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

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

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

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 →

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

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

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

A randomised control study of a fully automated internet based smoking cessation programme.

Objective: The objective of this project was to test the short term (90 days) efficacy of an automated behavioural intervention for smoking cessation, the "1-2-3 Smokefree" programme, delivered via an internet website. Design: Randomised control trial. Subjects surveyed at baseline, immediately post-intervention, and 90 days later. Settings: The study and the intervention occurred entirely via the internet site. Subjects were recruited primarily via worksites, which referred potential subjects to the website. Subjects: The 351 qualifying subjects were notified of the study via their worksite and required to have internet access. Additionally, subjects were required to be over 18 years of age, smoke cigarettes, and be interested in quitting smoking in the next 30 days. Eligible subjects were randomly assigned individually to treatment or control condition by computer algorithm. Intervention: The intervention consisted of a video based internet site that presented current strategies for smoking cessation and motivational materials tailored to the user's race/ethnicity, sex, and age. Control subjects received nothing for 90 days and were then allowed access to the programme. Main outcome measures: The primary outcome measure was abstinence from smoking at 90 day follow up. Results: At follow up, the cessation rate at 90 days was 24.1% (n = 21) for the treatment group and 8.2% (n = 9) for the control group (p = 0.002). Using an intent-to-treat model, 12.3% (n = 21) of the treatment group were abstinent, compared to 5.0% (n = 9) in the control group (p = 0.015). Conclusions: These evaluation results suggest that a smoking cessation programme, with at least short term efficacy, can be successfully delivered via the internet.

Tobacco control · randomised controlled trial · 142 citationsread the source →

Metabolic effects of intermittent hypoxia in mice: steady versus high-frequency applied hypoxia daily during the rest period.

Intermittent hypoxia (IH) is a frequent occurrence in sleep and respiratory disorders. Both human and murine studies show that IH may be implicated in metabolic dysfunction. Although the effects of nocturnal low-frequency intermittent hypoxia (IH(L)) have not been extensively examined, it would appear that IH(L) and high-frequency intermittent hypoxia (IH(H)) may elicit distinct metabolic adaptations. To this effect, C57BL/6J mice were randomly assigned to IH(H) (cycles of 90 s 6.4% O(2) and 90 s 21% O(2) during daylight), IH(L) (8% O(2) during daylight hours), or control (CTL) for 5 wk. At the end of exposures, some of the mice were subjected to a glucose tolerance test (GTT; after intraperitoneal injection of 2 mg glucose/g body wt), and others were subjected to an insulin tolerance test (ITT; 0.25 units Humulin/kg body wt), with plasma leptin and insulin levels being measured in fasting conditions. Skeletal muscles were harvested for GLUT4 and proliferator-activated receptor gamma coactivator 1-α (PGC1-α) expression. Both IH(H) and IH(L) displayed reduced body weight increases compared with CTL. CTL mice had higher basal glycemic levels, but GTT kinetics revealed marked differences between IH(L) and IH(H), with IH(L) manifesting the lowest insulin sensitivity compared with either IH(H) or CTL, and such findings were further confirmed by ITT. No differences emerged in PGC1-α expression across the three experimental groups. However, while cytosolic GLUT4 protein expression remained similar in IH(L), IH(H), and CTL, significant decreases in GLUT4 membrane fraction occurred in hypoxia and were most pronounced in IH(L)-exposed mice. Thus IH(H) and IH(L) elicit differential glucose homeostatic responses despite similar cumulative hypoxic profiles.

American journal of physiology. Regulatory, integrative and comparative physiology · 61 citationsread the source →

Time-varying associations of pre-migration and post-migration stressors in refugees' mental health during resettlement: a longitudinal study in Australia.

Background: Understanding the time-varying association of pre-migration and post-migration stressors in refugees' mental health could help in designing tailored health promotion services at different resettlement stages and improving the efficiency of resource allocation. In this study, we explored these time-varying associations. Methods: We used data from the first four waves (October, 2013, to February, 2017) of a national refugee-based longitudinal study, the Building a New Life in Australia (BNLA) project. Post-traumatic stress disorder (PTSD) and high risk of severe mental illness (HR-SMI) were used to assess mental health. The independent variables included the number of potentially traumatic events experienced during the pre-migration process, and a range of post-migration stressors. We used logistic regression models to analyse the relative importance of variables and time-varying associations between the pre-migration potentially traumatic events, post-migration resettlement stressors, and refugees' mental health. Analyses were stratified by gender, and sociodemographic covariates included age, marital status, education level, country of birth, and weekly income. Results: 2399 participants were surveyed in Wave 1 of the BNLA project in 2013-14, of whom 2009 (83·7%) responded in Wave 2 in 2014-15, 1894 (78·9%) in Wave 3 in 2015-16, and 1929 (80·4%) in Wave 4 in 2016-17. The three most important factors associated with mental health in each wave differed for male and female refugees, but the socioeconomic stressors of loneliness and adjustment to life in Australia were consistently prominent. Positive associations between socioeconomic stressors and mental ill-health were found for both genders, with a peak at Wave 2 (adjusted odds ratio [AOR] among men, 1·60 [95% CI 1·26-2·03], p=0.0001 for PTSD; AOR 1·86 [1·35-2·55], p=0·0001 for HR-SMI; and among women, AOR 1·81 [1·27-2·57], p=0·0009 for PTSD; AOR 2·24 [1·49-3·38], p=0·0001 for HR-SMI). Associations between loneliness and mental health fluctuated, but were significant for both genders in Wave 4 (among men, AOR 1·90 [1·21-2·99], p=0·0051 for PTSD; AOR 3·70 [2·18-6·27], p<0·0001 for HR-SMI; and among women, AOR 3·65 [2·08-6·39], p<0·0001 for PTSD; AOR 3·68 [2·02-6·69], p<0·0001 for HR-SMI). The association between difficulties in adjustment to life in Australia and male refugees' mental ill-health increased continuously during the resettlement period. Interpretation: Gender-specific and time-sensitive services should be considered to improve refugees' mental health. For both genders, improved economic conditions that complement social security benefits deserve attention and are relevant throughout the resettlement process. At the later stage of resettlement, services to reduce loneliness could be carried out, and reducing stressors related to adjustment to life in the host country is especially needed for male refugees. Funding: None.

The lancet. Psychiatry · 63 citationsread the source →

Bullying and Suicide: A Public Health Approach

Several recent studies have found an association between bullying and depression [[1]Wang J. Iannotti R.J. Luk J.W. Nansel T.R. Co-occurrence of victimization from five subtypes of bullying: Physical, verbal, social exclusion, spreading rumors, and cyber.J Pediatr Psychol. 2010; 35: 1103-1112Crossref PubMed Scopus (223) Google Scholar] or bullying and suicide-related behaviors [[2]Kim Y.S. Leventhal B. Suicide and bullying. A review. Int J Adolesc Med Health. 2008; 20: 133-154Crossref PubMed Scopus (324) Google Scholar], and one study found evidence consistent with a causal link, at least for girls [3Klomek A.B. Sourander A. Niemela S. et al. Childhood bullying behaviors as a risk for suicide attempts and completed suicides: A population-based birth cohort study.J Am Acad Child Adolesc Psychiatry. 2009; 48: 254-261Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar, 4Klomek A.B. Sourander A. Gould A. The association of suicide and bullying in childhood to young adulthood: A review of cross-sectional and longitudinal research findings. Can J Psychiatry. 2010; 55: 282-288PubMed Google Scholar]. These studies, in conjunction with extensive media coverage of the deaths by suicide of several young people who were victims of bullying, led the Centers for Disease Control and Prevention (CDC) to convene an expert panel focusing on the relationship between bullying involvement and suicide-related behaviors. The purpose of the panel, held in September 2010, was to synthesize the latest research about the relationship between youth involvement in bullying (youth who bully, youth who are bullied, and those who bully and are bullied) and suicide-related behaviors (attempts, fatalities, and risk factors associated with suicide, such as depression). Experts on the topics of bullying and suicide presented their research about the relationship between these two behaviors; their work is contained in this supplement. The panel and this special issue provide clarity around the complicated issues of bullying and suicide among youth. Three key themes emerged: (1) bullying among youth is a significant public health problem; it is prevalent and frequently has detrimental effects; (2) there is a strong association between bullying and suicide-related behaviors, but this relationship is often mediated by other factors, including depression and delinquency; and (3) there are public health strategies that can be applied to the prevention of bullying and suicide. Bullying is a significant public health problem because it is prevalent and harmful. Between 20% and 56% of young people are involved in bullying annually [5Centers for Disease Control and Prevention. Youth risk behavior surveillance—United States, 2011. MMWR, Surveillance Summaries 2012;61(no. SS-4). Available at: www.cdc.gov/mmwr/pdf/ss/ss6104.pdf. Google Scholar, 6Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 7Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Thus, in a classroom of 30 students, between 6 and 17 students are involved in bullying as a victim, perpetrator, or both (bully-victim). The specific rate of bullying victimization and perpetration varies according to age, type of bullying, time period over which bullying behaviors are assessed, and by subgroup. Younger (middle school-aged) children are more likely to be involved in bullying than high school-aged children [[8]Robers S. Zhang J. Truman J. Indicators of school crime and safety: 2011 (NCES 2012-002/NCJ 236021). National Center for Education Statistics, U.S. Department of Education, and Bureau of Justice Statistics, Office of Justice Programs, U.S. Department of Justice, Washington, DC2012Google Scholar]. Verbal bullying is generally more prevalent than physical or cyber-bullying and bullying is more likely to occur over a longer time period—“ever” or over the “past year” as opposed to “the past few months” [[9]David-Ferdon C. Hertz M.F. Electronic media and youth violence: A CDC issue brief for researchers. Centers for Disease Control, Atlanta, GA2009Google Scholar]. Specific subgroups are more likely to be victimized. For example, bullying victimization is more prevalent upon lesbian and gay youth—60% report victimization during the past 30 days prior to the survey compared with 28.8% of heterosexual youth [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. For young people involved in bullying in any capacity—youth who bully others, who are bullied, or who both bully and are bullied, this involvement is correlated with poor mental and physical health and engagement in other risk behaviors. Youth who are bullied are more likely to be depressed or anxious [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar], have lower academic achievement, report feeling like they do not belong at school [[12]Glew G.M. Fan M. Katon W. et al. Bullying, psychosocial adjustment, and academic performance in elementary school. Arch Pediatr Adolesc Med. 2005; 159: 1026-1031Crossref PubMed Scopus (384) Google Scholar], have poorer social and emotional adjustment, greater difficulty making friends, poorer relationships with classmates, and greater loneliness [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Bully-victims are more likely than those who bully, those who are bullied, or their uninvolved peers to report being physically hurt by a family member, to witness family violence, and exhibit suicide-related behaviors [[14]McKenna M. Hawk E. Mullen J. Hertz M. The association between bullying behavior and health risks among middle school and high school students in Massachusetts, 2009.Morbidity and Mortality Weekly Review. 2011; 60: 465-471PubMed Google Scholar]. Those who bully others are more likely to drink alcohol and use cigarettes, to have poorer academic achievement and poorer perceived school climate, but to also report greater ease of making friends [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Involvement in bullying can also have long-lasting, detrimental effects months or even years after the bullying occurs. Young people who are bullied are more likely than uninvolved youth to develop depression and anxiety and report abdominal pain and feeling tense over the course of a school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. One study examining the impact of bullying victimization of those who were between 9, 11, and 13 years of age when they were victimized found, that over a 7-year period, youth who were bullied were more likely to develop generalized anxiety and panic disorder as adults while bully-victims were more likely to subsequently suffer from depression, panic disorder, and suicidality [[15]Copeland W.E. Wolke D. Angold A. Costello E.J. Adult psychiatric outcomes of bullying and being bullied by peers in childhood and adolescence.JAMA Psychiatry. 2013; 70: 419-426Crossref PubMed Scopus (746) Google Scholar]. Another longitudinal study found that those who were perpetrators of bullying at age 14 were more likely to receive a diagnosis of antisocial personality disorder, to have low job status at age 18 years, and to use drugs at ages 27–32 years [[16]Farrington D.P. Ttofi M.M. Bullying as a predictor of offending, violence and later life outcomes. Crim Behav Ment Health. 2011; 21: 90-98Crossref PubMed Scopus (169) Google Scholar]. The articles in this special issue generally show a strong association between involvement in bullying behaviors and suicide-related behaviors. In Espelage and Holt's work with middle school students, suicidal ideation and attempts were significantly more prevalent among victims, bully-victims and perpetrators, with rates of ideation and attempts among those involved as a victim, perpetrator, or bully-victims three to five times higher than the rate of uninvolved youth [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar]. Likewise, in Borowsky's study of 6th, 9th, and 12th graders, 1.2% of uninvolved youth made a suicide attempt, compared with 5% for those who frequently bullied others verbally or socially; 6.5% for those who were frequent victims of verbal/social bullying; and 11.1% for those who were frequent bully-victims of verbal/social bullying [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. In Kowalski and Limber's paper, depression, anxiety, self-esteem, self-reported health problems, absences from school, leaving school because of illness, and grades were, with only one exception, significantly related to students' involvement in cyber-bullying others, being cyber-bullied, bullying others through traditional means, and being bullied through traditional means [[7]Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Those who witness bullying but are not directly involved are also at increased risk. Rivers and Noret [[18]Rivers I. Noret N. Potential suicide ideation and its association with observing bullying at school.J Adolesc Health. 2013; 53: S32-S36Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar] report that students who observed bullying behavior were significantly more likely than those uninvolved in bullying to report symptoms of interpersonal sensitivity (feelings of being hurt and feelings of inferiority) and greater helplessness. However, the papers in this issue also convey the complexity of the relationship between bullying and suicide-related behaviors. In Espelage and Holt's work [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar], after controlling for delinquency and depression there was no increased risk of suicide-related behaviors for perpetrators; the increased risk did remain for victims. Klomek's [[19]Klomek A.B. Kleinman M. Altschuler E. et al. Suicidal adolescents' experiences with bullying perpetration and victimization during high school as risk factors for later depression and suicidality.J Adolesc Health. 2013; 53: S37-S42Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar] comparison of young people with bullying involvement and psychiatric symptoms (depression, suicidality, or substance use) at an initial screen to those with psychiatric symptoms but no bullying involvement found, at 2-year follow-up, that only perpetrators of bullying were significantly more likely to be functionally impaired than bullying-uninvolved students. In King's study of hospitalized suicidal youth, those who reported perpetrating bullying were more likely than uninvolved youth to have severe suicidal thoughts and psychosocial impairment, and to abuse substances. However, at 12-month follow-up, only the difference in psychosocial impairment remained. Interestingly, over the course of 1-year treatment for the suicidality, the rate of bullying perpetration declined [[20]King C.A. Horwitz A. Berona J. Jiang Q. Acutely suicidal adolescents who engage in bullying behavior: 1-year trajectories.J Adolesc Health. 2013; 53: S43-S50Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. In Karch's analysis of suicide fatalities among youth, bullying involvement was one of a myriad of factors precipitating a death by suicide. A quarter of young suicide victims had school problems, but only 12.4% of these school problems were attributed to bullying [[21]Karch D.L. Logan J. McDaniel D.D. et al. Precipitating circumstances of suicide among youth aged 10–17 years by sex: Data from the National Violent Death Reporting System, 16 States, 2005–2008.J Adolesc Health. 2013; 53: S51-S53Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar]. Other salient circumstances included depressed mood and/or other current mental health problems (37%); intimate partner problems (25%); history of suicide attempts (18%); and substance abuse problems (16%). Suicide attempts and substance use were risk factors that co-occurred with suicide ideation in Borowsky et al. as well [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all groups (victims, perpetrators, and bully-victims) a history of self-harm within the prior year and greater emotional distress (feelings of sadness, hopelessness, worry, stress, or pressure) drastically increased risk for suicide. For victims and bully-victims, a history of sexual abuse, a mental health problem, or running away from home in the past year increased the likelihood of suicidal thinking or behavior [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. More than half of the youth who were bully-victims and who expressed suicidal ideation or reported making an attempt also witnessed family violence, had a history of physical abuse, smoked cigarettes, used marijuana, skipped school because of safety concerns, or carried a weapon at school. Youth who were involved in bullying and reported suicide-related thoughts or behaviors also had higher mean scores for distractibility/impulsivity and lower mean scores for parent connectedness, connectedness to other adults, perceived caring by teachers, perceived caring by friends, liking school, academic achievement, physical activity, perceived school safety, and perceived neighborhood safety [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all three bullying-involved groups, parent connectedness (feeling like you can talk to mom/dad about problems; that mom/dad care about you) was protective for suicidal ideation and attempts. Other protective factors for victims included stronger connections to nonparental adults, stronger perceived caring by friends, and liking school. For bully-victims, greater perceived caring by friends was also protective [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. That there is a relationship between bullying and depression and that this relationship may help to explain the relationship between bullying and suicide is fairly consistent across papers. However, the direction of this relationship is unclear. Do youth who are bullied become depressed or are depressed youth more likely to be bullied? A study from the Netherlands suggests the answer may be “both.” Researchers found that victims of bullying had significantly higher chances of developing new psychosomatic and psychosocial problems over the course of a school year compared with children who were not bullied. However, children with preexisting depressive symptoms or anxiety were also significantly more likely to be newly victimized over the course of the school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. Despite the complexity of the relationship between bullying and suicide, there is no doubt that bullying involvement can have detrimental effects and prevention of bullying could improve health and mental health outcomes for many youth. The findings in these articles underscore the complexity of the relationship between bullying and suicide. A critical difference distinguishes an association between bullying and suicide from a causal relationship, with significant implications for prevention. Conveying that bullying alone causes suicide at best minimizes, and at worst ignores, the other factors that may contribute to death by suicide. This neglect may result in too narrow a focus of preventive action. We echo the call made by others for an integrated approach to preventing suicide and youth violence by focusing on shared risk and protective factors including individual coping skills, family and school social support, and supportive school environments [[22]Lubell K.M. Vetter J.B. Suicide and youth violence prevention: The promise of an integrated approach. Aggression and Violent Behavior. 2006; 11: 167-175Crossref Scopus (71) Google Scholar]. Strengthening social connectedness and ensuring access to supportive adults may pay dividends in impacting both bullying and suicide behaviors. Supportive home and school environments where young people feel connected are just one overlapping protective factor. Borowksy's findings regarding connection to parents, other adults, school, and friends reflect the need for multiple strategies that focus on both the school and home environments and that move beyond the individual skill-building level to foster supportive environments [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. The case for a supportive environment on bullying and suicide prevention is supported by Hatzenbuehler's work. In the paper contained in this special issue, he reports findings that lesbian and gay youths living in counties with fewer school districts with antibullying policies that specifically mentioned sexual orientation as a protected group were nearly two times more likely to have attempted suicide in the past year compared with those living in counties where more districts had these policies [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. Williams and Guerra reported that youth who describe their school climate as being trusting, fair, and pleasant have lower involvement in verbal, physical, and Internet bullying perpetration [[23]Williams K.R. Guerra N.G. Prevalence and predictors of internet bullying.J Adolesc Health. 2007; 41: S14-S21Abstract Full Text Full Text PDF PubMed Scopus (669) Google Scholar]. As reflected in CDC's strategic direction on suicide [[24]Centers for Disease Control and Prevention (CDC). Connectedness as a strategic direction for the prevention of suicidal behavior. Available at: http://www.cdc.gov/violenceprevention/pdf/suicide_strategic_direction-one-pager-a.pdf. Google Scholar], approaches intended to build connections between youth and school and home environments, as well as communities, are essential to suicide prevention. Sources of Strength is a school-based suicide-prevention program that trains youth opinion leaders to change the norms and behaviors of their peers by conducting well-defined messaging activities with adult mentoring, as well as increasing perceptions of adult support for suicidal youths and the acceptability of seeking help M. et of the Sources of Strength suicide prevention program by leaders in high J Health. 2010; PubMed Scopus Google Scholar]. work also the of connections to support prevention. As an example, the youth suicide prevention found that who reported a stronger connection to youth in their program were as likely to suicidal youth. the research also that the bullying prevention are A of school bullying strategies that school approaches that included multiple and at of school more often reduced victimization and bullying than the that only included or social groups A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. there is about the prevention of bullying and suicide, there is also do not studies over the past two have the of bullying prevention However, studies have in the States, these have not A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. is evidence that youth violence prevention that for such as and also rates of bullying The impact of and on bullying and A Pediatr Adolesc Med. PubMed Scopus Google Scholar]. More work is to strategies that bullying from among youth in the In that depression is a significant risk for bullying and suicide as well as a of other behaviors. We need to to mental among young people and their and to do in and However, the and impact of bullying, it is to move while these strategies are being We can by and strategies that have at increasing protective factors and risk factors associated with both bullying and suicide. is not that bullying in is it that bullying occur in the in and health their focus beyond just to those who are involved in bullying or suicide-related behaviors, but also in strategies to bullying and suicidal behavior from in the

