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Randomized Clinical Trial of Parent-Focused Treatment and Family-Based Treatment for Adolescent Anorexia Nervosa.

Objective: There have been few randomized clinical trials (RCTs) for adolescents with anorexia nervosa (AN). Most of these posit that involving all family members in treatment supports favorable outcomes. However, at least 2 RCTs suggest that separate parent and adolescent sessions may be just as effective as conjoint treatment. This study compared the relative efficacy of family-based treatment (FBT) and parent-focused treatment (PFT). In PFT, the therapist meets with the parents only, while a nurse monitors the patient. Method: Participants (N = 107) aged 12 to 18 years and meeting DSM 4(th)Edition criteria for AN or partial AN were randomized to either FBT or PFT. Participants were assessed at baseline, end of treatment (EOT), and at 6 and 12 months posttreatment. Treatments comprised 18 outpatient sessions over 6 months. The primary outcome was remission, defined as ≥95% of median body mass index and Eating Disorder Examination Global Score within 1 SD of community norms. Results: Remission was higher in PFT than in FBT at EOT (43% versus 22%; p = .016, odds ratio [OR] = 3.03, 95% CI = 1.23-7.46), but did not differ statistically at 6-month (PFT 39% versus FBT 22%; p = .053, OR = 2.48, CI = 0.989-6.22), or 12-month (PFT 37% versus FBT 29%; p = .444, OR = 1.39, 95% CI = 0.60-3.21) follow-up. Several treatment effect moderators of primary outcome were identified. Conclusion: At EOT, PFT was more efficacious than FBT in bringing about remission in adolescents with AN. However, differences in remission rates between PFT and FBT at follow-up were not statistically significant. Clinical trial registration information: A Randomised Controlled Trial of Two Forms of Family-Based Treatment and the Effect on Percent Ideal Body Weight and Eating Disorders Symptoms in Adolescent Anorexia Nervosa; http://www.anzctr.org.au/; ACTRN12610000216011.

Journal of the American Academy of Child and Adolescent Psychiatry · randomised controlled trial · 142 citationsread the source →

A review and meta-analysis of the effect of weight loss on all-cause mortality risk.

Overweight and obesity are associated with increased morbidity and mortality, although the range of body weights that is optimal for health is controversial. It is less clear whether weight loss benefits longevity and hence whether weight reduction is justified as a prime goal for all individuals who are overweight (normally defined as BMI>25 kg/m2). The purpose of the present review was to examine the evidence base for recommending weight loss by diet and lifestyle change as a means of prolonging life. An electronic search identified twenty-six eligible prospective studies that monitored subsequent mortality risk following weight loss by lifestyle change, published up to 2008. Data were extracted and further analysed by meta-analysis, giving particular attention to the influence of confounders. Moderator variables such as reason for weight loss (intentional, unintentional), baseline health status (healthy, unhealthy), baseline BMI (normal, overweight, obese), method used to estimate weight loss (measured weight loss, reported weight loss) and whether models adjusted for physical activity (adjusted data, unadjusted data) were used to classify subgroups for separate analysis. Intentional weight loss per se had a neutral effect on all-cause mortality (relative risk (RR) 1.01; P = 0.89), while weight loss which was unintentional or ill-defined was associated with excess risk of 22 to 39 %. Intentional weight loss had a small benefit for individuals classified as unhealthy (with obesity-related risk factors) (RR 0.87 (95 % CI 0.77, 0.99); P = 0.028), especially unhealthy obese (RR 0.84 (95 % CI 0.73, 0.97); P = 0.018), but appeared to be associated with slightly increased mortality for healthy individuals (RR 1.11 (95 % CI 1.00, 1.22); P = 0.05), and for those who were overweight but not obese (RR 1.09 (95 % CI 1.02, 1.17); P = 0.008). There was no evidence for weight loss conferring either benefit or risk among healthy obese. In conclusion, the available evidence does not support solely advising overweight or obese individuals who are otherwise healthy to lose weight as a means of prolonging life. Other aspects of a healthy lifestyle, especially exercise and dietary quality, should be considered. However, well-designed intervention studies are needed clearly to disentangle the influence of physical activity, diet strategy and body composition, in order to define appropriate advice to those populations that might be expected to benefit.

Nutrition research reviews · meta-analysis · 179 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 →

Mindfulness training increases momentary positive emotions and reward experience in adults vulnerable to depression: a randomized controlled trial.

Objective: To examine whether mindfulness-based cognitive therapy (MBCT) increases momentary positive emotions and the ability to make use of natural rewards in daily life. Method: Adults with a life-time history of depression and current residual depressive symptoms (mean age = 43.9 years, SD = 9.6; 75% female; all Caucasian) were randomized to MBCT (n = 64) or waitlist control (CONTROL; n = 66) in a parallel, open-label, randomized controlled trial. The Experience Sampling Method was used to measure momentary positive emotions as well as appraisal of pleasant activities in daily life during 6 days before and after the intervention. Residual depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (Hamilton, 1960). Results: MBCT compared to CONTROL was associated with significant increases in appraisals of positive emotion (b* = .39) and activity pleasantness (b* = .22) as well as enhanced ability to boost momentary positive emotions by engaging in pleasant activities (b* = .08; all ps < .005). Associations remained significant when corrected for reductions in depressive symptoms or for reductions in negative emotion, rumination, and worry. In the MBCT condition, increases in positive emotion variables were associated with reduction of residual depressive symptoms (all ps < .05). Conclusions: MBCT is associated with increased experience of momentary positive emotions as well as greater appreciation of, and enhanced responsiveness to, pleasant daily-life activities. These changes were unlikely to be pure epiphenomena of decreased depression and, given the role of positive emotions in resilience against depression, may contribute to the protective effects of MBCT against depressive relapse.

Journal of consulting and clinical psychology · randomised controlled trial · 177 citationsread the source →

Referral criteria for outpatient specialty palliative cancer care: an international consensus.

Although outpatient specialty palliative-care clinics improve outcomes, there is no consensus on who should be referred or the optimal timing for referral. In response to this issue, we did a Delphi study to develop consensus on a list of criteria for referral of patients with advanced cancer at secondary or tertiary care hospitals to outpatient palliative care. 60 international experts (26 from North America, 19 from Asia and Australia, and 11 from Europe) on palliative cancer care rated 39 needs-based criteria and 22 time-based criteria in three iterative rounds. Nearly all experts responded in each round. Consensus was defined by an a-priori agreement of 70% or more. Panellists reached consensus on 11 major criteria for referral: severe physical symptoms, severe emotional symptoms, request for hastened death, spiritual or existential crisis, assistance with decision making or care planning, patient request for referral, delirium, spinal cord compression, brain or leptomeningeal metastases, within 3 months of advanced cancer diagnosis for patients with median survival of 1 year or less, and progressive disease despite second-line therapy. Consensus was also reached on 36 minor criteria for specialist palliative-care referral. These criteria, if validated, could provide guidance for identification of patients suitable for outpatient specialty palliative care.

The Lancet. Oncology · review · 175 citationsread the source →

Epidemiology of Substance Use among Forced Migrants: A Global Systematic Review.

Introduction: Forced migration is occurring at unprecedented levels. Forced migrants may be at risk for substance use for reasons including coping with traumatic experiences, co-morbid mental health disorders, acculturation challenges and social and economic inequality. This paper aimed to systematically review the literature examining substance use among forced migrants, and identify priority areas for intervention and future research. Methods: Seven medical, allied health and social science databases were searched from inception to September 2015 in accordance with PRISMA guidelines to identify original peer-reviewed articles describing any findings relating to alcohol and/or illicit drug use among refugees, internally displaced people (IDPs), asylum seekers, people displaced by disasters and deportees. A descriptive synthesis of evidence from quantitative studies was conducted, focusing primarily on studies which used validated measures of substance use. Synthesis of evidence from qualitative studies focused on identifying prominent themes relating to the contexts and consequences of substance use. Critical Appraisal Skills Programme (CASP) checklists were used to assess methodological quality of included studies. Results: Forty-four quantitative (82% cross-sectional), 16 qualitative and three mixed-methods studies were included. Ten studies were rated as high methodological quality (16%), 39 as moderate quality (62%) and 14 as low quality (22%). The majority of research was conducted among refugees, IDPs and asylum seekers (n = 55, 87%), predominantly in high-income settings. The highest-quality prevalence estimates of hazardous/harmful alcohol use ranged from 17%-36% in camp settings and 4%-7% in community settings. Few studies collected validated measures of illicit drug use. Seven studies compared substance use among forced migrants to other migrant or native-born samples. Among eight studies which conducted multivariable analysis, male sex, trauma exposure and symptoms of mental illness were commonly identified correlates of substance use. Conclusion: Our understanding of substance use among forced migrants remains limited, particularly regarding persons displaced due to disasters, development and deportation. Despite a growing body of work among refugee-background populations, few studies include refugees in low and middle-income countries, where over 80% of the global refugee population resides. Findings suggest a need to integrate substance use prevention and treatment into services offered to forced migrants, particularly in camp settings. Efforts to develop and evaluate interventions to reduce substance use and related harms are needed.

PloS one · systematic review · 122 citationsread the source →

Gender Differences in Misdiagnosis and Delayed Diagnosis among Adults with Autism Spectrum Disorder with No Language or Intellectual Disability.

Autism Spectrum Disorder (ASD) is often unrecognized, especially in mild forms and in women. Studies evaluating features associated with missed/misdiagnosis in men and women with ASD are warranted. 61 subjects (22 females, 39 males, age 28.5 ± 10.8 years) with ASD with no language/intellectual deficit were enrolled in the service for the treatment of psychiatric comorbidities in adults with ASD of the ASST Fatebenefratelli-Sacco in Milan (Italy). A detailed clinical history was gathered, and two self-report questionnaires (Autism Spectrum Quotient-AQ and Adult Autism Subthreshold Spectrum-AdAS Spectrum) were administered. 75.4% received their ASD diagnosis average eight years later than the first evaluation by mental health services. Compared to males, females showed a significantly greater delay in referral to mental health services and a significantly higher age at diagnosis of ASD. Among men, diagnostic delay inversely correlated with scores on the AdAS Spectrum total, Verbal communication, Empathy and Inflexibility and adherence to routine domains. Among women, diagnostic delay positively correlated with the Attention to detail score while the age at diagnosis of ASD positively correlated with the AdAS Spectrum Verbal communication and Restricted interests and rumination domain scores. Females were less likely to be correctly diagnosed and more likely to be misdiagnosed at first evaluation than men. Females reported significantly higher scores than men in the Hyper/Hyporeactivity to sensory input domain only among subjects who were misdiagnosed. Our findings provide gender-specific information about ASD patients seeking help for comorbid conditions and might be a primary ground for future research.

Brain sciences · 67 citationsread the source →

The construction and operational models of internet hospitals in China: a hospital-based survey study.

Background: China has empowered and continues to empower internet hospitals, which saw an increase in their development due to the pandemic, to fight against COVID-19. The construction and operational models of internet hospitals can be categorized as self-constructed and self-managed models, self-constructed and enterprise-run models, hospital and enterprise joint-owned models, and hosted by a third-party platform. Despite the growing importance of internet hospitals, there have been few systematic summaries of their construction and operational models. The primary purpose of the study was to understand the construction and operational models of internet hospitals in China. Methods: Data was collected from 39 internet hospitals and 356 medical staff between September 2020 and April 2021, via internet hospital and hospital staff surveys. T-tests were used to compare the continuous variables, while Chi-square tests were employed to compare the proportions of categorical variables. The self-perception of the internet hospitals' services was assessed using a 5-point Likert scale on 16 aspects and a root cause analysis was conducted to identify the root causes and influencing factors of current deficiencies experienced by internet hospitals. Results: Among the 39 internet hospitals, 22 (56.4%) were self-constructed and self-managed. Compared to other models of Internet hospitals, self-constructed and self-managed hospitals had lower percentages of professionals providing online services (P = 0.006), numbers of doctors outside of the entity (P = 0.006), numbers of online nurses (P = 0.004), and the ratio of online nurses to offline doctors (P < 0.001). Of the 16 aspects evaluated with regards to the medical staff's self-perception of the internet hospital services, the highest scores were given for fee transparency, fee rationality, travel cost capital, patience and responsibility, and consultation behaviors. The root causes included five aspects: human, channels, prices, services, and time. Conclusions: While the self-constructed and self-managed model was found to be the most prevalent form of internet hospital in China, the different models of internet hospitals can have an impact on both the quantity and quality of online healthcare services. This study contributes to the existing literature on internet hospitals' construction and operational models, offering additional policy implications for telemedicine management.

BMC health services research · 18 citationsread the source →

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

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

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

The relevance of cognitive emotion regulation to psychotic symptoms - A systematic review and meta-analysis.

Numerous studies emphasise the pivotal role of negative affect in the formation and maintenance of positive symptoms, which moves emotion regulation (ER) as a contributing factor into focus. We systematically reviewed and meta-analysed case-control studies reporting cross-sectional, correlative and experimental data of ER strategies in patients with psychotic disorders. In total, 42 studies were eligible, providing data for 2498 subjects and 3381 healthy controls. Questionnaire-based cross-sectional data (k=39) indicated strongest effects for rumination (g=-0,67 [-0,85 to -0,48]), self-blaming (g=-0,56; [-0,76 to -0,37]) and distraction (g=0,55 [0,11 to 0,98]). Suppression was more frequently (g=-0,36 [-0,56 to -0,16]) and cognitive reappraisal less frequently used (g=0,41 [0,28 to 0,55]), but heterogeneity was high. Correlative data (k=6) supported the assumption of an association between maladaptive strategies and positive symptoms (r=0,34 [0,22 to 0,44]). Less evidence of group differences was found in the experimental studies (k=3). The findings support the notion that ER is markedly impaired in patients with psychotic disorders. However, future research will need to further clarify the extent to which difficulties continue to exist after controlling for context and emotion intensity. The large effects for rumination and self-blaming point to promising treatment targets but also raise questions concerning the specifity of findings.

Clinical psychology review · meta-analysis · 81 citationsread the source →

Comparison of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation before and during the COVID-19 pandemic: a systematic review and meta-analysis.

Background: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897. Findings: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05). Interpretation: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents. Funding: None.

The lancet. Psychiatry · meta-analysis · 164 citationsread the source →

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

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

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

Stress response and the adolescent transition: performance versus peer rejection stressors.

