Julia McNabb-Baltar

Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy

Senataxin recently was identified as the mutated gene in ataxia‐oculomotor apraxia 2, which is characterized by ataxia, oculomotor apraxia, and increased α‐fetoprotein levels. In this study, we evaluated 24 ataxic patients from 10 French‐Canadian families. All cases have a homogeneous phenotype consisting of a progressive ataxia appearing between 2 and 20 (mean age, 14.8) years of age with associated dysarthria, saccadic ocular pursuit, distal amyotrophy, sensory and motor neuropathy, and increased α‐fetoprotein levels but absence of oculomotor apraxia. Linkage disequilibrium was observed with markers in the ataxia‐oculomotor apraxia 2 locus on chromosome 9q34. We have identified four mutations in senataxin in the French‐Canadian population including two novel missense mutations: the 5927T→G mutation changes the leucine encoded by codon 1976 to an arginine in the helicase domain (L1976R), and the 193G→A mutation changes a glutamic acid encoded by codon 65 into a lysine in the N‐terminal domain of the protein (E65K). The common L1976R mutation is shared by 17 of 20 (85%) carrier chromosomes. The study of this large French‐Canadian cohort better defines the phenotype of this ataxia and presents two novel mutations in senataxin including the more common founder mutation in the French‐Canadian population. Ann Neurol 2005;57:408–414

Meta‐analysis: rectal indomethacin for the prevention of post‐ERCP pancreatitis

Despite initial evidence in the literature, nonsteroidal anti‐inflammatory drugs (NSAIDs) have not been widely used to prevent post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).

Clinical manifestations of portal hypertension.

The portal hypertension is responsible for many of the manifestations of liver cirrhosis. Some of these complications are the direct consequences of portal hypertension, such as gastrointestinal bleeding from ruptured gastroesophageal varices and from portal hypertensive gastropathy and colopathy, ascites and hepatorenal syndrome, and hypersplenism. In other complications, portal hypertension plays a key role, although it is not the only pathophysiological factor in their development. These include spontaneous bacterial peritonitis, hepatic encephalopathy, cirrhotic cardiomyopathy, hepatopulmonary syndrome, and portopulmonary hypertension.

A population-based assessment of the burden of acute pancreatitis in the United States.

Objectives The aim of this study is to investigate the incidence and mortality of emergency department (ED) visits in the United States attributed to acute pancreatitis (AP) and quantify predictors of admission and mortality. Methods Using the nationwide ED sample, all ED visits between 2006 and 2009 for AP were extracted. Multivariable analyses were fitted for prediction of admission and mortality. Results A weighted sample of 1,224,121 patient visits with AP was captured. Of those, 75.4% resulted in admission and 0.7% died. Between 2006 and 2009, the incidence of AP ED visits increased from 9.9 to 10.6 per 10,000 person-years. Patients were more likely to be admitted if sicker (Charlson Comorbidity Index score ≥3; OR, 6.48; P < 0.001) and if the etiology of pancreatitis was alcoholic versus biliary (OR, 2.20; P < 0.001). They were more likely to die if sicker (Charlson Comorbidity Index score ≥3; OR, 1.51; P < 0.001) and covered with Medicare or Medicaid versus private insurance (OR, 1.40; P < 0.001 and OR, 1.45; P < 0.001, respectively). Conclusions Emergency department visits for AP represent a significant burden on US health care. Although mortality is lower than previously reported, significant disparities exist in patients presenting with AP with regard to admission and mortality rates. Further investigations are needed to assess these disparities.

The Atlanta Classification, Revised Atlanta Classification, and Determinant-Based Classification of Acute Pancreatitis: Which Is Best at Stratifying Outcomes?

Objectives To determine which classification is more accurate in stratifying severity. Methods The study used a retrospective analysis of a prospective acute pancreatitis database (June 2005–December 2007). Acute pancreatitis severity was stratified according to the Atlanta classification (AC) 1992, the revised Atlanta classification (RAC) 2012, and the determinant-based classification (DBC) 2012. Receiver operating characteristic analysis (area under the curve) compared the accuracy of each classification. Logistic regression identified predictors of mortality. Results 338 patients were analyzed: 13% had persistent organ failure (POF) (>48 hours), of whom 37% had multisystem POF, and 11% had pancreatic necrosis, of whom 19% had infected necrosis. Mortality was 4.1%. For predicting mortality (area under the curve), the RAC (0.91) and DBC (0.92) were comparable (P = 0.404); both outperformed the AC (0.81) (P < 0.001). For intensive care unit admission, the RAC (0.85) and DBC (0.85) were comparable (P = 0.949); both outperformed the AC (0.79) (P < 0.05). There were 2 patients in the critical category of the DBC. Multisystem POF was an independent predictor of mortality (odds ratio, 75.0; 95% confidence interval, 13.7–410.6; P < 0.001), whereas single-system POF, sterile necrosis, and infected necrosis were not. Conclusion The RAC and DBC were generally comparable in stratifying severity. The paucity of patients in the critical category in the DBC limits its utility. Neither classification accounts for the impact of multisystem POF, which was the strongest predictor of mortality.

