Genetics, epigenetics, and neurobiology of childhood-onset depression: an umbrella review.

Depression is a serious and persistent psychiatric disorder that commonly first manifests during childhood. Depression that starts in childhood is increasing in frequency, likely due both to evolutionary trends and to increased recognition of the disorder. In this umbrella review, we systematically searched the extant literature for genetic, epigenetic, and neurobiological factors that contribute to a childhood onset of depression. We searched PubMed, EMBASE, OVID/PsychInfo, and Google Scholar with the following inclusion criteria: (1) systematic review or meta-analysis from a peer-reviewed journal; (2) inclusion of a measure assessing early age of onset of depression; and (3) assessment of neurobiological, genetic, environmental, and epigenetic predictors of early onset depression. Findings from 89 systematic reviews of moderate to high quality suggest that childhood-onset depressive disorders have neurobiological, genetic, environmental, and epigenetic roots consistent with a diathesis-stress theory of depression. This review identified key putative markers that may be targeted for personalized clinical decision-making and provide important insights concerning candidate mechanisms that might underpin the early onset of depression.

Systematic evidence review and meta-analysis of outcomes associated with cancer genetic counseling.

PURPOSE: Genetic counseling (GC) is standard of care in genetic cancer risk assessment (GCRA). A rigorous assessment of the data reported from published studies is crucial to ensure the evidence-based implementation of GC. METHODS: We conducted a systematic review and meta-analysis of 17 patient-reported and health-services-related outcomes associated with pre- and post-test GC in GCRA in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-five of 5393 screened articles met inclusion criteria. No articles reporting post-test GC outcomes met inclusion criteria. For patient-reported outcomes, pre-test GC significantly decreased worry, increased knowledge, and decreased perceived risk but did not significantly affect patient anxiety, depression, decisional conflict, satisfaction, or intent to pursue genetic testing. For health-services outcomes, pre-test GC increased correct genetic test ordering, reduced inappropriate services, increased spousal support for genetic testing, and expedited care delivery but did not consistently improve cancer prevention behaviors nor lead to accurate risk assessment. The GRADE certainty in the evidence was very low or low. No included studies elucidated GC effect on mortality, cascade testing, cost-effectiveness, care coordination, shared decision making, or patient time burden. CONCLUSION: The true impact of GC on relevant outcomes is not known low quality or absent evidence. Although a meta-analysis found that pre-test GC had beneficial effects on knowledge, worry, and risk perception, the certainty of this evidence was low according to GRADE methodology. Further studies are needed to support the evidence-based application of GC in GCRA.

Global incidence of non-alcoholic fatty liver disease: A systematic review and meta-analysis of 63 studies and 1,201,807 persons.

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults without NAFLD at baseline to evaluate the global incidence of ultrasound-diagnosed NAFLD. RESULTS: A total of 63 eligible studies (1,201,807 persons) were analyzed. Studies were from Mainland China/Hong Kong (n = 26), South Korea (n = 22), Japan (n = 14), other (n = 2, Sri Lanka, Israel); 63.8% were clinical center studies; median study year 2000 to 2016; 87% were good quality. Among the 1,201,807 persons at risk, 242,568 persons developed NAFLD, with an incidence rate of 4,612.8 (95% CI 3,931.5-5,294.2) per 100,000 person-years and no statistically significant differences by study sample size (p = 0.90) or study setting (p = 0.055). Males had higher incidence vs. females (5,943.8 vs. 3,671.7, p = 0.0013). Both the obese (vs. non-obese) and the overweight/obese groups (vs. normal weight) were about threefold more likely to develop NAFLD (8,669.6 vs. 2,963.9 and 8,416.6 vs. 3,358.2, respectively) (both p <0.0001). Smokers had higher incidence than non-smokers (8,043.2 vs. 4,689.7, p = 0.046). By meta-regression, adjusting for study year, study setting, and study location, study period of 2010 or after and study setting were associated with increased incidence (p = 0.010 and p = 0.055, respectively). By country, China had a higher NAFLD incidence compared to non-China regions (p = 0.012) and Japan a lower incidence compared to non-Japan regions (p = 0.005). CONCLUSIONS: NAFLD incidence is increasing with a current estimate of 4,613 new cases per 100,000 person-years. Males and overweight/obese individuals had significantly higher incidence rates compared to females and those of normal weight. Public health interventions for prevention of NAFLD are needed with a special emphasis on males, overweight/obese individuals, and higher risk regions. IMPACT AND IMPLICATIONS: Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of people worldwide and appears to be increasing, but data to estimate the incidence rate are limited. In this meta-analytic study of over 1.2 million people, we estimated an incidence rate of NAFLD of 46.13 per 1,000 person-years with significant differences by sex, BMI, geography, and time-period. As treatment options for NAFLD remain limited, prevention of NAFLD should remain the focus of public health strategies. Studies such as these can help policy makers in determining which and whether their interventions are impactful.