Little is known about normative variation in stress response over the adolescent transition. This study examined neuroendocrine and cardiovascular responses to performance and peer rejection stressors over the adolescent transition in a normative sample. Participants were 82 healthy children (ages 7-12 years, n = 39, 22 females) and adolescents (ages 13-17, n = 43, 20 females) recruited through community postings. Following a habituation session, participants completed a performance (public speaking, mental arithmetic, mirror tracing) or peer rejection (exclusion challenges) stress session. Salivary cortisol, salivary alpha amylase (sAA), systolic and diastolic blood pressure (SBP, DBP), and heart rate were measured throughout. Adolescents showed significantly greater cortisol, sAA, SBP, and DBP stress response relative to children. Developmental differences were most pronounced in the performance stress session for cortisol and DBP and in the peer rejection session for sAA and SBP. Heightened physiological stress responses in typical adolescents may facilitate adaptation to new challenges of adolescence and adulthood. In high-risk adolescents, this normative shift may tip the balance toward stress response dysregulation associated with depression and other psychopathology. Specificity of physiological response by stressor type highlights the importance of a multisystem approach to the psychobiology of stress and may also have implications for understanding trajectories to psychopathology.

Development and psychopathology · 408 citationsread the source →

Do the parent-child relationship and parenting behaviors differ between families with a child with and without chronic illness? A meta-analysis.

Objective: The present meta-analysis compared the quality of the parent-child relationship as well as parenting behaviors and styles of families with a child with chronic physical illness with families of healthy children or test norms. Methods: Empirical studies were identified with the help of electronic databases and cross-referencing. Based on 325 included studies, random-effects meta-analysis was performed. Results: Although most effect sizes were small or very small, the parent-child relationship tended to be less positive if a child had a chronic physical illness (g = -.16 standard deviation units). In addition, lower levels of parental responsiveness (emotional warmth; g = -.22) as well as higher levels of demandingness (control, monitoring; g = .18) and overprotection (g = .39) were observed in these families. However, effect sizes were heterogeneous and only significant for a limited number of diseases. There was also some evidence for higher levels of authoritarian (g = .24) and neglectful parenting (g = .51) as well as lower levels of authoritative parenting compared with families with healthy children (g = -.13). Effect sizes varied, in part, by length of illness, child age, rater, assessment method, and target of comparison. Conclusions: We conclude that most families with a child with chronic physical illness adapt well with regard to the parent-child relationship and parenting behaviors/styles. Nonetheless, some families of children with specific diseases-such as epilepsy, hearing impairment, and asthma-may have difficulties finding appropriate levels of protective behaviors, control, and parental warmth and building positive mutual relationships between parents and children.

Journal of pediatric psychology · meta-analysis · 119 citationsread the source →

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

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

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

Couple Interventions for Chronic Pain: A Systematic Review.

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

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

Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in outpatients with anorexia nervosa (ANTOP study): randomised controlled trial.

Background: Psychotherapy is the treatment of choice for patients with anorexia nervosa, although evidence of efficacy is weak. The Anorexia Nervosa Treatment of OutPatients (ANTOP) study aimed to assess the efficacy and safety of two manual-based outpatient treatments for anorexia nervosa--focal psychodynamic therapy and enhanced cognitive behaviour therapy--versus optimised treatment as usual. Methods: The ANTOP study is a multicentre, randomised controlled efficacy trial in adults with anorexia nervosa. We recruited patients from ten university hospitals in Germany. Participants were randomly allocated to 10 months of treatment with either focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual (including outpatient psychotherapy and structured care from a family doctor). The primary outcome was weight gain, measured as increased body-mass index (BMI) at the end of treatment. A key secondary outcome was rate of recovery (based on a combination of weight gain and eating disorder-specific psychopathology). Analysis was by intention to treat. This trial is registered at http://isrctn.org, number ISRCTN72809357. Findings: Of 727 adults screened for inclusion, 242 underwent randomisation: 80 to focal psychodynamic therapy, 80 to enhanced cognitive behaviour therapy, and 82 to optimised treatment as usual. At the end of treatment, 54 patients (22%) were lost to follow-up, and at 12-month follow-up a total of 73 (30%) had dropped out. At the end of treatment, BMI had increased in all study groups (focal psychodynamic therapy 0·73 kg/m(2), enhanced cognitive behaviour therapy 0·93 kg/m(2), optimised treatment as usual 0·69 kg/m(2)); no differences were noted between groups (mean difference between focal psychodynamic therapy and enhanced cognitive behaviour therapy -0·45, 95% CI -0·96 to 0·07; focal psychodynamic therapy vs optimised treatment as usual -0·14, -0·68 to 0·39; enhanced cognitive behaviour therapy vs optimised treatment as usual -0·30, -0·22 to 0·83). At 12-month follow-up, the mean gain in BMI had risen further (1·64 kg/m(2), 1·30 kg/m(2), and 1·22 kg/m(2), respectively), but no differences between groups were recorded (0·10, -0·56 to 0·76; 0·25, -0·45 to 0·95; 0·15, -0·54 to 0·83, respectively). No serious adverse events attributable to weight loss or trial participation were recorded. Interpretation: Optimised treatment as usual, combining psychotherapy and structured care from a family doctor, should be regarded as solid baseline treatment for adult outpatients with anorexia nervosa. Focal psychodynamic therapy proved advantageous in terms of recovery at 12-month follow-up, and enhanced cognitive behaviour therapy was more effective with respect to speed of weight gain and improvements in eating disorder psychopathology. Long-term outcome data will be helpful to further adapt and improve these novel manual-based treatment approaches. Funding: German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), German Eating Disorders Diagnostic and Treatment Network (EDNET).

Lancet (London, England) · randomised controlled trial · 230 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 →

Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer: Outcomes From the ENABLE III Randomized Controlled Trial.

Purpose: To determine the effect of early versus delayed initiation of a palliative care intervention for family caregivers (CGs) of patients with advanced cancer. Patients and methods: Between October 2010 and March 2013, CGs of patients with advanced cancer were randomly assigned to receive three structured weekly telephone coaching sessions, monthly follow-up, and a bereavement call either early after enrollment or 3 months later. CGs of patients with advanced cancer were recruited from a National Cancer Institute cancer center, a Veterans Administration Medical Center, and two community outreach clinics. Outcomes were quality of life (QOL), depression, and burden (objective, stress, and demand). Results: A total of 122 CGs (early, n = 61; delayed, n = 61) of 207 patients participated; average age was 60 years, and most were female (78.7%) and white (92.6%). Between-group differences in depression scores from enrollment to 3 months (before delayed group started intervention) favored the early group (mean difference, -3.4; SE, 1.5; d = -.32; P = .02). There were no differences in QOL (mean difference, -2; SE, 2.3; d = -.13; P = .39) or burden (objective: mean difference, 0.3; SE, .7; d = .09; P = .64; stress: mean difference, -.5; SE, .5; d = -.2; P = .29; demand: mean difference, 0; SE, .7; d = -.01; P = .97). In decedents' CGs, a terminal decline analysis indicated between-group differences favoring the early group for depression (mean difference, -3.8; SE, 1.5; d = -.39; P = .02) and stress burden (mean difference, -1.1; SE, .4; d = -.44; P = .01) but not for QOL (mean difference, -4.9; SE, 2.6; d = -.3; P = .07), objective burden (mean difference, -.6; SE, .6; d = -.18; P = .27), or demand burden (mean difference, -.7; SE, .6; d = -.23; P = .22). Conclusion: Early-group CGs had lower depression scores at 3 months and lower depression and stress burden in the terminal decline analysis. Palliative care for CGs should be initiated as early as possible to maximize benefits.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 342 citationsread the source →

Combined prevention for substance use, depression, and anxiety in adolescence: a cluster-randomised controlled trial of a digital online intervention.

Background: Substance use, depression, and anxiety in adolescence are major public health problems requiring new scalable prevention strategies. We aimed to assess the effectiveness of a combined online universal (ie, delivered to all pupils) school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. Methods: We did a multicentre, cluster-randomised controlled trial in secondary schools in Australia, with pupils in year 8 or 9 (aged 13-14 years). Participating schools were randomly assigned (1:1:1:1) to one of four intervention conditions: (1) Climate Schools-Substance Use, focusing on substance use only; (2) Climate Schools-Mental Health, focusing on depression and anxiety only; (3) Climate Schools-Combined, focusing on the prevention of substance use, depression, and anxiety; or (4) active control. The interventions were delivered in school classrooms in an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. The interventions were delivered for 2 years and primary outcomes were knowledge related to alcohol, cannabis, and mental health; alcohol use, including heavy episodic drinking; and depression and anxiety symptoms at 12, 24, and 30 months after baseline. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785) and an extended follow-up is underway. Findings: Between Sept 1, 2013, and Feb 28, 2014, we recruited 88 schools (12 391 pupils), of whom 71 schools and 6386 (51·5%) pupils were analysed (17 schools dropped out and 1308 pupils declined to participate). We allocated 18 schools (1739 [27·25%] pupils; 1690 [97·2%] completed at least one follow-up) to the substance use condition, 18 schools (1594 [25·0%] pupils; 1560 [97·9%] completed at least one follow-up) to the mental health condition, 16 schools (1497 [23·4%] pupils; 1443 [96·4%] completed at least one follow-up) to the combined condition, and 19 schools (1556 [23·4%] pupils; 1513 [97·2%] completed at least one follow-up) to the control condition. Compared with controls, the combined intervention group had increased knowledge related to alcohol and cannabis at 12, 24, and 30 months (standardised mean difference [SMD] for alcohol 0·26 [95% CI 0·14 to 0·39] and for cannabis 0·17 [0·06 to 0·28] at 30 months), increased knowledge related to mental health at 24 months (0·17 [0·08 to 0·27]), reduced growth in their odds of drinking and heavy episodic drinking at 12, 24, and 30 months (odds ratio for drinking 0·25 [95% CI 0·12 to 0·51], and for heavy episodic drinking 0·15 [0·04 to 0·58] at 30 months), and reduced increases in anxiety symptoms at 12 and 30 months (SMD -0·12 [95% CI -0·22 to -0·01] at 30 months). We found no difference in symptoms or probable diagnosis of depression. The combined intervention group also showed improvement in alcohol use outcomes compared with the substance use and mental health interventions and improvements in anxiety outcomes when compared with the mental health intervention only. Interpretation: Combined online prevention of substance use, depression, and anxiety led to increased knowledge of alcohol, cannabis, and mental health, reduced increase in the odds of any drinking and heavy episodic drinking, and reduced symptoms of anxiety over a 30-month period. These findings provide the first evidence of the effectiveness of an online universal school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. Funding: Australian National Health and Medical Research Council.

The Lancet. Digital health · randomised controlled trial · 62 citationsread the source →

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

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

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

Effect of the Goals of Care Intervention for Advanced Dementia: A Randomized Clinical Trial.

Importance: In advanced dementia, goals of care decisions are challenging and medical care is often more intensive than desired. Objective: To test a goals of care (GOC) decision aid intervention to improve quality of communication and palliative care for nursing home residents with advanced dementia. Design, setting, and participants: A single-blind cluster randomized clinical trial, including 302 residents with advanced dementia and their family decision makers in 22 nursing homes. Interventions: A GOC video decision aid plus a structured discussion with nursing home health care providers; attention control with an informational video and usual care planning. Main outcomes and measures: Primary outcomes at 3 months were quality of communication (QOC, questionnaire scored 0-10 with higher ratings indicating better quality), family report of concordance with clinicians on the primary goal of care (endorsing same goal as the "best goal to guide care and medical treatment," and clinicians' "top priority for care and medical treatment"), and treatment consistent with preferences (Advance Care Planning Problem score). Secondary outcomes at 9 months were family ratings of symptom management and care, palliative care domains in care plans, Medical Orders for Scope of Treatment (MOST) completion, and hospital transfers. Resident-family dyads were the primary unit of analysis, and all analyses used intention-to-treat assignment. Results: Residents' mean age was 86.5 years, 39 (12.9%) were African American, and 246 (81.5%) were women. With the GOC intervention, family decision makers reported better quality of communication (QOC, 6.0 vs 5.6; P = .05) and better end-of-life communication (QOC end-of-life subscale, 3.7 vs 3.0; P = .02). Goal concordance did not differ at 3 months, but family decision makers with the intervention reported greater concordance by 9 months or death (133 [88.4%] vs 108 [71.2%], P = .001). Family ratings of treatment consistent with preferences, symptom management, and quality of care did not differ. Residents in the intervention group had more palliative care content in treatment plans (5.6 vs 4.7, P = .02), MOST order sets (35% vs 16%, P = .05), and half as many hospital transfers (0.078 vs 0.163 per 90 person-days; RR, 0.47; 95% CI, 0.26-0.88). Survival at 9 months was unaffected (adjusted hazard ratio [aHR], 0.76; 95% CI, 0.54-1.08; P = .13). Conclusions and relevance: The GOC decision aid intervention is effective to improve end-of-life communication for nursing home residents with advanced dementia and enhance palliative care plans while reducing hospital transfers. Trial registration: clinicaltrials.gov Identifier: NCT01565642.

JAMA internal medicine · randomised controlled trial · 193 citationsread the source →

What may help or hinder the implementation of computerized decision support systems (CDSSs): a focus group study with physicians.

Objectives: To identify potential barriers and facilitators to implementing computerized decision support systems (CDSSs) in health care as perceived by clinicians. Methods: We carried out a qualitative focus group study with primary and secondary health care settings in six areas of Finland. A total of 39 interviewed physicians, of whom 22 practised in primary care and 17 in secondary care. The main outcome measures physicians' expectations, preconceived barriers and facilitators were explicitly identified by the participants during the interviews. Results: Identified barriers were earlier experience of dysfunctional computer systems in health care, potential harm to doctor-patient relationship, obscured responsibilities, threats to clinician's autonomy and potential extra workload due to excessive reminders. Identified facilitators were self-control of frequency and contents of CDSS and noticeable help of CDSS in clinical practice. It was easy for the physicians to think of applications and clinical topics for CDSS that could help them to avoid mistakes and improve work processes. Conclusions: Physicians had relatively positive attitudes towards the idea of CDSS. They expected flexibility, individuality and reliability of the CDSS. The rather high level of computerized practices and wide use of electronic guidelines probably have paved the way for the CDSS in Finland.

Family practice · 85 citationsread the source →

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

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

European urology · clinical trial · 222 citationsread the source →

Shame, guilt, and depressive symptoms: a meta-analytic review.

