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Effectiveness of the IDAP Treatment Program for Male Perpetrators of Intimate Partner Violence: A Controlled Study of Criminal Recidivism.

Despite substantial problems with intimate partner violence (IPV) worldwide, the empirical support remains weak for the effectiveness of recidivism-reducing interventions for IPV perpetrators. We conducted a controlled study of the effectiveness of the Integrated Domestic Abuse Program (IDAP), a manual-based group intervention for adult male IPV offenders. A consecutive series of 340 convicted male IPV offenders who began IDAP in the Swedish Prison and Probation Services 2004 to 2007 were compared with 452 contemporary, convicted male IPV offender controls. We obtained follow-up reconviction data from the National Crime Register and used Cox regression to model the effectiveness of IDAP versus regular treatment. Treated and control subjects were all followed until March 2, 2011, for an average time-at-risk of 4.6 years (median 4.4, SD = 1.0). Twenty-five percent ( n = 84) of IDAP participants recidivated in any violence versus 23% of controls ( n = 104); corresponding figures for IPV specifically were 19% ( n = 65) and 19% ( n = 84), respectively. Intention-to-treat analyses adjusted for individual baseline risk and follow-up time suggested marginally and non-significantly lower reconviction rates in IDAP participants versus controls (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = [0.69, 1.23] for any violence and HR = 0.92, 95% CI = [0.66, 1.28] for IPV, respectively). Hence, possible recidivism-reducing effects of IDAP in this cross-cultural validation were small and impossible to secure statistically. To remedy the frustrating lack of proven effective treatments for IPV offenders, better interventions should be developed and tested. Such efforts could benefit from improved knowledge about IPV-specific, causal risk factors and more powerful treatment combinations.

Journal of interpersonal violence · 16 citationsread the source →

Disorders of eating behavior: correlation between hypothalamo-pituitary-thyroid function and psychopathological aspects.

Altered pituitary-thyroid (PT) function (TSH, FT4, FT3 plasma levels) was correlated with symptoms of Eating Disorders (ED) in 137 patients (65 ANR, 12 ANP, 19 ANBP, 26 BN, 8 EDNOS-AN, 7 EDNOS-BN) and 30 controls. PT hormone concentrations were assessed by immunofluorimetry and psychopathology by EDI-2 and HSCL-90. Values of TSH were decreased in ANP, BN, EDNOS-AN, of T4 in ANR, ANP, AN-BP, of T3 in ANR, ANP, ANBP, BN, EDNOS-AN, EDNOS-BN. TSH values correlated negatively with ineffectiveness in BN and EDNOS-AN, and with depression in EDNOS-AN. FT4 values correlated positively with perfectionism in ANR, ANP and ANBP, with interoceptive awareness in EDNOS-AN, and negatively with depression in EDNOS-AN and with body dissatisfaction in EDNOS-BN. FT3 values correlated positively with perfectionism in ANBP and BN, with ineffectiveness in ANR and ANP, with depression in EDNOS-AN, with hostility in ANR and EDNOS-BN, with interpersonal sensibility in ANP, with somatization in EDNOS-BN, and negatively with interpersonal distrust in EDNOS-AN. Prospective studies are needed to confirm whether or not altered PT parameters correlate with ED symptoms during the course of the diseases.

Psychoneuroendocrinology · clinical trial · 12 citationsread the source →

HIV combination prevention and declining orphanhood among adolescents, Rakai, Uganda, 2001-18: an observational community cohort study.

Background: Orphanhood increased markedly in the 1980s and 1990s in sub-Saharan Africa because of HIV-related mortality. Little is known about the contribution of HIV interventions, such as antiretroviral therapy (ART) and male medical circumcision, to more recent trends in orphanhood. In this study, we examined trends over time in maternal-only, paternal-only, and double orphanhood among adolescents before and after ART and male medical circumcision became widely available in the Rakai region of south-central Uganda. We sought to understand the association between adolescent orphanhood and HIV combination prevention (community-level ART use and prevalence of male medical circumcision). We hypothesised that increasing combination prevention, including greater use of ART and higher prevalence of male medical circumcision, would be associated with a lower probability of orphanhood. Methods: We examined the prevalence of orphanhood among adolescents aged 15-19 years, before and after roll-out of ART in mid-2004 and male medical circumcision in 2007, using data from 28 continuously followed communities within the Rakai Community Cohort Study. We used multinomial logistic regression with clustered SEs to estimate adjusted relative risk ratios (RRs) for maternal-only, paternal-only, and double orphanhood compared with non-orphanhood over 11 survey rounds between 2001 and 2018. Controlling for community HIV prevalence, household socioeconomic status, and adolescent age, we examined the association between community prevalence of ART use among people living with HIV and prevalence of male circumcision, including traditional circumcision. The primary outcome was orphanhood among adolescents aged 15-19 years. Findings: Orphanhood declined from 52% (920 of 1768 participants) in 2001-02 to 23% (592 of 2609 participants) by 2016-18 (p<0·0001), while double orphanhood declined from 20% (346 of 1768 participants) to 3% (86 of 2609 participants) (p<0·0001). Community prevalence of ART use among people living with HIV increased from 11% (105 of 945 participants) in 2005-06 to 78% (1163 of 1485 participants) in 2016-18. Male circumcision rates rose from 19% (147 of 790 participants) in 2005-06 to 65% (3535 of 5433 participants) in 2016-18. In the multinomial logistic regression model, a 10% increase in community prevalence of ART use was associated with a decrease in maternal orphanhood (adjusted relative RR 0·90, 95% CI 0·85-0·95) and double orphanhood (0·80, 0·75-0·85). In the post-ART era, a 10% increase in the community prevalence of male circumcision was associated with a decrease in paternal orphanhood (2005-18, adjusted relative RR 0·92, 0·87-0·97) and double orphanhood (0·91, 0·85-0·98). Interpretation: Widespread availability and uptake of HIV combination prevention was associated with marked reductions in orphanhood among adolescents. Reductions in orphanhood promise improved health and social outcomes for young people. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases.

The lancet. HIV · cohort or longitudinal · 5 citationsread the source →

Aggregated COVID-19 suicide incidences in India: Fear of COVID-19 infection is the prominent causative factor.

Many Indian COVID-19 suicide cases are turning the press-media attention and flooding in the social media platforms although, no particular studies assessed the COVID-19 suicide causative factors to a large extent. Therefore, the present study presents 69 COVID-19 suicide cases (aged 19 to 65 years; 63 cases were males). The suicide causalities are included as follows - fear of COVID-19 infection (n=21), followed by financial crisis (n=19), loneliness, social boycott and pressure to be quarantine, COVID-19 positive, COVID-19 work-related stress, unable to come back home due to lockdown, unavailability of alcohol etc. Considering the extreme psychological impacts related to COVID-19, there emerges a need for countrywide extensive tele-mental health care services.

Psychiatry research · editorial or comment · 225 citationsread the source →

A review and content analysis of engagement, functionality, aesthetics, information quality, and change techniques in the most popular commercial apps for weight management.

Background: There are thousands of apps promoting dietary improvement, increased physical activity (PA) and weight management. Despite a growing number of reviews in this area, popular apps have not been comprehensively analysed in terms of features related to engagement, functionality, aesthetics, information quality, and content, including the types of change techniques employed. Methods: The databases containing information about all Health and Fitness apps on GP and iTunes (7,954 and 25,491 apps) were downloaded in April 2015. Database filters were applied to select the most popular apps available in both stores. Two researchers screened the descriptions selecting only weight management apps. Features, app quality and content were independently assessed using the Mobile App Rating Scale (MARS) and previously-defined categories of techniques relevant to behaviour change. Inter-coder reliabilities were calculated, and correlations between features explored. Results: Of the 23 popular apps included in the review 16 were free (70%), 15 (65%) addressed weight control, diet and PA combined; 19 (83%) allowed behavioural tracking. On 5-point MARS scales, apps were of average quality (Md = 3.2, IQR = 1.4); "functionality" (Md = 4.0, IQR = 1.1) was the highest and "information quality" (Md = 2.0, IQR = 1.1) was the lowest domain. On average, 10 techniques were identified per app (range: 1-17) and of the 34 categories applied, goal setting and self-monitoring techniques were most frequently identified. App quality was positively correlated with number of techniques included (rho = .58, p < .01) and number of "technical" features (rho = .48, p < .05), which was also associated with the number of techniques included (rho = .61, p < .01). Apps that provided tracking used significantly more techniques than those that did not. Apps with automated tracking scored significantly higher in engagement, aesthetics, and overall MARS scores. Those that used change techniques previously associated with effectiveness (i.e., goal setting, self-monitoring and feedback) also had better "information quality". Conclusions: Popular apps assessed have overall moderate quality and include behavioural tracking features and a range of change techniques associated with behaviour change. These apps may influence behaviour, although more attention to information quality and evidence-based content are warranted to improve their quality.

The international journal of behavioral nutrition and physical activity · review · 228 citationsread the source →

Perceived Control and Work-Related Stress Mediate the Effects of Grit on Depression among Employees.

We developed and evaluated an interpersonal model of depression in employees, where passion and perseverance affect occupational stress and perceived control, which in turn affect risk of depression. The participants were employees of 18 private companies and local government organizations in Korea aged 19 to 65 years. A total of 11,422 participants completed questionnaires including the Korean version of the Grit scale, the occupational stress scale, the perceived control subscale in the perceived stress scale, and the Center for Epidemiologic Studies Depression Scale. Mediation analysis was performed to determine relationships among trait-level passion and perseverance, work-related stress, perceived control, and depression. Passion and perseverance preceded depression in employees. Higher occupational stress and lower perceived control mediated the association between passion and depression, and between perseverance and depression. Passion and perseverance exert preventive effects on depression by decreasing workplace stress and elevating perceived control. Future studies should investigate the effects of psychological characteristics on the development of depression in employees.

Brain sciences · 3 citationsread the source →

Occupational stress and depression of Korean employees: Moderated mediation model of burnout and grit.

Background: The present study investigated an interpersonal model of development of depressive symptoms in employees, where occupational stress affects burnout, which in turn affects risk for depression, and whether this mediation is moderated by grit. Methods: A total of 11,421 participants, aged 19 to 65 years, who were employees of 18 private companies and local government organizations in Korea were included. They completed questionnaires, including the Korean version of occupational stress scale, Oldenburg Burnout Inventory, Center for Epidemiologic Studies Depression scale and Grit scale. Mediation and moderation analyses were carried out in the Statistical Package for the Social Sciences PROCESS macro. Results: The association between occupational stress and depressive symptoms was mediated by exhaustion (b = -0.256, 95 % CI [0.244, 0.268]) and disengagement (b = -0.052, 95 % CI [0.039, 0.065]). Moreover, the effect of exhaustion on depressive symptoms was moderated by each grit, with the effect being stronger for employees with low grit (b = 0.939, p < 0.001 for passion and b = 0.629, p < 0.001 for perseverance) than for those with high grit (b = 0.944, p < 0.001 for passion and b = 0.686, p < 0.001 for perseverance). Limitations: The cross-sectional design of the study does not allow causal inferences. Conclusions: These findings contribute to the understanding of how occupational stress predicts depressive symptoms in the workplace and provide practical implications for preventing burnout and nurturing grit to protect employees' mental health in the workplace.

Journal of affective disorders · 16 citationsread the source →

Randomized Sham-Controlled Pilot Study of Neurocardiac Function in Patients With Acute Ischaemic Stroke Undergoing Heart Rate Variability Biofeedback.

Background: Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS). Methods: We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV via standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed via survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months. Results: We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, p = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, p = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, p = 0.029], which was not seen after sham biofeedback (SDNN: p = 0.63, RMSSD: p = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function (p = ns). Conclusions: Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism. Clinical Trial Registration: www. ClinicalTrials.gov, identifier: NCT03865225.

Frontiers in neurology · 13 citationsread the source →

Couple therapy for depression.

Background: Couple therapy for depression has the twofold aim of modifying negative interaction patterns and increasing mutually supportive aspects of intimate relationships, changing the interpersonal context of depression. Couple therapy is included in several guidelines among the suggested treatments for depression. Objectives: 1. The main objective was to examine the effects of couple therapy compared to individual psychotherapy for depression.2. Secondary objectives were to examine the effects of couple therapy compared to drug therapy and no/minimal treatment for depression. Search methods: The Cochrane Common Mental Disorders Group Controlled Trials Register (CCMDCTR), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid) and PsycINFO (Ovid) were searched to 19 February 2018. Relevant journals and reference lists were checked. Selection criteria: Randomised and quasi-randomised controlled trials examining the effects of couple therapy versus individual psychotherapy, drug therapy, or no treatment/minimal treatment for depression were included in the review. Data collection and analysis: We considered as primary outcomes the depressive symptom level, the depression persistence, and the dropouts; the relationship distress level was a secondary outcome. We extracted data using a standardised spreadsheet. Where data were not included in published papers, we tried to obtain the data from the authors. We synthesised data using Review Manager software version 5.3. We pooled dichotomous data using the relative risk (RR), and continuous data calculating the standardised mean difference (SMD), together with 95% confidence intervals (CIs). We employed the random-effects model for all comparisons and also calculated a formal test for heterogeneity, the natural approximate Chi2 test. Main results: We included fourteen studies from Europe, North America, and Israel, with 651 participants. Eighty per cent of participants were Caucasian. Therefore, the findings cannot be considered as applicable to non-Western countries or to other ethnic groups in Western countries. On average, participants had moderate depression, preventing the extension of results to severely depressed patients. Almost all participants were aged between 36 and 47 years. There was no evidence of difference in effect at the end of treatment between couple therapy and individual psychotherapy, either for the continuous outcome of depressive symptoms, based on nine studies with 304 participants (SMD -0.17, 95% CI -0.44 to 0.10, low-quality evidence), or the proportion of participants remaining depressed, based on six studies with 237 participants (RR 0.94, 95% CI 0.72 to 1.22, low-quality evidence). Findings from studies with 6-month or longer follow-up confirmed the lack of difference between the two conditions. No trial gave information on harmful effects. However, we considered rates of treatment discontinuation for any reason as a proxy indicator of adverse outcomes. There was no evidence of difference for dropout rates between couple therapy and individual psychotherapy, based on eight studies with 316 participants (RR 0.85, 95% CI 0.51 to 1.41, low-quality evidence).Few data were available for the comparison with drug therapy. Data from a small study with 12 participants showed no difference for the continuous outcome of depressive symptoms at end of treatment (SMD -0.51, 95% CI -1.69 to 0.66, very low-quality evidence) and at 6-month follow-up (SMD -1.07, 95% CI -2.45 to 0.31, very low-quality evidence). Data on dropouts from two studies with 95 participants showed a clear advantage for couple therapy (RR 0.31, 95% CI 0.15 to 0.61, very low-quality evidence). However, this finding was heavily influenced by a single study, probably affected by a selection bias favouring couple therapy. The comparison between couple therapy plus drug therapy and drug therapy alone showed no difference in depressive symptom level, based on two studies with 34 participants (SMD -1.04, 95% CI -3.97 to 1.89, very low-quality evidence) and on dropouts, based on two studies with 45 participants (RR 1.03, 95% CI 0.07 to 15.52, very low-quality evidence).The comparison with no/minimal treatment showed a large significant effect favouring couple therapy both for depressive symptom level, based on three studies with 90 participants: (SMD -0.95, 95% CI -1.59 to -0.32, very low-quality evidence) and persistence of depression, based on two studies with 65 participants (RR 0.48, 95% CI 0.32 to 0.70, very low-quality evidence). No data were available for dropouts for this comparison. Concerning relationship distress, the comparison with individual psychotherapy showed that couple therapy appeared more effective in reducing distress level at the end of treatment, based on six studies with 187 participants (SMD -0.50, CI -0.97 to -0.02, very low-quality evidence) and the persistence of distress, based on two studies with 81 participants (RR 0.71, 95% CI 0.51 to 0.98, very low-quality evidence). The quality of evidence was heavily affected by substantial heterogeneity (I2 = 59%). In the analysis restricted to studies including only distressed couples, no heterogeneity was found and the effect in distress level at the end of treatment was larger (SMD -1.10, 95% CI -1.59 to -0.61). Very few data on this outcome were available for other comparisons. We assessed the certainty of the evidence using the GRADE system. The results were weakened by the low quality of evidence related to the effects on depressive symptoms, in comparison with individual psychotherapy, and by very low quality evidence for all other comparisons and for the effects on relationship distress. Most studies were affected by problems such as the small number of cases, performance bias, assessment bias due to the non-blinding outcome assessment, incomplete outcome reporting and the allegiance bias of investigators. Heterogeneity was, in particular, a problem for data about relationship distress. Authors' conclusions: Although there is suggestion that couple therapy is as effective as individual psychotherapy in improving depressive symptoms and more effective in improving relations in distressed couples, the low or very low quality of the evidence seriously limits the possibility of drawing firm conclusions. Very few data were available for comparisons with no/minimal treatment and drug therapy. Future trials of high quality should test in large samples with a long follow-up of the effects of couple therapy in comparison to other interventions in discordant couples with a depressed partner, considering the role of relationship quality as a potential effect mediator in the improvement of depression.

The Cochrane database of systematic reviews · meta-analysis · 21 citationsread the source →

Interventions for the treatment of metastatic extradural spinal cord compression in adults.

Background: Metastatic extradural spinal cord compression (MESCC) is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects. This is an updated version of the original Cochrane review published in theCochrane Database of Systematic Reviews (Issue 4, 2008). Objectives: To determine the efficacy and safety of radiotherapy, surgery and corticosteroids in MESCC. Search methods: In March 2015, we updated previous searches (July 2008 and December 2013) of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS, CANCERLIT, clinical trials registries, conference proceedings, and references, without language restrictions. We also contacted experts for relevant published, unpublished and ongoing trials. Selection criteria: Randomised controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC. Data collection and analysis: Three authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. Where possible, we pooled relative risks with their 95% confidence intervals, using a random effects model if heterogeneity was significant. We assessed overall evidence-quality using the GRADE approach. Main results: This update includes seven trials involving 876 (723 evaluable) adult participants (19 to 87 years) in high-income countries. Most were free of the risk of bias. Different radiotherapy doses and schedulesTwo equivalence trials in people with MESCC and a poor prognosis evaluated different radiotherapy doses and schedules. In one, a single dose (8 Gray (Gy)) of radiotherapy (RT) was as effective as short-course RT (16 Gy in two fractions over one week) in enhancing ambulation in the short term (65% versus 69%; risk ratio (RR) was 0.93, (95% confidence interval (CI) 0.82 to 1.04); 303 participants; moderate quality evidence). The regimens were also equally effective in reducing analgesic and narcotic use (34% versus 40%; RR 0.85, 95% CI 0.62 to 1.16; 271 participants), and in maintaining urinary continence (90% versus 87%; RR 1.03, 95% CI 0.96 to 1.1; 303 participants) in the short term (moderate quality evidence). In the other trial, split-course RT (30 Gy in eight fractions over two weeks) was no different from short-course RT in enhancing ambulation (70% versus 68%; RR 1.02, 95% CI 0.9 to 1.15; 276 participants); reducing analgesic and narcotic use (49% versus 38%; RR 1.27, 95% CI 0.96 to 1.67; 262 participants); and in maintaining urinary continence (87% versus 90%; RR 0.97, 0.93 to 1.02; 275 participants) in the short term (moderate quality evidence). Median survival was similar with the three RT regimens (four months). Local tumour recurrence may be more common with single-dose compared to short-course RT (6% versus 3%; RR 2.21, 95% CI 0.69 to 7.01; 303 participants) and with short-course compared to split-course RT (4% versus 0%; RR 0.1, 95% CI 0.01 to 1.72; 276 participants), but these differences were not statistically significant (low quality evidence). Gastrointestinal adverse effects were infrequent with the three RT regimens (moderate quality evidence), and serious adverse events or post-radiotherapy myelopathy were not noted. We did not find trials comparing radiotherapy schedules in people with MESCC and a good prognosis. Surgery plus radiotherapy compared to radiotherapyLaminectomy plus RT offered no advantage over RT in one small trial with 29 participants (very low quality evidence). In another trial that was stopped early for apparent benefit, decompressive surgery plus RT resulted in better ambulatory rates (84% versus 57%; RR 1.48, 95% CI 1.16 to 1.90; 101 participants, low quality evidence). Narcotic use may also be lower, and bladder control may also be maintained longer than with than RT in selected patients (low quality evidence). Median survival was longer after surgery (126 days versus 100 days), but the proportions surviving at one month (94% versus 86%; RR 1.09, 95% CI 0.96 to 1.24; 101 participants) did not differ significantly (low quality evidence). Serious adverse events were not noted. Significant benefits with surgery occurred only in people younger than 65 years. High dose corticosteroids compared to moderate dose or no corticosteroidsData from three small trials suggest that high-dose steroids may not differ from moderate-dose or no corticosteroids in enhancing ambulation (60% versus 55%; RR 1.08, 95% CI 0.81 to 1.45; 3 RCTs, 105 participants); survival over two years (11% versus 10%; RR 1.11, 95% CI 0.24 to 5.05; 1 RCT, 57 participants); pain reduction (78% versus 91%; RR 0.86, 95% CI 0.62 to 1.20; 1 RCT, 25 participants); or urinary continence (63% versus 53%; RR 1.18, 95% CI 0.66 to 2.13; 1 RCT, 34 participants; low quality evidence). Serious adverse effects were more frequent with high-dose corticosteroids (17% versus 0%; RR 8.02, 95% CI 1.03 to 62.37; 2 RCTs, 77 participants; moderate quality evidence).None of the trials reported satisfaction with care or quality of life in participants. Authors' conclusions: Based on current evidence, ambulant adults with MESCC with stable spines and predicted survival of less than six months will probably benefit as much from one dose of radiation (8 Gy) as from two doses (16 Gy) or eight doses (30 Gy). We are unsure if a single dose is as effective as two or more doses in preventing local tumour recurrence. Laminectomy preceding radiotherapy may offer no benefits over radiotherapy alone. Decompressive surgery followed by radiotherapy may benefit ambulant and non-ambulant adults younger than 65 years of age, with poor prognostic factors for radiotherapy, a single area of compression, paraplegia for less than 48 hours, and a predicted survival of more than six months. We are uncertain whether high doses of corticosteroids offer any benefits over moderate doses or indeed no corticosteroids; but high-dose steroids probably significantly increases the risk of serious adverse effects. Early detection; and treatment based on neurological status, age and estimated survival, are crucial with all treatment modalities. Most of the evidence was of low quality. High-quality evidence from more trials is needed to clarify current uncertainties, and some studies are in progress.

