Etanercept leads to a rapid recovery of a Dabrafenib-/Trametinib-associated toxic epidermal necrolysis-like severe skin reaction.

Targeted therapy with BRAF- and MEK-Inhibitors (BRAFi, MEKi) provides an excellent therapeutic option for patients with malignant melanomas with a BRAF-Mutation. Mild cutaneous adverse events have been common under the BRAF- and MEK-Inhibitor therapy, on the contrary, severe cutaneous adverse reactions to drugs (SCARs) are rarely reported. We present the case of a 59- year-old female patient who after the resection of cutaneous in-transit metastases of a malignant melanoma received one adjuvant cycle of Nivolumab followed by a switch of the therapy to an oral BRAFi/MEKi therapy. 3-4 Weeks after the therapy switch she developed high fever, chills, progredient general weakness, headaches, abdominal complaints, generalised rash as well as thrombocytopaenia, eosinophilia, elevated liver enzymes, declining kidney, and pulmonary function as well as a maculopapular exanthema. She was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS) and quickly started recovery after initiation of a high steroid substitution. Under steroid dose reduction, the exanthema worsened and toxic epidermal necrolysis (TEN) was histologically diagnosed. After a series of unsuccessful therapeutic approaches (high dose steroid, human immunoglobulins and ciclosporin) the patient received a single dose of the TNF-alpha inhibitor etanercept, which led to a quick recovery. This case demonstrates that DRESS and TEN can present a spectrum of possibly transitioning SCARs providing a diagnostic and therapeutic challenge. Nevertheless, in a such complicated therapeutic setting, etanercept may be lifesaving even after multiple previous unsuccessful therapies. This effective approach provides evidence SCARs due to BRAF/MEK targeted therapy may be driven by TNF-alpha.

Injection Site Reaction to Various Insulins as Type III Allergy With Urticarial Vasculitis in a Patient With Type I Diabetes Mellitus.

ABSTRACT: Injection site reactions are defined as skin reactions at the injection site to drugs administered subcutaneously. Pathophysiologically, these reactions are based on different immunological mechanisms. We report the case of a 49-year-old patient with type 1 diabetes mellitus (first diagnosis in 1994 at the age of 23 years). Continuous subcutaneous insulin infusion using an insulin pump has been used for many years. The patient presented to the department of dermatology with progressive symptoms in the area of the insulin injection sites on the lower abdomen, accompanied by pain, burning, erythema, tenderness, and the formation of subcutaneous nodules. Previous attempts to use different insulins and to change the injection sites did not improve his symptoms. Furthermore, the symptoms appeared within hours after the insulin pump was attached, so that the injection site has to be changed as soon as every 48 hours. No anaphylactic shock was reported at any time. Multiple histological specimens were obtained from an older lesion on the abdomen as well as from test sites after standard allergological tests (prick and intradermal tests) of various insulins. Histologically, these biopsies showed the image of an extensive deep-reaching small vessel vasculitis with the aspect of an urticarial vasculitis and confirmed the diagnosis of an injection-site reaction that can be characterized as a type III hypersensitivity reaction.

Clinical considerations for insulin pharmacotherapy in ambulatory care, part two: review of primary literature and an evidence-based approach for treatment.

IN BRIEF This article reinforces the dosing guidance from the package inserts of available insulin products and supplemental information provided by the manufacturers of insulin products. It reviews and evaluates pertinent primary literature detailing algorithms for the initiation and titration of insulin therapy that have helped to shape current clinical practice guidelines. The article discusses the clinical applicability of the evidence on insulin pharmacotherapy and offers recommendations for initiation and titration of various insulin products for insulin-requiring people with type 2 diabetes in the ambulatory care setting.

Impact of health literacy level on aspects of medication nonadherence reported by underserved patients with type 2 diabetes.