Recent theoretical and empirical work has facilitated the drawing of sharp conceptual distinctions between shame and guilt. A clear view of these distinctions has permitted development of a research literature aimed at evaluating the differential associations of shame and guilt with depressive symptoms. This study quantitatively summarized the magnitude of associations of shame and guilt with depressive symptoms. Two hundred forty-two effect sizes were obtained from 108 studies employing 22,411 participants. Shame showed significantly stronger associations with depressive symptoms (r = .43) than guilt (r = .28). However, the association of shame and depressive symptoms was statistically indistinguishable from the associations of 2 maladaptive variants of guilt and depressive symptoms (contextual-maladaptive guilt, involving exaggerated responsibility for uncontrollable events, r = .39; generalized guilt, involving "free-floating" guilt divorced from specific contexts, r = .42). Other factors also moderated the effects. External shame, which involves negative views of self as seen through the eyes of others, was associated with larger effect sizes (r = .56) than internal shame (r = .42), which involves negative views of self as seen through one's own eyes. Depressive symptom measures that invoked the term guilt yielded stronger associations between guilt and depressive symptoms (r = .33) than depressive symptom measures that did not (r = .21). Age, sex, and ethnicity (proportion of Whites to Asians) did not moderate the effects. Although these correlational data are ambiguous with respect to their causal interpretation, results suggest that shame should figure more prominently in understandings of the emotional underpinnings of depressive symptoms.

Psychological bulletin · meta-analysis · 355 citationsread the source →

Appearance-related teasing, body dissatisfaction, and disordered eating: A meta-analysis.

A meta-analysis was conducted to determine the relationship between appearance and weight-based teasing and three outcome measures: body dissatisfaction, restrictive eating, and bulimic behaviors. Four meta-analyses were conducted. Fifty effect sizes (N=10,618) resulted in a moderate effect size of .39 for the relationship between weight teasing and body dissatisfaction; 24 effect sizes (N=7190) resulted in an effect size of .32 for the relationship between appearance teasing and body dissatisfaction; 20 effect sizes (N=4792) resulted in an effect size of .35 for the relationship between weight teasing and dietary restraint; and 22 effect sizes (N=5091) resulted in an effect size of .36 for the relationship between weight teasing and bulimic behaviors. Significant moderators that emerged were teasing measure type, publication type, study type, age group, and gender. The findings offer further support for the inclusion of strategies in body image and eating disorders' prevention and intervention programs that focus on handling negative, appearance-related commentary.

Body image · meta-analysis · 203 citationsread the source →

Screening for breast cancer with mammography.

Background: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. Objectives: To assess the effect of screening for breast cancer with mammography on mortality and morbidity. Search methods: We searched PubMed (22 November 2012) and the World Health Organization's International Clinical Trials Registry Platform (22 November 2012). Selection criteria: Randomised trials comparing mammographic screening with no mammographic screening. Data collection and analysis: Two authors independently extracted data. Study authors were contacted for additional information. Main results: Eight eligible trials were identified. We excluded a trial because the randomisation had failed to produce comparable groups. The eligible trials included 600,000 women in the analyses in the age range 39 to 74 years. Three trials with adequate randomisation did not show a statistically significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on total cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).Total numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42), as were number of mastectomies (RR 1.20, 95% CI 1.08 to 1.32). The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data available in only two trials). Authors' conclusions: If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. To help ensure that the women are fully informed before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.

The Cochrane database of systematic reviews · meta-analysis · 418 citationsread the source →

Association of behaviour change techniques with effectiveness of dietary interventions among adults of retirement age: a systematic review and meta-analysis of randomised controlled trials.

Background: There is a need for development of more effective interventions to achieve healthy eating, enhance healthy ageing, and to reduce the risk of age-related diseases. The aim of this study was to identify the behaviour change techniques (BCTs) used in complex dietary behaviour change interventions and to explore the association between BCTs utilised and intervention effectiveness. Methods: We undertook a secondary analysis of data from a previous systematic review with meta-analysis of the effectiveness of dietary interventions among people of retirement age. BCTs were identified using the reliable CALO-RE taxonomy in studies reporting fruit and vegetable (F and V) consumption as outcomes. The mean difference in F and V intake between active and control arms was compared between studies in which the BCTs were identified versus those not using the BCTs. Random-effects meta-regression models were used to assess the association of interventions BCTs with F and V intakes. Results: Twenty-eight of the 40 BCTs listed in the CALO-RE taxonomy were identified in the 22 papers reviewed. Studies using the techniques 'barrier identification/problem solving' (93 g, 95% confidence interval (CI) 48 to 137 greater F and V intake), 'plan social support/social change' (78 g, 95%CI 24 to 132 greater F and V intake), 'goal setting (outcome)' (55 g 95%CI 7 to 103 greater F and V intake), 'use of follow-up prompts' (66 g, 95%CI 10 to 123 greater F and V intake) and 'provide feedback on performance' (39 g, 95%CI -2 to 81 greater F and V intake) were associated with greater effects of interventions on F and V consumption compared with studies not using these BCTs. The number of BCTs per study ranged from 2 to 16 (median = 6). Meta-regression showed that one additional BCT led to 8.3 g (95%CI 0.006 to 16.6 g) increase in F and V intake. Conclusions: Overall, this study has identified BCTs associated with effectiveness suggesting that these might be active ingredients of dietary interventions which will be effective in increasing F and V intake in older adults. For interventions targeting those in the peri-retirement age group, 'barrier identification/problem solving' and 'plan for social support/social change' may be particularly useful in increasing the effectiveness of dietary interventions.

BMC medicine · meta-analysis · 78 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

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

Clinical outcomes on B/F/TAF and dolutegravir-based regimens at 12 months following regimen switch: an observational cohort study.

Background: This retrospective observational study evaluated the clinical use and treatment outcomes in virologically suppressed people with HIV (PWH) switching to either bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)-based regimens (single- and multi-tablet formulations (STR and MTR)). Methods: We analyzed electronic medical and dispensing records from Trio Health HIV Research Network for treatment-experienced PWH ≥ 18 years suppressed (viral load [VL] < 200 copies/mL) at switch to B/F/TAF, DTG STR (DTG/3TC, DTG/RPV, DTG/3TC/ABC) or most common DTG MTRs with VL at 12 months (+/-3) since switch between April 2019 and December 2024. Univariate comparisons: chi-square or t-test; characteristics associated with virologic suppression at 12 months: multivariable logistic regression [LR], controlling for age, gender, race, baseline CD4 count, regimen, and adherence (proportion days covered [PDC] ≥ 80%). Results: Of 3141 PWH, 66% switched to B/F/TAF, 27% to DTG STR, and 7% to DTG MTRs. Baseline characteristics differed significantly between groups: B/F/TAF group had a higher proportion of males (81% vs. 67% DTG MTR) and Black individuals (40% vs. 31% DTG STR), while the DTG STR and MTR groups had higher proportions of PWH with cardiovascular disease (35% and 39% respectively vs. 32% on B/F/TAF) and eGFR < 60 mL/min/1.73 m² (18% and 22% respectively vs. 8% on B/F/TAF). At 12 months post switch, proportion of individuals with PDC ≥ 80% was higher in the DTG STR group (76%) compared to DTG MTR (67%) and B/F/TAF (69%) with similar virologic suppression across groups (98%, 98%, and 97% respectively). In multivariable LR, there was an association of White race, PDC ≥ 80%, and CD4 ≥ 200 cells/mm3 with greater probability of suppression at 12 months. Conclusions: Despite differences in baseline characteristics and regimen adherence between individuals switched to B/F/TAF, DTG STRs, and MTRs, both B/F/TAF and DTG-based regimens were associated with high rates of virologic suppression. This data strongly supports the inclusion of these simple and safe regimens as switch options in virologically suppressed PWH. Baseline differences in patient demographics and characteristics may have impacted the adherence on B/F/TAF compared to DTG STR, however virologic outcomes were preserved, demonstrating the forgiveness of B/F/TAF in populations potentially facing adherence challenges.

AIDS research and therapy · cohort or longitudinalread the source →

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

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

JAMA pediatrics · clinical trial · 75 citationsread the source →

Association of perpetrator relationship to abusive head trauma clinical outcomes.

The diagnosis of abusive head trauma (AHT) remains a significant public health problem with limited prevention success. Providing protection from further harm is often challenged by the difficulty in identifying the alleged perpetrator (AP) responsible for this pediatric trauma. The objective of this study was to evaluate demographic and clinical characteristics of children with AHT and the relationship between APs and their victims in a large, multi-site sample. Understanding the AHT risks from various caregivers may help to inform current prevention strategies. A retrospective review of all cases of AHT diagnosed by child protection teams (CPT) from 1/1/04 to 6/30/09 at four children's hospitals was conducted. Clinical characteristics of children with AHT injured by non-parental perpetrators (NPP) were compared to parental perpetrators (PP). There were 459 children with AHT; 313 (68%) had an identified AP. The majority of the 313 children were <1 year of age (76%), Caucasian (63%), male (58%), receiving public assistance (80%), and presented without a history of trauma (62%); mortality was 19%. Overall, APs were: father (53%), parent partner (22%), mother (8%), babysitter (8%), other adult caregiver (5%); NPP accounted for 39% of APs. NPPs were more likely to cause AHT in children ≥ 1 year (77% vs. 23%, p<0.001) compared to PP. Independent associations to NPP included: older child, absence of a history of trauma, retinal hemorrhages, and male perpetrator gender. While fathers were the most common AP in AHT victims, there is a significant association for increased risk of AHT by NPPs in the older child, who presents with retinal hemorrhages, in the hands of a male AP. Further enhancement of current prevention strategies to address AHT risks of non-parental adults who provide care to children, especially in the post-infancy age seems warranted.

Child abuse & neglect · cohort or longitudinal · 34 citationsread the source →

Experiential virtual scenarios with real-time monitoring (interreality) for the management of psychological stress: a block randomized controlled trial.

Background: The recent convergence between technology and medicine is offering innovative methods and tools for behavioral health care. Among these, an emerging approach is the use of virtual reality (VR) within exposure-based protocols for anxiety disorders, and in particular posttraumatic stress disorder. However, no systematically tested VR protocols are available for the management of psychological stress. Objective: Our goal was to evaluate the efficacy of a new technological paradigm, Interreality, for the management and prevention of psychological stress. The main feature of Interreality is a twofold link between the virtual and the real world achieved through experiential virtual scenarios (fully controlled by the therapist, used to learn coping skills and improve self-efficacy) with real-time monitoring and support (identifying critical situations and assessing clinical change) using advanced technologies (virtual worlds, wearable biosensors, and smartphones). Methods: The study was designed as a block randomized controlled trial involving 121 participants recruited from two different worker populations-teachers and nurses-that are highly exposed to psychological stress. Participants were a sample of teachers recruited in Milan (Block 1: n=61) and a sample of nurses recruited in Messina, Italy (Block 2: n=60). Participants within each block were randomly assigned to the (1) Experimental Group (EG): n=40; B1=20, B2=20, which received a 5-week treatment based on the Interreality paradigm; (2) Control Group (CG): n=42; B1=22, B2=20, which received a 5-week traditional stress management training based on cognitive behavioral therapy (CBT); and (3) the Wait-List group (WL): n=39, B1=19, B2=20, which was reassessed and compared with the two other groups 5 weeks after the initial evaluation. Results: Although both treatments were able to significantly reduce perceived stress better than WL, only EG participants reported a significant reduction (EG=12% vs. CG=0.5%) in chronic "trait" anxiety. A similar pattern was found for coping skills: both treatments were able to significantly increase most coping skills, but only EG participants reported a significant increase (EG=14% vs CG=0.3%) in the Emotional Support skill. Conclusions: Our findings provide initial evidence that the Interreality protocol yields better outcomes than the traditionally accepted gold standard for psychological stress treatment: CBT. Consequently, these findings constitute a sound foundation and rationale for the importance of continuing future research in technology-enhanced protocols for psychological stress management. Trial registration: ClinicalTrials.gov: NCT01683617; http://clinicaltrials.gov/show/NCT01683617 (Archived by WebCite at http://www.webcitation.org/6QnziHv3h).

Journal of medical Internet research · randomised controlled trial · 68 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 →

Prevalence and severity of college student bereavement examined in a randomly selected sample.

The authors used stratified random sampling to assess the prevalence and severity of bereavement in college undergraduates, providing an advance over findings that emerge from convenience sampling methods or from anecdotal observations. Prior research using convenience sampling indicated that 22% to 30% of college students are within 12 months of having experienced the death of a family member or friend. Using an ethnically diverse sample from a private, Midwestern university, 118 randomly selected students answered demographic and life experience questions and indicated whether a family member or friend had died within the last 24 months. Those who reported experiencing such a loss also completed the PG-13, a questionnaire used to assess prolonged grief disorder. Results indicated that 30% of the sample was within 12 months of experiencing a loss and 39% was within 24 months of experiencing a loss. Two of the students bereaved at 12 months (1.7% of the sample) were classified as having prolonged grief disorder. A limiting factor in this study is the homogeneity of the sample in terms of geographic location and religious preference. The authors concluded that a significant portion of college students are bereaved at any given time, confirmed previous estimates of the prevalence rate, and noted university assistance may be needed to prevent academic decline.

Death studies · randomised controlled trial · 46 citationsread the source →

Efficacy of a novel biphasic controlled-release methylphenidate formula in adults with attention-deficit/hyperactivity disorder: results of a double-blind, placebo-controlled crossover study.

Objective: To evaluate the efficacy and safety of a new biphasic multilayer-release (MLR) methylphenidate formulation in a double-blind, placebo-controlled crossover study of adults with attention-deficit/hyperactivity disorder (ADHD). Method: Adults 18 to 60 years of age with a DSM-IV diagnosis of ADHD entered a no-medication baseline week and were then randomly assigned to once-daily MLR methylphenidate or matching placebo. Patients were titrated to optimal effect over 1 to 3 weeks followed by 2 weeks of treatment on a stable dose. The same titration protocol was repeated with the alternate treatment. Clinical Global Impressions scale (CGI) and Conners' Adult ADHD Rating Scales (Self-rated, CAARS-S, and Observer-rated, CAARS-O) were collected at weekly clinic visits. The study was conducted between October 2003 and April 2004. Results: Fifty patients were randomly assigned to treatment, and 39 were analyzed in a per-protocol population (23 men, 16 women; mean age = 37.9 years). CGI-Improvement scores of subjects taking MLR methylphenidate were significantly improved compared with placebo (Global Improvement: 2.6 vs. 3.7; p = .0015). MLR methylphenidate produced improvements over placebo on the ADHD Index T scores of the CAARS-S (12.2 vs. 5.4 [change from baseline score]; p = .0083) and the CAARS-O (10.9 vs. 6.6 [change from baseline score]; p = .1404). The most frequent adverse events for MLR methylphenidate and placebo were headache (26% and 24%, respectively), anorexia (22% and 6%), insomnia (22% and 8%), nervousness (20% and 4%), and nausea (16% and 8%). There were no serious adverse events. Conclusions: Once-daily MLR methylphenidate produces significant improvements in ADHD symptoms and situational behavior in adult patients with ADHD, with a prolonged duration of effect and minimal side effects, thus having the potential to improve compliance and, therefore, treatment outcomes in routine clinical use.

