Real-world tertiary referral centre experience stopping nucleos(t)ide analogue therapy in patients with chronic hepatitis B.

BACKGROUND: Identifying strategies for stopping nucleos(t)ide analogues (NUC) in patients with chronic hepatitis B (CHB) is a major goal in CHB management. Our study describes our tertiary-centre experience stopping nucleos(t)ide analogues (NUC) in CHB. METHODS: We conducted a retrospective cohort study of all individuals with CHB seen at the Calgary Liver Unit between January 2009 and May 2020 who stopped NUC. We collected baseline demographics and HBV lab parameters before and after stopping NUC with results stratified by off-treatment durability. Clinical flare was defined as alanine aminotransferase (ALT) over twice the upper limit of normal and virological flare as HBV DNA >2000 IU/mL. RESULTS: Forty-seven (3.5%) of the 1337 individuals with CHB stopped NUC therapy. During follow-up, six patients (12.8%) restarted NUCs because of a flare. All flares occurred within six months of discontinuation. Median time to restart treatment was 90 days (Q1 65, Q3 133). Upon restarting, all showed suppression of HBV DNA and ALT normalization. Factors associated with restarting NUC therapy included hepatitis B e antigen (HBeAg) positive status at first appointment and longer NUC consolidation therapy. Age, sex, ethnicity, liver stiffness measurement, choice of NUC, and quantitative hepatitis B surface antigen (qHBsAg) level at stopping were not associated with sustained response off-treatment. Six patients had functional cure with HBsAg loss. CONCLUSIONS: Stopping long-term NUC is feasible in HBeAg negative CHB. Hepatic flares can occur despite low levels of qHBsAg. Finite NUC therapy can be considered in eligible patients who are adherent to close monitoring and follow-up, particularly in the first six months after stopping NUC therapy.

The Impact of Comorbidities on Calgary Hospital Utilization in Patients With Chronic Obstructive Pulmonary Disease and Heart Failure.

Background Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are chronic conditions with high acute care utilization. Disease-specific order sets were developed for patients with COPD or HF in Calgary to reduce total days in hospital for this population of patients. However, many patients have comorbidities which may contribute to hospital utilization; thus, disease-specific order sets may not be an optimal solution to reduce overall acute care utilization. Methods Inpatient data on Calgary hospitalizations for COPD or HF between April 1, 2017 - March 31, 2019 and associated diagnoses were identified. Outcomes included total days in hospital and length of stay for COPD and HF patients stratified by number of comorbidities. Results Total days in hospital increased with the number of comorbidities for both conditions. During the study period, 131 patients with COPD and no comorbidities had a median length of stay of three days (IQR: 3) compared to 3,911 COPD patients with one to five comorbidities with a median length of stay of seven days (IQR: 9). There were 47 patients with HF and no comorbidities with a median length of stay of four days (IQR: 5) compared to 6,273 HF patients with one to five comorbidities with a median length of stay of nine days (IQR: 12). Common comorbidities included hypertension, type 2 diabetes, and acute renal failure. COPD and HF are frequently comorbid.  Conclusions Total days in hospital for patients with COPD or HF is positively correlated with the number of comorbidities. COPD or HF patients with between one to five comorbidities (compared to those with no comorbidities, and those with more than five comorbidities) represent the majority of total days in hospital, and the majority of patients. This highlights the importance of focusing on patients with comorbidities in efforts to reduce hospital utilization, and suggests that concurrent management of commonly occurring comorbidities for HF and COPD patients may be necessary to achieve this goal.

Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis.

BACKGROUND: Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies. METHODS: Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations. RESULTS: Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8-46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero. CONCLUSIONS: Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.

Experiences of breast feeding at work for physicians, residents and medical students: a scoping review.