Athletes in medicine: A systematic review of performance of athletes in medicine.

INTRODUCTION: As interest in medicine grows, admissions committees must review an increasingly competitive pool of medical school and residency candidates. Nearly all admissions committees have moved towards a holistic review, which considers an applicant's experiences and attributes in addition to academic metrics. As such, identifying nonacademic predictors of success in medicine is necessary. Parallels between skills necessary to succeed in athletics and in medicine have been drawn, including teamwork, discipline and resiliency. This systematic review synthesises the current literature to evaluate the relationship between participation in athletics and performance in medicine. METHODS: The authors searched five databases to conduct a systematic review following PRISMA guidelines. Included studies assessed medical students, residents or attending physicians in the United States or Canada and used prior athletic participation as a predictor or explanatory variable. The review examined associations between prior athletic participation and outcomes in medical school, residency and/or as an attending physician. RESULTS: Eighteen studies evaluating medical students (78%), residents (28%) or attending physicians (6%) met inclusion criteria for this systematic review. Twelve (67%) studies specifically assessed participants based on skill level, and five (28%) studies specifically assessed participants based on type of athletic participation (team versus individual). Sixteen studies (89%) found that former athletes performed significantly better than their counterparts (p < 0.05). These studies found significant associations between prior athletic participation and better outcomes in multiple performance indicators, including exam scores, faculty ratings, surgical errors and burnout. CONCLUSIONS: Current literature, although limited, suggests that prior participation in athletics may be a predictor of success in medical school and residency. This was demonstrated through objective scoring methods, such as USMLE, and subjective outcomes, such as faculty ratings and burnout. Specifically, multiple studies indicate that former athletes demonstrated increased surgical skill proficiency and decreased burnout as medical students and residents.

2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS: Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS: We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS: Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.

Increased Risk of Liver-Related Outcomes in Chronic Hepatitis B Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chronic hepatitis B (CHB) patients with metabolic syndrome (MetS) may present increased risk of liver-related outcomes (LROs), but prior studies were limited by small sample size and/or conflicting results. Using a systematic review and meta-analytic approach, we aimed to determine the association between MetS and LROs in CHB. METHODS: Two researchers independently screened studies from the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to January 21, 2020, and extracted the data. Estimates were pooled using a random-effects model. RESULTS: We screened 2,228 articles and included 10 eligible studies (18,360 CHB patients, 2,557 with MetS). MetS was significantly associated with LROs overall (odds ratio = 2.45, 95% confidence interval = 1.39-4.32) but not the individual LRO components but subgroup analyses were limited by small study numbers. DISCUSSION/CONCLUSION: MetS is associated with almost 3-folds higher risk of LROs in CHB and should be considered in management decisions. However, additional studies are needed.

Comparison of EUS-guided endoscopic transpapillary and percutaneous gallbladder drainage for acute cholecystitis: a systematic review with network meta-analysis.