The Journal of clinical psychiatry · randomised controlled trial · 37 citationsread the source →

The Edinburgh Postnatal Depression Scale for Fathers: A contribution to the validation for an Italian sample.

Objective: The aims of the study are to contribute to the validation of the Edinburgh Postnatal Depression Scale (EPDS; Cox et al., 1987) on a sample of Italian fathers (both men in the perinatal period than those with grown-up children) and to analyze its factorial structure. Methods: Four hundred thirty-six fathers participated; specifically, we used two samples. The first was composed of 334 fathers, 39 of which were depressed new fathers. We conducted explorative factor analysis and receiver operator characteristic analysis. The second sample was composed of 102 fathers, 22 of which were depressed new fathers. We conducted confirmative factor analysis on this second sample. We administered the Italian version of the EPDS (Carpiniello et al., 1997; Benvenuti et al., 1999), the Beck Depression Inventory-II (Ghisi et al., 2006) and the Center for Epidemiological Studies Depression Scale (Fava, 1983). Results: The test seems to detect not depression but a state of distress including depressive symptoms, anxiety and unhappiness. Results showed a two-factor structure, different from that of mothers. The optimal cutoff for Italian fathers is 12/13. Conclusions: The EPDS is a valid and reliable instrument, useful in the perinatal period for screening fathers at risk for perinatal distress and in need of psychological support.

General hospital psychiatry · cohort or longitudinal · 47 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 →

Emerging Adulthood and College‐aged Youth: An Overlooked Age for Weight‐related Behavior Change

Obesity is a major public health concern, and effective population-wide intervention strategies aimed at reducing obesity are needed. Although a growing body of literature has explored modifiable determinants of excess weight gain in adults and, to a lesser extent, in children, other important ages have been understudied. Though once considered to be an age of optimal health and well-being, the transition from adolescence to young adulthood is gaining recognition as an important time for health promotion and disease prevention. Not only is the presence of obesity and unhealthy lifestyle characteristics at this life stage associated with increased chronic disease risk, but this also may be a critical time during which young people establish independence and adopt lasting health behavior patterns. The objectives of this article are to: (i) describe emerging adulthood as a developmentally unique life stage, (ii) highlight epidemiologic evidence documenting adverse changes in diet, physical activity, and weight during this stage, (iii) discuss the influence of food and beverage marketing targeting emerging adults, and (iv) illustrate the need for health promotion and intervention efforts that could target young adults through settings such as postsecondary institutions. Over the past 50 years, major population-level demographic shifts including increases in postsecondary education and delays in marriage and childbearing have occurred. These shifts have opened the door for a period of “emerging adulthood,” typically defined as 18–25 years of age (1). This period is marked by important transitions such as leaving home and increasing autonomy in decision-making; however at the same time, adult responsibilities such as financial independence and residential and employment stability are still in flux. This period of emerging adulthood may be an important, yet overlooked, age for establishing long-term health behavior patterns. Several factors differentiate emerging adulthood from other life stages and have specific relevance to the formation of health behavior patterns, including identity development and shifting interpersonal influences. One defining characteristic of this life stage is the development of a self identity. Emerging adulthood is a time for the exploration of new ideologies and behaviors which allow individuals to express their individuality. Given previous research showing that identity (e.g., incorporating healthy lifestyle characteristics in the concept of one's self) is an important indicator of lasting health behavior change, emerging adulthood may be a particularly important time for establishing and intervening on long-term health behavior patterns (2,3). In addition, other psychosocial attributes associated with beneficial health behaviors (e.g., self-efficacy) develop or become established during this period of emerging adulthood (4), providing support for the unique importance of this life stage in long-term behavioral patterning. Emerging adulthood may also be a time for changing support systems and shifting interpersonal influences. Although the influence of parents and family is well established in the literature on childhood and, to a lesser extent, adolescent diet and physical activity patterns, little research has examined these issues among young adults. Young adults spend more leisure time alone compared to other age group (except retirees ≥55 years) (5) and are often assumed to be more disconnected from their family. However, some research suggests that closer relationships with parents (6,7) and siblings (8) may evolve as youth transition into college and adulthood (9,10). As youth become more independent, family and social network influences begin to shift and may serve different roles, as compared to that which they served in childhood and adolescence. Much additional research is needed to understand the evolving social influences in the emerging adult years and the extent to which this may influence health behavior patterns. Given the overall paucity of research in this area, more work is needed to understand better how the unique characteristics of emerging adulthood may contribute to establishing long-term behavioral patterns and the possible vulnerability of this life stage to various influences. The transition from adolescence to adulthood and the determinants of eating and physical activity is understudied. However, national trend data suggest that this is a risky period for the development of obesity, as well as unhealthy diet and physical activity practices. Weight gain. Research from national surveys and longitudinal cohorts has identified the transition between adolescence and adulthood as a period of increased risk for excess weight gain. Nationally representative cross-sectional survey data from the Behavioral Risk Factor Surveillance System indicated that from 1991 to 1998, the greatest magnitude of increase in obesity prevalence was among 18–29-year olds (increasing from 7.1 to 12.1%) (11). The prevalence of obesity among young adults more than doubled in the past 30 years. The most recent National Health and Nutrition Examination Survey (NHANES) data indicate that the prevalence has continued to increase since 1999 (ref. 12). Currently, 28.5% of 20–39-year olds are obese and 57.1% are overweight or obese (12). Nationally representative longitudinal cohort data from the National Longitudinal Study of Adolescent Health (Add Health) (13), assessing 9,795 adolescents (baseline age: 13–20 years in 1996), found that the 5-year incidence of obesity was nearly 13% (follow-up age: 19–26 years in 2001), whereas only 1.6% shifted from being obese to nonobese. In comparison to NHANES (1971–1974), the Add Health cohort showed substantial secular changes in the BMI distribution over time, particularly among individuals aged 19–26 years (13). In addition, findings from the CARDIA (Coronary Artery Risk Development in Young Adults) (14,15) longitudinal cohort illustrate both 5- and 10-year increases in weight among individuals 18–30 years of age at baseline (1985). Five-year weight gain was greater for men aged 18–24 years compared to men aged 25–30 years (14). Furthermore, the largest 10-year weight gains were seen among those in their early- to mid-twenties, as compared to those in their thirties (15). Physical activity. Although longitudinal data are limited, there is evidence of dramatic changes in lifestyle characteristics during this period. Cohort data from Add Health indicate that although most adolescents fail to meet national guidelines for physical activity (33.6%), even fewer meet these guidelines as young adults (12.7%) (16). In addition, findings from Project EAT (Eating Among Teens), a 5-year longitudinal cohort study of Minnesota adolescents, confirm such adverse changes in activity patterns during the transition from high school to young adulthood (17). Findings showed longitudinal changes in moderate to vigorous physical activity, particularly among girls (decreasing from 5.1 to 3.5 h/week aged from 16 to 20 years), and leisure time computer use, particularly among boys (increasing from 10.4 to 14.2 h/week aged from 16 to 20 years). Overall, many changes in physical activity patterns began during the transition from junior to senior high school and continued during the transition from high school to post-high school. One notable exception is moderate to vigorous physical activity among boys, which only began to decline during the transition after high school. Furthermore, a recent analysis of the National Health Interview survey data (18) indicated that age-related declines in physical activity are particularly pronounced between 15 and 18 years of age and continue through age 21. Physical activity has been shown to decline even further with specific life events typically following emerging adulthood (such as moving into a live-in relationship, getting married, and becoming a parent), but generally do not appear to continue to decline with age after mid-adulthood (30–64 years) (18). Thus health-promotion efforts to increase activity during emerging adulthood may be particularly important. Dietary intake. Research also suggests that declines in overall-diet quality may accompany these unfavorable shifts in activity patterns during the transition to adulthood (19,20). For example, fast food consumption has been associated with weight gain over time, and findings from national survey data indicate that fast food restaurant use is highest in young adulthood: 52% of 20–39 years reported eating fast food on one or both days of the Continuing Survey of Food Intakes by Individuals (1994–1996, 1998) (21). These data also indicate that soft drink intake is highest among 19–39-year olds compared to other age groups (22). In addition, NHANES data illustrate that a majority of young adults (aged 20–29 years) consume <1 serving/day of fruit (males 63%, females 59%) and vegetables (including potatoes, males 19%, females 20%) (23). Unfortunately, however, the collapsing of ages 19–39 years does not allow for an examination of the emerging adult period. Longitudinal findings from Project EAT also indicate adverse changes in dietary intake. For example, total fruit and vegetable intake decreased significantly (by >½ serving/day) during the 5-year transition period after high school (24). Add Health data indicate that fast food consumption markedly increased and consumption of breakfast decreased across a 5-year transition between adolescence and adulthood (25). The Bogalusa Heart Study (19), a longitudinal study of a biracial cohort following children >15 years into young adulthood, also showed a substantial decline in diet quality as individuals progressed through this transition. Findings indicate that individuals consumed less fruits/fruit juice and milk (19) and more sweetened beverages, salty snacks, and beef as young adults (19–28 years) than as children. Several studies have reported that despite changes in diet quality, there is substantial tracking in dietary intake between adolescence and young adulthood, as well as into later adulthood (20,26,27). Weight status also shows a high degree of tracking over time (28). Thus setting a “trajectory” for beneficial health behavior patterns and dietary intake during this time may be an important step toward initiating lasting healthy behaviors. Furthermore, a growing number of individuals are now becoming obese during adolescence and are exposed to a wide array of precursors to poor-diet quality and inactivity before the emerging adult years. For example, secular trends suggest declining rates of family meals and home food preparation (29), potentially leaving young adults without the skills to prepare foods and plan healthful meals on their own. Thus, challenges lie in reversing the effects of adverse adolescent exposures during the emerging adult years and promoting healthful long-term behavior patterns in all segments of the population. Dietary intake is influenced by a variety of factors, including individual, interpersonal, institutional, and macro-system influences. Although many of these influences are thought to be shared by a wide range of age groups, food and beverage marketing may be a particularly potent macro-level influence for emerging adults. The food, beverage and restaurant industries are estimated to have spent >$11 billion on advertising in 2004 alone (30). Young adults aged 18–24 years are a highly desirable market, particularly among fast food and soft drink companies. Marketing campaigns geared toward young adults, particularly males, have brought increased sales to fast food restaurant chains in the past decade (31,32,33,34). These campaigns have been specifically designed to increase product recognition, sales and brand loyalty among this group and have been widely promoted in young adult media markets. A number of these successful campaigns have targeted issues such as fast food late night dining and value pricing (32,35). For example, in launching its late night “Fourthmeal” campaign (with “Fourthmeal” marketed as “the meal between dinner and breakfast”), Taco Bell cites industry research in its press release indicating that nearly 50% of males aged 18–29 years are eating out after 7 pm (32). Industry research also suggests that young males spend well above market averages in these visits, averaging over $7.00 (ref. 36). To our knowledge, similar peer-reviewed evidence in the scientific literature is not available to confirm these trends. A number of these successful industry-driven campaigns have received recognition from the marketing and advertising community, for example, receiving EFFIE Awards (prestigious annual advertising awards) for their work in effectively targeting young adults. Honored campaigns include: • Hardee's. In 2001, industry research found that among its target markets Hardee's was “the most avoided restaurant in the fast food category” (31). Launching a major initiative targeting frequent fast food consumers, the company conducted “a segmentation analysis … to create a landscape from which we selected a more meaningful target for Hardee's. We called this target ‘Young Hungry Guys.’ This group is defined as young burger eaters (men 16–34) who want a more adult-like place to eat the burgers they love. This group seeks out big burgers as their food of choice, has the most growth potential for Hardee's and represent the heaviest usage in the fast food category” (31). With this, the Thickburger was introduced (providing ∼850–1,400 calories/burger). As a result, the company grew from the lowest to the highest ranked leading quick-service restaurant among young male fast food consumers (31). • Burger King. In February 2004 after significantly declining sales, Burger King refocused its efforts on its heaviest users, identified as males aged 16–34 years (34). To do so, they introduced the large-sized Angus Steak Burger. Describing its creative strategy, the marketing team states that “since the beginning of time, men have been eating large amounts of meat cooked over fires. For thousands of years, society has been wired to associate this kind of indulgence with power, pleasure and status. The problem is our culture is on an anti-indulgence craze the likes of which we have never seen before. Our strategy was to give our target permission to indulge in a great tasting burger and not apologize for it. And nothing gives them permission better than the affordable, deeply satisfying fire-grilled Angus Steak Burger…” (34). After increasing its market share among young men, this single-menu item subsequently accounted for 10% of sales dollars for Burger King. • Jack in the Box. After from the of a Jack in the that its was to create with the of the fast food young men, ages These were the fast food most began a marketing campaign on to to this including the campaign a of a media targeting males 18–24 years, Jack in the sales more than doubled from over billion in drink have also emerging adults as an important market For example, has major marketing campaigns targeting men, with the and In to promoting and advertising their through soft drink have to the of beverage by new targeting this age such as and (e.g., Thus, in we have little in the of public health to health among young adults, food and beverage marketing particularly from the fast food and soft drink have been targeting this age group over the past decade to establish brand loyalty and a of aged years are postsecondary In the development of health-promotion such may be well for emerging adult behaviors. However, that this life stage has been an of particularly in of obesity evidence is available to specific behaviors of college we have the which is from is a of research behaviors among other of such as those or obesity and weight Obesity is a major health among from the Health National Health an of indicated that the prevalence of overweight was including of these individuals who are obese Among the there has been recognition of the weight gain associated with college however, little research has explored this and its Several studies have shown that college is by substantial weight gain. the of gain an of with the of overweight or obese as as by the of the In females who home to to college have been shown to be to as to gain or more above their weight compared to females who not home indicating an important influence of some in the college on Furthermore, previous research suggests that this weight gain is specifically to important changes in body increased decreased Although some weight college has been estimated that gain weight during their years research following across years of that this weight gain is over time, with females on gaining and males gaining from to senior Although some growth may be to continued gains in particularly among males, many college youth may be on a of weight gain. 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For example, once research is available to postsecondary food strategies to healthy food pricing and be to intervention strategies in these However, although have scientific in recent years, important factors specific to this age group not be Emerging adults and college youth many new to healthy lifestyle characteristics (e.g., high challenges in time and targeting and strategies in these may be highly effective in obesity particularly in with research also to be and and by which we may be to target emerging adults who are not postsecondary institutions. Although research in other of health promotion suggests that emerging adults who are not postsecondary may represent particularly youth research to has examined health behaviors among this work in this is by the through we these Although and postsecondary may a to develop health-promotion strategies targeting large groups of there is a continued need to develop through which also be that we do not the research is also needed to the for health which may also for many individuals during the emerging adult years, particularly as begin to ideologies of autonomy are on with those of on responsibilities and to This growing of and may in that an important influence diet and physical behaviors. For example, such as may in to eat or to increasing for Emerging adults may begin to their as parents and be more to healthy and to a healthy lifestyle that they be the and ideologies of emerging adults, particularly in the specific of diet and physical activity, be in effective health-promotion and intervention may be successful in these to health In additional research is needed to understand how to health-promotion strategies to the of college and other emerging adults who are not in postsecondary institutions. Although substantial evidence that this is an important and period for adverse behavior change, little work to has to understand the modifiable determinants of factors among emerging adults, and intervention strategies have been and in this population. Given that a large of aged 18–24 years in postsecondary the setting a setting for health-promotion intervention efforts targeting this age The of

Obesity · 1316 citationsread the source →

Barriers to referral to inpatient palliative care units in Japan: a qualitative survey with content analysis.

