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Altered secretion of cortisol, the primary effector of the hypothalamus–pituitary–adrenal axis, has been proposed as a means by which traumatic experiences compromise later mental health. However, despite the popularity of cortisol as a potential biomarker for stress and adversity, findings are inconsistent, and little is known about the impact of war-related trauma on stress physiology of children and adolescents. Here we aimed to evaluate the relationships between war exposure, current living conditions, hair cortisol concentrations (HCC) and post-traumatic stress disorder (PTSD) symptoms in a large cohort of Syrian refugee children and adolescents (6–18 years) and their caregiver. This longitudinal observational study assessed Syrian refugee children and adolescents in two waves, 1 year apart, within informal tented settlements in Lebanon. The relationships between war exposure, time since leaving Syria, PTSD symptoms and HCC were investigated using linear mixed-model regression utilising both waves of data collected (Y1: N = 1574, Y2: N = 923). Hair cortisol concentration was positively, but weakly associated with the number of war-related events experienced. This was limited to those who were at least 12 years old at the time of war exposure. Conversely, HCC decreased with time since leaving Syria. HCC was also associated with PTSD symptoms but not with the quality of their current living conditions. This study revealed that changes to hypothalamic-pituitary-adrenal axis activity may accompany both earlier war exposure and current PTSD symptoms in children and adolescents. Additionally, early adolescence may be a particularly sensitive time in terms of trauma-related changes to the hypothalamic-pituitary-adrenal axis.

Objectives: Analytical frameworks are graphical representation of the key questions answered by a systematic review and can support the development of guideline recommendations. Our objectives were to a) conduct a systematic review to identify, describe and compare all analytical frameworks published as part of a systematic and guideline development process related to colorectal cancer (CRC), and b) to use this case study to develop guidance on how to conduct systematic reviews of analytical frameworks. Methods: We developed a search strategy to identify eligible studies in Medline and Embase from 1996 until December 2020. We also manually searched guideline databases and websites to identify all guidelines and systematic reviews in CRC that used an analytical framework. We assessed the quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool. The systematic review was registered in International Prospective Register of Systematic Reviews, registration CRD42020172117. Results: We screened 34,505 records and identified 1,166 guidelines and 3,127 systematic reviews on CRC of which five met our inclusion criteria. These five publications included four analytical frameworks in colorectal cancer (one update). We also describe our methodological approach to systematic reviews for analytical frameworks and underlying concepts for developing analytical framework using a bottom-up or top-down approach. Conclusion: Few guidelines and systematic reviews are utilizing analytical frameworks in the development of recommendations. Development of analytical frameworks should begin with a systematic search for existing analytical frameworks and follow a structured conceptual approach for their development to support guideline recommendations. Our methods may be helpful in achieving these objectives.

Background: Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps in guiding management decisions is controversial. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision-making about thrombophilia testing. Methods: ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used. Recommendations were subject to public comment. Results: The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. Conclusions: The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and conditional recommendations for thrombophilia testing in the following scenarios: a) patients with VTE associated with non-surgical major transient or hormonal risk factors; b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; c) individuals with a family history of antithrombin, protein C or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors, and for guidance to avoid COC/HRT; d) pregnant women with a family history of high-risk thrombophilia types; e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.

AIMS: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost-effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD. DESIGN: A prediction model was developed for DSM-IV AD onset by age 25 years using an ensemble machine-learning algorithm known as 'Super Learner'. Shapley additive explanations (SHAP) assessed variable importance. SETTING AND PARTICIPANTS: Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys. MEASUREMENTS: The primary outcome to be predicted was onset of life-time DSM-IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview. FINDINGS: AD prevalence by age 25 was 5.1% among the 10 687 individuals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78; 95% confidence interval (CI) = 0.74-0.81] higher than any individual candidate risk model (0.73-0.77) and an area under the precision-recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%]; however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders. CONCLUSIONS: A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models. ispartof: Addiction vol:118 issue:5 pages:954-966 ispartof: location:England status: published

