The impact of appointment-based medication synchronization on medication taking behaviour and health outcomes: A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Proactive synchronization of medication refills through an appointment-based model (ABM) is a community pharmacy-based intervention targeting adherence to medications. We aimed to systematically review evidence on the impact of the ABM on medication taking behaviour, health resource utilization, clinical outcomes and the preferences of patients and providers. METHODS: We conducted a systematic literature search of MEDLINE and Scopus from database inception through 6 February 2017. Studies were included if they were original investigations evaluating the impact of the ABM on at least one outcome of interest and published in the peer-reviewed literature as a full-text manuscript in the English language. Outcomes included medication taking behaviour, clinical and economic outcomes, health resource utilization, and patient or provider satisfaction. Data were synthesized qualitatively. RESULTS: Five studies, mostly observational in design and with low risk of bias, were included. Objective measures of medication taking behaviour were consistently improved in patients enrolled in an ABM vs control, indicating an association between appointment-based medication synchronization with improved adherence and decreased likelihood of non-persistence. A single decision analysis indicates a cost savings over 1 year associated with the appointment-based medication synchronization programme modelled, for hypertension, diabetes and hyperlipidaemia. Limited data regarding health resource utilization and clinical outcomes and patient or provider satisfaction exist and are currently inconclusive. WHAT IS NEW AND CONCLUSION: The ABM provides a unique, patient-centred service to improve medication adherence amongst patients taking chronic medications while demonstrating a positive financial return on investment. Future research is needed to determine the impact of the ABM on final health outcomes.

Comparative efficacy and safety of antidiabetic drug regimens added to stable and inadequate metformin and thiazolidinedione therapy in type 2 diabetes.

AIMS: Determine the efficacy and safety of antidiabetic agents added-on to metformin and a thiazolidinedione (TZD) in patients with inadequately controlled type 2 diabetes (T2D). METHODS: MEDLINE and CENTRAL were searched for randomised controlled trials (RCTs) evaluating the addition of an antidiabetic agent in patients with T2D inadequately controlled on stable, optimised metformin and TZD therapy (≥ 1500 mg metformin and ≥ 50% maximum TZD dose for ≥ 4 weeks). Frequentist network meta-analysis was performed on identified studies. RESULTS: Eleven RCTs evaluating dipeptidyl peptidase-4 inhibitors (linagliptin, sitagliptin), sulfonylureas (SUs) (glibenclamide, glimepiride), glucagon-like peptide-1 (GLP-1) analogues (exenatide, liraglutide, dulaglutide, taspoglutide) and sodium-glucose cotransporter2 (SGLT2) inhibitors (canagliflozin, empagliflozin) were identified. The mean reduction in HbA1c from baseline was significant for all agents (range, 0.55-1.17%) vs. placebo. SUs were associated with weight gain (range, 3.31-7.29 kg), while weight loss was seen with all GLP-1 analogues (range, 1.53-2.20 kg) and SGLT2 inhibitors (range, 2.08-2.95 kg) vs. placebo. Relative risk of hypoglycaemia was increased with dulaglutide, exenatide and glimepiride vs. placebo (RR range, 2.65-6.17); and trended higher with all other agents except linagliptin. GLP-1 analogues and canagliflozin reduced systolic blood pressure vs. placebo (range, 2.39-5.05 mmHg). No agent with available data increased the risk of urinary or genital tract infection vs. placebo. CONCLUSION: When added to stable, optimised metformin and TZD, all evaluated antidiabetic agents reduced HbA1c; albeit not to the same degree. Moreover, agents differed in their effects on body weight, hypoglycaemia and systolic blood pressure.

Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta-analysis.