Objectives: We investigated the barriers to referral to inpatient palliative care units (PCUs) through a qualitative study across various sources of information, including terminal cancer patients, their families, physicians, and nurses. Materials and methods: There were 63 participants, including 13 advanced cancer patients, 10 family members, 20 physicians, and 20 nurses in palliative care and acute care cancer settings from five regional cancer institutes in Japan. Semi-structured interviews were conducted regarding barriers to referral to PCU, and data were analyzed by content analysis method. Results: A total of 21 barriers were identified by content analysis. The leading barriers were (1) a negative image of PCUs by patients and families (n = 39), (2) delay of termination of anti-cancer treatment by physicians in the general wards (n = 24), (3) unwillingness to end anti-cancer treatment and denial of the fatal nature of the disease by patients and families (n = 22), (4) patient's wish to receive care from familiar physicians and nurses (n = 20), and (5) insufficient knowledge of PCUs by medical staff in general wards (n = 17). Conclusions: To correct these unfavorable images and misconceptions of PCUs, it is important to eliminate the negative image of PCUs from the general population, patients, families, and medical staffs. In addition, early introduction of palliative care options to patients and communication skills training regarding breaking bad news are relevant issues for a smooth transition from anti-cancer treatment to palliative care.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · cohort or longitudinal · 52 citationsread the source →

The generalized anxiety spectrum: prevalence, onset, course and outcome.

Background: Generalized anxiety disorder (GAD) is generally considered to be a chronic condition, waxing and waning in severity; however prospective investigation of the course of GAD in community samples is lacking. This study seeks to fill that gap, by identifying the whole spectrum of generalized anxiety syndromes, sub-typing them according to their duration and frequency of occurrence, and evaluating their long-term course and outcome in the community. Method: The prospective Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults (N = 591) (aged 20 years at first interview) by six interviews over a period of 20 years (1979-1999). GAD syndromes were defined by DSM-III symptom criteria without applying any exclusion criteria. A spectrum of generalized anxiety was defined by duration: 6 months (DSM-IV), 1 month (DSM-III), < or = 2 weeks (with weekly occurrence over one year), and anxiety symptoms. From 1978 (screening) to 1999 the annual presence of symptoms and treatment was assessed. Persistence of anxiety was defined by the almost daily presence of symptoms over the previous 12 months. Results: The annual incidence of DSM-III GAD increased considerably between the ages of 20 and 40. The average age of onset of symptoms was 15.6 years; in 75% of cases it occurred before the age of 20. 75 of 105 DSM-III GAD cases had at least one follow-up. At their individual last follow-up, 12 of those 75 subjects (16%) were re-diagnosed as having GAD, 22 (29%) manifested subthreshold syndromes or anxiety symptoms, while 39 cases, the majority, (52%) were symptom-free; 5 of the 12 re-diagnosed GAD cases were persistent (corresponding to 7% of all 75 initial GAD cases). In their twenties they were treated at some time in 6% of all years, but in their thirties this figure rose to 12%. At their individual last follow-up 26% of 6-month GAD subjects and 22% of 1-month GAD subjects were still being treated. Treated vs. non-treated subjects did not differ in terms of gender but did differ in severity, persistence and in comorbidity with bipolar-II disorder, social phobia, obsessive-compulsive syndromes and substance-use disorders. Limitations: Results are based on a relatively small sample and cannot be generalized to adults aged over 40 years. Conclusions: The course of DSM-III-defined GAD may not be chronic, as previously suggested, but mainly recurrent with intervening symptom-free periods of recovery in about half of cases. Over a period of 20 years there was more improvement than progression within the anxiety spectrum.

European archives of psychiatry and clinical neuroscience · 52 citationsread the source →

Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application

Clinically and experimentally, primary tumor formation and metastasis are distinct processes — locally growing tumors can progress without the development of metastases. This observation prompted the hypothesis that the molecular processes regulating tumorigenicity and metastasis are distinguishable and could be targeted therapeutically. During the process of transformation and subsequent progression to a malignant phenotype, both genetic and epigenetic alterations alter a cell's ability to perceive and respond to signals that regulate normal tissue homeostasis. A minority of tumorigenic cells accrue the full complement of alterations that enables them to disseminate from the primary tumor, survive insults from the immune system and biophysical forces, and respond to growth-promoting and/or inhibitory signals from the distant tissues and thrive there. Identification of genes and proteins that specifically inhibit the ability of cells to form metastases (e.g., metastasis suppressors) is providing new insights into the molecular mechanisms that regulate this complex process. This review will highlight: (a) the functional identification of metastasis suppressors, (b) the signaling cascades and cellular phenotypes which are controlled or modulated by metastasis suppressors, and (c) opportunities for translation and clinical trials that are based on mechanistic studies regarding metastasis suppressors. The identification of nm23, the first metastasis suppressor gene, provided functional evidence for the existence of genes that specifically regulate metastasis (1, 2). Subsequent to this initial discovery, researchers used in vivo studies to identify additional metastasis suppressors. These pioneering studies used an unbiased approach to identify such candidates by demonstrating that ectopic expression of the putative suppressor gene inhibited the development of spontaneous macroscopic metastases without significantly affecting primary tumor growth (3–5). Recently, this definition has been extended to include genes which specifically inhibit metastatic colonization (i.e., experimental metastasis formation using i.v. injection). The use of in vivo assays is required because in vitro assays are often of inadequate complexity to sufficiently model the entire process of metastasis. Furthermore, there are currently no in vitro models that allow the study of preferential growth within different target tissues. Table 1 lists the proteins which have bona fide metastasis suppressor activity in vivo (i.e., suppression of metastasis following ectopic expression into metastatic cell lines). It is interesting to note that metastasis suppressor activity for many of these genes would not have been predicted a priori based on their known cellular function(s). Furthermore, the unbiased, functional strategy identified novel genes for which no cellular function was known at the time of discovery. Metastasis suppressors can impart their suppressive activity at one or more of the steps in the metastatic cascade (6). For example, in vivo studies showed that metastatic cancer cells which express ectopic KISS1, JNKK1/MKK4, MKK6, MKK7, TXNIP, nm23-H1, or SSeCKS proteins could successfully disseminate and lodge at secondary sites, but are suppressed in their ability to colonize (i.e., form overt metastases) target tissues (7–12). After lodging at secondary sites, disseminated cells may die, persist as nondividing cells, or initiate growth (13). Such pivotal cellular decisions depend on both the expression of a specific gene profile as well as the activation status of key signaling pathways and the cumulative inputs of timing, amplitude, and duration of signaling responses. In short, cells expressing metastasis suppressors grow at primary sites, but fail to proliferate at secondary or metastatic sites, suggesting differential responses to site-specific external signals. Although the observation that a gene of interest functions as a metastasis suppressor is an excellent starting point, research is now focused on the biochemical and molecular mechanisms by which metastasis suppressor proteins execute their in vivo functions. Metastasis suppressors vary widely in their cellular locations and biochemical functions. Such proteins could display either extracellular (e.g., KISS1) or intracellular localization patterns. Within the cell, they are located in various cellular compartments, from the plasma membrane (e.g., cadherin, KAI1, CD44), cytoskeleton (e.g., RhoGDI2, gelsolin), cytosol (e.g., JNKK1/MKK4, nm23-H1, RKIP), mitochondria (e.g., caspase 8), and nucleus (e.g., BRMS1, CRSP3, TXNIP) (14–21).Cells respond to external stimuli by using a limited number of signaling pathways. Signaling specificity is achieved, at least in part, by combinatorial spatiotemporal activation of signaling proteins. The summation of these signaling events, enabled by a cell-specific gene expression profile, is a tailored, situation-appropriate response. During the process of transformation and progression to a malignant phenotype, both genetic and epigenetic alterations influence a cell's ability to perceive and respond to signals which regulate normal tissue homeostasis. The accumulation of such alterations during progressive rounds of cell division could endow a minority of tumorigenic cells with the ability to disseminate from the primary tumor. It is likely that as a result of these changes, metastatic cells are no longer bound by tissue-of-origin–derived signaling specificity and acquire the ability to modulate their responses to the changing environments encountered throughout the metastatic cascade. Current data supports a model in which ectopic expression of metastasis suppressor proteins may restore, at least in part, the endogenous signaling repertoire of earlier, more benign cellular generations, thereby blocking metastasis formation. In this light, metastasis formation can be viewed as the result of a cell's ability to respond to multiple growth milieus as opposed to being restricted to growth in the microenvironment of the tissue of origin. Defining pathways regulating metastatic growth requires the integration and interpretation of data obtained over experimental settings ranging from the molecular interactions of specific proteins, to communication between signaling networks within single cells, and ultimately cellular interactions among populations of cells that yield a particular disease state. This line of inquiry is a particular challenge in studies of metastasis regulation because of the complexity and diversity of downstream events that take place in metastasis formation. The majority of metastasis suppressors identified participate in highly conserved eukaryotic signal transduction pathways. Based on their known biochemical functions, we have divided the metastasis suppressors into four general signaling categories: cytoskeletal signaling, mitogenic pathways, stress-activated pathways, and survival pathways (Fig. 1). Although it may seem straightforward to place a metastatic suppressor into a linear signaling pathway, it is important to be mindful that these pathways are, in fact, dynamic networks that exist in series and parallel leading to crosstalk and interplay; phenomena known as emergent properties. The cytoskeleton is a dynamic structure that enables motility, deformability, and flexibility, while maintaining cellular architecture. For most nonhematopoietic cells, motility is an ancillary function; however, as a nonhematopoietic cell transitions from the benign to the invasive to the metastatic state, motility becomes an increasingly paramount ability. Without a dynamic actin cytoskeleton, a tumor cell would be incapable of intravasation or extravasation, and the cellular deformability is necessary to complete the metastatic cascade. Not surprisingly, several proteins involved in cellular motility have been implicated as metastasis suppressors. The Rho family of GTP-binding proteins, which include Rho, Rac, and Cdc42, are central players in the regulation of actin dynamics. The Rho-GTPase family consists of small 20 to 30 kDa monomeric GTP-binding proteins that bind GDP/GTP and hydrolyze GTP, leading to the activation of downstream effector molecules (22). In this signaling scheme, metastasis suppressors have been identified as upstream inhibitors of the Rho family (23), or downstream effectors (24). RhoGDIs inhibit Rho family members by impeding the dissociation of GDP from Rho proteins, thereby locking the Rho protein in its inactive state, preventing Rho proteins from interacting with effector targets, and/or sequestering Rho-GTPases in the cytosol (25). RHOGDI2 was shown to suppress experimental lung metastasis but not affect in vitro growth or in vivo tumorigenicity. The Src-suppressed C kinase substrate is a protein kinase C substrate with protein scaffolding properties that have been shown to be a negative regulator of Rho family members (26). Reexpression of Src-suppressed C kinase substrate suppressed secondary lung metastases in nude mice and increased cell-cell adhesion, yet had little effect on primary tumor growth (10). Furthermore, Src-suppressed C kinase substrate reexpression at physiologic levels suppresses podosome formation and correlates with the induction of normal actin cytoskeletal structures and cell morphology, but not with the inhibition of Src kinase activity in cells (26).The finding that RhoGDI displayed the ability to suppress metastasis suggested that the downstream molecules it inhibits may have metastasis-promoting activities. This hypothesis seems to hold true in that mice deficient in RhoC, a target of RhoGDI, displayed a marked decrease in metastasis potential (27). Furthermore, specific inhibition of a downstream effector of Rho, ROCK, decreased tumor cell invasiveness in vitro and reduced the dissemination of tumor cells implanted in the peritoneal cavity in vivo (28). RhoGDI2 has also been shown to regulate secreted growth factors such as endothelin 1 (ET-1), which contribute to metastasis and will be discussed below (29). This prometastasic activation of effectors downstream of the Rho family is not universal. Gelsolin is a downstream effector of Rac that regulates the length of actin via its filament severing and capping activities. Overexpression of gelsolin has been shown to inhibit metastasis in vivo (24). Counterintuitively, gelsolin is an indispensable protein of podosomes, which are thought to play an active role in tissue invasion and matrix remodeling through their regulation of matrix metalloprotease (MMP) activity (30, 31).Cell interactions with the extracellular matrix and with neighboring cells trigger numerous responses that have essential roles in the regulation of behavior and fate. Integrin-mediated cell adhesions provide bidirectional links between the microenvironment and the cytoskeleton. This crosstalk between a cell and its local environment occurs whether the cell is benign, malignant, or metastatic. In this light, the cytoskeleton serves as a conduit for the integration and processing of intracellular and extracellular information; however, changes in the cytoskeletal program during pathologic progression may alter how this information is integrated and processed. Two metastasis suppressors have been shown to have interactions with integrins. Connective tissue growth factor is a 38-kDa cysteine-rich heparin-binding protein which is a secreted growth factor that can bind to integrins on the cell surface (32). Ectopic expression of connective tissue growth factor inhibited metastatic colonization by lung cancer cells (33). In contrast, the KAI1 metastasis suppressor protein is a member of the tetraspanin family of proteins and has been shown to interact with a myriad of cell surface proteins including other tetraspans (i.e., CD9, CD81), integrins β1 and β2, MHCII growth factor receptors, and intracellular signaling proteins such as protein kinase C (34). It has been hypothesized that KAI1 modulates integrin and growth receptor signaling by accelerating the rate of internalization via a protein kinase C–dependent pathway, thereby modulating cell adhesion and cell migration (34). Furthermore, KAI1 has been shown to decrease the integrin- and ligand-induced activation of the receptor tyrosine kinase c-Met, and independently decreases integrin-induced Src activation. Both c-Met and Src are thought to be required for invasion (35). A final observation with respect to the involvement of integrins in metastasis suppressor activity concerns caspase-8 function. Loss of caspase-8 in neuroblastoma cells leads to increased survival and an increased incidence of metastasis. The induction of caspase-8-mediated apoptosis seems to be due to unligated integrins because decreased expression of unligated integrins enhanced cell survival (36–38).Claudin-4 is a component of tight junctions which form the most apical component of intercellular junctional complexes where they establish cell polarity and cellular functions such as permeability (39, 40). These intercellular junctions not only carry out adhesive functions but also contain crucial components of signaling pathways that regulate epithelial proliferation and differentiation. Complementary in vitro and in vivo studies identified claudin-4 as an inhibitor of invasion and metastasis in pancreatic cancer cells and a target of transforming growth factor-β and extracellular signal-regulated kinase (ERK) signaling (40, 41).RECK, a membrane glycoprotein that encodes a GPI-anchored glycoprotein harboring three protease inhibitor–like domains, has been shown to negatively regulate MMP-2, MMP-9, and MT1-MMPs in vitro, suggesting that it is an important regulator of extracellular matrix remodeling. Furthermore, RECK-null mouse embryos displayed markedly elevated MMP activity. Interestingly, RECK is down-regulated by Ras signaling, a commonly altered pathway in many malignant cells (42).The role of some putative metastasis suppressors is more complex. There are several of a protein as a metastasis suppressor in one model and a potential tumor suppressor in For example, is a glycoprotein that responses of the cell to their cellular Although it has been in the that of has been shown to suppress metastasis in the cancer system other have that may metastatic activity a of the invasion and of and has been suggested to be a is not the only protein to have an role in metastasis. are a of that cell-cell adhesion in various tissues in a function is controlled by its Both and seem to inhibit cell migration and the in vivo metastatic potential of cells other studies have suggested that may invasion It is important to note that cancer cells of tissue used in several of the The tissue specificity of metastasis suppressor function is with the and integration information through signal transduction is a secreted protein and is hypothesized to processing by The are known as or not be secreted in to its metastatic suppressor activity has yet to be at the identification of upstream of identified a metastasis suppressor activity for CRSP3, a of the receptor of cells with suppressed metastasis and was with an of providing a potential between these and metastasis regulation stress-activated protein and pathways in parallel to the protein kinase In to the of with and have been with cell and apoptosis in to and changes, and growth factor specifically either or The protein is a kinase that has been shown to and the and in to a of extracellular can function as a metastasis suppressor in both and cancer Complementary in vitro and in vivo assays showed that the kinase activity of is required for the suppression of overt metastases and is to Subsequent studies identified metastasis suppressor for and in and interest is the finding that in cancer signals through the of the pathway to suppress metastasis in cancer signals through the of the pathway to suppress metastasis In vivo studies that both and suppress the formation of overt metastases by the ability of disseminated cells to colonize the lung identification of a metastasis suppressor function for protein also or protein mechanistic between the to cellular and of metastatic ability. is an endogenous inhibitor of a component of a system that has been implicated in cancer progression The levels of in cells are by endogenous as the in to to and including The primary of cellular is the is through of membrane or in to to with molecular or thereby highly or a of events that result in cell and of metastasis. this and ectopic expression of modulates these events to suppress metastasis formation is currently pathway is by mitogenic such as growth growth or which receptor tyrosine and The of mitogenic factors to cell surface a series of that with the activation of various factors and proteins and regulation may at in this is through both the of a kinase for a as well as protein expression levels of regulation are by intracellular localization and with scaffolding or proteins. These events may be important for regulating metastatic In the of metastasis the protein with the by to and the kinase suppressor of Ras a protein that has a role in the regulation of Ras activity and activation of the pathway has been shown to regulate signaling, suggesting that metastasis suppression activity may be by the inhibition of signaling kinase inhibitor protein was identified as a metastasis suppressor gene in functions as a negative upstream regulator of signaling and kinase interact with at sites, and of either inhibits of the Both be in to inhibition may suppress metastasis by of metastasis suppressors, and are with the signaling The signaling pathway a key role in many of cell survival and 1 are of an inhibitory and a and signals from various cellular proteins such as and an integration for the activation of and downstream to a that a of downstream targets, the and also regulates a of target proteins that cell proliferation and survival The levels of are and several particular interest is the which to signaling metastasis suppressor protein has been with the of cells showed decreases in endogenous levels of (i.e., of This finding is with a model in which changes in signaling the ability of disseminated cells to survive in the and grow at secondary In contrast, expression of the metastasis suppressor is modulated by clinical is the finding that expression correlates significantly with in both and cancer and that the in as a significantly of and cancer survival either evidence from the cell molecular and genetic studies that the metastatic process requires many steps to The of only one in this of in vivo events the process and a This enabled the identification of metastasis suppressor proteins. the of the however, the is not as straightforward because which signaling in the metastatic process are is not have insights into this by metastatic colonization as the in the metastatic cascade that is from a of A clinical will this to of invasive are with metastatic and (i.e., These that many with invasive disease disseminated cancer cells at preventing the of disseminated cells into the metastatic (i.e., the process of would a for cancer This approach more at preventing cancer cells from the primary tumor for the that this process has place the is first with In where this process has not yet local such as and can the the for additional at the an for metastasis preventing the growth of disseminated tumor cells into an overt clinical metastasis or the metastases. the approach not the in hold disease in providing increased of the with both of these is the identification of at for disease that they may at metastatic that can be to this include both tumor as well as molecular of the primary tumor to the development of metastasis a it has been to of the disseminated tumor cells at a secondary as the and as being distinct from that at the primary with to the tumor tumor cells distinct in the primary and secondary sites, and these interactions can or include locally and as well as cell-cell interactions in environments such as the and these with the of metastasis suppressor protein one can to there are to metastasis suppressor proteins. The of these on of the leading to of metastasis suppressor protein For example, the gene is it that of a normal gene would be the In contrast, was secondary to suppressed for example, at the endogenous gene seem we will provide an of approach from that have the of the first identified metastasis a of metastasis suppressor protein function in disseminated tumor In many cancer is with metastasis that occurs A study used gene to and whether this would cancer metastasis in an model of this A cell line of metastatic potential to the by in vivo was used to the of reexpression on metastasis. of these cells, an expressing was This in expression of the gene in most of the tumor cells in in and was with a in the number of metastases and a of This of of the of induction as a approach The of this approach are also to the of which is a disease that the In with gene is and the with i.v. development from the also the of the metastasis gene but the approach reexpression of the endogenous gene as a the was to a that would expression and allow at to on at of the This of would a that is and with an and have been to For example, was to expression in a cell line elevated the expression of cells out an of the the that elevated the expression of metastatic cell is a used at in and as well as at in cancer Furthermore, elevated expression and inhibited colonization and this effect was through The effect of on the of expression was in an in vivo model system for the of metastases the cell line to lung mice to or in of mice to of The number of metastases mouse was reduced by to on the metastases in reduced by to in the inhibited the number and of metastases in this This in metastases was with reexpression in the lung a of in with metastases and and tumors is of gene expression alterations with of metastasis suppressor protein A would be that functional of metastasis suppressor proteins is with gene expression changes, and cellular Recently, this with the that of metastasis suppressor proteins is with the of was used to a novel These studies focused on RhoGDI2, a suppressor of metastasis in an model of cancer metastasis reduced expression was to be with decreased survival for with cancer that RhoGDI2 as a on the expression of genes and to identify such genes in a of the lung metastasis model and primary clinical of RhoGDI2 protein is currently they to proteins or pathways downstream of These genes required to be following the of RhoGDI2 protein from the cells, and be of being inhibited by or to the changes in gene expression following of RhoGDI2 expression in metastatic cells, several proteins including This finding was by the between RhoGDI2 expression levels and of in tumor (29). Furthermore, inhibition of the endothelin with of the endothelin receptor such as to metastatic suppression in cells deficient for RhoGDI2 (29). The endothelin has been shown to regulate tissue cell cell and remodeling also has on cells in the and lung important of cancer metastasis In to such may growth factor and factor and growth factor one in the proliferation of and cells tumor also a role for in metastases from and and supports a model in which cells, in providing a microenvironment for these that trials with endothelin may be for with cancer following of the primary The for its use in the from the effect these have had in preventing experimental metastasis. These however, not the of these in metastatic but this is yet to be The molecular shown between and RhoGDI2 is because of endothelin receptor A such as with clinical In fact, in with in a the most events and that is well In this there was no at to in other of was not by this the of this effector approach to other metastasis suppressor proteins could identify potential novel for in other for and during the of key of this