The Cochrane database of systematic reviews · meta-analysis · 39 citationsread the source →

Effects of non-health-targeted policies on migrant health: a systematic review and meta-analysis.

Background: Government policies can strongly influence migrants' health. Using a Health in All Policies approach, we systematically reviewed evidence on the impact of public policies outside of the health-care system on migrant health. Methods: We searched the PubMed, Embase, and Web of Science databases from Jan 1, 2000, to Sept 1, 2017, for quantitative studies comparing the health effects of non-health-targeted public policies on migrants with those on a relevant comparison population. We searched for articles written in English, Swedish, Danish, Norwegian, Finnish, French, Spanish, or Portuguese. Qualitative studies and grey literature were excluded. We evaluated policy effects by migration stage (entry, integration, and exit) and by health outcome using narrative synthesis (all included studies) and random-effects meta-analysis (all studies whose results were amenable to statistical pooling). We summarised meta-analysis outcomes as standardised mean difference (SMD, 95% CI) or odds ratio (OR, 95% CI). To assess certainty, we created tables containing a summary of the findings according to the Grading of Recommendations Assessment, Development, and Evaluation. Our study was registered with PROSPERO, number CRD42017076104. Findings: We identified 43 243 potentially eligible records. 46 articles were narratively synthesised and 19 contributed to the meta-analysis. All studies were published in high-income countries and examined policies of entry (nine articles) and integration (37 articles). Restrictive entry policies (eg, temporary visa status, detention) were associated with poor mental health (SMD 0·44, 95% CI 0·13-0·75; I2=92·1%). In the integration phase, restrictive policies in general, and specifically regarding welfare eligibility and documentation requirements, were found to increase odds of poor self-rated health (OR 1·67, 95% CI 1·35-1·98; I2=82·0%) and mortality (1·38, 1·10-1·65; I2=98·9%). Restricted eligibility for welfare support decreased the odds of general health-care service use (0·92, 0·85-0·98; I2=0·0%), but did not reduce public health insurance coverage (0·89, 0·71-1·07; I2=99·4%), nor markedly affect proportions of people without health insurance (1·06, 0·90-1·21; I2=54·9%). Interpretation: Restrictive entry and integration policies are linked to poor migrant health outcomes in high-income countries. Efforts to improve the health of migrants would benefit from adopting a Health in All Policies perspective. Funding: Swedish Council for Health, Working Life, and Social Research; UK Medical Research Council; Scottish Government Chief Scientist Office.

The Lancet. Global health · meta-analysis · 123 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, setting, and participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main outcomes and measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial registration: ClinicalTrials.gov Identifier: NCT02665481.

JAMA · randomised controlled trial · 109 citationsread the source →

Prognostic importance and long-term determinants of self-rated health after initial acute myocardial infarction.

Background: Self-rated health (SRH) is a valid measure of health and its trajectories over time have been found to predict mortality. A better understanding of the determinants of changes in SRH is required, particularly post-myocardial infarction (MI), where rapid changes in health may occur. Objectives: To evaluate the prognostic importance of SRH and the determinants of its long-term trajectory in patients with MI. Patients and methods: Between February 1992 and February 1993, 1521 consecutive patients aged <or=65 years (19% women) discharged from all hospitals in central Israel after initial acute MI were enrolled and followed-up for a mean of 12 years. Extensive data were obtained at study entry, with SRH measured at baseline (retrospective assessment of pre-MI health status) and at 5 and 10 years. Results: Baseline SRH showed a strong graded association with mortality post-MI. The association was further strengthened when changes in SRH over time were taken into account. Using generalized estimating equations, independent predictors of poor SRH at follow-up were Asian/African origin, low education, poor income, low baseline SRH, comorbidity, impaired ejection fraction, diabetes, dyslipidemia, obesity, and physical inactivity. In a subsample with available psychosocial measures (n = 668), low social support and sense of coherence and high anxiety and depression were also predictive of poor SRH. Conclusions: SRH is an important risk marker after MI and its long-term trajectory is accurately predicted by demographic, socioeconomic, clinical, and psychosocial measures. Monitoring of SRH post-MI is therefore warranted.

Medical care · 47 citationsread the source →

Choosing between staying at home or moving: A systematic review of factors influencing housing decisions among frail older adults.

Background: Most older adults wish to stay at home during their late life years, but physical disabilities and cognitive impairment may force them to face a housing decision. However, they lack relevant information to make informed value-based housing decisions. Consequently, we sought to identify the sets of factors influencing the housing decision-making of older adults. Methods: We performed a systematic literature search for studies evaluating any factors influencing the housing decisions among older adults over 65 years old without cognitive disabilities. Primary research from any study design reported after 1990 in a peer-reviewed journal, a book chapter or an evaluated doctoral thesis and written in English, French or Spanish were eligible. We extracted the main study characteristics, the participant characteristics and any factors reported as associated with the housing decision. We conducted a qualitative thematic analysis from the perspective of the meaning and experience of home. Results: The search resulted in 660 titles (after duplicate removal) from which 86 studies were kept for analysis. One study out of five reported exclusively on frail older adults (n = 17) and two on adults over 75 years old. Overall, a total of 88 factors were identified, of which 71 seem to have an influence on the housing decision-making of older adults, although the influence of 19 of them remains uncertain due to discrepancies between research methodologies. No conclusion was made regarding 12 additional factors due to lack of evidence. Conclusion: A wealth of factors were found to influence housing decisions among older adults. However, very few of them have been studied extensively. Our results highlight the importance of interdisciplinary teamwork to study the influence of a broader range of factors as a whole. These results will help older adults make the best possible housing decision based on their unique situation and values.

PloS one · systematic review · 99 citationsread the source →

Continuing education meetings and workshops: effects on professional practice and healthcare outcomes.

Background: Educational meetings are used widely by health personnel to provide continuing medical education and to promote implementation of innovations or translate new knowledge to change practice within healthcare systems. Previous reviews have concluded that educational meetings can result in small changes in behaviour, but that effects vary considerably. Investigations into which characteristics of educational meetings might lead to greater impact have yielded varying results, and factors that might explain heterogeneity in effects remain unclear. This is the second update of this Cochrane Review. Objectives: • To assess the effects of educational meetings on professional practice and healthcare outcomes • To investigate factors that might explain the heterogeneity of these effects SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ERIC, Science Citation Index Expanded (ISI Web of Knowledge), and Social Sciences Citation Index (last search in November 2016). Selection criteria: We sought randomised trials examining the effects of educational meetings on professional practice and patient outcomes. Data collection and analysis: Two review authors independently extracted data and assessed risk of bias. One review author assessed the certainty of evidence (GRADE) and discussed with a second review author. We included studies in the primary analysis that reported baseline data and that we judged to be at low or unclear risk of bias. For each comparison of dichotomous outcomes, we measured treatment effect as risk difference adjusted for baseline compliance. We expressed adjusted risk difference values as percentages, and we noted that values greater than zero favour educational meetings. For continuous outcomes, we measured treatment effect as per cent change relative to the control group mean post test, adjusted for baseline performance; we expressed values as percentages and noted that values greater than zero favour educational meetings. We report means and 95% confidence intervals (CIs) and, when appropriate, medians and interquartile ranges to facilitate comparisons to previous versions of this review. We analysed professional and patient outcomes separately and analysed 22 variables that were hypothesised a priori to explain heterogeneity. We explored heterogeneity by using univariate meta-regression and by inspecting violin plots. Main results: We included 215 studies involving more than 28,167 health professionals, including 142 new studies for this update. Educational meetings as the single intervention or the main component of a multi-faceted intervention compared with no intervention • Probably slightly improve compliance with desired practice when compared with no intervention (65 comparisons, 7868 health professionals for dichotomous outcomes (adjusted risk difference 6.79%, 95% CI 6.62% to 6.97%; median 4.00%; interquartile range 0.29% to 13.00%); 28 comparisons, 2577 health professionals for continuous outcomes (adjusted relative percentage change 44.36%, 95% CI 41.98% to 46.75%; median 20.00%; interquartile range 6.00% to 65.00%)) • Probably slightly improve patient outcomes compared with no intervention (15 comparisons, 2530 health professionals for dichotomous outcomes (adjusted risk difference 3.30%, 95% CI 3.10% to 3.51%; median 0.10%; interquartile range 0.00% to 4.00%); 28 comparisons, 2294 health professionals for continuous outcomes (adjusted relative percentage change 8.35%, 95% CI 7.46% to 9.24%; median 2.00%; interquartile range -1.00% to 21.00%)) The certainty of evidence for this comparison is moderate. Educational meetings alone compared with other interventions • May improve compliance with desired practice when compared with other interventions (6 studies, 1402 health professionals for dichotomous outcomes (adjusted risk difference 9.99%, 95% CI 9.47% to 10.52%; median 16.5%; interquartile range 0.80% to 16.50%); 2 studies, 72 health professionals for continuous outcomes (adjusted relative percentage change 12.00%, 95% CI 9.16% to 14.84%; median 12.00%; interquartile range 0.00% to 24.00%)) No studies met the inclusion criteria for patient outcome measurements. The certainty of evidence for this comparison is low. Interactive educational meetings compared with didactic (lecture-based) educational meetings • We are uncertain of effects on compliance with desired practice (3 studies, 370 health professionals for dichotomous outcomes; 1 study, 192 health professionals for continuous outcomes) or on patient outcomes (1 study, 54 health professionals for continuous outcomes), as the certainty of evidence is very low Any other comparison of different formats and durations of educational meetings • We are uncertain of effects on compliance with desired practice (1 study, 19 health professionals for dichotomous outcomes; 1 study, 20 health professionals for continuous outcomes) or on patient outcomes (1 study, 113 health professionals for continuous outcomes), as the certainty of evidence is very low. Factors that might explain heterogeneity of effects Meta-regression suggests that larger estimates of effect are associated with studies judged to be at high risk of bias, with studies that had unit of analysis errors, and with studies in which the unit of analysis was the provider rather than the patient. Improved compliance with desired practice may be associated with: shorter meetings; poor baseline compliance; better attendance; shorter follow-up; professionals provided with additional take-home material; explicit building of educational meetings on theory; targeting of low- versus high-complexity behaviours; targeting of outcomes with high versus low importance; goal of increasing rather than decreasing behaviour; teaching by opinion leaders; and use of didactic versus interactive teaching methods. Pre-specified exploratory analyses of behaviour change techniques suggest that improved compliance with desired practice may be associated with use of a greater number of behaviour change techniques; goal-setting; provision of feedback; provision for social comparison; and provision for social support. Compliance may be decreased by the use of follow-up prompts, skills training, and barrier identification techniques. Authors' conclusions: Compared with no intervention, educational meetings as the main component of an intervention probably slightly improve professional practice and, to a lesser extent, patient outcomes. Educational meetings may improve compliance with desired practice to a greater extent than other kinds of behaviour change interventions, such as text messages, fees, or office systems. Our findings suggest that multi-strategy approaches might positively influence the effects of educational meetings. Additional trials of educational meetings compared with no intervention are unlikely to change the review findings; therefore we will not further update this review comparison in the future. However, we note that randomised trials comparing different types of education are needed.

The Cochrane database of systematic reviews · systematic review · 139 citationsread the source →

Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Multifactorial and multiple component interventions for preventing falls in older people living in the community.

Background: Falls and fall-related injuries are common, particularly in those aged over 65, with around one-third of older people living in the community falling at least once a year. Falls prevention interventions may comprise single component interventions (e.g. exercise), or involve combinations of two or more different types of intervention (e.g. exercise and medication review). Their delivery can broadly be divided into two main groups: 1) multifactorial interventions where component interventions differ based on individual assessment of risk; or 2) multiple component interventions where the same component interventions are provided to all people. Objectives: To assess the effects (benefits and harms) of multifactorial interventions and multiple component interventions for preventing falls in older people living in the community. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, trial registers and reference lists. Date of search: 12 June 2017. Selection criteria: Randomised controlled trials, individual or cluster, that evaluated the effects of multifactorial and multiple component interventions on falls in older people living in the community, compared with control (i.e. usual care (no change in usual activities) or attention control (social visits)) or exercise as a single intervention. Data collection and analysis: Two review authors independently selected studies, assessed risks of bias and extracted data. We calculated the rate ratio (RaR) with 95% confidence intervals (CIs) for rate of falls. For dichotomous outcomes we used risk ratios (RRs) and 95% CIs. For continuous outcomes, we used the standardised mean difference (SMD) with 95% CIs. We pooled data using the random-effects model. We used the GRADE approach to assess the quality of the evidence. Main results: We included 62 trials involving 19,935 older people living in the community. The median trial size was 248 participants. Most trials included more women than men. The mean ages in trials ranged from 62 to 85 years (median 77 years). Most trials (43 trials) reported follow-up of 12 months or over. We assessed most trials at unclear or high risk of bias in one or more domains. Forty-four trials assessed multifactorial interventions and 18 assessed multiple component interventions. (I2 not reported if = 0%).Multifactorial interventions versus usual care or attention controlThis comparison was made in 43 trials. Commonly-applied or recommended interventions after assessment of each participant's risk profile were exercise, environment or assistive technologies, medication review and psychological interventions. Multifactorial interventions may reduce the rate of falls compared with control: rate ratio (RaR) 0.77, 95% CI 0.67 to 0.87; 19 trials; 5853 participants; I2 = 88%; low-quality evidence. Thus if 1000 people were followed over one year, the number of falls may be 1784 (95% CI 1553 to 2016) after multifactorial intervention versus 2317 after usual care or attention control. There was low-quality evidence of little or no difference in the risks of: falling (i.e. people sustaining one or more fall) (RR 0.96, 95% CI 0.90 to 1.03; 29 trials; 9637 participants; I2 = 60%); recurrent falls (RR 0.87, 95% CI 0.74 to 1.03; 12 trials; 3368 participants; I2 = 53%); fall-related hospital admission (RR 1.00, 95% CI 0.92 to 1.07; 15 trials; 5227 participants); requiring medical attention (RR 0.91, 95% CI 0.75 to 1.10; 8 trials; 3078 participants). There is low-quality evidence that multifactorial interventions may reduce the risk of fall-related fractures (RR 0.73, 95% CI 0.53 to 1.01; 9 trials; 2850 participants) and may slightly improve health-related quality of life but not noticeably (SMD 0.19, 95% CI 0.03 to 0.35; 9 trials; 2373 participants; I2 = 70%). Of three trials reporting on adverse events, one found none, and two reported 12 participants with self-limiting musculoskeletal symptoms in total. Multifactorial interventions versus exerciseVery low-quality evidence from one small trial of 51 recently-discharged orthopaedic patients means that we are uncertain of the effects on rate of falls or risk of falling of multifactorial interventions versus exercise alone. Other fall-related outcomes were not assessed. Multiple component interventions versus usual care or attention controlThe 17 trials that make this comparison usually included exercise and another component, commonly education or home-hazard assessment. There is moderate-quality evidence that multiple interventions probably reduce the rate of falls (RaR 0.74, 95% CI 0.60 to 0.91; 6 trials; 1085 participants; I2 = 45%) and risk of falls (RR 0.82, 95% CI 0.74 to 0.90; 11 trials; 1980 participants). There is low-quality evidence that multiple interventions may reduce the risk of recurrent falls, although a small increase cannot be ruled out (RR 0.81, 95% CI 0.63 to 1.05; 4 trials; 662 participants). Very low-quality evidence means that we are uncertain of the effects of multiple component interventions on the risk of fall-related fractures (2 trials) or fall-related hospital admission (1 trial). There is low-quality evidence that multiple interventions may have little or no effect on the risk of requiring medical attention (RR 0.95, 95% CI 0.67 to 1.35; 1 trial; 291 participants); conversely they may slightly improve health-related quality of life (SMD 0.77, 95% CI 0.16 to 1.39; 4 trials; 391 participants; I2 = 88%). Of seven trials reporting on adverse events, five found none, and six minor adverse events were reported in two. Multiple component interventions versus exerciseThis comparison was tested in five trials. There is low-quality evidence of little or no difference between the two interventions in rate of falls (1 trial) and risk of falling (RR 0.93, 95% CI 0.78 to 1.10; 3 trials; 863 participants) and very low-quality evidence, meaning we are uncertain of the effects on hospital admission (1 trial). One trial reported two cases of minor joint pain. Other falls outcomes were not reported. Authors' conclusions: Multifactorial interventions may reduce the rate of falls compared with usual care or attention control. However, there may be little or no effect on other fall-related outcomes. Multiple component interventions, usually including exercise, may reduce the rate of falls and risk of falling compared with usual care or attention control.

The Cochrane database of systematic reviews · systematic review · 293 citationsread the source →

Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study.

Background: Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women as options are scarce for those who cannot or do not want to take hormone therapy. Fezolinetant is one of the first non-hormonal neurokinin 3 receptor antagonists in development for the treatment of vasomotor symptoms due to menopause. This study investigated the safety and efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. Methods: SKYLIGHT 1 is a randomised, double-blind, placebo-controlled, 12-week, phase 3 trial with a 40-week active treatment extension. This trial was done at 97 facilities across the USA, Canada, Czech Republic, Hungary, Poland, Spain, and the UK. Women aged 40-65 years with an average of seven or more moderate-to-severe hot flashes per day were randomly assigned (1:1:1) to once-daily exact-matched placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Randomisation was done using a web-based interactive response system and investigators, project team members, clinical staff, and participants were masked to treatment assignment. Coprimary endpoints were mean change in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12. The efficacy and safety analyses comprised all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT04003155) and is completed. Findings: Between July 11, 2019, and Aug 11, 2021, 2205 women were recruited of whom 175 were assigned to placebo, 176 to fezolinetant 30 mg, and 176 to fezolinetant 45 mg (175 in the placebo group, 174 in the fezolinetant 30 mg group, and 173 in the fezolinetant 45 mg received at least one dose [safety analysis set]). One participant randomly assigned to fezolinetant 45 mg received fezolinetant 30 mg in error, so the efficacy analysis set (full analysis set) consisted of 173 in the fezolinetant 30 mg group and 174 in the fezolinetant 45 mg group. 23 participants in the placebo group, 31 in the fezolinetant 30 mg group, and 13 in the fezolinetant 45 mg group discontinued treatment before week 12, mostly due to adverse events or participant withdrawal. Compared with placebo, fezolinetant 30 mg and fezolinetant 45 mg significantly reduced the frequency of vasomotor symptoms at week 4 (difference in change in least squares mean -1·87 [SE 0·42; p<0·001], -2·07 [SE 0·42; p<0·001]) and week 12 (-2·39 [SE 0·44; p<0·001], -2·55 [SE 0·43; p<0·001]). Compared with placebo, fezolinetant 30 mg and 45 mg significantly reduced the severity of vasomotor symptoms at week 4 (-0·15 [0·06; p=0·012], -0·19 [0·06; p=0·002]) and week 12 (-0·24 [0·08; p=0·002], -0·20 [0·08; p=0·007]). Improvements in frequency and severity of vasomotor symptoms were observed after 1 week and maintained over 52 weeks. During the first 12 weeks, treatment-emergent adverse events occurred in 65 (37%) of 174 women in the fezolinetant 30 mg group, 75 (43%) of 173 in the fezolinetant 45 mg group, and 78 (45%) of 175 in the placebo group. The incidence of liver enzyme elevations was low (placebo n=1; fezolinetant 30 mg n=2; fezolinetant 45 mg n=0) and these events were generally asymptomatic, transient, and resolved while on treatment or after treatment discontinuation. Interpretation: Data support the clinical use of fezolinetant as a non-hormonal treatment for vasomotor symptoms associated with menopause. The study was placebo-controlled for 12 weeks followed by a 40-week blinded extension to assess the maintenance of effect. Furthermore, the population studied was diverse and representative of the potential target population for fezolinetant therapy. Further characterisation of the benefit of fezolinetant on quality of life, including on symptoms of mood and sexual wellbeing, merits investigation. Funding: Astellas Pharma.

