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.

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.

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.

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.

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.

Functional neurological disorder and functional somatic syndromes among sexual and gender minority people: A scoping review.

OBJECTIVE: To describe the current literature on functional neurological disorder and functional somatic syndromes among sexual and gender minority people (SGM). METHODS: A search string with descriptors of SGM identity and functional disorders was entered into PubMed, Embase, Web of Science, PsycInfo, and CINAHL for articles published before May 24, 2022, yielding 3121 items entered into Covidence, where 835 duplicates were removed. A neurologist and neuropsychiatrist screened titles and abstracts based on predefined criteria, followed by full-text review. A third neurologist adjudicated discrepancies. Eligible publications underwent systematic data extraction and statistical description. RESULTS: Our search identified 26 articles on functional disorders among SGM people. Most articles were case (13/26, 46%) or cross-sectional (4/26, 15%) studies. Gender minority people were represented in 50% of studies. Reported diagnoses included fibromyalgia (n = 8), functional neurological disorder (n = 8), somatic symptom disorder (n = 5), chronic fatigue syndrome (n = 3), irritable bowel syndrome (n = 2), and other functional conditions (n = 3). Three cohort studies of fibromyalgia or somatic symptom disorder reported an overrepresentation of gender minority people compared to cisgender cohorts or general population measures. Approximately half of case studies reported pediatric or adolescent onset (7/13, 54%), functional neurological disorder diagnosis (7/13, 54%), and symptom improvement coinciding with identity-affirming therapeutic interventions (7/13, 58%). CONCLUSION: Despite a methodologically rigorous literature search, there are limited data on functional neurological disorder and functional somatic syndromes among SGM people. Several studies reported increased prevalence of select conditions among transgender people. More observational studies are needed regarding the epidemiology and clinical course of functional disorders among SGM people.

American Thoracic Society documents: an official American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guideline--Evaluation of Suspected Pulmonary Embolism in Pregnancy.

BACKGROUND: Pulmonary embolism (PE) is a leading cause of maternal mortality in the developed world. Along with appropriate prophylaxis and therapy, prevention of death from PE in pregnancy requires a high index of clinical suspicion followed by a timely and accurate diagnostic approach. METHODS: To provide guidance on this important health issue, a multidisciplinary panel of major medical stakeholders was convened to develop evidence-based guidelines for evaluation of suspected pulmonary embolism in pregnancy using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. In formulation of the recommended diagnostic algorithm, the important outcomes were defined to be diagnostic accuracy and diagnostic yield; the panel placed a high value on minimizing cumulative radiation dose when determining the recommended sequence of tests. RESULTS: Overall, the quality of the underlying evidence for all recommendations was rated as very low or low with some of the evidence considered for recommendations extrapolated from studies of the general population. Despite the low quality evidence, strong recommendations were made for three specific scenarios: performance of chest radiography (CXR) as the first radiation-associated procedure; use of lung scintigraphy as the preferred test in the setting of a normal CXR; and performance of computed-tomographic pulmonary angiography (CTPA) rather than digital subtraction angiography (DSA) in a pregnant woman with a nondiagnostic ventilation-perfusion (V/Q) result. DISCUSSION: The recommendations presented in this guideline are based upon the currently available evidence; availability of new clinical research data and development and dissemination of new technologies will necessitate a revision and update.

An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy.

BACKGROUND: Pulmonary embolism (PE) is a leading cause of maternal mortality in the developed world. Along with appropriate prophylaxis and therapy, prevention of death from PE in pregnancy requires a high index of clinical suspicion followed by a timely and accurate diagnostic approach. METHODS: To provide guidance on this important health issue, a multidisciplinary panel of major medical stakeholders was convened to develop evidence-based guidelines for evaluation of suspected pulmonary embolism in pregnancy using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. In formulation of the recommended diagnostic algorithm, the important outcomes were defined to be diagnostic accuracy and diagnostic yield; the panel placed a high value on minimizing cumulative radiation dose when determining the recommended sequence of tests. RESULTS: Overall, the quality of the underlying evidence for all recommendations was rated as very low or low, with some of the evidence considered for recommendations extrapolated from studies of the general population. Despite the low-quality evidence, strong recommendations were made for three specific scenarios: performance of chest radiography (CXR) as the first radiation-associated procedure; use of lung scintigraphy as the preferred test in the setting of a normal CXR; and performance of computed-tomographic pulmonary angiography (CTPA) rather than digital subtraction angiography (DSA) in a pregnant woman with a nondiagnostic ventilation-perfusion (V/Q) result. DISCUSSION: The recommendations presented in this guideline are based upon the currently available evidence; availability of new clinical research data and development and dissemination of new technologies will necessitate a revision and update.

