-
1.
Medication Discontinuation in the IMPROVE-IT Trial.
Navar, AM, Roe, MT, White, JA, Cannon, CP, Lokhnygina, Y, Newby, LK, Giugliano, RP, Tershakovec, AM, Braunwald, E, Califf, RM, et al
Circulation. Cardiovascular quality and outcomes. 2019;(1):e005041
-
-
Free full text
-
Abstract
BACKGROUND Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials. METHODS AND RESULTS We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8-85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%-51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2-8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P=0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates. CONCLUSIONS Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.
-
2.
Changing predictors of statin initiation in US women over two decades.
Kinsey, TL, Stürmer, T, Poole, C, Rothman, KJ, Glynn, RJ
Pharmacoepidemiology and drug safety. 2019;(3):305-314
-
-
Free full text
-
Abstract
PURPOSE To describe changing roles of predictors of statin initiation before and after incident coronary heart disease, and before and after publication of National Cholesterol Education Program Adult Treatment Panel-III (ATP-III) guidelines in a cohort of US women. METHODS We identified 34 382 women enrolled into the Women's Health Study from 1993 to 1995 and followed up until 2012. Proportions of previous nonusers initiating statins were described over time. We used multivariable linear regression models to estimate adjusted initiation proportion differences (IPDs) for initiation overall, separately before and after incident coronary heart disease, and separately for ATP-II and ATP-III time periods. RESULTS Key predictors of initiation overall were self-reported total cholesterol, and previous incident coronary heart disease, cerebrovascular disease, and diabetes. Adjusted IPDs (percentage) for total cholesterol > 240 vs <200 mg/dL were 7.5 (95% confidence interval [CI], 7.0-8.0) and 9.3 (95% CI, 8.7-9.9) during ATP-II and ATP-III time periods, respectively. Adjusted IPDs in women with diabetes were 7.0 (95% CI, 6.3-7.8) and 11.9 (95% CI, 6.7-17.0) for primary and secondary prevention, respectively, and 3.1 (95% CI, 2.1-4.0) and 9.2 (95% CI 8.2-10.2) for before and after ATP-III, respectively. CONCLUSIONS Secular trends reflected evolution toward risk factor-based treatment indications for statin initiation with increased initiation among diabetics and women with normal and borderline cholesterol. The role of serum cholesterol changed over time, though the character was scale (multiplicative vs additive) dependent. In pharmacoepidemiologic studies of statins, strength of confounding by important variables sometimes unmeasured in claims data, such as cholesterol level, may be calendar time dependent.
-
3.
Medication use in infants admitted with bronchiolitis.
Oakley, E, Brys, T, Borland, M, Neutze, J, Phillips, N, Krieser, D, Dalziel, SR, Davidson, A, Donath, S, Jachno, K, et al
Emergency medicine Australasia : EMA. 2018;(3):389-397
Abstract
BACKGROUND There are no medications known that improve the outcome of infants with bronchiolitis. Studies have shown the management of bronchiolitis to be varied. OBJECTIVES To describe medication use at the seven study hospitals from a recent multi-centre randomised controlled trial on hydration in bronchiolitis (comparative rehydration in bronchiolitis [CRIB]). METHODS A retrospective analysis of extant data of infants between 2 months (corrected for prematurity) and 12 months of age admitted with bronchiolitis identified through the CRIB trial. CRIB study records, medical records, pathology and radiology databases were used to collect data using a standardised form and entered in a single site database. Medications investigated included salbutamol, adrenaline, steroids, ipratropium bromide, normal saline, hypertonic saline, steroids and antibiotics. RESULTS There were 3456 infants available for analysis, of which 42.0% received at least one medication during hospitalisation. Medication use varied by site between 27.0 and 48.7%. The most frequently used medication was salbutamol (25.5%). Medication use in general, and salbutamol use in particular, increased by 8.2 and 9.3%, respectively, per month after 4 months of age; from 22.9 and 3.6% at 4 months to 81.4 and 68.8% at 11 months. In infants admitted to the intensive care unit (ICU) compared with those not admitted to ICU 81.6 and 39.5%, respectively, received medication at one point during the hospital stay. CONCLUSIONS Medication was used for infants with bronchiolitis frequently and variably in Australia and New Zealand. Medication use increased with age. Better strategies for translating evidence into practice are needed.
-
4.
Factors Influencing Physician Counseling on Cardiovascular Risk.