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Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. 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J Physiol | ISI | Google and modulation of sympathetic nerve activity to muscle in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and is not associated with of the exercise reflex in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google C, and Y. The effect of on the circadian control of human core body temperature is Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of adenosine receptors in the does not affect the in awake rats. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google JK, A, and circadian and during two Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and sympathetic nerve and heart rate spectral effects of lower body negative pressure. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Francis Johnson and of heart failure after myocardial in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google A, and of lower body pressure on muscle sympathetic nerve activity response to Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and Adenosine initial depression of in the rat in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google R, and and circadian phase in a diurnal the Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Johnson alterations and autonomic in an model of Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google MA, and The interaction of the Bainbridge and in the conscious Res | ISI | Google A, and handgrip exercise arterial control of sympathetic in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve regulation to is in rats. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and in heart rate variability. J Physiol | ISI | Google and function and cardiovascular interactions and Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and interval variability in isolated working rat hearts at various conditions and Res | PubMed | Google A, A, and and autonomic of in patients with mild Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Malpas SC. Neural on cardiovascular and Am J Physiol Heart Physiol 2002.Link | ISI | Google and thermoregulation in and rats in a Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and effects on reflex responses to mental stress in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and reflex during orthostatic in Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and and responses to and are in rats. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and and in a by cycle. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of humoral heart rate regulation in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Armour and within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol 285: 2003.Link | ISI | Google Rentero N, A, and McAllen of cardiac vagal motoneurons in rat nucleus ambiguus. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and modulate control of heart rate in conscious rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and central actions of angiotensin to increase arterial pressure. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulate control of renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulation of cardiovascular and autonomic function in role of Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Inhibition of sympathetic responses at birth in by of the paraventricular Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and JP. pattern of during acute and chronic in conscious adult rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Armour and of chronic cardiac on of canine intracardiac neurons in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and levels and circadian rhythm of activity in the a model of Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve response of suprachiasmatic nucleus and Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google

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

Plastic Surgery Faces the Web: Analysis of the Popular Social Media for Plastic Surgeons.

Background: The use of social media is growing tremendously along with its impact on the practice of plastic surgery, for better or for worse. Patients are increasingly using social media to obtain information about either the procedure or the surgeon. Objectives: The aims of this study were to examine social media posting regarding plastic surgery and to analyze successful online communication methods of the plastic surgeons with the public. Methods: A prospective analysis of 3 popular, global social media networks was performed, using the English language key phrases "plastic surgery" and "#plastic_surgery." Three hundred posts related to plastic surgery published on Instagram, YouTube, and Facebook in November 2017 were assessed by the following parameters: author identity, subject (self-promotion, educational, commercial, and personal posts), "social media currency" (likes, shares, comments, and views), and if special effects (videos, photos, etc.) or viral subjects such as reality stars or shaming were utilized. Results: Sixty-three percentage of the posts on Instagram originated with plastic surgeons, compared with 18% on Facebook and only 13% on YouTube (P < 0.01); together, the plastic surgeons' posts comprise 31% of the total posts, whereas 49% of posts published by commercial companies (P < 0.01). Most of the posts on Instagram were self-promotional (83%), in comparison to Facebook (29%) or YouTube (6%); P < 0.01. YouTube posts are more personal in nature compared with Instagram and Facebook [39%, 7%, 9%, respectively (P < 0.01)]. Educational content in the posts accounts for only 16% of them, P < 0.01. Shaming is seen in 21% of the posts, especially in Facebook (39%), and mainly related to famous public figures (25%); P < 0.05. Celebrity endorsed posts received more attention in every aspect of social media currency (likes, comments, shares, and views). The use of images of women attracts attention and is widely used in social media posts of plastic surgery (68%). Posts that chose to include videos (22%) are generously rewarded. Online shaming also attracts attention, mostly found in Facebook (39%), and mainly of a public figure (25%). The 10 most powerful attention drawing motives were jokes, attractive female plastic surgeons, celebrities, personal stories, provocative surgeries, videos or photos of surgeries, sex, shaming, and patient education. Conclusion: Social media have become an important tool for self-promotion and a means to providing better customer service. This trend applies to the plastic surgeon as well. The study's main insights were to use Instagram, personal stories, educational post, videos and other unique inputs, and involve celebrities in the posts. In general, it would be wise to invest and understand these communication platforms, as they have become the path to dominate the field.

Plastic and reconstructive surgery. Global open · 48 citationsread the source →

Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study.

Background: Identification of patients at high risk of treatment-resistant schizophrenia at the time of schizophrenia diagnosis would be of great clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to non-clozapine antipsychotics. However, little is known about predictors of treatment resistance in this patient population. We used a treatment-based proxy for treatment-resistant schizophrenia to identify candidate predictors of treatment resistance at first hospital contact with a schizophrenia diagnosis. Methods: In this population-based cohort study, we obtained Danish national registry data for all adult patients (≥18 years) with incident schizophrenia diagnosed between Jan 1, 1996, and Dec 31, 2006, and followed up until Dec 31, 2010. Our main proxy definition of treatment-resistant schizophrenia was the earliest instance of either clozapine initiation or hospital admission for schizophrenia after having had two periods of different antipsychotic monotherapy. We did multivariable Cox proportional hazards regression analysis to estimate the association between baseline candidate predictors and treatment resistance. Findings: 8624 patients fulfilled the criteria for inclusion. In multivariable complete-case analyses, 1703 (21%) of 8044 patients fulfilled the main proxy definition of treatment-resistant schizophrenia during a median follow-up of 9·1 years (IQR 6·3-11·9). Younger age (hazard ratio 0·96 [95% CI 0·95-0·97]), living in a less urban area (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia. Interpretation: Our study identifies several candidate predictors that could potentially be included in future prediction models for treatment-resistant schizophrenia. Notably, established risk factors for schizophrenia did not predict treatment resistance, suggesting that treatment-resistant disease might be a distinct subtype of schizophrenia and not merely a more severe form. Funding: European Community's Seventh Framework Programme.

The lancet. Psychiatry · 127 citationsread the source →

Measuring education in the context of health inequalities

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

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

On Weight and Waiting: Delay Discounting in Anorexia Nervosa Pretreatment and Posttreatment.

Background: Individuals with anorexia nervosa (AN) override the drive to eat, forgoing immediate rewards in favor of longer-term goals. We examined delay discounting and its neural correlates in AN before and after treatment to test a potential mechanism of illness persistence. Methods: Inpatients with AN (n = 59) and healthy control subjects (HC, n = 39) performed a delay discounting task at two time points. A subset (n = 30 AN, n = 22 HC) participated in functional magnetic resonance imaging scanning during the task. The task consisted of a range of monetary choices with variable delay times, yielding individual discount rates-the rate by which money loses value over time. Results: Before treatment, the AN group showed a preference for delayed over earlier rewards (i.e., less steep discount rates) compared with HC; after weight restoration, AN did not differ from HC. Underweight AN showed slower response times for earlier versus delayed choices; this reversed with treatment. Underweight AN showed abnormal neural activity in striatum and dorsal anterior cingulate; normalization of behavior was associated with increased activation in reward regions (striatum and dorsal anterior cingulate) and decision-making regions (dorsolateral prefrontal cortex and parietal cortex). Conclusions: The undernourished state of AN may amplify the tendency to forgo immediate rewards in favor of longer-term goals. The results suggest that behavior that looks phenotypically like excessive self-control does not correspond with enhanced prefrontal recruitment. Rather, the results point to alterations in cingulostriatal circuitry that offer new insights on the potential role of abnormalities in decision-making neural systems in the perpetuation of AN.

Biological psychiatry · 121 citationsread the source →

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

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

JAMA network open · 48 citationsread the source →

Factors associated with mental health outcomes in a Muslim community following the Christchurch terrorist attack.

Background: On 15 March 2019, a white supremacist terrorist attacked two mosques in Christchurch, New Zealand. Fifty-one people were killed and another 40 sustained non-fatal gunshot injuries. Aims: To examine the mental health of the Muslim community, and individual and exposure-related factors associated with mental health outcomes. Method: This is the baseline analysis of a longitudinal study of adults from the Muslim community interviewed 11-32 months after the shootings. It included a diagnostic interview (MINI), measures of sociodemographic factors, prior mental health, prior traumatic events, exposure in the attacks, discrimination, life stressors, social support and religious coping. Logistic regression models examined associations with mental health outcomes. Results: The sample comprised 189 participants (mean age 41 (s.d. = 13); 60% female), and included: bereaved, 17% (n = 32); injured survivors 12% (n = 22); non-injured survivors, 19% (n = 36); family members of survivors, 35% (n = 67); and community members without the above exposures, 39% (n = 74). Overall, 61% had at least one mental disorder since the attacks. Those bereaved (P < 0.01, odds ratio 4.28, 95% CI 1.75-10.49) and survivors, whether injured (P < 0.001, odds ratio 18.08, 95% CI 4.70-69.60) or not (P < 0.01, odds ratio 5.26, 95% CI 1.99-13.89), had greater odds of post-traumatic stress disorder. Those bereaved (P < 0.001, odds ratio 5.79, 95% CI 2.49-13.46) or injured (P = 0.04, odds ratio 4.43, 95% CI 1.07-18.28) had greater odds of depression. Conclusions: Despite unique features of this attack on a Muslim population, findings accord with previous studies. They suggest generalisability of psychopathology after terror attacks, and that being bereaved or directly experiencing such events is associated with adverse mental health outcomes. Trial registration number: The study is registered on the Australian NZ Clinical Trials Registry (ACTRN12620000909921).

BJPsych open · 3 citationsread the source →

Health of men, women, and children in post-trafficking services in Cambodia, Thailand, and Vietnam: an observational cross-sectional study.

Background: Trafficking is a crime of global proportions involving extreme forms of exploitation and abuse. Yet little research has been done of the health risks and morbidity patterns for men, women, and children trafficked for various forms of forced labour. Methods: We carried out face-to-face interviews with a consecutive sample of individuals entering 15 post-trafficking services in Cambodia, Thailand, and Vietnam. We asked participants about living and working conditions, experience of violence, and health outcomes. We measured symptoms of anxiety and depression with the Hopkins Symptoms Checklist and post-traumatic stress disorder with the Harvard Trauma Questionnaire, and used adjusted logistic regression models to estimate the effect of trafficking on these mental health outcomes, controlling for age, sector of exploitation, and time in trafficking. Findings: We interviewed 1102 people, of whom 1015 reached work destinations. Participants worked in various sectors including sex work (329 [32%]), fishing (275 [27%]), and factories (136 [13%]). 481 (48%) of 1015 experienced physical violence, sexual violence, or both, with 198 (35%) of 566 women and girls reporting sexual violence. 478 (47%) of 1015 participants were threatened and 198 (20%) were locked in a room. 685 (70%) of 985 who had data available worked 7 days per week and 296 (30%) of 989 worked at least 11 hours per day. 222 (22%) of 983 had a serious injury at work. 61·2% (95% CI 58·2-64·2) of participants reported symptom of depression, 42·8% (39·8-45·9) reported symptoms of anxiety, and 38·9% (36·0-42·0) reported symptoms of post-traumatic stress disorder. 5·2% (4·0-6·8) had attempted suicide in the past month. Participants who experienced extremely excessive overtime at work, restricted freedom, bad living conditions, threats, or severe violence were more likely to report symptoms of depression, anxiety, and post-traumatic stress disorder. Interpretation: This is the first health study of a large and diverse sample of men, women, and child survivors of trafficking for various forms of exploitation. Violence and unsafe working conditions were common and psychological morbidity was associated with severity of abuse. Survivors of trafficking need access to health care, especially mental health care. Funding: Anesvad Foundation and International Organization for Migration International Development Fund.

The Lancet. Global health · 87 citationsread the source →

Potential impact of midwives in preventing and reducing maternal and neonatal mortality and stillbirths: a Lives Saved Tool modelling study.

Background: Strengthening the capacity of midwives to deliver high-quality maternal and newborn health services has been highlighted as a priority by global health organisations. To support low-income and middle-income countries (LMICs) in their decisions about investments in health, we aimed to estimate the potential impact of midwives on reducing maternal and neonatal deaths and stillbirths under several intervention coverage scenarios. Methods: For this modelling study, we used the Lives Saved Tool to estimate the number of deaths that would be averted by 2035, if coverage of health interventions that can be delivered by professional midwives were scaled up in 88 countries that account for the vast majority of the world's maternal and neonatal deaths and stillbirths. We used four scenarios to assess the effects of increasing the coverage of midwife-delivered interventions by a modest amount (10% every 5 years), a substantial amount (25% every 5 years), and the amount needed to reach universal coverage of these interventions (ie, to 95%); and the effects of coverage attrition (a 2% decrease every 5 years). We grouped countries in three equal-sized groups according to their Human Development Index. Group A included the 30 countries with the lowest HDI, group B included 29 low-to-medium HDI countries, and group C included 29 medium-to-high HDI countries. Findings: We estimated that, relative to current coverage, a substantial increase in coverage of midwife-delivered interventions could avert 41% of maternal deaths, 39% of neonatal deaths, and 26% of stillbirths, equating to 2·2 million deaths averted per year by 2035. Even a modest increase in coverage of midwife-delivered interventions could avert 22% of maternal deaths, 23% of neonatal deaths, and 14% of stillbirths, equating to 1·3 million deaths averted per year by 2035. Relative to current coverage, universal coverage of midwife-delivered interventions would avert 67% of maternal deaths, 64% of neonatal deaths, and 65% of stillbirths, allowing 4·3 million lives to be saved annually by 2035. These deaths averted would be particularly concentrated in the group B countries, which currently account for a large proportion of the world's population and have high mortality rates compared with group C. Interpretation: Midwives can help to substantially reduce maternal and neonatal mortality and stillbirths in LMICs. However, to realise this potential, midwives need to have skills and competencies in line with recommendations from the International Confederation of Midwives, to be part of a team of sufficient size and skill, and to work in an enabling environment. Our study highlights the potential of midwives but there are many challenges to the achievement of this potential. If increased coverage of midwife-delivered interventions can be achieved, health systems will be better able to provide effective coverage of essential sexual, reproductive, maternal, newborn, and adolescent health interventions. Funding: New Venture Fund.

The Lancet. Global health · 263 citationsread the source →

The importance of mindfulness in psychosocial distress and quality of life in dermatology patients.

Background: Mindfulness, defined as purposively and nonjudgementally paying attention in the present moment, could be used within psychosocial interventions to reduce the distress associated with social anxiety and avoidance found in many skin conditions. However, little is known about the relationship between naturally occurring levels of mindfulness and distress in dermatology patients. Objectives: To examine the relationship between mindfulness and psychosocial distress in a dermatological population. It was hypothesized that higher levels of mindfulness would be associated with lower levels of social anxiety, anxiety, depression and skin shame, and with better quality of life. Methods: Adult dermatology outpatients (n = 120) from one hospital completed items assessing subjective severity, skin shame, fear of negative evaluation, anxiety and depression, quality of life, and levels of mindfulness. Results: Considering depression, 14% reported mild, 5% moderate and 2·5% severe symptoms. For anxiety, 22% reported mild, 23% moderate and 6% severe symptoms. In addition, 33·4% reported clinically significant social anxiety. After controlling for subjective severity, mindfulness explained an additional 19% of the variance in depression, 39% in anxiety, 41% in social anxiety, 13% in skin shame and 6% in dermatological quality of life. One specific facet of mindfulness (acting with awareness) was found to be the most consistent predictor of distress. Conclusions: The findings indicate that higher levels of mindfulness are associated with lower distress. This suggests that facilitating mindfulness may be helpful in reducing distress in dermatology patients, and the use of mindfulness techniques warrants further investigation.

The British journal of dermatology · 40 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

Urinary Microbiome and Cytokine Levels in Women With Interstitial Cystitis.

Objective: To investigate differences in the urinary microbiome and cytokine levels between women with and without interstitial cystitis and to correlate differences with scores on standardized symptom severity scales and depression and anxiety screening tools. Methods: Our cross-sectional study compared women presenting to a pelvic floor clinic and diagnosed with interstitial cystitis over a 6-month period with age-matched women in a control group from the same institution. Participants provided a catheterized urine sample and completed symptom severity, quality-of-life, depression, and anxiety screening questionnaires. Urinary microbiomes generated through bacterial ribosomal RNA sequencing and cytokine levels were analyzed using a standard immunoassay. Nonparametric analyses were used for all comparisons. Results: Participants with interstitial cystitis reported more disability, bothersome urinary symptoms, genitourinary pain, and sexual dysfunction and scored higher on depression and anxiety screens compared with women in the control group. The urine of participants with interstitial cystitis contained fewer distinct operational taxonomic units (2 [median range 2-7, interquartile range 1] compared with 3.5 [median, range 2-22, interquartile range 5.25], P=.015) and was less likely to contain Lactobacillus acidophilus (1/14 [7%] compared with 7/18 [39%], P=.05) compared with women in the control group. L acidophilus was associated with less severe scores on the Interstitial Cystitis Symptoms Index (1 [median, range 0-17, interquartile range 5] compared with 10 [median, range 0-14, interquartile range 11], P=.005) and the Genitourinary Pain Index (0 [median, range 0-42, interquartile range 22] compared with 22.5 [median, range 0-40, interquartile range 28], P=.03). Participants with interstitial cystitis demonstrated higher levels of macrophage-derived chemokine (13.32 [median, range 8.93-17.05, interquartile range 15.86] compared with 0 [median, range 8.93-22.67, interquartile range 10.35], P=.037) and interleukin-4 (1.95 [median, range 1.31-997, interquartile range 11.84] compared with 1.17 [median, range 0.44-3.26, interquartile range 1.51], P=.029). There was a positive correlation between interleukin-4 and more severe scores on the Interstitial Cystitis Symptoms Index (r=0.406, P=.013). No associations between the presence of lactobacillus species and cytokine levels were observed. Conclusion: The urinary microbiome of participants with interstitial cystitis was less diverse, less likely to contain Lactobacillus species, and associated with higher levels of proinflammatory cytokines. It is unknown whether this represents causality and whether the effect of alterations to the urinary microbiome is mediated through an inflammatory response.

Obstetrics and gynecology · 93 citationsread the source →

Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding: National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation: For the Chinese translation of the abstract see Supplementary Materials section.

The lancet. Psychiatry · 591 citationsread the source →

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

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

Frontiers in Psychology · 12 citationsread the source →

Controlled cohort evaluation of the LiveLighter mass media campaign's impact on adults' reported consumption of sugar-sweetened beverages.

Objective: To evaluate the LiveLighter 'Sugary Drinks' campaign impact on awareness, knowledge and sugar-sweetened beverage (SSB) consumption. Design: Cohort study with population surveys undertaken in intervention and comparison states at baseline (n=900 each), with 78% retention at follow-up (intervention: n=673; comparison: n=730). Analyses tested interactions by state (intervention, comparison) and time (baseline, follow-up). Setting and participants: Adults aged 25-49 years residing in the Australian states of Victoria and South Australia. Intervention: The 6-week mass media campaign ran in Victoria in October/November 2015. It focused on the contribution of SSBs to the development of visceral 'toxic fat', graphically depicted around vital organs, and ultimately serious disease. Paid television advertising was complemented by radio, cinema, online and social media advertising, and stakeholder and community engagement. Primary outcome measure: Self-reported consumption of SSBs, artificially sweetened drinks and water. Secondary outcome measures: Campaign recall and recognition; knowledge of the health effects of overweight and SSB consumption; perceived impact of SSB consumption on body weight and of reduced consumption on health. Results: A significant reduction in frequent SSB consumption was observed in the intervention state (intervention: 31% compared with 22%, comparison: 30% compared with 29%; interaction p<0.01). This was accompanied by evidence of increased water consumption (intervention: 66% compared with 73%; comparison: 68% compared with 67%; interaction p=0.09) among overweight/obese SSB consumers. This group also showed increased knowledge of the health effects of SSB consumption (intervention: 60% compared with 71%, comparison: 63% compared with 59%; interaction p<0.05) and some evidence of increased prevalence of self-referent thoughts about SSB's relationship to weight gain (intervention: 39% compared with 45%, comparison: 43% compared with 38%; interaction p=0.06). Conclusions: The findings provide evidence of reduced SSB consumption among adults in the target age range following the LiveLighter campaign. This is notable in a context where public health campaigns occur against a backdrop of heavy commercial product advertising promoting increased SSB consumption.