BACKGROUND AND AIMS: The optimal method of gallbladder drainage (GBD) for acute cholecystitis in nonsurgical candidates is uncertain. The aim of the current study was to conduct a network meta-analysis comparing the 3 methods of GBD (percutaneous [PT], endoscopic transpapillary [ETP], and EUS-guided). METHODS: A comprehensive literature search for all comparative studies assessing the efficacy of either 2 or all modalities used for treatment of acute cholecystitis in patients at high risk for cholecystectomy was performed. Primary outcomes of technical and clinical success and postprocedure adverse events were assessed. Secondary outcomes were reintervention, unplanned readmissions, recurrent cholecystitis, and mortality. RESULTS: Ten studies were identified, comprising 1267 patients (472 EUS-GBD, 493 PT-GBD, and 302 ETP-GBD). In the network ranking estimate, PT-GBD and EUS-GBD had the highest likelihood of technical success (EUS-GBD vs PT-GBD vs ETP-GBD: 2.00 vs 1.02 vs 2.98) and clinical success (EUS-GBD vs PT-GBD vs ETP-GBD: 1.48 vs 1.55 vs 2.98). EUS-GBD had the lowest risk of recurrent cholecystitis (EUS-GBD vs PT-GBD vs ETP-GBD: 1.089 vs 2.02 vs 2.891). PT-GBD had the highest risk of reintervention (EUS-GBD vs PT-GBD vs ETP-GBD: 1.81 vs 2.99 vs 1.199) and unplanned readmissions (EUS-GBD vs PT-GBD vs ETP-GBD: 1.582 vs 2.944 vs 1.474), whereas ETP-GBD was associated with the lowest rates of mortality (EUS-GBD vs PT-GBD vs ETP-GBD: 2.62 vs 2.09 vs 1.29). CONCLUSIONS: The 3 modalities of GBD have their respective advantages and disadvantages. Selection of technique will depend on available expertise. In centers with expertise in endoscopic GBD, the techniques are preferred over PT-GBD with improved outcomes. (Clinical trial registration number: CRD42020181972.).

Epidemiology of Injuries Sustained by Civilians and Local Combatants in Contemporary Armed Conflict: An Appeal for a Shared Trauma Registry Among Humanitarian Actors.

BACKGROUND: Conflict-related injuries sustained by civilians and local combatants are poorly described, unlike injuries sustained by US, North Atlantic Treaty Organization, and coalition military personnel. An understanding of injury epidemiology in twenty-first century armed conflict is required to plan humanitarian trauma systems capable of responding to population needs. METHODS: We conducted a systematic search of databases (e.g., PubMed, Embase, Web of Science, World Health Organization Catalog, Google Scholar) and grey literature repositories to identify records that described conflict-related injuries sustained by civilians and local combatants since 2001. RESULTS: The search returned 3501 records. 49 reports representing conflicts in 18 countries were included in the analysis and described injuries of 58,578 patients. 79.3% of patients were male, and 34.7% were under age 18 years. Blast injury was the predominant mechanism (50.2%), and extremities were the most common anatomic region of injury (33.5%). The heterogeneity and lack of reporting of data elements prevented pooled analysis and limited the generalizability of the results. For example, data elements including measures of injury severity, resource utilization (ventilator support, transfusion, surgery), and outcomes other than mortality (disability, quality of life measures) were presented by fewer than 25% of reports. CONCLUSIONS: Data describing the needs of civilians and local combatants injured during conflict are currently inadequate to inform the development of humanitarian trauma systems. To guide system-wide capacity building and quality improvement, we advocate for a humanitarian trauma registry with a minimum set of data elements.

