Project description:Background/Aims: Statin intolerance leads to poor adherence to statin therapy, resulting in a failure to achieve desired cholesterol reduction and adverse outcomes. The LILRB5 Asp247Gly genotype has been identified as being associated with statin intolerance and statin-induced myalgia. We conducted a randomized clinical trial to examine its role in immune response through T regulatory cell aggregation and in achieving cholesterol reduction targets. Methods: A double-blind, cross-over, recruit-by-genotype trial was undertaken. A total of 18 participants who had either the Asp247Asp (T/T) genotype or the Gly247Gly (C/C) genotype were recruited to the study. Participants were randomised to receive placebo or atorvastatin 80 mg daily for 28 days. Following a washout period of 3 weeks, they were then switched to the opposite treatment. Biochemical and immunological measurements as well as interviews were performed prior to and after both treatment periods. Within genotype group comparisons were performed using repeated measures Wilcoxon tests. Two-way repeated measures ANOVA with genotype and treatment as factors were used to compare changes in biochemical parameters between groups during placebo and atorvastatin periods. Results: Individuals with the Asp247Asp genotype had a greater increase in creatine kinase (CK) compared to those with Gly247Gly genotype in response to atorvastatin (p = 0.03). Those with Gly247Gly genotype had a mean non-HDL cholesterol reduction of 2.44 (95% CI:1.59 - 3.29) mmol/L while in Asp247Asp genotype group the mean reduction was 1.28 (95%CI: 0.48 - 2.07) mmol/L. The interaction between the genotype and atorvastatin treatment for total cholesterol (p = 0.007) and non-HDL cholesterol response was significant (p = 0.025). Immunological assessment showed no significant changes in aggregation of T regulatory cells by genotype. Conclusion: The Asp247Gly variant in LILRB5, previously associated with statin intolerance, was associated with differential increases in creatine kinase and total cholesterol and non-HDL cholesterol-lowering response to atorvastatin. Taken together, these results suggest that this variant could have utility in precision cardiovascular therapy.

Project description:IntroductionThe results of laboratory testing are crucial basis for clinicians to prescribe antimicrobial. Laboratory testing is a highly complex process, and increasing evidence suggests that errors and obstacles in the pre-analytical process (PP) will affect reasonable antimicrobial use. However, PP was an easily neglected link in hospital infection management and the current situation of it and the influencing factors of management are not clear.MethodsA cross-sectional survey was conducted in the department of clinical, specimen collection, transportation, and inspection in 109 secondary and tertiary hospitals in Central China. The rate of antimicrobial susceptibility test request (AST) and related indexes of above departments were calculated to describe the situation. Management characteristics (frequency of training etc.) were described as proportions and fractional probit regression analysis was used to determine the influencing factors.ResultsThe average rate of non restricted-use antimicrobial was 63%, the restricted-use was 86%, the special-use was 95%. The zero obstacle rate of specimen collection was 27.3%, of specimen transportation was 19.4% and of inspection feedback was 61.7%. There was a difference between the secondary and tertiary hospitals on non restricted-use (X2 = 22.968, P < 0.001); restricted-use (X2 = 29.466, P < 0.001); special-use (X2 = 27.317, P < 0.001). Taking non restricted-use as an example, training (OR = 0.312, 95%CI: 0.148,0.429), low-frequency appraisal (OR = 0.153, 95%CI: 0.082,0.224), guidance (OR = 0.32, 95%CI: 0.237,0.403) and information technology (OR = 0.104, 95%CI: 0.009,0.199) were positive factors.ConclusionsThere were substantial differences in the rate of AST request in clinical department between secondary and tertiary hospitals. The zero obstacle rate in collection, transportation and inspection department were still low. In most departments, training and performance appraisal were positive factors, guidance and information technology were positive supporting factors.