OBJECTIVE: To review and summarise the available literature regarding breastfeeding experiences of medical students, residents and physicians. ELIGIBILITY CRITERIA: Articles of any design, including non-peer reviewed data that examine the experiences of breast feeding of medical students, residents and staff physicians. INFORMATION SOURCES: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid EMBASE, Scopus and Web of Science. RISK OF BIAS: All peer-reviewed studies underwent risk-of-bias assessment using relevant tools, depending on the study design. INCLUDED STUDIES: We included 71 citations; 51 surveys, 3 narrative descriptions, 9 editorials or letters to the editor, and 3 reviews. SYNTHESIS OF RESULTS: Included articles were heterogeneous with respect to their study design, target population and outcomes reported. Most articles had a high risk of bias. Only five articles reported the impact of an intervention. DESCRIPTION OF EFFECT: Despite heterogeneity, the majority of articles described important barriers to breast feeding for physicians, residents and medical students. These barriers were similar across studies, and included inadequate and inaccessible space, time constraints and inflexible scheduling, and lack of colleague support. The consequences of these barriers included low milk supply and early discontinuation of breast feeding. STRENGTHS AND LIMITATIONS OF EVIDENCE: Due to the observed heterogeneity of articles identified in this review, we are unable to assess trends in barriers or duration of breastfeeding over time. INTERPRETATION: Interventions to overcome systemic and cultural barriers to breast feeding are needed to meet legal obligations of workplaces for physicians and trainees. These interventions should be formally evaluated using implementation science or quality improvement methods.

Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression.

OBJECTIVE: Depression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD. DESIGN: The Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn's disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn's disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA). RESULTS: We identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC. CONCLUSION: Patients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn's disease and UC. These results may impact counselling and management of depression and IBD.

Increasing Rates of Arthroplasty for Psoriatic Arthritis in the United Kingdom Between 1995 and 2010.

OBJECTIVE: Arthroplasty requirements among patients with psoriatic arthritis (PsA) are not well known. This information is important to clinical and policy stakeholders for health-system planning and may serve as a surrogate for estimation of the efficacy of disease-modifying therapy. METHODS: We utilized The Health Improvement Network (THIN), a large general practice medical records database in the UK, to assess rates of primary total arthroplasty among patients with PsA and the general population between the years 1995 and 2010. Linear regression was used to estimate arthroplasty rates for the 2 cohorts during the study period, and Poisson regression was used to determine age- and sex-adjusted incidence rate ratios (IRRs) between the PsA and general population cohorts. RESULTS: We identified 5,619 patients with incident PsA and 5,090,814 eligible patients from the general population between 1995 and 2010. In total, 187 primary total arthroplasties were documented in patients with PsA, and 80,163 primary total arthroplasties were documented in the general population. A trend of increasing arthroplasty rates was observed for both the PsA (R2 = 0.809; P < 0.0001) and general population (R2 = 0.890; P < 0.0001) cohorts during the study period. After adjustment for age and sex, patients with PsA had a first arthroplasty incidence rate that was twice that of the general population (IRR 2.01 [95% confidence interval 1.73-2.34]; P < 0.0001), notably beyond the year 2003 when biologic therapies were introduced. CONCLUSION: Both the general population and patients with PsA have experienced increasing rates of first arthroplasty from 1995 to 2010, although the overall incidence rate was significantly higher for those with PsA.

Depression as a risk factor for the development of rheumatoid arthritis: a population-based cohort study.

OBJECTIVES: Major depressive disorder (MDD) is associated with increased levels of systemic proinflammatory cytokines, including tumour necrosis factor alpha. As these cytokines are pathogenic in autoimmune diseases such as rheumatoid arthritis (RA), our aim was to explore on a population-level whether MDD increases the risk of developing RA. METHODS: A retrospective cohort study was conducted using The Health Improvement Network (THIN) database (from 1986 to 2012). Observation time was recorded for both the MDD and referent cohorts until patients developed RA or were censored. Cox proportional hazards models were used to determine the risk of developing RA among patients with MDD, accounting for age, sex, medical comorbidities, smoking, body mass index and antidepressant use. RESULTS: A cohort of 403 932 patients with MDD and a referent cohort of 5 339 399 patients without MDD were identified in THIN. Cox proportional hazards models revealed a 31% increased risk of developing RA among those with MDD in an unadjusted model (HR=1.31, 95% CI 1.25 to 1.36, p<0.0001). When adjusting for all covariates, the risk remained significantly increased among those with MDD (HR=1.38, 95% CI 1.31 to 1.46, p<0.0001). Antidepressant use demonstrated a confounding effect that was protective on the association between MDD and RA. CONCLUSION: MDD increased the risk of developing RA by 38%, and antidepressants may decrease this risk in these patients. Future research is necessary to confirm the underlying mechanism of MDD on the pathogenesis of RA.

