suffers from gynecological cancer. Sexuality research around the globe must be perceived and researched in terms of cultural, spiritual, ethnic, and religious contexts. Sexual problems in women with gynecological cancer may be associated with adverse effects of surgical, hormonal, and chemical treatments, as well as by the cancer itself. Fortunately, emotional, sexual, and quality of life outcomes improve as less morbid, more minimally invasive surgical treatments for gynecological cancers develop [12]. Chemotherapy-induced ovarian failure in cancer patients is associated with all the possible symptoms of a sudden menopause, combined with the emotional impact not only of the cancer, but loss of physical well-being and fertility all at the same time. Vaginal dryness can be a major problem to those women who wish to have sex [27], and appropriate vaginal moisturizers and lubricants can help. The issue of vaginal estrogen is still debated, but should be discussed with the patient, weighing up the risk − benefit ratio for each individual. Vaginal estrogen will, in most cases, alleviate the dryness, but there may be concerns about using hormones, especially in relation to breast cancer where the evidence is unclear. The scientific data, however, support the safety of low dose vaginal estrogen therapy [28]. It is not well understood that following a few weeks of vaginal estrogen, the vagina thickens and cornifies and estrogen is not absorbed as a result. Newer treatments such as selective estrogen receptor modulators have been used in place of vaginal estrogen in women without cancer [29], and may prove good alternatives in the future [30]. There are non-hormonal vaginal moisturizers and lubricants to make sexual intercourse more comfortable. Unfortunately, some commercial sexual lubricants can be hyperosmolar and could cause epithelial disruption, facilitating HIV transmission [31]. Simple lubricants such as olive oil or liquid glycerin have been used successfully in interventions to alleviate pain on intercourse due to vaginal dryness, combining their use with physiotherapy and psychosexual counselling. Treatments with pelvic external beam radiotherapy and/or with brachytherapy may cause vaginal shortening, tightening, and lack of pliability. The use of vaginal dilators to overcome these complications is widespread, despite lack of conclusive evidence, either for or against, either with or without a coating of estrogen cream [32]. Unsurprisingly, the intrusion of inserting a plastic (or sometimes glass) tube into a tender vagina after treatment is a task that may carry a deep psychological and emotional impact [33], and will have resultant poor compliance. Radiation oncologists agree that information about dilator use should be given before treatment [34], and that sufficient patient information and support are essential to improve compliance. Sensitivity to emotions and women's views and personal values in relation to sexuality are essential supports to encouraging dilator use [35]. Any of the above problems cannot fail to have an emotional impact on the woman and on her partner. Many sexual difficulties are automatically blamed on the organic disruption caused by cancer and its treatments; however, once any clearly indicated treatments have been given, in a sizable proportion of cases, the sexual difficulty will remain unresolved. Many sexual difficulties are psychogenic, and no amount of skilled clinical treatments will help if not linked closely to appropriate counselling, psychological, or psychosexual therapy. This form of intervention will enable the woman to expose and reflect on her sexual difficulties, in the context of her life and relationship not only since the cancer, but beforehand. This is often a time when past problems, such as childhood abuse, or problems with her current partner will surface. Some partners are disgusted by the physical impacts of cancer, and the relationship will suffer. On the other hand, some partners become more supportive and the cancer leads to stronger relationships [36]. Classic psychosexual therapy, using brief, focused psychotherapeutic techniques is the mainstay of treatment. It can be used with an individual or a couple, of any sexual orientation or cultural or religious background. This is a way of listening reflectively to the patient, so that they can gain their own insights into their sexual problem. The issue of genital examination is considered if relevant, as it enables the woman to connect with her genital area, and may trigger deep-seated thoughts or anxieties that the woman had blocked emotionally. This, of course, is a technique used only by clinicians who are qualified to examine the patient [37]. Clinical psychologists and counsellors trained in psychosexual work also treat women with sexual problems. Globally, because the availability of trained personnel differs, many simple innovative treatment interventions have been tried. A brief intervention using a well-accepted treatment, cognitive behavioral therapy (CBT), combined with sexual health education had positive results on patients who had risk-reducing salpingo-oophorectomy [21]. Psychosexual interventions work [38], and like all psychodynamic interventions only require a trained counsellor and a means of allowing access to the patient. The internet has enabled access to health care for many people around the world who are not able to travel long and difficult land journeys to direct provision of health care. An online intervention with a professional moderator has proven acceptable to gynecological cancer patients with a sexual difficulty [39], and another internet-based sexual difficulties intervention with counselling sessions