Project description:ImportanceMissed test results, defined as test results not followed up within an appropriate time frame, are common and lead to delays in diagnosis and treatment.ObjectiveTo evaluate the effect of a quality improvement collaborative, the Virtual Breakthrough Series (VBTS), on the follow-up rate of 2 types of test results prone to being missed: chest imaging suspicious for lung cancer and laboratory findings suggestive of colorectal cancer.Design, setting, and participantsThis stepped-wedge cluster-randomized clinical trial was conducted between February 2020 and March 2022 at 12 Department of Veterans Affairs (VA) medical centers, with a predefined 3-cohort roll-out. Each cohort was exposed to 3 phases: preintervention, action, and continuous improvement. Follow-up ranged from 0 to 12 months, depending on cohort. Teams at each site were led by a project leader and included diverse interdisciplinary representation, with a mix of clinical and technical experts, senior leaders, nursing champions, and other interdisciplinary team members. Analysis was conducted per protocol, and data were analyzed from April 2022 to March 2024.InterventionAll teams participated in a VBTS, which included instruction on reducing rates of missed test results at their site.Main outcomes and measuresThe primary outcome was changes in the percentage of abnormal test result follow-up, comparing the preintervention phase with the action phase. Secondary outcomes were effects across cohorts and the intervention's effect on sites with the highest and lowest preintervention follow-up rates. Previously validated electronic algorithms measured abnormal imaging and laboratory test result follow-up rates.ResultsA total of 11 teams completed the VBTS and implemented 47 (mean, 4 per team; range, 3-8 per team; mode, 3 per team) unique interventions to improve missed test results. A total of 40 027 colorectal cancer-related tests were performed, with 5130 abnormal results, of which 1286 results were flagged by the electronic trigger (e-trigger) algorithm as being missed. For lung cancer-related studies, 376 765 tests were performed, with 7314 abnormal results and 2436 flagged by the e-trigger as being missed. There was no significant difference in the percentage of abnormal test results followed up by study phase, consistent across all 3 cohorts. The estimated mean difference between the preintervention and action phases was -0.78 (95% CI, -6.88 to 5.31) percentage points for the colorectal e-trigger and 0.36 (95% CI, -5.19 to 5.9) percentage points for the lung e-trigger. However, there was a significant effect of the intervention by site, with the site with the lowest follow-up rate at baseline increasing its follow-up rate from 27.8% in the preintervention phase to 55.6% in the action phase.Conclusions and relevanceIn this cluster-randomized clinical trial of the VBTS intervention, there was no improvement in the percentage of test results receiving follow-up. However, the VBTS may offer benefits for sites with low baseline performance.Trial registrationClinicalTrials.gov Identifier: NCT04166240.

Project description:Importance"Nudges" that influence decision making through subtle cognitive mechanisms have been shown to be highly effective in a wide range of applications, but there have been few experiments to improve clinical practice.ObjectiveTo investigate the use of a behavioral "nudge" based on the principle of public commitment in encouraging the judicious use of antibiotics for acute respiratory infections (ARIs).Design, setting, and participantsRandomized clinical trial in 5 outpatient primary care clinics. A total of 954 adults had ARI visits during the study timeframe: 449 patients were treated by clinicians randomized to the posted commitment letter (335 in the baseline period, 114 in the intervention period); 505 patients were treated by clinicians randomized to standard practice control (384 baseline, 121 intervention).InterventionsThe intervention consisted of displaying poster-sized commitment letters in examination rooms for 12 weeks. These letters, featuring clinician photographs and signatures, stated their commitment to avoid inappropriate antibiotic prescribing for ARIs.Main outcomes and measuresAntibiotic prescribing rates for antibiotic-inappropriate ARI diagnoses in baseline and intervention periods, adjusted for patient age, sex, and insurance status.ResultsBaseline rates were 43.5% and 42.8% for control and poster, respectively. During the intervention period, inappropriate prescribing rates increased to 52.7% for controls but decreased to 33.7% in the posted commitment letter condition. Controlling for baseline prescribing rates, we found that the posted commitment letter resulted in a 19.7 absolute percentage reduction in inappropriate antibiotic prescribing rate relative to control (P = .02). There was no evidence of diagnostic coding shift, and rates of appropriate antibiotic prescriptions did not diminish over time.Conclusions and relevanceDisplaying poster-sized commitment letters in examination rooms decreased inappropriate antibiotic prescribing for ARIs. The effect of this simple, low-cost intervention is comparable in magnitude to costlier, more intensive quality-improvement efforts.Trial registrationclinicaltrials.gov identifier: NCT01767064.