Journal of Adolescent Health · editorial or comment · 170 citationsread the source →

Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus.

Background: Hepatitis is a viral infection of the liver. It is mainly transmitted between people through contact with infected blood, frequently from mother to baby in-utero. Hepatitis B poses significant risk to the fetus and up to 85% of infants infected by their mothers at birth develop chronic hepatitis B virus (HBV) infection. Hepatitis B immunoglobulin (HBIG) is a purified solution of human immunoglobulin that could be administered to the mother, newborn, or both. HBIG offers protection against HBV infection when administered to pregnant women who test positive for hepatitis B envelope antigen (HBeAg) or hepatitis B surface antigen (HBsAg), or both. When HBIG is administered to pregnant women, the antibodies passively diffuse across the placenta to the child. This materno-fetal diffusion is maximal during the third trimester of pregnancy. Up to 1% to 9% infants born to HBV-carrying mothers still have HBV infection despite the newborn receiving HBIG plus active HBV vaccine in the immediate neonatal period. This suggests that additional intervention such as HBIG administration to the mother during the antenatal period could be beneficial to reduce the transmission rate in utero. Objectives: To determine the benefits and harms of hepatitis B immunoglobulin (HBIG) administration to pregnant women during their third trimester of pregnancy for the prevention of mother-to-child transmission of hepatitis B virus infection. Search methods: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), SCOPUS, African Journals OnLine, and INDEX MEDICUS up to June 2016. We searched ClinicalTrials.gov and portal of the WHO International Clinical Trials Registry Platform (ICTRP) in December 2016. Selection criteria: We included randomised clinical trials comparing HBIG versus placebo or no intervention in pregnant women with HBV. Data collection and analysis: Two authors extracted data independently. We analysed dichotomous outcome data using risk ratio (RR) and continuous outcome data using mean difference (MD) with 95% confidence intervals (CI). For meta-analyses, we used a fixed-effect model and a random-effects model, along with an assessment of heterogeneity. If there were statistically significant discrepancies in the results, we reported the more conservative point estimate. If the two estimates were equal, we used the estimate with the widest CI as our main result. We assessed bias control using the Cochrane Hepato-Biliary Group suggested bias risk domains and risk of random errors using Trial Sequential Analysis (TSA). We assessed the quality of the evidence using GRADE. Main results: All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo. Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. Authors' conclusions: Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.

The Cochrane database of systematic reviews · meta-analysis · 42 citationsread the source →

The relationships between perfectionism and symptoms of depression, anxiety and obsessive-compulsive disorder in adults: a systematic review and meta-analysis.

Perfectionism is a transdiagnostic process associated with depression, anxiety, and obsessive-compulsive disorder (OCD). The focus of this systematic review and meta-analysis was to examine evidence for the association between perfectionistic strivings and perfectionistic concerns with symptoms of depression, general anxiety, social anxiety, task anxiety, and OCD in adults. A total of 416 studies were included, with 113,118 participants aged 17 to 90 years (M = 23.83). Perfectionistic concerns had significant medium correlations with anxiety, OCD and depressive symptoms (pooled r = .38 to .43). Perfectionistic strivings had significant, small correlations with OCD, depression and all anxiety outcomes (pooled r = .10 to .21), except social anxiety where there was no association. Results demonstrate perfectionistic concerns have a stronger relationship with psychological distress than perfectionistic strivings, but strivings are significantly related to distress. Future research should examine the causal relationships between perfectionism dimensions and psychopathology.

Cognitive behaviour therapy · meta-analysis · 19 citationsread the source →

Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis.

Background: Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder. Methods: For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features. Findings: We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21-3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25-1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10-2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45-5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39-2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41-2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13-1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43-2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45-2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09-1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07-1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88-2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality. Interpretation: Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder. Funding: None.

The lancet. Psychiatry · meta-analysis · 278 citationsread the source →

Burden, risk factors, and comorbidities of behavioural and emotional problems in Kenyan children: a population-based study.

Background: Three-quarters of the burden of mental health problems occurs in low-and-middle-income countries, but few epidemiological studies of these problems in preschool children from sub-Saharan Africa have been published. Behavioural and emotional problems often start in early childhood, and this might be particularly important in Africa, where the incidence of perinatal and early risk factors is high. We therefore aimed to estimate the prevalence and risk factors of behavioural and emotional problems in young children in a rural area on the Kenyan coast. Methods: We did a population-based epidemiological study to assess the burden of behavioural and emotional problems in preschool children and comorbidities in the Kilifi Health and Demographic Surveillance System (KHDSS, a database formed of the population under routine surveillance linked to admissions to Kilifi County Hospital). We used the Child Behaviour Checklist (CBCL) to assess behavioural and emotional problems. We then determined risk factors and medical comorbidities associated with behavioural and emotional problems. The strength of associations between the risk factors and the behavioural and emotional problems was estimated using generalised linear models, with appropriate distribution and link functions. Findings: 3539 families were randomly selected from the KHDSS. Of these, 3273 children were assessed with CBCL. The prevalence of total behavioural and emotional problems was 13% (95% CI 12-14), for externalising problems was 10% (9-11), and for internalising problems was 22% (21-24). The most common CBCL syndrome was somatic problems (21%, 20-23), whereas the most common DSM-IV-oriented scale was anxiety problems (13%, 12-14). Factors associated with total problems included consumption of cassava (risk ratio 5·68, 95% CI 3·22-10·03), perinatal complications (4·34, 3·21-5·81), seizure disorders (2·90, 2·24-3·77), and house status (0·11, 0·08-0·14). Seizure disorders, burn marks, and respiratory problems were important comorbidities of behavioural and emotional problems. Interpretation: Behavioural and emotional problems are common in preschool children in this Kenyan rural area and are associated with preventable risk factors. Behavioural and emotional problems and associated comorbidities should be identified and addressed in young children. Funding: Wellcome Trust.

The lancet. Psychiatry · 43 citationsread the source →

Interventions for improving sleep quality in people with chronic kidney disease.

Background: Sleep disorders are commonly experienced by people with chronic kidney disease (CKD). Several approaches for improving sleep quality are used in clinical practice including relaxation techniques, exercise, acupressure, and medication. Objectives: To assess the effectiveness and associated adverse events of interventions designed to improve sleep quality among adults and children with CKD including people with end-stage kidney disease (ESKD) treated with dialysis or kidney transplantation. Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 8 October 2018 with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: We included randomised controlled trials (RCTs) or quasi-randomised RCTs of any intervention in which investigators reported effects on sleep quality. Two authors independently screened titles and abstracts of identified records. Data collection and analysis: Two review authors independently extracted data and assessed the risk of bias for included studies. The primary outcomes were sleep quality, sleep onset latency, sleep duration, sleep interruption, and sleep efficiency. Risks of bias were assessed using the Cochrane tool. Evidence certainty was assessed using the GRADE approach. We calculated treatment estimates as risk ratios (RR) for dichotomous outcomes or mean difference (MD) or standardised MD (SMD) for continuous outcomes to account for heterogeneity in measures of sleep quality. Main results: Sixty-seven studies involving 3427 participants met the eligibility criteria. Thirty-six studies involving 2239 participants were included in meta-analyses. Follow-up for clinical outcomes ranged between 0.3 and 52.8 weeks (median 5 weeks). Interventions included relaxation techniques, exercise, acupressure, cognitive-behavioural therapy (CBT), educational interventions, benzodiazepine treatment, dopaminergic agonists, telephone support, melatonin, reflexology, light therapy, different forms of peritoneal dialysis, music, aromatherapy, and massage. Incomplete reporting of key methodological details resulted in uncertain risk of bias in many studies. In very low certainty evidence relaxation techniques had uncertain effects on sleep quality and duration, health-related quality of life (HRQoL), depression, anxiety, and fatigue. Studies were not designed to evaluate the effects of relaxation on sleep latency or hospitalisation. Exercise had uncertain effects on sleep quality (SMD -1.10, 95% CI -2.26 to 0.05; I2 = 90%; 5 studies, 165 participants; very low certainty evidence). Exercise probably decreased depression (MD -9.05, 95% CI -13.72 to -4.39; I2 = 0%; 2 studies, 46 participants; moderate certainty evidence) and fatigue (SMD -0.68, 95% CI -1.07 to -0.29; I2 = 0%; 2 studies, 107 participants; moderate certainty evidence). Compared with no acupressure, acupressure had uncertain effects on sleep quality (Pittsburgh Sleep Quality Index (PSQI) scale 0 - 21) (MD -1.27, 95% CI -2.13 to -0.40; I2 = 89%; 6 studies, 367 participants: very low certainty evidence). Acupressure probably slightly improved sleep latency (scale 0 - 3) (MD -0.59, 95% CI -0.92 to -0.27; I2 = 0%; 3 studies, 173 participants; moderate certainty evidence) and sleep time (scale 0 - 3) (MD -0.60, 95% CI -1.12 to -0.09; I2 = 68%; 3 studies, 173 participants; moderate certainty evidence), although effects on sleep disturbance were uncertain as the evidence certainty was very low (scale 0 - 3) (MD -0.49, 95% CI -1.16 to 0.19; I2 = 97%). In moderate certainty evidence, acupressure probably decrease fatigue (MD -1.07, 95% CI -1.67 to -0.48; I2 = 0%; 2 studies, 137 participants). Acupressure had uncertain effects on depression (MD -3.65, 95% CI -7.63 to 0.33; I2 = 27%; 2 studies, 137 participants; very low certainty evidence) while studies were not designed to evaluate the effect of acupressure on HRQoL, anxiety, or hospitalisation. It was uncertain whether acupressure compared with sham acupressure improved sleep quality (PSQI scale 0 to 21) because the certainty of the evidence was very low (MD -2.25, 95% CI -6.33 to 1.82; I2 = 96%; 2 studies, 129 participants), but total sleep time may have been improved (SMD -0.34, 95% CI -0.73 to 0.04; I2 = 0%; 2 studies, 107 participants; low certainty evidence). 2 =2 =There were no studies designed to directly examine and/or correlate efficacy of any interventions aimed at improving sleep that may have been attempted for the spectrum of sleep disordered breathing. No studies reported treatment effects for children. Adverse effects of therapies were very uncertain. Authors' conclusions: The evidence base for improving sleep quality and related outcomes for adults and children with CKD is sparse. Relaxation techniques and exercise had uncertain effects on sleep outcomes. Acupressure may improve sleep latency and duration, although these findings are based on few studies. The effects of acupressure were not confirmed in studies in which sham acupressure was used as the control. Given the very low certainly evidence, future research will very likely change the evidence base. Based on the importance of symptom management to patients, caregivers and clinicians, future studies of sleep interventions among people with CKD should be a priority.

The Cochrane database of systematic reviews · systematic review · 45 citationsread the source →

Mindfulness Meditation Reduces Intraocular Pressure, Lowers Stress Biomarkers and Modulates Gene Expression in Glaucoma: A Randomized Controlled Trial.

Background: Reducing intraocular pressure (IOP) in primary open-angle glaucoma (POAG) is currently the only approach to prevent further optic nerve head damage. However, other mechanisms such as ischemia, oxidative stress, glutamate excitotoxicity, neurotrophin loss, inflammation/glial activation, and vascular dysregulation are not addressed. Because stress is a key risk factor affecting these mechanisms, we evaluated whether mindfulness-based stress reduction can lower IOP and normalize typical stress biomarkers. Materials and methods: In a prospective, randomized trial 90 POAG patients (180 eyes; age above 45 y) were assigned to a waitlist control or mindfulness meditation group which practiced daily for 21 days. We measured IOP (primary endpoint), quality of life (QOL), stress-related serum biomarkers [cortisol, β-endorphins, IL6, TNF-α, brain-derived neurotrophic factor (BDNF), reactive oxygen species (ROS), total antioxidant capacity (TAC)], and whole genome expression. Results: Between-group comparisons revealed significantly lowered IOP in meditators (OD: 18.8 to 12.7, OS 19.0 to 13.1 mm Hg) which correlated with significantly lowered stress-biomarker levels including cortisol (497.3 to 392.3 ng/mL), IL6 (2.8 to 1.5 ng/mL), TNF-α (57.1 to 45.4 pg/mL), ROS (1625 to 987 RLU/min/104 neutrophils), and elevated β-endorphins (38.4 to 52.7 pg/mL), BDNF (56.1 to 83.9 ng/mL), and TAC (5.9 to 9.3) (all P<0.001). These changes correlated well with gene expression profiling. Meditators improved in QOL (P<0.05). Conclusions: A short course of mindfulness-based stress reduction by meditation in POAG, reduces IOP, improves QOL, normalizes stress biomarkers, and positively modifies gene expression. Mindfulness meditation can be recommended as adjunctive therapy for POAG.

Journal of glaucoma · randomised controlled trial · 85 citationsread the source →

Using a Mobile Application in the Treatment of Dysregulated Anger Among Veterans.

Objective: Anger is a symptom of post-traumatic stress disorder (PTSD) associated with a range of clinical and functional impairments, and may be especially prevalent among veterans with PTSD. Effective anger management therapies exist but may be undermined by poor engagement or lack of treatment availability. Finding ways to engage veterans in anger management therapy or to improve access can be helpful in improving clinical outcomes. This randomized controlled trial compared anger management treatment (AMT) with AMT augmented by a mobile application (app) system, Remote Exercises for Learning Anger and Excitation Management (RELAX). Methods: Participants were 58 veterans enrolled in 12 sessions of either AMT alone or AMT with the RELAX system (AMT + RELAX). The RELAX system includes the RELAX app, a wearable heart rate monitor, a remote server, and a web-based therapist interface. RELAX allows the user to practice skills, monitor symptoms, and record physiological data. The server collects data on app use. A web-based interface allows the therapist to access data on between-session practice, and skills use. Measures administered at baseline, post-treatment, and 3-and 6-month follow-up include state and trait anger, dimensions of anger, PTSD, depression, interpersonal functioning, and satisfaction. We used multilevel modeling to account for the nesting of time points within participants and participants within treatment groups. Predictors were Treatment Condition (AMT + RELAX and AMT), Linear Time (baseline, post-treatment, 3-and 6-month follow-up), and Quadratic Time and Treatment Condition × Linear Time interaction. All analyses were conducted using SPSS 21 (Armonk, New York). Approval was obtained from the institutional review board. Results: Across groups, the treatment dropout rate was 13.8%; of those who remained in treatment, 90% received an adequate dose of treatment (10 or more sessions). There were no significant differences between groups on attendance or treatment completion. Participants in both treatments demonstrated statistically significant and clinically meaningful reductions in anger severity and significant post-treatment reductions in PTSD. Veterans did not report significant changes in depression or interpersonal functioning. Veterans in the AMT + RELAX group reported spending significantly less time on homework assignments, and they rated the AMT + RELAX app as helpful and easy to use, with these ratings improving over time. Conclusion: Findings suggest that AMT + RELAX was beneficial in reducing anger symptoms and promoting efficient use of the between-session practice; however, AMT + RELAX did not outperform AMT. This study is an important contribution as it is one of the first randomized controlled trials to study the efficacy of a technology-enhanced, evidence-based psychotherapy for anger management. Findings are limited because of small sample size and modifications to the technology during the trial. However, the results highlight the possible benefits of mobile app-supported treatment, including increasing the accessibility of treatment, lowering therapist workload, reducing costs of treatment, reducing practice time, and enabling new activities and types of treatments. This study presents preliminary evidence that mobile apps can be a valuable addition to treatment for patients with anger difficulties. Future research should evaluate how much therapist involvement is needed to support anger management.

