Thiazide Prescribing Research Articles

Thiazide Discontinuation in Chronic Kidney Disease Hypertension Management: A Retrospective Chart Review.

Thiazides are utilized in general hypertension management, however, their role in chronic kidney disease (CKD) hypertension management remains unclear. Although data support thiazide efficacy in advanced CKD, the adverse effect profile (including estimated glomerular filtration rate [eGFR] decline and electrolyte abnormalities) may lead to thiazide discontinuation. The authors assessed the thiazide discontinuation rate in Kaiser Permanente Southern California members with moderate-to-severe CKD and hypertension. This study was a multicenter retrospective analysis evaluating Kaiser Permanente Southern California members with hypertension and CKD 3B or 4 who filled a thiazide prescription in 2021, with follow-up through 2022. The outcomes were thiazide discontinuation rate, reason for thiazide discontinuation, time to thiazide discontinuation, and discontinuing practitioner specialty. Mean changes in blood pressure and eGFR from baseline were also evaluated. Of the 401 patients followed for 1 year after thiazide initiation, 65 patients discontinued a thiazide (discontinuation rate: 16.2%, mean time to discontinuation: 7.5 months). Of the 201 patients followed for 2 years after thiazide initiation, 57 patients discontinued a thiazide (discontinuation rate: 28.4%, mean time to discontinuation: 15.5 months). The most commonly documented thiazide discontinuation reason was increased serum creatinine (30% of total reasons at 1 year and 39% of total reasons at 2 years). Most patients with hypertension and CKD 3B or 4 continued on a thiazide with favorable blood pressure lowering effects and modest eGFR decline. Thiazides may be considered viable antihypertensive options with close renal function monitoring for patients with moderate-to-severe CKD.

Hospital Readmissions for Fluid Overload among Individuals with Diabetes and Diabetic Kidney Disease: Risk Factors and Multivariable Prediction Models

Aims: Hospital readmissions due to recurrent fluid overload in diabetes and diabetic kidney disease can be avoided with evidence-based interventions. We aimed to identify at-risk patients who can benefit from these interventions by developing risk prediction models for readmissions for fluid overload in people living with diabetes and diabetic kidney disease. Methods: This was a single-center retrospective cohort study of 1,531 adults with diabetes and diabetic kidney disease hospitalized for fluid overload, congestive heart failure, pulmonary edema, and generalized edema between 2015 and 2017. The multivariable regression models for 30-day and 90-day readmission for fluid overload were compared with the LACE score for discrimination, calibration, sensitivity, specificity, and net reclassification index (NRI). Results: Readmissions for fluid overload within 30 days and 90 days occurred in 8.6% and 17.2% of patients with diabetes, and 8.2% and 18.3% of patients with diabetic kidney disease, respectively. After adjusting for demographics, comorbidities, clinical parameters, and medications, a history of alcoholism (HR 3.85, 95% CI: 1.41–10.55) and prior hospitalization for fluid overload (HR 2.50, 95% CI: 1.26–4.96) were independently associated with 30-day readmission in patients with diabetic kidney disease, as well as in individuals with diabetes. Additionally, current smoking, absence of hypertension, and high-dose intravenous furosemide were also associated with 30-day readmission in individuals with diabetes. Prior hospitalization for fluid overload (HR 2.43, 95% CI: 1.50–3.94), cardiovascular disease (HR 1.44, 95% CI: 1.03–2.02), eGFR ≤45 mL/min/1.73 m2 (HR 1.39, 95% CI: 1.003–1.93) was independently associated with 90-day readmissions in individuals with diabetic kidney disease. Additionally, thiazide prescription at discharge reduced 90-day readmission in diabetic kidney disease, while the need for high-dose intravenous furosemide predicted 90-day readmission in diabetes. The clinical and clinico-psychological models for 90-day readmission in individuals with diabetes and diabetic kidney disease had better discrimination and calibration than the LACE score. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetes was 22.4% and 28.9%, respectively. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetic kidney disease was 5.6% and 38.9%, respectively. Conclusion: The risk models can potentially be used to identify patients at risk of readmission for fluid overload for evidence-based interventions, such as patient education or transitional care programs to reduce preventable hospitalizations.

Thiazide Diuretic Utilization Within the VA.

The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends chlorthalidone as the preferred thiazide diuretic. We aimed to better understand thiazide prescribing patterns within the US Department of Veterans Affairs (VA). A retrospective analysis was conducted of patients with a prescription for hydrochlorothiazide (HCTZ), chlorthalidone, indapamide, or any combination products containing these from January 1, 2016, to January 21, 2022. The primary objective was to determine the utilization rates of each thiazide in the active cohort, assessed via χ2 test with Bonferroni correction. Secondary objectives included concomitant potassium or magnesium supplementation, blood pressure rates and control, and thiazide use from January 1, 2016, to December 31, 2021. Of 628,994 active thiazide prescriptions, utilization rates differed significantly between thiazide groups (P < .001). Rates for HCTZ, chlorthalidone, and indapamide were 84.6%, 14.9%, and 0.5%, respectively. HCTZ use decreased from 90.2% to 83.5% (P < .001) and chlorthalidone use increased from 9.3% to 16.0% (P < .001). Between thiazide groups, rates of blood pressure control were not significantly different (P = .58). Potassium or magnesium supplementation was significantly different between groups (P < .001). The highest concomitant supplementation was with indapamide followed by chlorthalidone and HCTZ with rates of 27.1%, 22.6%, and 12.4%, respectively. Despite guideline recommendations for chlorthalidone, HCTZ is the most prescribed thiazide diuretic within the VA. However, there was a significant trend toward increased chlorthalidone prescribing from 2016 to 2021. Application of these data may guide further research to increase guideline-recommended therapy.

Clinical Effectiveness of Calcium Oxalate Stone Treatments

Introduction: Lowering kidney stone risk and urine calcium oxalate supersaturation is a primary clinical focus for kidney stone prevention and can be achieved with multiple strategies. Common strategies include advice to increase fluid intake, restrict dietary sodium, or prescribing a thiazide-type diuretic. We investigated how physicians make these decisions in real-world practice and evaluate their efficacy based on 24-h urine collections. Methods: We reviewed medical charts for 203 kidney stone formers with idiopathic calcium stones from University of Chicago Kidney Stone Clinic between 2005 and 2020. Patients had three 24-h urines before an initial pre-treatment clinic visit and one follow-up 24-h urine. We analyzed changes in urine composition based on treatment advice using t tests and ANOVA. Results: Patients who received advice to increase fluid intake had lower urine volume at baseline (1.5 vs. 2.5 L/day, p < 0.001) and larger increase in urine volume at follow-up (0.6 vs. 0.1 L/day, p < 0.001) compared to those who did not receive the advice. Patients who were advised to restrict dietary sodium had a higher urine sodium at baseline (208 vs. 139 mEq/day, p < 0.001), a larger reduction in urine sodium (−28 vs. 13 mEq/day, p = 0.002), and larger reduction in urine calcium (−74 vs. −28 mg/day, p = 0.005) compared with those not advised to restrict dietary sodium. Patients started on a thiazide had a higher baseline urine calcium (281 vs. 213 mg/day) and larger reduction in urine calcium (−83 vs. −9 mg/day, p < 0.001) compared with patients not started on a thiazide. In combination, thiazide prescriptions with dietary sodium restriction reduced urine calcium by 99 mg/day and reduced calcium oxalate supersaturation from 8.0 to 5.5 and calcium phosphate supersaturation from 1.4 to 1.0. Conclusion: Providers use 24-h urine data to guide treatment strategy decisions. These strategies achieved the intended effects on urine composition and lowered kidney stone risk.

Clinical Decision Support to Address Racial Disparities in Hypertension Control in an Integrated Delivery System: Evaluation of a Natural Experiment.