Project description:ImportanceThe use of statins in patients with symptomatic peripheral artery disease remains suboptimal despite strong clinical practice guideline recommendations; however, it is unknown whether rates are associated with substantial improvements after lower extremity revascularization.ObjectiveTo report longitudinal trends of statin use in patients with peripheral artery disease undergoing lower extremity revascularization and to identify the clinical and procedural characteristics associated with prescriptions for new statin therapy at discharge.Design, setting, and participantsThis was a retrospective cross-sectional study using data from the Vascular Quality Initiative registry of patients who underwent lower extremity peripheral artery disease revascularization from January 1, 2014, through December 31, 2019. The Vascular Quality Initiative is a multicenter registry database including academic and community-based hospitals throughout the US. Patients aged 18 years or older undergoing lower extremity revascularization with available statin data (preprocedure and postprocedure) were included. Those not receiving statin therapy for medical reasons were excluded from final analyses.ExposuresPatients undergoing lower extremity revascularization for whom statin therapy is indicated.Main outcomes and measuresMultivariate logistic regression was used to determine the clinical and procedural characteristics associated with new statin prescription for patients not already taking a statin preprocedure. The overall rates of statin prescription as well as rates of new statin prescription at discharge were determined. In addition, the clinical, demographic, and procedural characteristics associated with new statin prescription were analyzed.ResultsThere were 172 025 procedures corresponding to 125 791 patients (mean [SD] age, 67.7 [11.0] years; 107 800 men [62.7%]; and 135 405 White [78.7%]) included in the analysis. Overall rates of statin prescription at discharge improved from 17 299 of 23 093 (75%) in 2014 to 29 804 of 34 231 (87%) in 2019. However, only 12 790 of 42 020 patients (30%) not already taking a statin at the time of revascularization during the study period were newly discharged with a statin medication. New statin prescription rates were substantially lower after endovascular intervention (7745 of 29 581 [26%]) than after lower extremity bypass (5045 of 12 439 [41%]). Body mass index of 30 or greater (odds ratio [OR], 1.13; 95% CI, 1.04-1.24; P < .001), diabetes (diet-controlled vs no diabetes, OR, 1.22; 95% CI, 1.05-1.41; P = .01), smoking (current vs never, OR, 1.32; 95% CI, 1.21-1.45; P < .001), hypertension (OR, 1.19; 95% CI, 1.09-1.29; P < .001), and coronary heart disease (OR, 1.26; 95% CI, 1.17-1.35; P < .001) were associated with an increased likelihood of new statin prescription after endovascular intervention, whereas female sex, older age, antiplatelet use, and prior peripheral revascularization were associated with a decreased likelihood.Conclusions and relevanceIn this cross-sectional study, although statin use was associated with a substantial improvement after lower extremity revascularization, more than two-thirds of patients not already taking a statin preprocedure remained not taking a statin at discharge. Further investigations to understand the clinical implications of these findings and develop clinician- and system-based interventions are needed.

Project description:UnlabelledPatients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms.MethodsWe queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy.ResultsThe risk of muscle symptoms was associated with age (odds ratio 1.6 [95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, and it was the statin most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually tolerant") and 29% (n = 28) never reestablished statin therapy ("never tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually tolerated statins, and eventually tolerant patients achieved lower treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < .001). Never tolerant patients also developed muscle symptoms on nonstatins (16% vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]).ConclusionAge, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never reestablished statin therapy. Such patients developed muscle symptoms even on nonstatin lipid-lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship between FH and statin-associated muscle symptoms so all FH patients can be adequately treated.

Dataset Information

Should we test for SLCO1B1 genotype before prescribing statins?-a discussion of clinical trial results.

Publications

Should we test for SLCO1B1 genotype before prescribing statins?-a discussion of clinical trial results.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets