Assessment of a modified MINDS-based protocol for management of alcohol withdrawal syndrome on an inpatient medical service.

OBJECTIVE: To determine if a novel symptom-based alcohol withdrawal syndrome (AWS) protocol in a US Veterans cohort leads to significant clinical improvements in patient outcomes and safety. BACKGROUND: Prior studies of AWS management, oftentimes using the revised version of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) index, have demonstrated the effectiveness of symptom-triggered therapy for AWS. The Minnesota Detoxification Scale (MINDS) is an alternative to the CIWA-Ar index but remains unevaluated outside of the intensive care unit (ICU) setting. This study assesses outcomes in AWS management prior to and after the implementation of a novel MINDS-based AWS protocol (SDAWP) utilizing a revised MINDS index (MINDS-rev) in an inpatient medical ward setting. METHODS: Retrospective cohort study including encounters prior to (n = 342) and after (n = 338) the implementation of the protocol. Pre- and post-protocol encounters were selected by combinations of diagnostic codes and charting elements. Outcome measures of AWS management were obtained in both groups. The primary endpoint was median total benzodiazepine exposure. Secondary outcomes included median length of hospitalization, median duration of benzodiazepine administration, and the incidence of complications. RESULTS: The median total benzodiazepine exposure in the post-SDAWP group was significantly lower than the pre-SDAWP group (21.2 vs. 12.0 mg, p < 0.0001) and for a significantly shorter median duration of time (4.0 vs. 3.0 days, p < 0.0001). There was no significant difference in the median length of stay (4.0 vs. 4.0 days, p = 0.50). The incidence of delirium tremens (21 vs. 7, p = 0.01) and need for transfer to a higher level of care (33 vs. 12, p = 0.002) was significantly lower in the post-SDAWP group. CONCLUSION: The SDAWP has provided significant improvements in AWS management in our institution and may potentially serve as a template for wider use in other inpatient settings.

Association of Treatment With 5α-Reductase Inhibitors With Time to Diagnosis and Mortality in Prostate Cancer.

Importance: 5α-Reductase inhibitors (5-ARIs), commonly used to treat benign prostatic hyperplasia, reduce serum prostate-specific antigen (PSA) concentrations by 50%. The association of 5-ARIs with detection of prostate cancer in a PSA-screened population remains unclear. Objective: To test the hypothesis that prediagnostic 5-ARI use is associated with a delayed diagnosis, more advanced disease at diagnosis, and higher risk of prostate cancer-specific mortality and all-cause mortality than use of other or no PSA-decreasing drugs. Design, Setting, and Participants: This population-based cohort study linked the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records for 80 875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from January 1, 2001, to December 31, 2015. Patients were followed up until death or December 31, 2017. Data analysis was performed from March 2018 to May 2018. Exposures: Prediagnostic 5-ARI use. Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality (PCSM). Secondary outcomes included time from first elevated PSA (defined as PSA≥4 ng/mL) to diagnostic prostate biopsy, cancer grade and stage at time of diagnosis, and all-cause mortality (ACM). Prostate-specific antigen levels for 5-ARI users were adjusted by doubling the value, consistent with previous clinical trials. Results: Median (interquartile range [IQR]) age at diagnosis was 66 (61-72) years; median [IQR] follow-up was 5.90 (3.50-8.80) years. Median time from first adjusted elevated PSA to diagnosis was significantly greater for 5-ARI users than 5-ARI nonusers (3.60 [95% CI, 1.79-6.09] years vs 1.40 [95% CI, 0.38-3.27] years; P < .001) among patients with known prostate biopsy date. Median adjusted PSA at time of biopsy was significantly higher for 5-ARI users than 5-ARI non-users (13.5 ng/mL vs 6.4 ng/mL; P < .001). Patients treated with 5-ARI were more likely to have Gleason grade 8 or higher (25.2% vs 17.0%; P < .001), clinical stage T3 or higher (4.7% vs 2.9%; P < .001), node-positive (3.0% vs 1.7%; P < .001), and metastatic (6.7% vs 2.9%; P < .001) disease than 5-ARI nonusers. In a multivariable regression, patients who took 5-ARI had higher prostate cancer-specific (subdistribution hazard ratio [SHR], 1.39; 95% CI, 1.27-1.52; P < .001) and all-cause (HR, 1.10; 95% CI, 1.05-1.15; P < .001) mortality. Conclusions and Relevance: Results of this study demonstrate that prediagnostic use of 5-ARIs was associated with delayed diagnosis and worse cancer-specific outcomes in men with prostate cancer. These data highlight a continued need to raise awareness of 5-ARI-induced PSA suppression, establish clear guidelines for early prostate cancer detection, and motivate systems-based practices to facilitate optimal care for men who use 5-ARIs.

Diagnosing and managing common food allergies: a systematic review.

CONTEXT: There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies. OBJECTIVE: To perform a systematic review of the available evidence on the prevalence, diagnosis, management, and prevention of food allergies. DATA SOURCES: Electronic searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials. Searches were limited to English-language articles indexed between January 1988 and September 2009. STUDY SELECTION: Diagnostic tests were included if they had a prospective, defined study population, used food challenge as a criterion standard, and reported sufficient data to calculate sensitivity and specificity. Systematic reviews and randomized controlled trials (RCTs) for management and prevention outcomes were also used. For foods where anaphylaxis is common, cohort studies with a sample size of more than 100 participants were included. DATA EXTRACTION: Two investigators independently reviewed all titles and abstracts to identify potentially relevant articles and resolved discrepancies by repeated review and discussion. Quality of systematic reviews and meta-analyses was assessed using the AMSTAR criteria, the quality of diagnostic studies using the QUADAS criteria most relevant to food allergy, and the quality of RCTs using the Jadad criteria. DATA SYNTHESIS: A total of 12,378 citations were identified and 72 citations were included. Food allergy affects more than 1% to 2% but less than 10% of the population. It is unclear if the prevalence of food allergies is increasing. Summary receiver operating characteristic curves comparing skin prick tests (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.81-0.93) and serum food-specific IgE (AUC, 0.84; 95% CI, 0.78-0.91) to food challenge showed no statistical superiority for either test. Elimination diets are the mainstay of therapy but have been rarely studied. Immunotherapy is promising but data are insufficient to recommend use. In high-risk infants, hydrolyzed formulas may prevent cow's milk allergy but standardized definitions of high risk and hydrolyzed formula do not exist. CONCLUSION: The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis.

Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families.

PURPOSE: Because the clinical significance of immunoglobulin abnormalities reported in relatives of familial Waldenström macroglobulinemia (WM) patients is unknown, we initiated a follow-up study of three WM families originally evaluated 27 years previously. EXPERIMENTAL DESIGN: Of 29 eligible first-degree relatives of WM patients, 27 (93%) had originally participated in clinical and electrophoretic evaluations. We re-contacted all participants for prospective follow-up electrophoretic analysis and other studies. RESULTS: Initially, five relatives had IgM monoclonal gammopathy (IgM MG), and four had IgM polyclonal gammopathy (PG). Twenty-two relatives (81%) were re-evaluated. Median follow-up was 17 years (range, 7-27). At re-contact, all IgM MG persisted or progressed, including three that evolved to WM. Among the four with PG, two new IgM MG cases developed. Overall, seven relatives (26%) had IgM MG, and five (18%) had IgM PG. CONCLUSIONS: Although based on small numbers, this study provides the longest comprehensive follow-up of WM families to date. IgM MG seems to be a phenotypic marker of WM susceptibility in some families and may have a high risk of progression to WM. IgM PG may also be important in WM families. These observations require validation in larger studies and, if confirmed, may be used to identify a cohort (relatives with IgM MG) for future prevention strategies.

Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries.

The G101W founder mutation is the most common CDKN2A mutation in Italy, Spain, and France. As the background of modifying genes, environmental exposures, and sun behavior vary across countries, studying G101W carriers from distinct countries offers a unique opportunity to evaluate possible modifying factors in melanoma development. We evaluated 76 G101W cases and 59 carrier controls from France, Italy, Spain, and the United States. Hair color and dysplastic nevi distributions differed significantly in cases and controls across the 4 study groups. Cases also varied significantly for eye color, freckling, and nevi. The distribution of MC1R variants in cases differed significantly across study groups because 12% of Italian melanoma patients had > or =2 MC1R variants vs. >50% for the other case groups. Several MC1R covariates showed significant associations with melanoma risk in all groups combined and in the American, French, and Spanish samples; no significant findings were observed in the Italian sample. In multiple-case families, the number and type of MC1R variants varied significantly between multiple-primary-melanoma and single-primary-melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of MC1R variants increased. The variation in the effects of the cutaneous phenotypic and MC1R factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline CDKN2A mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered.

Menthol cigarettes, smoking cessation, atherosclerosis, and pulmonary function: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: African American smokers are more likely to experience tobacco-related morbidity and mortality than European American smokers, and higher rates of menthol cigarette smoking may contribute to these disparities. METHODS: We prospectively measured cumulative exposure to menthol and nonmenthol cigarettes and smoking cessation behavior (1985-2000), coronary calcification (2000), and 10-year change in pulmonary function (1985-1995) in African American and European American smokers recruited in 1985 for the Coronary Artery Risk Development in Young Adults Study. RESULTS: We identified 1535 smokers in 1985 (972 menthol and 563 nonmenthol); 89% of African Americans preferred menthol vs 29% of European Americans (P<.001). After adjustment for ethnicity, demographics, and social factors, we found nonsignificant trends in menthol smokers toward lower cessation (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.49-1.02; P = .06) and recent quit attempt (OR, 0.77; 95% CI, 0.56-1.06; P = .11) rates and a significant increase in the risk of relapse (OR, 1.89; 95% CI, 1.17-3.05; P = .009). Per pack-year of exposure, however, we found no differences from menthol in tobacco-related coronary calcification (adjusted OR, 1.27; 95% CI, 1.01-1.60 for menthol cigarettes and 1.33; 95% CI, 1.06-1.68 for nonmenthol cigarettes per 10-pack-year increase; P = .75 for comparison) or 10-year pulmonary function decline (adjusted excess decline in forced expiratory volume in 1 second, 84 mL; 95% CI, 32-137 for menthol cigarettes and 80 mL; 95% CI, 30-129 for nonmenthol cigarettes, per 10-pack-year increase; P = .88 for comparison). CONCLUSION: Menthol and nonmenthol cigarettes seem to be equally harmful per cigarette smoked in terms of atherosclerosis and pulmonary function decline, but menthol cigarettes may be harder to quit smoking.

MC1R germline variants confer risk for BRAF-mutant melanoma.

Germline variants in MC1R, the gene encoding the melanocortin-1 receptor, and sun exposure increase risk for melanoma in Caucasians. The majority of melanomas that occur on skin with little evidence of chronic sun-induced damage (non-CSD melanoma) have mutations in the BRAF oncogene, whereas in melanomas on skin with marked CSD (CSD melanoma) these mutations are less frequent. In two independent Caucasian populations, we show that MC1R variants are strongly associated with BRAF mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma associated with MC1R is due to an increase in risk of developing melanomas with BRAF mutations.