Lancet (London, England) · randomised controlled trial · 172 citationsread the source →

Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial.

Background: A pneumococcal conjugate vaccine (PCV) specifically focused on serotypes associated with adult residual disease burden is urgently needed. We aimed to assess V116, an investigational 21-valent PCV, that contains pneumococcal polysaccharides (PnPs), which account for 74-94% of invasive pneumococcal disease in adults aged 65 years or older. Methods: We did a phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, non-inferiority and superiority trial. The phase 1 study was done at two clinical sites in the USA, and the phase 2 study was done in 18 clinical sites in the USA. Eligible participants were healthy adults with or without chronic medical conditions assessed as stable, aged 18-49 years in the phase 1 trial and aged 50 years or older in the phase 2 trial. Participants were excluded if they had a history of invasive pneumococcal disease or other culture-positive pneumococcal disease within the past 3 years, known hypersensitivity to a vaccine component, known or suspected impairment of immunological function, were pregnant or were breastfeeding, or had previously received any pneumococcal vaccine. Participants had to abstain from sexual activity or use protocol approved contraception. All participants were centrally randomly assigned to a vaccine group using an interactive response technology system. Participants and investigators were masked to group assignment. In phase 1, participants were randomly assigned (1:1:1) to receive a single dose of V116-1 (2 μg per pneumococcal polysaccharide [PnP] per 0·5 mL) or V116-2 (4 μg per PnP per 1·0 mL) or the 23-valent unconjugated PnP vaccine, PPSV23 (25 μg per PnP per 0·5 mL). In phase 2, participants were randomly assigned (1:1) to receive one dose of V116 (4 μg per PnP per 1·0 mL) or PPSV23 (25 μg per PnP per 0·5 mL), stratified by age. Safety analyses included all randomly assigned participants who received study vaccine; immunogenicity analyses were per protocol. For both phases, the primary safety outcome was the proportion of participants with solicited injection-site adverse events and solicited systemic adverse events up to day 5 after vaccination and the proportion of participants with vaccine-related serious adverse events to 6 months after vaccination. In phase 2, primary immunogenicity outcomes were to test non-inferiority of V116 compared with PPSV23 as measured by serotype-specific opsonophagocytic antibody geometric mean titres (OPA-GMT) ratios for the serotypes common to the two vaccines at 30 days after vaccination (using a 0·33 margin) and to test superiority of V116 compared with PPSV23 as measured by serotype-specific OPA-GMT ratios for the serotypes unique to V116 at 30 days after vaccination (using a 1·0 margin). This trial is registered with Clinicaltrials.gov, NCT04168190. Findings: Between Dec 6 and 26, 2019, 92 volunteers were screened and 90 (98%) enrolled for phase 1 (59 [66%] women; 31 [34%] men); 30 participants were assigned to each group and received study vaccine. 30 (100%) participants in the V116-1 group, 29 (97%) in the V116-2 group, and 30 (100%) participants in the PPSV23 group were included in the per-protocol immunogenicity evaluation. From Sept 23, 2020, to Jan 12, 2021, 527 volunteers were screened, and 510 (97%) participants were enrolled in the phase 2 trial. 508 participants (>99%; 254 [100%] of 254 participants randomly assigned to the V116 group and 254 [99%] of 256 randomly assigned to PPSV23 group) received study vaccine (281 [55%] women; 227 [45%] men). 252 (99%) of 254 of participants in the V116 group and 254 (99%) of 256 participants in the PPSV23 group were included in the primary immunogenicity analyses. There were no vaccine-related serious adverse events or vaccine-related deaths in either study phase. In both phases, the most common solicited injection site adverse event was injection site pain (phase 1 22 [73%] participants in V116-1 group, 23 [77%] participants in V116-2 group, and 17 [57%] participants in the PPSV23 group; phase 2 118 [46%] of 254 participants in the V116 group and 96 [38%] of 254 in the PPSV23 group]. The most common solicited systemic adverse events in phase 1 was fatigue (eight [27%] participants in the V116-1 group, eight [27%] participants in the V116-2 group, and five [17%] participants in PPSV23 group) and myalgia (eight [27%] participants in the V116-1 group, nine (30%) participants in the V116-2 group, and four (13%) participants in the PPSV23 group]. In phase 2, the most frequently reported solicited systemic adverse event was fatigue (49 [19%] participants in V116 group, and 31 [12%] participants in PPSV23 group). In both phases, most of the solicited adverse events in all vaccine groups were mild and of short duration (≤3 days). V116 met non-inferiority criteria compared with PPSV23 for the 12 shared serotypes and met superiority criteria compared to PPSV23 for the nine unique serotypes. Interpretation: V116 was well tolerated with a safety profile generally similar to PPSV23; consistent with licensed pneumococcal conjugate vaccines. Functional OPA antibodies were induced to all V116 vaccine serotypes. The vaccine was non-inferior to PPSV23 for the 12 serotypes common to both vaccines and superior to PPSV23 for the nine unique serotypes in V116. Our findings support the development of V116 for prevention of pneumococcal disease in adults. Funding: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA.

The Lancet. Infectious diseases · randomised controlled trial · 73 citationsread the source →

The effects of volunteering on loneliness among lonely older adults: the HEAL-HOA dual randomised controlled trial.

Background: Previous randomised controlled trials have largely relied on self-reported volunteer work to assess the effects of volunteering and have rarely provided structured volunteering activities during the intervention period. The present study aimed to investigate the effects of social volunteering work over 12 months on loneliness among older adults during the COVID-19 pandemic. Methods: A dual randomised controlled trial was done in Hong Kong to investigate the long-term effects of telephone-delivered psychosocial interventions by older Chinese volunteers who were screened as lonely, for older adult recipients who had low income, lived alone, felt lonely, and were digitally excluded. Participants were included if they were aged 50-70 years; had provided consent to be trained and serve as a volunteer for at least 2 h per week for 6 months; had at least 3 years of secondary school education; had no severe self-reported physical, mental, or cognitive health problems; were not working full or part-time; had engaged in formal volunteering fewer than four times within the past year; and were lonely (ie, had a score of at least 6 on the three-item UCLA Loneliness Scale). Participants were allocated into either the volunteering or control group (psychoeducation programme) using a random number method. The details of group allocation were concealed as the research assistant responsible for randomisation was different to the research assistants responsible for recruitment and assessments (who were masked to the condition). Following a 6-week training, the volunteers delivered a psychosocial intervention to older intervention recipients for 6 months. The primary outcome was loneliness measured with the 20-item UCLA Loneliness Scale and the De Jong Gierveld (DJG) Loneliness Scales at 6 months and 12 months. Assessments were performed before training (baseline; T1), at 6 months (T2), and at 12 months after training (T3). The intention-to-treat principle was used to compare the effects of volunteering between the two groups. The trial was registered in the Clinical Trials Registry of the University of Hong Kong Clinical Trials Centre (HKUCTR-2929). This trial has completed. Findings: Between May 3, 2021, and Oct 6, 2022, a total of 375 individuals were recruited to the trial, including 84 males (22%) and 291 females (78%). 185 were randomly assigned to the volunteering group (56 to deliver a mindfulness intervention, 65 to deliver a behavioural activation intervention, and 64 to deliver a befriending intervention) and 190 were assigned to the control group. 311 (83%) of 375 participants were 60 years or older (median 64 years [SD 4·86]). Participants in the volunteering group reported a significantly lower level of loneliness at T2 (dppc2 ranged from -0·41 to -0·70) compared with T1 than participants in the control condition. There was a significant decrease in loneliness measured using the UCLA Loneliness Scale at T2 in the volunteering group but such a decline was not shown in the control group (condition × time interaction, estimate 0·19 [95% CI 0·08 to 0·29], p=0·00058, dppc2=-0·41). Similarly, when measured with the DJG Loneliness Scale, there was a significantly greater decrease in loneliness in the volunteering group compared with the control group at T2, including a medium to large effect size on total DJG scores (estimate 1·34 [95% CI 0·83 to 1·84], p<0·0001, dppc2=-0·70) and a medium effect size on emotional (estimate 0·63 [0·35 to 0·90], p<0·0001, dppc2=-0·59) and social subscales (estimate 0·71 [95% CI 0·37 to 1·05], p<0·0001, dppc2=-0·58). Although most of the positive effects of volunteering were not sustained at T3, the volunteers who continued to volunteer for more than 2 h per week at T3 reported lower levels of loneliness than those who did not maintain volunteering. Interpretation: This randomised controlled trial demonstrates the beneficial effect of volunteering on reducing loneliness in older adults who feel lonely, and that this benefit can be maintained through continued participation in voluntary work. Future intervention programmes should strengthen older adults' commitment to volunteer. Funding: Research Grants Committee of the Hong Kong Special Administrative Region, China.

The lancet. Healthy longevity · randomised controlled trial · 16 citationsread the source →

Clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder (PARADES): a pragmatic, multicentre, observer-blind, randomised controlled superiority trial.

Background: Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods: We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings: Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (58%) participants in the psychoeducation group had experienced a next bipolar episode compared with 98 (65%) participants in the peer-support group; time to next bipolar episode did not differ between groups (hazard ratio [HR] 0·83, 95% CI 0·62-1·11; p=0·217). Planned moderator analysis showed that psychoeducation was most beneficial in participants with few (one to seven) previous bipolar episodes (χ2; HR 0·28, 95% CI 0·12-0·68; p=0·034). Four (1%) participants (one in the psychoeducation group and three in the peer-support group) died during follow-up; these deaths were deemed unrelated to the study interventions or procedures. Interpretation: Structured group psychoeducation was no more clinically effective than similarly intensive unstructured peer support, but was more acceptable and improved outcome in participants with fewer previous bipolar episodes. Optimum provision of structured psychological interventions, such as group psychoeducation, early in the course of bipolar disorder might have important benefits on the course of illness, and merits further research. Funding: National Institute for Health Research.

The lancet. Psychiatry · randomised controlled trial · 42 citationsread the source →

Impact of a combined multimodal-aerobic and multimodal intervention compared to standard aerobic treatment in breast cancer survivors with chronic cancer-related fatigue - results of a three-armed pragmatic trial in a comprehensive cohort design.

Background: Cancer-related fatigue (CRF) and insomnia are major complaints in breast cancer survivors (BC). Aerobic training (AT), the standard therapy for CRF in BC, shows only minor to moderate treatment effects. Other evidence-based treatments include cognitive behavioral therapy, e.g., sleep education/restriction (SE) and mindfulness-based therapies. We investigated the effectiveness of a 10-week multimodal program (MT) consisting of SE, psycho-education, eurythmy- and painting-therapy, administered separately or in combination with AT (CT) and compared both arms to AT alone. Methods: In a pragmatic comprehensive cohort study BC with chronic CRF were allocated randomly or by patient preference to (a) MT, (b) CT (MT + AT) or (c) AT alone. Primary endpoint was a composite score of the Pittsburgh Sleep Quality Index and the Cancer Fatigue Scale after 10 weeks of intervention (T1); a second endpoint was a follow-up assessment 6 months later (T2). The primary hypothesis stated superiority of CT and non-inferiority of MT vs. AT at T1. A closed testing procedure preserved the global α-level. The intention-to-treat analysis included propensity scores for the mode of allocation and for the preferred treatment, respectively. Results: Altogether 126 BC were recruited: 65 were randomized and 61 allocated by preference; 105 started the intervention. Socio-demographic parameters were generally balanced at baseline. Non-inferiority of MT to AT at T1 was confirmed (p < 0.05), yet the confirmative analysis stopped as it was not possible to confirm superiority of CT vs. AT (p = 0.119). In consecutive exploratory analyses MT and CT were superior to AT at T1 and T2 (MT) or T2 alone (CT), respectively. Conclusions: The multimodal CRF-therapy was found to be confirmatively non-inferior to standard therapy and even yielded exploratively sustained superiority. A randomized controlled trial including a larger sample size and a longer follow-up to evaluate multimodal CRF-therapy is highly warranted. Trial register: DRKS-ID: DRKS00003736 . Recruitment period June 2011 to March 2013. Date of registering 19 June 2012.

BMC cancer · randomised controlled trial · 41 citationsread the source →

Repetitive transcranial magnetic stimulation (rTMS) for panic disorder in adults.

Background: Panic disorder (PD) is a common type of anxiety disorder, characterized by unexpected and repeated panic attacks or fear of future panic attacks, or both. Individuals with PD are often resistant to pharmacological or psychological treatments and this can lead to the disorder becoming a chronic and disabling illness. Repetitive transcranial magnetic stimulation (rTMS) can deliver sustained and spatially selective current to suppress or induce cortical excitability, and its therapeutic effect on pathological neuronal activity in people with PD has already been examined in case studies and clinical trials. However, a systematic review is necessary to assess the efficacy and safety of rTMS for PD. Objectives: To assess the effects of repetitive transcranial magnetic stimulation (rTMS) for panic disorder (PD) in adults aged 18 to 65 years, either as a monotherapy or as an augmentation strategy. Search methods: An electronic search of the Cochrane Depression, Anxiety and Neurosis Review Group Controlled Trials Register (CCDANCTR) was conducted to 19 February 2014. The CCDANCTR includes reports of relevant randomised controlled trials (RCTs) from MEDLINE (1950 to date), EMBASE (1974 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL) (all years). Additional searches were conducted in Psyndex and the main Chinese medical databases. Selection criteria: RCTs or quasi-randomised trials evaluating rTMS for PD in people aged between 18 and 65 years, either as a monotherapy or as an augmentation strategy. Data collection and analysis: Two review authors independently selected studies and extracted data and verified the data by cross-checking. Disagreements were resolved by discussion. For binary data, we calculated fixed-effect model risk ratio (RR) and its 95% confidence interval (CI). For continuous data, we calculated fixed-effect model standardized mean difference (SMD) and its 95% CI. Main results: Two RCTs (n = 40) were included in this review. The included trials compared rTMS with sham rTMS; no trials comparing rTMS with active treatments (electroconvulsive therapy (ECT), pharmacotherapy, psychotherapy) met our inclusion criteria. Both included studies used 1 Hz rTMS over the right dorso-lateral prefrontal cortex (DLPFC) for two or four weeks as an augmentation treatment for PD. However, in both studies the data for the primary outcome, panic symptoms as measured by the Panic Disorder Severity Scale (PDSS), were skewed and could not be pooled for a quantitative analysis. For this primary outcome one trial with 25 participants reported a superior effect of rTMS in reducing panic symptoms compared with sham rTMS (t = 3.04, df = 16.57, P = 0.007), but this trial had a 16% dropout rate and so was deemed as having a high risk of attrition bias. The other trial found that all 15 participants exhibited a reduction in panic symptoms but there was no significant difference between rTMS and sham rTMS (Mann Whitney U test, P > 0.05). Regarding the acceptability of rTMS, no significant difference was found between rTMS and sham rTMS in dropout rates or in reports of side effects. The quality of evidence contributing to this review was assessed as very low. Assessments of the risk of bias for the two studies were hampered by the lack of information provided in the reports, especially on methods of sequence generation and whether allocation concealment had been applied. Of the remaining sources of bias, we considered one of the studies to have been at risk of attrition bias. Authors' conclusions: Only two RCTs of rTMS were available and their sample sizes were small. The available data were insufficient for us to draw any conclusions about the efficacy of rTMS for PD. Further trials with large sample sizes and adequate methodology are needed to confirm the effectiveness of rTMS for PD.

The Cochrane database of systematic reviews · meta-analysis · 27 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). Length of survival an AIDS has also been with neighborhood measures of income and the of highly a of health at the population may also a role in shaping HIV/AIDS patterns, associations between HIV/AIDS and income at the neighborhood have not been well segregation by race/ethnicity is neighborhood-level that may an important role in HIV/AIDS may affect infectious disease patterns through the and isolation of persons in one increasing the probability of transmission within that For example, found that measures of residential isolation were protective for at risk of disease. Indirect effects of segregation are associated with of neighborhood and with for those in poor neighborhoods segregation may to understanding disease we of studies examining neighborhood segregation in relation to HIV/AIDS that have been The physical environment of neighborhoods has also been examined in relation to infectious disease. et al. examined gonorrhea and neighborhood physical environment in New by using an of physical to explore and to this the of physical such as and a in social in a of community this concept to public et al. found a significant between neighborhood physical and gonorrhea rates, a by a ecologic study of US physical environment may HIV risk by illicit drug use such as injection behaviors and of the mechanisms through which the observed associations may be and associations between the physical environment and HIV/AIDS is research is to support the design of neighborhood-level HIV/AIDS interventions. has differences are not result from social and economic by policies. are and to p. 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Epidemiologic Reviews · meta-analysis · 394 citationsread the source →

Distract or reappraise? Age-related differences in emotion-regulation choice.

Does aging impact strategy choice with regard to regulating negative emotions? Based on the assumption that older adults are highly motivated to quickly defuse negative states, we predicted that older adults, relative to young adults, would show an increased preference for distraction (a cognitive disengagement strategy) over reappraisal (a cognitive engagement strategy) in the face of negative material. A stronger preference for distraction, in turn, should be associated with higher affective well-being at older ages, as it helps to avoid high physiological arousal. Young (19-28 years, n = 38) and older (65-75 years, n = 39) adults completed a laboratory task of emotion-regulation choice in which they viewed negative pictures of high and low intensity and chose between distraction and reappraisal to regulate their emotional response. Confirming predictions, age was associated with an increased preference to choose distraction over reappraisal. Among older but not young adults, the relative preference for distraction to reappraisal predicted higher state-affective well-being. In addition, across age groups, the preference for distraction over reappraisal was positively predicted by stimulus intensity and negatively by cognitive resources. Findings support the notion of an age-related shift toward disengagement strategies to regulate negative emotions, which maps onto older adults' prohedonic orientation and holds affective benefits.

Emotion (Washington, D.C.) · 100 citationsread the source →

Substance use disorders comorbid with mood and anxiety disorders in the Australian general population.

Introduction and aims: Substance use disorders (SUDs) are common and frequently co-occur with mood and anxiety disorders. This paper provides a detailed analysis of patterns, prevalence and correlates of mood and anxiety disorders among those with a (i) pure SUD; (ii) SUD plus a mood or anxiety disorder (SUDs + 1); and (iii) SUD plus a mood and anxiety disorder (SUDs + 2). Design and methods: Data came from the 2007 National Survey of Mental Health and Wellbeing; a nationally representative household survey of 8841 Australians aged 16-85 years. Results: The 12-month prevalence of SUDs was 5.1%. Of those with a 12-month SUD, 65% met the criteria for pure SUDs, 19% for SUDs + 1 and 16% for SUDs + 2. Major depression was the most common mood disorder in both comorbid groups. One-third of SUDs + 1 experienced social phobia, while over half of SUDs + 2 experienced generalised anxiety disorder. Compared with pure SUDs, SUDs + 1 experienced two times more and SUDs + 2 experienced over four times more days out of role in the preceding 30 days. Both comorbid groups were more likely to experience severe levels of impairment. SUDs + 2 were over 18 times more likely to experience suicidal thoughts in the same year. SUDs + 1 were over three times and SUDs + 2 were over 10 times more likely to have had one or more consultations with a health professional in the previous year. Discussions and conclusions: These findings highlight the complexities inherent with responding to and treating multiple comorbidities among substance users and emphasise the need for coordinated, cohesive responses from drug and alcohol treatment services.[Prior K, Mills K, Ross J, Teesson M. Substance use disorders comorbid with mood and anxiety disorders in the Australian general population. Drug Alcohol Rev 2017;36:317-324].

Drug and alcohol review · 37 citationsread the source →

Women's heart health at mid-life: what is the role of psychosocial stress?

