Proximal Tubal Patency Demonstrated Through Air Infusion During Flexible Office Hysteroscopy Is Predictive of Whole Tubal Patency.

STUDY OBJECTIVE: To determine whether air bubbles infused into saline during flexible office hysteroscopy can accurately predict tubal patency. DESIGN: Diagnostic accuracy study (Canadian Task Force classification II-1). SETTING: An academic hospital. PATIENTS: Women undergoing office hysteroscopy and ultrasound. INTERVENTIONS: Air infusion into saline during office hysteroscopy. MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were whether air bubbles traverse the ostia at hysteroscopy, whether there is patency at abdominal surgery, and the rate of cul-de-sac (CDS) fluid accumulation from office hysteroscopy. Four hundred thirty-five patients underwent office hysteroscopy with air infusion, 89 of whom also had abdominal surgery. Depending on interpretation, sensitivity to tubal occlusion was 98.3% to 100%, and specificity was 83.7% with standard chromopertubation pressures; 95.3% to 100% of the time proximal patency was observed, whole tubal patency was observed through chromopertubation for patients with surgical data. Changes in CDS fluid volume from before to after office hysteroscopy were also used as an indirect proxy for tubal patency. Patients with risk factors for occlusion such as known or suspected tubal disease, known or suspected adhesions, and sonographic identification of adhesions through the sliding sign were all less likely to demonstrate a change in CDS fluid volume after hysteroscopy than women without these risk factors (p < .0001). Bilateral dispersion of air bubbles during hysteroscopy better predicted shifts in CDS volume than these risk factors and demonstrated shifts comparable with bilateral patency at laparoscopy (p < .001). CONCLUSION: Air-infused saline at office hysteroscopy can accurately assess tubal patency. Additionally, bilateral patency identified through office hysteroscopy may predict bilateral patency at surgery better than several commonly used historic and sonographic variables.

Resistant nonalcoholic fatty liver disease amelioration with rosuvastatin and pioglitazone combination therapy in a patient with metabolic syndrome.

OBJECTIVE: To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy. CASE SUMMARY: A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient's ALT and AST serum concentrations had normalized. Repeat liver ultrasound demonstrated improvement in steatosis grading and reduction in liver size. These improvements occurred despite a 4.5-kg weight gain since starting rosuvastatin and pioglitazone. DISCUSSION: Pharmacotherapy in NAFLD is not well validated, particularly combination therapy. Medications that target obesity-related consequences are commonly used, although evidence regarding biochemical and histological improvement is inconclusive. Consideration should be given to the use of combination of thiazolidinediones and statins for rapid biochemical improvement and long-term histological impact. CONCLUSIONS: The improvement in this patient's biochemical and ultrasonographic markers of resistant, severe NAFLD was rapid and sustained with combination therapy. This case represents a potential solution for initiating or maintaining statin therapy in patients with NAFLD who are at high cardiovascular risk.

New obesity agents: lorcaserin and phentermine/topiramate.

OBJECTIVE: To evaluate the evidence for lorcaserin and phentermine/topiramate in the treatment of obesity. DATA SOURCES: Literature was accessed through PubMed (June 1975-March 2013) using the search terms lorcaserin, phentermine, topiramate, or phenter mine/topiramate. Additionally, reference citations from publications identified were reviewed. Additional information was obtained from the Food and Drug Administration (FDA)-approved prescribing information and FDA briefing documents. STUDY SELECTION AND DATA EXTRACTION: English-language articles focusing on Phase 3 clinical trials for obesity were critiqued. Data from preclinical and Phase 1 and/or 2 trials are reported when appropriate. Six prospective Phase 3 trials were reviewed. DATA SYNTHESIS: Obesity has reached epidemic proportions, affecting more than one third of adults in the US. Two medication products, lorcaserin and phenter mine/topiramate, have recently received FDA approval as adjuncts to a reduced-calorie diet and increased physical activity among individuals with a body mass index greater than or equal to 30 kg/m(2) or greater than or equal to 27 kg/m(2) with an obesity-related comorbidity, such as hypertension, dyslipidemia, or diabetes. Lorcaserin is a selective serotonin 5-HT2C agonist that regulates food intake, while the combination of phentermine/topiramate causes appetite suppression and enhanced satiety. Three Phase 3 randomized, placebo-controlled trials reported approximately 75% and 45% of patients achieved greater than or equal to 5% weight loss with phentermine/topiramate and lorcaserin, respectively. CONCLUSIONS: With lifestyle modification, phentermine/topiramate appears most effective in terms of weight loss. Lorcaserin demonstrates moderate efficacy. Long-term cardiovascular outcomes studies are needed to confirm the safety and benefit of these new obesity agents.