Oral vs intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review of randomized trials comparing oral vs intravenous (IV) iron therapy to treat postpartum anemia. DATA SOURCES: Data sources were as follows: PubMed (1972-2017); Cochrane Central Register of Controlled Trials, CENTRAL (1972-2017); CINAHL (1972-2017); Web of Science; Excerpta Medica Database, and EMBASE (1972-2017). STUDY ELIGIBILITY CRITERIA: We included randomized trials comparing oral vs IV iron monotherapy to treat postpartum anemia (classified as a hemoglobin <12 g/dL). STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed with the Cochrane risk of bias assessment tool. The primary outcome was hemoglobin concentration at 6 weeks postpartum. Secondary outcomes included hemoglobin concentration at 1-5 weeks postpartum, ferritin concentration at 1-6 weeks postpartum, and maternal adverse outcomes. For meta-analysis, mean differences and odds ratios using a random effects model were calculated. Risk of heterogeneity was reported as I2. RESULTS: A total of 15 randomized trials met our inclusion criteria (n = 1001 and 1 181 women receiving oral iron and IV iron, respectively); 4 studies reported data for our primary outcome. We observed higher postpartum week 6 hemoglobin concentrations in the IV iron group compared to the oral iron group (mean difference, 0.9 g/dL; 95% confidence interval (CI), 0.4-1.3; P = .0003). Compared to oral iron, women receiving IV iron had higher hemoglobin concentrations at postpartum weeks 1, 2, and 3; higher ferritin concentrations at postpartum weeks 1, 2, 4, and 6; an increased likelihood of skin flushing (odds ratio [OR], 6.95; 95% CI, 1.56-31.03; P = .01; I2 = 0%); and a decreased likelihood of constipation (OR, 0.08; 95% CI, 0.03-0.21; P < .00001, I2 = 27%) and dyspepsia (OR, 0.07; 95% confidence interval, 0.01-0.42; P = .004; I2 = 0%). The reported event rate for anaphylaxis among women receiving IV iron was 0.6%. CONCLUSION: In this systematic review, among women with postpartum anemia, hemoglobin concentrations at 6 weeks postpartum were almost 1 g/dL higher in women who received IV iron compared to oral iron. The safety profile of IV iron was also reassuring. Given the weaker hemoglobin response and higher risk of gastrointestinal side effects with oral iron use, our findings suggest that IV iron be considered as a viable treatment option for postpartum iron deficiency anemia.

Combination therapy in overactive bladder-untapped research opportunities: A systematic review of the literature.

AIMS: Overactive bladder (OAB) affects over 17% of the population and significantly effect the health-related quality of life. The treatments for OAB include first line (lifestyle modification, pelvic floor muscle training), second line (anticholinergic or beta-3 agonist medications), and third line therapies (intradetrusor botulinum toxin injection, sacral neurostimulation [SNM], or percutaneous tibial nerve stimulation [PTNS]). For those with urinary incontinence secondary to OAB, complete continence is the goal of therapy, though cure rates are only 5% to 40%. The use of combination therapies can be employed in refractory OAB, however, the efficacy of pooled modalities is relatively unknown. Our objective was to determine the volume of data supporting combination therapy in treating OAB. METHODS: We systematically reviewed PubMed, EMBASE, the Cochrane Library, and Google Scholar for articles published before October 2018. Each was independently reviewed by two reviewers and examined in detail if they met inclusion criteria. RESULTS: A total of 32 studies met inclusion criteria and were reviewed. Most large prospective studies evaluated combinations of medications with behavioral therapy or medications together. Combination therapy studies of third-line treatments were rare and centered on medication with PTNS. No studies examined intradetrusor botulinum toxin injections in combination with another therapy and only one retrospective study briefly examined SNM therapy in combination with medication. CONCLUSION: Combination therapy, with certain first, second, and third-line OAB therapies, appears to be efficacious. There is a further need for carefully designed combination therapy studies, particularly those including third line modalities.

Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD. METHODS: We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies. RESULTS: We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding. CONCLUSIONS: Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.

The Role of Cone-Beam CT in Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

PURPOSE: To review available evidence for use of cone-beam CT during transcatheter arterial chemoembolization in hepatocellular carcinoma (HCC) for detection of tumor and feeding arteries. MATERIALS AND METHODS: Literature searches were conducted from inception to May 15, 2016, in PubMed (MEDLINE), Scopus, and Cochrane Central Register of Controlled Trials. Searches included "cone beam," "CBCT," "C-arm," "CACT," "cone-beam CT," "volumetric CT," "volume computed tomography," "volume CT," AND "liver," "hepatic*," "hepatoc*." Studies that involved adults with HCC specifically and treated with transcatheter arterial chemoembolization that used cone-beam CT were included. RESULTS: Inclusion criteria were met by 18 studies. Pooled sensitivity of cone-beam CT for detecting tumor was 90% (95% confidence interval [CI], 82%-95%), whereas pooled sensitivity of digital subtraction angiography (DSA) for tumor detection was 67% (95% CI, 51%-80%). Pooled sensitivity of cone-beam CT for detecting tumor feeding arteries was 93% (95% CI, 91%-95%), whereas pooled sensitivity of DSA was 55% (95% CI, 36%-74%). CONCLUSIONS: Cone-beam CT can significantly increase detection of tumors and tumor feeding arteries during transcatheter arterial chemoembolization. Cone-beam CT should be considered as an adjunct tool to DSA during transcatheter arterial chemoembolization treatments of HCC.

Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. RESULTS: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). CONCLUSION: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Precision medicine within health professions education: Defining a research agenda for emergency medicine using a foresight and strategy technique (FaST) review.

Background: Precision medicine, sometimes referred to as personalized medicine, is rapidly changing the possibilities for how people will engage health care in the near future. As technology to support precision medicine exponentially develops, there is an urgent need to proactively improve our understanding of precision medicine and pose important research questions (RQs) related to its inclusion in the education and training of future emergency physicians. Methods: A seven-step process was employed to develop a research agenda exploring the intersection of precision and emergency medicine education/training. A literature search of articles about precision medicine was conducted first, which informed the creation of future four scenarios in which trainees and practicing physicians regularly discuss and incorporate precision medicine tools into their discussions and work. Based on these futurist narratives, potential education RQs were generated by an expert panel. A total of 59 initial questions were subsequently categorized and refined to a priority list through a nominal group voting method. The top/priority questions were presented at the 2023 SAEM Consensus Conference on Precision Medicine, Austin, Texas, for further input. Results: Eight high-value education RQs were developed, reflecting a holistic view of the challenges and opportunities for precision medicine education in the knowledge, skills, and attitudes relevant to emergency medicine. These questions contend with topics such as most effective pedagogical methods; intended resulting outcomes and behaviors; the generational differences between practicing emergency physicians, educators, and future trainees; and the desires and expectations of patients. Conclusions: Emergency medicine and emergency physicians must be prepared to understand precision medicine and incorporate this information into their "toolbox" of thinking, problem solving, and communication with patients and colleagues. This research agenda on how best to educate future emergency physicians in the use of personalized data to provide optimal health care is the focus of this article.

Prevalence of Neurological Soft Signs at Presentation in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Importance: Studies of brain imaging and movements during REM sleep indicate basal ganglia involvement in pediatric acute-onset neuropsychiatric syndrome (PANS). Characterizing neurological findings commonly present in patients with PANS could improve diagnostic accuracy. Objective: To determine the prevalence of neurological soft signs which may reflect basal ganglia dysfunction (NSS-BG) in youth presenting with PANS and whether clinical characteristics of PANS correlate with NSS-BG. Design, Setting, and Participants: 135 new patients who were evaluated at the Stanford Children's Immune Behavioral Health Clinic between November 1, 2014 and March 1, 2020 and met strict PANS criteria were retrospectively reviewed for study inclusion. 16 patients were excluded because they had no neurological exam within the first three visits and within three months of clinical presentation. Main Outcomes and Measures: The following NSS-BG were recorded from medical record review: 1) glabellar tap reflex, 2) tongue movements, 3) milkmaid's grip, 4) choreiform movements, 5) spooning, and 6) overflow movements. We included data from prospectively collected symptoms and impairment scales. Results: The study included 119 patients: mean age at PANS onset was 8.2 years, mean age at initial presentation was 10.4 years, 55.5% were male, and 73.9% were non-Hispanic White. At least one NSS-BG was observed in 95/119 patients (79.8%). Patients had 2.1 NSS-BG on average. Patients with 4 or more NSS-BG had higher scores of global impairment (p=0.052) and more symptoms (p=0.008) than patients with 0 NSS-BG. There was no significant difference in age at visit or reported caregiver burden. On Poisson and linear regression, the number of NSS-BG was associated with global impairment (2.857, 95% CI: 0.092-5.622, p=0.045) and the number of symptoms (1.049, 95% CI: 1.018-1.082, p=0.002), but not age or duration of PANS at presentation. Conclusions and Relevance: We found a high prevalence of NSS-BG in patients with PANS and an association between NSS-BG and disease severity that is not attributable to younger age. PANS may have a unique NSS-BG profile, suggesting that targeted neurological exams may support PANS diagnosis.

2023 Society for Academic Emergency Medicine Consensus Conference on Precision Emergency Medicine: Development of a policy-relevant, patient-centered research agenda.

OBJECTIVES: Precision medicine is data-driven health care tailored to individual patients based on their unique attributes, including biologic profiles, disease expressions, local environments, and socioeconomic conditions. Emergency medicine (EM) has been peripheral to the precision medicine discourse, lacking both a unified definition of precision medicine and a clear research agenda. We convened a national consensus conference to build a shared mental model and develop a research agenda for precision EM. METHODS: We held a conference to (1) define precision EM, (2) develop an evidence-based research agenda, and (3) identify educational gaps for current and future EM clinicians. Nine preconference workgroups (biomedical ethics, data science, health professions education, health care delivery and access, informatics, omics, population health, sex and gender, and technology and digital tools), comprising 84 individuals, garnered expert opinion, reviewed relevant literature, engaged with patients, and developed key research questions. During the conference, each workgroup shared how they defined precision EM within their domain, presented relevant conceptual frameworks, and engaged a broad set of stakeholders to refine precision EM research questions using a multistage consensus-building process. RESULTS: A total of 217 individuals participated in this initiative, of whom 115 were conference-day attendees. Consensus-building activities yielded a definition of precision EM and key research questions that comprised a new 10-year precision EM research agenda. The consensus process revealed three themes: (1) preeminence of data, (2) interconnectedness of research questions across domains, and (3) promises and pitfalls of advances in health technology and data science/artificial intelligence. The Health Professions Education Workgroup identified educational gaps in precision EM and discussed a training roadmap for the specialty. CONCLUSIONS: A research agenda for precision EM, developed with extensive stakeholder input, recognizes the potential and challenges of precision EM. Comprehensive clinician training in this field is essential to advance EM in this domain.

Uptake of genetic testing by relatives of lynch syndrome probands: a systematic review.