Effective, equity-promoting interventions implemented by health care systems are needed to address health care disparities and population-level health disparities. We evaluated the impact of a clinical decision support tool to improve evidence-based thiazide diuretic prescribing among Black patients to address racial disparities in hypertension control. We employed an interrupted time series design and qualitative interviews to evaluate the implementation of the tool. Our primary outcome measure was the monthly rate of thiazide use among eligible patients before and after implementation of the tool (January 2013-December 2016). We modeled month-to-month changes in thiazide use for Black and White patients, overall, and by sex and medical center racial composition. We conducted key informant interviews to identify modifiable facilitators and barriers to implementation of the tool across medical centers. Of the 318,720 patients, 15.5% were Black. We observed no change in thiazide use or blood pressure control following the implementation of the tool in either racial subgroup. There was a slight but statistically significant reduction (2.32 percentage points, p < 0.01) in thiazide use among Black patients following the removal the tool that was not observed among White patients. Factors affecting the tool's implementation included physician and pharmacist resistance to thiazide use and a lack of ongoing promotion of the tool. The clinical decision support tool was insufficient to change prescribing practices and improve blood pressure control among Black patients. Future interventions should consider physician attitudes about thiazide prescribing and the importance of multilevel approaches to address hypertension disparities.

Antihypertensive Prescribing for Uncomplicated, Incident Hypertension: Opportunities for Cost Savings

BackgroundA range of first-line similarly effective medications ranging in price are recommended for treating uncomplicated hypertension. Considering drug costs alone, thiazides and thiazide-like diuretics are the most cost-efficient option. We determined incident prescribing of thiazides for newly diagnosed hypertension as first-line treatment in Alberta, factors that predicted receiving thiazides vs more costly medications, and how much could be saved if more patients were prescribed thiazides. MethodsUsing a retrospective cohort design, factors predicting receiving thiazides vs other agents were determined using mixed effects logistic regression. Cost savings were simulated by shifting patients from other antihypertensive medications to thiazides and calculating the difference. ResultsWithin our cohort of 89,548 adults, only 12% received thiazides as first-line treatment whereas 44% received angiotensin converting enzyme inhibitors, 17% received angiotensin receptor blockers, 16% received calcium channel blockers, and 10% received β-blockers. Antihypertensive medications were typically prescribed by office-based, general practitioners (88%). Being male and receiving a prescription from a physician with ≥ 20 years of practice and a high clinical workload were associated with increased odds of receiving nonthiazides. In the extreme case that all patients received thiazides as their first prescription, spending would have been reduced by a maximum of 95% (CAD$1.8 million). ConclusionsOnly 12% of Albertan adults with incident, uncomplicated hypertension were prescribed thiazides as first-line treatment. With the opportunity for drug cost savings, future research should evaluate the risk of adverse events and side effects across the drug classes and whether the costs associated with managing those risks could offset the savings achieved through increased thiazide use.

Association of patient preferences on medication discussion in hypertension: Results from a randomized clinical trial.

Patient-centered care has received significant attention and is an integral component of high-quality healthcare. While it is often assumed that most prefer a patient-centered role orientation, such preferences exist along a continuum with some patients preferring a more provider-centered role. The present study examines patient preference data from a randomized clinical trial designed to test the efficacy of a patient activation intervention to promote thiazide prescribing for veteran patients with uncontrolled hypertension. Patient preferences for involvement in healthcare were assessed using the 9-item Sharing subscale of the Patient-Practitioner Orientation Scale (PPOS). The primary aim was to examine differences in discussion of thiazide use in the clinical encounter by those scoring high versus low on the PPOS. Five hundred ninety-five veteran patients were randomized to either one of three intervention groups or a usual care control group. The adjusted odds ratios (OR) for the three intervention groups relative to the control group indicated that thiazide discussion increased as a function of intervention intensity across both high and low PPOS groups. ORs for the most intensive intervention group were 3.72 (95% CI=1.61-8.65, p<.01) for high PPOS patients and 6.71 (95% CI=2.59-10.67, p<.001) for low PPOS patients. Results suggest that this patient activation intervention is effective for veteran patients representing a range of preferred involvement. Consideration of such preferences may be useful in tailoring future interventions in the healthcare context.

In-Hospital Serum Uric Acid Change Predicts Adverse Outcome in Patients With Heart Failure

BackgroundElevated serum uric acid (UA) is associated with an increased risk of adverse outcome in patients with heart failure (HF), but it remains unknown whether the change of serum UA level during the treatment of acute decompensated HF (ADHF) predicts adverse events. Methods and ResultsWe retrospectively analyzed consecutive 1562 patients who were hospitalized for ADHF. Serum UA levels both at admission and discharge were available in 1246 patients (78 years of age, range 69–84 years, 40% female). UA values increased or unchanged (group I) in 766 patients and it decreased in the remaining patients (group D). Group I was characterized by older age, higher proportion of females, preserved left ventricular ejection fraction, and the features of less severity of HF such as lower plasma N-terminal pro B-type natriuretic peptide level and lower percentage of catecholamine use. Nevertheless, group I was associated with higher incidence of the primary end point defined as the composite of all-cause death and ADHF rehospitalization (P = .013, log-rank test). UA change, but not UA at discharge, was an independent predictor of the primary end point (hazard ratio 1.30, interquartile range 1.04–1.64, P = .022). Age, estimated glomerular filtration rate, left ventricular ejection fraction, dose of loop diuretics, and thiazide prescription at discharge were independently associated with the UA change. ConclusionsIn patients with HF, UA change through the treatment of ADHF might predict future adverse outcome.

Some patient interventions increased thiazide prescriptions and improved blood pressure control.

Source Citation Kaboli P, Howren MB, Ishani A, et al. Efficacy of patient activation interventions with or without financial incentives to promote prescribing of thiazides and hypertension control:...

Efficacy of Patient Activation Interventions With or Without Financial Incentives to Promote Prescribing of Thiazides and Hypertension Control

ImportanceEvidence-based guidelines recommend thiazide diuretics as a first-line therapy for uncomplicated hypertension; however, thiazides are underused, and hypertension remains inadequately managed.ObjectiveTo test the efficacy of a patient activation intervention with financial incentives to promote thiazide prescribing.Design, Setting, and ParticipantsThe Veterans Affairs Project to Implement Diuretics, a randomized clinical trial, was conducted at 13 Veterans Affairs primary care clinics from August 1, 2006, to July 31, 2008, with 12 months of follow-up. A total of 61 019 patients were screened to identify 2853 eligible patients who were not taking a thiazide and not at their blood pressure (BP) goal; 598 consented to participate. Statistical analysis was conducted from December 1, 2017, to September 12, 2018.InterventionsPatients were randomized to a control group (n = 196) or 1 of 3 intervention groups designed to activate patients to talk with their primary care clinicians about thiazides and hypertension: group A (n = 143) received an activation letter, group B (n = 128) received a letter plus a financial incentive, and group C (n = 131) received a letter, financial incentive, and a telephone call encouraging patients to speak with their primary care clinicians.Main Outcomes and MeasuresPrimary outcomes were thiazide prescribing and BP control. A secondary process measure was discussion between patient and primary care clinician about thiazides.ResultsAmong 598 participants (588 men and 10 women), the mean (SD) age for the combined intervention groups (n = 402) was 62.9 (8.8) years, and the mean baseline BP was 148.1/83.8 mm Hg; the mean (SD) age for the control group (n = 196) was 64.1 (9.2) years, and the mean baseline BP was 151.0/83.4 mm Hg. At index visits, the unadjusted rate of thiazide prescribing was 9.7% for the control group (19 of 196) and 24.5% (35 of 143) for group A, 25.8% (33 of 128) for group B, and 32.8% (43 of 131) for group C (P < .001). Adjusted analyses demonstrated an intervention effect on thiazide prescribing at the index visit and 6-month visit, which diminished at the 12-month visit. For BP control, there was a significant intervention effect at the 12-month follow-up for group C (adjusted odds ratio, 1.73; 95% CI, 1.06-2.83; P = .04). Intervention groups exhibited improved thiazide discussion rates in a dose-response fashion: group A, 44.1% (63 of 143); group B, 56.3% (72 of 128); and group C, 68.7% (90 of 131) (P = .004).Conclusions and RelevanceThis patient activation intervention about thiazides for hypertension resulted in two-thirds of patients having discussions and nearly one-third initiating a prescription of thiazide. Adding a financial incentive and telephone call to the letter resulted in incremental improvements in both outcomes. By 12 months, improved BP control was also evident. This low-cost, low-intensity intervention resulted in high rates of discussions between patients and clinicians and subsequent thiazide treatment and may be used to promote evidence-based guidelines and overcome clinical inertia.Trial RegistrationClinicalTrials.gov Identifier: NCT00265538

The Delivery Science Rapid Analysis Program: A Research and Operational Partnership at Kaiser Permanente Northern California.