PURPOSE: To investigate the prevalence and predictors of perceived helpfulness of treatment in persons with a history of DSM-IV social anxiety disorder (SAD), using a worldwide population-based sample.METHODS: The World Health Organization World Mental Health Surveys is a coordinated series of community epidemiological surveys of non-institutionalized adults; 27 surveys in 24 countries (16 in high-income; 11 in low/middle-income countries; N = 117,856) included people with a lifetime history of treated SAD.RESULTS: In respondents with lifetime SAD, approximately one in five ever obtained treatment. Among these (n = 1322), cumulative probability of receiving treatment they regarded as helpful after seeing up to seven professionals was 92.2%. However, only 30.2% persisted this long, resulting in 65.1% ever receiving treatment perceived as helpful. Perceiving treatment as helpful was more common in female respondents, those currently married, more highly educated, and treated in non-formal health-care settings. Persistence in seeking treatment for SAD was higher among those with shorter delays in seeking treatment, in those receiving medication from a mental health specialist, and those with more than two lifetime anxiety disorders.CONCLUSIONS: The vast majority of individuals with SAD do not receive any treatment. Among those who do, the probability that people treated for SAD obtain treatment they consider helpful increases considerably if they persisted in help-seeking after earlier unhelpful treatments.

BackgroundThe most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.MethodsFace-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.Results3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.ConclusionADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Purpose Lesbian, gay, and bisexual (LGB) individuals, and LB women specifically, have an increased risk for psychiatric morbidity, theorized to result from stigma-based discrimination. To date, no study has investigated the mental health disparities between LGB and heterosexual AQ1individuals in a large cross-national population-based comparison. The current study addresses this gap by examining differences between LGB and heterosexual participants in 13 cross-national surveys, and by exploring whether these disparities were associated with country-level LGBT acceptance. Since lower social support has been suggested as a mediator of sexual orientation-based differences in psychiatric morbidity, our secondary aim was to examine whether mental health disparities were partially explained by general social support from family and friends. Methods Twelve-month prevalence of DSM-IV anxiety, mood, eating, disruptive behavior, and substance disorders was assessed with the WHO Composite International Diagnostic Interview in a general population sample across 13 countries as part of the World Mental Health Surveys. Participants were 46,889 adults (19,887 males; 807 LGB-identified). Results Male and female LGB participants were more likely to report any 12-month disorder (OR 2.2, p Conclusion These results provide cross-national evidence for an association between sexual minority status and psychiatric morbidity, and highlight that for women, but not men, this association was partially mediated by perceived openness with family. Future research into individual-level and cross-national sexual minority stressors is needed.

Multiple paternity is common to all sea turtle species, but its causes and consequences are hard to ascertain and the behaviors and success of males difficult to observe. This study aims to describe patterns of multiple paternity for olive ridley turtles Lepidochelys olivacea at Playa de Escobilla, an ‘arribada’ (mass-nesting) site on the Mexican Pacific coast with over a million clutches laid each reproductive season. A total of 15 females and their hatchlings were sampled during 3 arribada events which occurred over the 2016-2017 nesting season. Females and hatchlings (N = 329) were genotyped at 5 microsatellite loci, from which we inferred the alleles of 46 contributing males. Multiple paternity was detected in 60% of the analyzed clutches, which were sired by a range of 2 to 7 males. Multiple paternity rates differed significantly across arribada events, suggesting more males achieved fertilizations earlier in the breeding season. Paternal contribution in 6 of the clutches with multiple paternity was skewed towards a single male; the remaining clutches had a homogeneous male contribution. However, our results are based on relatively small within-arribada sample sizes. The frequency of multiple paternity among turtle clutches laid on this arribada beach could be related to the density of breeding individuals in the reproductive patch off Playa de Escobilla, rather than to the nesting population size or female size.

Resumen El objetivo de este articulo es ofrecer una vision actualizada sobre el lugar del autotrasplante renal en el tratamiento de las afecciones renales complejas como los aneurismas de la arteria renal, las estenosis extensas del ureter y algunos tumores renales bilaterales o que se desarrollan en un rinon unico anatomico o funcional. Estas intervenciones se realizaban inicialmente por una doble via de acceso, lumbar e iliaca, o por una incision medial xifopubica. Las tecnicas quirurgicas han evolucionado mucho con la utilizacion de la laparoscopia y mas recientemente con la asistencia robotica. Han permitido que se recobre el interes por este procedimiento al disminuir la morbilidad y la mortalidad a la vez que se mantiene el mismo nivel de seguridad que con la cirugia abierta. Sin embargo, esta cirugia debe quedar limitada a centros expertos que cuenten con cirujanos experimentados tanto en el trasplante renal como en la laparoscopia robotica.

Background: COVID-19–related acute illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19. Methods: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. Results: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19–related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. Conclusion: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19–related acute illness.

Background: COVID-19–related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19. Methods: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines. Results: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19–related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. Conclusions: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19–related critical illness.

BACKGROUND: Although randomized trials show that specific phobia treatments can be effective, it is unclear whether patients experience treatment as helpful in clinical practice. We investigated this issue by assessing perceived treatment helpfulness for specific phobia in a cross-national epidemiological survey.METHODS: Cross-sectional population-based WHO World Mental Health (WMH) surveys in 24 countries (n=112,507) assessed lifetime specific phobia. Respondents who met lifetime criteria were asked whether they ever received treatment they considered helpful and the number of professionals seen up to the time of receiving helpful treatment. Discrete-event survival analysis was used to calculate conditional-cumulative probabilities of obtaining helpful treatment across number of professionals seen and of persisting in help-seeking after prior unhelpful treatment.RESULTS: 23.0% of respondents reported receiving helpful treatment from the first professional seen, whereas cumulative probability of receiving helpful treatment was 85.7% after seeing up to 9 professionals. However, only 14.7% of patients persisted in seeing up to 9 professionals, resulting in the proportion of patients ever receiving helpful treatment (47.5%) being much lower than it could have been with persistence in help-seeking. Few predictors were found either of perceived helpfulness or of persistence in help-seeking after earlier unhelpful treatments.LIMITATIONS: Retrospective recall and lack of information about either types of treatments received or objective symptomatic improvements limit results.CONCLUSIONS: Despite these limitations, results suggest that helpfulness of specific phobia treatment could be increased, perhaps substantially, by increasing patient persistence in help-seeking after earlier unhelpful treatments. Improved understanding is needed of barriers to help-seeking persistence.

Aims Children's responses to war and displacement are varied; many struggle, while others appear resilient. However, research into these outcomes disproportionately focuses on cross-sectional data in high-income countries. We aimed to (1) investigate change in resilience across two timepoints in a highly vulnerable sample of Syrian refugee children in Lebanon, and (2) explore predictors of their mental health problems across time. Methods In total, 982 Syrian child–caregiver dyads living in refugee settlements in Lebanon completed questionnaires via interview at baseline and follow-up one year later. We categorised children into groups based on their risk for mental health problems across both timepoints (stable high risk/SHR, deteriorating, improving, stable low risk) according to locally validated cut-offs on measures of post-traumatic stress disorder (PTSD), depression and behavioural problems. Analyses of covariance identified how the groups differed on a range of individual and socio-environmental predictors, followed up by cross-lagged panel models (CLPMs) to investigate the directionality of the relationships between significantly related predictors and symptoms. Results The sample showed a meaningful amount of change in mental health symptoms from baseline to follow-up. Over half (56.3%) of children met SHR criteria and 10.3% deteriorated over time, but almost one-quarter (24.2%) showed meaningful improvement, and 9.2% were consistently at low risk for mental health problems at both timepoints. Several predictors differentiated the groups, particularly social measures. According to CLPMs, maternal acceptance (β = −0.07) predicted child mental health symptoms over time. Self-esteem (β = −0.08), maternal psychological control (β = 0.10), child maltreatment (β = 0.09) and caregiver depression (β = 0.08) predicted child symptoms and vice versa (βse = −0.11, βb = 0.07, βmpc = 0.08, βcm = 0.1, βcd = 0.11). Finally, child symptoms predicted loneliness (β = 0.12), bullying (β = 0.07), perceived social support (β = −0.12), parent–child conflict (β = 0.13), caregiver PTSD (β = 0.07), caregiver anxiety (β = 0.08) and the perceived refugee environment (β = −0.09). Conclusions Our results show risk and resilience are dynamic, and the family environment plays a key role in children's response to war and displacement. Conversely, children also have a significant impact on the family environment and caregiver's own mental health. Interventions to promote resilience in refugee children should therefore consider family-wide mechanisms.