Military medicine · randomised controlled trial · 21 citationsread the source →

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →

A randomised controlled trial of a relationship-focussed mobile phone application for improving adolescents' mental health.

Background: This study evaluated the acceptability and effectiveness of a relationship-focussed mobile phone application (WeClick) for improving depressive symptoms and other mental health outcomes in adolescents. Methods: A randomised controlled trial involving 193 youth (M age: 14.82, SD: 0.94, 86.5% female) from Australia was conducted. Youth were recruited via the Internet and randomly allocated to the intervention or a 4-week wait list control condition, stratified for age and gender. The primary outcome was change in depressive symptom scores measured using the Patient Health Questionnaire for Adolescents (PHQ-A) at baseline, 4-week post-test and 12-week follow-up. Secondary outcomes included anxiety, psychological distress, wellbeing, help-seeking intentions for mental health, social self-efficacy and social support. Participants in the intervention condition received access to the intervention for four weeks. Thematic analysis was utilised to identify and examine acceptability. Results: The change in PHQ-A scores from baseline to 4-week post-test did not differ significantly (d = 0.26, p = .138) between the intervention (Mchange = -2.9, SD = 5.3) and wait list control conditions (Mchange = -1.7, SD = 4.3). However, significant between-group improvements were observed in wellbeing (d = 0.37, p = .023), help-seeking intentions (d = 0.36, p = .016) and professional help-seeking intentions for mental health problems (d = 0.36, p = .008). Increases in help-seeking intentions were sustained at follow-up in the intervention condition. No differential effects were found for generalised anxiety, separation anxiety, social self-efficacy or for any social support outcomes. Over 90% of participants indicated the app was enjoyable, interesting and easy to use. The app provided 'advice and direction' (n = 42; 46.15%), an 'opportunity for self-reflection' (n = 33; 36.3%) and 'normalised experiences' (n = 21; 23.1%). Conclusions: The WeClick app was found to be effective for improving wellbeing and help-seeking intentions for mental health in adolescents. A larger, adequately powered trial is now required to establish differential effects on depressive symptoms. This trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12618001982202.

Journal of child psychology and psychiatry, and allied disciplines · randomised controlled trial · 50 citationsread the source →

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

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

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

Virtual Reality Smartphone-Based Intervention for Smoking Cessation: Pilot Randomized Controlled Trial on Initial Clinical Efficacy and Adherence.

Background: Obstacles to current tobacco cessation programs include limited access and adherence to effective interventions. Digital interventions offer a great opportunity to overcome these difficulties, yet virtual reality has not been used as a remote and self-administered tool to help increase adherence and effectiveness of digital interventions for tobacco cessation. Objective: This study aimed to evaluate participant adherence and smoking cessation outcomes in a pilot randomized controlled trial of the digital intervention Mindcotine (MindCotine Inc) using a self-administered treatment of virtual reality combined with mindfulness. Methods: A sample of 120 participants was recruited in the city of Buenos Aires, Argentina (mean age 43.20 years, SD 9.50; 57/120, 47.5% female). Participants were randomly assigned to a treatment group (TG), which received a self-assisted 21-day program based on virtual reality mindful exposure therapy (VR-MET) sessions, daily surveys, and online peer-to-peer support moderated by psychologists, or a control group (CG), which received the online version of the smoking cessation manual from the Argentine Ministry of Health. Follow-up assessments were conducted by online surveys at postintervention and 90-day follow-up. The primary outcome was self-reported abstinence at postintervention, with missing data assumed as still smoking. Secondary outcomes included sustained abstinence at 90-day follow-up, adherence to the program, and readiness to quit. Results: Follow-up rates at day 1 were 93% (56/60) for the TG and 100% (60/60) for the CG. At postintervention, the TG reported 23% (14/60) abstinence on that day compared with 5% (3/60) in the CG. This difference was statistically significant (χ21=8.3; P=.004). The TG reported sustained abstinence of 33% (20/60) at 90 days. Since only 20% (12/60) of participants in the CG completed the 90-day follow-up, we did not conduct a statistical comparison between groups at this follow-up time point. Among participants still smoking at postintervention, the TG was significantly more ready to quit compared to the CG (TG: mean 7.71, SD 0.13; CG: mean 7.16, SD 0.13; P=.005). A total of 41% (23/56) of participants completed the treatment in the time frame recommended by the program. Conclusions: Results provide initial support for participant adherence to and efficacy of Mindcotine and warrant testing the intervention in a fully powered randomized trial. However, feasibility of trial follow-up assessment procedures for control group participants needs to be improved. Further research is needed on the impact of VR-MET on long-term outcomes. Trial registration: ISRCTN Registry ISRCTN50586181; http://www.isrctn.com/ISRCTN50586181.

Journal of medical Internet research · randomised controlled trial · 45 citationsread the source →

A Community Health Worker-Led Positive Psychology Intervention for African American Older Adults With Chronic Pain.

Background and objectives: Experiencing structural racism over the life course contributes to disproportionate pain-related disability among African American older adults. Positive STEPS, delivered by community health workers, is a culturally congruent chronic pain self-management intervention that incorporates positive psychology principles and gives attention to social determinants of pain and pain management. Research design and methods: We conducted a randomized pilot trial among older adults with chronic musculoskeletal pain in an underserved, primarily African American community (Detroit, Michigan). The 7-week intervention included weekly telephone sessions with a community health worker; web-based videos teaching pain self-management skills; positive activities (e.g., Life Review, Gratitude Jar); and use of wearable activity trackers. Outcomes were measured at baseline and 8-week follow-up. We assessed participant retention, engagement, and satisfaction. Results: Study completers (n = 46; 90% retention) were 93% African American, 89% female, mean 72 years, and completed 5.7 of 7 sessions. Intervention participants versus controls showed greater improvement in PROMIS Pain Interference (4.3-point T-score decrease vs. 0.4-point increase; p = .01) and the Pain Self-Efficacy Questionnaire (p = .007). Furthermore, compared with controls, significantly more intervention participants reported "better" or "much better" global functioning (86% vs. 25%; p = .000) and pain (67% vs. 21%; p = .003) since baseline. Improvements in physical functioning, social participation, and resilience were noted, but differences were not significant. Participant feedback on the intervention was overwhelmingly positive. Discussion and implications: A community health worker-led chronic pain self-management intervention combining positive activities with self-management skills training demonstrated the potential to enhance pain-related functioning among a vulnerable group of older adults. Clinical trial number: NCT04321239.

The Gerontologist · randomised controlled trial · 16 citationsread the source →

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 →

Efficacy and cost-effectiveness of therapist-guided internet cognitive behavioural therapy for paediatric anxiety disorders: a single-centre, single-blind, randomised controlled trial.

Background: Paediatric anxiety disorders are associated with substantial disability and long-term adverse consequences, but only a small proportion of affected children have access to evidence-based treatment. Internet-delivered cognitive behavioural therapy (ICBT) could help increase accessibility but needs further rigorous assessment. We aimed to assess the efficacy and cost-effectiveness of ICBT in the treatment of paediatric anxiety disorders. Methods: We did a single-blind randomised controlled trial in a clinical research unit within the Child and Adolescent Mental Health Services in Stockholm (Sweden). Eligible participants were children aged 8-12 years with a diagnosis of a principal anxiety disorder (seperation anxiety disorder, generalised anxiety disorder, specific phobia, social anxiety disorder, or panic disorder) of at least moderate severity. We randomly allocated participants (1:1) to ICBT or internet-delivered child-directed play, an active comparator aimed to improve parent-child relationships and increase a child's self-esteem without directly targeting anxiety. Block sizes for the randomisation varied between four and six and were generated using a computer random-number generator, and the allocation was concealed from the researchers by opaque sealed envelopes. Both treatment programmes comprised 12 modules presented over 12 weeks with weekly asynchronous online therapist support, and consisted of texts, films, illustrations, and exercises. The primary outcome was severity rating of the principal anxiety disorder 12-weeks post-treatment, via the Anxiety Disorder Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders-IV (a rating of at least 4 corresponds to meeting the criteria for the principal diagnosis), assessed by clinicians masked to treatment allocation. All participants were included in the primary analysis (intention-to-treat). This trial is registered at ClinicalTrials.gov, number NCT02350257. Findings: Between March 11, 2015, and Oct 21, 2016, 131 participants were recruited and allocated to either ICBT (n=66) or internet-delivered child-directed play (n=65). The clinician-assessed severity rating of the principal anxiety disorder improved significantly after the 12-weeks treatment period for participants in both ICBT (within-group effect size 1·22, 95% CI 0·78-1·65) and the active control (0·72, 0·44-1·00) groups. However, greater improvement was seen with ICBT than with the active control (estimated mean difference 0·79, 95% CI 0·42-1·16, p=0·002; between-group effect size 0·77, 95% CI 0·40-1·15). 29 (48%) participants in the ICBT group no longer had their principal diagnosis, compared to nine (15%) in the active control group (odds ratio 5·41, 95% CI 2·26 to 12·90, p<0·0001); the number needed to treat for ICBT to gain one additional participant in remission was three (95% CI 2·85 to 3·15). ICBT resulted in an average societal-cost saving of €493·05 (95% CI 477·17 to 508·92) per participant. No severe adverse events were reported. Interpretation: ICBT is an efficacious and cost-effective treatment for paediatric anxiety disorders that should be considered for implementation in routine clinical care. Funding: The Swedish Research Council for Health, Working Life and Welfare, and Stockholm County Council.

The Lancet. Child & adolescent health · randomised controlled trial · 51 citationsread the source →

The Effect of Heart Rate Variability Biofeedback Training on Mental Health of Pregnant and Non-Pregnant Women: A Randomized Controlled Trial.

In this study, we examined the efficacy of heart rate variability (HRV)-biofeedback on stress and stress-related mental health problems in women. Furthermore, we examined whether the efficacy differed between pregnant and non-pregnant women. Fifty women (20 pregnant, 30 non-pregnant; mean age 31.6, SD = 5.9) were randomized into an intervention (n = 29) or a waitlist condition (n = 21). All participants completed questionnaires on stress, anxiety, depressive symptoms, sleep, and psychological well-being on three occasions with 6-week intervals. Women in the intervention condition received HRV-biofeedback training between assessment 1 and 2, and women in the waitlist condition received the intervention between assessment 2 and 3. The intervention consisted of a 5-week HRV-biofeedback training program with weekly 60⁻90 min. sessions and daily exercises at home. Results indicated a statistically significant beneficial effect of HRV-biofeedback on psychological well-being for all women, and an additional statistically significant beneficial effect on anxiety complaints for pregnant women. No significant effect was found for the other stress-related complaints. These findings support the use of HRV-biofeedback as a stress-reducing technique among women reporting stress and related complaints in clinical practice to improve their well-being. Furthermore, it supports the use of this technique for reducing anxiety during pregnancy.

International journal of environmental research and public health · randomised controlled trial · 23 citationsread the source →

Smoking cessation for people with severe mental illness (SCIMITAR+): a pragmatic randomised controlled trial.

Background: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness. Methods: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete. Findings: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13). Interpretation: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting. Funding: National Institute for Health Research Health Technology Assessment Programme.

The lancet. Psychiatry · randomised controlled trial · 134 citationsread the source →

Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 Randomized Clinical Trial.

Importance: Atopic dermatitis is associated with substantial patient and caregiver burden. Currently available treatments for atopic dermatitis are inadequate or contraindicated for some patients. Abrocitinib (PF-04965842) is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of atopic dermatitis. Objective: To investigate the efficacy and safety of abrocitinib for patients with moderate to severe atopic dermatitis. Design, setting, and participants: A phase 2b, randomized, double-blinded, placebo-controlled, parallel-group trial was conducted from April 15, 2016, to April 4, 2017, at 58 centers in Australia, Canada, Germany, Hungary, and the United States among 267 patients 18 to 75 years of age with a clinical diagnosis of moderate to severe atopic dermatitis for 1 year or more and inadequate response or contraindication to topical medications for 4 weeks or more within 12 months. Efficacy was assessed in the full analysis set, which was a modified intention-to-treat population that included all patients who received 1 dose or more of the study drug except for 4 patients from 1 site. Interventions: Participants were randomly assigned 1:1:1:1:1 to receive abrocitinib (200 mg, 100 mg, 30 mg, or 10 mg) or placebo once daily for 12 weeks. Main outcomes and measures: The primary outcome was the proportion of patients achieving an Investigator's Global Assessment of clear (0) or almost clear (1) with an improvement from baseline of 2 grades or more at week 12. The secondary outcome was the percentage change from baseline in the Eczema Area and Severity Index at week 12. Results: Of the 267 participants, 144 were women (mean [SD] age, 40.8 [16.1] years). At week 12, 21 of 48 patients receiving 200 mg of abrocitinib (43.8%; P < .001, 2-sided), 16 of 54 patients receiving 100 mg of abrocitinib (29.6%; P < .001), and 3 of 52 patients receiving placebo (5.8%) achieved grades of clear or almost clear on the Investigator's Global Assessment scale with improvement of 2 grades or more; these rates correspond to maximum effect model-based estimates of 44.5% (95% CI, 26.7%-62.3%) for those receiving 200 mg of abrocitinib, 27.8% (95% CI, 14.8%-40.9%) for those receiving 100 mg of abrocitinib, and 6.3% (95% CI, -0.2% to 12.9%) for those receiving placebo. Reductions in the Eczema Area and Severity Index were 82.6% (90% CI, 72.4%-92.8%; P < .001) for those receiving 200 mg of abrocitinib, 59.0% (90% CI, 48.8%-69.3%; P = .009) for those receiving 100 mg of abrocitinib, and 35.2% (90% CI, 24.4%-46.1%) for those receiving placebo. Adverse events were observed in 184 of 267 patients (68.9%); the most frequently reported adverse events (in ≥3 patients in any group) were dermatitis atopic, upper respiratory tract infection, headache, nausea, and diarrhea. Dose-dependent decreases in platelet count were observed but trended upward toward baseline levels after week 4. Conclusions and relevance: Once-daily oral abrocitinib was effective and well tolerated for short-term use in adults with moderate to severe atopic dermatitis. Additional trials are necessary to evaluate long-term efficacy and safety. Trial registration: ClinicalTrials.gov identifier: NCT02780167.

JAMA dermatology · randomised controlled trial · 197 citationsread the source →

A complex behavioural change intervention to reduce the risk of diabetes and prediabetes in the pre-conception period in Malaysia: study protocol for a randomised controlled trial.

Background: Over the past two decades, the population of Malaysia has grown rapidly and the prevalence of diabetes mellitus in Malaysia has dramatically increased, along with the frequency of obesity, hyperlipidaemia and hypertension. Early-life influences play an important role in the development of non-communicable diseases. Indeed, maternal lifestyle and conditions such as gestational diabetes mellitus or obesity can affect the risk of diabetes in the next generation. Lifestyle changes can help to prevent the development of type 2 diabetes mellitus. This is a protocol for an unblinded, community-based, randomised controlled trial in two arms to evaluate the efficacy of a complex behavioural change intervention, combining motivational interviewing provided by a community health promoter and access to a habit formation mobile application, among young Malaysian women and their spouses prior to pregnancy. Method/design: Eligible subjects will be Malaysian women in the age group 20 to 39 years, who are nulliparous, not diagnosed with diabetes and own a smartphone. With an alpha-value of 0.05, a statistical power of 90 %, 264 subjects will need to complete the study. Subjects with their spouses will be randomised to either the intervention or the control arm for an 8-month period. The primary endpoint is change in waist circumference from baseline to end of intervention period and secondary endpoints are changes in anthropometric parameters, biochemical parameters, change in health literacy level, dietary habits, physical activity and stress level. Primary endpoint and the continuous secondary endpoints will be analysed in a linear regression model, whereas secondary endpoints on an ordinal scale will be analysed by using the chi-squared test. A multivariate linear model for the primary endpoint will be undertaken to account for potential confounders. This study has been approved by the Medical Research and Ethics Committee of the Ministry of Health Malaysia (protocol number: NMRR-14-904-21963) on 21 September 2015. Discussion: This study protocol describes the first community-based randomised controlled trial, to examine the efficacy of a complex intervention in improving the pre-pregnancy health of young Malaysian women and their spouses. Results from this trial will contribute to improve policy and practices regarding complex behavioural change interventions to prevent diabetes in the pre-conception period in Malaysia and other low- and middle-income country settings. Trial registration: This trial is registered with ClinicalTrials.gov (www.clinicaltrials.gov) on 30 November 2015, Identifier: NCT02617693 .

Trials · randomised controlled trial · 18 citationsread the source →

A randomized trial of telepsychiatry for post-traumatic stress disorder.

We compared the efficacy of telepsychiatry and same-room treatment of combat-related post-traumatic stress disorder (PTSD) using cognitive behavioural therapy in 14 weekly, 90-min treatment sessions. Of 97 patients referred for study participation, 38 were randomized (17 into telepsychiatry, 21 into same-room), and approximately 25 (the number differed by instrument) had at least one post-baseline assessment. Measures of clinical and process outcomes were examined. No group differences were found on clinical outcomes at three-month follow-up. Satisfaction with treatment ratings was similar in both groups, with 'strong satisfaction' indicated by veterans in both modalities. Attendance and drop-out were similar in the two groups. The same-room group reported more comfort in talking with their therapist at post-treatment and had better treatment adherence. The results provide preliminary support for the use of telepsychiatry in the treatment of PTSD to improve access to care.

Journal of telemedicine and telecare · randomised controlled trial · 122 citationsread the source →

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression.

Objective: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. Methods: Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. Results: One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects. Conclusions: SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.

The American journal of psychiatry · clinical trial · 594 citationsread the source →

The effectiveness of a stress coping program based on mindfulness meditation on the stress, anxiety, and depression experienced by nursing students in Korea.

This study examined the effectiveness of a stress coping program based on mindfulness meditation on the stress, anxiety, and depression experienced by nursing students in Korea. A nonequivalent, control group, pre-posttest design was used. A convenience sample of 41 nursing students were randomly assigned to experimental (n=21) and control groups (n=20). Stress was measured with the PWI-SF (5-point) developed by Chang. Anxiety was measured with Spieberger's state anxiety inventory. Depression was measured with the Beck depression inventory. The experimental group attended 90-min sessions for eight weeks. No intervention was administered to the control group. Nine participants were excluded from the analysis because they did not complete the study due to personal circumstances, resulting in 16 participants in each group for the final analysis. Results for the two groups showed (1) a significant difference in stress scores (F=6.145, p=0.020), (2) a significant difference in anxiety scores (F=6.985, p=0.013), and (3) no significant difference in depression scores (t=1.986, p=0.056). A stress coping program based on mindfulness meditation was an effective intervention for nursing students to decrease their stress and anxiety, and could be used to manage stress in student nurses. In the future, long-term studies should be pursued to standardize and detail the program, with particular emphasis on studies to confirm the effects of the program in patients with diseases, such as cancer.

Nurse education today · randomised controlled trial · 108 citationsread the source →

A communication strategy and brochure for relatives of patients dying in the ICU.

Background: There is a need for close communication with relatives of patients dying in the intensive care unit (ICU). We evaluated a format that included a proactive end-of-life conference and a brochure to see whether it could lessen the effects of bereavement. Methods: Family members of 126 patients dying in 22 ICUs in France were randomly assigned to the intervention format or to the customary end-of-life conference. Participants were interviewed by telephone 90 days after the death with the use of the Impact of Event Scale (IES; scores range from 0, indicating no symptoms, to 75, indicating severe symptoms related to post-traumatic stress disorder [PTSD]) and the Hospital Anxiety and Depression Scale (HADS; subscale scores range from 0, indicating no distress, to 21, indicating maximum distress). Results: Participants in the intervention group had longer conferences than those in the control group (median, 30 minutes [interquartile range, 19 to 45] vs. 20 minutes [interquartile range, 15 to 30]; P<0.001) and spent more of the time talking (median, 14 minutes [interquartile range, 8 to 20] vs. 5 minutes [interquartile range, 5 to 10]). On day 90, the 56 participants in the intervention group who responded to the telephone interview had a significantly lower median IES score than the 52 participants in the control group (27 vs. 39, P=0.02) and a lower prevalence of PTSD-related symptoms (45% vs. 69%, P=0.01). The median HADS score was also lower in the intervention group (11, vs. 17 in the control group; P=0.004), and symptoms of both anxiety and depression were less prevalent (anxiety, 45% vs. 67%; P=0.02; depression, 29% vs. 56%; P=0.003). Conclusions: Providing relatives of patients who are dying in the ICU with a brochure on bereavement and using a proactive communication strategy that includes longer conferences and more time for family members to talk may lessen the burden of bereavement. (ClinicalTrials.gov number, NCT00331877.)

The New England journal of medicine · randomised controlled trial · 820 citationsread the source →

Changing eating behaviours to treat childhood obesity in the community using Mandolean: the Community Mandolean randomised controlled trial (ComMando)--a pilot study.

Background: Around one in five children in England is obese when they leave primary school. Thus far, it has not been demonstrated that primary care interventions to manage childhood obesity can achieve significant weight reduction. Training obese children to eat more slowly as an adjunct to other healthy lifestyle behaviour change has been shown to increase weight reduction in a hospital setting. Objectives: This pilot study aimed to test recruitment strategies, treatment adherence, clinic attendance and participants' experiences of using a device [Mandolean® (previously Mandometer®, Mikrodidakt AB, Lund, Sweden)] to slow down speed of eating as an adjunct to dietary and activity advice in treating obesity in primary school-aged children. Design: A two-arm, parallel, randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected. Participants were randomised by the Bristol Randomised Trials Collaboration randomisation service with allocation stratified by hub and minimised by age of the child, gender, and baseline body mass index (BMI) standard deviation score (BMI z-value) of the child, and by BMI of the study parent (obese/not obese). Setting: General practices across Bristol, North Somerset and South Gloucestershire primary care trusts. Participants: Children (BMI ≥ 95th percentile) aged 5-11 years and their families. Intervention: Standard care comprised dietary and activity advice by trained practice nurses. Adjunctive Mandolean training (the intervention) educated participants to eat meals more slowly and to rate levels of fullness (satiety). Mandolean is a small computer device attached to a weighing scale that provides visual and oral feedback during meals while generating a visual representation of levels of satiety during the meal. Participants were encouraged to eat their main meal each day from the Mandolean. One parent was also given a Mandolean to use when eating with the child. Outcome measures: Outcomes for the pilot were recruitment of 36 families to the trial in the 9-month pilot phase, that meals would be eaten at least five times a week off a Mandolean by 90% of patients randomised to the intervention arm, that 80% of patients in both arms would attend the weight management clinic appointment 3 months post randomisation and that > 60% of children using Mandolean would demonstrate a reduction in speed of eating from baseline within 3 months of randomisation. Results: None of the criteria for progression to the main trial were reached. Despite numerous pathways being available for referral, only 21 (13 to standard care, eight to intervention arm; 58%) of the target 36 families were recruited in the pilot phase. Less than 20% of those randomised to Mandolean used the device at least five times a week. The > 60% target for slowing down of eating speed by 3 months was unmet. Attendance at the weight management clinic in general practice hubs for both arms of the study at 3 months was 44% against a target of 80%. Conclusions: This pilot trial failed to meet its objectives in terms of recruitment, treatment adherence, demonstration of a reduction in speed of eating in sufficient numbers of children, and attendance at follow-up appointments. Despite a high prevalence of childhood obesity in the geographical area and practices signing up for the trial, this study, like many others, demonstrates a failure of families to engage with and respond to primary care weight management interventions. We need to understand why the target population seems inured to the health message that childhood obesity is a significant health-care issue and identify the barriers to seeking help and then acting on positive health behaviour retraining. Only when we have fully understood the general public's perceptions of childhood obesity and have identified ways of engaging target populations can we hope to develop interventions that can work in a primary or community-based setting. Trial registration: Current Controlled Trials ISRCTN90561114. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 47. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 31 citationsread the source →

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Background: We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Methods: Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Results: Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). Conclusions: nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients.

Cephalalgia : an international journal of headache · clinical trial · 140 citationsread the source →

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

Background: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events. Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Pain physician · guideline · 225 citationsread the source →

Palliative care education in Swiss undergraduate medical curricula: a case of too little, too early.

Palliative medicine education is an important strategy in ensuring that the needs of terminally ill patients are met. A review was conducted in 2007 of the undergraduate curricula of all five of Switzerland's medical schools to identify their palliative care-related content and characteristics. The average number of mandatory hours of palliative care education is 10.2 h (median 8 h; range 0-27 h), significantly short of the 40 h recommended by the European Palliative Care Association's Education Expert Group. The median time allocated to designated palliative care blocks is 3 h (range 0-8 h). Most of the education occurs before the clinical years, and there are no mandatory clinical rotations. Three schools offer optional clinical rotations but these are poorly attended (<10% of students). Although a number of domains are covered, ethics-related content predominates; 21 of a total of 51 obligatory hours (41%). Communication related to palliative care is largely limited to 'breaking bad news'. In two of the schools, the teaching is done primarily by palliative care physicians and nurses (70% or more of the teaching). In the others, it is done mostly by educators in other clinical specialties and ethics (approximately 90% of the teaching). These findings show significant deficiencies.

Palliative medicine · cohort or longitudinal · 19 citationsread the source →

Sleep duration and health in young adults.

Background: Both long and short sleep durations have been associated with negative health outcomes in middle-aged and older adults. This study assessed the relationship between sleep duration and self-rated health in young adults. Methods: Using anonymous questionnaires, data were collected from 17 465 university students aged 17 to 30 years who were taking non-health-related courses at 27 universities in 24 countries. The response rate was greater than 90%. Sleep duration was measured by self-report; the health outcome was self-rated health; and age, sex, socioeconomic background, smoking, alcohol consumption, body mass index, physical activity, depression (Beck Depression Inventory), recent use of health services, and country of origin were included as covariates. Results: Sixty-three percent of respondents slept for 7 to 8 hours; 21% were short sleepers (6%, <6 hours; 15%, 6-7 hours); and 16% were long sleepers (10%, 8-10 hours; 6%, >10 hours). Compared with the reference category (7-8 hours), the adjusted odds ratio of poor health was 1.56 (95% confidence interval [CI], 1.22-1.99) for respondents sleeping 6 to 7 hours and 1.99 (95% CI, 1.31-3.03) for those sleeping less than 6 hours. The same significant pattern was seen when the results were analyzed separately by sex. When respondents from Japan, Korea, and Thailand (characterized by relatively short sleep durations) were excluded, the adjusted odds ratios were 1.33 (95% CI 1.03-1.73) and 1.62 (95% CI, 1.06-2.48) for those sleeping 6 to 7 hours and less than 6 hours, respectively. There were no significant associations between self-rated health and long sleep duration. Conclusion: Our data suggest that short sleep may be more of a concern than long sleep in young adults.

Archives of internal medicine · cohort or longitudinal · 255 citationsread the source →

A systematic review of the behaviour change techniques and digital features in technology-driven type 2 diabetes prevention interventions.

Objectives: Our aim was to conduct a systematic review to determine which technology-driven diabetes prevention interventions were effective in producing clinically significant weight loss, and to identify the behaviour change techniques and digital features frequently used in effective interventions. Methods: We searched five databases (CINAHL, EMBASE, MEDLINE, PsychINFO, and Pubmed) from inception to September 2018 and reviewed 19 experimental and non-experimental studies of 21 technology-driven diet plus physical activity interventions for adults (≥18 years) at risk of developing type 2 diabetes. Behaviour change techniques were coded using the BCT taxonomy v1, and digital features were identified via thematic analysis of intervention descriptions. Results: Sixty-three per cent of interventions were effective in the short term (achieving ≥3% weight loss at ≤6 months), using an average of 5.6 more behaviour change techniques than non-effective interventions, and 33% were effective in the long term (achieving ≥5% weight loss at ≥12 months), using 3.7 more behaviour change techniques than non-effective interventions. The techniques of social support (unspecified), goal setting (outcome/behaviour), feedback on behaviour, and self-monitoring of outcome(s) of behaviour were identified in over 90% of effective interventions. Interventions containing digital features that facilitated health and lifestyle education, behaviour/outcome tracking, and/or online health coaching were most effective. Conclusion: The integration of specific behaviour change techniques and digital features may optimise digital diabetes prevention interventions to achieve clinically significant weight loss. Additional research is needed to identify the mechanisms in which behaviour change techniques and digital features directly influence physical activity, dietary behaviours, and intervention engagement.

Digital health · review · 121 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 →

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 →

Does child maltreatment predict alcohol use disorders in young adulthood? A cohort study of linked notifications and survey data.

Background and aims: Most studies of the association between child maltreatment and subsequent problem alcohol use are retrospective. We studied the association of prospectively substantiated child maltreatment with problem alcohol use in adulthood. Design: We used a prospective cohort record linkage correlational design using data from a statutory child protection agency of prospectively substantiated child maltreatment linked to a birth cohort from a major metropolitan maternity hospital. Setting: The Mater-University of Queensland Study of Pregnancy in Brisbane, Australia. Participants: Of the 3762 young people at the 21-year follow-up, 169 (4.5%) had a history of substantiated maltreatment by 16 years. This was most commonly emotional abuse (n = 90). Measurements: The main outcome was heavy alcohol use at the 21-year follow-up, defined as four or more standard drinks per day. Secondary outcomes were life-time and 12-month diagnoses of alcohol use disorders in  2531 participants who completed the Composite International Diagnostic Interview-auto (CIDI-auto) version. Predictor variables were physical, sexual and emotional abuse, as well as neglect. Findings: At follow-up, 407 of the 3762 participants reported heavy alcohol use (10.8%). On adjusted analyses, participants who had experienced emotional abuse were significantly more likely to report heavy alcohol use at the time of interview (adjusted odds ratio = 1.856; 95% confidence interval = 1.038-3.319; P = 0.037). Neglect was associated with a life-time CIDI diagnosis of an alcohol use disorder. Other types of child maltreatment were not significantly associated with any of the outcomes. Conclusions: Prospectively identified experience of childhood emotional abuse and neglect appears to be positively associated with problem alcohol use at age 21.

Addiction (Abingdon, England) · 27 citationsread the source →

The detrimental effects of allostasis: allostatic load as a measure of cumulative stress.

Since its inception in the 1980s, through further developments during the 1990s, and continuing today, the paradigm of allostatic load (AL) has becomed an important paradigm for predicting senescence and mortality. AL is a cumulative measure of the effects of multiple stressors and the process of responding to stressors on the soma. AL measurements of individuals is being tested on various samples and species and being reported across a variety of medical and social science journals. From the ISI Web of Science, all articles published between January 2000 and June 2005 with AL in any default category were obtained and transferred to Endnote. These articles, categorized as theory/review or data-driven, human or animal, and variability in risk factors used to estimate AL, are reviewed here. Only two of 90 reports were published in anthropological journals, likely, at least partly, because research on AL has focused more on western, industrialized populations where data are more easily obtained. From 2000-2005, 12 of 42 data-driven reports focused on elderly humans. Studies of animal models also are common (0 in 2000, but 4 in 2004 covering 21 species). During the last year, multiple additional potential physiological variables have been tested as measures of AL (10 to 20 in any one article). In the past half decade, AL also has been introduced to a wide range of disciplines, including psychology, anthropology, gerontology, veterinary medicine, and medical specialties, as a viable research theme. AL appears to provide a useful method for determining cumulative somatic stress such as that seen with senescence and frailty at older ages.

Journal of physiological anthropology · review · 50 citationsread the source →

Consensus Statement on 21-Hydroxylase Deficiency from The Lawson Wilkins Pediatric Endocrine Society and The European Society for Paediatric Endocrinology

