Ernest H. Law

Corticosteroids in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Current Evidence and Implications for Future Research

Objective: To review the evidence for the use of steroids in adults presenting with Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or overlap. Data Sources: EMBASE (1974 to April 2014), MEDLINE (1946 to April 2014), Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970 to January 2014) were searched using the terms: prednisone, methylprednisolone, dexamethasone, prednisolone, steroids, glucocorticoids, corticosteroids, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and SJS/TEN overlap. Study Selection and Data Extraction: English-language, full reports of experimental and observational studies were included. Bibliographies from pertinent publications were reviewed for additional references. Prespecified outcomes included survival, survival to discharge, hospitalization without intensive care, length of intensive care stay, duration of hospitalization, ophthalmological complications, infection rates, and adverse events. Data Synthesis: Six studies that used steroids for SJS, TEN, and/or overlap were included. All studies were retrospective cohort studies with no case-control or cross-sectional studies; 5 studies reported on steroid doses, and 2 studies reported time from disease onset to steroid use (2-4 days). Only 1 of 6 studies reported a statistically significant impact on mortality with steroids use (odds ratio = 0.4; 95% CI = 0.2-0.9). Adverse event rates were not reported in any of the studies. Conclusions: A review of the current evidence reveals a need for prospective, randomized controlled studies to provide more definitive conclusions on steroid use in patients with SJS, TEN, and/or overlap.

Association Between Proton Pump Inhibitors and Microscopic Colitis: Implications for Practice and Future Research.

Objective: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. Data Sources: We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis. Study Selection: Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC. Data Extraction/Synthesis: A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC. Conclusions: There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.

Racial and ethnic differences in risk of second primary cancers among breast cancer survivors

Disparities exist in breast cancer (BC) outcomes between racial and ethnic groups in the United States. Reasons for these disparities are multifactorial including differences in genetics, stage at presentation, access to care, and socioeconomic factors. Less is documented on racial/ethnic differences in subsequent risk of second primary cancers (SPC). The purpose of this study is to evaluate the risk of SPC among different racial/ethnic groups of women with BC. We conducted a retrospective cohort study of 134,868 Non-Hispanic White, 17,484 Black, 18,034 Hispanic, and 19,802 Asian/Pacific Islander (API) women with stages I–III BC in twelve Surveillance, Epidemiology and End Results Program registries between 2001 and 2010. Standardized incidence ratios (SIR), 95xa0% confidence intervals (CI), and absolute excess risks were calculated by comparing incidence of SPC in the cohort to incidence in the general population for specific cancer sites by race/ethnicity and stratified by index BC characteristics. All women were at increased risks of second primary BC and acute myeloid leukemia (AML), with higher risk among more advanced stage index BC. Black and API women had higher SIRs for AML [4.86 (95xa0% CI 3.05–7.36) and 5.00 (95xa0% CI 3.26–7.32)], respectively] which remained elevated among early-stage (I) BC cases. Women with a history of invasive BC have increased risk of SPC, most notable for second primary BC and AML. These risks for secondary cancers differ by race/ethnicity. Studies evaluating possible genetic and biobehavioral mechanisms underlying these differences are warranted. Strategies for BC adjuvant treatment and survivorship care may require further individualization with consideration given to race/ethnicity.

Differential benefit risk assessment of DOACs in the treatment of venous thromboembolism: focus on dabigatran

Venous thromboembolism includes deep vein thrombosis and pulmonary embolism and is a serious medical condition that requires anticoagulation as part of treatment. Currently, standard therapy consists of parenteral anticoagulation followed by a vitamin K antagonist (VKA). The pharmacokinetic and pharmacodynamic profiles of the direct oral anticoagulants (DOACs) differ from VKAs, which overcome some of the limitations of VKAs and have practical implications on their use in clinical situations. Dabigatran is a prodrug that undergoes primarily renal elimination and does not affect cytochrome P450 enzymes. Assays to quantify the degree of anticoagulation and the therapeutic level of DOAC are either unavailable for routine clinical use or require specific calibration. Routine monitoring of DOACs is not recommended at this time. Dabigatran, rivaroxaban, and apixaban are DOACs that have been studied for treatment of venous thromboembolism. Clinical trials comparing DOACs with standard therapy have shown them to be non-inferior for acute and extended therapy. Each DOAC has a unique benefit and harm profile that should be considered prior to use. The distinguishing characteristics of dabigatran include a requirement of parenteral anticoagulation prior to acute treatment, clinical trial results comparing it with a VKA for extended treatment, association with upper gastrointestinal adverse events, and increased risk of gastrointestinal bleed. Rivaroxaban is the only DOAC that has once-daily dosing while apixaban is the only DOAC that has lower risk of overall, major, and gastrointestinal bleeding compared with VKA. A common drawback of DOACs is the lack of an available reversal agent. Clinical trials of reversal agents are ongoing and one application for approval has been submitted to the US Food and Drug Administration. Selection of a DOAC for acute and extended therapy requires a shared decision-making approach that includes a comprehensive assessment of the benefits and harms of each individual DOAC.

Increasing uptake of comparative effectiveness and patient-centered outcomes research among stakeholders: Insights from conference discussion

The goal of comparative effectiveness research (CER) and patient-centered outcomes research (PCOR) is to improve health outcomes by providing stakeholders with evidence directly relevant to decision making. In January 2017, the Pharmaceutical Research and Manufacturers Association Foundation, alongside the Academy for Managed Care Pharmacy, organized a conference aimed at engaging experts and opinion leaders representing clinicians, patients and payers to identify and discuss barriers and strategies to enhancing uptake and use of CER/PCOR. This report summarizes the conference discussion in the following sections: preconference survey; summary of barriers and strategies to the uptake of CER/PCOR identified by conference attendees; and future perspectives on the field.

Evaluation of patients with type 2 diabetes mellitus receiving treatment during the pre-diabetes period: Is early treatment associated with improved outcomes?

AIMnThis study evaluates the association of pretreatment with oral antidiabetics (OADs) on clinical outcomes and health resource utilization among commercially insured type II diabetes mellitus (T2DM) patients in the United States.nnnMETHODSnUsing administrative data (Truven MarketScan® Research Databases), patients diagnosed with T2DM between 2007 and 2014 with ⩾6months continuous enrolment pre- and post-diagnosis were evaluated. Pretreatment was defined as OAD use at least 3months prior to T2DM diagnosis. Time-to-insulin initiation and healthcare costs were compared by OAD pretreatment status.nnnRESULTSnOf the 866,605 patients studied, 241,856 (27.9%) were pretreated prior to T2DM diagnosis. Mean follow-up was 2.9years for pretreatment and 3.1years for those without pretreatment. Monthly diabetes-related pharmacy costs were significantly higher among pretreated patients (

Clinical Trajectories, Healthcare Resource Use, and Costs of Diabetic Nephropathy Among Patients with Type 2 Diabetes: A Latent Class Analysis

66 versus

Choice Blindness and Health-State Choices among Adolescents and Adults

36, p<0.0001), as were overall monthly pharmacy costs (

Healthcare Resource Use, Costs, and Disease Progression Associated with Diabetic Nephropathy in Adults with Type 2 Diabetes: A Retrospective Observational Study

255 versus

The Role of Personality in Treatment-related Outcome Preferences among Future Pharmacists

198, p<0.0001). Pretreated patients had lower mean monthly costs, both total (