Canagliflozin, a novel SGLT2 inhibitor for treatment of type 2 diabetes.

OBJECTIVE: To evaluate the available clinical data on canagliflozin and provide formulary considerations as to its place in the current treatment approach of type 2 diabetes mellitus (T2DM). DATA SOURCES: A systematic review of the literature in MEDLINE and Web of Science was performed through July 2013 using the key words and medical subject headings canagliflozin, JNJ-28431754, TA-7284, and sodium-glucose co-transporter 2 inhibitor. A manual search of references from reports of clinical trials or review articles was performed to identify additional relevant studies. STUDY SELECTION AND DATA EXTRACTION: Citations eligible for inclusion were in vitro or in vivo evaluations of canagliflozin with no restrictions on patient population or indication used. Data related to the patient populations and outcomes of interest were extracted from each citation. DATA SYNTHESIS: Five clinical trials (n = 2775 subjects) have been published evaluating canagliflozin in patients with T2DM. A single study evaluated canagliflozin monotherapy, while the others included various add-on therapies. Four studies included placebo groups with 2 others using sitagliptin as an active control. Compared with placebo (+0.14%), canagliflozin monotherapy at doses of 100 to 300 mg/d decreases hemoglobin A1c by -0.77% to -1.03% from baseline. Reductions in fasting plasma glucose, body weight, and systolic blood pressure were seen. Because of the increase in glucosuria with the drug, patients (especially females) are at increased risk of genital mycotic infections. The overall safety of canagliflozin (eg, cardiovascular, oncologic, pancreatic, bone) is also yet to be fully elucidated. CONCLUSIONS: Canagliflozin is comparable to second-line oral medications in terms of effectiveness but has limitations in affordability and long-term safety data.

Denosumab, a RANK ligand inhibitor, for postmenopausal women with osteoporosis.

OBJECTIVE: To review the evidence for use of denosumab for the treatment of postmenopausal osteoporosis. DATA SOURCES: A search of MEDLINE and EMBASE databases was conducted during January 2012, using the terms denosumab and osteoporosis, with index dates of 2000 to 2011. Additional information was gathered from Amgen and references cited in articles retrieved. STUDY SELECTION AND DATA EXTRACTION: English-language articles including clinical trials involving denosumab for treatment of osteoporosis and review articles were reviewed. Articles using denosumab in males or as treatment for conditions other than osteoporosis or osteopenia were excluded. DATA SYNTHESIS: Many clinical trials have supported the safety and efficacy of denosumab in postmenopausal women with bone loss. It has been shown to improve bone mineral density, decrease markers of bone turnover, and prevent new vertebral fractures. It shows improvement over placebo in studies and has at least similar efficacy to alendronate in measurements of bone mineral density, with less risk for osteonecrosis of the jaw and atypical fracture, but with an increased risk of infections and neoplasms. European cost-effectiveness studies have also demonstrated that denosumab is a cost-effective choice compared to risedronate and no treatment for fracture prevention for postmenopausal women with osteoporosis. CONCLUSIONS: Denosumab has demonstrated efficacy and safety as a first-line treatment for postmenopausal osteoporosis in multiple clinical trials over at least 6 years. It may be most cost-effective for women who are unable or refuse to take bisphosphonate drugs.

Infectious complications of newer agents in the fight against diabetes.

Infectious complications have been reported with antidiabetic medications. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors have been associated with upper respiratory tract infections and urinary tract infections. Sodium-glucose cotransporter 2 inhibitors have been associated with lower limb amputations, urinary tract infections, genital mycotic infections, and Fournier gangrene.

Frontline perspective on credentialing and privileging of ambulatory care pharmacists.

OBJECTIVES: To present the current state of, and frontline advice on, the implementation of successful credentialing and privileging processes for practicing pharmacists in the United States. METHODS: The American Society of Health-System Pharmacists (ASHP) Section Advisory Group on Compensation and Practice Sustainability surveyed ambulatory care pharmacists via ASHP Connect about the status, structure and oversight of their ambulatory care clinical practice sites with credentialed and privileged (C&P) pharmacists. KEY FINDINGS: Over 80% of survey respondents identified themselves as a C&P pharmacist, and over 90% indicated it is 'Important' or 'Very Important' for pharmacists to be C&P. Qualitative survey responses indicated the most important considerations for establishing or expanding a credentialing and privileging process for ambulatory care pharmacists were 'don't re-create the wheel', 'establish a physician champion and/or obtain leadership buy-in', 'be persistent and patient', 'develop a guidance document' and 'work within existing processes'. CONCLUSIONS: Starting a credentialing and privileging process is critical in preparation for, or response to, provider status recognition of pharmacists in the United States. When used with existing guidance documents on credentialing and privileging, 'front line' advice from practicing pharmacists can help promote expanded roles for pharmacists within healthcare systems.