Caesarean section to prevent transmission of hepatitis B: A meta-analysis

BACKGROUND Vertical transmission of hepatitis B virus (HBV) occurs in up to 10% to 20% of births. OBJECTIVE To assess whether Caesarean section, compared with vaginal delivery, prevents HBV transmission. METHODS A systematic review and meta-analysis was conducted. Two investigators independently searched PubMed, EMBASE and other databases for relevant studies published between 1988 and 2013. A manual search of relevant topics and major conferences for abstracts was also conducted. Randomized trials, cohort and case-control studies assessing the effect of delivery mode on vertical transmission of HBV were included. Studies assessing antiviral therapy and patients with coinfection were excluded. The primary outcome was HBV transmission rates according to delivery method. RESULTS Of the 430 studies identified, 10 were included. Caesarean section decreased the odds of HBV transmission by 38% compared with vaginal delivery (OR 0.62 [95% CI 0.40 to 0.98]; P=0.04) based on a random-effects model. Significant heterogeneity among studies was found (I²=63%; P=0.003), which was largely explained by variation in hepatitis B immune globulin (HBIG) administration. Meta-regression showed a significant linear association between the percentage of infants receiving HBIG per study and the log OR (P=0.005), with the least benefit observed in studies with 100% HBIG administration. Subgroup analysis of hepatitis B e-antigen-positive women who underwent Caesarean section did not show a significant reduction in vertical transmission. DISCUSSION Caesarean section may protect against HBV transmission; however, convincing benefit could not be demonstrated due to significant study heterogeneity from variable HBIG administration, highlighting the importance of HBIG in HBV prevention. CONCLUSION More high-quality studies are needed before any recommendations can be made.

The impact of Medicare eligibility on cancer screening behaviors

INTRODUCTION Lack of health insurance limits access to preventive services, including cancer screening. We examined the effects of Medicare eligibility on the appropriate use of cancer screening services in the United States. METHODS We performed a cross-sectional analysis of the 2012 Behavioral Risk Factor and Surveillance System (analyzed in 2014). Univariable and logistic regression analyses were performed for participants aged 60-64 and 66-70 to examine the effects of Medicare eligibility on prevalence of self-reported screening for colorectal, breast, and prostate cancers. Sub-analyses were performed among low-income (<

State-of-the-art management of acute bleeding peptic ulcer disease

25,000 annual/household) individuals. RESULTS Medicare-eligible individuals were significantly more likely to undergo all examined preventive services (colorectal cancer OR: 1.90; 95% CI 1.79-2.04; prostate cancer OR: 1.29; 95% CI 1.17-1.43; breast cancer OR: 1.23; 95% CI 1.10-1.37) and the effect was most pronounced among low-income individuals (colorectal cancer OR: 2.04; 95% CI 1.8-2.32; prostate cancer OR: 1.39; 95% CI 1.12-1.72; breast cancer OR: 1.42, 95% CI 1.20-1.67). Access to a healthcare provider was the strongest independent predictor of undergoing appropriate screening, ranging from OR 2.73 (95% CI 2.20-3.39) for colorectal cancer screening in the low-income population to OR 4.79 (95% CI 3.95-5.81) for breast cancer screening in the overall cohort. The difference in screening prevalence was most pronounced when comparing Medicare-eligible participants to uninsured Medicare-ineligible participants (+33.2%). CONCLUSIONS Medicare eligibility impacts the prevalence of cancer screening, likely as a result of increased access to primary care. Low-income individuals benefit most from Medicare eligibility. Expanded public insurance coverage to these individuals may improve access to preventive services.

Pancreatic enzyme supplements are not effective for relieving abdominal pain in patients with chronic pancreatitis: Meta-analysis and systematic review of randomized controlled trials.

The management of patients with non variceal upper gastrointestinal bleeding has evolved, as have its causes and prognosis, over the past 20 years. The addition of high-quality data coupled to the publication of authoritative national and international guidelines have helped define current-day standards of care. This review highlights the relevant clinical evidence and consensus recommendations that will hopefully result in promoting the effective dissemination and knowledge translation of important information in the management of patients afflicted with this common entity.

Data on Medicare eligibility and cancer screening utilization

Background. Pancreatic enzyme supplementation is widely used to treat pain in patients with chronic pancreatitis, despite little evidence for efficacy. We performed a systematic review of the literature and a meta-analysis to investigate its effectiveness. Methods. All randomized controlled parallel or crossover trials in patients with chronic pancreatitis comparing pancreatic enzyme supplementation to placebo were included. The main outcome was improvement in pain score or reduced analgesic consumption. Two independent reviewers extracted data. Mantel-Haenszel random effect model meta-analysis was used whenever methodologically appropriate. Results. Five out of 434 retrieved studies were included in the systematic review. All studies used relatively similar methodology. Four studies using enteric-coated pancreatic enzyme supplementation failed to show any improvement in pain as compared to placebo. The only study using non-enteric-coated enzymes did show reduction in the pain score. There was significant heterogeneity among studies in both analyses. Random model meta-analysis of three studies showed no significant difference in the mean of daily pain score (mean difference: 0.09 (1.57–1.39), p = 0.91) or average weekly analgesic consumption (mean difference: −0.30 (−2.37–1.77), p = 0.77) between the periods of administering pancreatic enzyme supplementation versus placebo. Conclusion. Pancreatic enzyme supplements do not seem to relieve abdominal pain in patients with chronic pancreatitis and should not be prescribed solely for this purpose, given their significant cost and potential side effects.