Alexander Turchin

Discontinuation of Statins in Routine Care Settings: A Cohort Study

BACKGROUND Systematic data on discontinuation of statins in routine practice of medicine are limited. OBJECTIVE To investigate the reasons for statin discontinuation and the role of statin-related events (clinical events or symptoms believed to have been caused by statins) in routine care settings. DESIGN A retrospective cohort study. SETTING Practices affiliated with Brigham and Womens Hospital and Massachusetts General Hospital in Boston. PATIENTS Adults who received a statin prescription between 1 January 2000 and 31 December 2008. MEASUREMENTS Information on reasons for statin discontinuations was obtained from a combination of structured electronic medical record entries and analysis of electronic provider notes by validated software. RESULTS Statins were discontinued at least temporarily for 57 292 of 107 835 patients. Statin-related events were documented for 18 778 (17.4%) patients. Of these, 11 124 had statins discontinued at least temporarily; 6579 were rechallenged with a statin over the subsequent 12 months. Most patients who were rechallenged (92.2%) were still taking a statin 12 months after the statin-related event. Among the 2721 patients who were rechallenged with the same statin to which they had a statin-related event, 1295 were receiving the same statin 12 months later, and 996 of them were receiving the same or a higher dose. LIMITATIONS Statin discontinuations and statin-related events were assessed in practices affiliated with 2 academic medical centers. Utilization of secondary data could have led to missing or misinterpreted data. Natural-language-processing tools used to compensate for the low (30%) proportion of reasons for statin discontinuation documented in structured electronic medical record fields are not perfectly accurate. CONCLUSION Statin-related events are commonly reported and often lead to statin discontinuation. However, most patients who are rechallenged can tolerate statins long-term. This suggests that many of the statin-related events may have other causes, are tolerable, or may be specific to individual statins rather than the entire drug class. PRIMARY FUNDING SOURCE National Library of Medicine, Diabetes Action Research and Education Foundation, and Chinese National Key Program of Clinical Science.

Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward.

OBJECTIVE Hypoglycemia is associated with adverse outcomes in mixed populations of patients in intensive care units. It is not known whether the same risks exist for diabetic patients who are less severely ill. In this study, we aimed to determine whether hypoglycemic episodes are associated with higher mortality in diabetic patients hospitalized in the general ward. RESEARCH DESIGN AND METHODS This retrospective cohort study analyzed 4,368 admissions of 2,582 patients with diabetes hospitalized in the general ward of a teaching hospital between January 2003 and August 2004. The associations between the number and severity of hypoglycemic (≤50 mg/dl) episodes and inpatient mortality, length of stay (LOS), and mortality within 1 year after discharge were evaluated. RESULTS Hypoglycemia was observed in 7.7% of admissions. In multivariable analysis, each additional day with hypoglycemia was associated with an increase of 85.3% in the odds of inpatient death (P = 0.009) and 65.8% (P = 0.0003) in the odds of death within 1 year from discharge. The odds of inpatient death also rose threefold for every 10 mg/dl decrease in the lowest blood glucose during hospitalization (P = 0.0058). LOS increased by 2.5 days for each day with hypoglycemia (P < 0.0001). CONCLUSIONS Hypoglycemia is common in diabetic patients hospitalized in the general ward. Patients with hypoglycemia have increased LOS and higher mortality both during and after admission. Measures should be undertaken to decrease the frequency of hypoglycemia in this high-risk patient population.

Classifying and Predicting Errors of Inpatient Medication Reconciliation

BackgroundFailure to reconcile medications across transitions in care is an important source of potential harm to patients. Little is known about the predictors of unintentional medication discrepancies and how, when, and where they occur.ObjectiveTo determine the reasons, timing, and predictors of potentially harmful medication discrepancies.DesignProspective observational study.PatientsAdmitted general medical patients.MeasurementsStudy pharmacists took gold-standard medication histories and compared them with medical teams’ medication histories, admission and discharge orders. Blinded teams of physicians adjudicated all unexplained discrepancies using a modification of an existing typology. The main outcome was the number of potentially harmful unintentional medication discrepancies per patient (potential adverse drug events or PADEs).ResultsAmong 180 patients, 2066 medication discrepancies were identified, and 257 (12%) were unintentional and had potential for harm (1.4 per patient). Of these, 186 (72%) were due to errors taking the preadmission medication history, while 68 (26%) were due to errors reconciling the medication history with discharge orders. Most PADEs occurred at discharge (75%). In multivariable analyses, low patient understanding of preadmission medications, number of medication changes from preadmission to discharge, and medication history taken by an intern were associated with PADEs.ConclusionsUnintentional medication discrepancies are common and more often due to errors taking an accurate medication history than errors reconciling this history with patient orders. Focusing on accurate medication histories, on potential medication errors at discharge, and on identifying high-risk patients for more intensive interventions may improve medication safety during and after hospitalization.