Duration of Antibiotic Therapy for Bacterial Meningitis in Young Infants: A Systematic Review.

BACKGROUND AND OBJECTIVES: Recommendations for parenteral antibiotic therapy duration in bacterial meningitis in young infants are based predominantly on expert consensus. Prolonged durations are generally provided for proven and suspected meningitis and are associated with considerable costs and risks. The objective of the study was to review the literature on the duration of parenteral antibiotic therapy and outcomes of bacterial meningitis in infants <3 months old. METHODS: We searched PubMed, Embase, and the Cochrane Library for publications until May 31, 2021. Eligible studies were published in English and included infants <3 months old with bacterial meningitis for which the route and duration of antibiotic therapy and data on at least 1 outcome (relapse rates, mortality, adverse events, duration of hospitalization, or neurologic sequelae) were reported. RESULTS: Thirty-two studies were included: 1 randomized controlled trial, 25 cohort studies, and 6 case series. The randomized controlled trial found no difference in treatment failure rates between 10 and 14 days of therapy. One cohort study concluded that antibiotic courses >21 days were not associated with improved outcomes as compared with shorter courses. The remaining studies had small sample sizes and/or did not stratify outcomes by therapy duration. Meta-analysis was not possible because of the heterogeneity of the treatments and reported outcomes. CONCLUSIONS: Rigorous, prospective clinical trial data are lacking to determine the optimal parenteral antibiotic duration in bacterial meningitis in young infants. Given the associated costs and risks, there is a pressing need for high-quality comparative effectiveness research to further study this question.

Meta-analysis: global prevalence, trend and forecasting of non-alcoholic fatty liver disease in children and adolescents, 2000-2021.

BACKGROUND: NAFLD is increasing in children. AIMS: To determine the recent trend and forecast the future global prevalence of paediatric NAFLD METHODS: We searched PubMed, Embase, Web of Science and Cochrane library databases from inception to 1 May 2021 for studies of children and adolescents (≤21 years) with NAFLD. Obesity was defined with weight at ≥95th percentile and overweight as 85th to <95th percentile as per the Center for Disease Control BMI-for-age percentile cut-offs. RESULTS: From 3350 titles and abstracts, we included 74 studies (276,091 participants) from 20 countries/regions. We included 14 studies in the general NAFLD prevalence analysis, yielding an overall prevalence of 7.40% (95% CI: 4.17-12.81) regardless of the diagnostic method, and 8.77% (95% CI: 3.86-18.72) by ultrasound. Among continents with more than one study, the prevalence of NAFLD was 8.53% (95% CI: 5.71-12.55) for North America, 7.01% (95% CI: 3.51-13.53) for Asia, and 1.65% (95% CI: 0.97-2.80) for Europe. NAFLD prevalence regardless of the diagnostic method was 52.49% (95% CI: 46.23-58.68, 9159 participants) and 39.17% (95% CI: 30.65-48.42, 5371 participants) among obese and overweight/obese participants, respectively. For the general population, trend analysis from 2000 to 2017 indicates an increasing global prevalence of paediatric NAFLD from 4.62% to 9.02% at a yearly increase of 0.26%, whereas forecast analysis predicts a prevalence of 30.7% by 2040. CONCLUSION: The prevalence of paediatric NAFLD varies by region and is 52.49% overall among the obese population and 7.40% in the general population. It is predicted to reach 30.7% by 2040.

Evidence-based surgery for laparoscopic cholecystectomy.