Despite over 50 yr of experience with steroid replacement therapy, the management of congenital adrenal hyperplasia (CAH) remains difficult, and clinical practice varies substantially throughout the world. To consider the evidence for best practice, to formulate management guidelines, and to consider innovative therapies, The Lawson Wilkins Pediatric Endocrine Society (LWPES) and The European Society for Pediatric Endocrinology (ESPE) convened a meeting in Gloucester, MA, March 14–17, 2002. The 40 participating physicians, psychologists, scientists, and surgeons from 12 countries on 4 continents agreed with the following consensus statement; this statement is concerned exclusively with CAH caused by 21-hydroxylase deficiency and does not address the other, rarer forms of CAH. The newborn female with CAH and ambiguous external genitalia requires urgent expert medical attention. The ambiguity is highly distressing to the family; therefore, immediate comprehensive evaluation is needed by referral to, or a visit by, a pediatric endocrinologist. An important goal is to ensure that the parents develop a positive relationship with their child. A well-organized multidisciplinary team (including specialists in pediatric endocrinology, psychosocial services, pediatric surgery/urology, and genetics) is essential for the diagnosis and management of the infant with ambiguous genitalia. It is important that the coordinator of the team has experience in the long-term care of the patient with CAH and provides a consistent message to the parents. Every newborn with ambiguous genitalia, a suspected diagnosis of CAH, or an abnormal result in a newborn screen for 17-hydroxyprogesterone (17OHP) should be evaluated by a pediatric endocrinologist. The evaluation of an infant with ambiguous genitalia includes a complete history, a physical examination, a reliable ultrasound investigation of the internal genitalia and adrenals, karyotype or fluorescence in situ hybridization for sex chromosome material, and a rapid, reliable plasma or serum measurement of 17OHP. Premature newborns may need serial measurements of 17OHP to differentiate false positive results from affected infants with CAH. Neonatal mass screening for 21-hydroxylase deficiency identifies both male and female affected infants, prevents incorrect sex assignment, and decreases mortality and morbidity (1–4). Therefore, newborn screening for CAH is beneficial and is recommended. Newborn screening is sufficiently specific and sensitive to detect almost all infants with classical CAH and some infants with nonclassical CAH (NCCAH). Sampling of blood spots should be performed, ideally between 48 and 72 h of age, and sent to the screening laboratory without delay. At present, direct binding assays for blood-spot 17OHP are the only practical method for screening. Each screening laboratory needs to establish validated cut-off levels related to gestational age and birth-weight, because 17OHP levels decline with increasing gestational age. Only laboratories with excellent internal and external quality control, demonstrated accuracy, and a rapid turn-around time on a large number of samples should be used. The laboratory should report immediately any abnormal result to the physician responsible for the patient. A reliable CAH screening program requires both clinical evaluation and laboratory investigation for diagnostic confirmation. A positive screening result needs to be confirmed either by a validated 17OHP measurement of a second serum/plasma sample, a urine sample for a steroid profile, or analysis of the CYP21 gene. Newborn screening, using 17OHP, may detect other forms of CAH. In uncertain cases, additional specific tests are required. Measurements of androstenedione, aldosterone, cortisol, and testosterone by direct immunoassays are of limited value for diagnosis in the newborn. Molecular genetic analysis is not essential for the diagnosis but may be helpful to confirm the basis of the defect, to aid in genetic counseling, and to establish the diagnosis in uncertain cases. Ten mutations account for 90–95% of the affected alleles, but molecular genetic analysis is complicated by multiple copies of the genes and the possibility of multiple mutations on one allele (5, 6). The clinical features may not correlate with the genetic mutation in a small percentage of cases. Parental DNA samples are essential to segregate alleles. Salt wasters may not be apparent in the first days, or even weeks, after birth by electrolyte measurements. Salt wasters may be differentiated from simple virilizers by serial serum/plasma and/or urine electrolytes, plasma renin activity (PRA) or direct renin, and the results of CYP21 molecular analysis. Prenatal treatment has been advocated for fetuses at risk for classic CAH but is not appropriate for nonclassic CAH. The appropriateness, ethics, and outcomes of the prenatal treatment of CAH with dexamethasone remain controversial (7, 8). However, based on more than 200 fetuses treated to term and more than 1000 partially treated fetuses, it is clear that very early institution of treatment ameliorates the genital virilization in all affected females and completely eliminates it in more than 85% (7, 9). Variations in outcome may be attributable to starting treatment late, interruption of treatment, and individual differences in dexamethasone metabolism and androgen sensitivity. No consistent untoward effects have been reported, and birth weight is not reduced. However, few treated fetuses have reached adulthood, and long-term prospective studies have not been done. Thus, all agree that the results to date are very good, but long-term safety has not yet been proven in patients treated to term or in the 7 of 8 fetuses in whom treatment is stopped because they are male or unaffected. Treated mothers experience greater weight gain, edema, and striae than untreated mothers, but present data do not show increased risk of hypertension or gestational diabetes (9). Feto/maternal glucocorticoid physiology and pharmacology are poorly understood. Available data indicate that human fetal cortisol levels are low, approximately 20 nm or 0.7 μg/dl (10); the administered dose of dexamethasone may result in fetal concentrations of glucocorticoid that greatly exceed normal levels. However, the data on serum cortisol values in the fetus are scanty, and fetal serum dexamethasone values have not been reported. Several recent reports have raised concerns about the use of short-term, very-high-dose glucocorticoids in late pregnancy or in premature infants (11). Animal studies have reported numerous complications from long-term, high-dose treatment of pregnant rodents and primates. Treatment of pregnant rats with 20 μg/kg·d dexamethasone was associated with decreased birth weight and adult hypertension, whereas similar treatment of pregnant sheep caused no apparent complications. However, the relevance of any of these studies to human physiology is not known. Components of a prenatal treatment program include prepregnancy genetic counseling and genotyping of the proband and parents, followed by diagnosis on fetal DNA obtained by chorionic villous biopsy. Fetal sex should be determined by Y chromosome PCR or karyotype. Allele-specific PCR should identify at least 90% of affected alleles. This number can be increased to nearly 100% with microsatellite analysis; Southern blotting; and, occasionally, DNA sequencing (5, 6). Competent core laboratories should study large numbers of samples. Inclusion criteria for prenatal treatment include: 1) a previously affected sibling or first-degree relative with known mutations causing classic CAH, proven by DNA analysis; 2) reasonable expectation that the father is the same as the proband’s; 3) availability of rapid, high-quality genetic analysis; 4) therapy started less than 9 wk after the last menstrual period; 5) no plans for therapeutic abortion; and 6) reasonable expectation of patient compliance. The optimal dosage and timing is 20 μg/kg maternal body weight·d, in three divided doses, starting as soon as pregnancy is confirmed, and no later than 9 wk after the last menstrual period. Treatment is continued to term in the affected female fetus and discontinued in all other fetuses. Maternal blood pressure (BP), weight, glycosuria, HbA1C plasma cortisol, dehydroepiandrosterone sulfate, and androstenedione should be measured initially and then every 2 months, adding plasma or urinary estriol after 15–20 wk of gestation. There is substantial difference of opinion concerning whether prenatal treatment of CAH is a research endeavor. However, all are agreed that this requires a team consisting of a pediatric endocrinologist, an expert in high-risk obstetrics, a genetic counselor, and a reliable molecular genetics laboratory. It is not the “standard of care” for obstetricians in the community. The treatment of 7 out of 8 fetuses who cannot be helped by prenatal treatment creates an ethical dilemma for which there is no clear answer, and parents should be aware of this. We believe that this specialized and demanding therapy should be undertaken by designated teams using nationally or multinationally approved protocols, subject to institutional review boards or ethics committees in recognized centers. Written informed consent must be obtained after the balanced review of the risks and benefits of treatment. Families and clinicians should be obliged to undertake prospective follow-up of prenatally treated children whether they have CAH or not. The data should be entered into a central database audited by an independent safety committee. Study protocols should consider all psychological/behavioral and somatic effects of excess prenatal glucocorticoids and androgens that have been observed in animal experiments or in human studies. Long-term follow-up into late adolescence is mandatory. Relevant control populations should be identified. These studies should also include the partially treated fetuses. Funding agencies, such as the National Institutes of Health or the European Commission, should be encouraged to support such long-term studies. The decision about surgery should be made by the parents, together with the clinical team, after complete disclosure of all relevant clinical information and all available options have been discussed and after informed consent has been obtained. The goals of surgery are: 1) genital appearance compatible with gender; 2) unobstructed urinary emptying without incontinence or infections; and 3) good adult sexual and reproductive function. Once a decision has been made to raise a newborn as female, surgery for those with virilized genitalia caused by CAH is recommended when the patient has a high proximal junction between the vagina and urethra (12, 13). Surgery on infants with ambiguous genitalia requires a high degree of expertise and should only be performed in centers with significant experience. Based on recent clinical experience, the recommended time for surgery is at age 2–6 months; although, at present, this is not universal practice. It is important to note that surgery at this stage is technically easier than at later stages. When the degree of virilization is less (minimal clitoromegaly and the junction between the vagina and urethra near the perineum), surgery may not be necessary. In such cases, the decision to operate should be based on appropriate contrast studies of the urinary tract and examination under anesthesia, with cystoscopy. Surgery to reduce clitoral size requires careful consideration. Total removal of the clitoris should never be performed. If clitoral reduction is elected, it is crucial to preserve the neurovascular bundle, the glans, and the preputial skin related to the glans (14, 15). The early operation should be a one-stage complete repair using the newest techniques of vaginoplasty, clitoral, and labial surgery (12–14, 16) and should be carried out at a center with experience of at least 3–4 cases/yr. Revision vaginoplasty is often required at adolescence, and the timing should be decided with the patient and family. Patients who wish to consider further procedures should be treated by a surgeon experienced in the current techniques. Surgery between the age of 12 months and adolescence is not recommended in the absence of complications causing medical problems. Vaginal dilatations are contraindicated at this stage, although this procedure is often useful in adolescence and in adulthood. Repeated genital examinations should be minimized. Genital photography should be discouraged and only be done with parental consent and, except in infancy, performed only under anesthesia. At each designated center, one surgical team should be responsible for all surgery involving ambiguous genitalia. There should be close cooperation between centers to broaden experience, to audit results, and to allow adequate evaluation of outcomes. We acknowledge that there are concerns about early surgery. However, surgical techniques have improved. We urge caution in judging outcome from outdated procedures. Systematic studies are needed to evaluate ultimate function for all girls undergoing surgery. It is recognized that 46,XX children with significant virilization may present at a later age. Consideration for sex reassignment must be undertaken only after thorough psychological evaluation of patient and family. Surgery appropriate to gender assignment should be undertaken after a period of endocrine treatment. Females with CAH show behavioral masculinization, most pronounced in gender role behavior, less so in sexual orientation, and rarely in gender identity (17–19). Even in females with psychosexual problems, general psychological adjustment seems to be similar to that of females without CAH. Currently, there is insufficient evidence to support rearing a 46,XX infant at Prader stage 5 as male. Whereas studies of women whose surgery was performed 20–30 yr ago indicate a range of psychosexual difficulties, there is reason for optimism that outcome will be better with current surgical and medical treatment. We recognize a need for greater availability of professional psychological services and support groups for patients and families. Decisions concerning sex assignment and associated genital surgery must consider the culture in which a child and her/his family are embedded. As the pace of societal change, including the flexibility of gender role, increases, more frequent review of management policies and long-term outcomes is important. Recognizing that treatment does not mimic physiologic secretion, the goal is to replace deficient steroids while minimizing adrenal sex hormone and glucocorticoid excess, preventing virilization, optimizing growth, and protecting potential fertility. Outcome is not always ideal. Consensus is based on clinical experience. During infancy, initial reduction of markedly elevated adrenal sex hormones may require up to 25 mg hydrocortisone (HC)/m2·d, but typical dosing is 10–15 mg/m2·d divided three times daily. HC oral suspension is not recommended (20); divided or of HC should be in requires to cortisol for HC is the of first doses, infancy, may and other Therefore, complete adrenal should be data to or Whereas HC is and glucocorticoids may be an at or near the of and need to be daily. may be because this is the The dose should be approximately one the dose of The dosage of dexamethasone is daily. of these more glucocorticoids should include in to weight, and other clinical and laboratory These steroids have with In children with age, such as in with CAH, of therapy may central treatment with a classic CAH patients should be treated with at diagnosis in the newborn period. in early range from whereas typical are on the therapy will reduce and levels and the dosage of glucocorticoid required. The need for should be based on and are often needed in infancy, at in The method of diagnosis a with However, a of 17OHP may also as a reliable screening Treatment is only recommended for patients those with an age with a with the family menstrual and the may be based on physical and of or steroid measurements may include serum/plasma electrolytes, serum 17OHP, androstenedione, and/or and or direct renin, every months and every months The time from the last glucocorticoid dose should be the of the adrenal should be into Patients adequate replacement therapy may have hormone levels the normal measurements include urinary or blood and laboratory data will indicate a need for dose physical growth, and indicate or Patients with CAH should medical and information concerning therapy for should have an of HC or glucocorticoid levels of cortisol patients should be increased of glucocorticoids when or when to oral after and surgery. in may also require steroid and such as does not require increased dosing should be times the glucocorticoid dose for patients to oral and patients and those to oral steroids require or concentrations should be and and replacement may be required. or patients may or When an may be followed by of for and dosage are as for children than yr of age, 25 mg followed by for children yr of age, 50 mg followed by and for and mg followed by CAH and should be by and and made available to other pediatric endocrine of useful as family include: and The practice of frequent genital examinations in females should be Therefore, there is clinical or laboratory evidence of control or one to the and size of the genital examinations should not be performed. In females or the of the use of or of sexual genital examination with to the of the may need to be performed. the patient and/or family should be of the for the examinations and support of the patient both classic and and family should be a of the comprehensive care and management of these and/or patients should be the of and counseling at the time of the initial sexual gender role, and related to with a should be the pediatric or for infants, and with CAH. In late adolescence or even early adulthood, care is to an internal in the same institution or clinical We that a team should also as a a and a with specific expertise and in the treatment of such should be that with treatment is important to normal and reduce the risk of a mass by may not be of clinical physical examinations and, as and of both to in the of such removal of a glucocorticoid may be in or The of the genital repair in and adult women needs to be and should be about and other sexual as as is useful with should be an increased risk of However, the risk is not available and may on the and degree of with The risk of women with CAH or an affected fetus is women with CAH should be and in a center and experienced to such that do not the such as HC and should be used. should be when in prenatal should be to maternal serum testosterone concentrations near the range of normal for pregnancy When surgery has been performed, to to the genital When is performed, of HC have to be increased and after A should be present to care of the newborn and to diagnostic procedures when an affected child is to the results of prenatal by is in adrenal androgens and the of It should be only in therapy is in of HC and is with institution of at the of The patient must be throughout for of adrenal The procedure should only be carried out long-term follow-up is and in the of approved clinical studies. The use of in CAH is on but of with Based on the of an in male sexual it was that the effects of elevated androgens on adult be by using an to androgen and/or an to of androgen to studies in CAH show control of and at glucocorticoid dosage Long-term safety data are not and reproductive effects are not known. function has to be Patients with CAH from of and of the adrenal as deficiency This may a role in to therapeutic are under genetic diagnosis for CAH is but further research is required to therapy is not in with this CAH patients on glucocorticoid treatment have levels. in adult patients with have beneficial effects of replacement but the relevance in CAH is have the potential for activity of glucocorticoids At present, there are no specific that are of or and clinical experience with is Therefore, the use of these cannot be at A of patients with CAH with an of Thus, an is by patients with CAH, and the adult is substantially less than However, some CAH patients to normal adult A small of CAH patients have been treated with for 2 either or in with a This and but adult data are not yet These are to all of the management of this in from diagnosis adulthood. The multidisciplinary of management is with the that such expert teams need appropriate and There remain important in about this and these have been therapeutic are as require evaluation into practice. In the should on early optimal medical and surgical treatment, and to compliance. The for support of the consensus meeting in The following convened in Gloucester, March 14–17, and to this The and The also the of and congenital adrenal European Society for Pediatric Lawson Wilkins Pediatric Endocrine nonclassical plasma renin

The Journal of Clinical Endocrinology & Metabolism · review · 331 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. Am J Respir Crit Care Med. 1998;158:1585-92. [PMID: 9817712] CrossrefMedlineGoogle Scholar5. Barnes PJ, Karin M. Nuclear factor-B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066-71. [PMID: 9091804] CrossrefMedlineGoogle Scholar6. Donovan CE, Mark DA, He HZ, Liou HC, Kobzik L, Wang Y, . NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation. J Immunol. 1999;163:6827-33. [PMID: 10586083] MedlineGoogle Scholar7. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996;87:953-9. [PMID: 8945521] CrossrefMedlineGoogle Scholar8. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem. 2001;70:81-120. [PMID: 11395403] CrossrefMedlineGoogle Scholar9. Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol. 2000;20:6891-903. [PMID: 10958685] CrossrefMedlineGoogle Scholar10. Gao L, Cueto MA, Asselbergs F, Atadja P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem. 2002;277:25748-55. [PMID: 11948178] CrossrefMedlineGoogle Scholar11. Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, . Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med. 2002;166:392-6. [PMID: 12153977] CrossrefMedlineGoogle Scholar12. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms [Editorial]. Clin Sci (Lond). 1998;94:557-72. [PMID: 9854452] CrossrefMedlineGoogle Scholar13. Barnes PJ. Molecular mechanisms of corticosteroids in allergic diseases. Allergy. 2001;56:928-36. [PMID: 11576070] CrossrefMedlineGoogle Scholar14. Schwiebert LM, Stellato C, Schleimer RP. The epithelium as a target of glucocorticoid action in the treatment of asthma. Am J Respir Crit Care Med. 1996; 154:S16-9; discussion S19-20. [PMID: 8756782] Google Scholar15. Herrscher RF, Kasper C, Sullivan TJ. Endogenous cortisol regulates immunoglobulin E-dependent late phase reactions. J Clin Invest. 1992;90:596-603. [PMID: 1644926] CrossrefMedlineGoogle Scholar16. Barnes PJ. Therapeutic strategies for allergic diseases. Nature. 1999;402:B31-8. [PMID: 10586893] CrossrefMedlineGoogle Scholar17. Yudt MR, Cidlowski JA. The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Mol Endocrinol. 2002;16:1719-26. [PMID: 12145329] CrossrefMedlineGoogle Scholar18. Leung DY, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, . Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor . J Exp Med. 1997;186:1567-74. [PMID: 9348314] CrossrefMedlineGoogle Scholar19. Hecht K, Carlstedt-Duke J, Stierna P, Gustaffson J, Bronnegard M, Wilkstrom AC. Evidence that the -isoform of the human glucocorticoid receptor does not act as a physiologically significant repressor. J Biol Chem. 1997;272:26659-64. [PMID: 9334248] CrossrefMedlineGoogle Scholar20. Bodwell JE, Webster JC, Jewell CM, Cidlowski JA, Hu JM, Munck A. Glucocorticoid receptor phosphorylation: overview, function and cell cycle-dependence. J Steroid Biochem Mol Biol. 1998;65:91-9. [PMID: 9699861] CrossrefMedlineGoogle Scholar21. Reichardt HM, Kaestner KH, Tuckermann J, Kretz O, Wessely O, Bock R, . DNA binding of the glucocorticoid receptor is not essential for survival. Cell. 1998;93:531-41. [PMID: 9604929] CrossrefMedlineGoogle Scholar22. Ito K, Jazrawi E, Cosio B, Barnes PJ, Adcock IM. p65-activated histone acetyltransferase activity is repressed by glucocorticoids: mifepristone fails to recruit HDAC2 to the p65-HAT complex. J Biol Chem. 2001;276:30208-15. [PMID: 11395507] CrossrefMedlineGoogle Scholar23. Yao TP, Ku G, Zhou N, Scully R, Livingston DM. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. Proc Natl Acad Sci U S A. 1996;93:10626-31. [PMID: 8855229] CrossrefMedlineGoogle Scholar24. Kurihara I, Shibata H, Suzuki T, Ando T, Kobayashi S, Hayashi M, . Expression and regulation of nuclear receptor coactivators in glucocorticoid action. Mol Cell Endocrinol. 2002;189:181-9. [PMID: 12039076] CrossrefMedlineGoogle Scholar25. Hall SE, Lim S, Witherden IR, Tetley TD, Barnes PJ, Kamal AM, . Lung type II cell and macrophage annexin I release: differential effects of two glucocorticoids. Am J Physiol. 1999;276:L114-21. [PMID: 9887063] MedlineGoogle Scholar26. Newton R, Hart LA, Stevens DA, Bergmann M, Donnelly LE, Adcock IM, . Effect of dexamethasone on interleukin-1beta-(IL-1)-induced nuclear factor-B (NF-B) and B-dependent transcription in epithelial cells. Eur J Biochem. 1998;254:81-9. [PMID: 9652398] CrossrefMedlineGoogle Scholar27. Heck S, Bender K, Kullmann M, Gottlicher M, Herrlich P, Cato AC. IB-independent downregulation of NF-B activity by glucocorticoid receptor. EMBO J. 1997;16:4698-707. [PMID: 9303314] CrossrefMedlineGoogle Scholar28. Reichardt HM, Tuckermann JP, Gottlicher M, Vujic M, Weih F, Angel P, . Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor. EMBO J. 2001;20:7168-73. [PMID: 11742993] CrossrefMedlineGoogle Scholar29. Hart L, Lim S, Adcock I, Barnes PJ, Chung KF. Effects of inhaled corticosteroid therapy on expression and DNA-binding activity of nuclear factor B in asthma. Am J Respir Crit Care Med. 2000;161:224-31. [PMID: 10619824] CrossrefMedlineGoogle Scholar30. Imhof A, Wolffe AP. Transcription: gene control by targeted histone acetylation. Curr Biol. 1998;8:R422-4. [PMID: 9637914] CrossrefMedlineGoogle Scholar31. Peterson CL. HDAC's at work: everyone doing their part. Mol Cell. 2002;9:921-2. [PMID: 12049726] CrossrefMedlineGoogle Scholar32. Berger SL. An embarrassment of niches: the many covalent modifications of histones in transcriptional regulation. Oncogene. 2001;20:3007-13. [PMID: 11420715] CrossrefMedlineGoogle Scholar33. Bannister AJ, Schneider R, Kouzarides T. Histone methylation: dynamic or static? Cell. 2002;109:801-6. [PMID: 12110177] CrossrefMedlineGoogle Scholar34. Kagoshima M, Wilcke T, Ito K, Tsaprouni L, Barnes PJ, Punchard N, . Glucocorticoid-mediated transrepression is regulated by histone acetylation and DNA methylation. Eur J Pharmacol. 2001;429:327-34. [PMID: 11698053] CrossrefMedlineGoogle Scholar35. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074-80. [PMID: 11498575] CrossrefMedlineGoogle Scholar36. Bergmann M, Barnes PJ, Newton R. Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR. Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol. 2002;22:7802-11. [PMID: 12391149] CrossrefMedlineGoogle Scholar41. Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting 2-agonists and corticosteroids. Eur Respir J. 2002;19:182-91. [PMID: 11843317] CrossrefMedlineGoogle Scholar42. Adcock IM, Stevens DA, Barnes PJ. Interactions of glucocorticoids and 2-agonists. Eur Respir J. 1996;9:160-8. [PMID: 8834349] CrossrefMedlineGoogle Scholar43. Mak JC, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ. Protective effects of a glucocorticoid on downregulation of pulmonary 2-adrenergic receptors in vivo. J Clin Invest. 1995;96:99-106. [PMID: 7615841] CrossrefMedlineGoogle Scholar44. Mak JC, Hisada T, Salmon M, Barnes PJ, Chung KF. 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. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseasesLipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in ToadsThe central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to interventionAsthma and COVID-19: Emphasis on Adequate of as of and as a Effect of the resistance in asthma: and molecular effects of on a of allergic between and and gene expression of glucocorticoid and receptors from the for of human respiratory with glucocorticoids in the treatment of asthma: of the oral corticosteroids and persistent in from the asthma to bronchial asthma as for A of of Melatonin and Glucocorticoid with in the a between Melatonin and of in Steroid Drug by of proteins during the Efficacy of to in a of corticosteroids in asthma: the between and the novel mode of action of the Association and 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Annals of Internal Medicine · review · 370 citationsread the source →

Thymoquinone Antifungal Activity against Candida glabrata Oral Isolates from Patients in Intensive Care Units-An In Vitro Study.