Rakita, V, Homko, CJ, Kashem, A, Memon, N, Bove, AA
Journal of primary care & community health. 2016;(2):65-70
Abstract
BACKGROUND AND IMPORTANCE A significant reduction in cardiovascular disease (CVD) mortality is related to aggressive management of modifiable CVD risk factors. Therefore, patients at increased risk for CVD should not only benefit from standard pharmacotherapy but also from counseling regarding lifestyle behavioral changes. OBJECTIVE To determine the patient factors that influence provision of cardiovascular risk reduction counseling from physicians, as well as the frequencies of counseling. DESIGN, SETTING, AND PARTICIPANTS Secondary analysis of a prospective, randomized trial among an underserved inner-city and rural population (n = 388) with a 10% or greater CVD risk (Framingham 10-year risk score). Subjects were followed for 1 year and were seen for quarterly assessments, which included evaluation of weight, blood pressure, lipid, and glucose status. At each of the 4 quarterly visits, subjects were asked if their physician had discussed or made recommendations regarding lifestyle behaviors, specifically diet, weight loss, and exercise. RESULTS The average patient age was 61.3 ± 10.1 years, average A1c was 6.7 ± 1.6%, average total cholesterol was 201 ± 44 mg/dL. The average body mass index (BMI) was 31.8 ± 6.4 kg/m2, and the average blood pressure was 146 ± 18/82 ±11 mm Hg. Using binary logistic regression analysis, BMI (P < .025) was the only clinical factor related to physician lifestyle counseling. All other risk factors showed no statistical relationship. CONCLUSION The data indicate that BMI is the major factor associated with whether or not physicians provide counseling regarding nutrition and weight loss. Physicians may be missing important opportunities to influence behavior in patients at high risk for CVD by limiting their focus to obese patients.
-
5.
A theory-based process evaluation alongside a randomised controlled trial of printed educational messages to increase primary care physicians' prescription of thiazide diuretics for hypertension [ISRCTN72772651].
Presseau, J, Grimshaw, JM, Tetroe, JM, Eccles, MP, Francis, JJ, Godin, G, Graham, ID, Hux, JE, Johnston, M, Légaré, F, et al
Implementation science : IS. 2016;(1):121
Abstract
BACKGROUND Pragmatic trials of implementation interventions focus on evaluating whether an intervention changes professional behaviour under real-world conditions rather than investigating the mechanism through which change occurs. Theory-based process evaluations conducted alongside pragmatic randomised trials address this by assessing whether the intervention changes theoretical constructs proposed to mediate change. The Ontario Printed Educational Materials (PEM) cluster trial was designed to increase family physicians' guideline-recommended prescription of thiazide diuretics. The trial found no intervention effect. Using the theory of planned behaviour (TPB), we hypothesised that changes in thiazide prescribing would be reflected in changes in intention, consistent with changes in attitude and subjective norm, with no change to their perceived behavioural control (PBC), and tested this alongside the RCT. METHODS We developed and sent TPB postal questionnaires to a random sub-sample of family physicians in each trial arm 2 months before and 6 months after dissemination of the PEMs. We used analysis of covariance to test for group differences using a 2 × 3 factorial design. We content-analysed an open-ended question about perceived barriers to thiazide prescription. Using control group data, we tested whether baseline measures of TPB constructs predicted self-reported thiazide prescribing at follow-up. RESULTS Four hundred twenty-six physicians completed pre- and post-intervention questionnaires. Baseline scores on measures of TPB constructs were high: intention mean = 5.9 out of 7 (SD = 1.4), attitude mean = 5.8 (SD = 1.1), subjective norm mean = 5.8 (SD = 1.1) and PBC mean = 6.2 (SD = 1.0). The arms did not significantly differ post-intervention on any of the theory-based constructs, suggesting a possible ceiling effect. Content analysis of perceived barriers suggested post-intentional barriers to prescribing thiazides most often focused on specific patient clinical characteristics and potential side effects. Baseline intention (β = 0.63, p < 0.01) but not PBC (β = 0.04, p = 0.78) predicted 42.6 % of the variance in self-reported behaviour at follow-up in the control group. CONCLUSIONS Congruent with the Ontario Printed Educational Messages trial results and aligned with the TPB, we saw no impact of the intervention on any TPB constructs. The theoretical basis of this evaluation suggests possible explanations for the failure of the PEM intervention to change professional behaviour, which can directly inform the design and content of future theory-based PEM interventions to change professional behaviour. TRIAL REGISTRATION ISRCTN, Canada ISRCTN72772651.
-
6.
Managing Osteoporosis: A Survey of Knowledge, Attitudes and Practices among Primary Care Physicians in Israel.
Fogelman, Y, Goldshtein, I, Segal, E, Ish-Shalom, S
PloS one. 2016;(8):e0160661
Abstract
BACKGROUND Osteoporosis is a systemic skeletal disorder characterized by impaired bone quality and microstructural deterioration leading to an increased propensity to fractures. This is a major health problem for older adults, which comprise an increasingly greater proportion of the general population. Due to a large number of patients and the insufficient availability of specialists in Israel and worldwide, osteoporosis is treated in large part by primary care physicians. We assessed the knowledge of primary care physicians on the diagnosis and treatment of osteoporosis. METHODS Physician's knowledge, sources of knowledge acquisition and self-evaluation of knowledge were assessed using a multiple choice questionnaire. Professional and demographic characteristics were assessed as well. RESULTS Of 490 physicians attending a conference, 363 filled the questionnaires (74% response rate). The physicians demonstrated better expertise in diagnosis than in medications (mechanism of action, side effects or contra-indications) but less than for other treatment related decisions. Overall, 50% demonstrated adequate knowledge of calcium and vitamin D supplementation, 51% were aware of the main therapeutic purpose of osteoporosis pharmacotherapy and 3% were aware that bisphosphonates should be avoided in patients with impaired renal function. Respondents stated frontal lectures at meetings as their main source of information on the subject. CONCLUSION The study indicates the need to intensify efforts to improve the knowledge of primary care physicians regarding osteoporosis, in general; and osteoporosis pharmacotherapy, in particular.
-
7.
Printed educational messages fail to increase use of thiazides as first-line medication for hypertension in primary care: a cluster randomized controlled trial [ISRCTN72772651].
Zwarenstein, M, Grimshaw, JM, Presseau, J, Francis, JJ, Godin, G, Johnston, M, Eccles, MP, Tetroe, J, Shiller, SK, Croxford, R, et al
Implementation science : IS. 2016;(1):124
Abstract
BACKGROUND Evidence on the effectiveness of printed educational messages in contributing to increasing evidence-based clinical practice is contradictory. Nonetheless, these messages flood physician offices, in an attempt to promote treatments that can reduce costs while improving patient outcomes. This study evaluated the ability of printed educational messages to promote the choice of thiazides as the first-line treatment for individuals newly diagnosed with hypertension, a practice supported by good evidence and included in guidelines, and one which could reduce costs to the health care system. METHODS The study uses a pragmatic, cluster randomized controlled trial (randomized by physician practice group). SETTING The setting involves all Ontario general/family practice physicians. Messages advising the use of thiazides as the first-line treatment of hypertension were mailed to each physician in conjunction with a widely read professional newsletter. Physicians were randomized to receive differing versions of printed educational messages: an "insert" (two-page evidence-based article) and/or one of two different versions of an "outsert" (short, directive message stapled to the outside of the newsletter). One outsert was developed without an explicit theory and one with messages developed targeting factors from the theory of planned behaviour or neither (newsletter only, with no mention of thiazides). The percentage of patients aged over 65 and newly diagnosed with hypertension who were prescribed a thiazide as the sole initial prescription medication. The effect of the intervention was estimated using a logistic regression model estimated using generalized estimating equation methods to account for the clustering of patients within physician practices. RESULTS Four thousand five hundred four physicians (with 23,508 patients) were randomized, providing 97 % power to detect a 5 % absolute increase in prescription of thiazides. No intervention effect was detected. Thiazides were prescribed to 27.6 % of the patients who saw control physicians, 27.4 % for the insert, 26.8 % for the outsert and 28.3 % of the patients who saw insert + outsert physicians, p = 0.54. CONCLUSIONS The study conclusively failed to demonstrate any impact of the printed educational messages on increasing prescribing of thiazide diuretics for first-line management of hypertension. TRIAL REGISTRATION ISRCTN72772651.
-
8.
Diabetes care and complications in primary care in the Tshwane district of South Africa.
Webb, EM, Rheeder, P, Van Zyl, DG
Primary care diabetes. 2015;(2):147-54
Abstract
AIMS: To describe the diabetic population receiving primary care from the Tshwane district public health services and to assess the quality of care of members of this population, their level of disease control and the extent of their complications. METHODS A cluster-randomised trial was conducted in 12 primary care clinics in Tshwane district. A total of 599 diabetic patients attending these clinics for review were consecutively interviewed and clinically examined. Data on the care received was also obtained from their clinical records for the previous 12 months. Patients randomised to the active arm of the study were screened for complications. RESULTS The mean age was 58 years and 80.5% had a body mass index (BMI) ≥25 kg/m(2). Sixty-eight percent of patients were female. Acceptable glycaemic control and LDL-cholesterol were found for only 27% and 33% of patients, respectively (HbA1c<7%; LDL<2.5 mmol/l). Despite more than 79% of patients reporting to be hypertensive, 68% of patients had a systolic blood pressure above 130 mmHg and 64% had a diastolic blood pressure above 80 mmHg. Evaluating patient records of the preceding year, screening for eye complications was only reported in 8.2%, feet complications in 6.5%, kidney complications in 21.4% and cardiovascular complications in 7.8%. The screening prevalences found were 29% for retinopathy, 22% for maculopathy, 5% for neuropathy (neurothesiometer), 7% for nephropathy (eGFR stages 3-5), 17% for possible infarction (Rose questionnaire) and 36% for severe erectile dysfunction (SHIM questionnaire). CONCLUSION Diabetes care and screening for complications at primary care level in the Tshwane district were found to be sub-optimal. Measures should be taken to address this.
-
9.
Effectiveness of an intervention designed to optimize statins use: a primary prevention randomized clinical trial.
Fàbregas, M, Berges, I, Fina, F, Hermosilla, E, Coma, E, Méndez, L, Medina, M, Calero, S, Serrano, E, Morros, R, et al
BMC family practice. 2014;:135
Abstract
BACKGROUND Although hypercholesterolemia is considered a cardiovascular risk factor, in isolation it is not necessarily sufficient cause for a cardiovascular event. To improve event prediction, cardiovascular risk calculators have been developed; the REGICOR calculator has been validated for use in our population. The objective of this project is to develop an intervention with general practitioners (GPs) and evaluate its impact on prescription adequacy of cholesterol-lowering drugs in primary prevention of cardiovascular disease and in controlling the costs associated with this disease. METHODS This nonblinded, cluster-randomized clinical trial analyzes data from primary care electronic medical records (ECAP) and other databases. Inclusion criteria are patients aged 35 to 74 years with no known cardiovascular disease and a new prescription for cholesterol-lowering drugs during the 2-year study period. Dependent variables include the following: RETIRA, defined as new cholesterol-lowering drugs initiated during the year preceding the intervention, considered inadequate, and withdrawn during the study period; EVITA, defined as new cholesterol-lowering drugs initiated during the study period and considered inadequate; COST, defined as the total cost of inadequate new treatments prescribed; and REGISTER, defined as the recording of cardiovascular risk factors. Independent variables include the GP's quality-of-care indicators and randomly assigned study group (intervention vs control), patient demographics, and clinical variables. Aggregated descriptive analysis will be done at the GP level and multilevel analysis will be performed to estimate the intervention effect, adjusted for individual and GP variables. DISCUSSION The study objective is to generate evidence about the effectiveness of implementing feedback information programs directed to GPs in the context of Primary Care. The goal is to improve the prescription adequacy of lipid-lowering therapies for primary prevention. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01997671. November 28, 2013.
-
10.
Optimal type 2 diabetes mellitus management: the randomised controlled OPTIMISE benchmarking study: baseline results from six European countries.
Hermans, MP, Brotons, C, Elisaf, M, Michel, G, Muls, E, Nobels, F, ,
European journal of preventive cardiology. 2013;(6):1095-105
Abstract
BACKGROUND Micro- and macrovascular complications of type 2 diabetes have an adverse impact on survival, quality of life and healthcare costs. The OPTIMISE (OPtimal Type 2 dIabetes Management Including benchmarking and Standard trEatment) trial comparing physicians' individual performances with a peer group evaluates the hypothesis that benchmarking, using assessments of change in three critical quality indicators of vascular risk: glycated haemoglobin (HbA1c), low-density lipoprotein-cholesterol (LDL-C) and systolic blood pressure (SBP), may improve quality of care in type 2 diabetes in the primary care setting. DESIGN This was a randomised, controlled study of 3980 patients with type 2 diabetes. METHODS Six European countries participated in the OPTIMISE study (NCT00681850). Quality of care was assessed by the percentage of patients achieving pre-set targets for the three critical quality indicators over 12 months. Physicians were randomly assigned to receive either benchmarked or non-benchmarked feedback. All physicians received feedback on six of their patients' modifiable outcome indicators (HbA1c, fasting glycaemia, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), LDL-C and triglycerides). Physicians in the benchmarking group additionally received information on levels of control achieved for the three critical quality indicators compared with colleagues. RESULTS At baseline, the percentage of evaluable patients (N = 3980) achieving pre-set targets was 51.2% (HbA1c; n = 2028/3964); 34.9% (LDL-C; n = 1350/3865); 27.3% (systolic blood pressure; n = 911/3337). CONCLUSIONS OPTIMISE confirms that target achievement in the primary care setting is suboptimal for all three critical quality indicators. This represents an unmet but modifiable need to revisit the mechanisms and management of improving care in type 2 diabetes. OPTIMISE will help to assess whether benchmarking is a useful clinical tool for improving outcomes in type 2 diabetes.