Why physicians do not prescribe a thiazide diuretic.
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ABSTRACT:
SUBMITTER: Sutton E
PROVIDER: S-EPMC8673042 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Thiazide diuretics are recommended as first line antihypertensive treatment, but may contribute to new onset diabetes. We aimed to describe change in fasting glucose (FG) during prolonged thiazide treatment in an observational setting.We conducted an observational, non-randomized, open label, follow-up study of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 studies. We enrolled previous participants from the PEAR or PEAR-2 studies with at least 6 months of continuous treatment with either hydrochlorothiazide (HCTZ) or chlorthalidone. Linear regression was used to identify associations with changes in FG after prolonged thiazide and thiazide-like diuretic treatment.A total of 40 participants were included with a mean 29 (range 8-72) months of thiazide treatment. FG increased 6.5 (SD 13.0) mg/dL during short-term thiazide treatment and 3.6 (SD 15.3) mg/dL FG during prolonged thiazide treatment. Increased FG at follow-up was associated with longer thiazide treatment duration (?=0.34, p=0.008) and lower baseline FG (?=-0.46, p=0.02). ? blocker treatment in combination with prolonged thiazide diuretic treatment was also associated with increased FG and increased 2-h glucose obtained from OGTT.Our results indicate that prolonged thiazide treatment duration is associated with increased FG and that overall glycemic status worsens when thiazide/thiazide-like diuretics are combined with ? blockers.
| S-EPMC4074403 | biostudies-literature
Project description:IntroductionThe incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences.MethodsIn the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians.ResultsIn 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2-9.8 ml/min/1.73 m2), and those with edema, "low GFR", and acidosis, the lowest (4.6-6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2).ConclusionsDI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.
| S-EPMC5737975 | biostudies-literature
Project description:We conducted a genome-wide association study to identify novel genes influencing diastolic blood pressure (BP) response to hydrochlorothiazide, a commonly prescribed thiazide diuretic preferred for the treatment of high BP. Affymetrix GeneChip Human Mapping 100K Arrays were used to measure single nucleotide polymorphisms across the 22 autosomes in 194 non-Hispanic black subjects and 195 non-Hispanic white subjects with essential hypertension selected from opposite tertiles of the race- and sex-specific distributions of age-adjusted diastolic BP response to hydrochlorothiazide (25 mg daily, PO, for 4 weeks). The black sample consisted of 97 "good" responders (diastolic BP response [mean+/-SD]=-18.3+/-4.2 mm Hg; age=47.1+/-6.1 years; 51.5% women) and 97 "poor" responders (diastolic BP response=-0.18+/-4.3; age=47.4+/-6.5 years; 51.5% women). Haplotype trend regression identified a region of chromosome 12q15 in which haplotypes constructed from 3 successive single nucleotide polymorphisms (rs317689, rs315135, and rs7297610) in proximity to lysozyme (LYZ), YEATS domain containing 4 (YEATS4), and fibroblast growth receptor substrate 2 (FRS2) were significantly associated with diastolic BP response (nominal P=2.39 x 10(-7); Bonferroni corrected P=0.024; simulated experiment-wise P=0.040). Genotyping of 35 additional single nucleotide polymorphisms selected to "tag" linkage disequilibrium blocks in these genes provided corroboration that variation in LYZ and YEATS4 was associated with diastolic BP response in a statistically independent data set of 291 black subjects and in the sample of 294 white subjects. These results support the use of genome-wide association analyses to identify novel genes influencing antihypertensive drug responses.
| S-EPMC2692710 | biostudies-literature
Project description:Adequate pain management is one of the biggest challenges of the modern healthcare system. Physician perception of patient subjective pain, which is crucial to pain management, is susceptible to a host of potential biases. Here we explore the timing of physicians' work as a previously unrecognized source of systematic bias in pain management. We hypothesized that during night shifts, sleep deprivation, fatigue, and stress would reduce physicians' empathy for others' pain, leading to underprescription of analgesics for patient pain relief. In study 1, 67 resident physicians, either following a night shift or not, performed empathy for pain assessment tasks and simulated patient scenarios in laboratory conditions. As predicted, following a night shift, physicians showed reduced empathy for pain. In study 2, we explored this phenomenon in medical decisions in the field. We analyzed three emergency department datasets from Israel and the United States that included discharge notes of patients arriving with pain complaints during 2013 to 2020 (n = 13,482). Across all datasets, physicians were less likely to prescribe an analgesic during night shifts (compared to daytime shifts) and prescribed fewer analgesics than generally recommended by the World Health Organization. This effect remained significant after adjusting for patient, physician, type of complaint, and emergency department characteristics. Underprescription for pain during night shifts was particularly prominent for opioids. We conclude that night shift work is an important and previously unrecognized source of bias in pain management, likely stemming from impaired perception of pain. We consider the implications for hospitals and other organizations employing night shifts.
