Citations

Objective: To critically examine the feasibility, benefits, and limitations of an inpatient penicillin skin testing service and how pharmacists can be utilized. Data Sources: A PubMed search was performed from July 2016 through September 2016 using the following search terms: penicillin skin testing, penicillin allergy, β-lactam allergy. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All English-language studies assessing the use of penicillin skin testing as well as management and clinical outcomes of patients with a β-lactam allergy were evaluated. Data Synthesis: The prevalence of people self-identifying as penicillin allergic ranges from 10% to 20% in the United States. Being improperly labeled as penicillin allergic is associated with higher health care costs, worse clinical outcomes, and an increased prevalence of multidrug-resistant infections. Penicillin skin testing can be a tool used to clarify penicillin allergies and has been demonstrated to be a successful addition to antimicrobial stewardship programs in multiple health care settings. Prior to implementing a penicillin skin testing service, institutions will need to perform a feasibility analysis of who will supply labor and accept the financial burden as well as identify if the positive benefits of a penicillin skin testing service overcome the limitations of this diagnostic test. Conclusion: We conclude that institutions with high percentages of patients receiving non–β-lactams because of penicillin allergy labels would likely benefit the most from a penicillin skin testing service.

ObjectiveTo assess the safety and efficacy of short‐term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity.MethodsAdolescents (ages 12–18 years) with severe obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m2) were recruited for this double‐blind, randomized, placebo‐controlled trial. Participants completed 4 weeks of meal replacement therapy followed by randomization (1:1) to either 24 weeks of topiramate 75 mg/day or placebo. Mean changes were compared between groups.ResultsThirty adolescents (mean age 15.2 ± 1.7 years, mean BMI 40.3 ± 4.6 kg/m2) completed the meal replacement phase and were randomized; 21 completed the study. The difference in mean percent change in BMI between the topiramate and placebo groups was not significant (−1.9%; 95% CI: −5.2% to +1.5%; P = 0.291). Significant improvements in visceral fat and very‐low‐density lipoprotein cholesterol were observed in the topiramate compared with the placebo group. There were no concerning changes in neurocognitive function or bone health.ConclusionsIn this pilot study, 4 weeks of meal replacement therapy followed by 24 weeks of low‐dose topiramate compared with meal replacement therapy alone did not result in significant BMI reduction for adolescents with severe obesity.

Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

Background/Aims: Due to the progressive nature of type 2 diabetes mellitus (T2DM), deterioration in a patient’s general health is inevitable. Hence, the overall health of a T2DM patient is poor. Markers of worsening overall health such as metabolic abnormalities are predominant in the progression to any of the T2DM complications, which mask patterns of progression to individual complications, thereby making it difficult to predict which particular complication a patient will progress to (i.e. direction of progression). We aim to unmask the patterns and develop the most distinctive and predictive markers of progression to each individual complication. Methods: We take a two-step modeling approach using 94,536 T2DM patients’ 10-year, de-identified data from the OptumLabs™ Data Warehouse, a database that includes retrospective administrative claims data on commercially insured and Medicare Advantage enrollees, as well as electronic medical record data from a nationwide network of provider groups. First, we build a “general progression” model that predicts development of any new complication and captures markers of general health deterioration. Next, we develop “differential progression” models that predict progression to individual complications. We use least absolute shrinkage and selection operator (LASSO)-penalized Cox regressions to select variables and penalize the “differential progression” models against the “general progression” model such that “differential progression” patterns become unmasked. Significance of markers is determined via permutation test and predictive performance is evaluated through bootstrap estimation. Results: For a 6-year follow-up period, 31,968 (34%) of all patients progressed to at least one complication: chronic kidney disease (12%), ischemic heart disease (11%), cerebrovascular disease (8%), congestive heart failure (5%), peripheral vascular disease (5%), and renal failure (1%). In this ongoing research, we anticipate our predictive model to demonstrate improved interpretation of progression to each individual complication without causing reduced predictive performance. Conclusion: We study the progression of T2DM to multiple complications systematically and comprehensively by applying data mining techniques on the large amount of claims and clinical data from the OptumLabs Data Warehouse. By unmasking previously masked patterns and developing markers that suggest progression to a specific target complication, our study findings will assist clinicians in the management and treatment of T2DM.

Background: Knee laxity in the setting of suspected anterior cruciate ligament (ACL) injury is frequently assessed through physical examination using the Lachman, pivot-shift, and anterior drawer tests. The degree of laxity noted on these examinations may influence treatment decisions and prognosis. Hypothesis: Increased preoperative knee laxity would be associated with increased risk of subsequent revision ACL reconstruction and worse patient-reported outcomes 2 years postoperatively. Study Design: Cohort study; Level of evidence, 2. Methods: From an ongoing prospective cohort study, 2333 patients who underwent primary isolated ACL reconstruction without collateral or posterior cruciate ligament injury were identified. Patients reported by the operating surgeons as having an International Knee Documentation Committee (IKDC) grade D for Lachman, anterior drawer, or pivot-shift examination were classified as having high-grade laxity. Multiple logistic regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with increased odds of undergoing revision ACL reconstruction within 2 years of the index procedure, controlling for patient age, sex, Marx activity level, level of competition, and graft type. Multiple linear regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with worse IKDC score or Knee injury and Osteoarthritis Outcome Score Knee-Related Quality of Life subscale (KOOS-QOL) scores at a minimum 2 years postoperatively, controlling for baseline score, patient age, ethnicity, sex, body mass index, marital status, smoking status, sport participation, competition level, Marx activity rating score, graft type, and articular cartilage and meniscus status. Results: Pre-reconstruction laxity data were available for 2325 patients (99.7%). Two-year revision data were available for 2259 patients (96.8%), and patient-reported outcomes were available for 1979 patients (84.8%). High-grade preoperative laxity was noted in 743 patients (31.9%). The mean postoperative IKDC score was 81.8 ± 15.9, and the mean KOOS-QOL score was 72.0 ± 22.0. The presence of high-grade pre-reconstruction laxity was associated with significantly increased odds of ACL graft revision (odds ratio [OR] = 1.87 [95% CI, 1.19-2.95]; P = .007). The presence of high-grade pre-reconstruction laxity was not associated with any difference in postoperative IKDC (β = −0.56, P = .44) or KOOS-QOL (β = 0.04, P = .97). Conclusion: The presence of high-grade pre-reconstruction knee laxity as assessed by manual physical examination under anesthesia is associated with significantly increased odds of revision ACL surgery but has no association with patient-reported outcome scores at 2 years after ACL reconstruction.