Effect of an Electronic Medication Reconciliation Application and Process Redesign on Potential Adverse Drug Events A Cluster-Randomized Trial

BACKGROUND Medication reconciliation at transitions in care is a national patient safety goal, but its effects on important patient outcomes require further evaluation. We sought to measure the impact of an information technology-based medication reconciliation intervention on medication discrepancies with potential for harm (potential adverse drug events [PADEs]). METHODS We performed a controlled trial, randomized by medical team, on general medical inpatient units at 2 academic hospitals from May to June 2006. We enrolled 322 patients admitted to 14 medical teams, for whom a medication history could be obtained before discharge. The intervention was a computerized medication reconciliation tool and process redesign involving physicians, nurses, and pharmacists. The main outcome was unintentional discrepancies between preadmission medications and admission or discharge medications that had potential for harm (PADEs). RESULTS Among 160 control patients, there were 230 PADEs (1.44 per patient), while among 162 intervention patients there were 170 PADEs (1.05 per patient) (adjusted relative risk [ARR], 0.72; 95% confidence interval [CI], 0.52-0.99). A significant benefit was found at hospital 1 (ARR, 0.60; 95% CI, 0.38-0.97) but not at hospital 2 (ARR, 0.87; 95% CI, 0.57-1.32) (P = .32 for test of effect modification). Hospitals differed in the extent of integration of the medication reconciliation tool into computerized provider order entry applications at discharge. CONCLUSIONS A computerized medication reconciliation tool and process redesign were associated with a decrease in unintentional medication discrepancies with potential for patient harm. Software integration issues are likely important for successful implementation of computerized medication reconciliation tools.

Hypoglycemia, With or Without Insulin Therapy, Is Associated With Increased Mortality Among Hospitalized Patients

OBJECTIVE Hypoglycemia is associated with increased mortality in hospitalized patients. We investigated the relationship between spontaneous hypoglycemia versus insulin-associated hypoglycemia and mortality in hospitalized patients. RESEARCH DESIGN AND METHODS Data for this retrospective cohort study were obtained from electronic databases of patients admitted between 1 April 2008 and 30 November 2010. Patients with one or more blood glucose values ≤50 mg/dL on point-of-care glucose testing were considered hypoglycemic. Patients treated with insulin were assumed to have insulin-associated hypoglycemia. Age-, sex-, and race-matched patients with all blood glucose values >70 mg/dL were selected as controls. The Charlson comorbidity index (CCI) was used to control for severity of illness. RESULTS There were four groups: 1) noninsulin-treated hypoglycemia (NTH) (n = 135), 2) insulin-treated hypoglycemia (ITH) (n = 961), 3) noninsulin-treated control (NTC) (n = 1,058), and 4) insulin-treated control (ITC) (n = 736). Mortality was higher in the ITH group compared with the ITC group (20.3 vs. 4.5%, P < 0.0001), with a relatively higher CCI (1.8 vs. 1.5%, P < 0.0001), but much higher in the NTH group compared with the NTC group (34.5 vs. 1.1%, P < 0.0001), with much higher CCI (2.4 vs. 1.1%, P < 0.0001). Mortality was higher in the NTH group compared with the ITH group (P < 0.0001) but lower in the NTC group compared with the ITC group (P < 0.0001). After controlling for age, sex, CCI, and admission to the intensive care unit, insulin treatment was associated with a lower mortality among the hypoglycemic patients; hazard ratio of death in the ITH group relative to the NTH group was 0.34 (95% CI 0.25–0.47, P < 0.0001). CONCLUSIONS Insulin-associated and spontaneous hypoglycemia are associated with increased mortality among hospitalized patients.

Using Regular Expressions to Abstract Blood Pressure and Treatment Intensification Information from the Text of Physician Notes

This case study examined the utility of regular expressions to identify clinical data relevant to the epidemiology of treatment of hypertension. We designed a software tool that employed regular expressions to identify and extract instances of documented blood pressure values and anti-hypertensive treatment intensification from the text of physician notes. We determined sensitivity, specificity and precision of identification of blood pressure values and anti-hypertensive treatment intensification using a gold standard of manual abstraction of 600 notes by two independent reviewers. The software processed 370 Mb of text per hour, and identified elevated blood pressure documented in free text physician notes with sensitivity and specificity of 98%, and precision of 93.2%. Anti-hypertensive treatment intensification was identified with sensitivity 83.8%, specificity of 95.0%, and precision of 85.9%. Regular expressions can be an effective method for focused information extraction tasks related to high-priority disease areas such as hypertension.

