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To determine if a global mid-upper arm circumference (MUAC) cut-off can be established to classify underweight in adults (men and non-pregnant women).
We conducted an individual participant data meta-analysis (IPDMA) to explore the sensitivity (SENS) and specificity (SPEC) of various MUAC cut-offs for identifying underweight among adults (defined as BMI < 18·5 kg/m2). Measures of diagnostic accuracy were determined every 0·5 cm across MUAC values from 19·0 to 26·5 cm. A bivariate random effects model was used to jointly estimate SENS and SPEC while accounting for heterogeneity between studies. Various subgroup analyses were performed.
Twenty datasets from Africa, South Asia, Southeast Asia, North America and South America were included.
All eligible participants from the original datasets were included.
The total sample size was 13 835. Mean age was 32·6 years and 65 % of participants were female. Mean MUAC was 25·7 cm, and 28 % of all participants had low BMI (<18·5 kg/m2). The area under the receiver operating characteristic curve for the pooled dataset was 0·91 (range across studies 0·61–0·98). Results showed that MUAC cut-offs in the range of ≤23·5 to ≤25·0 cm could serve as an appropriate screening indicator for underweight.
MUAC is highly discriminatory in its ability to distinguish adults with BMI above and below 18·5 kg/m2. This IPDMA is the first step towards determining a global MUAC cut-off for adults. Validation studies are needed to determine whether the proposed MUAC cut-off of 24 cm is associated with poor functional outcomes.
Introduction: Wide variability exists in emergency department (ED) syncope management. The Canadian Syncope Risk Score (CSRS) was derived and validated to predict the probability of 30-day serious outcomes after ED disposition. The objective was to identify barriers and facilitators among physicians for CSRS use to stratify risk and guide disposition decisions Methods: We conducted semi-structured interviews with physicians involved in ED syncope care at 8 Canadian sites. We used purposive sampling, contacting ED physicians, cardiologists, internists, and hospitalists until theme saturation was reached. Interview questions were designed to understand whether the CSRS recommendations are consistent with current practice, barriers and facilitators for application into practice, and intention for future CSRS use. Interviews were conducted via telephone or videoconference. Two independent raters coded interviews using an inductive approach to identify themes, with discrepancies resolved through consensus. Our methods were consistent with the Knowledge to Action Framework, which highlights the need to assess barriers and facilitators for knowledge use and for adapting new interventions into local contexts. Results: We interviewed 14 ED physicians, 7 cardiologists, and 10 hospitalists/internists across 8 sites. All physicians reported the use of electrocardiograms for patients with syncope, a key component in the CSRS criteria. Almost all physicians reported that the low risk recommendation (discharge without specific follow-up) was consistent with current practice, while less consistency was seen for moderate (15 days outpatient monitoring) and high risk recommendations (outpatient monitoring and/or admission). Key barriers to following the CSRS included a lack of access to outpatient monitoring and uncertainty over timely follow-up care. Other barriers included patient/family concerns, social factors, and necessary bloodwork. Facilitators included assisting with patient education, reassurance of their clinical gestalt, and optimal patient factors (e.g. reliability to return, support at home, few comorbidities). Conclusion: Physicians are receptive to using the CSRS tool for risk stratification and decision support. Implementation should address identified barriers, and adaptation to local settings may involve modifying the recommended clinical actions based on local resources and feasibility.
Introduction: Emergency department (ED) syncope management is extremely variable. We developed practice recommendations based on the validated Canadian Syncope Risk Score (CSRS) and outpatient cardiac monitoring strategy with physician input. Methods: We used a 2-step approach. Step-1: We pooled data from the derivation and validation prospective cohort studies (with adequate sample size) conducted at 11 Canadian sites (Sep 2010 to Apr 2018). Adults with syncope were enrolled excluding those with serious outcome identified during index ED evaluation. 30-day adjudicated serious outcomes were arrhythmic (arrhythmias, unknown cause of death) and non-arrhythmic (MI, structural heart disease, pulmonary embolism, hemorrhage)]. We compared the serious outcome proportion among risk categories using Cochran-Armitage test. Step-2: We conducted semi-structured interviews using observed risk to develop and refine the recommendations. We used purposive sampling of physicians involved in syncope care at 8 sites from Jun-Dec 2019 until theme saturation was reached. Two independent raters coded interviews using an inductive approach to identify themes; discrepancies were resolved by consensus. Results: Of the 8176 patients (mean age 54, 55% female), 293 (3.6%; 95%CI 3.2-4.0%) experienced 30-day serious outcomes; 0.4% deaths, 2.5% arrhythmic, 1.1% non-arrhythmic outcomes. The serious outcome proportion significantly increased from low to high-risk categories (p < 0.001; overall 0.6% to 27.7%; arrhythmic 0.2% to 17.3%; non-arrhythmic 0.4% to 5.9% respectively). C-statistic was 0.88 (95%CI0.86–0.90). Non-arrhythmia risk per day for the first 2 days was 0.5% for medium-risk, 2% for high-risk and very low thereafter. We recruited 31 physicians (14 ED, 7 cardiologists, 10 hospitalists/internists). 80% of physicians agreed that low risk patients can be discharged without specific follow-up with inconsistencies around length of ED observation. For cardiac monitoring of medium and high-risk, 64% indicated that they don't have access; 56% currently admit high-risk patients and an additional 20% agreed to this recommendation. A deeper exploration led to following refinement: discharge without specific follow-up for low-risk, a shared decision approach for medium-risk and short course of hospitalization for high-risk patients. Conclusion: The recommendations were developed (with online calculator) based on in-depth feedback from key stakeholders to improve uptake during implementation.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
We used multivariable analyses to assess whether meeting core elements was associated with antibiotic utilization. Compliance with 7 elements versus not doing so was associated with higher use of broad-spectrum agents for community-acquired infections [days of therapy per 1,000 patient days: 155 (39) vs 133 (29), P = .02] and anti-methicillin-resistant S. aureus agents [days of therapy per 1,000 patient days: 145 (37) vs 124 (30), P = .03].
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.
Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.
Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls’ AGD. In total, 300 mother–daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.
Cross-sectional studies suggest that the serotonin transporter promoter region polymorphism (5-HTT gene-linked polymorphic region, 5HTTLPR) moderates the relationship between childhood abuse and major depressive disorder.
To examine whether the 5HTTLPR polymorphism moderates the effect childhood abuse has on 5-year depressive symptom severity trajectories in adulthood.
At 5-year follow-up, DNA from 333 adult primary care attendees was obtained and genotyped for the 5HTTLPR polymorphism. Linear mixed models were used to test for a genotype × childhood abuse interaction effect on 5-year depressive symptom severity trajectories.
After covariate adjustment, homozygous s allele carriers with a history of severe childhood abuse had significantly greater depressive symptom severity at baseline compared with those without a history of severe childhood abuse and this effect persisted throughout the 5-year period of observation.
The 5HTTLPR s/s genotype robustly moderates the effects of severe childhood abuse on depressive symptom severity trajectories in adulthood.
Introduction/Innovation Concept: Free Open Access Medical education (FOAM) is a rapidly emerging medium for the dissemination of medical knowledge, especially in Emergency Medicine. However, the most contributors to FOAM are EM attendings who write on established platforms which they also maintain. EM learners have difficulty breaking into this quickly evolving field. In an effort to encourage FOAM involvement of trainees early in their careers, CanadiEM recruited 10 junior residents and medical students with the purpose of developing the skills necessary to contribute to FOAM. These Junior Editors actively participate in the blog workflow, developing writing, editorial, and management skills necessary to operate a high-traffic EM website. Methods: Potential candidates were recruited by placing an advertisement and application on the CanadiEM website. 10 medical students or junior residents were invited to online group video interviews and were all accepted as Junior Editors (JE). Senior CanadiEM staff held online training sessions for all new JEs on how to use Wordpress to create, edit and publish posts, as well as basics in Search Engine Optimization. The junior editors collaboratively developed an instructional document containing the information they learned during these sessions. JEs then volunteered for editorial jobs via an online messaging system (Slack) as they became available. After uploading the draft of each post, the final products are reviewed by senior Editor and feedback was given to each JE. Curriculum, Tool, or Material: All JEs have learned to use the Wordpress blogging platform to create, edit, and upload posts; optimize blog posts for search engines. Following their own interests, some JEs have also learned to edit podcasts, promote the blog on social media resources (Twitter and Facebook), create infographics, and copy-edit blog posts. Conclusion: After 8 months, the JE program has yielded 6 very active editors who maintain a strong blog workflow, have well-developed social media skills, and are actively involved in developing their own content for future posts. The JE program is a strong pathway to introduce medical trainees to both the technical and creative aspects of FOAM and serves as a novel approach to transition students from passive utilization of online content to active contributors.
Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.
Background: Improved respiratory care of Duchenne muscular dystrophy (DMD) patients has unmasked cardiomyopathy as a major source of morbidity and mortality. There is currently no consensus regarding the management of DMD-associated cardiomyopathy (DMD-CM). The objective of this systematic review was to evaluate the efficacy of pharmacological therapies for prevention and management of DMD-CM, and determine the optimal timing to commence these interventions. Methods: A systematic search was conducted in October 2015 and updated in January 2016 using MEDLINE, EMBASE and CINAHL databases and 9 grey literature sources for studies evaluating the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta-blockers (BB) or aldosterone antagonists (AA) in DMD patients. References of retrieved records were searched. Quality assessment was conducted using the Downs and Black Quality Assessment Checklist. PRISMA reporting guidelines were used. Results: The 11 included studies were of low methodological quality. However, the use of an ACEi, ARB, BB and AA tended to improve or preserve left ventricular systolic function and delay the progression of cardiomyopathy. Conclusions: While there is evidence supporting the use of heart failure medication in patients with DMD-CM, data regarding these interventions for delaying the onset of DMD-CM and when to initiate therapy is lacking.