Background: Women in mid-life experience unique stressors, including transitions within their family roles, informal caregiving, job stress, and perceived discrimination. The impact of these stressors on cardiovascular health in women during mid-life is of growing interest in both the popular and scientific literature. The objective of this review is to summarize the recent literature on stress and cardiovascular health in mid-life women. We focus on stressors that are relevant to mid-life women, including social stress and discrimination, and long-term risk of CVD events and subclinical CVD measures. Methods: We systematically reviewed the literature published between January 2012 and April 2018 for studies examining stress in mid-life and either CVD endpoints or subclinical CVD outcomes. Eligible studies included at least one psychosocial stress exposure, a CVD or subclinical CVD outcome, and either included only female participants, reported sex-stratified analyses or tested for a sex*stress interaction. Results: We identified 37 studies published since 2012 that met our criteria and included women between the ages of 40 and 65, including 3 case-control studies, 15 cross-sectional studies, and 19 prospective cohort studies. Because clinical CVD events typically occur after age 65 in women, only 22 studies were available that evaluated stress and hard CVD events in samples with mid-life women. Results from these studies suggested an increased and significant risk of CVD due to stress. Of the 15 studies that included subclinical CVD outcomes, the majority showed that mid-life women experiencing greater levels of stress had more subclinical CVD, as indicated by carotid intima-media thickness, flow-mediated dilation and arterial stiffness; however, several studies reported null associations. Conclusions: General life stress, including perceived stress and life events, in mid-life was significantly related to later-life CVD risk and mid-life subclinical CVD in the majority of studies published in the past six years. Job stress was inconsistently related to CVD risk in women, and fewer studies examined characteristics of other social roles, such as marriage, motherhood or caregiving. Perceived discrimination also was associated with CVD events and subclinical CVD in some samples of mid-life women. Further investigation into specific stressors relevant to women in mid-life, including caregiving and marital stress, are needed to understand the full extent to which life stress impacts CVD risk in mid-life women.

Women's midlife health · review · 19 citationsread the source →

Activity monitoring in patients with depression: a systematic review.

Background: Altered physical activity is an important feature of depression. It is manifested in psychomotor retardation, agitation and withdrawal from engagement in normal activities. Modern devices for activity monitoring (actigraphs) make it possible to monitor physical activity unobtrusively but the validity of actigraphy as an indicator of mood state is uncertain. We carried out a systematic review of digital actigraphy in patients with depression to investigate the associations between measured physical activity and depression. Methods: Systematic review and meta-analysis. Studies were identified from Medline, EMBASE and Psycinfo databases and included if they were either case control or longitudinal studies of actigraphy in adults aged between 18 and 65 diagnosed with a depressive disorder. Outcomes were daytime and night-time activity and actigraphic measures of sleep. Results: We identified 19 eligible papers from 16 studies (412 patients). Case control studies showed less daytime activity in patients with depression (standardised mean difference -0.76, 95% confidence intervals -1.05 to -0.47). Longitudinal studies showed moderate increase in daytime activity (0.53, 0.20 to 0.87) and a reduction in night-time activity (-0.36, -0.65 to -0.06) over the course of treatment. Limitations: All study participants were unblinded. Only seven papers included patients treated in the community. Conclusions: Actigraphy is a potentially valuable source of additional information about patients with depression. However, there are no clear guidelines for use of actigraphy in studies of patients with depression. Further studies should investigate patients treated in the community. Additional work to develop algorithms for differentiating behaviour patterns is also needed.

Journal of affective disorders · systematic review · 170 citationsread the source →

Outreach for chlamydia and gonorrhoea screening: a systematic review of strategies and outcomes.

Background: High Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) prevalence have been reported in populations that do not regularly access health centres for sexually transmissible infections (STI) testing. We reviewed current outreach strategies used to increase access to STI testing and their outcomes. Methods: We systematically reviewed the literature for English language studies published between 1 January 2005 and 28 January 2011 describing CT and/or NG screening programs in non-clinical outreach settings. Results: We identified 25 programs, with the majority occurring in either Australia (32%) or the United States (32%). The most common target groups were young people aged 15-29 years (52%), men who have sex with men (24%) and sex workers (8%). The median CT positivity was 7.7% (Inter Quartile Range [IQR]: 3.0%-11.1%, n=19 programs), and median NG positivity was 2.6% (IQR: 0.0%-8.0%, n=10). The median participation rate was 53% (IQR: 23.9%-81.3%), and a median of 79.6% (IQR: 55.1%-89.4%) of participants were tested, with a median of 100 tests conducted per program (IQR: 65-331, range: 11-1808). Across all settings the participation rate was highest among target groups gathering in community service venues (community centres, parenting centres, homeless shelters) (median=81.4%, n=4), and social venues (sporting venues or bars) (80.4%, n=1). Lower participation rates were found in street/public community areas (median=23.9%, n=3) and sex on premises venues (10.4% and 24.3%, n=2). Conclusions: The review indicated that although CT and NG outreach programs reached a relatively small number of people the yield of infections is high. Settings which appear to be more effective at encouraging participation appear to be those within an existing venue, rather than in public areas.

BMC public health · systematic review · 32 citationsread the source →

A longitudinal, randomized, controlled trial of advance care planning for teens with cancer: anxiety, depression, quality of life, advance directives, spirituality.

Purpose: To test the feasibility, acceptability and safety of a pediatric advance care planning intervention, Family-Centered Advance Care Planning for Teens With Cancer (FACE-TC). Methods: Adolescent (age 14-20 years)/family dyads (N = 30) with a cancer diagnosis participated in a two-armed, randomized, controlled trial. Exclusion criteria included severe depression and impaired mental status. Acceptability was measured by the Satisfaction Questionnaire. General Estimating Equations models assessed the impact of FACE-TC on 3-month post-intervention outcomes as measured by the Pediatric Quality of Life Inventory 4.0 Generic Core Scale, the Pediatric Quality of Life Inventory 4.0 Cancer-Specific Module, the Beck Depression and Anxiety Inventories, the Spiritual Well-Being Scale of the Functional Assessment of Chronic Illness Therapy-IV, and advance directive completion. Results: Acceptability was demonstrated with enrollment of 72% of eligible families, 100% attendance at all three sessions, 93% retention at 3-month post-intervention, and 100% data completion. Intervention families rated FACE-TC worthwhile (100%), whereas adolescents' ratings increased over time (65%-82%). Adolescents' anxiety decreased significantly from baseline to 3 months post-intervention in both groups (β = -5.6; p = .0212). Low depressive symptom scores and high quality of life scores were maintained by adolescents in both groups. Advance directives were located easily in medical records (100% of FACE-TC adolescents vs. no controls). Oncologists received electronic copies. Total Spirituality scores (β = 8.1; p = .0296) were significantly higher among FACE-TC adolescents versus controls. The FACE-TC adolescents endorsed the best time to bring up end-of-life decisions: 19% before being sick, 19% at diagnosis, none when first ill or hospitalized, 25% when dying, and 38% for all of the above. Conclusions: Family-Centered Advance Care Planning for Teens With Cancer demonstrated feasibility and acceptability. Courageous adolescents willingly participated in highly structured, in-depth pediatric advance care planning conversations safely.

The Journal of adolescent health : official publication of the Society for Adolescent Medicine · randomised controlled trial · 111 citationsread the source →

A randomised controlled multicentre trial of treatments for adolescent anorexia nervosa including assessment of cost-effectiveness and patient acceptability - the TOuCAN trial.

Objective: To evaluate the clinical effectiveness and cost-effectiveness of inpatient compared with outpatient treatment and general (routine) treatment in Child and Adolescent Mental Health Services (CAMHS) against specialist treatment for young people with anorexia nervosa. In addition, to determine young people's and their carers' satisfaction with these treatments. Design: A population-based, pragmatic randomised controlled trial (RCT) was carried out on young people age 12 to 18 presenting to community CAMHS with anorexia nervosa. Setting: Thirty-five English CAMHS in the north-west of England co-ordinated through specialist centres in Manchester and Liverpool. Participants: Two hundred and fifteen young people (199 female) were identified, of whom 167 (mean age 14 years 11 months) were randomised and 48 were followed up as a preference group. Interventions: Randomised patients were allocated to either inpatient treatment in one of four units with considerable experience in the treatment of anorexia nervosa, a specialist outpatient programme delivered in one of two centres, or treatment as usual in general community CAMHS. The outpatient programmes spanned 6 months of treatment. The length of inpatient treatment was determined on a case-by-case basis on clinical need with outpatient follow-up to a minimum of 6 months. Main outcome measures: Follow-up assessments were carried out at 1, 2 and 5 years. The primary outcome measure was the Morgan-Russell Average Outcome Scale (MRAOS) and associated categorical outcomes. Secondary outcome measures included physical measures of weight, height, body mass index (BMI) and % weight for height. Research ratings included the Health of the National Outcome Scale for Children and Adolescents (HoNOSCA). Self report measures comprised the user version of HoNOSCA (HoNOSCA-SR), the Eating Disorder Inventory 2 (EDI-2), the Family Assessment Device (FAD) and the recent Mood and Feelings Questionnaire (MFQ). Information on resource use was collected in interview at 1, 2 and 5 years using the Child and Adolescent Service Use Schedule (CA-SUS). Satisfaction was measured quantitatively using a questionnaire designed for the study and qualitative (free) responses on it. The questionnaire data were supplemented by qualitative analysis of user and carer focus groups. Results: Of the 167 patients randomised, 65% adhered to the allocated treatment. Adherence was lower for inpatient treatment (49%) than for general CAMHS (71%) or specialist outpatient treatment (77%) (p = 0.013). Every subject was traced at both 1 and 2 years, with the main outcome measure completed (through contact with the subject, family members or clinicians), by 94% at 1 year, 93% at 2 years, but only 47% at 5 years. A validated outcome category was assigned for 98% at 1 year, 96% at 2 years and 60% at 5 years. There was significant improvement in all groups at each time point, with the number achieving a good outcome being 19% at 1 year, 33% at 2 years and 64% (of those followed up) at 5 years. Analysis demonstrated no difference in treatment effectiveness of randomisation to inpatient compared with outpatient treatment, or, specialist over generalist treatment at any time point, when baseline characteristics were taken into account. Generalist CAMHS treatment was slightly more expensive over the first 2 years of the study, largely because greater numbers were subsequently admitted to hospital after the initial treatment phase. The specialist outpatient programme was the dominant treatment in terms of incremental cost-effectiveness. Specialist treatments had a higher probability of being more cost-effective than generalist treatments and outpatient treatment had a higher probability of being more cost-effective than inpatient care. Parental satisfaction with treatment was generally good, though better with specialist than generalist treatment. Young people's satisfaction was much more mixed, but again better with specialist treatment, including inpatient care. Conclusion: Poor adherence to randomisation (despite initial consent to it), limits the assessment of the treatment effect of inpatient care. However, this study provides little support for lengthy inpatient psychiatric treatment on clinical or health economic grounds. These findings are broadly consistent with existing guidelines on the treatment of anorexia nervosa, which suggest that outpatient treatments should be offered to the majority, with inpatient treatment offered in rare cases, though our findings lend little support to a stepped-care approach in which inpatient care is offered to outpatient non-responders. Outpatient care, supported by brief (medical) inpatient management for correction of acute complications may be a preferable approach. The health economic analysis and user views both support NICE guidelines, which suggest that anorexia nervosa should be managed in specialist services that have experience and expertise in its management. Comprehensive general CAMHS might, however, be well placed to manage milder cases. Further research should focus on the specific components of outpatient psychological therapies. Although family-based treatments are well established, trials have not established their effectiveness compared with good-quality individual psychological therapies and the combination of individual and family approaches is untested. Further research is needed to establish which patients (if any) might respond to inpatient psychiatric treatment when unresponsive to outpatient care, the positive and negative components of it and the optimum length of stay. Trial registration: NRR number (National Research Register) N0484056615; Current Controlled Trials ISRCTN39345394.

Health technology assessment (Winchester, England) · randomised controlled trial · 56 citationsread the source →

Video decision support tool for advance care planning in dementia: randomised controlled trial.

Objective: To evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia, and the stability of those preferences after six weeks. Design: Randomised controlled trial conducted between 1 September 2007 and 30 May 2008. Setting Four primary care clinics (two geriatric and two adult medicine) affiliated with three academic medical centres in Boston. Participants: Convenience sample of 200 older people (>or=65 years) living in the community with previously scheduled appointments at one of the clinics. Mean age was 75 and 58% were women. Intervention: Verbal narrative alone (n=106) or with a video decision support tool (n=94). Main outcome measures: Preferred goal of care: life prolonging care (cardiopulmonary resuscitation, mechanical ventilation), limited care (admission to hospital, antibiotics, but not cardiopulmonary resuscitation), or comfort care (treatment only to relieve symptoms). Preferences after six weeks. The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care. Results: Among participants receiving the verbal narrative alone, 68 (64%) chose comfort care, 20 (19%) chose limited care, 15 (14%) chose life prolonging care, and three (3%) were uncertain. In the video group, 81 (86%) chose comfort care, eight (9%) chose limited care, four (4%) chose life prolonging care, and one (1%) was uncertain (chi(2)=13.0, df=3, P=0.003). Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher, good or better health status, greater health literacy, white race, and randomisation to the video arm. In multivariable analysis, participants in the video group were more likely to prefer comfort care than those in the verbal group (adjusted odds ratio 3.9, 95% confidence interval 1.8 to 8.6). Participants were re-interviewed after six weeks. Among the 94/106 (89%) participants re-interviewed in the verbal group, 27 (29%) changed their preferences (kappa=0.35). Among the 84/94 (89%) participants re-interviewed in the video group, five (6%) changed their preferences (kappa=0.79) (P<0.001 for difference). Conclusion: Older people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description. They also have more stable preferences over time. Trial registration: Clinicaltrials.gov NCT00704886.

BMJ (Clinical research ed.) · randomised controlled trial · 207 citationsread the source →

Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: results from the OMEGA study of the Dutch breast cancer trialists' group.

Aim: To evaluate the association between baseline comprehensive geriatric assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly metastatic breast cancer (MBC) patients treated with first-line palliative chemotherapy. Patients and methods: MBC patients (≥65 years) were randomized between pegylated liposomal doxorubicine or capecitabine. CGA included instrumental activities of daily living (IADL), cognition using the mini-mental state examination (MMSE), mood using the geriatric depression scale (GDS), comorbidity using the Charlson index, polypharmacy and nutritional status using the body mass index. Frailty on CGA was defined as one or more of the following: IADL ≤ 13, MMSE ≤ 23, GDS ≥ 5, BMI ≤ 20, ≥5 medications or Charlson ≥2. The cut-off for frailty on the GFI was ≥4. Results: Of the randomized 78 patients (median age 75.5 years, range 65.8-86.8 years), 73 were evaluable for CGA; 52 (71%) had one or more geriatric conditions. Grade 3-4 chemotherapy-related toxicity was experienced by 19% of patients without geriatric conditions compared to 56% of patients with two geriatric conditions and 80% of those with three or more (p = 0.002). Polypharmacy was the only individual factor significantly associated with toxicity (p = 0.001). GFI had a sensitivity of 69% and a specificity of 76% for frailty on CGA, and was not significantly associated with survival or toxicity. Conclusion: In this study of elderly patients with MBC, the number of geriatric conditions correlated with grade 3-4 chemotherapy-related toxicity. Therefore, in elderly patients for whom chemotherapy is being considered, a CGA could be a useful addition to the decision-making process.

Breast (Edinburgh, Scotland) · randomised controlled trial · 91 citationsread the source →

Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study.

Background: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. Methods: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Findings: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]). Interpretation: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes. Funding: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

The Lancet. Neurology · cohort or longitudinal · 381 citationsread the source →

Prevalence of and Factors Related to Discordance About Prognosis Between Physicians and Surrogate Decision Makers of Critically Ill Patients.

Importance: Misperceptions about prognosis by individuals making decisions for incapacitated critically ill patients (surrogates) are common and often attributed to poor comprehension of medical information. Objective: To determine the prevalence of and factors related to physician-surrogate discordance about prognosis in intensive care units (ICUs). Design, setting, and participants: Mixed-methods study comprising quantitative surveys and qualitative interviews conducted in 4 ICUs at a major US medical center involving surrogate decision makers and physicians caring for patients at high risk of death from January 4, 2005, to July 10, 2009. Main outcomes and measures: Discordance about prognosis, defined as a difference between a physician's and a surrogate's prognostic estimates of at least 20%; misunderstandings by surrogates (defined as any difference between a physician's prognostic estimate and a surrogate's best guess of that estimate); differences in belief (any difference between a surrogate's actual estimate and their best guess of the physician's estimate). Results: Two hundred twenty-nine surrogate decision makers (median age, 47 [interquartile range {IQR}, 35-56] years; 68% women) and 99 physicians were involved in the care of 174 critically ill patients (median age, 60 [IQR, 47-74] years; 44% women). Physician-surrogate discordance about prognosis occurred in 122 of 229 instances (53%; 95% CI, 46.8%-59.7%). In 65 instances (28%), discordance was related to both misunderstandings by surrogates and differences in belief about the patient's prognosis; 38 (17%) were related to misunderstandings by surrogates only; 7 (3%) were related to differences in belief only; and data were missing for 12. Seventy-five patients (43%) died. Surrogates' prognostic estimates were much more accurate than chance alone, but physicians' prognostic estimates were statistically significantly more accurate than surrogates' (C statistic, 0.83 vs 0.74; absolute difference, 0.094; 95% CI, 0.024-0.163; P = .008). Among 71 surrogates interviewed who had beliefs about the prognosis that were more optimistic than that of the physician, the most common reasons for optimism were a need to maintain hope to benefit the patient (n = 34), a belief that the patient had unique strengths unknown to the physician (n = 24), and religious belief (n = 19). Conclusions and relevance: Among critically ill patients, discordant expectations about prognosis were common between patients' physicians and surrogate decision makers and were related to misunderstandings by surrogates about physicians' assessments of patients' prognoses and differences in beliefs about patients' prognoses.

JAMA · cohort or longitudinal · 151 citationsread the source →

Low psychological resilience is associated with depression in patients with cardiovascular disease.

Background: Psychological resilience is associated with an improved capacity to cope with chronic health challenges such as cardiovascular disease. Aims: The aim of this cross-sectional study was to examine the relationship between psychological resilience and symptoms of depression in a non-acute cardiac outpatient population. Methods: A total of 419 adult cardiac outpatients (288 men; mean±SD age 66.26±14.04 years) attending cardiovascular clinics completed the Sense of Coherence (SOC13) scale as a measure of psychological resilience and the Cardiac Depression Scale (CDS26) prior to their consultation. Results: The total SOC13 score (mean±SD 64.02±14.24, range 19-91) was within the moderate range. Older patients (⩾65 years) were significantly more resilient than those aged <65 ( p<0.01). Psychological resilience (SOC13) was negatively correlated with depression (CDS26) ( r=-0.79; p<0.001) and inversely associated with affective, cognitive and somatic symptoms of depression. Psychological resilience, particularly meaningfulness, accounted for more of the variance in affective features of depression than for somatic features. Conclusion: These findings show that low psychological resilience was related to depression in this cohort of cardiac outpatients, particularly affective symptoms such as anhedonia and hopelessness. The SOC13 scale offers a complementary measure of psychological status that could be used to monitor, and possibly predict, patient coping and response to treatment throughout the cardiovascular disease trajectory.

European journal of cardiovascular nursing · 41 citationsread the source →

Factors associated with oral health-related quality of life in community-dwelling elderly persons with disabilities.

Objectives: To examine, in community-dwelling elderly persons with disabilities, the association between oral health-related quality of life (OHRQOL) as measured using the 14-item Oral Health Impact Profile (OHIP-14) and specific oral health, health, and disability status variables; life satisfaction; living alone; and low income. Design: Observational cross-sectional. Setting: A Medicare demonstration conducted in 19 counties in three states. Participants: Six hundred forty-one disabled, cognitively intact, community-dwelling individuals aged 65 and older. Measurements: The subjects' OHRQOL was assessed using the OHIP-14, which was scored using three different methods. Data on oral health, health and functional status, life satisfaction, prior health services use, and sociodemographics were collected using interviewer-administered questionnaires. Results: The participants' mean age was 79.1, and they were dependent in an average of 1.8 activities of daily living (ADLs); 43.1% were edentulous, 77.4% wore a denture, 40.4% felt that they were currently in need of dental treatment, and 64.7% had not had a dental examination in the previous 6 months. Seven of the 16 variables of interest had significant bivariate relationships using three OHIP scoring methods. Logistic regression analysis found that poor OHRQOL was significantly associated with perceived need for dental treatment (odds ratio (OR)=2.61), poor self-rated health (OR=2.29), poor (OR=2.00) and fair (OR=1.73) mental health, fewer than 17 teeth (OR=1.74), and relatively poor cognitive functioning (OR=1.52). Conclusion: OHRQOL is associated with some (perceived need for dental treatment, poor self-rated health, worse mental health, fewer teeth, and relatively poor cognitive status) but not all (e.g., ADL and instrumental ADL dependence) measures of oral health, health, and disability status and not with life satisfaction, living alone, or low income.