Background: Laparoscopic cholecystectomy is frequently performed for acute cholecystitis and symptomatic cholelithiasis. Considerable variation in the execution of key steps of the operation remains. We conducted a systematic review of evidence regarding best practices for critical intraoperative steps for laparoscopic cholecystectomy. Methods: We identified 5 main intraoperative decision points in laparoscopic cholecystectomy: (1) number and position of laparoscopic ports; (2) identification of cystic artery and duct; (3) division of cystic artery and duct; (4) indications for subtotal cholecystectomy; and (5) retrieval of the gallbladder. PubMed, EMBASE, and Web of Science were queried for relevant studies. Randomized controlled trials and systematic reviews were included for analysis, and evidence quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Fifty-two articles were included. Although all port configurations were comparable from a safety standpoint, fewer ports sometimes resulted in improved cosmesis or decreased pain but longer operative times. The critical view of safety should be obtained for identification of the cystic duct and artery but may be obtained through fundus-first dissection and augmented with cholangiography or ultrasound. Insufficient evidence exists to compare harmonic-shear, clipless ligation against clip ligation of the cystic duct and artery. Stump closure during subtotal cholecystectomy may reduce rates of bile leak and reoperation. Use of retrieval bag for gallbladder extraction results in minimal benefit. Most studies were underpowered to detect differences in incidence of rare complications. Conclusion: Key operative steps of laparoscopic cholecystectomy should be informed by both compiled data and surgeon preference/patient considerations.

Pediatric casualties in contemporary armed conflict: A systematic review to inform standardized reporting.

BACKGROUND: Children represent a significant percentage of casualties in modern conflict. Yet, the epidemiology of conflict-related injury among children is poorly understood. A comprehensive analysis of injuries sustained by children in 21st-century armed conflict is necessary to inform planning of local, military, and humanitarian health responses. METHODS: We conducted a systematic search of databases including PubMed, Embase, Web of Science, World Health Organization Catalog, and Google Scholar to identify records that described conflict-related injuries sustained by children since 2001. RESULTS: The search returned 5,264 records. 9 eligible reports without potentially duplicative data were included in analysis, representing 5,100 pediatric patients injured in 5 conflicts. Blast injury was the most frequent mechanism (57%), compared to 24.8% in adults. Mortality was only slightly higher among children (11.0% compared to 9.8% among adults; p <0.05). Non-uniform reporting prevented pooled analysis and limited the conclusions that could be drawn. CONCLUSIONS: Children sustain a higher proportion of blast injury than adults in conflict. Existing data do support the conclusion that child casualties have higher mortality than adults overall; however, this difference is slighter than has been previously reported. Specific subpopulations of children appear to have worse outcomes. Overall, non-uniform reporting renders currently available data insufficient to understand the needs of children injured in modern conflict.

Systematic review with meta-analysis: prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B.

BACKGROUND: As the prevalence of hepatitis steatosis (HS) increases, the prevalence of HS among those with chronic hepatitis B (CHB) may also be increasing but data on the effect of HS on CHB disease progression are lacking. AIMS: To determine the prevalence of HS in CHB and associated factors, prevalence of fibrosis and its association with HS. METHODS: Two researchers independently searched the literature and extracted data. We included full-length original articles of adults with CHB that evaluated. Prevalence estimates were pooled using a random-effects model. Associations between HS and fibrosis were assessed by pooled odds ratios (ORs) or mean differences (MD). RESULTS: Of the 2821 records screened, 54 eligible studies (28 648 patients) were analysed. The pooled prevalence of HS in CHB was 32.8% (95% CI, 28.9-37.0) with higher prevalence in men and obese patients. Older age, male sex and metabolic factors were associated with HS while an inverse association was observed between HS and HBeAg (OR 0.82, 95% CI, 0.75-0.91) and HBV DNA levels (MD -0.38, 95% CI -1.16--0.42). The pooled prevalence of significant fibrosis (≥F2 or ≥F3) was similar between patients with CHB with or without HS (40.1% vs 42.22%, P = 0.68). HS was not significantly associated with fibrosis (pooled OR 0.87, 95% CI 0.54-1.39, 20 studies, 6232 patients). CONCLUSIONS: Approximately 30% of patients with CHB had HS, which was positively associated with male sex, diabetes and metabolic factors, and was negatively associated with HBeAg and HBV DNA. HS was not significantly associated with increased fibrosis.

Evidence-based surgery for laparoscopic appendectomy: A stepwise systematic review.

INTRODUCTION: Appendectomy is a common emergency surgery performed globally. Despite the frequency of laparoscopic appendectomy, consensus does not exist on the best way to perform each procedural step. We identified literature on key intraoperative steps to inform best technical practice during laparoscopic appendectomy. METHODS: Research questions were framed using the population, indication, comparison, outcome (PICO) format for 6 key operative steps of laparoscopic appendectomy: abdominal entry, placement of laparoscopic ports, division of mesoappendix, division of appendix, removal of appendix, and fascial closure. These questions were used to build literature queries in PubMed, EMBASE, and the Cochrane Library databases. Evidence quality and certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) definitions. RESULTS: Recommendations were rendered for 6 PICO questions based on 28 full length articles. Low quality evidence favors direct trocar insertion for abdominal entry and establishment of pneumoperitoneum. Single port appendectomy results in improved cosmesis with unclear clinical implications. There was insufficient data to determine the optimal method of appendiceal stump closure, but use of a specimen extraction bag reduces rates of superficial surgical site infection and intra-abdominal abscess. Port sites made with radially dilating trocars are less likely to necessitate closure and are less likely to result in port site hernia. When port sites are closed, a closure device should be used. CONCLUSION: Key operative steps of laparoscopic appendectomy have sufficient data to encourage standardized practice.