IntroductionHealth care researchers and delivery system leaders share a common mission to improve health care quality and outcomes. However, differing timelines, incentives, and priorities are often a barrier to research and operational partnerships. In addition, few funding mechanisms exist to generate and solicit analytic questions that are of interest to both research and to operations within health care settings, and provide rapid results that can be used to improve practice and outcomes.MethodsThe Delivery Science Rapid Analysis Program (RAP) was formed in 2013 within the Kaiser Permanente Northern California Division of Research, sponsored by The Permanente Medical Group. A steering committee consisting of both researchers and clinical leaders solicits and reviews proposals for rapid analytic projects that will use existing data and are feasible within 6 months and with up to $30,000 (approximately 25%–50% full‐time equivalent) of programmer/analyst effort. Review criteria include the importance of the analytic question for both research and operations, and the potential for the project to have a significant impact on care delivery within 12 months of completion.ResultsThe RAP funded 5 research and operational analytic projects between 2013 and 2017. These projects spanned a wide range of clinical areas, including lupus, pediatric obesity, diabetes, e‐cigarette use, and hypertension. The hypertension RAP project, which focused on optimizing thiazide prescribing in Black/African American patients with hypertension, led to new insights that inform an equitable care quality metric designed to reduce blood pressure control disparities throughout the Kaiser Permanente Northern California region.ConclusionsPrograms that actively encourage research and operational analytic partnerships have significant potential to improve care, enhance research collaborations, and contribute to the building and sustaining of learning health systems.

A retrospective case-control study evaluating thiazide-induced hyponatraemia-related hospitalisation among older Singaporeans

Introduction: Thiazide diuretics are recommended as first-line therapy for hypertension in older adults. However, thiazides are also associated with hyponatraemia-related hospitalisations in older patients. This study aims to determine the predictors of hospitalisation due to thiazides usage in older adults. Methods: This is a retrospective matched case-control study. Patients aged ⩾65 admitted due to adverse drug reactions based on International Classification of Diseases, Ninth Revision (ICD9) codes from the period of 1 June to 31 December 2011 in Singapore General Hospital were extracted. Patients with the ICD9 code E944.3 Saluretics causing adverse effects in therapeutic use and who experienced thiazide-induced hyponatraemia were identified. Controls were identified from a pool of patients from outpatient clinics who were prescribed thiazide during the study period. Each case was matched to four controls based on gender and race. Patients’ demographics, length of stay, and cost of hospital admission were obtained. Results: In total, 19 cases with thiazide-induced hyponatraemia were matched with 76 controls. Cases were older than control (78.8±6.1 vs. 75.6±7.0, p=0.052), with the majority being females (84.2%) and Chinese (94.7%). The mean length of stay was 4 (±3) days; the mean cost of stay was SGD 1118 (±898). Serum potassium levels and concurrent use of beta-blockers were identified as unadjusted possible predictors for hospitalisation due to thiazide-induced hyponatraemia. Conclusion: Potential predictors of hospitalisation due to thiazide-induced hyponatraemia include low potassium levels and concurrent use of beta-blockers. Identification of predictors is crucial to guide safe and effective prescribing of thiazides in older patients.

Patterns and Correlates of Baseline Thiazide-Type Diuretic Prescription in the Systolic Blood Pressure Intervention Trial.

Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness.

Optimal age of commencing and discontinuing thiazide therapy to protect against fractures.

A study of national Danish patient data with regard to thiazide diuretics vs. non-treatment. We find that after age 83years, thiazides increase the 10-year risk of major fractures. We also find that thiazides can be stopped after 63years old to possibly protect against fracture occurrence. The purpose of this study was to retrospectively examine the optimal age for commencing and discontinuing thiazide therapy to protect from osteoporotic fractures. A population-based, retrospective matched cohort study was done using national data of 2.93 million Danish subjects. Ten-year crude and adjusted age-grouped hazard ratios (HRs) of fracture occurrence were stratified by age of commencing thiazides compared to non-exposure. Separate analyses were done on Anatomical Therapeutic Chemical Classification System (ATC) codes C03AA and C03AA + C03AB compiled. Ten-year crude HRs of fracture occurrence for discontinuing vs. continuing thiazides were estimated and stratified by age for the two groups. For C03AB alone (97.1% of thiazide prescriptions), adjusted 10-year HRs of fracture occurrence were significantly increased for thiazide commencement after age 83years and comparable to non-exposure for commencement between ages 50 and 83years. For C03AA + C03AB, 10-year adjusted HRs of fracture occurrence were significantly increased from ages 73years and upwards. Crude 10-year HRs of fracture occurrence were significantly decreased for discontinuing vs. continuing thiazides at or after age 63years for C03AB and age 77years for C03AA + C03AB. No significantly protective effect of thiazides was found on fracture occurrence compared to non-users, but evidence that thiazides increase the 10-year adjusted HR risk of fractures if prescribed after the age of 83years for C03AB and 73years for C03AA + C03AB. Discontinuing thiazides at or after age 63years for C03AB or 77years for C03AA & C03AB significantly decreases the 10-year risk of fractures compared to continuing thiazides. Further prospective studies are warranted.

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

BackgroundPragmatic 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.MethodsWe 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.ResultsFour 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.ConclusionsCongruent 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 registrationISRCTN, Canada ISRCTN72772651 Electronic supplementary materialThe online version of this article (doi:10.1186/s13012-016-0485-4) contains supplementary material, which is available to authorized users.

Engineering practice variation through provider agreement: a cluster-randomized feasibility trial.

PurposeMinimal-risk randomized trials that can be embedded in practice could facilitate learning health-care systems. A cluster-randomized design was proposed to compare treatment strategies by assigning clusters (eg, providers) to “favor” a particular drug, with providers retaining autonomy for specific patients. Patient informed consent might be waived, broadening inclusion. However, it is not known if providers will adhere to the assignment or whether institutional review boards will waive consent. We evaluated the feasibility of this trial design.Subjects and methodsAgreeable providers were randomized to “favor” either hydrochlorothiazide or chlorthalidone when starting patients on thiazide-type therapy for hypertension. The assignment applied when the provider had already decided to start a thiazide, and providers could deviate from the strategy as needed. Prescriptions were aggregated to produce a provider strategy-adherence rate.ResultsAll four institutional review boards waived documentation of patient consent. Providers (n=18) followed their assigned strategy for most of their new thiazide prescriptions (n=138 patients). In the “favor hydrochlorothiazide” group, there was 99% adherence to that strategy. In the “favor chlorthalidone” group, chlorthalidone comprised 77% of new thiazide starts, up from 1% in the pre-study period. When the assigned strategy was followed, dosing in the recommended range was 48% for hydrochlorothiazide (25–50 mg/day) and 100% for chlorthalidone (12.5–25.0 mg/day). Providers were motivated to participate by a desire to contribute to a comparative effectiveness study. A study promotional mug, provider information letter, and interactions with the site investigator were identified as most helpful in reminding providers of their study drug strategy.ConclusionProviders prescribed according to an assigned drug-choice strategy most of the time for the purpose of a comparative effectiveness study. This simple design could facilitate research participation and behavior change in non-research clinicians. Waiver of patient consent can broaden the representation of patients, providers, and settings.

CHLORTHALIDONE COMPARED TO HYDROCHLOROTHIAZIDE IN REDUCING CARDIOVASCULAR EVENTS: SYSTEMATIC REVIEW AND NETWORK META-ANALYSES

Hydrochlorothiazide (HCTZ) is the thiazide widely prescribed to treat hypertension. (e.g., HCTZ represented 96p of all thiazide prescriptions in the Veterans Administration [Ernst 2010].) Some have recently expressed a preference for chlorthalidone (CTDN). However, no head-to-head randomized

Evaluations of Hospitalizations Associated With Thiazide‐Associated Hyponatremia

J Clin Hypertens (Greenwich). 2012;14:158–164. ©2012 Wiley Periodicals, Inc.The prevalence of hypertension in the United States has grown dramatically in recent years. Thiazide diuretics have played a major role in the rising rate of blood pressure (BP) control. Accompanying this has been the appearance of adverse drug events, including hospitalizations associated with thiazide‐associated hyponatremia (HTAH). Hyponatremia is a common yet often overlooked side effect of this drug class. Identification of HTAH risk factors may aid in creating strategies to prevent hospitalizations. This is a retrospective, case‐controlled study of 10,805 patients (1802 cases, 9003 controls) examining HTAH risk factors within a group‐model integrated‐care organization. Multivariate analysis revealed that age (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.58–1.93), angiotensin‐converting enzyme (ACE) inhibitor use (OR, 1.53; 95% CI, 1.16–2.00), and hypokalemia (OR, 40.94; 95% CI, 26.46–66.33) were most associated with HTAH. Urinary tract infection (UTI), type 2 diabetes, hyperlipidemia, and gastroesophageal reflux disease (GERD) were also found to be HTAH risk factors. Potassium supplements (OR, 0.60; 95% CI, 0.44–0.83) and weight (OR, 0.91; 95% CI, 0.88–0.93) had protective effects. A predictive model was developed to determine overall HTAH risk given the presence of individual risk factors. Age, weight, hypokalemia, GERD, type 2 diabetes, UTI, and ACE inhibitor use independently correlated with an increased risk of HTAH. This model may be applied in clinical practice to guide thiazide prescribing.

Risk of falls associated with antihypertensive medication: self‐controlled case series

To quantify the possible role of confounding in our earlier estimates of the risk of falls amongst older people who have been prescribed antihypertensives. Self-controlled case series analysis of 9862 individuals older than 60 years of age with a first fall recorded between years 2003 and 2006 and at least 12 months of recorded history before the first fall, taken from 386 UK general practices contributing data to The Health Improvement Network primary care database. Conditional Poisson regression to estimate incidence rate ratios for periods of exposure and non-exposure, adjusting for the effect of age. Incidence rate ratio of first fall in days 1-21 of the first episode of thiazide prescription is 2.80 (95%CI 1.7-4.57). For beta-blockers, the rate ratio in day 22 onwards is 1.23 (95%CI 1.02-1.48) in the very first episode of medication and 1.21 (95%CI 1.02-1.42) in subsequent episodes but is not significant in other periods of exposure. The incidence rate of first falls in day 22 of any episode of calcium channel blocker prescription is 0.75 (95%CI 0.60-0.92). The study provides evidence that at least some of our earlier estimates were subject to confounding. Nevertheless, thiazide prescription remains associated with an increased risk of first fall, and this effect is strongest in the first 3 weeks of prescription. Our study demonstrates that the case series method provides an effective way to assess the extent of residual confounding in case-control studies.

Profiles of discontinuation and switching of thiazide diuretics: a cohort study among 9398 Chinese hypertensive patients

This study tested the hypothesis that younger, male patients or new clinic visitors, who were prescribed thiazide diuretics were more likely to have drug discontinuation and switching. All adult patients who visited any primary care clinic in one territory of Hong Kong, and who were prescribed a thiazide diuretic from January 2004 to June 2007 were included. The rates of discontinuation and switching, separately, 180 days after thiazide prescriptions were measured. Factors associated with discontinuation and switching were evaluated by multiple regression analyses. Among 9398 patients, 12.5% discontinued and 10.8% switched their prescriptions, whereas prescriptions of other patients remained the same. Younger patients (< 50 years (reference value); adjusted odds ratio (AOR) for 50-59 years=0.74, 95% confidence interval (CI) 0.61-0.90, P=0.002; AOR (60-69 years)=0.57, 95% CI 0.46-0.70, P < 0.001; AOR (≥ 70 years)=0.88, 95% CI 0.73-1.06, P=0.174), male subjects (AOR=1.23, 95% CI 1.07-1.40, P=0.003) and new visitors (AOR (repeat visitors)=0.55, 95% CI 0.47-0.65, P < 0.001) were more likely to be discontinuers. These associations between younger age (< 50 years (reference value); AOR (50-59) years=0.85, 95% CI 0.70-1.04, P=0.112; AOR (60-69 year)=0.79, 95% CI 0.65-0.98, P=0.028; AOR (≥ 70 years)=0.70, 95% CI 0.57-0.85, P < 0.001), male gender (AOR=1.29, 95% CI 1.12-1.48, P < 0.001) and new visitors (AOR (repeat visitors)=0.57, 95% CI 0.48-0.67, P < 0.001) were also significant for medication switching. Clinicians should monitor the medication-taking behavior more closely among patients aged 50-59 years, male subjects and new clinic visitors when thiazide was prescribed.