BACKGROUND: Medication adherence can be affected by many factors, including health literacy. The purpose of this study is to determine (1) if a relationship exists between health literacy and self-reported or objectively measured medication adherence and (2) which aspect or aspects of medication nonadherence are most associated with health literacy. SUBJECTS AND METHODS: This is a multicenter, cross-sectional survey study of adult patients with type 2 diabetes mellitus (T2DM), taking one or more antidiabetes medication for ≥6 months with a hemoglobin A1c (HbA1c) measure on record. Data collected included patient demographics (age, gender, race, language, highest level of education, injectable diabetes medication use, last HbA1c, and diabetes medication refill history) and two survey instruments (the Morisky eight-item Medication Adherence Scale [MMAS-8] and the short-form Test of Functional Health Literacy in Adults [s-TOFHLA]). Descriptive statistics and bivariate correlations were assessed, along with linear and logistic regression. RESULTS: One hundred ninety-two patients with an average HbA1c level of 8.1% were included. Of these subjects, 32.8% had limited health literacy as measured by the s-TOFHLA, 58.9% had low adherence as measured by MMAS-8, and 65.1% were nonadherent based on cumulative medication gap (CMG) analysis. Age was associated with s-TOFHLA (-0.411; P<0.01) and MMAS-8 (0.157; P<0.05) scores. HbA1c was associated with MMAS-8 (-0.209; P<0.01) and CMG (0.152; P<0.05) scores. There was no significant association between s-TOFHLA and MMAS-8 or CMG. However, s-TOFHLA was positively related to MMAS-8 question 8, assessing difficulty remembering to take medications (P=0.017). CONCLUSIONS: Health literacy level is not associated with self-reported or objectively measured medication adherence in underserved patients with T2DM. Lower health literacy scores are associated with a patient experiencing difficulty remembering to take medications.

The Hip Lag Sign--prospective blinded trial of a new clinical sign to predict hip abductor damage.

This study introduces and validates the Hip Lag Sign, a new clinical parameter to determine hip abductor damage, which appears to be one major cause for greater trochanteric pain syndrome. 26 patients who underwent standardized MRI-examination were prospectively enrolledbetween October 2009 and March 2012. A standard physical examination of the hip was performed, including the Hip Lag Sign as it is defined for the first time in this work. Hip Lag Sign results were statistically compared toMR images, to pain levels measured with the visual analogue scale and to results of the modified Harris Hip Score as a universal and well established diagnostic tool for the hip. Chi2- and Mann-Whitney-U-analysis were applied. Diagnostic accuracy was tested with 2×2-table-calculations.Kappa statistics were used to analyze inter-observer variability. A positive Hip Lag Sign is significantly associated with MRI-proven hip abductor damage (p<0.001). The Hip Lag Sign has a sensitivity of 89.47% and a specificity of 96.55%. The positive and negative predictive values are 94.44%, resp. 93.33%. Its diagnostic Odds Ratio is 239.000 (p<0.001; 95%-CI: 20.031-2827.819). The number needed to diagnose was 1.16.Inter-observer consistency was 98.1% and kappa statistics for inter-observer variability were 0.911. The Hip Lag Sign is specific and sensitive, easy and fast to perform and allows a reliable assessment on the hip abductors' status, especially when there is no access to further diagnostic devices such as MRI for example due to restricted resources like in developing countries. Thus, we recommend the inclusion of the Hip Lag Sign into everyday hip examinations, especially dealing with patients suffering from greater trochanteric pain syndrome.

Clinical Considerations for Insulin Pharmacotherapy in Ambulatory Care, Part One: Introduction and Review of Current Products and Guidelines.

In Brief This article describes available insulin products and published guidelines to aid clinicians in making treatment decisions for insulin-dependent patients with type 2 diabetes. It establishes the need for a thorough evaluation of the literature regarding ambulatory insulin dosing to further inform providers who manage insulin therapy for patients with type 2 diabetes.

Safety and efficacy of allopurinol in chronic kidney disease.

OBJECTIVE: To review the evidence surrounding the use of allopurinol in chronic kidney disease (CKD) and discuss safety and efficacy considerations of such use. DATA SOURCES: A literature search was conducted through MEDLINE (1950-July 2013), PubMed (1965-July 2013), and International Pharmaceutical Abstracts (1970-July 2013) using the search terms allopurinol and kidney or renal. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated for inclusion. DATA SYNTHESIS: Gout management with allopurinol in patients with CKD can be challenging because of the risk of adverse events and uncertain efficacy. Not all gout treatment guidelines provide recommendations for allopurinol use specifically in patients with CKD. Literature regarding the safety and efficacy of dosing allopurinol in CKD has shown inconsistent results and is based primarily on retrospective, case cohort or observational data. Some trials have demonstrated an increased risk of allopurinol-induced adverse reactions in patients with CKD, whereas others have not confirmed renal insufficiency as a risk factor. More CKD patients achieved a target uric acid level in studies where the allopurinol dose was titrated to effect as compared with those studies in which patients were given renally adjusted or untitrated allopurinol doses. CONCLUSIONS: Studies evaluating allopurinol use in patients with CKD have reported inconsistent findings relative to safety and efficacy. Providers should be aware of the potential risk of allopurinol hypersensitivity syndrome as well as the need for reducing the initiation dose and gradual titration of allopurinol to safely achieve a target serum urate level in this population.