The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040.

BACKGROUND: NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD. METHODS: We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD-8 studies) patients. RESULTS: The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983-2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD. CONCLUSION: NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.

Systematic review: safety and efficacy of extended-duration antiviral chemoprophylaxis against pandemic and seasonal influenza.

BACKGROUND: Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic. PURPOSE: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza. DATA SOURCES: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries. STUDY SELECTION: Randomized, placebo-controlled, double-blind human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events. DATA EXTRACTION: 2 reviewers independently assessed study quality and abstracted information from eligible studies. DATA SYNTHESIS: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. Chemoprophylaxis with NAIs decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], -3.9 percentage points [CI, -5.8 to -1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, -0.4 percentage point [CI, -1.6 to 0.9 percentage point]). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, -0.2 to 0.4 percentage point]), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir. LIMITATIONS: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine. CONCLUSION: Extended-duration zanamivir and oseltamivir chemoprophylaxis seems to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.

Safety of Foregoing Operation for Small Bowel Obstruction in the Virgin Abdomen: Systematic Review and Meta-Analysis.

Our objective was to assess the safety of foregoing surgery in patients without abdominopelvic surgery history presenting with small bowel obstruction (SBO). Classic dogma has counseled early surgical intervention for SBO in the virgin abdomen-patients without abdominopelvic surgery history-given their presumed higher risk of malignant or potentially catastrophic etiologies compared with those who had undergone previous abdominal operations. The term virgin abdomen was coined before widespread use of CT, which now elucidates many SBO etiologies. Despite recent efforts to re-evaluate clinical management standards, the prevalence of SBO etiologies in the virgin abdomen and the current management landscape (nonoperative vs operative) in these patients remain unclear. Our random-effects meta-analysis of 6 studies including 442 patients found the prevalence of malignant etiologies in patients without abdominopelvic surgery history presenting with SBO varied from 7.7% (95% CI 3.0 to 14.1) to 13.4% (95% CI 7.6 to 20.3) on sensitivity analysis. Most malignant etiologies were not suspected before surgery. De novo adhesions (54%) were the most common etiology. More than half of patients underwent a trial of nonoperative management, which often failed. Subgroups of patients likely have variable risk profiles for underlying malignant etiologies, yet no study had consistent follow-up data and we did not find convincing evidence that foregoing operative management altogether in this population can be generally recommended.

Management of cyclic vomiting syndrome in adults: Evidence review.

BACKGROUND: This evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults. METHODS: We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant? RESULTS: We found very low-quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co-morbid conditions and complementary therapies. CONCLUSIONS: This evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes.

Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome.

Cannabis is commonly used in cyclic vomiting syndrome (CVS) due to its antiemetic and anxiolytic properties. Paradoxically, chronic cannabis use in the context of cyclic vomiting has led to the recognition of a putative new disorder called cannabinoid hyperemesis syndrome (CHS). Since its first description in 2004, numerous case series and case reports have emerged describing this phenomenon. Although not pathognomonic, a patient behavior called "compulsive hot water bathing" has been associated with CHS. There is considerable controversy about how CHS is defined. Most of the data remain heterogenous with limited follow-up, making it difficult to ascertain whether chronic cannabis use is causal, merely a clinical association with CVS, or unmasks or triggers symptoms in patients inherently predisposed to develop CVS. This article will discuss the role of cannabis in the regulation of nausea and vomiting, specifically focusing on both CVS and CHS, in order to address controversies in this context. To this objective, we have collated and analyzed published case series and case reports on CHS in order to determine the number of reported cases that meet current Rome IV criteria for CHS. We have also identified limitations in the existing diagnostic framework and propose revised criteria to diagnose CHS. Future research in this area should improve our understanding of the role of cannabis use in cyclic vomiting and help us better understand and manage this disorder.