The number of Candida spp. infections and drug resistance are dramatically increasing worldwide, particularly among immunosuppressed patients, and it is urgent to find novel compounds with antifungal activity. In this work, the antifungal and antibiofilm activity of thymoquinone (TQ), a key bioactive constituent of black cumin seed Nigella sativa L., was evaluated against Candida glabrata, a WHO 'high-priority' pathogen. Then, its effect on the expression of C. glabrata EPA6 and EPA7 genes (related to biofilm adhesion and development, respectively) were analyzed. Swab samples were taken from the oral cavity of 90 hospitalized patients in ICU wards, transferred to sterile falcon tubes, and cultured on Sabouraud Dextrose Agar (SDA) and Chromagar Candida for presumptive identification. Next, a 21-plex PCR was carried out for the confirmation of species level. C. glabrata isolates underwent antifungal drug susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), amphotericin B (AMB), and TQ according to the CLSI microdilution method (M27, A3/S4). Biofilm formation was measured by an MTT assay. EPA6 and EPA7 gene expression was assessed by real-time PCR. From the 90 swab samples, 40 isolates were identified as C. glabrata with the 21-plex PCR. Most isolates were resistant to FLZ (n = 29, 72.5%), whereas 12.5% and 5% were ITZ and AMB resistant, respectively. The minimum inhibitory concentration (MIC50) of TQ against C. glabrata was 50 µg/mL. Importantly, TQ significantly inhibited the biofilm formation of C. glabrata isolates, and EPA6 gene expression was reduced significantly at MIC50 concentration of TQ. TQ seems to have some antifungal, antibiofilm (adhesion) effect on C. glabrata isolates, showing that this plant secondary metabolite is a promising agent to overcome Candida infections, especially oral candidiasis.

Metabolites · 9 citationsread the source →

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

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

The lancet. Psychiatry · 52 citationsread the source →

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review.

Top-tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour-nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter-ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta-analyses (NMAs) and meta-analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co-primary outcomes were disease-specific symptom reduction and all-cause discontinuation ("acceptability"). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co-primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta-analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention-deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive-compulsive disorder; CBT in post-traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence-based information for clinical decision making.

World psychiatry : official journal of the World Psychiatric Association (WPA) · 114 citationsread the source →

An objective assessment of children's exposure to brand marketing in New Zealand (Kids'Cam): a cross-sectional study.

Background: Marketing promotes values of consumerism and overconsumption, and negatively affects children's wellbeing and psychological development. The threat marketing poses to planetary health is just being realised. However, little is known about children's exposure to marketing at an aggregate level. Using an objective method of wearable cameras, we aimed to determine the nature and extent of children's exposure to marketing. Methods: Kids'Cam was a cross-sectional study of children aged 11-13 years in New Zealand, from which we randomly selected a sample of 90 children. Children wore cameras from when they woke up until they went to sleep for four consecutive days (Thursday-Sunday) that captured images at an angle of 136° every 7 s for exposure to marketing. Marketing brands were categorised into three groups: core food and social marketing messages, harmful commodities (eg, non-core food, alcohol, and gambling), or other. Exposure rates by marketing medium, setting, and product category were calculated using negative binomial regression models. Findings: From June 21, 2014, to June 30, 2015, we recruited 168 children, and randomly selected data from 90 children for the present study. Children in this study were exposed to a mean of 554 brands per 10 h day (95% CI 491-625), nearly a brand a minute, through multiple mediums (predominantly brand labels [36% of exposures] and product packaging [22%]) and mostly in schools (43%) and at home (30%). Food and beverages (20% of exposures) were the dominant product category. The most pervasive marketing brands typically sold a range of products across more than one product category (eg, children were exposed to Nike on average 20 exposures per day). Children were exposed to more than twice as many harmful commodities (mean 76 per 10 h day [95% CI 55-105]) as core food and social marketing messages (32 [26-39]) per day. Interpretation: We found that children are repeatedly exposed to marketing through multiple mediums and across all settings, and our findings suggests that marketing privileges particular messages, for example, marketing of harmful commodities. Given the key role marketing plays in establishing and supporting consumption norms, and perpetuating the normalisation of overconsumption which contributes to environmental degradation, these findings suggest an urgent need to reduce marketing to promote planetary health. Funding: This research was funded by a University of Otago, Dean's Research Grant. The Kids'Cam study was funded by a Health Research Council of New Zealand Programme Grant (13/724).

The Lancet. Planetary health · 10 citationsread the source →

Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide.

Childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and is a known risk factor for suicidal behavior. In this study we sought to determine whether the impact of childhood trauma on suicide risk might be modified by FKBP5, an HPA-axis regulating gene. Sixteen FKBP5 haplotype-tagging single nucleotide polymorphisms (SNPs) were genotyped in a sample of African Americans: 398 treatment-seeking patients with substance dependence (90% men; 120 suicide attempters) and 432 nonsubstance-dependent individuals (40% men; 21 suicide attempters). In all, 474 participants (112 suicide attempters) also completed the Childhood Trauma Questionnaire (CTQ). Primary haplotype analyses were conducted with the four SNPs implicated in earlier studies: rs3800373, rs9296158, rs1360780, and rs9470080. We found that childhood trauma was associated with suicide attempt (P<0.0001). Although there was no main effect of the two major yin yang haplotypes in the four SNP haplotype blocks, there was a haplotype influence on suicide risk (p=0.006) only in individuals exposed to high levels of childhood trauma. In this group, 51% with two copies of the risk haplotype, 36% with one copy, and 20% with no copies had attempted suicide. The total logistic regression model accounted for 13% of the variance in attempted suicide. Analyses of the 16 SNPs showed significant main effects on suicide attempt of rs3777747, rs4713902, and rs9470080 and interactive effects of rs3800373, rs9296158, and rs1360780 with CTQ score on suicide attempt. These data suggest that childhood trauma and variants of the FKBP5 gene may interact to increase the risk for attempting suicide.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 198 citationsread the source →

Association between neighbourhood deprivation and hypertension in a US-wide Cohort.

Background: Socioeconomic status (SES) at the individual level is associated with hypertension risk. Less is known about neighbourhood level SES or how neighbourhood and individual level SES may jointly affect hypertension risk. Methods: The Area Deprivation Index (ADI) includes 17 census-based measures reflecting neighbourhood SES. The ADI was linked to enrolment addresses of 47 329 women in the Sister Study cohort and categorised as ≤10% (low deprivation), 11%-20%, 21%-35%, 36%-55% and >55% (high deprivation). Hypertension was defined as either high systolic (≥140 mm Hg) or diastolic (≥90 mm Hg) blood pressure or taking antihypertensive medication. We used log binomial regression to investigate the cross-sectional association between ADI and hypertension and evaluated interactions between ADI and race/ethnicity and between ADI and individual SES. Results: The highest ADI level of >55% was associated with increased prevalence of hypertension, compared with the lowest level of ADI≤10%, in a model adjusted for age, race/ethnicity, educational attainment and annual household income (prevalence ratio=1.26, 95% CI 1.21 to 1.32). We observed interaction between race/ethnicity and ADI (interaction contrast ratio (ICR)=1.9; 95% CI 0.94 to 2.8 comparing non-Hispanic Black women with ADI >55% to non-Hispanic White women with ADI≤10%) and between household income and ADI (ICR 0.38; 95% CI 0.12 to 0.65 comparing participants with household income ≤US$49 999 and ADI>55% to those with household income >US$100 000 and ADI≤10%). Conclusions: These findings suggest that neighbourhood deprivation measured by ADI may be a risk factor for hypertension and that ADI may act synergistically with race/ethnicity and individual household income to contribute to hypertension.

Journal of epidemiology and community health · 41 citationsread the source →

Prospective Study on Salivary Evening Melatonin and Sleep before and after Pinealectomy in Humans.

Melatonin is secreted systemically from the pineal gland maximally at night but is also produced locally in many tissues. Its chronobiological function is mainly exerted by pineal melatonin. It is a feedback regulator of the main circadian pacemaker in the hypothalamic suprachiasmatic nuclei and of many peripheral oscillators. Although exogenous melatonin is approved for circadian rhythm sleep disorders and old-age insomnia, research on endogenous melatonin in humans is hindered by the great interindividual variability of its amount and circadian rhythm. Single case studies on pinealectomized patients report on disrupted but also hypersomnic sleep. This is the first systematic prospective report on sleep with respect to pinealectomy due to pinealocytoma World Health Organization grade I without chemo- or radiotherapy. Before and after pinealectomy, 8 patients completed questionnaires on sleep quality and circadian rhythm (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire), 2 nights of polysomnography, salivary evening melatonin profiles, and qualitative assessment of 2 weeks of actigraphy and sleep logs. Six patients were assessed retrospectively up to 4 years after pinealectomy. Before pinealectomy, all but 1 patient showed an evening melatonin rise typical for indifferent chronotypes. After pinealectomy, evening saliva melatonin was markedly diminished, mostly below the detection limit of the assay (0.09 pg/mL). No systematic change in subjective sleep quality or standard measures of polysomnography was found. Mean pre- and postoperative sleep efficiency was 94% and 95%, and mean sleep-onset latency was 21 and 17 min, respectively. Sleep-wake rhythm during normal daily life did not change. Retrospective patients had a reduced sleep efficiency (90%) and more stage changes, although this was not significantly different from prospective patients. In conclusion, melatonin does seem to have a modulatory, not a regulatory, effect on standard measures of sleep. Study output is limited by small sample size and because only evening melatonin profiles were assessed.

Journal of biological rhythms · 32 citationsread the source →

Adverse Childhood Experiences Promote Increased and Selective Caregiving in Adulthood.

Adverse childhood experiences (ACEs) prompt parentification, which is related to providing regular caregiving as adults. This study examines the association between the number and types of ACEs and caregiving as adults, and to whom caregiving is extended. Analyses were based on 90,666 adults from 13 states in the U.S. in 2020-2024 and involved binomial and multinomial logistic regression, adjusted for selected covariates. Approximately 21% of participants provided regular care and 66% had ≥1 ACEs. Each of 11 ACEs considered was positively associated with providing regular care. As the number of types of ACEs increased, the odds of providing regular care increased. The strongest ACE predictor of providing regular care was living with a parent or adult who was depressed, mentally ill, or suicidal, and the weakest was when the parents were divorced, separated, or an unmarried couple. Among those receiving regular care, if the caregiver had more ACEs versus less, they were significantly less likely to care for a parent or grandparent but more likely to care for a spouse, child, sibling, or friend or non-relative.

International journal of environmental research and public healthread the source →

"There Was a Sense That Our Load Had Been Lightened": Evaluating Outcomes of Virtual Ethics Rounds for Veterinary Team Members.

Clinical ethics support services (CESS) are employed in healthcare to improve patient care and help team members develop skills to recognize and navigate ethically challenging situations (ECS). The objective of this study was to evaluate the impact of ethics rounds, one form of CESS, on veterinary team members. An anonymous, online mixed-methods survey incorporating a 15-item instrument designed to assess the outcomes of moral case deliberation originally developed for human healthcare workers (the Euro-MCD 2.0), was developed. The survey was administered to veterinary team members prior to and following participation in a 90-min virtual ethics rounds session. A total of 23 sessions of virtual ethics rounds were held. In total, 213 individuals participated, and 89 completed both surveys (response rate 41.8%). Most respondents were female (n = 70, 81%). Most were veterinarians (n = 51, 59%), followed by other veterinary team members (practice manager, animal attendant) (n = 18, 21%), veterinary nurses or animal health technicians (n = 10, 12%) and veterinary students (n = 8, 9%). Age ranged from 20 to 73 (median 41, IQR 32-52, n = 87). While there was no statistically significant difference between overall modified Euro-MCD 2.0 scores between T1 and T2, there were statistically significant changes in 7 out of 15 Euro-MCD 2.0 items in the domains of moral competence and moral teamwork. Reflexive thematic analysis of free-text responses identified themes including the types, impact and barriers to resolving ECS, the impacts of ethics rounds on veterinary team members and constraints preventing veterinary team members from speaking up in the face of ECS. While participants largely described the impact of ethics rounds as beneficial (for example, by facilitating clarification of thinking about ECS, allowing participants to see ECS from the perspective of others and providing a safe space for discussion), reflecting on ECS could be stressful for participants. Active participation in ethics rounds may be inhibited in the context of power imbalance, or in settings where bullying occurs. Overall, carefully facilitated ethics rounds has the potential to improve the ability of veterinary team members to identify and navigate ECS, and potentially mitigate moral distress.

Frontiers in veterinary science · 8 citationsread the source →

Effects of the COVID-19 Pandemic and Telehealth on Antenatal Screening and Services, Including for Mental Health and Domestic Violence: An Australian Mixed-Methods Study.

Introduction: Australian antenatal care includes specific screening and service provision for domestic and family violence (DFV) and mental health. However, the COVID-19 pandemic resulted in major care changes, including greatly expanded telehealth. Given difficulties in a safe assessment and management of disclosures via telehealth, DFV and mental health service provision might be substantially impacted. This study therefore aimed to assess COVID-19 effects on DFV and mental health screening, as well as broader service provision from the perspective of local maternity service providers. Methods: Mixed-methods study of staff surveys and interviews of staff directly involved in pregnancy care (doctors, midwives, and allied health) in three Sydney (Australia) maternity units, from October 2020 to March 2021. Surveys and interviews interrogated perceived effects of the COVID-19 pandemic on delivery (ensuring required services occurred), timeliness, and quality of (a) overall maternity care and (b) DFV and mental health screening and care; and also advantages and disadvantages of telehealth. Surveys were descriptively analyzed. Interviews were conducted online, recorded, and transcribed verbatim prior to thematic analysis. Results: In total, 17 interviews were conducted and 109 survey responses were received. Breakdown of survey respondents was 67% of midwives, 21% of doctors, and 10% of allied health. Over half of survey respondents felt the pandemic had a negative effect on delivery, timeliness, and quality of overall pregnancy care, and DFV and mental health screening and management. Perceived telehealth positives included convenience for women (73%) and reducing women's travel times (69%). Negative features included no physical examination (90%), difficulty regarding non-verbal cues (84%), difficulty if interpreter required (71%), and unsure if safe to ask some questions (62%). About 50% felt telehealth should continue post-pandemic, but for <25% of visits. Those perceived suitable for telehealth were low-risk and multiparous women, whereas those unsuited were high-risk pregnancy, non-English speaking, and/or mental health/psychosocial/DFV concerns. "Change to delivery of care" was the central interview theme, with subthemes of impact on mental health/DFV screening, telehealth (both positive and negative), staff impact (e.g., continuity of care disruption), and perceived impact on women and partners. Discussion: While telehealth may have an ongoing, post-pandemic role in Australian maternity care, staff believe that this should be limited in scope, mostly for low-risk pregnancies. Women with high risk due to physical health or mental health, DFV, and/or other social concerns were considered unsuited to telehealth.