Long-term outcome analysis of liver transplantation for severe hepatic trauma.

BACKGROUND: Liver transplantation (LTX) for severe hepatic trauma and its sequelae is a rare but potentially lifesaving option at the far end of the operative spectrum. METHODS: This study analyzes 12 cases with LTX for hepatic trauma and its consequences from two transplant centers. A total of 2,701 consecutive liver transplants unrelated to trauma served as a control group. χ and Mann-Whitney U-tests, Kaplan-Meier analysis with log-rank tests, and Cox regression analysis were applied. Addressed were issues before, during, and after LTX. Major study end points were patient and graft survival. RESULTS: The posttrauma transplant recipients are significantly younger (p = 0.014), with a significantly shorter graft survival (p = 0.038), resulting in a significantly higher retransplantation rate (p = 0.043). Of the 12 patients, 11 underwent surgical treatment for hepatic trauma before LTX with 7 of 12 patients experiencing liver necrosis at the time of LTX. Short-term survival and long-term survival are not significantly different between trauma and nontrauma patients. Severity of liver trauma (Moore Score) and concomitant injuries (Injury Severity Score [ISS]) have no significant impact on patient and graft survival. Four patients with hepatic trauma were treated with two-stage LTX with anhepatic phases between 14 hours and 28 hours. Two of those patients reached long-term survival (20-22 years). CONCLUSION: LTX for severe liver trauma and its consequences seems justified in extreme cases. The high frequency of liver necrosis at the time of LTX may indicate possible shortcomings in liver packing technique or liver resection for hemorrhage control. Thus, severe hepatic trauma requires treatment by experienced liver surgeons and emergency physicians. LEVEL OF EVIDENCE: Therapeutic study, level IV.

An elective course on postgraduate residency training.

OBJECTIVE: To develop, implement, and assess the impact of an elective course for pharmacy students on postgraduate pharmacy residency training. DESIGN: An elective course on residency training was developed using short lectures, group discussions, and active-learning strategies, such as small-group exercises, mock match, and mock interview. ASSESSMENT: Students were asked to self-assess their understanding and abilities related to residency training at the beginning and end of the semester based on course objectives. The median post-semester responses increased for all objectives compared to baseline (p<0.05). CONCLUSION: A residency elective using a variety of teaching methods increased student knowledge and confidence in their skills regarding residency training.

Rosiglitazone, myocardial ischemic risk, and recent regulatory actions.

OBJECTIVE: To review the evidence surrounding rosiglitazone and ischemic cardiovascular risk and discuss the Food and Drug Administration (FDA) decision to revise safety information and restrict access to the drug. DATA SOURCES: A literature search was conducted through MEDLINE (1950-January 2012), PubMed (1966-January 2012), and International Pharmaceutical Abstracts (1970-December 2011) using the search terms rosiglitazone and cardiovascular risk. Regulatory documents from the FDA and the Center for Drug Evaluation and Research, as well as reference citations from publications identified, were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated for inclusion. DATA SYNTHESIS: Literature regarding rosiglitazone and ischemic cardiovascular risk has shown inconsistent results. Meta-analyses by the FDA, GlaxoSmithKline, and several independent research groups suggest an increased risk for myocardial infarction (MI), while others have not. Long-term, controlled trials not designed to evaluate cardiovascular outcomes did not find a significant increase in cardiovascular events and had low event rates overall. The RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes) trial is the only prospective randomized trial to date designed to evaluate cardiovascular outcomes of rosiglitazone; the results were limited because of issues with study design and event adjudication. The only direct comparisons between rosiglitazone and pioglitazone are observational studies in which pioglitazone had a more favorable MI risk profile. CONCLUSIONS: Data involving rosiglitazone and an association with ischemic cardiovascular risk have yielded variable results. The FDA made the decision to restrict access to rosiglitazone in September 2010 by requiring GlaxoSmithKline to submit a risk evaluation and mitigation strategy (REMS). Drug labeling was revised in February 2011, and the rosiglitazone REMS program took full effect in November 2011.