Impact of sitagliptin on markers of beta-cell function: a meta-analysis.

BACKGROUND: Progressive beta-cell dysfunction and beta-cell failure are fundamental pathogenic consequences of type 2 diabetes. Dipeptidyl peptidase-IV inhibitors may exhibit improvement on preclinical measures of both beta-cell function, homeostasis model assessment of beta-cell (HOMA-beta) index, and beta-cell dysfunction, proinsulin/insulin ratio (PI/IR), correlating to beta-cell survival. RESEARCH DESIGN AND METHODS: A systematic literature search through July 2008 was conducted to extract a consensus of randomized, controlled trials of sitagliptin therapy on measures of beta-cell function. A random-effects model meta-analysis evaluated effects on HOMA-beta and PI/IR versus placebo. Several subgroup analyses, including active control, were conducted. Studies were included if they met the following criteria: (1) randomized trials on sitagliptin; (2) placebo or active control; and (3) data reported on HOMA-beta or PI/IR. RESULTS: A total of 11 trials (n = 3039) reported effects on HOMA-beta and 8 trials (n = 2325) on PI/IR versus placebo. Four trials (n = 1425) were included in the active control subgroup analysis. Sitagliptin significantly improved HOMA-beta index by 12.03% [95% confidence interval (CI), 9.45-14.60] versus placebo. Sitagliptin also significantly decreased PI/IR -0.06 (95% CI, -0.08 to -0.04). Sitagliptin was inferior to active control for HOMA-beta index [5.64% (95% CI, 0.38-10.90)], but not different in terms of PI/IR [0.01 (95% CI, -0.04 to 0.06)]. CONCLUSIONS: Despite significant improvement in HOMA-beta index and PI/IR from placebo, there does not seem to be a benefit of dipeptidyl peptidase-IV inhibitors over other agents with respect to beta-cell function/activity. Long-term prevention of beta-cell dysfunction cannot be ruled out.

Admission type is a paradoxical predictor of performance in problem-based learning courses.

INTRODUCTION: To determine if a difference in problem-based learning (PBL) performance or student attrition exists based on admission type. METHODS: This retrospective review analyzed admission type and student academic performance in the PBL course series from 2002 to 2009. Student scores were compiled based on admission type: provisional (high school), traditional with degree (bachelor's or higher), and traditional without degree (some college). ANOVA was performed on overall scores amongst the three admission types. Continuous data were analyzed using two-sided unpaired t-tests, and dichotomous data were analyzed using chi-square test. RESULTS: 600 students received at least one score in the third-year (P3) PBL course series. 56% of students (n = 333) were admitted traditional without degree, while the remainder were split between provisional (n = 125) and traditional with degree (n = 142) admission. Provisionally admitted students had significantly higher scores than either of the other groups (p < 0.001 for both) and significantly fewer students failed a course versus either of the other groups (p < 0.001 for both). Additionally, traditional without degree students had significantly higher averages and fewer failing grades compared to traditional with degree students (p < 0.01 for both) over the eight years analyzed. CONCLUSIONS: This study's results suggest that degrees may not be predictive of success during PBL in the P3 year. Further work is needed in order to truly assess predictive nature of this and other factors among prospective pharmacy students.

Effect of fish oil supplement administration method on tolerability and adherence: a randomized pilot clinical trial.

OBJECTIVES: Anecdotally, several strategies have been suggested in order to improve tolerability of fish oil supplements, but there is little evidence supporting any of these strategies. The aim of this study was to determine if there is a difference among four methods of oral administration of fish oil supplementation in terms of tolerability and adherence. METHODS: A randomized, prospective, open-label, four-arm pilot study was conducted on 60 healthy adult subjects randomized to different fish oil supplement administration methods with (1) milk, (2) food, (3) an empty stomach, and (4) frozen capsules prior to ingestion. Each subject was instructed to take two capsules three times daily for 30 consecutive days. Adherence was assessed by pill counts. Adverse effects were assessed by survey and patient exit interview. RESULTS: No apparent differences were demonstrated among the four administration groups in terms of adherence, reasons for non-adherence, or self-reported adverse effects. CONCLUSIONS: Method of administration did not affect rates of adherence or incidence of adverse effects in a small cohort of healthy adults taking fish oil supplement capsules for 30 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT01471366. Registered November 16, 2011.

Practical management of dyslipidemia with elevated lipoprotein(a).

OBJECTIVE: To report a case and describe a practical approach to treating dyslipidemia in a very-high-risk patient with elevated lipoprotein(a) [Lp(a)]. SETTING: Pharmacist-managed lipid clinic, from November 2006 to July 2007. PATIENT DESCRIPTION: A 50-year-old white woman with a recent history of multiple myocardial infarctions presented for management of dyslipidemia. CASE SUMMARY: At baseline, the patient had elevated low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), and Lp(a) (306 nmol/L) levels and low high-density lipoprotein cholesterol (HDL-C) levels. Early initiation of combination therapy with a statin and niacin extended release (ER) titration was started. After 3 months, despite progressive weight gain caused by dietary indiscretion, LDL-C decreased by 24% and TG and TC levels reached goal. Lp(a) levels did not change. Niacin ER titration continued, pravastatin was maximized, and ezetimibe 10 mg daily was started. Despite dramatic 9-month weight gain (68 lb total), LDL-C and HDL-C reached goal and Lp(a) levels decreased by 33% (204 nmol/L) after niacin ER maximization. RESULTS: Lp(a) is an emerging risk factor in cardiovascular disease (CVD). Elevated Lp(a) (>30 mg/dL) has been implicated as both an independent and an additive risk factor for CVD and stroke, particularly in women. In this case, the patient did not reach the optimal goal (<30 mg/dL) but did experience more than 30% reduction in Lp(a) levels. Although multiple factors, including subclinical hypothyroidism, hormonal changes, and renal disease, increase Lp(a) levels, few beneficial treatment options exist (i.e., estrogen and niacin). Although the exact mechanism of action is unknown, niacin ER has been documented to reduce Lp(a) by 36% to 38%. Some effect of ezetimibe on Lp(a) in this patient cannot be ruled out. CONCLUSION: This case illustrates a practical use of currently available therapy options to address Lp(a) as a secondary cardiovascular risk factor. Niacin is a preferred option for Lp(a) lowering in very-high-risk patients with coronary heart disease and dyslipidemia. The importance of moderate reductions in Lp(a) is not known.

Thiazolidinediones and risk of repeat target vessel revascularization following percutaneous coronary intervention: a meta-analysis.

OBJECTIVE: Thiazolidinediones (TZDs) (rosiglitazone and pioglitazone) are a class of antidiabetes agents that have a high affinity for peroxisome proliferator-activated receptor-gamma. TZDs initiate a multitude of physiologic processes that may elicit benefits as systemic agents for the prevention of restenosis requiring revascularization following percutaneous coronary intervention (PCI). Numerous trials have evaluated the impact of TZDs on repeat target vessel revascularization (TVR) in patients following PCI; however, several limitations (small sample size, inconclusive results, and risk factor stratification) complicate definitive conclusions. A meta-analysis was performed to evaluate the impact of TZDs on repeat TVR following PCI. RESEARCH DESIGN AND METHODS: Included trials met the following criteria: 1) prospective, randomized controlled trials evaluating available TZDs versus standards of care; 2) well-described protocol; 3) minimum of 6 months of follow-up; and 4) data provided on repeat TVR. Data are presented as relative risks (RRs) with 95% CIs. RESULTS: Seven clinical trials (n = 608) met the inclusion criteria. Upon meta-analysis, the risk of repeat TVR was significantly reduced in patients who received TZD therapy compared with standards of care (RR 0.35 [95% CI 0.22-0.57]). In studies using rosiglitazone (0.45 [0.25-0.83]) and pioglitazone (0.24 [0.11-0.51]), risk of repeat TVR was significantly reduced. Risk of repeat TVR was also significantly reduced among patients with (0.34 [0.19-0.63]) and without (0.37 [0.18-0.77]) diabetes. CONCLUSIONS: Results from this meta-analysis suggest that TZDs effectively reduce the risk of repeat TVR following PCI.

Development of critical thinking in health professions education: A meta-analysis of longitudinal studies.

INTRODUCTION: While reports of critical thinking exist in the health professions literature, development of critical thinking across a broad range of health-professions students has not been systematically reviewed. METHODS: In this meta-analysis, multiple databases and journals were searched through February 2016 to identify longitudinal studies using standardized tests of critical thinking [California Critical Thinking Skills Test (CCTST), Health Science Reasoning Test (HSRT), and Defining Issues Test (DIT)] in any language. Two reviewers extracted information and collected information regarding primary author, publishing journal, health profession, critical thinking test, and time1/time2 means and standard deviations. Standardized mean differences (SMD) with 95% confidence intervals (CI) were reported using a random-effects model. RESULTS: Four hundred sixty-two studies were screened, and 79 studies (representing 6884 students) were included. Studies contained 37 CCTST, 22 DIT, and 20 HSRT. Health professions comprised nursing, pharmacy, physical therapy, occupational therapy, dentistry, medicine, veterinary medicine, dental hygiene, clinical laboratory sciences, and allied health. Cohen's kappa was strong (0.82) for inter-reviewer agreement. Both the CCTST (SMD = 0.37, 95% CI = 0.23-0.52) and DIT (SMD = 0.28, 95%CI = 0.18-0.39) demonstrated significant increases in total scores, but the HSRT (SMD = 0.03, 95%CI = -0.05-0.12) did not show improvement. DISCUSSION/CONCLUSIONS: In this meta-analysis, students from the majority of health professions consistently showed improvement in development of critical thinking. In this diverse population, only the CCTST and DIT appeared responsive to change.

Impact of statins on risk of stroke: a meta-analysis.

BACKGROUND: Evidence from randomized, controlled trials suggests that reduction of low-density lipoprotein cholesterol with hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) therapy in patients at high risk for cardiovascular disease reduces the incidence of ischemic stroke; however, data from large epidemiologic observational studies suggest an inverse relationship between risk of hemorrhagic stroke and cholesterol levels. OBJECTIVE: To perform a meta-analysis of randomized controlled trials to assess the effect of statin therapy on all cerebrovascular events (CVEs), ischemic stroke, and hemorrhagic stroke. METHODS: A systematic literature search of MEDLINE, EMBASE, Cumulative Index to Nursing & Allied Health Literature, and Web of Science citations from June 1975 through September 2006 was performed to identify randomized controlled trials of statin therapy. Trials were included if they met the following criteria: (1) controlled clinical trials of statin therapy versus placebo, (2) well-described protocol, and (3) data reported on incidence of all CVEs, ischemic stroke, or hemorrhagic stroke. All data were independently extracted by 3 investigators. RESULTS: Weighted averages are reported as relative risk with 95% confidence intervals. A total of 26 trials (N = 100,560) reported incidence on all CVEs. Six trials (n = 37,292) reported incidence of ischemic stroke and 9 trials (n = 57,895) were included in the hemorrhagic stroke analysis. Statin therapy significantly reduced the risk of all CVEs (RR 0.83; 95% CI 0.76 to 0.91) and the risk of ischemic stroke (RR 0.79; 95% CI 0.63 to 0.99). Statin therapy did not significantly reduce risk of hemorrhagic stroke (RR 1.11; 95% CI 0.77 to 1.60). CONCLUSIONS: Statin therapy significantly reduces risk of developing all CVEs and ischemic stroke; however, it is associated with a nonsignificant increase in risk of hemorrhagic stroke.

Evidence-based review of statin use in patients with HIV on antiretroviral therapy.

INTRODUCTION: As a result of improved safe and effective therapeutic options for human immunodeficiency virus (HIV), life expectancy of those living with HIV is increasing leading to new challenges (e.g., management of chronic diseases). Some chronic diseases (e.g., cardiovascular disease [CVD]), are up to two times more prevalent in patients with HIV. Statins are a mainstay of therapy for prevention of CVD; but, clinicians should be aware that not all statins are appropriate for use in the HIV population, especially those receiving antiretroviral therapy (ART). The purpose of this article is to review the pharmacokinetic and clinical data for statin therapy in HIV-infected patients receiving ART. METHODS: A systematic literature search using PubMed and MEDLINE databases was performed using each statin drug name combined with HIV, pharmacokinetics, AIDS, and/or human immunodeficiency virus. English language trials published from 1946 to November 2016 were considered, and results were limited to clinical efficacy trials. RESULTS: In general, atorvastatin and pravastatin are safe and effective for patients treated with protease-inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor-based ART. Rosuvastatin is generally considered safe if started at a low dose, but should be avoided if possible in patients receiving PI-based ART. Pitavastatin has limited supporting evidence, but appears safe for use based on its pharmacokinetic properties and low number of drug interactions. Fluvastatin, lovastatin, and simvastatin should be avoided in patients receiving ART due to drug interactions, adverse events, and/or limited clinical data. CONCLUSION: Clinicians need to be familiar with the intricacies of statin selection for the prevention of CVD in patients with HIV on ART.