proved more successful in improving sexuality issues than without a counsellor; however, there was no difference between the two groups in relation to emotional distress and quality of life [40]. Elsewhere, telephone interventions are being used, also with some success; however, it is clear that the knowledge, skills, and training of the health professional providing the intervention are relevant to the patient outcome. Multidisciplinary care should form the backbone of treatment of sexual difficulties in women with gynecological cancer, incorporating physical, psychoeducational, and psychosexual input. Team discussions, including clinicians, psychosexual therapists, and physiotherapists are well within the capabilities of many cancer centers, remembering that the patient and her partner are the focal point and should always be consulted. It is impossible to diagnose and treat a sexual problem if one does not acknowledge that it exists. Many studies in the past have identified lack of willingness of doctors and nurses to discuss sex, but sadly recent research has shown that not much has changed. For instance, in a cohort sample of 1154 US obstetrician − gynecologists, 60% did not ask patients about sexual problems [41]. Too often clinicians make value judgements about their patients including whether sexuality is an important part of their lives. Such assumptions may include biases about age, appearance, sexual preferences, and marital status of people who have sex. People with cancer and their partners have unmet sexual information and support needs [42], often due to the unwillingness of healthcare professionals to discuss sexual issues, even though they recognize it may be important to the patient. There are many barriers to talking about sex, affecting both the patient and the clinician, such as cultural background, and age and gender discrepancies between doctor and patient. There may be simple barriers, such as lack of privacy in a consultation, as often cancer patients are accompanied by family or close friends. Patients often state that they feel it is trivial to take up the doctor's time with non-life-threatening issues such as sex. Clinicians often cite lack of training as a reason that they are uncomfortable talking about sex and poor provision of this training has been noted [13]. Different models of communication skills training have been used and those undertaking the training have shown greater empathy and were more inclined to use open questions [43]. This technique of speaking to the patient in an open rather than interrogative manner can easily facilitate discussion of intimate issues. An even greater challenge in communication is the recognition that individuals are sexual beings up to the end of life. To some women in the palliative phase, sexual touch and closeness to their partner is of vital importance. Sadly this is rarely recognized and addressed by palliative care physicians [44]. It is important to remember that a minority of the female population identifies as lesbian, and that about 8% of the population is bisexual. While this should make no difference to the quality of sexual health care they receive, lesbians and bisexuals find it difficult to disclose their sexuality to clinicians, often inhibited by their cultural or religious background, and fears of facing discrimination [45]. If the clinician asks the patient at the outset if they have a sexual partner, and whether the partner is male or female, it will greatly enhance the quality of the doctor − patient interaction. Lesbian partners in particular can be very supportive during the cancer journey, and should be given the opportunity to be present if the patient wishes. Despite the recognized need for treatment of sexual problems in menopause and gynecological cancer, there is poor provision of specialist training to ensure that this important area of service provision is met [46]. Undergraduate teaching is important, but it is only by recognizing psychosexual medicine in formal gynecology or oncology training, as a compulsory requirement of the course, that this situation will begin to be addressed. Innovative online programs [47] can make a major impact on global training opportunities and give trainees around the world an opportunity to gain some skills and insight into treating sexual difficulties in a nonjudgmental way. Owing to the global prevalence of sexual problems associated with gynecological cancer, it should be within every gynecologist's or oncologist's duty of care to the patient to be aware of and have some understanding of how to diagnose and facilitate treatment for sexual problems in a nonjudgmental manner. This is true holistic medicine, recognizing not only the cancer, but the woman behind the symptoms, and requires awareness of the emotional, social, and relationship aspects of the patient's life. The ability of any person to enjoy a sexual life free of coercion, shame, disease, or pain in a consensual manner is a fundamental element of the human rights of women, and should be an unequivocally accepted as part of her gynecological cancer care. To make a difference, even in the absence of expensive and sophisticated cancer treatments, just acknowledging, listening, and offering support to the woman with sexual difficulties related to cancer will ultimately have a major benefit to her quality of life. The author has no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

International Journal of Gynecology & Obstetrics · 17 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 →

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

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

The lancet. Psychiatry · 52 citationsread the source →