Effect of Board Certification on Antihypertensive Treatment Intensification in Patients With Diabetes Mellitus

Background— Regular recertification is mandatory to maintain board certification status in all specialties. However, the evidence that physicians’ performance decreases with time since initial certification is limited. We therefore carried out a study to determine whether the frequency of antihypertensive treatment intensification for diabetic patients changes with time since their physicians’ last board certification. Methods and Results— In this retrospective cohort study, we analyzed treatment of 8127 hypertensive patients with diabetes mellitus treated by 301 internists at primary care practices affiliated with 2 large academic hospitals. Patient visits with documented blood pressure ≥130/85 mm Hg between January 1, 2000, and August 31, 2005, were studied. The association between the number of years since the physician’s last board certification and the probability of pharmacological antihypertensive treatment intensification at a given visit was analyzed. Frequency of treatment intensification decreased from 26.7% for physicians who were board certified the previous year to 6.9% for physicians who were board certified 31 years before the visit. Treatment intensification rate was 22.5% for physicians certified ≤10 years ago versus 16.9% for physicians last certified >10 years ago (P<0.0001). Multivariable analysis adjusted for patient and visit characteristics and physician age showed that for every decade since the physician’s last board certification, the probability of treatment intensification decreased by 21.3% (P=0.0097). Conclusion— Physician intensification of pharmacological therapy for blood pressure levels above the recommended treatment goals decreases with time since the last board certification. This finding supports the current policy of mandatory recertification.

Encounter frequency and serum glucose level, blood pressure, and cholesterol level control in patients with diabetes mellitus.

BACKGROUND More frequent patient-provider encounters may lead to faster control of hemoglobin A1c level, blood pressure (BP), and low-density lipoprotein (LDL) cholesterol (LDL-C) level (hereafter referred to as hemoglobin A1c, BP, and LDL-C) and improve outcomes, but no guidelines exist for how frequently patients with diabetes mellitus (DM) should be seen. METHODS This retrospective cohort study analyzed 26,496 patients with diabetes and elevated hemoglobin A1c, BP, and/or LDL-C treated by primary care physicians at 2 teaching hospitals between January 1, 2000, and January 1, 2009. The relationship between provider encounter (defined as a note in the medical record) frequency and time to hemoglobin A1c, BP, and LDL-C control was assessed. RESULTS Comparing patients who had encounters with their physicians between 1 to 2 weeks vs 3 to 6 months, median time to hemoglobin A1c less than 7.0% was 4.4 vs 24.9 months (not receiving insulin) and 10.1 vs 52.8 months (receiving insulin); median time to BP lower than 130/85 mm Hg was 1.3 vs 13.9 months; and median time to LDL-C less than 100 mg/dL was 5.1 vs 32.8 months, respectively (P<.001 for all). In multivariable analysis, doubling the time between physician encounters led to an increase in median time to hemoglobin A1c (not receiving [35%] and receiving [17%] insulin), BP (87%), and LDL-C (27%) targets (P<.001 for all). Time to control decreased progressively as encounter frequency increased up to once every 2 weeks for most targets, consistent with the pharmacodynamics of the respective medication classes. CONCLUSIONS Primary care provider encounters every 2 weeks are associated with fastest achievement of hemoglobin A1c, BP, and LDL-C targets for patients with diabetes mellitus.

Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway

VEGF signaling pathway inhibitor (anti‐VEGF) therapy is associated with hypertension, but little is known about predisposing clinical characteristics. This study describes the real‐world association between baseline clinical characteristics, blood pressure (BP) response, and survival in patients prescribed anti‐VEGF therapies.

Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort study.

Objectives To investigate the optimal systolic blood pressure goal above which new antihypertensive medications should be added or doses of existing medications increased (“systolic intensification threshold”) and to determine the relation between delays in medication intensification and follow-up and the risk of cardiovascular events or death. Design Retrospective cohort study. Setting Primary care practices in the United Kingdom, 1986-2010. Participants 88 756 adults with hypertension from The Health Improvement Network nationwide primary care research database. Main outcome measures Rates of acute cardiovascular events or death from any cause for patients with different hypertension treatment strategies (defined by systolic intensification threshold, time to intensification, and time to follow-up over the course of a 10 year treatment strategy assessment period) after adjustment for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or chronic kidney disease, Charlson comorbidity index, body mass index, medication possession ratio, and baseline blood pressure. Results During a median follow-up of 37.4 months after the treatment strategy assessment period, 9985 (11.3%) participants had an acute cardiovascular event or died. No difference in risk of the outcome was seen between systolic intensification thresholds of 130-150 mm Hg, whereas systolic intensification thresholds greater than 150 mm Hg were associated with progressively greater risk (hazard ratio 1.21, 95% confidence interval 1.13 to 1.30; P<0.001 for intensification threshold of 160 mm Hg). Outcome risk increased progressively from the lowest (0-1.4 months) to the highest fifth of time to medication intensification (hazard ratio 1.12, 1.05 to 1.20; P=0.009 for intensification between 1.4 and 4.7 months after detection of elevated blood pressure). The highest fifth of time to follow-up (>2.7 months) was also associated with increased outcome risk (hazard ratio 1.18, 1.11 to 1.25; P<0.001). Conclusions Systolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death. These findings support the importance of timely medical management and follow-up in the treatment of patients with hypertension.