Frontiers in global women's health · 10 citationsread the source →

Psychosexual health in gynecological cancer

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

International Journal of Gynecology & Obstetrics · 17 citationsread the source →

Transitional Care Units: Greater Than the Sum of Their Parts

Introduction In 1981, alarmed at the trend of incident patients selecting in-center hemodialysis over home therapies, Northwest Kidney Centers (NWK) established the first “dialysis orientation unit” under the direction of Dr. Joel Eschbach (1). The orientation unit provided a 2-month stabilization program emphasizing modality and diet education, patient “rehabilitation,” and transitioning safely to home dialysis. What was the historically “low” rate of home hemodialysis uptake that spurred development of this program? 50%. Today, any dialysis organization would consider a 50% home therapy start rate a resounding success. In subsequent years, nephrologists learned hard lessons about the dangers posed to patients in the first year of dialysis, particularly those “crashing in.“ It is now understood that the first 90 days of dialysis remain a period of high cost, high hospitalization rates, and mortality (2). This finding is often attributed to a lack of or insufficient nephrology predialysis care (3). US Renal Data System information suggests nearly 40% of patients with ESKD initiate dialysis without adequate preparation (2). Despite efforts to improve these statistics, so-called “suboptimal starts,” patients initiating dialysis in a hospital or with a central venous catheter (CVC), predominate making up 80% of the incident dialysis cohort (2). A detailed review of the causes of this phenomenon is beyond the scope of this article; however, one underappreciated contributor to suboptimal starts is unexpected and rapid loss of GFR in established CKD immediately preceding dialysis initiation. This situation catches patient and physician unaware, precluding or abbreviating participation in pre-ESKD care. Estimates of the number of patients experiencing this scenario are hampered by a lack of predialysis kidney function data, but a recent retrospective study noted that approximately 50% of patients may enter dialysis this way (4). Another study of incident patients with ESKD followed previously in long-term CKD clinics compared those initiating dialysis with a CVC against patients with an existing fistula or graft. The CVC group experienced double the rate of GFR loss in the 6 months preceding dialysis compared with the fistula/graft group (5). These studies imply that a sizeable portion of patients, irrespective of predialysis nephrology care, may not have access to adequate preparation due to sudden rapid GFR decline. Such individuals require “rescue therapy” in their first weeks and months of dialysis to navigate what has been rightly described “the trauma of dialysis initiation” (6,7). Goals of Transitional Dialysis Care Transitional dialysis care, referring to the medical and psychosocial support provided during the peridialysis initiation period, may take many forms from simple programs where designated staff provide focused chairside education to physically separate dialysis units providing broad support services. Although terminology is still evolving, specialized units dedicated to the needs of incident patients may be termed “transitional care units” (TCUs). These units share many characteristics with existing home training programs, and therefore, many goals of a TCU will already be familiar to clinicians. Gentle medical stabilization of the patient who is new to dialysis In-depth education on modality, nutrition, and financial aspects of ESKD Provide emotional and psychologic support Provide a welcoming environment and education for caregivers/partners Provide “patient navigation” services to facilitate multiple appointments, such as access and transplant Provide a supportive, low-risk environment to sample home therapies Although patient-centered goals have been the primary driver for establishing TCUs, in the era of value-based care, these units may also represent a cost-effective quality improvement intervention. This is accomplished by adopting proven elements of existing programs, such as checklists, patient navigators, teaching methods, etc., and placing them under a single geographic and programmatic “roof.” In doing so, it is possible a TCU model can attain similar quality improvements, such as Decreased access placement latency times Improved transplant referral timing and volume Improved adoption of home therapies Decreased hospitalizations and mortality A typical transitional care program may last 4–8 weeks and involves all members of the interdisciplinary care team providing scheduled chairside teaching and enhanced educational activities. At program conclusion, patients should emerge with an understanding of all aspects of their disease, allowing for truly informed decisions in areas such as modality and transplant. Early support interventions have the potential to reduce disparities in home therapies and transplant by reducing provider modality bias in favor of patient choice. Historical Perspectives on Transitional Care The first documented example of a TCU (established as the “Dialysis Orientation Unit” at NWK) brought together distributed patient care activities and work flows. The goal was to “rehabilitate the patient,” promote self-care, and allow the patient to attain a quality of life as close as possible to their pre-ESKD self (1). The program featured a physically separate unit, high staff-to-patient ratio, and close collaboration with the home training group. Unit staff members were selected not only on the basis of clinical skill but also on the ability to empathize and educate. Primary nursing was a focus, with a now hard to imagine 1:2 nurse-to-patient ratio. All new patients began in the orientation unit—no cherry picking was allowed. In the first year, 93 patients completed the training curriculum and spent an average of 9 weeks in the program. Results were impressive: 62% of patients transitioned to the home dialysis training unit; 24% of patients, unable or unwilling to dialyze at home, transitioned to “limited care”—similar to today’s “in-center self-care,” and only 10% joined the general in-center population (1). Over the next decade, more medically complex patients began to enter dialysis, and the early results proved difficult to maintain. However, before its closing in the mid-1990s, this early TCU example attained a still impressive 25% uptake rate of home therapies (1). In the 2000s, large United States-based dialysis providers initiated dedicated quality improvement programs targeting incident patients. Although these programs included many elements of the dedicated TCU model, they did not use the separate physical plant component. Demonstrable improvements were observed in hard outcomes, such as access placement rates, hospitalizations, and mortality (8). Although modality education was a component of these programs, effects on home therapy uptake were not reported. In Canada, a number of hospital-based dialysis entities with a “home first” focus established TCUs with an emphasis on psychosocial support and meaningful modality education. One such example, Humber River Hospital’s TCU, reported results of 180 incident dialysis starts in a six-station dedicated unit. In their hands, home dialysis uptake rates more than doubled for participants in the TCU (56%) versus nonparticipants (21%) (9). More striking, patients with “unplanned” dialysis starts had a 50% home therapy uptake rate when funneled through the TCU. Today in the United States, TCUs are just beginning to take root, with only anecdotal outcome data available. One such program at Satellite Dialysis, termed “Optimal Transitions,” has described early results. Their TCU uses traditional education and psychosocial support program pillars but adds a new element—a 5-day per week dialysis schedule using home dialysis machines to provide a gentler break-in experience (10). The final weeks of the program conclude with a dedicated “self-care” phase, where patients are given hands-on training and time to experiment with home dialysis therapy. Conclusions Aside from transplantation, there is currently no single intervention in kidney disease that is as impactful as improving the transition from CKD to ESKD. Despite recent improvements in referral timing and the overall proportion of patients receiving pre-ESKD care, a substantial population of patients remains vulnerable to poor health outcomes and is deprived of meaningful modality choice at dialysis initiation due to lack of adequate support and education. A TCU provides the framework to both medically and emotionally support these patients. These units stitch together multiple proven interventions to provide a supportive medical home. Operationally, transitional units can scale as needed. A dialysis clinic with low-incident patient volumes may dedicate as few as one to two stations to transitional care and easily handle a year’s worth of incident patients. Although the intervention is intensive from the patient perspective, the program is limited to a unit’s new patients only. Staff and physicians are not overwhelmed by wholesale changes to dialysis operations, like those seen in more complex alternative payment models. The expected increased time commitment for the physician is akin to a couple of extra clinic visits per week. However promising early TCU results may be, clinical trials remain necessary to justify upfront investments in such units. Increases in home therapy adoption seem the most assured outcome; however, larger study populations are required to show improvements in hospitalization rates, mortality, and access placement. By bringing incident patients, providers, and proven interventions together in one location, the TCU model may prove greater than the sum of its parts. Disclosures Dr. Bowman is the principal investigator on a proposed multisite trial of the effect of the transitional care unit concept. NxStage Medical Inc. has agreed to provide data hosting for this trial. All other expenses are self-funded by the participating units.

Clinical Journal of the American Society of Nephrology · 27 citationsread the source →

Domestic violence in pregnancy: prevalence and characteristics of the pregnant woman.

Aims and objectives: To determine the prevalence of domestic violence (physical, psychological or sexual) during pregnancy and to characterise these women. Background: Pregnant women are not immune to domestic violence and therefore may be subject to any form of physical, psychological or sexual violence by partners. Health professionals' knowledge and awareness are important in the identification and intervention of pregnant women who experience domestic violence. Methods: Quantitative, descriptive, correlational study, using a nonprobabilistic convenience sample consisting of a total of 852 postpartum women, of whom 370 were experiencing domestic violence according to the criteria adopted through the modified scale of prevalence, applied between February-June 2012 in two Portuguese public health institutions. Authorisation was given by the Ethics Committees/Administration Councils of both institutions involved and the National Committee of Data Protection. Results: The prevalence of DV during pregnancy was 43·4% (physical violence - 21·9%; psychological violence - 43·2%; and sexual violence - 19·6%). These women had the following profile: immigrant (OR = 5·70; IC95% 3·32-9·78), non-Caucasian (OR = 6·27; IC95% 3·76-10·46), single/divorced/widowed (OR = 2·28; IC95% 1·70-3·05), academic qualifications up to year 9 (OR = 4·94; IC95% 3·31-7·37); between 10-12 years of schooling (OR = 2·36; IC95% 1·70-3·29); unemployed (OR = 2·01; IC95% 1·50-2·69); and with a monthly income <1000 euros (OR = 1·90; IC95% 1·44-2·50). Through logistic regression, the following protective factors have been identified: nationality (Portuguese), race (Caucasian) and place of residence (city). Conclusions: Almost half of the sample had experienced some form of domestic violence. This is associated with certain sociodemographic factors identified in the study. Psychological violence was the most prevalent during pregnancy. Relevance to clinical practice: Knowledge of the prevalence and characteristics of pregnant women who experience domestic violence is of paramount importance in planning appropriate strategies for their needs during pregnancy. Results indicate the need for nurses to intervene when warning signs of domestic violence against pregnant women are detected.

Journal of clinical nursing · 30 citationsread the source →

Programmatic approaches to achieving equity for women in anesthesiology

Key points Women anesthesiologists can experience barriers and bias in the workplace, which varies in nature across their career and can negatively hinder professional development. Mitigation of these barriers and discrimination can be achieved through: (1) addressing individual bias, (2) closing the knowledge gap on the scope of bias, (3) deliberate representation, (4) strengthening professional networks, and (5) organized efforts to create policies that address gender inequity in the workplace. Women in anesthesiology is one example of several organized initiatives and programs that promote gender equity for women anesthesiologists of all identities. Introduction Women have long fought for equity in medicine and to be treated respectfully and professionally as physicians. One hundred seventy-five years ago, Elizabeth Blackwell was admitted to medical school as a joke, and since then, the viewpoint that medicine is emotionally undesirable, intellectually taxing, and physically draining for women has persisted. Pioneering women anesthesiologists, including Isabella Herb and Virginia Apgar, were discouraged from training as surgeons and pushed into the lower paying and “lower status” specialty of anesthesiology. Despite 50 years since the passage of Title IV, a Federal civil rights law that prohibits discrimination on the basis of sex in any educational program or activity that receives federal funding, and the fact that half of the medical students are women, there is still major attrition of women as they advance in anesthesiology residencies, careers, and leadership.1,2 Recent studies have attempted to examine the reasons for this inequity and bring awareness of the widespread discrimination and systemic bias affecting women anesthesiologists and their departure from medicine.1,3–8 Identifying as a woman in anesthesiology is multifaceted and nuanced. Women can be at different points in their professional careers and personal lives. This may be associated with a broad spectrum of identities, including but not limited to clinicians, academicians, activists, or advocates, as well as mothers, children, siblings, or partners. These identities also intersect with sexuality, race, ethnicity, culture, spirituality, and community. This diversity of lived experiences is why blanket assumptions about women anesthesiologists should be avoided. However, despite these varied identities, all women anesthesiologists are subject to institutional and cultural norms regarding gender. Therefore, the development of multiple initiatives and programs to promote gender equity for women anesthesiologists of all identities is paramount. In this article, we will review the scope of the gender problem in our specialty, discuss proposed strategies to enhance equity, and examine 1 organization’s approach to advocating for gender equity in anesthesiology. Scope of the problem Overworked, undervalued, harassed, and silenced. These are the sentiments of many women in anesthesiology. Many of the challenges encountered are synergized by a climate and culture that enable and fail to adequately address these issues.9 Gender disparities within anesthesiology exist because of systemic barriers and biases, limited number of women in anesthesiology leadership, and limited mentorship.5 The proportion of women physicians in anesthesiology ranks in the lower third among all medical specialties.10 Despite significant advances in the number of women entering medicine over the last few decades, anesthesiology programs have yet to achieve gender parity.7 Among anesthesiology residents, 33% are women. Women represent 25% of the overall anesthesiology workforce and 37% of the academic anesthesiology workforce, and these numbers remain relatively static.1,6,8 Meanwhile, other surgical and procedural subspecialties have doubled and tripled the percentage of women in their field and surpassed anesthesiology. Women anesthesiologists also are underrepresented in various positions of leadership or influence, and as authors and editors.4 They are paid significantly less than their male counterparts for equitable work, with an annual pay gap of 8%, or $32,000 a year, and are overall more likely to be in a lower salary range.5 Over a 30-year career span, this translates to roughly $1,000,000 in lost earnings.5 Even after adjusting for age, work experience, hours worked, academic productivity, and rank, the gap in gender pay remained and in fact, widened over the course of an anesthesiologist’s career.5 There are several systemic issues that hinder the recruitment, retention, and success of women in anesthesiology. Women physicians, relative to men, encounter additional hurdles to performing their jobs, especially at the early stages of their careers.11 Women physicians are more frequently asked about their age and experience compared with their men counterparts. A study found when treatment advice was given by an inexperienced physician, and participants reported relying significantly more on the advice of a man versus a woman.11 This suggests that some of the hurdles that women physicians face are rooted in the psychological biases of others rather than objective features of cases or treatment settings.11 The results of the few studies examining the effects of gender on daily practice in the specialty of anesthesiology are discouraging. A recent survey study assessing gender disparities perceived by women anesthesiologists found that majority (90%) of the respondents felt that women in medicine need to work harder than men to achieve the same career goals, and sexual harassment was experienced by 55%.12 Similarly, in a survey of women cardiothoracic anesthesiologists, 24% of respondents reported experiencing unwanted physical or sexual advances, and 45% reported experiencing verbal harassment.13 The majority of respondents also reported experiencing intimidation or derogatory language in the workplace.13 As well stated by the authors: “lack of psychological safety and respect in working environments increases the risk of communication failures, and intimidation in the setting of managing surgical patients increases stress and risk for burnout”.13 The original “pipeline theory” proposed that sex-based discrimination in academic medicine would diminish once women achieved a critical mass of > 30% of the academic workforce.14 Interestingly, “women who examine trends in sex disparities in the workplace are often ridiculed, labeled as whining, or determined to be less capable in their ability to lead.”15 Paired with that, women physicians are less likely to be addressed as “doctor,” they are more likely to be interrupted (at times in the middle of their preoperative assessment), and more likely to be labeled as “bossy” when asserting information.16 The culture of medicine is unlikely to change without improving formal reporting mechanisms of sex-based discrimination and sexual harassment.14 Unfortunately, the prevalence of sexist microaggressions against women anesthesiologists is still high, and this ongoing workplace mistreatment can cause chronic and severe distress.17 Sex equity is an issue of urgency in the practice of anesthesiology. Those in leadership positions have the additional responsibility of leveraging their power to influence the broader institutional culture.15 Having women at the top of organizations has been shown to improve organizational performance.18 Women represent approximately half of students entering medical school and ~41% of full-time academic faculty,19 yet women constitute a minority of leaders.20 Sex disparities continue to exist at the upper levels of leadership in academic anesthesiology.1 Only 18% of women are professors, and the percentage of women anesthesiology department chairs remains unchanged from 2006 to 2016 (12.7% vs. 14%).21 As of this writing, neither Anesthesia & Analgesia nor Anesthesiology has had a woman Editor-in-Chief. On that note, men and women have significant differences in measures of publication productivity, a recent study demonstrating that male anesthesiologists had a higher h-index, number of publications, and number of citations.22 Women have also been underrepresented in national meetings with fewer speaker opportunities.8 Overall, the extremely limited proportion of women professors and chairs in anesthesiology, presidents of professional societies, and senior editors of specialty journals speak for itself when it comes to a lack of visibility at the highest level of the specialty.9 Despite the many barriers that women experience, they are just as eager as men to assume leadership positions.23 The “glass ceiling” still exists within the culture of anesthesiology, benefiting the “masculine” attitudes in the competition for academic positions.24 We need to change this outdated culture and climate in anesthesiology and create and help elevate more women into a pathway of equity. Anesthesiologists and pregnancy Pregnancy and motherhood have a tremendous impact on sex discrimination in anesthesiology. A woman’s peak fertility often coincides with residency training and early career, a time when one’s career trajectory becomes established. This is also the time when the sex gap in academic promotion and productivity widens. Having children at that time is a challenge, and it is known that work demands adversely affect women anesthesiologists’ desired number of children and the desired age of childbearing. Anesthesiologists have the highest rate of maternal discrimination among all medical specialties.25 Sixty percent of anesthesiology residents reported a negative stigma around being pregnant and having children during training, and about half of trainees reported feeling discouraged from becoming pregnant or breastfeeding during training.7,26,27 Difficulties faced by women who are pregnant during training include inadequate maternity leave, insufficient access to lactation facilities at work, and negative culture surrounding pregnancy during training.26 Because of obstacles pertaining to motherhood, 1 in 10 female anesthesiologists would counsel a student against a career in anesthesiology.7 However, 86.2% of women anesthesiologists indicated that if given a choice again, they would still have their child during training despite these obstacles.26 Given the negative stigma associated with pregnancy in residency training, many women delay pregnancy until their early career, which typically occurs in the early 30s, leading to a higher likelihood of infertility.28 Approximately one-fourth of American female physicians are diagnosed with infertility at almost 34 years old, with a third of those due to diminished ovarian reserve, and this rate is significantly higher than the general population and other professionals that pursued higher education and careers.28,29 Contributing factors to the high rate of infertility among women in medicine may include stressors intrinsic to training, long hours, and night shifts.29 Infertility can lead to substantial depression, anxiety, burnout, and family planning regrets.28,29 Compounding the physical and emotional challenges of infertility is the exorbitant financial burden of treatment.29 In the United States, in vitro fertilization (IVF) costs ~$15,000 per round of treatment, not including the cost of medication.29 Unfortunately, fertility coverage for the majority of health professionals is lacking, and many medical institutions provide limited fertility coverage that will cover ~1 to 2 IVF cycles.29 In comparison, companies in the business, technology, and social media sector are recognizing the growing need for fertility coverage and are offering more comprehensive fertility, adoption, and surrogacy coverage, which has promoted physical and emotional well-being, job satisfaction, and enhanced employee recruitment and retention.29,30 In addition to cost, time is an additional barrier for seeking fertility treatment for anesthesiologists, and schedule modifications are often necessary. IVF typically requires the patient to present for multiple in-person monitoring appointments over a 2-week period during ovarian stimulation. On the basis of the outcome of the monitoring, an egg retrieval may be scheduled imminently, with little room for flexibility in timing. Without accommodation, women may need to take a vacation, paid or unpaid time off to undergo treatment, worsening the financial strain of infertility. Women anesthesiologists are also more likely to have pregnancy complications and miscarriages than the general population.31 Data suggests that women who work in the operating room have a higher incidence of first-trimester spontaneous abortions or a higher risk of birth defects.31 Women anesthesiologists report a higher rate of pregnancy complications [premature labor (8.8%), bedrest (7.8%), preeclampsia (6.5%), and a Neonatal Intensive Care Unit (NICU) stay for the baby (5.7%)], negative stigma for taking time off for pregnancy complications, and guilt in burdening colleagues with increased shifts and calls.26 Many attending anesthesiologists do not receive a modified work schedule during pregnancy.27 In some practice models, time off for pregnancy complications may not be paid and may decrease time for parental leave. Parental leave is an essential component to achieving postpartum physical and mental health and is crucial for infant bonding. trainees in parental leave was reported as and a of training programs not have a formal maternity leave trainees a of and for Approximately of anesthesiology residents felt their maternity leave was felt discouraged from taking more time and felt of with on However, of trainees also their programs as in of maternity leave In the American of Anesthesiologists a on which paid parental leave for after birth or of a In the American of Anesthesiology from the which residents to for an additional of leave without In the American of and a parental leave which for all to of parental leave, of for parental leave, without who as attending anesthesiologists report an parental leave time of and a of on the practice maternity leave may be of a of and leave This is in to other as and that have significant in paid parental leave, with companies offering to of paid other women anesthesiologists work postpartum to the to work and face the of lactation in the breastfeeding at a higher rate than the general they have a lower rate by infant age of the report the desired breastfeeding and having lactation In time and lack of can it to there are that are becoming more they may not work for all women. the has a on Among Anesthesia in to lactation in the of with the demands of work, women anesthesiologists face the burden of of of or motherhood, women physicians an of more hours per on are more likely to be the for children or the and are less likely to have a In addition to the women the and mental in labor about the of and labor on the emotional about in and managing is the of and emotional labor and is to as the in the of the The these to the by the to the culture of medicine and in the United In the stages of the some anesthesiologists were on unpaid leave of others work hours because of increased at A survey from the of Anesthesiologists at the time that women anesthesiologists were or given more often than those women who continue working on the they an and as there was about the of the They were to the and the to their from the and the of their children as As a more women anesthesiologists, work hours, to work, and medicine In with school and a on many women their time to on and an of more hours per than on and in a 33% in hours and academic productivity as compared with The percentage of with women as authors during the early stages of the despite the of in the sex gap in academic crucial for academic were also for women physicians as and there was time for because of personal or institutional the provide the flexibility to from the prevalence of and also Overall, the an increased burden on women anesthesiologists to the family and with and the sex gap in academic productivity and strategies to enhance gender equity in anesthesiology strategies to achieve gender equity in our we to gender equity in and policies and in and medical The in all that the to achieving sex equity in our is and is more than women with and leadership However, we that systemic change can be achieved by which were present in all the we (1) addressing individual bias, (2) closing the knowledge gap on the scope of bias, (3) deliberate representation, (4) strengthening professional networks, and (5) organized efforts to create policies that address gender inequity in the workplace. individual bias to create a culture of in a or and training in equity, and is to address individual equity, and training and education can cover a of systemic to as bias, and and can be in a of from individual to There are organizations that provide training, and as and are efforts lead to the of policies and leadership that women in the workplace, should gender equity to be a of the and should in the of sex equity into organizational and the knowledge gap on the scope of bias should be and reported to the of women anesthesiologists, barriers to their and systemic Data include performing of and professional need to be about professional is and among and should be and to and should be There to be deliberate and of women in recruitment, retention, promotion and in including women and their in any or policies are that affect work culture is should be or than that if more than 1 woman is there is a higher likelihood that a woman will achieve a has been in diversity by the of and which to the of women. additional strategies to enhance should by the job of an and should equity rather than flexibility and choice is leave policies with job and for workplace of for and other and policies should be to enhance the of women anesthesiologists at all There should be for and sex-based professional has been on the of women, but there are other that are as including and and help to women and their are and They can and promote women, their and their experience, the woman’s is for the of and media has increased the visibility of women anesthesiologists and has without the to in-person and However, deliberate formal or are also known development and leadership training for women that on and visibility can with efforts to create policies that address sex inequity in the workplace is to that there are challenges to a sex and the gender that are in workplace Women are known as and the of of a is for lactation and by the workplace that is and enhance is to the workplace a more for women to women are not on the promotion and should be In organized efforts to provide professional leadership training, and for women anesthesiologists at the and national levels are This not to enhance the of women but also to help women and address the systemic issues they encounter in a of an example organizations have been that are to improving equity for women These include national organizations in and of the anesthesiology organizations of Anesthesiologists on Women of Women in American of Anesthesia and Women in Anesthesia and and for Care Women in Care and leadership development and for Anesthesiology and Women of in Anesthesiology Women of Anesthesiology A of programs that there is and to provide professional development to discuss the organizational approach to gender equity in anesthesiology, we will on 1 Women in Anesthesiology is a in by to the professional and personal development of women also the recruitment, retention, and job of women in anesthesiology and a culture of and faced challenges residency and early career as a without the of a from the for and after other women of Women Women in the was to provide a addressing systemic were on addressing (1) lack of professional respect in with male (2) personal and professional and (3) of and to promote women to leadership efforts the of social media to women across and to provide education and to the affecting women efforts were by women in early and who were experiencing the of work for in leadership across societies, and institutions was pursued regarding enhanced and of women for and education regarding the of having women in leadership As a not associated with a efforts are in systemic change in other anesthesiology work, social media and in the of for and at efforts by of the of have national leave of and lactation in the and the on and the on were by who in The nature of also for on social and health issues to anesthesiologists, including and on these issues by and for to more in efforts that are to In addition to professional development for women and men an and a women anesthesiologists as national and to as the a and the operating have on to or In a social and on the provide on to women The of are these and annual including the and and on levels are by and a in-person the However, as a of full-time working women physicians, their careers and personal 1 of the has been the and to a and for our there have been many associated with the and development of 1 of the is the recent of a is well known that anesthesiology has remained other in the recruitment of women to the it would anesthesiologists that women medical students are more likely to a surgical than anesthesiology as a The a recent from the on to a program at students to about anesthesiology, address the challenges that women anesthesiologists and provide a national for from in medical the student are women of and their for and will help to improve the diversity of our has on the initiatives include a for all practice a professional and an in-person medical education In will continue to in medical students and physicians by programs and a The has for women in but that there is still work to be is in the of the to be of all and to improve for identities. In of our work has in for change in but culture change is by at the and institutional The by and other organizations at sex equity a of to into and to a systemic approach to of Despite numbers there is still major attrition of women in anesthesiology as they advance in their Sex disparities within anesthesiology exist because of systemic barriers and biases, with in cultural norms to which results in many women anesthesiologists feeling and discrimination from their women anesthesiologists with and leadership training is inadequate to address this and studies the need for systemic change to address inequity as enhanced representation, and as Women in Anesthesiology and other to equity for women anesthesiologists of all identities are paramount. of The authors that they have to