AIMS: Guidelines for type 2 diabetes recommend add-on agents when metformin alone fails to provide adequate glycaemic control. However, early combination therapy may benefit health outcomes. We conducted a systematic review and meta-analysis to investigate this question. METHODS: We searched MEDLINE and Cochrane CENTRAL (up to July 2012) without language restrictions. We sought randomized controlled trials (RCTs) evaluating initial combination therapy with metformin versus metformin monotherapy in patients with untreated type 2 diabetes. Weighted mean differences (WMDs) for changes from baseline and relative risks (RRs) [with 95% confidence intervals (CIs)] were calculated using random-effects model. RESULTS: In 15 RCTs (N = 6693), the mean age range was 48.4-62.7 years; mean baseline glycosylated haemoglobin (A1c) was 7.2-9.9% and mean diabetes duration was 1.6-4.1 years, with median follow-up of 6 months and with 13 comparisons for A1c change, 14 comparisons for A1c goal attainment of <7% and 13 comparisons for change in fasting plasma glucose (FPG). Drugs combined with metformin included thiazolidinediones (TZDs), insulin secretagogues, dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium glucose transporterase (SGLT-2) inhibitors. Compared to metformin alone, combination therapy with metformin provided statistically significant reductions in A1c (WMD -0.43%, 95% CI -0.56, -0.30), increases in attainment of A1c goal of less than 7% (RR 1.40, 95% CI 1.33-1.48) and reductions in FPG (WMD -14.30 mg/dl, 95% CI -16.09, -12.51). CONCLUSIONS: These results suggest a potential benefit of initial combination therapy on glycaemic outcomes in diabetes compared to metformin monotherapy across a wide range of baseline A1c levels. Further research should explore if early combination treatment may also affect longer term health outcomes in diabetes.

Prevention of interferon-alpha-associated depression with antidepressant medications in patients with hepatitis C virus: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis evaluating the efficacy and safety of antidepressant medications for the prevention of interferon-alpha (INF-α)-associated depression in patients with chronic hepatitis C virus (HCV). DATA SOURCES: Medline, Cochrane Central and PsycInfo from inception to September 2012, without limitations using terms describing hepatitis C and the individual drug names. STUDY SELECTION: We reviewed 132 citations for inclusion using the following criteria: randomised controlled trials in patients with chronic HCV initiating INF-α comparing prophylactic use of an antidepressant vs. placebo and reporting at least one outcome of interest [depression, completion of antiviral therapy, sustained virologic response (SVR), and serious adverse events and bleeding]. DATA EXTRACTION: Trial characteristics, assessment of risk of bias and data needed for analyses were extracted by two independent investigators using a standard extraction form. Disagreements were reviewed by a third investigator. RESULTS: A DerSimonian and Laird random-effects model was used for analysis. Heterogeneity and publication bias were evaluated where applicable. Of the seven included trials, the risk of bias was low in four and unclear in the remaining three. All trials evaluated selective serotonin reuptake inhibitors (SSRIs). Prophylactic use of a SSRI significantly reduced the risk of depression by 41% compared with placebo [RR, relative risk 0.59 (0.37-0.93)]. The impact of SSRIs on completion of antiviral therapy, SVR and serious adverse events was not found to be significant. CONCLUSIONS: SSRIs prevent depression in patients with HCV treated with INF-α therapy. The impact of SSRIs on completion of antiviral therapy or on the development of adverse events is less clear.

Systematic review of the cost-effectiveness of varenicline vs. bupropion for smoking cessation.

The purpose of this systematic review was to review the cost-effectiveness of first-line non-nicotine therapies (varenicline and bupropion SR) for smoking cessation, identify differences in the models used and their conclusions of cost-effectiveness, and to determine which variables, if any, impact conclusions of cost-effectiveness. A systematic literature search was conducted in MEDLINE, PsychINFO, the National Health Service Economic Evaluation Database, the Health Technology Database and the Tufts Cost-effectiveness Analysis Registry from the earliest possible date through May 2011. To be included, studies had to compare cost-effectiveness of varenicline to bupropion using either a Markov model or discrete event simulation and be published as a full text manuscript in English or Spanish. Study selection and data extraction were done in duplicate with disagreement resolved through discussion. Data regarding the model characteristics, results and conclusions were extracted as were details to assess the quality of the study. Model characteristics and cost-effectiveness results were compared across studies and summarised qualitatively. Ten unique studies were included, all of which were Markov models. Eight studies used the Benefits of Smoking Cessation on Outcomes (BENESCO) model and all found varenicline to dominate bupropion. The two non-BENESCO models found varenicline to be cost-effective. Conclusions regarding the cost-effectives were changed upon sensitivity analysis with the following variables: time horizon, cost of bupropion, efficacy of either drug, age and the incidence of smoking related disease. Varenicline dominated bupropion in most cost-effectiveness models. However, applicability of models to clinical practice and variables which changed conclusion of cost-effectiveness should be considered in the interpretation of results.

Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation.