BMJ open · 38 citationsread the source →

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

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

The lancet. Psychiatry · 158 citationsread the source →

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 →

Charting the Future of Cancer Health Disparities Research: A Position Statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute

The academic field of cancer health disparities was stimulated by the U.S. civil rights movement. Concerns about civil rights led to concerns about equality in health care. The first publications to make the observation that black Americans have higher rates of death as a result of certain cancers compared with white Americans were published by the early 1970s (1, 2). The discipline concerned with these differences was first called “minority health research” and later “special populations health” or “special populations research.” The National Cancer Institute (NCI) defines cancer health disparities as adverse differences in cancer incidence, cancer prevalence, cancer mortality, cancer survivorship, and burden of cancer or related health conditions that exist among specific population groups in the United States (3). However, with greater and renewed acknowledgment of health disparities as rooted within the context of historical and contextual inequities in the United States, many health disparities are considered health inequities (4).The National Cancer Act of 1971 created the Surveillance, Epidemiology, and End Results (SEER) program within the NCI. This program began collecting incidence, mortality, and survival data by race in the early 1970s from a number of population-based registries around the United States. The SEER program improved documentation of differences in outcomes and analyzed them through its black–white studies (5). These studies especially demonstrated differences in treatment patterns, with a higher proportion of blacks receiving inappropriate cancer care compared with whites. The discipline grew from a focus on black–white differences to encompass differences in outcomes for a number of racial and ethnic groups, as well as for cohorts defined by age, sex, socioeconomic status (SES), and other social determinants of health. There is now even greater appreciation for disparities among communities, whether rural versus urban or even by state or region. The definition of health outcomes also broadened beyond death rates. The field of health disparities was once simply a description of population differences and a call for cultural competence among health care providers. Today, the field is transdisciplinary, integrating basic science, clinical science, policy, epidemiology, and the social sciences. It involves people trained in diverse nonmedical fields, such as education, economics, sociology, religion, geography, and anthropology. The field is also dynamic. It changes as better and more granular statistics, greater understanding of causes of health disparities, and new challenges to mitigate these underlying causes have emerged. As an example, in the 1970s, the breast cancer death rate for black and white American women was the same. Today, the death rate is substantially higher for blacks compared with whites (6). Policy changes have also created opportunities and challenges. The Affordable Care Act has allowed for Medicaid expansion in each state. Expansion has been adopted by 32 states and the District of Columbia. This will create a new challenge, because poor residents of some states have expanded access to care and residents of other states do not. It is essential that any future policy changes should be carefully designed to increase, rather than decrease, equitable access to care throughout the cancer continuum. Population categorizations also are being redefined. The Asian category includes Korean Americans and Pakistani Americans. The Pacific Islander category, often merged with the Asian category, includes native Hawaiians and Samoans. These populations are incredibly heterogeneous and have dramatically different cancer statistics. In 2015, representatives from four leading cancer organizations, the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology (ASCO), and the NCI, began to meet to discuss the state of health disparities in the United States. These discussions involved the state of cancer health disparities research and what could be done to move it forward. The discussions were purposely not meant as a comprehensive review of cancer health disparities research. Rather, the meeting and the resulting document aimed to identify issues in health disparities research and make specific recommendations to improve the way disparities research is conducted and disseminated. This statement presents a unified strategy among four of the leading cancer organizations in the United States to promote cooperation among investigators in all areas of the cancer health disparities research community, to ensure that cancer research benefits all populations and patients regardless of race, ethnicity, age, gender identity, sexual orientation, SES, or the communities in which they live. Disparities in outcomes across the cancer continuum have been identified in numerous medically underserved populations, including racial and ethnic minorities and patients of lower SES. In addition to individual social status, social contextual and community factors, such as neighborhood safety, social cohesion, availability of healthy foods, and residential segregation, play an important role in health of both individuals and populations. All of these factors can intersect to generate larger disparities (7, 8).To understand and fully address cancer health disparities, complete, consistent, and accurate collection of patient, community, and structural factors that put people at risk for disparate outcomes is essential. Unfortunately, cancer health disparities research has often been fraught with missing, inaccurate, or overly simplified patient-level data, and most research has failed to consider the community-level factors described above (9–11).For the most part, the manner in which data are collected and integrated in disparities research is suboptimal. The literature is characterized by variable methodology for collection of the factors that put patients and communities at risk for disparate care and outcomes. For example, although race and ethnicity are distinct constructs, they are often conflated such that a person is identified as Hispanic without identification of his or her race. Many studies that investigate cancer care or outcomes according to socioeconomic position have only area-level data on socioeconomic position, whereas others use only composite measures. While valuable in many cases in identifying disparities, such measures fall short in providing the richness of data needed to understand an individual's socioeconomic position. Health literacy and numeracy are rarely assessed in practice and are not available in administrative and research databases. Finally, methods for uniform data collection of information on sexual orientation and gender identity are in their infancy, despite calls for such data collection from the Institute of Medicine, among others (12).Disparities in cancer incidence are pronounced and longstanding. Drivers of these disparities are multifactorial and multilevel, and they include sociodemographic factors, access to health care, risk factor profiles and lifestyle/health habits, cultural perceptions, biologic differences, and genetic predisposition. Disparities in cancers for which single etiologic factors account for a substantial proportion of disease (e.g., human papillomavirus and cervical cancer, or Helicobacter pylori and stomach cancer) can be reasonably understood and explained, but disparities for many of the common etiologically heterogeneous cancers, such as breast, prostate, and colorectal cancers, remain much less well understood. Multilevel approaches are needed to advance knowledge relevant to addressing disparities in cancer incidence rates. One approach is to design and implement observational studies focused on a population in which disparities exist to advance knowledge about etiology and to inform novel prevention strategies. A successful example of such an effort is the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a multicenter consortium that has combined data and biospecimens from 7,500 African American patients with breast cancer and 17,000 healthy controls, representing the largest study of breast cancer in African American women in the United States (14). It has yielded a number of insights on multilevel risk factors specific to the major molecular subtypes of breast cancer among African American women (15–17).There is also a need for studies focused on identifying the genetic contributors to cancer health disparities. Recent work has focused on the prioritization of candidate variants relevant to prostate cancer risk within the context of genetic ancestry (based on ancestry informative markers) across those with European, African, Japanese, or Latino ancestry (18). Furthermore, the African Ancestry Prostate Cancer Genome-Wide Association Studies (GWAS) Consortium has reported on susceptibility loci for aggressive prostate cancer specific to men of African ancestry (19).Although some cancer risk factors are well established, the biologic mechanisms through which their impact on cancer risk varies across different populations remain incompletely understood. For example, variations in diet are hypothesized to be the primary driver of the dramatic variations in colorectal cancer incidence rates observed across populations. Recent research has evaluated the impact that different diets have on microbiota composition and function, which in turn affects the production of metabolites that either promote mucosal health or are proinflammatory/neoplastic in the gut. A study that compared Americans with African ancestry (who have a relatively high incidence of colorectal cancer) with rural South Africans (who have a comparatively very low colorectal cancer incidence rate) demonstrated that a typical U.S. diet with high meat and fat intake increases mucosal proliferation rates (a marker of cancer risk) when fed to both populations, whereas typical high-fiber South African diets were associated with low proliferation rates when fed to both groups. This demonstrates that diet can have a profound and fairly immediate impact on the gut microbiome that can either promote or suppress tumors (20).Cancer outcome disparities are well documented for racial and ethnic minorities, and presentation at more advanced stages of cancer explains much of this difference. However, even when controlling for the stage of cancer at diagnosis, the survival disparities persist. What is most concerning is that rather than improving over time, for cancers such as colon cancer, the stage-specific disparities are actually worsening (21). The reason for this growing disparity is not completely clear but involves socioeconomic issues such as education status and the level of insurance and access to medical care. Even in studies that normalize socioeconomic issues (with the limitations cited in the Defining Measures section), disparities that disproportionally affect U.S. minority populations can still be demonstrated for several cancers and may highlight the not-so-well-understood interplay between genetic predisposition and environmental exposure, such as lifestyle and diet, that modifies cancer risk (22, 23). Ultimately, growing postdiagnosis survival disparities are caused by the interplay of system, social, biologic, and environmental factors. Documenting and addressing each of these and their interactions are key to eliminating these disparities. The role of system-level and social determinants in explaining cancer health disparities is best demonstrated by recognizing that disparities vary widely across the United States; some states show almost no disparities, whereas others show striking ones (24). We also know that disparities in treatment of cancer differ and that when treatment differences are accounted for, either through the use of standardized therapies on a clinical trial or through multivariable modeling, cancer-specific survival disparities often disappear. We also have clear examples of successful system-level reform (21, 25, 26). We know, therefore, this is a solvable problem. The key step toward improving care and reducing cancer health disparities requires accurate measurement of meaningful variables, fed back in real time to key stakeholders in the system, followed by meaningful action and continued monitoring to ensure that the action was successful. Determining meaningful measurement across the cancer spectrum may vary by sociocultural factors and require patient and stakeholder input. These system-based practices formed the core of a recent Institute of Medicine report, “Systems Practices for the Care of Socially At-Risk Populations” (27). Systems can be thought of at a macro level, such as state, county, or city governments, all the way down to the individual practice or physician level. Implementation science can inform the best approaches to ensure delivery of high-quality cancer care. Cancers can start as a result of chronic inflammation, and inflammation can modify the behavior of cancer. Biomarkers, such as elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) that can be detected from inflammation-laden cancers, are associated with worse patient outcome and increased metastasis and appear to be more common among African Americans. Microsatellite-unstable (MSI) cancers, which have an overall good prognosis, may be half as common among African Americans compared with whites (28). Both EMAST and MSI have implications for (1) chemotherapeutic response and (2) immunotherapeutic response. In terms of race, these aspects have not been studied. Furthermore, there is much evidence that the microbiome can influence (1) inflammation, (2) response to chemotherapy, and (3) cancer or precancerous lesion formation; also, the microbiome itself can be determined by diet and other factors. These aspects have not been examined with race in mind. Additionally, driver genes may be different within the same type of cancer from patients with different genetic backgrounds, which have implications for correct, definitive therapeutic approaches (29).Most studies that use human specimens to study aspects of cancer and race or ethnicity come from limited individual collections with sparse clinical–epidemiologic information, with rare exception. The exceptions tend to be NCI-funded projects, such as the North Carolina Colon Cancer Study, in which peer review and thoughtful input about how the collection was made with controls, surveys, and linked information to make the collection more meaningful, comprehensive in information, potentially useful for other future studies, and possessed of longevity. However, these types of collections or biorepositories, which include tumor and nontumor specimens, have not been created from diverse samples representative of the U.S. Census population. Current models of health care delivery are highly focused on the use of technology and innovation to improve patient outcomes across disease processes, as demonstrated by the focus on precision medicine in cancer treatment (32–36). Although oncology attempts to embrace this approach, the impact of innovative treatments has been hampered by poor translation of innovation into health care systems and patients from diverse community settings (37, 38). As precision medicine in cancer is accelerated as part of the Beau Biden Cancer Moonshot and other initiatives, the importance of community engagement to ensure that all patients benefit from these advances cannot be overlooked. Cancer health disparities must be taken into consideration in the design, execution, and evaluation of all such programs. Community-engaged research (CER) has been documented as an effective, beneficial method for engaging communities and formulating research that has relevance and impact for both researchers and affected communities (39–42). Involving relevant community stakeholders in research at the planning stages allows for a deeper understanding of community needs, allows researchers to have an iterative method for evaluating research questions in an active realistic milieu, and simultaneously creates a valuable vehicle for active dissemination of the research findings into the communities they are intended to serve. CER offers the potential to improve processes and outcomes in several areas, including care delivery, continuity of care, managing comorbidities, and supportive care (42).Unfortunately, there is a dearth of support for oncology health professionals who choose to work in CER, given its necessity for infrastructure and relationship building, the complex personal interactions with communities and community organizations, and the need to establish long-term benefits to the community after the research project is completed. Importantly, CER requires not only a broad range of expertise across multiple disciplines, but also investigators skilled in a team science approach (43). The benefit of this type of team science has been touted across disciplines; however, its implementation has been limited (44).A lack of workforce diversity has been identified as a barrier to improving access to care for underserved minority groups as well as to advancing research on health disparities (45, 46). Organizations, including ASCO and the American Society of Hematology, have sought to increase workforce diversity in oncology through awards and mentoring programs that expose minorities to in oncology at the medical and In the to Cancer Health Disparities and the American Association for Cancer several programs aimed at the of researchers in cancer and cancer health disparities research. of these types are needed to an oncology workforce that the diversity of the patients it CER not often with most and will require on of the research in both and such an it will remain to create a between CER and the that in cancer are the most important and available to evidence for care and of patients with cancer and individuals at risk for cancer that advanced new approaches from clinical care and diverse oncology the of clinical is to evidence that is both and future must include research questions that consider the multifactorial and multilevel that populations with the cancer This to advance disparities research within the cancer clinical within a new of for in cancer clinical and common for providing trial information have been to for rural patients and patients with lower SES, limited low health and The high and of chronic and of risk factors for chronic such as and must inform to these populations fully in cancer As an example, African Americans a burden of the that from studies, and it is to which could be reasonably as or could be or within the study In addition to those from cancer prevention and treatment also has that populations often are later in the and do not support and rates are key that influence the outcome of clinical cancer studies, those in which minorities have higher disease such as breast, prostate, and cancers In and treatment and rates lower rates exist for those patients who from to and Many such as and to the However, community engagement is to address the and challenges that the clinical CER has been demonstrated to promote building, and the and dissemination of information needed for and long-term As an example, the evaluated the of community health to promote and in and rural populations and that community health can be trained to as research and can be for of and cancer clinical trial and require an of often to be collected at multiple time thought should be given to how best to the of and the study (e.g., and needed to support collection and of specimens from and that to field of cancer health disparities has into a complex science and an field of cancer research. 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