BACKGROUND & AIMS: Screening of persons with newly diagnosed colorectal cancer for Lynch syndrome can yield substantial benefits at acceptable costs, presuming sufficient uptake of genetic testing by first-degree relatives of Lynch syndrome probands. We performed a systematic review of the literature to determine the frequency of and factors associated with genetic testing of first-degree relatives of Lynch syndrome probands. METHODS: We searched 4 databases (CINAHL, PsycInfo, PUBMED, and SCOPUS) for articles published through May 2011 reporting uptake of genetic testing by relatives of Lynch syndrome probands. Two investigators independently screened articles to determine whether they met inclusion criteria; data were collected on study population, genetic counseling, and genetic testing. A narrative, qualitative systematic review was performed. RESULTS: We identified 1258 potentially relevant articles; 533 underwent full-text review, and 8 were included in the final analysis. Of first-degree relatives of Lynch syndrome probands, 52% or less received genetic testing. For each proband, 3.6 or fewer relatives underwent genetic testing. Demographic factors (age <50 years, female sex, parenthood, level of education, employment, participation in medical studies), psychological factors (lack of depressive symptoms), and possibly family history (greater number of relatives with cancer) were associated with uptake of genetic testing. CONCLUSIONS: Genetic testing appears to be underutilized by first-degree relatives of patients with Lynch syndrome. The clinical benefit and economic feasibility of screening persons with colorectal cancer for Lynch syndrome depend on optimizing family-wide uptake of genetic testing. Future research and clinical efforts should focus on ways to overcome barriers to genetic testing.

Are organic foods safer or healthier than conventional alternatives?: a systematic review.

BACKGROUND: The health benefits of organic foods are unclear. PURPOSE: To review evidence comparing the health effects of organic and conventional foods. DATA SOURCES: MEDLINE (January 1966 to May 2011), EMBASE, CAB Direct, Agricola, TOXNET, Cochrane Library (January 1966 to May 2009), and bibliographies of retrieved articles. STUDY SELECTION: English-language reports of comparisons of organically and conventionally grown food or of populations consuming these foods. DATA EXTRACTION: 2 independent investigators extracted data on methods, health outcomes, and nutrient and contaminant levels. DATA SYNTHESIS: 17 studies in humans and 223 studies of nutrient and contaminant levels in foods met inclusion criteria. Only 3 of the human studies examined clinical outcomes, finding no significant differences between populations by food type for allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. Two studies reported significantly lower urinary pesticide levels among children consuming organic versus conventional diets, but studies of biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful differences. All estimates of differences in nutrient and contaminant levels in foods were highly heterogeneous except for the estimate for phosphorus; phosphorus levels were significantly higher than in conventional produce, although this difference is not clinically significant. The risk for contamination with detectable pesticide residues was lower among organic than conventional produce (risk difference, 30% [CI, -37% to -23%]), but differences in risk for exceeding maximum allowed limits were small. Escherichia coli contamination risk did not differ between organic and conventional produce. Bacterial contamination of retail chicken and pork was common but unrelated to farming method. However, the risk for isolating bacteria resistant to 3 or more antibiotics was higher in conventional than in organic chicken and pork (risk difference, 33% [CI, 21% to 45%]). LIMITATION: Studies were heterogeneous and limited in number, and publication bias may be present. CONCLUSION: The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria. PRIMARY FUNDING SOURCE: None.

Comprehensive guidance for antibiotic dosing in obese adults: 2022 update.

Drug dosing in obese patients continues to be challenging due to a lack of high-quality evidence to guide dosing recommendations. We first published guidance for antibiotic dosing in obese adults in 2017, in which we critically reviewed articles identified from a broad search strategy to develop dosing recommendations for 35 antimicrobials. In this updated narrative review, we searched Pubmed, Web of Science, and the Cochrane Library using Medical Subject Headings including anti-infectives, specific generic antimicrobial names, obese, pharmacokinetics, and others. We reviewed 393 articles, cross-referenced select cited references, and when applicable, referenced drug databases, package inserts, and clinical trial data to update dosing recommendations for 41 antimicrobials. Most included articles were pharmacokinetic studies, other less frequently included articles were clinical studies (mostly small, retrospective), case reports, and very rarely, guidelines. Pharmacokinetic changes are frequently reported, can be variable, and sometimes conflicting in this population, and do not always translate to a documented difference in clinical outcomes, yet are used to inform dosing strategies. Extended infusions, high doses, and therapeutic drug monitoring remain important strategies to optimize dosing in this population. Additional studies are needed to clinically validate proposed dosing strategies, clarify optimal body size descriptors, dosing weight scalars, and estimation method of renal function in obese patients.