Various antiplatelet and anticoagulation options are available for stroke prevention in patients with atrial fibrillation (AF). Currently, it is unclear whether these agents differ in their propensity to cause major gastrointestinal bleeding (MGIB). To our knowledge, no systematic evaluation of MGIB rates from randomised controlled trials (RCTs) of pharmacological stroke prevention in patients with AF has been conducted. Two independent investigators conducted systematic literature searches in MEDLINE and CENTRAL from the earliest possible date through November 2010. To be included, RCTs had to evaluate an adult population with AF or flutter and report data on the incidence of MGIB. Peto's odds ratios (ORs) with associated 95% confidence intervals (CIs) were calculated for all possible pair-wise comparisons of pharmacological stroke prevention alternatives. A total of 16 unique trials (n = 42,983) met inclusion criteria. The reported incidence of MGIB in placebo or control arms of identified trials was as high as 1.5%. Upon pair-wise meta-analysis of different pharmacological strategies, adjusted-dose vitamin K antagonists (VKAs) were found to be associated with a higher odds of MGIB compared with placebo/control (OR 3.21, 95% CI 1.32-7.82) and aspirin (or triflusal or indobufen) (OR 1.92, 95% CI 1.08-3.41). The addition of aspirin (or triflusal) to an adjusted-dose VKA resulted in greater odds of MGIB compared with aspirin alone (OR 4.72, 95% CI 1.35-16.49) and adjusted-dose VKA alone (OR 2.66, 95% CI 1.05-6.74). While aspirin increased the odds of MBIG by 3.23-fold compared with placebo/control, this finding did not reach statistical significance. The combination of aspirin and clopidogrel increased patients' odds of MGIB compared with aspirin alone (OR 1.93, 95% CI 1.46-2.56). Dabigatran was associated with a 30% increased odds of MGIB compared with adjusted-dose VKA (OR 1.30, 95% CI 1.06-1.59); however, ximelagatran was not. Low-intensity VKA therapy, alone or in combination with aspirin, was not associated with increased odds of MGIB compared with any (active-) comparator. The MGIB is a concern for patients with AF receiving pharmacological stroke prevention. Current RCT data suggest that dabigatran and adjusted-dose VKA therapy are associated with the highest odds of MGIB. Aspirin was not found to increase patients' odds of MGIB; however, this finding may be the result of type 2 error. Dual therapy resulting from the addition of an antiplatelet agent was typically associated with further increased odds of MGIB compared with monotherapy.

Initiating buprenorphine to treat opioid use disorder without prerequisite withdrawal: a systematic review.

BACKGROUND: Opioid withdrawal symptoms prior to buprenorphine initiation may be intolerable and as a result, alternative strategies have emerged. We aim to systematically review the efficacy and safety of buprenorphine initiation that aims to omit prerequisite withdrawal. METHODS: We conducted a systematic literature search of MEDLINE and CENTRAL from 1996 through April 10, 2020, augmented with searches in Google Scholar and www.clinicaltrials.gov . A study was included if it was in patients with substance use disorder or chronic pain that were taking a full mu opioid agonist and transitioning to buprenorphine without preceding withdrawal, and reported withdrawal during initiation as an outcome. Two investigators independently screened citations and articles for inclusion, collected data using a standardized data collection tool, and assessed study risk of bias. RESULTS: We included 15 case reports/series, reporting 24 unique cases, in our qualitative synthesis. No controlled studies were identified. Microdosing and bridging with a buprenorphine patch were the most common strategies reported. Transition to buprenorphine with complete cessation of opioid agonists was achieved in 87.5% (n = 21) of cases. Withdrawal during initiation occurred in 58.3% (n = 14) of cases, two of which were at least moderate in severity. CONCLUSION: Buprenorphine initiation strategies that omit prerequisite withdrawal have emerged. Low quality evidence from case reports suggests withdrawal during initiation is common but most often mild in severity. There is an unmet need for controlled studies to inform their efficacy and safety compared with traditional strategies, including outcomes during initiation and in the long-term.

Improving diabetic retinopathy screening through a statewide telemedicine program at a large federally qualified health center.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of acquired blindness in U.S. adults. Early detection prevents progression. Screening rates are only 10% in medically underserved populations. METHODS: A statewide telemedicine-based program within primary care centers was implemented to improve DR screening, detection and referrals for underserved patients. STUDY DESIGN: Retrospective, descriptive study. RESULTS: A total of 568 adults were screened during a comprehensive nurse visit from July 2009-June 2010 and had complete data available. Nearly 60% were minorities and 24% were uninsured. A total of 145 cases of DR were identified. The majority were recommended to return in one year for follow-up, while 75 were referred to a specialist. CONCLUSIONS: Telemedicine using digital imaging technology in the primary care office is a strategy that can be used to screen underserved and at-risk patients for DR, increase compliance with screening, and streamline specialist referrals.