Establishing an evidence-based diagnostic system informed by the biological (dys)function of the nervous system is a major priority in psychiatry. This objective, however, is often challenged by difficulties in identifying homogeneous clinical populations. Melancholia, a biological and endogenous subtype for major depressive disorder, presents a canonical test case in the search of biological nosology.
We employed a unique combination of naturalistic functional magnetic resonance imaging (fMRI) paradigms – resting state and free viewing of emotionally salient films – to search for neurobiological signatures of depression subtypes. fMRI data were acquired from 57 participants; 17 patients with melancholia, 17 patients with (non-melancholic) major depression and 23 matched healthy controls.
Patients with melancholia showed a prominent loss of functional connectivity in hub regions [including ventral medial prefrontal cortex, anterior cingulate cortex (ACC) and superior temporal gyrus] during natural viewing, and in the posterior cingulate cortex while at rest. Of note, the default mode network showed diminished reactivity to external stimuli in melancholia, which correlated with the severity of anhedonia. Intriguingly, the subgenual ACC, a potential target for treating depression with deep brain stimulation (DBS), showed divergent changes between the two depression subtypes, with increased connectivity in the non-melancholic and decreased connectivity in the melancholic subsets.
These findings reveal neurobiological changes specific to depression subtypes during ecologically valid behavioural conditions, underscoring the critical need to respect differing neurobiological processes underpinning depressive subtypes.
Despite high levels of mental illness, Vietnamese youth have limited access to mental health care. Internet interventions, evidence-based psychotherapy treatments delivered through the internet, have the potential to increase access to mental health for youth in Vietnam. This study explored the perceptions of youths and parents toward internet interventions for youth mental health.
Four focus groups were conducted with youths (n = 20) and parents (n = 20) in Danang, Vietnam. The Technology Acceptance Model was used a framework for focus group questions. The data were analyzed using direct content analysis.
Most youths and parents agreed that the internet serves well as a care delivery model. Participants expressed that the web would be useful for psychoeducation and sharing and receiving information with others. Both groups reported lack of awareness of web-based interventions and logistical concerns regarding access as main barriers. In addition, many parents were concerned about internet addiction. Specific adaptations in Vietnam such as standalone internet service centers and partnering with local organizations may benefit uptake of internet interventions.
This study suggests that internet-based programs for youth mental health, particularly interventions incorporating psychoeducation and social networking components, will be well received in Vietnam. Barriers need to be addressed to successfully implement internet-based treatment. Future initiatives should incorporate acceptance models to improve development of internet interventions for youth.
The Vibrio cholerae O1 (VCO1) El Tor biotype appeared during the seventh cholera pandemic starting in 1961, and new variants of this biotype have been identified since the early 1990s. This pandemic has affected Vietnam, and a large outbreak was reported in southern Vietnam in 2010. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analyses (MLVA) were used to screen 34 VCO1 isolates from the southern Vietnam 2010 outbreak (23 patients, five contact persons, and six environmental isolates) to determine if it was genetically distinct from 18 isolates from outbreaks in southern Vietnam from 1999 to 2004, and two isolates from northern Vietnam (2008). Twenty-seven MLVA types and seven PFGE patterns were identified. Both analyses showed that the 2008 and 2010 isolates were distinctly clustered and separated from the 1999–2004 isolates.
Reports of bloodstream infections caused by methicillin-resistant Staphylococcus aureus among chronic hemodialysis patients to 2 Centers for Disease Control and Prevention surveillance systems (National Healthcare Safety Network Dialysis Event and Emerging Infections Program) were compared to evaluate completeness of reporting. Many methicillin-resistant S. aureus bloodstream infections identified in hospitals were not reported to National Healthcare Safety Network Dialysis Event.
Infect. Control Hosp. Epidemiol. 2016;37(2):205–207
Data were extracted from the case records of UK patients admitted with laboratory-confirmed influenza A(H1N1)pdm09. White and non-White patients were characterized by age, sex, socioeconomic status, pandemic wave and indicators of pre-morbid health status. Logistic regression examined differences by ethnicity in patient characteristics, care pathway and clinical outcomes; multivariable models controlled for potential confounders. Whites (n = 630) and non-Whites (n = 510) differed by age, socioeconomic status, pandemic wave of admission, pregnancy, recorded obesity, previous and current smoking, and presence of chronic obstructive pulmonary disease. After adjustment for a priori confounders non-Whites were less likely to have received pre-admission antibiotics [adjusted odds ratio (aOR) 0·43, 95% confidence interval (CI) 0·28–0·68, P < 0·001) but more likely to receive antiviral drugs as in-patients (aOR 1·53, 95% CI 1·08–2·18, P = 0·018). However, there were no significant differences by ethnicity in delayed admission, severity at presentation for admission, or likelihood of severe outcome.