Psoriasis and the risk of foot and ankle tendinopathy or enthesopathy in the absence of psoriatic arthritis: a population-based study.

OBJECTIVES: Imaging studies in patients with cutaneous psoriasis have demonstrated asymptomatic bone and tendon changes, commonly of the foot and ankle. We sought to determine if patients with cutaneous psoriasis have an increased risk of clinically significant foot and ankle tendinopathy or enthesopathy compared with the general population. METHODS: Patients with cutaneous psoriasis and a general population cohort were identified in The Health Improvement Network, a general practice medical records database from the UK. All patients with psoriatic arthritis were excluded. Cox proportional-hazards models (α=0.05) estimated the HR for development of foot and ankle tendinopathy or enthesopathy among patients with psoriasis, with adjustment for numerous covariates. RESULTS: In total, 78 630 patients with cutaneous psoriasis and 5 983 338 persons from the general population were identified. In an unadjusted model, patients with cutaneous psoriasis had a 25% increased risk of developing foot and ankle tendinopathy or enthesopathy compared with the general population (HR 1.25, 95% CI 1.20 to 1.30, p<0.0001). The HR remained unchanged and statistically significant after adjusting for covariates, and in sensitivity analyses. CONCLUSIONS: These data suggest that patients with psoriasis can have foot and ankle tendinopathy or enthesopathy without having psoriatic arthritis, presenting a diagnostic challenge to physicians. Further research is needed to elucidate mechanisms contributing to this increased risk.

The impact of depression and antidepressant usage on primary biliary cholangitis clinical outcomes.

BACKGROUND: Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients. METHODS: We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA). RESULTS: We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07-0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05-0.83). CONCLUSIONS: In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients.

Career and research outcomes of the physician-scientist training program at the University of Calgary: a retrospective cohort study.

BACKGROUND: Physician-scientists are integral to medical research, with medical programs throughout Canada invested in training hybrid physician-scientists. Few data exist as to whether these programs are generating the diversity, gender equity and numbers of trainees essential for the future of medical research and teaching. We aimed to identify factors that contribute to research productivity, diversity and retention of individuals as physician-scientists. METHODS: We completed a retrospective cohort study, for the period 1973 to 2015, of the University of Calgary Leaders in Medicine Program in Calgary, Alberta. Participants were coregistered in graduate (master's or PhD) and medical degree programs. Primary outcomes included number of publications and the eventual career paths of graduates, with individuals characterized as physicians or physician-scientists on the basis of these metrics. RESULTS: Of the 307 individuals who were coregistered in or had completed a joint graduate and medical degree, 125 (40.7%) were PhD students/graduates, and 182 (59.3%) were master's trainees/graduates. While in the joint program, male PhD students consistently published more frequently than female PhD students. There was no significant difference in publication records between male and female master's students. Of the 172 individuals who were 5 years or more beyond graduation, 47 (27.3%) were classified as physician-scientists; these individuals consisted of 28 (40.6%) of the 69 PhD graduates and 19 (18.4%) of the 103 master's graduates. INTERPRETATION: Overall, our study shows that graduates receiving both clinical and research training, through master's or PhD programs, continue to be involved in research in their subsequent careers.

Depression Is Associated with an Increased Risk of Psoriatic Arthritis among Patients with Psoriasis: A Population-Based Study.

The factors that contribute to the development of psoriatic arthritis (PsA) among patients with psoriasis are not well known; however, systemic inflammation is believed to be important. On the basis of recent laboratory work demonstrating that major depressive disorder (MDD) is associated with increased systemic inflammation, we hypothesized that patients with psoriasis who develop MDD are at increased risk of subsequently developing PsA. We utilized The Health Improvement Network, a primary care medical records database, to identify 73,447 individuals with psoriasis. Patients were followed up to 25 years until the development of the primary outcome of PsA or the censor date. The exposure of interest was the development of MDD. Cox proportional-hazards models showed that patients with psoriasis who developed MDD were at significantly increased risk of subsequently developing PsA compared with patients who did not develop MDD, even after accounting for numerous covariates (hazard ratio 1.37, 95% confidence interval 1.05-1.80, P = 0.021). This result was maintained through numerous sensitivity analyses. These data support the hypothesis that MDD increases the risk of developing PsA among patients with psoriasis, suggesting a need for heightened prevention and management of MDD in patients with psoriasis.