Journal of the American Geriatrics Society · cohort or longitudinal · 48 citationsread the source →

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

Unlabelled: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. Methods: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. Results: Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. Conclusion: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

Respiratory medicine · cohort or longitudinal · 199 citationsread the source →

Loneliness, social support networks, mood and wellbeing in community-dwelling elderly.

Objective: Both loneliness and social networks have been linked with mood and wellbeing. However, few studies have examined these factors simultaneously in community-dwelling participants. The aim of this study was to examine the relationship between social network, loneliness, depression, anxiety and quality of life in community dwelling older people living in Dublin. Methods: One thousand two hundred and ninety-nine people aged 65 and over, recruited through primary care practices, were interviewed in their own homes using the GMS-AGECAT. Social network was assessed using Wenger's typology. Results: 35% of participants were lonely, with 9% describing it as painful and 6% as intrusive. Similarly, 34% had a non-integrated social network. However, the two constructs were distinct: 32% of participants with an integrated social network reported being lonely. Loneliness was higher in women, the widowed and those with physical disability and increased with age, but when age-related variables were controlled for this association was non-significant. Wellbeing, depressed mood and hopelessness were all independently associated with both loneliness and non-integrated social network. In particular, loneliness explained the excess risk of depression in the widowed. The population attributable risk (PAR) associated with loneliness was 61%, compared with 19% for non-integrated social network. Taken together they had a PAR of 70% Conclusions: Loneliness and social networks both independently affect mood and wellbeing in the elderly, underlying a very significant proportion of depressed mood.

International journal of geriatric psychiatry · cohort or longitudinal · 318 citationsread the source →

Telemedicine Applications for Cancer Rehabilitation: Scoping Review.

Background: Cancer is a significant public health issue worldwide. Treatments such as surgery, chemotherapy, and radiation therapy often cause psychological and physiological side effects, affecting patients' ability to function and their quality of life (QoL). Physical activity is crucial to cancer rehabilitation, improving physical function and QoL and reducing cancer-related fatigue. However, many patients face barriers to accessing cancer rehabilitation due to socioeconomic factors, transportation issues, and time constraints. Telerehabilitation can potentially overcome these barriers by delivering rehabilitation remotely. Objective: The aim of the study is to identify how telemedicine is used for the rehabilitation of patients with cancer. Methods: This scoping review followed recognized frameworks. We conducted an electronic literature search on PubMed for studies published between January 2015 and May 2023. Inclusion criteria were studies reporting physical therapy telerehabilitation interventions for patients with cancer, including randomized and nonrandomized controlled trials, feasibility studies, and usability studies. In total, 21 studies met the criteria and were included in the final review. Results: Our search yielded 37 papers, with 21 included in the final review. Randomized controlled trials comprised 47% (n=10) of the studies, with feasibility studies at 33% (n=7) and usability studies at 19% (n=4). Sample sizes were typically 50 or fewer participants in 57% (n=12) of the reports. Participants were generally aged 65 years or younger (n=17, 81%), with a balanced gender distribution. Organ-specific cancers were the focus of 66% (n=14) of the papers, while 28% (n=6) included patients who were in the posttreatment period. Web-based systems were the most used technology (n=13, 61%), followed by phone call or SMS text messaging-based systems (n=9, 42%) and mobile apps (n=5, 23%). Exercise programs were mainly home based (n=19, 90%) and included aerobic (n=19, 90%), resistance (n=13, 61%), and flexibility training (n=7, 33%). Outcomes included improvements in functional capacity, cognitive functioning, and QoL (n=10, 47%); reductions in pain and hospital length of stay; and enhancements in fatigue, physical and emotional well-being, and anxiety. Positive effects on feasibility (n=3, 14%), acceptability (n=8, 38%), and cost-effectiveness (n=2, 9%) were also noted. Functional outcomes were frequently assessed (n=19, 71%) with tools like the 6-minute walk test and grip strength tests. Conclusions: Telerehabilitation for patients with cancer is beneficial and feasible, with diverse approaches in study design, technologies, exercises, and outcomes. Future research should focus on developing standardized methodologies, incorporating objective measures, and exploring emerging technologies like virtual reality, wearable or noncontact sensors, and artificial intelligence to optimize telerehabilitation interventions. Addressing these areas can enhance clinical practice and improve outcomes for remote rehabilitation with patients.

JMIR cancer · review · 17 citationsread the source →

Influenza vaccine as a coronary intervention for prevention of myocardial infarction.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Influenza is one of the leading infectious causes of morbidity and mortality globally, and evidence is accumulating that it can precipitate acute myocardial infarction (AMI). This is thought to be due to a range of factors including inflammatory release of cytokines, disruption of atherosclerotic plaques and thrombogenesis, which may acutely occlude a coronary artery. There is a large body of observational and clinical trial evidence that shows that influenza vaccine protects against AMI. Estimates of the efficacy of influenza vaccine in preventing AMI range from 15% to 45%. This is a similar range of efficacy compared with the accepted routine coronary prevention measures such as smoking cessation (32-43%), statins (19-30%) and antihypertensive therapy (17-25%). Influenza vaccine should be considered as an integral part of CVD management and prevention. While it is recommended in many guidelines for patients with CVD, rates of vaccination in risk groups aged <65 years are very low, in the range of 30%. The incorporation of vaccination into routine CVD prevention in patient care requires a clinical practice paradigm change.

Heart (British Cardiac Society) · review · 94 citationsread the source →

Voluntary work for the physical and mental health of older volunteers: A systematic review.

Background: The increasing imbalance between the number of older adults not working and the number of adults in the age range of labour force participation (age range 20-64) has long been a fundamental public policy challenge in the Organization for Economic Co-operation and Development member countries. At a societal level, this growing imbalance raises serious concerns about the viability and funding of social security, pensions and health programmes. At an individual level, the concern is probably more that of aging well with the prospect of many years in retirement. Some research suggests that retiring for some carries the risk of a fast decline in health. Volunteering can play a significant role in people's lives as they transition from work to retirement, as it offers a "structured" means of making a meaningful contribution in society once the opportunity to do so through work has been cut off. Some older people consider voluntary work as a way to replicate aspects of paid work lost upon retirement, such as organisational structure and time discipline. In many countries, volunteering of the older adults is increasing and programmes designed specifically for this subpopulation are emerging. Volunteering may contribute to both individuals aging well and society aging well, as volunteering by the older adults at the same time relieves the societal burden if it helps maintain health and functionality for those who volunteer. It thus remains to be established to what extent volunteering impacts on the physical and mental health of those who volunteer. Objectives: The main objective of this review is to answer the following research question: what are the effects of volunteering on the physical and mental health of people aged 65 years or older? Search strategy: Relevant studies were identified through electronic searches of bibliographic databases, governmental and grey literature repositories, hand search in specific targeted journals, citation tracking, contact to international experts and internet search engines. The database searches were carried out to December 2018 and other resources were searched in September 2019 and October 2019. We searched to identify both published and unpublished literature. The searches were international in scope. Reference lists of included studies and relevant reviews were also searched. Selection criteria: The intervention of interest was formal volunteering which can be described as voluntary, on-going, planned, helping behaviour that intend to increase the well-being of strangers, offers no monetary compensation and typically occurs within an organisational context. We included older people aged 65 or over who are engaged in formal voluntary work. The primary focus was on measures of physical and mental health. All study designs that used a well-defined control group were eligible for inclusion. Studies that utilised qualitative approaches were not included. Data collection and analysis: The total number of potential relevant studies constituted 17,046 hits. A total of 90 studies, met the inclusion criteria and were critically appraised by the review authors. The 90 studies analysed 47 different populations. Only 26 studies (analysing 19 different populations) could be used in the data synthesis. Forty-six studies could not be used in the data synthesis as they were judged to have too high risk of bias and, in accordance with the protocol, were excluded from the meta-analysis on the basis that they would be more likely to mislead than inform. Eighteen studies did not provide enough information enabling us to calculate an effects size and standard error or did not provide results in a form enabling us to use it in the data synthesis. Finally, of the 26 studies that could be used in the data synthesis, two pairs of studies used the same two data sets and reported on the same outcome(s), thus in addition two studies were not used in the data synthesis. Meta-analysis of both physical health outcomes and mental health outcomes were conducted on each metric separately. All analyses were inverse variance weighted using random effects statistical models that incorporate both the sampling variance and between study variance components into the study level weights. Random effects weighted mean effect sizes were calculated using 95% confidence intervals (CIs).Sensitivity analysis was carried out by restricting the meta-analysis to a subset of all studies included in the original meta-analysis and was used to evaluate whether the pooled effect sizes were robust across components of risk of bias. Results: The 24 studies (analysing 19 different populations), used for meta analysis were from Australia, Ireland, Israel, Japan, Korea and United States, three were a randomised controlled trial and 21 were NRS. The baseline time period (the year the voluntary work that was analysed was measured) spanned by the included studies is 30 years, from 1984 to 2014 and on average the baseline year was 2001. On average the number of follow up years was 5, although with great variation from 0 to 25 years. The average number of volunteers analysed (not reported in four studies) was 2,369, ranging from 15 to 27,131 and the average number of controls was 13,581, ranging from 13 to 217.297. In total the average number of participants analysed was 14,566, ranging from 28 to 244.428.Ten studies analysed the effect of voluntary work on mortality, however, eight studies reported a hazard ratio and two studies reported an odds ratio. We analysed these two types of effect sizes separately. A hazard ratio <1 indicates that the treated, the volunteers is favoured. That is, the conditional mortality rate is lower for volunteers. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.67-0.91. The random effects weighted mean hazard ratio was 0.76 (95% CI, 0.72-0.80) and statistically significant. The two studies that reported odds ratios of mortality supported this result. There was no heterogeneity between the studies in either of the meta analyses. Three studies analysed the effect of voluntary work on incident functional disability, using a hazard ratio as effect measure. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.70-0.99. The random effects weighted mean hazard ratio was 0.83 (95% CI, 0.72-0.97) and statistically significant. There was a small amount of heterogeneity between the studies. Two studies analysed the effect of voluntary work on decline in instrumental activities of daily living, using an odds ratio as effect measure. Both reported results indicated an effect favouring the volunteers (0.63 and 0.83). The random effects weighted mean odds ratio was 0.73 (95% CI, 0.53-1.01) and not statistically significant. There is no heterogeneity between the two studies. Three studies analysed the effect of voluntary work on maintenance of functional competence, using an odds ratio as effect measure. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.67-0.83. The random effects weighted mean odds ratio was 0.81 (95% CI, 0.70-0.94) and statistically significant. There is no heterogeneity between the studies. In addition a number of other physical outcomes were reported in a single study only. Three studies analysed the effect of voluntary work on depression, and reported results that enabled the calculation of standardised mean difference (SMD) and variance. The effect sizes are measured such that a positive effect size favours the volunteers. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.05-0.66. The random effects weighted SMD was 0.12 (95% CI, 0.00-0.23) and statistically significant. There is a very small amount of heterogeneity between the studies. In addition, a number of other mental health outcomes were reported in a single study only. We did not find any adverse effects. There were no appreciable changes in the results across components of risk of bias as indicated by the sensitivity analysis. Authors' conclusions: The review aimed to examine effects on all types of physical and mental health outcomes. With the exception of mortality, there was insufficient evidence available. The available evidence, however, does suggest that there is an effect on the mortality of volunteers, although the effect is small. We found evidence that voluntary work reduces the mortality hazard of the volunteers aged 65 and above. The effect corresponds to a 43% chance of the volunteers dying first which should be compared to a fifty-fifty chance (50%) of dying first if the intervention had no effect. The evidence seems robust in the sense that we did not find any heterogeneity between the studies. As the intervention, unlike most other interventions in the social welfare area, is not costly, it could be prescribed to more older adults. In fact as the intervention in contrary to carrying a cost is a productive activity contributing directly to community well-being and has a positive effect on the volunteers it probably should be prescribed universally. However, due to the very nature of the intervention, it is voluntary and it cannot be prescribed. But more people could be encouraged to take up voluntary work if the opportunity was immediately available and visible.

Campbell systematic reviews · review · 33 citationsread the source →

How Do Corticosteroids Work in Asthma?

Reviews2 September 2003How Do Corticosteroids Work in Asthma?Peter J. Barnes, DM, DSc and Ian M. Adcock, PhDPeter J. Barnes, DM, DScFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this author and Ian M. Adcock, PhDFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-5_Part_1-200309020-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAsthma is the most common chronic disease in westernized countries. Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants. This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness. Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms. Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular ...References1. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62. [PMID: 11172168] CrossrefMedlineGoogle Scholar2. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515-96. [PMID: 9860804] MedlineGoogle Scholar3. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J. 1998;12:221-34. [PMID: 9701442] CrossrefMedlineGoogle Scholar4. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-B, in asthma. 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Glucocorticoids reverse IL-1-induced impairment of -adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases. Br J Pharmacol. 2002;135:987-96. [PMID: 11861327] CrossrefMedlineGoogle Scholar45. Eickelberg O, Roth M, Lorx R, Bruce V, Rudiger J, Johnson M, . Ligand-independent activation of the glucocorticoid receptor by 2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem. 1999;274:1005-10. [PMID: 9873044] CrossrefMedlineGoogle Scholar46. Pang L, Knox AJ. Regulation of TNF--induced eotaxin release from cultured human airway smooth muscle cells by 2-agonists and corticosteroids. FASEB J. 2001;15:261-269. [PMID: 11149914] CrossrefMedlineGoogle Scholar47. Korn SH, Wouters EF, Wesseling G, Arends JW, Thunnissen FB. Interaction between glucocorticoids and 2-agonists: and glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. Biochem Pharmacol. 1998;56:1561-9. [PMID: 9973176] CrossrefMedlineGoogle Scholar48. Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ. Glucocorticoid receptor activation following inhaled fluticasone and salmeterol [Abstract]. Am J Respir Crit Care Med. 2002;165:A616. Google Scholar49. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-8. [PMID: 12623857] CrossrefMedlineGoogle Scholar50. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, . A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99:8921-6. [PMID: 12070353] CrossrefMedlineGoogle Scholar51. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O'Connor BJ, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997;337:1412-8. [PMID: 9358138] CrossrefMedlineGoogle Scholar52. Ukena D, Harnest U, Sakalauskas R, Magyar P, Vetter N, Steffen H, . Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J. 1997;10:2754-60. [PMID: 9493656] CrossrefMedlineGoogle Scholar53. Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Thorax. 2000;55:837-41. [PMID: 10992535] CrossrefMedlineGoogle Scholar54. Szefler SJ, Leung DY. Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J. 1997;10:1640-7. [PMID: 9230260] CrossrefMedlineGoogle Scholar55. Barnes PJ. Steroid-resistant asthma. Eur Resp Rev. 2000;10:74-8. Google Scholar56. Spahn JD, Szefler SJ, Surs W, Doherty DE, Nimmagadda SR, Leung DY. A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654-9. [PMID: 8805670] MedlineGoogle Scholar57. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109:649-57. [PMID: 11941315] CrossrefMedlineGoogle Scholar58. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, . Increased glucocorticoid receptor in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600-4. [PMID: 10228133] CrossrefMedlineGoogle Scholar59. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, . Glucocorticoid receptor and in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7-13. [PMID: 10903212] CrossrefMedlineGoogle Scholar60. Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai JJ, Frew AJ, . Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis. 1991;144:1016-25. [PMID: 1952426] CrossrefMedlineGoogle Scholar61. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med. 1995;182:1951-8. [PMID: 7500041] CrossrefMedlineGoogle Scholar62. Matthews JG, Ito K, Barnes PJ, Adcock IM. Corticosteroid-resistant and corticosteroid-dependent asthma: two clinical phenotypes can be associated with the same in vitro defects in nuclear translocation and acetylation of histone 4 [Abstract]. Am J Respir Crit Care Med. 2000;161:A189. Google Scholar63. Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155:542-8. [PMID: 9032192] CrossrefMedlineGoogle Scholar64. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635-9. [PMID: 10556133] CrossrefMedlineGoogle Scholar65. Nightingale JA, Rogers DF, Fan Chung K, Barnes PJ. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med. 2000;161:479-86. [PMID: 10673189] CrossrefMedlineGoogle Scholar66. Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, . Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:24-31. [PMID: 12406856] CrossrefMedlineGoogle Scholar67. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15:1110-2. [PMID: 11292684] CrossrefMedlineGoogle Scholar68. Ito K, Watanabe S, Kharitonov S, Hanazawa T, Adcock IM, Barnes PJ. Histone deacetylase activity and gene expression in COPD patients [Abstract]. Eur Respir J. 2001;18:316S. MedlineGoogle Scholar69. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175-7. [PMID: 10988150] CrossrefMedlineGoogle Scholar70. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157:S1-53. [PMID: 9520807] CrossrefMedlineGoogle Scholar71. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, . A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J. 1994;13:4087-95. [PMID: 8076604] CrossrefMedlineGoogle Scholar72. Adcock IM, Nasuhara Y, Stevens DA, Barnes PJ. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-B and lack of I-B involvement. Br J Pharmacol. 1999;127:1003-11. [PMID: 10433509] CrossrefMedlineGoogle Scholar73. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, . Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245-55. [PMID: 9259316] CrossrefMedlineGoogle Scholar74. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, . Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol. 2001;166:1975-82. [PMID: 11160246] CrossrefMedlineGoogle Scholar75. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93-105. [PMID: 12151000] CrossrefMedlineGoogle Scholar76. Barnes PJ. New treatments for COPD. Nat Rev Drug Discov. 2002;1:437-46. [PMID: 12119745] CrossrefMedlineGoogle Scholar77. Ito K, Lim S, Chung KF, Barnes PJ, Adcock IM. Theophylline enhances histone deacetylase activity and restores glucocorticoid function during oxidative stress [Abstract]. Am J Respir Crit Care Med. 2002;165:A625. Google Scholar Author, Article, and Disclosure InformationAffiliations: From National Heart and Lung Institute, Imperial College, London, United Kingdom. Disclosures:Grants received: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca); Grants pending: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca).Corresponding Author: P.J. Barnes, DM, DSc, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom; e-mail, p.j.[email protected]ac.uk. 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Annals of Internal Medicine · review · 370 citationsread the source →