International Anesthesiology Clinics · 8 citationsread the source →

Global, regional, and national prevalence estimates of physical or sexual, or both, intimate partner violence against women in 2018.

Background: Intimate partner violence against women is a global public health problem with many short-term and long-term effects on the physical and mental health of women and their children. The Sustainable Development Goals (SDGs) call for its elimination in target 5.2. To monitor governments' progress towards SDG target 5.2, this study aimed to provide global, regional, and country baseline estimates of physical or sexual, or both, violence against women by male intimate partners. Methods: This study developed global, regional, and country estimates, based on data from the WHO Global Database on Prevalence of Violence Against Women. These data were identified through a systematic literature review searching MEDLINE, Global Health, Embase, Social Policy, and Web of Science, and comprehensive searches of national statistics and other websites. A country consultation process identified additional studies. Included studies were conducted between 2000 and 2018, representative at the national or sub-national level, included women aged 15 years or older, and used act-based measures of physical or sexual, or both, intimate partner violence. Non-population-based data, including administrative data, studies not generalisable to the whole population, studies with outcomes that only provided the combined prevalence of physical or sexual, or both, intimate partner violence with other forms of violence, and studies with insufficient data to allow extrapolation or imputation were excluded. We developed a Bayesian multilevel model to jointly estimate lifetime and past year intimate partner violence by age, year, and country. This framework adjusted for heterogeneous age groups and differences in outcome definition, and weighted surveys depending on whether they were nationally or sub-nationally representative. This study is registered with PROSPERO (number CRD42017054100). Findings: The database comprises 366 eligible studies, capturing the responses of 2 million women. Data were obtained from 161 countries and areas, covering 90% of the global population of women and girls (15 years or older). Globally, 27% (uncertainty interval [UI] 23-31%) of ever-partnered women aged 15-49 years are estimated to have experienced physical or sexual, or both, intimate partner violence in their lifetime, with 13% (10-16%) experiencing it in the past year before they were surveyed. This violence starts early, affecting adolescent girls and young women, with 24% (UI 21-28%) of women aged 15-19 years and 26% (23-30%) of women aged 19-24 years having already experienced this violence at least once since the age of 15 years. Regional variations exist, with low-income countries reporting higher lifetime and, even more pronouncedly, higher past year prevalence compared with high-income countries. Interpretation: These findings show that intimate partner violence against women was already highly prevalent across the globe before the COVID-19 pandemic. Governments are not on track to meet the SDG targets on the elimination of violence against women and girls, despite robust evidence that intimate partner violence can be prevented. There is an urgent need to invest in effective multisectoral interventions, strengthen the public health response to intimate partner violence, and ensure it is addressed in post-COVID-19 reconstruction efforts. Funding: UK Department for International Development through the UN Women-WHO Joint Programme on Strengthening Violence against Women Data, and UNDP-UN Population Fund-UNICEF-WHO-World Bank Special Programme of Research, Development, and Research Training in Human Reproduction, a cosponsored programme executed by WHO.

Lancet (London, England) · 682 citationsread the source →

Estimating the effect of HIV on cervical cancer elimination in South Africa: Comparative modelling of the impact of vaccination and screening.

Background: In 2020, the World Health Organization (WHO) launched its initiative to eliminate cervical cancer as a public health problem. To inform global efforts for countries with high HIV and cervical cancer burden, we assessed the impact of human papillomavirus (HPV) vaccination and cervical cancer screening and treatment in South Africa, on cervical cancer and the potential for achieving elimination before 2120, considering faster HPV disease progression and higher cervical cancer risk among women living with HIV(WLHIV) and HIV interventions. Methods: Three independent transmission-dynamic models simulating HIV and HPV infections and disease progression were used to predict the impact on cervical cancer incidence of three scenarios for all women: 1) girls' vaccination (9-14 years old), 2) girls' vaccination plus 1 lifetime cervical screen (at 35 years), and 3) girls' vaccination plus 2 lifetime cervical screens (at 35 and 45 years) and three enhanced scenarios for WLHIV: 4) vaccination of young WLHIV aged 15-24 years, 5) three-yearly cervical screening of WLHIV aged 15-49 years, or 6) both. Vaccination assumed 90% coverage and 100% lifetime protection with the nonavalent vaccine (against HPV-16/18/31/33/45/52/58). Cervical cancer screening assumed HPV testing with uptake increasing from 45% (2023), 70% (2030) to 90% (2045+). We also assumed that UNAIDS 90-90-90 HIV treatment and 70% male circumcision targets are reached by 2030. We examined three elimination thresholds: age-standardised cervical cancer incidence rates below 4 or 10 per 100,000 women-years, and >85% reduction in cervical cancer incidence rate. We conducted sensitivity analyses and presented the median age-standardised predictions of outcomes of the three models (minimum-maximum across models). Findings: Girls' vaccination could reduce age-standardised cervical cancer incidence from a median of 47.6 (40.9-79.2) in 2020 to 4.5 (3.2-6.3) per 100,000 women-years by 2120, averting on average ∼4% and ∼46% of age-standardised cumulative cervical cancer cases over 25 and 100 years, respectively, compared to the basecase. Adding 2 lifetime screens helped achieve elimination over the century among all women (2120 cervical cancer incidence: 3.6 (1.9-3.6) per 100,000 women-years), but not among WLHIV (10.8 (5.3-11.6)), and averted more cumulative cancer cases overall (∼45% over 25 years and ∼61% over 100 years compared to basecase) than girls' vaccination alone. Adding three-yearly cervical screening among WLHIV (to girls' vaccination and 2 lifetime cervical screens) further reduced age-standardised cervical cancer incidence to 3.3 (1.8-3.6) per 100,000 women-years overall and to 5.2 (3.9-8.5) among WLHIV by 2120 and averted on average 12-13% additional cumulative cancer cases among all women and 21-24% among WLHIV than girls' vaccination and 2 lifetime cervical screens over 25 years or longer. Long-term vaccine protection and using the nonavalent vaccine was required for elimination. Interpretation: High HPV vaccination coverage of girls and 2 lifetime cervical screens could eliminate cervical cancer among women overall in South Africa by the end of the century and substantially decrease cases among all women and WLHIV over the short and medium term. Cervical cancer elimination in WLHIV would likely require enhanced prevention strategies for WLHIV. Screening of WLHIV remains an important strategy to reduce incidence and alleviate disparities in cervical cancer burden between women with and without HIV, despite HIV interventions scale-up. Funding: World Health Organization. National Cancer Institute, National Institutes of Health. MRC Centre for Global Infectious Disease Analysis, UK Medical Research Council. National Institute of Child Health and Human Development research. Cancer Association of South Africa. Canadian Institutes of Health Research and the Fonds de recherche du Québec - Santé research.

EClinicalMedicine · 19 citationsread the source →

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

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

Journal of thermal biology · 6 citationsread the source →

Pediatric obesity: Causes, symptoms, prevention and treatment.

Pediatric or childhood obesity is the most prevalent nutritional disorder among children and adolescents worldwide. Approximately 43 million individuals are obese, 21-24% children and adolescents are overweight, and 16-18% of individuals have abdominal obesity. The prevalence of obesity is highest among specific ethnic groups. Obesity increases the risk of heart diseases in children and adults. Childhood obesity predisposes the individual to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and kidney diseases and causes reproductive dysfunction in adults. Obesity in children is a major health concern of the developed world. The National Health and Nutrition Examination Survey has reported that the prevalence of obesity is on the increase in all the pediatric age groups, in males and females, and in various ethnic and racial groups. Factors, such as eating habits, genetics, environment, metabolism, and lifestyle play an important role in the development of obesity. Over 90% of obesity cases are idiopathic and less than 10% are associated with genetic and hormonal causes. Obesity occurs when the body consumes more calories than it burns, through overeating and underexercising. The symptoms of obesity include breathing disorders, sleep apnea, chronic obstructive pulmonary disease, certain types of cancer such as prostate, bowel, breast and uterine, coronary heart disease, diabetes (type 2 in children), depression, liver and gallbladder problems, gastro-esophageal reflux disease, high blood pressure, high cholesterol, stroke, and joint diseases such as osteoarthritis, pain in knees and lower back. Environmental, behavioral such as consumption of convenience foods, genetic, and family factors contribute to pediatric obesity. Obesity can be countered through lower calorie consumption, weight loss and diet programs, as well as increased physical activity. A number of endogenous molecules including leptin, hypothalamic melanocortin 4 receptor, and mitochondrial uncoupling proteins, are known to affect body weight. These molecules serve as potential targets for the pharmacological manipulation of obesity. Sibutramine and orlistat are primariliy used for the treatment of adult obesity, which produces modest weight loss, of 3-8% compared to placebo. For children and obese adolescents, metformin is used in the case of insulin resistance and hyperinsulinemia. Octreotide is used for hypothalamic obesity. Bariatric surgery is performed for the treatment of severe childhood obesity. The causes, symptoms, prevention and treatment of pediatric obesity are described in the present review.

Experimental and therapeutic medicine · 106 citationsread the source →

Socioeconomic inequalities in adolescent health 2002-2010: a time-series analysis of 34 countries participating in the Health Behaviour in School-aged Children study.

Background: Information about trends in adolescent health inequalities is scarce, especially at an international level. We examined secular trends in socioeconomic inequality in five domains of adolescent health and the association of socioeconomic inequality with national wealth and income inequality. Methods: We undertook a time-series analysis of data from the Health Behaviour in School-aged Children study, in which cross-sectional surveys were done in 34 North American and European countries in 2002, 2006, and 2010 (pooled n 492,788). We used individual data for socioeconomic status (Health Behaviour in School-aged Children Family Affluence Scale) and health (days of physical activity per week, body-mass index Z score [zBMI], frequency of psychological and physical symptoms on 0-5 scale, and life satisfaction scored 0-10 on the Cantril ladder) to examine trends in health and socioeconomic inequalities in health. We also investigated whether international differences in health and health inequalities were associated with per person income and income inequality. Findings: From 2002 to 2010, average levels of physical activity (3·90 to 4·08 days per week; p<0·0001), body mass (zBMI -0·08 to 0·03; p<0·0001), and physical symptoms (3·06 to 3·20, p<0·0001), and life satisfaction (7·58 to 7·61; p=0·0034) slightly increased. Inequalities between socioeconomic groups increased in physical activity (-0·79 to -0·83 days per week difference between most and least affluent groups; p=0·0008), zBMI (0·15 to 0·18; p<0·0001), and psychological (0·58 to 0·67; p=0·0360) and physical (0·21 to 0·26; p=0·0018) symptoms. Only in life satisfaction did health inequality fall during this period (-0·98 to -0·95; p=0·0198). Internationally, the higher the per person income, the better and more equal health was in terms of physical activity (0·06 days per SD increase in income; p<0·0001), psychological symptoms (-0·09; p<0·0001), and life satisfaction (0·08; p<0·0001). However, higher income inequality uniquely related to fewer days of physical activity (-0·05 days; p=0·0295), higher zBMI (0·06; p<0·0001), more psychological (0·18; p<0·0001) and physical (0·16; p<0·0001) symptoms, and larger health inequalities between socioeconomic groups in psychological (0·13; p=0·0080) and physical (0·07; p=0·0022) symptoms, and life satisfaction (-0·10; p=0·0092). Interpretation: Socioeconomic inequality has increased in many domains of adolescent health. These trends coincide with unequal distribution of income between rich and poor people. Widening gaps in adolescent health could predict future inequalities in adult health and need urgent policy action. Funding: Canadian Institutes of Health Research.

Lancet (London, England) · 301 citationsread the source →