The International Incidence of Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: Understanding the epidemiology of traumatic brain injury (TBI) is essential to shape public health policy, implement prevention strategies, and justify allocation of resources toward research, education, and rehabilitation in TBI. There is not, to our knowledge, a systematic review of population-based studies addressing the epidemiology of TBI that includes all subtypes. We performed a comprehensive systematic review and meta-analysis of the worldwide incidence of TBI. METHODS: A search was conducted on May 23, 2014, in Medline and EMBASE according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Abstracts were screened independently and in duplicate to identify original research. Study quality and ascertainment bias were assessed in duplicate using a previously published tool. Demographic data and incidence estimates from each study were recorded, along with stratification by age, gender, year of data collection, and severity. RESULTS: The search strategy yielded 4944 citations. Two hundred and sixteen articles met criteria for full-text review; 144 were excluded. Hand searching resulted in ten additional articles. Eighty-two studies met all eligibility criteria. The pooled annual incidence proportion for all ages was 295 per 100,000 (95% confidence interval: 274-317). The pooled incidence rate for all ages was 349 (95% confidence interval: 96.2-1266) per 100,000 person-years. Incidence proportion and incidence rate were examined to see if associated with age, sex, country, or severity. CONCLUSIONS: We conclude that most TBIs are mild and most TBIs occur in males among the adult population. The incidence of TBI varies widely by ages and between countries. Despite being an important medical, economic, and social problem, the global epidemiology of TBI is still not well-characterized in the current literature. Understanding the incidence of TBI, particularly mild TBI, remains challenging because of nonstandardized reporting among neuroepidemiological studies.

The Prevalence and Incidence of Dementia Due to Alzheimer's Disease: a Systematic Review and Meta-Analysis.

BACKGROUND: Updated information on the epidemiology of dementia due to Alzheimer's disease (AD) is needed to ensure that adequate resources are available to meet current and future healthcare needs. We conducted a systematic review and meta-analysis of the incidence and prevalence of AD. METHODS: The MEDLINE and EMBASE databases were searched from 1985 to 2012, as well as the reference lists of selected articles. Included articles had to provide an original population-based estimate for the incidence and/or prevalence of AD. Two individuals independently performed abstract and full-text reviews, data extraction and quality assessments. Random-effects models were employed to generate pooled estimates stratified by age, sex, diagnostic criteria, location (i.e., continent) and time (i.e., when the study was done). RESULTS: Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 119 studies met the inclusion criteria. In community settings, the overall point prevalence of dementia due to AD among individuals 60+ was 40.2 per 1000 persons (CI95%: 29.1-55.6), and pooled annual period prevalence was 30.4 per 1000 persons (CI95%: 15.6-59.1). In community settings, the overall pooled annual incidence proportion of dementia due to AD among individuals 60+ was 34.1 per 1000 persons (CI95%: 16.4-70.9), and the incidence rate was 15.8 per 1000 person-years (CI95%: 12.9-19.4). Estimates varied significantly with age, diagnostic criteria used and location (i.e., continent). CONCLUSIONS: The burden of AD dementia is substantial. Significant gaps in our understanding of its epidemiology were identified, even in a high-income country such as Canada. Future studies should assess the impact of using such newer clinical diagnostic criteria for AD dementia such as those of the National Institute on Aging-Alzheimer's Association and/or incorporate validated biomarkers to confirm the presence of Alzheimer pathology to produce more precise estimates of the global burden of AD.

The Association of Smoking and Surgery in Inflammatory Bowel Disease is Modified by Age at Diagnosis.