Inflammation and Schizophrenia

An association between inflammatory abnormalities and schizophrenia has been found repeatedly. The purposes of this special feature are to clarify the key findings on inflammation in schizophrenia, identify major gaps in the literature, and suggest priorities for research in this area. Inflammation is one of the body’s first lines of defense in response to injury or infection, and increased inflammation is found in many diseases. Acute inflammation is a nonspecific response characterized by warmth, pain, and swelling. Leukocytes migrate to the area of injury and become activated, the blood supply to the area increases, and blood vessels become more permeable, allowing cells and molecules to leave blood vessels and enter the injured tissue. The inflammatory response also involves the complement system, a group of proteins that, when activated, combine to form a complex molecular structure that kills cells, usually bacteria and parasites. Cytokines are key molecules that regulate inflammation; they also have important roles in the immune system. They are produced by a wide variety of immune cells and cells outside of the immune system. The term cytokine derives from their ability to influence the movement of inflammatory cells, but they also have other functions. Chronic inflammation is usually a lower grade response, lacks the grossly visible signs of acute inflammation, and may be systemic rather than localized. Chronic inflammation plays a role in the pathophysiology of many chronic diseases, including cardiovascular and cerebrovascular disease, diabetes, Alzheimer’s disease, and some cancers. The characteristics of chronic inflammation differ somewhat in the brain from what occurs in other tissues. An important component of neuroinflammation is the microglial activation. The brain contains relatively few of the inflammatory cells that are found outside the brain. Microglia, which are related to the peripheral inflammatory cells, serve some of the protective functions such cells play in the rest of the body. Microglia are involved in other brain functions, including the pruning and maintenance of synapses, trafficking of neurotransmitters, and devouring—phagocytosis—of cell fragments and damaged cells. Activated microglia produce inflammatory cytokines and the phagocytose cells or proteins that provoke the inflammatory response. Microglial activation and subsequent proinflammatory cytokine production may disrupt the blood-brain barrier (BBB). An intact BBB usually tightly controls the entry of cytokines and leukocytes into brain tissue. Damage to the BBB impairs its ability to control which inflammatory cells and molecules enter the brain; other substances leak into brain tissue, and the brain is unable to function normally. A discussion of prenatal inflammation as a risk factor for schizophrenia is beyond the scope of the present special feature, and the reader is referred to previous reviews of human1,2 and animal studies.3–6 Numerous studies have found that people with schizophrenia have increased blood concentrations of inflammatory cytokines.7 Two important themes emerge from these studies. First, inflammatory abnormalities are present in subjects with first-episode, drug-naive psychosis (FEP) compared with controls, suggesting an association that may be independent of the effects of antipsychotic medications. Second, the concentrations of some inflammatory molecules may vary with the clinical status of patients: ie, there appear to be separate groups of state and trait markers. The state-related markers include interleukin (IL) 1-beta, IL-6, and transforming growth factor-beta. People with schizophrenia have higher concentrations of these cytokines than controls during an exacerbation of symptoms, but there is no difference during periods of clinical stability. IL-12, interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) appear to be trait markers. Concentrations of these cytokines are higher in patients with FEP than in controls, and in patients with chronic illness, during both periods of symptomatic worsening, than in controls. C-reactive protein (CRP), another proinflammatory molecule, also appears to be a state marker,8 and specific lymphocyte populations may also segregate into state and trait markers.9 Additional evidence for potential state-related markers in schizophrenia has been reviewed elsewhere.10 Two studies suggest that inflammatory molecules may predict subsequent relapse.11,12 Other studies have found abnormal levels of inflammatory parameters in the central nervous system (CNS) in schizophrenia, including cerebrospinal fluid (CSF) cytokine11 and leukocyte levels,13,14 CNS microglia and lymphocytes,15–19 CSF and CNS oxidative stress,20,21 and anti-N-methyl-D-aspartate receptor autoantibodies.22 There is also evidence suggesting that infections may be associated with illness relapse.23 Within schizophrenia, blood cytokine abnormalities have been associated with poorer cognitive function and measures of regional brain volume24–26 and negative symptoms.27–30 There are several randomized clinical trials of the nonsteroidal anti-inflammatory drugs (NSAIDs) celecoxib and aspirin as adjuncts to antipsychotics.31 Interpretation of this evidence is complex, as these studies have not consistently distinguished relapsed from clinically stable patients. Furthermore, if inflammation plays a role in psychotic relapse, the efficacy of anti-inflammatory treatments may “disappear” in a lengthy trial because the treatment would not have any effect once patients have returned to their clinical baseline. However, an adjunctive agent that accelerates a patient’s antipsychotic response would be valuable. Agents other than NSAIDs that have anti-inflammatory properties, used in adjunct to antipsychotics, have been found to be superior to placebo. There have been two trials of minocycline,32,33 a second-generation tetracycline with anti-inflammatory and antimicrobial effects, that were superior to placebo. The efficacy of minocycline may have “disappeared” over the course of one trial,33 raising the possibility of an effect restricted to relapsed patient and not in those at a stable baseline. Adenosine is a purine nucleoside that modulates many physiological processes and has anti-inflammatory effects. A meta-analysis found that adjunctive treatment with adenosine-modulating drugs is superior to the effects of placebo.34 These drugs were associated with significant symptomatic improvement in inpatients, but not in outpatients, supporting the concept that state/trait differences may be an important predictor of antipsychotic response to adjunctive agents. Oxidative stress refers to an increase in free radicals, highly reactive molecules generated from metabolism and environmental exposures that can damage cell membranes. Inflammation and oxidative stress strongly influence each other.35 Antioxidant drugs decrease oxidative stress. One trial found that adjunctive treatment with the antioxidant N-acetylcysteine significantly reduced psychopathology in schizophrenia.36 A trial of fish oil, which also has significant anti-inflammatory effects, was conducted in adolescents and young adults with subthreshold psychotic symptoms,37 ie, “prodromal” patients. Patients receiving fish oil were significantly less likely to progress to a psychotic disorder than subjects receiving a placebo. Interestingly, fish oil was prescribed for 12 weeks, but the protective benefits with regards to transition to psychosis remained significant for 40 weeks after cessation of treatment. Inflammation may be a common mediator of diverse prenatal risk factors for schizophrenia, including preterm labor; preeclampsia (pregnancy-induced hypertension); neonatal birth asphyxia; and maternal gestational diabetes, stress, and depression.2 Maternal serum concentrations of the cytokines IL-838 and TNF-alpha39 during pregnancy were associated with an increased risk of schizophrenia in the offspring. Animal studies suggest that inflammation during critical periods of neurodevelopment may permanently alter the “set-point” of the inflammatory system, with increased inflammation in adult offspring.40–45 Meta-analyses have confirmed the presence of other abnormalities in schizophrenia that are associated with inflammation: increased autoantibodies,22 oxidative stress,46 CRP,8 and circulating lymphocytes.9 Antibodies are crucial “weapons” the immune system uses against foreign proteins. Autoantibodies, antibodies against a person’s own proteins, are associated with cytokine abnormalities.47 Lymphocytes, a group of white blood cells that combat infections, produce antibodies, and are an important source of cytokines, are increased in schizophrenia.9 Some subsets of lymphocytes may be state markers for acute psychosis, whereas others may be trait markers.9 CRP is a protein synthesized by the liver in response to inflammation, particularly IL-6 and other cytokines. Inflammation and oxidative stress may contribute to the decreased blood and CNS membrane levels of polyunsaturated fatty acids observed in schizophrenia.48 There are other disorders outside of schizophrenia in which peripheral inflammation appears to impact brain function. Inflammation is a risk factor for Alzheimer’s disease and mild cognitive impairment,49 rheumatoid arthritis is a risk factor for dementia,50 and “sickness behavior” is induced by peripheral cytokines.51,52 Depression is also associated with increased inflammation.53 The effects in depressed patients of an antibody against the cytokine TNF-alpha54 support the concept that brain function is impacted by peripheral cytokines. There are other mechanisms by which peripheral inflammation might cause or reflect brain dysfunction in schizophrenia. Cytokines may directly modulate dopaminergic neurotransmission55–57 or indirectly modulate glutamatergic neurotransmission through tryptophan metabolism.58–61 There is also some movement of peripheral leukocytes into the brain parenchyma, and the interaction of cytokines with the vagus nerve influences brain function.62 Blood cytokines induce cytokine production in the cells that form the BBB, and cytokines may move into the brain via the circumventricular organs, which lack a BBB.62 Inflammation may also disrupt the BBB, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. Some have suggested that the increase in blood concentrations of the protein S100-beta in schizophrenia63 is consistent with abnormal function of the BBB in people with schizophrenia, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. However, circulating S100-beta has sources other than the brain.64,65 Several potentially confounding variables are important to consider in studies of inflammation. Antipsychotics increase the risk of weight gain and diabetes, which are associated with inflammation. However, there is evidence from meta-analyses of abnormal inflammatory parameters in FEP,8,9,22,46 suggesting that the association between schizophrenia and inflammation is not solely due to antipsychotics. Antipsychotic-naïve relatives of people with schizophrenia also have increased inflammation compared with controls.66–68 Other potentially confounding variables include body mass index, age, gender, smoking, alcohol and illicit drug use, and whether patients are fasting at the time of sampling.69 The proportion of studies that either matched patients and controls, or statistically controlled for many of these potential confounders, has been low.8,9,22,46 Inflammation is comorbid with other physiological abnormalities, including hypertension, impaired glucose tolerance (fasting blood glucose [FBG] 100–126mg/dl), diabetes (FBG > 126, or a random blood glucose >200mg/dl), and increased oxidative stress. The associations with these other conditions also support the plausibility of increased inflammation in schizophrenia. However, the comorbidity of these physiological measures in schizophrenia complicates the interpretation of adjunctive treatment trials: what is the best therapeutic target? Another complicating issue is the relationship of inflammation to neurotropic viruses. One study found that treatment of patients with antibodies to herpes simplex 1 virus with a herpes-specific antiviral drug improved cognition with impressive effect sizes, suggesting the presence of an ongoing problem related to the virus.70 The association of other infectious agents with schizophrenia also raises the question of what relationship might exist between inflammation and either chronic infections or the expression of genes derived from an infectious agent and integrated into human DNA. The background presented above can be used to guide future research. Attempts to replicate current findings in well-matched patients and controls would be helpful. Cytokine levels in subjects with prodromal psychosis have not been investigated. We would hypothesize that these subjects should have abnormal trait markers compared with controls; within prodromal subjects, those who develop clinical psychosis should have abnormal state markers compared with high-risk subjects who do not. The effects of fish oil in preventing conversion to psychosis in high-risk subjects should be investigated in relationship to its effects on inflammation. The therapeutic anti-inflammatory agents that have been studied to date, such as aspirin, celecoxib, and fish oil, have multiple actions. Specific antibodies against individual cytokines are used in the treatment of rheumatoid arthritis and have been studied in depression.54 A change in symptoms or cognition in response to these antibodies would directly implicate inflammation in the pathophysiology of schizophrenia. More longitudinal studies with serial measurement of inflammatory parameters across the clinical course of illness are needed. It would be useful to test the hypothesis that patients with treatment-resistant schizophrenia have a different inflammatory profile than other patients with schizophrenia.7 Although it seems likely that there is increased inflammation in the brain when there are cytokine increases in the peripheral blood, the response might not be exactly the same in these two compartments. For instance, the inflammatory cytokines with altered levels in the brain might not be the same as those that change in the blood. More studies of markers of inflammation in the CNS—including CSF, postmortem analyses, and imaging studies—are needed. Two strategies may increase the signal-to-noise ratio for adjunctive trials of anti-inflammatory agents. First, inflammation may play a role in some patients with schizophrenia but not others. Patients with evidence of inflammation in the peripheral blood may be more likely to respond to an anti-inflammatory treatment strategy than those without inflammation and should be the ones included in treatment studies. Second, acutely ill and stable patients should be studied in separate trials and considered separately in meta-analyses. Furthermore, baseline-to-end-point analyses may not appropriate for studies of relapsed patients because there may be faster improvement with the use of adjunctive anti-inflammatories but not a greater total improvement by the end of the study. Studies of inflammation in schizophrenia should assess possible relationships of inflammatory cells and molecules to symptoms and cognition. To date, few studies have considered these measures.8,9,22,46 The comorbidity of inflammation, oxidative stress, hypertension, and abnormal glucose concentrations raise the issue what is the most appropriate treatment target in schizophrenia. As a first step in understanding this issue, it would be helpful to investigate relationships between inflammation, oxidative stress, hypertension, and glucose intolerance on the one hand, and clinical variables on the other. Several studies found that first-degree relatives of people with schizophrenia have increased inflammation and oxidative stress.66–68 It would advance the field to test the hypothesis that relatives have abnormal concentrations of the trait markers for schizophrenia but not of the state markers associated with relapse. Inflammatory molecules do not work in isolation but have complex interactions among themselves and with other systems. Most previous studies have measured only a small number of molecules. Concurrent measurement of cytokines, leukocytes, oxidative stress, and related parameters would increase the ability to make broader inferences regarding inflammation. Furthermore, if groups or clusters of covarying molecules—ie, molecules that change simultaneously—could be defined within schizophrenia, investigation of these groups is likely to yield better signal-to-noise ratios than individual molecules and should have more biological validity. Does increased inflammation due to infections or physical trauma increase the risk of relapse? If so, do preventive measures (eg, antibiotic prophylaxis for recurrent urinary tract infections)23 decrease that risk? What is the relationship between inflammation and the presence of antibodies to herpes viruses, toxoplasmosis, etc? Although the evidence on inflammation in schizophrenia is provocative, the number of studies in some areas is small, and increased methodological rigor is needed. Nonetheless, the evidence from FEP and first-degree relatives of patients with schizophrenia supports the idea that increased inflammation is truly associated with schizophrenia. This research raises the possibility that further study of inflammation will lead to greater understanding of the etiology and pathophysiology of schizophrenia. Dr B.K. is a member of Advisory Boards for Genentech and Roche. In the past 3 years, Dr B.J.M has received grant support from the National Institute of Mental Health (K23MH098014), the Georgia Regents University (GRU) Intramural Scientist Training Program, the GRU Brain & Behavior and Immunotherapy Discovery Institutes, the University of Oulu (Finland), the Thule Institute of the University of Oulu, and Oy H. Lundbeck Ab; research support from the National Institutes of Health Clinical Loan Repayment Program; consultancy fees for surveys from Medefied Europe and Plaza Research, on behalf of Genetech/Roche; speaker fees for grand rounds lectures from the Maryland Psychiatric Research Center and the Texas A&M University and Scott and White Hospital Department of Psychiatry; and payment for a survey from e-Rewards Medical Market Research.

Schizophrenia Bulletin · review · 315 citationsread the source →

The Management of Preoperative Anxiety in Children: An Update

Anxiety in children undergoing surgery is characterized by subjective feelings of tension, apprehension, nervousness, and worry that may be expressed in various forms (1). Postoperative maladaptive behaviors, such as new onset enuresis, feeding difficulties, apathy and withdrawal, and sleep disturbances, may also result from anxiety before surgery. In fact, studies have indicated that up to 60% of all children undergoing surgery may present with negative behavioral changes at 2 wk postoperatively (1,2). Variables such as age, temperament, and anxiety of the child and parent in the preoperative holding area have been identified as predictors for these behavioral changes (1). Extreme anxiety during induction of anesthesia is also associated with an increase of these postoperative negative behavioral changes (3). In addition to behavioral manifestations, preoperative anxiety activates the human stress response, leading to increased serum cortisol, epinephrine, and natural killer cell activity (4,5). This stress response can be activated by many different noxious stimuli including fear, anxiety, pain, cold, major surgery, and infection. The main components of the stress system are the corticotropin-releasing hormone and the locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the hypothalamic pituitary-adrenal axis and the limbs of the autonomic system (5). There is also evidence for a bidirectional communication between the neuroendocrine system and the immune system. Stress activates the hypothalamic pituitary-adrenal axis, increases circulating glucocorticoids, and is associated with alterations of immune function and susceptibility to infection and neoplastic disease (6). The human response to surgical stress is characterized by a series of hormonal, immunological, and metabolic changes that together constitute the global surgical stress response (7,8). This perioperative response is considered a homeostatic mechanism for adapting to the perioperative injury. The effects of the surgical stress response, however, may be detrimental: neuroendocrine hormones (e.g., cortisol, catecholamines) and cytokines (e.g., interleukin-6) provoke a negative nitrogen balance and catabolism, delay wound healing, and cause postoperative immunosuppression (7,8). Children are particularly vulnerable to the global surgical stress response because of limited energy reserves, larger brain masses, and obligatory glucose requirements (9). Because acute psychological stress, such as preoperative anxiety, is associated with immediate stress hormone release, the contribution of perioperative psychological factors to the global perioperative stress response cannot be ignored. In adults, increased preoperative anxiety is associated with poor postoperative behavioral and clinical recovery (10,11). As an indicator of the importance of preoperative anxiety, a panel of 72 anesthesiologists recently ranked various anesthesia low-morbidity clinical outcomes based on importance and frequency. The five clinical outcomes with the highest combined score were incisional pain, nausea, vomiting, preoperative anxiety, and discomfort from IV insertion (12). Thus, consensus is evident among anesthesiologists about the need to treat anxiety before surgery. In a modern epidemiological framework, diseases can be characterized in terms of risk factors, interventions, and outcomes. In this update, we will review preoperative anxiety in children using this conceptual framework (Fig. 1).Figure 1: Conceptual framework of perioperative anxiety. Revised from (72).The Psychobiology of Separation Learning to cope with separation from a parent is necessary for a child’s normal development (13). Separation experiences such as going to school facilitate normal psychological development and personality organization. Other separation experiences, such as perioperative separation, may precipitate confusion and anxiety. Between these two extremes, there are many separation experiences with varying degrees of psychobiological stress. In the first weeks of life, infants are able to discriminate among people, but will accept care and comfort from adults other than their parents (14). By 3 mo of age, however, infants begin to respond differently to familiar and unfamiliar people. Older infants smile more at familiar people and may even try to engage their attention (14). Separation anxiety usually begins at 7–8 mo of age and peaks around 1 yr of age. In part, separation anxiety represents the infant’s acquisition of new cognitive abilities and object permanence. The intensity of separation anxiety declines with age, largely because of increasing cognitive abilities and memory capacity. Frequently, however, the increase in abilities does not immunize toddlers and preschoolers against the stress and distress of separations. The extent to which separation is traumatic or evokes adaptive responses reflects an individual child’s developmental age, parenting experiences, genetic endowment, and environmental stability. For children with biologically based vulnerabilities, such as a sensitivity to novelty and transitions, even expected separations may impose a greater degree of stress than for less sensitive children (13). How parents help the child mediate a separation experience play a crucial role in the child’s acute and long-term responses. In the extreme, the parent may be unable to mediate the experience for the child because of limitations such as severe anxiety. How well children have been cared for up to the time of the separation also influences their response to the stressor. Children deprived of attention in the home are at increased risk for stress in response to separations. Thus, the extent to which separations evoke adaptive responses reflects an individual child’s genetics, personality, parenting, and previous life experiences. Preoperative Anxiety: Identification Identifying risk factors for development of preoperative anxiety is important, as more resources can be directed toward vulnerable children. Children 1–5 yr old are at the highest risk for developing extreme anxiety (1). This is not surprising considering the psychobiology of separation anxiety. Children who are shy or inhibited and those who have a high intelligence quotient and lack good adaptive abilities are also at increased risk (15). Previous surgery or hospitalization and poor response to visits to the pediatrician’s office are also predictors for the development of preoperative anxiety. Finally, parental anxiety has been identified as a predictor for increased child’s anxiety. Preoperative Anxiety: Behavioral Modalities Preoperative Preparation Programs Most studies suggest that preoperative preparation programs reduce anxiety and enhance coping in children (16). These behavioral preparation programs have evolved significantly over recent decades. In the 1960s, preparation programs were designed to provide an orientation tour and narrative information and facilitate trust between the hospital staff, the child, and the parent (16). In the 1970s, modeling techniques were developed where children indirectly experienced the perioperative course by role rehearsal using dolls or by viewing a video (17). These modeling techniques were augmented in the late 1980s with child life preparation and the teaching of coping skills (17). Currently, development of coping skills is considered the most effective preoperative preparation intervention, followed by modeling, play therapy, operating room tour, and printed material (18). Although experts favor teaching of coping skills, most preparation programs in the United States consist of an orientation tour and printed information (18). Although coping preparation has been associated with reduction of anxiety in the preoperative holding area, no differences were found among the various preparation programs during induction, in the recovery room period, or postoperatively (19). Thus, the cost-effectiveness of child life specialists may or may not be justified by an associated reduction in preoperative anxiety. Psychological preparation programs should be tailored to individual needs such as age, developmental stage, and previous experience (20). The priority of the age criterion relates to both the anxiety such exposure might generate and the length of time over which children can cope with anticipation. In addition, timing of the program before surgery is an important variable (20). Children aged ≥6 yr benefit most if they participate in a preparation program ≥5 days before surgery and benefit least if the program is given only 1 day before surgery. This phenomenon is related to the way that children in this age group process new information. Finally, a child who has previously undergone surgery or has been hospitalized may develop an exaggerated emotional response to an information-based preparation program (20). As increased parental anxiety results in increased child’s anxiety (1), there is a need for interventions that are designed specifically for parents. Cassady et al. (21) demonstrated that parental preoperative anxiety decreased after viewing an educational videotape. We suggest that more parental interventions need to be developed and that a child’s anxiety should be evaluated as an outcome. Preoperative Anxiety: Behavioral Modalities Parental Presence during Induction of Anesthesia. Parents and children prefer to stay together during medical procedures such as immunizations, dental treatment, and induction of anesthesia (22). Some data indicate, however, that parental presence during induction of anesthesia (PPIA) is allowed in 26% of US hospitals and is encouraged in only 8% of hospitals (23). In contrast, 28% of hospitals have no formal hospital policy and parental presence is against hospital policy for 32% of hospitals in the US. The smallest use of this induction technique was reported in the South-Central region and the highest in the Northwest and the Northeast (23). Interestingly, anesthesiologists from Great Britain (GB) encourage PPIA significantly more than anesthesiologists from the US (23,24). The reasons for these differences may include the use of different induction techniques, less concern about legal ramifications in GB, and a stronger demand for parental presence in GB. Economic issues such as operating room (OR) efficiency, infrastructure issues, lack of induction rooms and patchy preoperative educational programs, probably limit the availability of PPIA in the US. Potential benefits from PPIA include reducing the need for preoperative sedatives and avoiding the fear and anxiety that may occur on separation to the OR. Other benefits, such as increasing the child’s compliance during induction, remain controversial. Objections to PPIA include concern about disruption of the OR routine, crowded ORs, and a possible adverse reaction of parents. In addition, increased parental anxiety can increase a child’s anxiety, prolong anesthetic induction, and place additional stress on the anesthesiologist. Although early observational studies suggested reduced anxiety if parents were present during induction (25), more recent randomized controlled trials indicate that routine parental presence is not beneficial (26–28). One study demonstrated that only children >4 yr of age, those who have a “calm” baseline personality, or those who have a parent with a “calm” baseline personality benefit from this intervention (26). When interpreting the results of these studies, however, it should be noted that the design of a randomized controlled study does not reflect the practice of all anesthesiologists. When data of survey studies are reviewed (23,24), it is noticed that most anesthesiologists use either PPIA or sedative premedication to treat preoperative anxiety. When sedative premedications were directly compared with PPIA, however, it was found that children receiving oral midazolam were significantly less anxious and more compliant during the induction process (27). A recent study examined whether a combination of PPIA and oral midazolam is more effective than oral midazolam alone (28). The investigators found that PPIA has no additive anxiolytic effects for children who received oral midazolam preoperatively. Parents who accompany their sedated children into the ORs, however, are significantly less anxious and more satisfied both with the separation process and with the overall anesthetic, nursing and surgical care provided (28). PPIA is also associated with important legal implications. Lewyn (29) described a case in which a mother was invited to accompany her son into an emergency treatment room. According to the court, the mother fainted and suffered an injury to the head. In its verdict the Illinois Supreme Court stated that a hospital, which allows a nonpatient to accompany a patient during treatment, does not have a duty to protect the nonpatient from fainting. However, if medical personnel invite the nonpatient to participate in the treatment, then the hospital has a legal responsibility toward the nonpatient. Interestingly, some hospitals in the US now require the parents to sign a written informed consent acknowledging the risk of being present during induction of anesthesia. We believe that future research interests should shift towards an emphasis on what parents actually do during induction of anesthesia, rather than simply on their presence. Allowing a parent into an OR without significant preparation may be counterproductive because some parent behaviors, such as criticism and commands, are associated with increased distress. Effective methods of training such as parental preparation programs can be developed for enhancing the effects of PPIA. Preoperative Anxiety: Pharmacological Modalities The reported rate of use of pharmacological modalities for the treatment of preoperative anxiety in the US varies widely among age groups and geographical locations (24). Premedicant sedative drugs are least often used with children <3 yr of age and most often used with adults <65 yr of age (25% vs 75%). Currently, the most commonly used sedative premedicant in the preoperative holding area is midazolam (85%), followed by ketamine (4%), transmucosal fentanyl (3%), and meperidine (2%) (Fig. 2). TABLETABLE The majority of children in the US are premedicated via the oral route (80%), followed by the intranasal route (8%), the IM route (6%), and the rectal route (3%).Figure 2: Types of premedicants used in the preoperative holding area (23).Table 1: Premedications Administered by the Oral RouteTable 2: Premedications Administered Transmucosally and RectallyMidazolam. Midazolam is a short-acting benzodiazepine that is very lipophilic at physiologic pH, which accounts for its rapid onset of action. Davis et al. (30) has demonstrated that intranasally administered midazolam in a dosage of 0.2–0.3 mg/kg in patients undergoing myringotomies led to satisfactory separation from parents and a satisfactory induction over 70% of the time and did not prolong recovery time and hospital discharge time. Midazolam administered intranasally is effective in reducing anxiety in children within 10–12 min (31). A major drawback of intranasally administered midazolam, however, is that at least 50% of children cry on administration because it transiently irritates the nasal passages. Midazolam can also be given as a nasal spray, which is effective in reducing procedural anxiety in children undergoing cancer therapy (32). Midazolam can be administrated sublingually at the same dosage as intranasally. Although sublingual administration of midazolam is associated with a decreased incidence of crying (18%), it may be difficult to prevent small children from either swallowing the midazolam or spitting it out immediately (33). Rectal administration of midazolam in doses of 0.5–1.0 mg/kg effectively reduces the anxiety of children before induction of anesthesia (34). Although the incidence of hiccups after IV midazolam is <2%, the incidence noted that in a recent study involving rectally administered midazolam was more than 20%(34). The investigators had no explanation as to the increased rate of hiccups other than the young age of the children, but they found that the hiccups were easily treated by ethyl chloride nasal spray (34). Orally administered midazolam (0.5 mg/kg) has been shown to significantly reduce preoperative anxiety in young children (27,28). Orally administered midazolam can be given in a dosage of 0.25 mg to 1.0 mg/kg up to total dose of 20 mg depending on the of surgery and the anxiety of the A and and midazolam in a of 2 in et al. examined different doses of the midazolam and found that 0.25 mg/kg in satisfactory and in a majority of patients within 20 This study also found that increasing the dose in an increase in the of patients with satisfactory and a time to onset of Other that the time for premedicated children from their parents is min with a sedative between 20 and min The of administered midazolam and in the discharge of patients is controversial. Although recent studies noted that administrated midazolam is not associated with a discharge two studies involving children undergoing that and recovery are in the children who oral midazolam study involving children who myringotomies using or anesthesia indicated that children who were given oral midazolam experienced significant in recovery time but no in discharge time from the hospital Finally, et al. have the of a combination of preoperative oral midazolam and The investigators found that requirements by and discharge was in children who had been given midazolam preoperatively. The investigators suggested that the increased postoperative may have been to of and midazolam on As indicated a significant of children experiences maladaptive behavioral changes after surgery (1). In children who were premedicated with oral midazolam had a significantly decreased incidence of negative behavioral changes during the first after surgery However, this study noted that by 2 wk postoperatively there were no significant differences between the midazolam and The mechanism by which midazolam the incidence of postoperative behavioral changes is not but it may be related to of the perioperative process Children who received a benzodiazepine for dental and were about the experience dental than children who were not about their dental This may be particularly important for children undergoing surgical in children after oral midazolam as early as min and anxiolytic effects are as early as min after administration This timing to onset of is of importance in surgery where the of is very Midazolam and can be with which The dose in children is mg/kg given IV in a of up to 1.0 mg Some children who are with will experience it is to for can also be intranasally in a dose of given by from a is a that is very which the a good for administration and Oral transmucosal fentanyl administered in the of a to a and as the was the first sedative by the and in for use in children. Oral transmucosal in and dosage is in a and given to children in the dosage of for sedative is often associated with which usually min after children begin to the children before induction of anesthesia does however, to decreased or with induction in young children In a small of can cause a leading to significant a in be present this is administered in children is associated with a incidence of postoperative and that is not easily by In fact, at least study was because of a very incidence of preoperative A significant of is that it the postoperative et al. reported that preoperative is as effective as IV fentanyl given for of postoperative in children undergoing is an that a of and from the of ketamine compared with other premedicants is that it less given in sedative doses A of ketamine as compared with other premedicants is the of increased and which can to can also cause and in children, which can parents if they are not informed about this increased incidence of postoperative is associated with preoperative administration of ketamine The effects are all dose related and can be with the use of a small dose of administered ketamine mg/kg) the time of onset of the of administered ketamine is also dose related with administered ketamine mg/kg) an onset of of min and ketamine leading to within 20 min administration may be associated with and during the postoperative recent studies have found that use of a benzodiazepine given to children undergoing ketamine did not the incidence of In addition, the incidence of postoperative and is no different in children receiving midazolam, or a combination of ketamine and midazolam together The IV preparation of ketamine can be with or to an oral of which is by most children. can be also be given intranasally rectally and IM mg/kg) care discharge time of children who received administered ketamine is reported not to be compared with administered midazolam provided that of surgery is than min administered IM in an emergency room however, was found to significantly delay discharge and increase compared with midazolam administered rectally or intranasally et al. reported that the combination of midazolam and ketamine administrated had a rate of satisfactory compared with with either oral was also found to be to IM and in children undergoing The provided and and there was less need for IV as compared with the IM is an first developed as an but found to have and sedative Orally administrated in a dose of anesthetic and for postoperative requirements by 50% in children premedicated with This in may be to the of as well as a administered is also as effective as administered fentanyl for postoperative in children undergoing The recovery of children who is to the recovery of children who oral but significantly less postoperative as compared with One major drawback for the use of as a sedative premedicant is its onset of action. has to be administered as early as min before surgery In children, is at min for administered and min for rectally administered for the research should on the development of sedatives that will be well have a very time for onset of and have of action. In addition, developed preoperative sedatives should such as and should anesthetic requirements and reduce postoperative Finally, new methods of sedative premedications should also be For of should be as well as oral transmucosal methods for other than usually at least 1 for effective serum of drugs to be is can significantly the of a and has been effective in fentanyl in adults within min at 2 Finally, the of treatment modalities such as should be research is in these The to for review of this

Anesthesia & Analgesia · review · 408 citationsread the source →

Improving national hospice/palliative care service symptom outcomes systematically through point-of-care data collection, structured feedback and benchmarking.

Purpose: Every health care sector including hospice/palliative care needs to systematically improve services using patient-defined outcomes. Data from the national Australian Palliative Care Outcomes Collaboration aims to define whether hospice/palliative care patients' outcomes and the consistency of these outcomes have improved in the last 3 years. Methods: Data were analysed by clinical phase (stable, unstable, deteriorating, terminal). Patient-level data included the Symptom Assessment Scale and the Palliative Care Problem Severity Score. Nationally collected point-of-care data were anchored for the period July-December 2008 and subsequently compared to this baseline in six 6-month reporting cycles for all services that submitted data in every time period (n = 30) using individual longitudinal multi-level random coefficient models. Results: Data were analysed for 19,747 patients (46 % female; 85 % cancer; 27,928 episodes of care; 65,463 phases). There were significant improvements across all domains (symptom control, family care, psychological and spiritual care) except pain. Simultaneously, the interquartile ranges decreased, jointly indicating that better and more consistent patient outcomes were being achieved. Conclusion: These are the first national hospice/palliative care symptom control performance data to demonstrate improvements in clinical outcomes at a service level as a result of routine data collection and systematic feedback.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 91 citationsread the source →

Sex and Gender Disparities in the COVID-19 Pandemic

Journal of Women's HealthVol. 29, No. 4 CommentaryFree AccessSex and Gender Disparities in the COVID-19 PandemicJewel Gausman and Ana LangerJewel GausmanWomen & Health Initiative, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Search for more papers by this author and Ana LangerAddress correspondence to: Ana Langer, MD, Women & Health Initiative, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 651 Huntington Avenue, FXB Building 6th Floor Office 643B, Boston, MA 02115 E-mail Address: [email protected]Women & Health Initiative, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Search for more papers by this authorPublished Online:17 Apr 2020https://doi.org/10.1089/jwh.2020.8472AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail In the case of the ongoing COVID-19 pandemic, sex-disaggregated data suggest that fewer women are dying from the disease than men.1 However, taking this observation at face value oversimplifies the biological, behavioral, and social and systemic factors that may cause differences to emerge with regard to how women and men experience both the disease and its consequences. As governments react with swift and severe measures in their ongoing fight to control the pandemic's spread, it is important to understand how these actions may disproportionately increase the risks for women both directly and indirectly with regard to sex and gender. Pregnant women are often among the most vulnerable groups during public health emergencies. In some cases, pregnant women face increased biological susceptibility to adverse health outcomes, as in the case of some respiratory infections. With other emergent coronaviruses, such as those responsible for severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), pregnant women who became infected were found to be more likely than nonpregnant women to experience severe complications.2 It is still too early to tell whether this will be the case with COVID-19.In the ongoing pandemic, other factors may have a ripple effect that put women at increased risk even if the disease itself does not. As made clear during the 2014 Ebola outbreak, the consequences of large-scale infectious disease outbreaks on uninfected pregnant women can be dire. Routine prenatal care appointments, if not interrupted or discontinued, may put women at increased risk of exposure to the virus. Overwhelmed hospitals struggling to function with staff and supply shortages may not be able to provide the high quality of care that all pregnant women and their newborns deserve, let alone respond to emergency obstetric complications. Furthermore, there is also a risk that life-saving treatments or vaccines will be denied to pregnant women over concern for fetal safety or a lack of data.3,4The fear of infection, concern for the well-being of friends and loved ones, uncertainty, disruption, and social isolation that have become part and parcel of daily life for many around the world will undoubtedly have profound effects on mental health on the population at large, but being pregnant during a global pandemic is likely to be even more frightening for many women. Although containment strategies, such as those that require women to deliver without a companion present, including partners and doulas, that have already been put into place in some cities in the United States,5 or those that separate newborns from their mothers immediately after birth if the mother is infected with COVID-196 may be clinically important to reduce transmission, they may also have profound short- and long-term mental health implications for women. Among women who have young children, previous research in Ethiopia, India, and Vietnam found that women who experience family-related stressful life events, such as illness or death within the household and financial uncertainty, are more likely to experience episodes of severe mental distress.7 With the ongoing need to social distance, family and community networks may struggle and pregnant and postpartum women may feel even more vulnerable and isolated over a lack of social support. The adverse effects of the pandemic in relation to women's reproductive health are not limited to pregnancy or motherhood. As movement restrictions are put into place, supply chains are disrupted, and businesses are shuttered, some women may be at increased risk of unintended pregnancy should it become difficult to obtain their regular contraceptive method or emergency contraceptives, if needed. Furthermore, some states within the United States have begun to impose restrictions on certain medical procedures that they deem to be elective, including abortion, suggesting they must be delayed until after the pandemic is over.8 Spikes in domestic violence during times of crisis are another area of grave concern for women's health, and as governments continue to put into place more extreme measures to enforce social distancing, for some women, more time at home may mean more time spent with an abusive partner. Fewer social interactions may also mean less accountability for perpetrators and fewer opportunities for others to intervene. Gender-related factors may also increase the impact of the COVID-19 pandemic on women globally. Women constitute a disproportionately high percentage of caregivers in both the formal and informal sectors.9 A large proportion of frontline health care professionals (nurses, community health workers, health technicians, etc.) is women who face a higher risk of infection, morbidity, and death as a result of their profession.9 At the same time, women more frequently serve as the primary caregivers within a household, which may further increase their risk of exposure. In the United States, 65% of unpaid family caregivers are estimated to be women and 80% of them care for someone aged 50 years or older.10 Outside of their caregiving role, women are overrepresented in the informal employment sector. In low-and middle-income countries, two-thirds of women who work do so as part of the informal economy with limited access to health care for themselves and their families.9 Containment and mitigation policies that limit women's ability to perform their duties without offering effective alternatives, such as closing of daycare facilities for their children or not providing paid sick leave, may result in unnecessary exposure to disease and increased family vulnerability. It is urgent that we adopt a gender lens to study the pandemic and its effects, including the policies and actions that are put into place at the global, country, and local levels. This may be especially important in disadvantaged populations and resource-poor communities, where women are especially vulnerable. The public health community must ensure that existing health and social services meant to support women in the face of their unique needs do not disappear in lieu of the all-encompassing focus on stopping the pandemic. Furthermore, we argue that special attention needs to be paid to ensure that informal caregivers are supported, informed, and protected. To avoid making existing gender disparities larger as a result of the pandemic, a special body at the U.S. Centers of Disease Control and Prevention is urgently needed to track sex disaggregated data and analyze policies related to COVID-19 using a gender lens. Author Disclosure StatementNo competing financial interests exist. Funding InformationNo funding was received for this article. References1. Cai H. Sex difference and smoking predisposition in patients with COVID-19. Lancet Respir Med 2020;pii: S2213-2600(20)30117-X. Medline, Google Scholar2. Favre G, Pomar L, Musso D, Baud D. 2019-nCoV epidemic: What about pregnancies? Lancet 2020;395:e40. Crossref, Medline, Google Scholar3. Rasmussen SA, Smulian JC, Lednicky JA, Wen TS, Jamieson DJ. Coronavirus disease 2019 (COVID-19) and pregnancy: What obstetricians need to know. Am J Obstet Gynecol 2020;pii: S0002-9378(20)30197-6. Medline, Google Scholar4. Weigel G. Novel coronavirus "COVID-19": Special considerations for pregnant women. Available at: https://www.kff.org/womens-health-policy/issue-brief/novel-coronavirus-covid-19-special-considerations-for-pregnant-women/?utm_source=Global+Health+NOW+Main+List Accessed March 17, 2020. Google Scholar5. Caron C, Syckle KV. Laboring alone: Some hospitals bar partners because of virus fears. The New York Times. 2020. Google Scholar6. American College of Obstetricians and Gynecologists. Practice advisory: Novel coronavirus 2019 (COVID-19). Available at: https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Novel-Coronavirus2019?IsMobileSet=false Accessed March 13, 2020. Google Scholar7. Gausman J, Austin SB, Subramanian S, Langer A. Adversity, social capital, and mental distress among mothers of small children: A cross-sectional study in three low and middle-income countries. PLoS One 2020;15:e0228435. Crossref, Medline, Google Scholar8. Tavernise S. Texas and Ohio include abortion as medical procedures that must be delayed. The New York Times. 2020. Google Scholar9. Langer A, Meleis A, Knaul FM, et al. Women and health: The key for sustainable development. Lancet 2015;386:1165–1210. Crossref, Medline, Google Scholar10. Feinberg L, Reinhard SC, Houser A, Choula R. Valuing the invaluable: 2011 update, the growing contributions and costs of family caregiving. Washington, DC: AARP Public Policy Institute, 2011:32. 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S. and May 2022 | Journal of Women's Health, Vol. 31, No. of women in clinical A for and Clinical Vol. and urban towards pandemic May 2022 | Vol. the The of during a January 2022 | & Psychology, Vol. 32, No. and During the and of the COVID-19 Pandemic in April 2022 | Frontiers in Vol. to Greater With the COVID-19 and to Journal of Health Psychology, Vol. 29, No. of to the of SARS-CoV-2 With Anxiety and A Study of March 2022 | International Journal of Public Health, Vol. in the Impact of COVID-19 Pandemic in in The Gender in Vol. No. 3Women's health and access COVID-19 Outlook, Vol. 70, No. of to COVID-19 Outcomes in a Longitudinal of February 2022 | Vol. No. as March 2022 | Saúde Vol. No. COVID-19 wave in during the of and its with higher February 2022 | PLOS ONE, Vol. 17, No. well-being and during the COVID-19 pandemic in the United A February 2022 | The Social Science Vol. to and February 2022 | Psychology, Vol. women's during the COVID-19 pandemic in June 2021 | and An International Vol. No. an and at the same in work and during the coronavirus April 2021 | International Journal of Psychology, Vol. No. and local A in the time of November 2021 | International Journal of Psychology, Vol. No. and the During June 2021 | & Vol. 26, No. of Medical Care among in the United States during the COVID-19 May 2022 | Journal of Public Health Research, Vol. 11, No. the Gender Disparities in COVID-19 and January 2022 | & Vol. with public health for COVID-19: a study of mothers with young children in the United February 2022 | Journal of in Vol. No. Perspectives on January and Among Adults During the to COVID-191 February in and and during the COVID-19 pandemic health and and Vol. in the COVID‐19 Effects of on December 2021 | British Journal of Vol. No. effects of the on for an emerging January 2022 | & Vol. No. Distress among Dental during the COVID-19 December 2021 | International Journal of Environmental Research and Public Health, Vol. 19, No. physical and social of health during the COVID-19 lockdown: a for of depression, and stress in the population during social isolation to the COVID-19 a cross-sectional study28 April 2021 | BMC Vol. No. and but same mortality of severe disease in March 2021 | BMC Medicine, Vol. No. Factors with and among community October 2021 | and Health, Vol. 17, No. differences in a of COVID-19 patients during the first and pandemic August 2021 | of Sex Vol. 12, No. in December 2021 | Journal of Clinical Medicine, Vol. 10, No. November 2021 | of Coronavirus Anxiety in Women on and Birth One of Coronavirus October 2021 | Journal of and Research, Vol. No. in and among Young Adults During Social to March 2021 | The Journal of Sex Research, Vol. No. of COVID-19 short- and long-term Disparities in and October 2021 | PLOS ONE, Vol. 16, No. analysis of on 2021 | Journal of in Medicine, Vol. No. of and Among COVID-19 by States in Women An September 2021 | and Vol. No. of COVID-19 using Public Gender and COVID-19: a Social Media of 2021 | Journal of Research, Vol. 5, No. for COVID-19 and its impact on in the Research on and Economics, Vol. No. differences in mental health of Canadian during the COVID-19 of and Health, Vol. No. Use and Relationship to Stress, and Perceived During the COVID-19 Pandemic in August 2021 | Frontiers in Public Health, Vol. and Lessons for August 2021 | PLOS ONE, Vol. 16, No. in How women in the United States in of of during the pandemic of March 2021 | Journal of Psychology, Vol. No. of in severe COVID-19 and Vol. No. the gender June 2021 | Journal of Perinatal Medicine, Vol. No. and the Related Factors in for COVID-19 at 2021 | International Journal of Health and Sciences, Vol. No. Gender Disparities and A Vol. No. impact of COVID‐19 on women to A of December | & Vol. No. of the and During the Covid-19 2021 | Frontiers in Psychology, Vol. in a January 2021 | Vol. No. responses to COVID-19 to Abuse & Vol. in and Practice During Social Among Young Adults in the May 2021 | Medicine, Vol. No. SARS-CoV-2 pandemic: A Health, Vol. and and after the pandemic April 2021 | Clinical and Research, Vol. No. on in August | Vol. 13, No. An to COVID-19 February 2022 | Journal of Women and Social Vol. No. in the and Outcomes of With May 2021 | Journal of Medicine, Vol. 16, No. of COVID-19: and May 2021 | Frontiers in Public Health, Vol. in the of February 2022 | Journal of Human Vol. No. and of the COVID-19 pandemic from the of in May 2021 | Journal of Social Work, Vol. No. the Pandemic: December April health disparities in vulnerable populations of psychiatric patients during the COVID-19 Journal of Vol. 11, No. 4The Gender of to in March 2021 | Feminist Economics, Vol. No. in Risk Factors and Mental Health During the of the COVID-19 Pandemic: A of U.S. Women A. E. E. and April 2021 | Journal of Women's Health, Vol. 30, No. and of and in March 2021 | Medicine, Vol. No. impact of COVID-19 on the mental health of and Science & Medicine, Vol. of and with in April 2021 | Vol. 12, No. health and well-being of staff during the coronavirus disease 2019 4 and in an March 2021 | Journal of Vol. of Gender in the and of Coronavirus Disease 2019 An of Health and and March 2021 | Journal of Women's Health, Vol. 30, No. of the COVID-19 pandemic on and Vol. of COVID-19 and of and Public Health, Vol. No. cross-sectional study of the of and with perceptions of to March 2021 | Open, Vol. 11, No. research and social of health: at the of of impact on and of Clinical Medicine, Vol. 17, No. differences in responses to SARS-CoV-2 in patients with January 2021 | Reports, Vol. No. and to COVID-19 in and January 2021 | Policy and Practice, Vol. impact of COVID-19 among and of November | & Health, Vol. 26, No. in case and mortality of coronavirus disease 2019 (COVID-19) among states in the United November | of Medicine, Vol. No. and pandemic risk and fear among September 2021 | Health and Behavioral Medicine, Vol. No. June 2021 | Vol. No. of and with of Coronavirus Related September 2021 | Vol. a January 2021 | Cadernos de Saúde Vol. No. and Among Vol. of Psychological Distress and Factors among During the COVID-19 Pandemic at in March 2021 | Disease and Vol. and on During the COVID-19 Pandemic in of Social Media October 2021 | Journal of Medical Research, Vol. 23, No. and and attitudes, and practices toward COVID-19 among birth of and Health Vol. 10, No. the of in COVID-19 October | Health Vol. No. in the of COVID-19 and political Vol. services in times of in of quality care for pregnant women and their October | Health Care for Women Vol. No. social support in the face of the December | Journal of & Vol. 12, No. with fear and during the COVID-19 pandemic in October | and Health, Vol. 16, No. and of People from by December | Journal of in Health, and Education, Vol. 10, No. is in gender and age for COVID-19 A December | Journal of and Vol. No. of SARS-CoV-2 Among Nursing and in September | Journal of Medicine, Vol. No. role of in the severity of learned from Vol. on gender disparities in the impact of the U.S. COVID-19 Research, Vol. Gender Women's Health and October | Frontiers in Global Women's Health, Vol. and the risk to and women during Journal of Vol. No. With Disparities in COVID-19 Outcomes in an Health Care October | JAMA Network Open, Vol. No. in the time of in August | Vol. 17, No. de la en en por September | Vol. No. de la COVID-19 en la de September | Vol. No. Perspectives to Health Research and Prevention During the COVID-19 | and Health Vol. 24, No. and Disease Disparities in the United in Vol. No. for a to | Global Public Health, Vol. No. and of in September | Vol. 11, No. and What is the Vol. No. we in Covid-19 women and men Vol. in of COVID-19: Insights a Vol. No. will The need to for the research on and the role of and and Vol. Impact and Factors During the of the Coronavirus (COVID-19) Pandemic Among the Population in June | Frontiers in Psychology, Vol. and of and the in SARS-CoV-2 to the in May | International Journal of Sciences, Vol. No. Coronavirus Disease 2019 the of August | Vol. Gender of to in January | Vol. Social of Vol. of of and Digital Vol. this Gausman and Ana and Gender Disparities in the COVID-19 of Women's in April 17,

Journal of Women s Health · editorial or comment · 306 citationsread the source →

Prevalence and factors associated with use of khat: a survey of patients entering HIV treatment programs in Ethiopia.

Background: Khat, a plant native to East Africa, has psychoactive constituents similar to amphetamine. Chronic khat use can lead to psychological dependence with multiple physical and mental health harms, complicating clinical management of people living with HIV. In two Ethiopian cities where khat is common, we evaluated prevalence and correlates of khat use among patients new to HIV care. Methods: During 2013-2014, we surveyed 322 patients recently enrolled in HIV clinics in Dire Dawa and Harar about khat use, demographics, smoking and alcohol use, clinical illness, food insecurity, and social support. We analyzed factors associated with khat use in the past year, as well as heaviest use of khat (based on greatest number of hours used in a typical month). Results: 242 (75%) respondents reported lifetime khat use; 209 (65%) reported khat use during the previous year. 54% of khat users started before age 19 years. Although 84% believed that using khat every day is dangerous for health if you have HIV, khat was used in the previous year a median of 5 h/days and 30 days/month; 21% said they felt a need to cut down or control their khat use but had difficulty doing so. Those using khat were more likely to report smoking (46%) and alcohol use (49%) compared to non-khat users (1 and 31% respectively). Those reporting heaviest khat use (≥180 h/typical month) were more likely to rate their health status as poor, have an underweight BMI (≤18.5 kg/m2), report more symptoms of chronic illness, and agree with more statements indicating a negative physical quality of life. In multivariate analysis, heavy users were more likely to be male, Muslim, and non-married. Conclusions: Khat use was common among HIV patients entering care, and associated with symptoms of poorer physical health. Over half started khat use when they were young. Although most believed khat is harmful for HIV patients, a number of respondents reported some difficulty controlling their drug use. In settings where khat is legal and widely utilized, developing interventions for responsible use represent an important health priority as part of comprehensive care for people living with HIV.

Addiction science & clinical practice · 13 citationsread the source →

Cognitive empathy across the lifespan.

Aim: To describe the development of cognitive empathy across the lifespan from a very large cohort using a standardized measure of cognitive empathy ability. Method: Participants (n=4545, age bands <5y to >75y, 60% female) were a convenience sample recruited voluntarily from visitors to the Glasgow Science Centre in the UK, who completed the Reading the Mind in the Eyes Test. Results: When compared to preceding age groups, we found significant developmental gains in empathy ability in children aged 6 to 7 years (p=0.048, d=0.45) and again at 10 to 12 years (p=0.042, d=0.23), followed by a slight reduction in ability during adolescence (p=0.087, d=-0.18), and functional maturity in those aged 19 to 25 years (p=0.001, d=0.76). Cognitive empathy abilities remained relatively stable across adulthood but gradually declined in people over 65 years, with notable decline in males over 75 years (p=0.001, d=-0.98). Females performed better than males at all ages. Interpretation: Understanding developmental issues in cognitive empathy could influence approaches to moral and social education for children, and health and social care support for older people. Standardized cognitive empathy tests could also provide novel approaches in the early detection of developmental vulnerabilities in a range of neurological conditions, and within neuropsychiatric and neurodegenerative disorders in which cognitive empathy is known to be impaired. What this paper adds: Cognitive empathy is a late-developing ability and changes across the lifespan. Cognitive empathy increases during childhood but with potentially altered abilities during adolescence. Cognitive empathy matures during early adulthood and gradually declines in older age. There is a female advantage in cognitive empathy abilities.

Developmental medicine and child neurology · 20 citationsread the source →

Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.

Endocrinology · 80 citationsread the source →

Long-term surgical and patient-reported outcomes of Hirschsprung Disease.

Background: Information is needed regarding the complex relationships between long-term functional outcomes and health-related quality of life (HRQoL) in Hirschsprung's Disease (HSCR). We describe long-term outcomes across multiple domains, completing a core outcome set through to adulthood. Methods: HSCR patients operated at a single center over a 35-year period (1978-2013) were studied. Patients completed detailed questionnaires on bowel and urologic function, and HRQOL. Patients with learning disability (LD) were excluded. Outcomes were compared to normative data. Data are reported as median [IQR] or mean (SD). Results: 186 patients (median age 28 [18-32] years; 135 males) completed surveys. Bowel function was reduced (BFS 17 [14-19] vs. 19 [19-20], p < 0•0001;η2 = 0•22). Prevalence and severity of fecal soiling and fecal awareness improved with age (p < 0•05 for both). Urinary incontinence was more frequent than controls, most of all in 13-26y females (65% vs. 31%,p = 0•003). In adults, this correlated independently with constipation symptoms (OR 3.18 [1.4-7.5],p = 0.008). HRQoL outcomes strongly correlated with functional outcome: 42% of children demonstrated clinically significant reductions in overall PedsQL score, and poor bowel outcome was strongly associated with impaired QOL (B = 22•7 [12•7-32•7],p < 0•001). In adults, GIQLI scores were more often impacted in patients with extended segment disease. SF-36 scores were reduced relative to population level data in most domains, with large effect sizes noted for females in General Health (g = 1.19) and Social Wellbeing (g = 0.8). Conclusion: Functional impairment is common after pull-through, but bowel function improves with age. Clustering of poor functional outcomes across multiple domains identifies a need for early recognition and long-term support for these patients.

Journal of pediatric surgery · 50 citationsread the source →

Augmenting Mental Health in Primary Care: A 1-Year Study of Deploying Smartphone Apps in a Multi-site Primary Care/Behavioral Health Integration Program.

Background: Integrating behavioral health (BH) services into primary care is an evidence-based intervention that can increase access to care, improve patient outcomes, and decrease costs. Digital technology, including smartphone apps, has the potential to augment and extend the reach of these integrated behavioral health services through self-management support impacting lifestyle behaviors. To date, the feasibility and acceptability of using mental health mobile apps within an integrated primary care setting has not yet been explored as part of routine clinical care. Objectives: The objectives of this study were to (a) test the feasibility of using mental health applications to augment integrated primary care services; (b) solicit feedback from patients and providers to guide implementation, and (c) develop a mental health apps toolkit for system-wide dissemination. Methods: Cambridge Health Alliance (CHA) is a safety-net healthcare system that includes three community hospitals and 12 Primary Care (PC) clinics serving nearly 150,000 ethnically and socioeconomically diverse patients around Boston. To select and disseminate mental health apps, a four-phase implementation was undertaken: (1) Evaluation of mental health mobile applications (2) Development of an apps toolkit with stakeholder input, (3) Conducting initial pilot at six primary care locations, and (4) Rolling out the app toolkit across 12 primary care sites and conducting 1-year follow-up survey. Results: Among BH providers, 24 (75%) responded to the follow-up survey and 19 (83%) indicated they use apps as part of their clinical care. Anxiety was the most common condition for which app use was recommended by providers, and 10 (42%) expressed interest in further developing their knowledge of mental health apps. Among patients, 35 (65%) of participants provided feedback; 23 (66%) reported the tools to be helpful, especially for managing stress and anxiety. Conclusions: Our findings indicate mental health apps are applicable and relevant to patients within integrated primary care settings in safety-net health systems. Behavioral health providers perceive the clinical value of using these tools as part of patient care, but require training to increase their comfort-level and confidence applying these tools with patients. To increase provider and patient engagement, mobile apps must be accessible, simple, intuitive and directly relevant to patients' treatment needs.

Frontiers in psychiatry · 40 citationsread the source →

Environmental Toxicant Exposure and Depressive Symptoms.

Importance: Recognizing associations between exposure to common environmental toxicants and mental disorders such as depression is crucial for guiding targeted mechanism research and the initiation of disease prevention efforts. Objectives: To comprehensively screen and assess the associations between potential environmental toxicants and depressive symptoms and to assess whether systemic inflammation serves as a mediator. Design, setting, and participants: A total of 3427 participants from the 2013-2014 and 2015-2016 waves of the National Health and Nutrition Examination and Survey who had information on blood or urine concentrations of environmental toxicants and depression scores assessed by the 9-item Patient Health Questionnaire (PHQ-9) were included. Statistical analysis was performed from July 1, 2023, to January 31, 2024. Exposures: Sixty-two toxicants in 10 categories included acrylamide, arsenic, ethylene oxide, formaldehyde, iodine, metals, nicotine metabolites, polycyclic aromatic hydrocarbons, volatile organic compound (VOC) metabolites; and perchlorate, nitrate, and thiocyanate. Main outcomes and measures: An exposome-wide association study and the deletion-substitution-addition algorithm were used to assess associations with depression scores (PHQ-9 ≥5) adjusted for other important covariates. A mediation analysis framework was used to evaluate the mediating role of systemic inflammation assessed by the peripheral white blood cell count. Results: Among the 3427 adults included, 1735 (50.6%) were women, 2683 (78.3%) were younger than 65 years, and 744 (21.7%) were 65 years or older, with 839 (24.5%) having depressive symptoms. In terms of race and ethnicity, 570 participants (16.6%) were Mexican American, 679 (19.8%) were non-Hispanic Black, and 1314 (38.3%) were non-Hispanic White. We identified associations between 27 chemical compounds or metals in 6 of 10 categories of environmental toxicants and the prevalence of depressive symptoms, including the VOC metabolites N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (odds ratio [OR], 1.74 [95% CI, 1.38, 2.18]) and total nicotine equivalent-2 (OR, 1.42 [95% CI, 1.26-1.59]). Men and younger individuals appear more vulnerable to environmental toxicants than women and older individuals. Peripheral white blood cell count mediated 5% to 19% of the associations. Conclusions and relevance: In this representative cross-sectional study of adults with environmental toxicant exposures, 6 categories of environmental toxicants were associated with depressive symptoms with mediation by systemic inflammation. This research provides insight into selecting environmental targets for mechanistic research into the causes of depression and facilitating efforts to reduce environmental exposures.

JAMA network open · 62 citationsread the source →

Intergenerational Chain of Violence, Adverse Childhood Experiences, and Elder Abuse Perpetration.

Importance: It is widely known that individuals with adverse childhood experiences (ACEs) have an increased risk of abusing their own children, thereby perpetuating the cycle of violence. However, the association between ACEs and elder abuse perpetration has not been fully examined. Objective: To examine the association between ACEs and elder abuse and the mediating factors. Design, setting, and participants: This cross-sectional study used data collected via the self-administered Japan COVID-19 and Society Internet Survey from September 12 to October 19, 2022. Men and women aged 20 to 64 years who responded to related questions were included. Data were analyzed from July 2023 to April 2024. Exposures: ACEs, defined as the experience of any of 7 items-interpersonal loss (parental loss and parental divorce), family psychopathology (parental mental disease and violence in family), abuse (physical and psychological abuse), and neglect-before the age of 18 years. Main outcomes and measures: The primary outcome was the perpetration of physical and/or psychological abuse against an older person (aged ≥65 years) self-reported via questionnaire. The direct and indirect effect estimates were determined using logistic regression analyses. Results: Of a total of 13 318 participants (mean [SD] age, 41.1 [12.1] years; 6634 female [49.8%]), 1133 (8.5%) reported perpetrating violence against older adults. Compared with individuals without ACEs, the odds ratios (ORs) for perpetrating violence were 3.22 (95% CI, 2.74-3.79) for those with 1 ACE and 7.65 (95% CI, 6.41-9.13) for those with 2 or more ACEs. In the mediation analysis, factors with large indirect effect estimates included depression (OR, 1.13; 95% CI, 1.11-1.14; proportion mediated [PM], 18.6%), mental illness other than depression (OR, 1.12; 95% CI, 1.10-1.14; PM, 17.3%), and self-rated health (OR, 1.04; 95% CI, 1.03-1.05; PM, 6.0%). Conclusions and relevance: These findings suggest that intergenerational cycles of violence may extend to any vulnerable group, not only children but also older adults. Further research into the prevention of ACEs and breaking these cycles of violence is warranted.

JAMA network open · 8 citationsread the source →

The early-life exposome: Description and patterns in six European countries.

Characterization of the "exposome", the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on chronic diseases. Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6-11 years in 6 European birth cohorts. Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures. In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities.

Environment international · 100 citationsread the source →

The association of gait speed and self-reported difficulty walking with social isolation: A nationally-representative study.

Background: Mobility assessments are commonly used among older adults as risk stratification for falls, preoperative function, frailty, and mortality. We determined if gait speed and self-reported difficulty walking are similarly associated with social isolation and loneliness, which are key markers of social well-being and linked to health outcomes. Methods: We used 2015-2016 data from the National Social life Health and Aging Project (NSHAP), an in-person nationally-representative survey of 2640 community-dwelling adults ≥65 years old. We measured gait speed (timed 3-m walk: unable to walk, ≥5.7 s, and <5.7 s), and self-reported difficulty walking one block or across the room (unable, "much," "some," or "no" difficulty). Social measures included loneliness (3-item UCLA scale), social isolation (12-item scale), and individual social activities (frequency socializing, religious participation, community participation, and volunteering). We used logistic regression to determine the adjusted probability of each social measure by gait speed and difficulty walking, adjusting for sociodemographic and health characteristics, and tested for interaction terms with age. Results: Participants were on average 75 years old (SD = 7.1), 54% female, 9% Black/African American, and 6% Hispanic. Difficulty walking one block was associated with (p < 0.05): social isolation (much difficulty: 26% vs no difficulty: 18%), low socializing (33% vs 19%), low volunteering (67% vs 53%), low community participation (54% vs 43%), low religious participation (51% vs 46%), and loneliness (25% vs 14%). Difficulty walking across the room was similarly strongly associated with social isolation and individual activities. The association between self-reported difficulty walking and social isolation was stronger at older ages (p-value of interaction <0.001). Conclusions: Self-reported mobility difficulty is a widely used clinical assessment that is strongly associated with loneliness and social isolation, particularly at older ages. Among persons with limited mobility, clinicians should consider a careful social history to identify social needs and interventions addressing mobility to enhance social connections.

Journal of the American Geriatrics Society · 17 citationsread the source →

Every Step Counts: Understanding the Success of Implementing The 10,000 Steps Project.

The 10,000 Steps program originated from a landmark whole-of-community multi-strategy intervention to increase physical activity (PA) in Rockhampton, Australia in 2001-2003. It used a social ecological framework to promote physical activity at the individual, population, environmental and policy level. Two of the fundamental aspects of the original program were goal setting (10,000 steps per day) and self-monitoring (use of a pedometer for daily step counts). A project website (www.10000steps.org.au) allowed registered participants to record their physical activity. Over time the program morphed into an e- & mHealth intervention without face-to-face elements. The program is now delivered via website and smartphone apps and employs activity trackers (pedometers, Fitbit, Garmin). To date the project has signed-up over 425,000 members who have logged 221 billion steps (∼43 million a day) on the website or app. More than 14,000 workplaces and community organisations have been involved with the program. A central element of the program, the 'Workplace Challenge' has been used by ∼65% of 10,000 Steps members, which on average increases physical activity by 159 min/week for those who participate in it. In 2011, the Queensland Government designated the 10,000 Steps program as their key physical activity workplace health promotion strategy. Multiple factors underpin the success of the program. The message is simple and clear: the project name, with its distinctive logo and tagline ('Every Step Counts') provides a clear and prescriptive target for the physical activity 'dose'. Using effective behaviour change techniques: goal setting (the 10,000 Steps concept), self-monitoring (steps are tracked), social support (participants organise as 'teams' to reach certain step goals) and gamification (teams competing against each other creating 'friendly competition'). Ongoing redevelopment: since inception, there have been three complete redesigns of the website (including a branding redesign), and new smartphone apps. More recently, the website was modified to allow syncing of steps using popular activity trackers. Resources to support implementation: the program provides resources (e.g. 'Active Workplace Guide') and has dedicated staff to respond to queries from workplaces and individuals to help overcome implementation barriers. Project staff continuously promote the program via media interviews, attendance at events, social media and marketing, advertising, and networking and collaboration. Ongoing evaluation has contributed to continuous funding: to ensure the program remains successful in a fast-changing technology environment, continuous evaluation has been necessary. These evaluation strategies, the success of the original project and the strong partnership with the program funder (Queensland Health) have all contributed to the long-term (19 years) support for the project.

Studies in health technology and informatics · 20 citationsread the source →

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study.

Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

The Lancet. Child & adolescent health · 44 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.

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