| S-EPMC9271188 | biostudies-literature
Project description:BackgroundThiazide diuretics are commonly prescribed to prevent kidney stones. However, it is unclear whether higher doses confer greater benefit.ObjectiveTo determine whether lower doses of thiazide diuretics confer a similar protective effect against kidney stone events as higher doses.DesignPopulation-based cohort study.SettingLinked health administrative databases in Ontario, Canada.PatientsOlder adults newly prescribed a thiazide diuretic between 2003 and 2014 were separated into 2 groups based on daily dose: low dose (?12.5 mg hydrochlorothiazide/chlorthalidone, or ?1.25 mg indapamide) or high dose.MeasurementsThe primary outcome was time to a kidney stone event, using diagnosis and procedure codes. A secondary outcome was kidney stone surgery.MethodsAn association between thiazide diuretic dose and a kidney stone event was estimated using Cox proportional hazards regression.ResultsA total of 536 of 105 239 patients (0.51%) experienced a kidney stone event. We did not detect a difference in kidney stone risk in the high-dose relative to the low-dose group (adjusted hazard ratio, 1.10; 95% confidence interval, 0.93-1.31). Results were similar when analysis was restricted to the more specific outcome of kidney stone surgery. Neither a history of prior kidney stones nor the type of thiazide diuretic modified the effect of diuretic dose on outcome.LimitationsPatients were >65 years old and we were unable to adjust for some potential confounders such as dietary factors.ConclusionsLower dose thiazide diuretics appear to confer a similar protective effect as higher dose thiazides against the development of kidney stones.
| S-EPMC6048667 | biostudies-literature
Project description:BackgroundPrior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure's definition has changed over time.AimTo determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics.Data sourcesA research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014).Study selectionRandomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling < 50 participants, those with a follow-up period of < 4 weeks, and conference abstracts were excluded.Data extractionIndependent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted.Data synthesisNinety-five studies were included (N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20 mmol/L (95% CI 0.15-0.25); I2 = 84%) (1 mmol/L = 18 mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent.ConclusionThiazide diuretics have a small and clinically unimportant impact on FPG.
| S-EPMC7280437 | biostudies-literature
Project description: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.
| S-EPMC4755350 | biostudies-literature
Project description:Objective: With 42% of all emergency department visits in the United States related to pain, physicians who work in this setting are tasked with providing adequate pain management to patients with varying primary complaints and medical histories. Complicating this, the United States is in the midst of an opioid overdose epidemic. State governments and national organizations have developed guidelines and legislation to curtail opioid prescriptions in acute care settings, while also incentivizing providers for patient satisfaction and completeness of pain control. In order to inform future policies that focus on provider pain medication prescribing, we sought to characterize the factors physicians weigh when considering treating pain with opioids in the emergency department. Methods: We conducted and transcribed open-ended, semistructured qualitative interviews with 52 physicians at a national emergency medicine conference. Results: Participants reported a wide range of factors contributing to their opioid prescribing patterns related to three domains: 1) provider assessment of pain characteristics, 2) patient-based considerations, and 3) practice environment. Pain characteristics include the characteristics of various acute and chronic pain syndromes, including physicians' empathy due to their own experiences with pain. Patient characteristics include "trustworthiness," race and ethnicity, and the concern for risk of misuse. Factors related to the practice environment include hospital policy, legislation/regulation, and guidelines. Conclusion: The decision to prescribe opioids to patients in the emergency department is complex and nuanced. Physicians are interested in guidance and are concerned about the competing pressures placed on their opioid prescribing due to incentives related to patient satisfaction scores on one hand and inflexible policies that do not allow for individualized, patient-centered decisions on the other.
| S-EPMC6124837 | biostudies-other
Project description:Human pregnane X receptor (hPXR) regulates the expression of drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) and drug transporters such as multidrug-resistance protein 1 (MDR1). PXR can be modulated by small molecules, including Federal Drug Administration (FDA)-approved drugs, thus altering drug metabolism and causing drug-drug interactions. To determine the role of FDA-approved drugs in PXR-mediated regulation of drug metabolism and clearance, we screened 1481 FDA-approved small-molecule drugs by using a luciferase reporter assay in HEK293T cells and identified the diuretic drug metolazone as an activator of hPXR. Our data showed that metolazone activated hPXR-mediated expression of CYP3A4 and MDR1 in human hepatocytes and intestine cells and increased CYP3A4 promoter activity in various cell lines. Mammalian two-hybrid assays showed that hPXR recruits its co-activator SRC-1 upon metolazone binding in HepG2 cells, explaining the mechanism of hPXR activation. To understand the role of other commonly-used diuretics in hPXR activation and the structure-activity relationship of metolazone, thiazide and non-thiazide diuretics drugs were also tested but only metolazone activates hPXR. To understand the molecular mechanism, docking studies and mutational analysis were carried out and showed that metolazone binds in the ligand-binding pocket and interacts with mostly hydrophobic amino acid residues. This is the first report showing that metolazone activates hPXR. Because activation of hPXR might cause drug-drug interactions, metolazone should be used with caution for drug treatment in patients undergoing combination therapy.
| S-EPMC4252478 | biostudies-literature
Project description:The clinical phenotypes of patients with Bartter syndrome type III sometimes closely resemble those of Gitelman syndrome. We report a patient with mild, adult-onset symptoms, such as muscular weakness and fatigue, who showed hypokalemic metabolic alkalosis, elevated renin-aldosterone levels with normal blood pressure, hypocalciuria and hypomagnesemia. She was also suffering from chondrocalcinosis. A diuretic test with furosemide and thiazide showed a good response to furosemide, but little response to thiazide. Although the clinical findings and diuretic tests predicted that the patient had Gitelman syndrome, genetic analysis found no mutation in SLC12A3. However, a novel missense mutation, p.L647F in CLCNKB, which is located in the CBS domain at the C-terminus of ClC-Kb, was discovered. Therefore, gene analyses of CLCNKB and SLC12A3 might be necessary to elucidate the precise etiology of the salt-losing tubulopathies regardless of the results of diuretic tests.
| S-EPMC4287957 | biostudies-literature