OBJECTIVES: We assessed the association of smoking at diagnosis of inflammatory bowel disease (IBD) on the need for an intestinal resection. METHODS: The Health Improvement Network was used to identify an inception cohort of Crohn's disease (n=1519) and ulcerative colitis (n=3600) patients from 1999-2009. Poisson regression explored temporal trends for the proportion of newly diagnosed IBD patients who never smoked before their diagnosis and the risk of surgery within 3 years of diagnosis. Cox proportional hazard models assessed the association between smoking and surgery, and effect modification was explored for age at diagnosis. RESULTS: The rate of never smokers increased by 3% per year for newly diagnosed Crohn's disease patients (incidence rate ratio (IRR) 1.03; 95% confidence interval (CI): 1.02-1.05), but not for ulcerative colitis. The rate of surgery decreased among Crohn's disease patients aged 17-40 years (IRR 0.96; 95% CI: 0.93-0.98), but not for ulcerative colitis. Smoking at diagnosis increased the risk of surgery for Crohn's disease patients diagnosed after the age of 40 (hazard ratio (HR) 2.99; 95% CI: 1.52-5.92), but not for those diagnosed before age 40. Ulcerative colitis patients diagnosed between the ages of 17 and 40 years and who quit smoking before their diagnosis were more likely to undergo a colectomy (ex-smoker vs. never smoker: HR 1.66; 95% CI: 1.04-2.66). The age-specific findings were consistent across sensitivity analyses for Crohn's disease, but not ulcerative colitis. CONCLUSIONS: In this study, the association of smoking and surgical resection was dependent on the age at diagnosis of IBD.

The Incidence of Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the condition's natural history. OBJECTIVE: This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender. METHODS: We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups. RESULTS: Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05). CONCLUSION: PD incidence generally increases with age, although it may stabilize in those who are 80+.

Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis.

BACKGROUND: Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply leads to a decrease in spina bifida (a birth defect of the spine). Still, many countries around the world have yet to approve mandatory fortification through government legislation. OBJECTIVES: We sought to perform a systematic review and meta-analysis of period prevalence of spina bifida by folic acid fortification status, geographic region, and study population. SEARCH METHODS: An expert research librarian used terms related to neural tube defects and epidemiology from primary research from 1985 to 2010 to search in EMBASE and MEDLINE. We searched the reference lists of included articles and key review articles identified by experts. SELECTION CRITERIA: Inclusion criteria included studies in English or French reporting on prevalence published between January 1985 and December 2010 that (1) were primary research, (2) were population-based, and (3) reported a point or period prevalence estimate of spina bifida (i.e., prevalence estimate with confidence intervals or case numerator and population denominator). Two independent reviewers screened titles and abstracts for eligible articles, then 2 authors screened full texts in duplicate for final inclusion. Disagreements were resolved through consensus or a third party. DATA COLLECTION AND ANALYSIS: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, abstracting data related to case ascertainment, study population, folic acid fortification status, geographic region, and prevalence estimate independently and in duplicate. We extracted overall data and any subgroups reported by age, gender, time period, or type of spina bifida. We classified each period prevalence estimate as "mandatory" or "voluntary" folic acid fortification according to each country's folic acid fortification status at the time data were collected (as determined by a well-recognized fortification monitoring body, Food Fortification Initiative). We determined study quality on the basis of sample representativeness, standardization of data collection and birth defect assessment, and statistical analyses. We analyzed study-level period prevalence estimates by using a random effects model (α level of < 0.05) for all meta-analyses. We stratified pooled period prevalence estimates by birth population, fortification status, and continent. RESULTS: Of 4078 studies identified, we included 179 studies in the systematic review and 123 in a meta-analysis. In studies of live births (LBs) alone, period prevalences of spina bifida were (1) lower in geographical regions with mandatory (33.86 per 100,000 LBs) versus voluntary (48.35 per 100,000 LBs) folic acid fortification, and (2) lower in studies of LBs, stillbirths, and terminations of pregnancy in regions with mandatory (35.22 per 100,000 LBs) versus voluntary (52.29 per 100,000 LBs) fortification. In LBs, stillbirths, and terminations of pregnancy studies, the lowest pooled prevalence estimate was in North America (38.70 per 100,000). Case ascertainment, surveillance methods, and reporting varied across these population-based studies. CONCLUSIONS: Mandatory legislation enforcing folic acid fortification of the food supply lags behind the evidence, particularly in Asian and European countries. This extensive literature review shows that spina bifida is significantly more common in world regions without government legislation regulating full-coverage folic acid fortification of the food supply (i.e., Asia, Europe) and that mandatory folic acid fortification resulted in a lower prevalence of spina bifida regardless of the type of birth cohort. African data were scarce, but needed, as many African nations are beginning to adopt folic acid legislation.

Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

BACKGROUND & AIMS: There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. METHODS: We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. RESULTS: In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). CONCLUSIONS: Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries.