Nicholas W. Carris

Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review

Doxycycline remains on intermittent shortage. Evidence supports the substitution of minocycline in skin and soft-tissue infections and carefully selected cases of pneumonia. Minocycline may be carefully considered in Lyme disease prophylaxis and Rickettsial disease in the complete absence of doxycycline.

Feasibility of Extended-interval Follow-up for Patients Receiving Warfarin.

AIMS The 2012 American College of Chest Physician Evidence-Based Management of Anticoagulant Therapy guidelines suggest an international normalized ratio (INR) testing interval of up to 12 weeks, rather than every 4 weeks, for patients with consistently stable INRs while taking vitamin K antagonists. We aimed to examine the feasibility of extended-interval follow-up in a real-world setting. METHODS Patients receiving stable warfarin therapy for ≥ 12 weeks at baseline began extended-interval follow-up with visits occurring at 6 weeks, 14 weeks, and every 12 weeks thereafter to a maximum of 68 weeks or until they were no longer suitable for extended-interval follow-up. A single INR excursion >0.3 from goal was permitted if a reversible precipitating factor was identified and the INR was expected to return to goal without dose adjustment. The primary outcome was the proportion of patients completing all study follow-up visits. RESULTS Of 48 patients enrolled, 47 had evaluable data. The most common indication for anticoagulation was atrial fibrillation/flutter (53.2%). At baseline, mean prior warfarin treatment duration was 6.7 ± 6 years and median number of weeks on a stable regimen was 24 weeks (IQR, 19-37.5). Eleven patients (23%) completed all study follow-up visits, whereas 17 (36%) did not maintain a stable INR past the 14-week follow-up. CONCLUSION A large proportion of patients with previously stable (≥ 3 months) INRs were not able to maintain stable INRs during extended-interval follow-up. More research is needed to identify patient characteristics predictive of success with extended-interval follow-up prior to broad implementation.

EPA-Registered Repellents for Mosquitoes Transmitting Emerging Viral Disease.

In many parts of the United States, mosquitoes were previously nuisance pests. However, they now represent a potential threat in the spread of viral diseases. The Aedes aegypti, Aedes albopictus, and Culex species mosquitoes are endemic to the United States and together may transmit a variety of viral diseases of growing concern, including West Nile virus, chikungunya, dengue fever, and Zika virus. The Centers for Disease Control and Prevention and the Environmental Protection Agency (EPA) recommend N,N‐diethyl‐meta‐toluamide (DEET) as a first‐line mosquito repellent, but for patients refusing to use DEET or other conventional repellents, guidance is limited to any EPA‐registered product. Therefore, we conducted a systematic review of the literature to identify which EPA‐registered personal mosquito repellent provides the best protection from A. aegypti, A. albopictus, and Culex spp. mosquitoes. We abstracted data from 62 published reports of EPA‐registered mosquito repellents. The conventional repellent picaridin has the strongest data to support its use as a second‐line agent, while IR3535 and oil of lemon eucalyptus are reasonably effective natural products. Citronella, catnip, and 2‐undecanone offer limited protection or have limited data. These results can be used by pharmacists and other health care professionals to advise patients on the selection of an EPA‐registered mosquito repellent. Regardless of the repellent chosen, it is vital for patients to follow all instructions/precautions in the product labeling to ensure safe and effective use.

First Pharmacological Therapy for Hypoactive Sexual Desire Disorder in Premenopausal Women Flibanserin

Objective: To review data regarding flibanserin, a recently approved therapy for hypoactive sexual desire disorder (HSDD). Data Sources: Literature search of MEDLINE (September 1995 to November 2015) was performed using the search term flibanserin. Reference lists from included articles were reviewed for pertinent citations. Study Selection and Data Extraction: We included phase-3 trials of flibanserin as a treatment for HSDD. Four reports of phase-3 trials were included. One extension study of four phase-3 trials and one phase-2 pharmacokinetic trial were also included. Data Synthesis: Though a strong placebo response was demonstrated, flibanserin consistently, yet marginally, showed improvement (compared with placebo) in the number of satisfying sexual events per month. The most common adverse events were dizziness (11.4%), somnolence (11.2%), nausea (10.4%), fatigue (9.2%), insomnia (4.9%), and dry mouth (2.4%). Conclusions: Flibanserin is effective in the treatment of HSDD. Flibanserin should be administered at bedtime to limit the risk for hypotension/syncope, accidental injury, and central nervous system (CNS) depression. Concomitant alcohol use contributes to significant CNS depression and hypotension/syncope with flibanserin and should be avoided according to the boxed warning. Careful patient assessment prior to the diagnosis of HSDD and the use of flibanserin is needed for safe use. Prescribing guidelines recommend discontinuing flibanserin at 8 weeks in the absence of benefit. Sexual dysfunction should be addressed in a patient-specific manner. Providers should exercise shared decision making in prescribing flibanserin for HSDD and discuss flibanserin’s benefits and alternative options.

New Pharmacological Therapies for Vasomotor Symptom Management Focus on Bazedoxifene/Conjugated Estrogens and Paroxetine Mesylate

Objective: To review 2 recently approved therapies for vasomotor symptoms (VMSs) of menopause. Data Sources: PubMed searches (June 2003 to May 2014) were conducted using the keywords paroxetine vasomotor and bazedoxifene vasomotor. References from relevant articles were reviewed for pertinent citations that were not identified in the PubMed search. Study Selection and Data Extraction: Phase 3 clinical trials of recently approved hormonal and nonhormonal therapies for the treatment of VMSs of menopause were selected. Studies that evaluated the use of paroxetine mesylate or bazedoxifene (BZA)/conjugated estrogens (CEs) for VMSs were included. Data Synthesis: Four studies for BZA/CEs were identified. One published report of low-dose paroxetine mesylate was identified that was a combined analysis of 2 phase 3 studies. Both agents significantly decrease the incidence of hot flushes compared with placebo and are approved for the treatment of moderate to severe VMSs associated with menopause. BZA/CEs is only approved for women with an intact uterus. In all circumstances, the use of BZA/CEs should be limited to the shortest duration possible. Paroxetine mesylate was not studied head-to-head against hormone therapy, but the magnitude of its effect on VMSs is less than expected with hormone therapy. Conclusions: BZA/CEs is an effective hormonal therapy for treating VMSs in women with an intact uterus. Paroxetine mesylate is the first nonhormonal therapy that the FDA has approved for VMSs, making both viable options for the treatment of VMSs of menopause.

Quality of Life in Treatment-Resistant Hypertension

Treatment-resistant hypertension (TRH) is an increasingly common and clinically challenging hypertension phenotype associated with adverse impact on cardiovascular events and death. Recent evidence, although limited, suggests that TRH may also adversely affect health-related quality of life (HrQoL) and other patient-reported outcomes. However, the precise mechanisms for this link remain unknown. A number of recent studies focusing on both the general hypertensive population and those with TRH suggest that patient awareness of difficult-to-control blood pressure, chronically elevated blood pressure levels, and the use of aggressive medication regimens with attendant cumulative adverse effects may play significant roles. This review summarizes the existing literature on HrQoL in persons with TRH, highlights literature from the general hypertensive population with relevance to TRH, and discusses important remaining questions regarding HrQoL in persons with TRH.

Metformin's impact on statin-associated muscle symptoms: An analysis of ACCORD study data and research materials from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center

Statins are widely prescribed, yet statin muscle pain limits their use, leading to increased cardiovascular risk. No validated therapy for statin muscle pain exists. The goal of the study was to assess whether metformin was associated with reduced muscle pain. A secondary analysis of data from the ACCORD trial was performed. An ACCORD sub‐study assessed patients for muscle cramps and leg/calve pain while walking, typical non‐severe statin muscle pain symptoms. We compared muscle pain between patients using a statin (n = 445) or both a statin and metformin (n = 869) at baseline. Overall patient characteristics were balanced between groups. Unadjusted analysis showed fewer reports of muscle cramps (35%) and leg/calve pain while walking (40%) with statins and metformin compared to statin only (muscle cramps, 42%; leg/calve pain while walking, 47%). Multivariable regression demonstrated a 22% odds reduction for muscle cramps (P = 0.049) and a 29% odds reduction for leg/calve pain while walking (P = 0.01). Metformin appears to reduce the risk of non‐severe statin muscle pain and additional research is needed to confirm the findings and assess metformins impact on statin adherence and related cardiovascular outcomes.

Evaluation of SAMe-TT2R2 Score on Predicting Success With Extended-Interval Warfarin Monitoring

Background: In patients with stable international normalized ratios, 12-week extended-interval warfarin monitoring can be considered; however, predictors of success with this strategy are unknown. The previously validated SAMe-TT2R2 score (considering sex, age, medical history, treatment, tobacco, and race) predicts anticoagulation control during standard follow-up (every 4 weeks), with lower scores associated with greater time in therapeutic range. Objective: To evaluate the ability of the SAMe-TT2R2 score in predicting success with extended-interval warfarin follow-up in patients with previously stable warfarin doses. Methods: In this post hoc analysis of a single-arm feasibility study, baseline SAMe-TT2R2 scores were calculated for patients with ≥1 extended-interval follow-up visit. The primary analysis assessed achieved weeks of extended-interval follow-up according to baseline SAMe-TT2R2 scores. Results: A total of 47 patients receiving chronic anticoagulation completed a median of 36 weeks of extended-interval follow-up. The median baseline SAMe-TT2R2 score was 1 (range 0-5). Lower SAMe-TT2R2 scores appeared to be associated with greater duration of extended-interval follow-up achieved, though the differences between scores were not statistically significant. No individual variable of the SAMe-TT2R2 score was associated with achieved weeks of extended-interval follow-up. Analysis of additional patient factors found that longer duration (≥24 weeks) of prior stable treatment was significantly associated with greater weeks of extended-interval follow-up completed (P = 0.04). Conclusion and Relevance: This pilot study provides limited evidence that the SAMe-TT2R2 score predicts success with extended-interval warfarin follow-up but requires confirmation in a larger study. Further research is also necessary to establish additional predictors of successful extended-interval warfarin follow-up.