Patient-reported helpfulness of treatment is an important indicator of quality in patient-centered care. We examined its pathways and predictors among respondents to household surveys who reported ever receiving treatment for major depression, generalized anxiety disorder, social phobia, specific phobia, post-traumatic stress disorder, bipolar disorder, or alcohol use disorder. Data came from 30 community epidemiological surveys - 17 in high-income countries (HICs) and 13 in low- and middle-income countries (LMICs) - carried out as part of the World Health Organization (WHO)'s World Mental Health (WMH) Surveys. Respondents were asked whether treatment of each disorder was ever helpful and, if so, the number of professionals seen before receiving helpful treatment. Across all surveys and diagnostic categories, 26.1% of patients (N=10,035) reported being helped by the very first professional they saw. Persisting to a second professional after a first unhelpful treatment brought the cumulative probability of receiving helpful treatment to 51.2%. If patients persisted with up through eight professionals, the cumulative probability rose to 90.6%. However, only an estimated 22.8% of patients would have persisted in seeing these many professionals after repeatedly receiving treatments they considered not helpful. Although the proportion of individuals with disorders who sought treatment was higher and they were more persistent in HICs than LMICs, proportional helpfulness among treated cases was no different between HICs and LMICs. A wide range of predictors of perceived treatment helpfulness were found, some of them consistent across diagnostic categories and others unique to specific disorders. These results provide novel information about patient evaluations of treatment across diagnoses and countries varying in income level, and suggest that a critical issue in improving the quality of care for mental disorders should be fostering persistence in professional help-seeking if earlier treatments are not helpful.

Pancreas transplantation exposes to high rates of complications, either vascular (thrombosis, stenosis, pseudoaneurysm, arteriovenous fistula) or nonvascular (fluid collection, graft rejection). With advances in percutaneous and endovascular techniques, interventional radiologists are increasingly involved in the management of these complications. In this article, we review the anatomical considerations relevant to pancreas transplantation, the techniques used for image-guided interventions for vascular and nonvascular complications, and the expected outcomes of these interventions.

There may be many predictors of venous thromboembolism (VTE) and bleeding in hospitalized medical patients, but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception through May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of 69 410 citations, we included 17 studies in our analysis: 14 that reported on VTE, and 3 that reported on bleeding. For VTE, moderate-certainty evidence showed a probable association with older age; elevated C-reactive protein (CRP), D-dimer, and fibrinogen levels; tachycardia; thrombocytosis; leukocytosis; fever; leg edema; lower Barthel Index (BI) score; immobility; paresis; previous history of VTE; thrombophilia; malignancy; critical illness; and infections. For bleeding, moderate-certainty evidence showed a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication, and presence of a central venous catheter. Elevated CRP, a lower BI, a history of malignancy, and elevated heart rate are not included in most VTE risk assessment models. This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding; it also informs guidelines for VTE prevention and future research.

BackgroundThere is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.MethodsRespondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.ResultsDropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.ConclusionsExtending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.

In 2015, the French Association of Urology, by the male lower urinary tract symptoms Committee, published a practices guideline for the management of prostatic hyperplasia in general practice. Five years after the publication of these recommendation, our objective is to assess their dissemination and their impact in general practice.A specially designed questionnaire was distributed online via the departmental councils of the order and to all regional unions of liberal doctors. The distribution to general practitioners was at the discretion of each organisation depending on local policies.Two hundred and eighty responses were collected. Fifty-five percent of the population was female. 83 % of the general practitioners did not report having knowledge of the practice guideline. 77 % of doctors stated that they had not received training or information on prostatic hyperplasia in the past 5 years. Among the notable results, 51 % of general practitioners declared performing a digital rectal examination. 44 % prescribed an endorectal ultrasound. Only 7 % of doctors were aware of the existence of minimally invasive surgical techniques.The practices guideline for the management of prostatic hyperplasia in general practice proposed in 2015 by the male lower urinary tract symptoms Committee seems to be little known by general practitioners. Dissemination of these recommendations solely through publication in Progrès en Urologie seems ill-suited to consideration by general practitioners, and it seems necessary to consider other modes of dissemination.4, grade C.