Irfan A. Dhalla

Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community

Background: Readmissions to hospital are common, costly and often preventable. An easy-to-use index to quantify the risk of readmission or death after discharge from hospital would help clinicians identify patients who might benefit from more intensive post-discharge care. We sought to derive and validate an index to predict the risk of death or unplanned readmission within 30 days after discharge from hospital to the community. Methods: In a prospective cohort study, 48 patient-level and admission-level variables were collected for 4812 medical and surgical patients who were discharged to the community from 11 hospitals in Ontario. We used a split-sample design to derive and validate an index to predict the risk of death or nonelective readmission within 30 days after discharge. This index was externally validated using administrative data in a random selection of 1 000 000 Ontarians discharged from hospital between 2004 and 2008. Results: Of the 4812 participating patients, 385 (8.0%) died or were readmitted on an unplanned basis within 30 days after discharge. Variables independently associated with this outcome (from which we derived the nmemonic “LACE”) included length of stay (“L”); acuity of the admission (“A”); comorbidity of the patient (measured with the Charlson comorbidity index score) (“C”); and emergency department use (measured as the number of visits in the six months before admission) (“E”). Scores using the LACE index ranged from 0 (2.0% expected risk of death or urgent readmission within 30 days) to 19 (43.7% expected risk). The LACE index was discriminative (C statistic 0.684) and very accurate (Hosmer–Lemeshow goodness-of-fit statistic 14.1, p = 0.59) at predicting outcome risk. Interpretation: The LACE index can be used to quantify risk of death or unplanned readmission within 30 days after discharge from hospital. This index can be used with both primary and administrative data. Further research is required to determine whether such quantification changes patient care or outcomes.

Opioid Dose and Drug-Related Mortality in Patients With Nonmalignant Pain

BACKGROUND Opioids are widely prescribed for chronic nonmalignant pain, often at doses exceeding those recommended in clinical practice guidelines. However, the risk-benefit ratio of high-dose opioid therapy is not well characterized. The objective of this study was to characterize the relationship between opioid dose and opioid-related mortality. METHODS We conducted a population-based nested case-control study of Ontario, Canada, residents aged 15 to 64 years who were eligible for publicly funded prescription drug coverage and had received an opioid from August 1, 1997, through December 31, 2006, for nonmalignant pain. The outcome of interest was opioid-related death, as determined by the investigating coroner. The risk of opioid-related death was compared among patients treated with various daily doses of opioids. RESULTS Among 607,156 people aged 15 to 64 years prescribed an opioid over the study period, we identified 498 eligible patients whose deaths were related to opioids and 1714 matched controls. After extensive multivariable adjustment, we found that an average daily dose of 200 mg or more of morphine (or equivalent), was associated with a nearly 3-fold increase in the risk of opioid-related mortality (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.79-4.63) relative to low daily doses (<20 mg of morphine, or equivalent). We found significant but attenuated increases in opioid-related mortality with intermediate doses of opioids (50-99 mg/d of morphine: OR, 1.92; 95% CI, 1.30-2.85; 100-199 mg/d of morphine: OR, 2.04; 95% CI, 1.28-3.24). CONCLUSION Among patients receiving opioids for nonmalignant pain, the daily dose is strongly associated with opioid-related mortality, particularly at doses exceeding thresholds recommended in recent clinical guidelines.

Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone

Introduction: Opioid-related mortality appears to be increasing in Canada. We examined the true extent of the problem and the impact of the introduction of long-acting oxycodone. Methods: We examined trends in the prescribing of opioid analgesics in the province of Ontario from 1991 to 2007. We reviewed all deaths related to opioid use between 1991 and 2004. We linked 3271 of these deaths to administrative data to examine the patients’ use of health care services before death. Using time-series analysis, we determined whether the addition of long-acting oxycodone to the provincial drug formulary in January 2000 was associated with an increase in opioid-related mortality. Results: From 1991 to 2007, annual prescriptions for opioids increased from 458 to 591 per 1000 individuals. Opioid-related deaths doubled, from 13.7 per million in 1991 to 27.2 per million in 2004. Prescriptions of oxycodone increased by 850% between 1991 and 2007. The addition of long-acting oxycodone to the drug formulary was associated with a 5-fold increase in oxycodone-related mortality (p < 0.01) and a 41% increase in overall opioid-related mortality (p = 0.02). The manner of death was deemed unintentional by the coroner in 54.2% and undetermined in 21.9% of cases. Use of health care services in the month before death was common: for example, of the 3066 patients for whom data on physician visits were available, 66.4% had visited a physician in the month before death; of the 1095 patients for whom individual-level prescribing data were available, 56.1% had filled a prescription for an opioid in the month before death. Interpretation: Opioid-related deaths in Ontario have increased markedly since 1991. A significant portion of the increase was associated with the addition of long-acting oxycodone to the provincial drug formulary. Most of the deaths were deemed unintentional. The frequency of visits to a physician and prescriptions for opioids in the month before death suggests a missed opportunity for prevention.

Incidence of potentially avoidable urgent readmissions and their relation to all-cause urgent readmissions

Background: Urgent, unplanned hospital readmissions are increasingly being used to gauge the quality of care. We reviewed urgent readmissions to determine which were potentially avoidable and compared rates of all-cause and avoidable readmissions. Methods: In a multicentre, prospective cohort study, we reviewed all urgent readmissions that occurred within six months among patients discharged to the community from 11 teaching and community hospitals between October 2002 and July 2006. Summaries of the readmissions were reviewed by at least four practising physicians using standardized methods to judge whether the readmission was an adverse event (poor clinical outcome due to medical care) and whether the adverse event could have been avoided. We used a latent class model to determine whether the probability that each readmission was truly avoidable exceeded 50%. Results: Of the 4812 patients included in the study, 649 (13.5%, 95% confidence interval [CI] 12.5%–14.5%) had an urgent readmission within six months after discharge. We considered 104 of them (16.0% of those readmitted, 95% CI 13.3%–19.1%; 2.2% of those discharged, 95% CI 1.8%–2.6%) to have had a potentially avoidable readmission. The proportion of patients who had an urgent readmission varied significantly by hospital (range 7.5%–22.5%; χ2 = 92.9, p < 0.001); the proportion of readmissions deemed avoidable did not show significant variation by hospital (range 1.2%–3.7%; χ2 = 12.5, p < 0.25). We found no association between the proportion of patients who had an urgent readmission and the proportion of patients who had an avoidable readmission (Pearson correlation 0.294; p = 0.38). In addition, we found no association between hospital rankings by proportion of patients readmitted and rankings by proportion of patients with an avoidable readmission (Spearman correlation coefficient 0.28, p = 0.41). Interpretation: Urgent readmissions deemed potentially avoidable were relatively uncommon, comprising less than 20% of all urgent readmissions following hospital discharge. Hospital-specific proportions of patients who were readmitted were not related to proportions with a potentially avoidable readmission.

The effect of cost on adherence to prescription medications in Canada

Background: Many patients do not adhere to treatment because they cannot afford their prescription medications, putting them at increased risk of adverse health outcomes. We determined the prevalence of cost-related nonadherence and investigated its associated characteristics, including whether a person has drug insurance. Methods: Using data from the 2007 Canada Community Health Survey, we analyzed the responses of 5732 people who answered questions about cost-related nonadherence to treatment. We determined the national prevalence of cost-related nonadherence and used logistic regression to evaluate the association between cost-related nonadherence and a series of demographic and socioeconomic variables, including province of residence, age, sex, household income, health status and having drug insurance. Results: Cost-related nonadherence was reported by 9.6% (95% confidence interval [CI] 8.5%–10.6%) of Canadians who had received a prescription in the past year. In our adjusted model, we found that people in poor health (odds ratio [OR] 2.64, 95% CI 1.77–3.94), those with lower income (OR 3.29, 95% CI 2.03–5.33), those without drug insurance (OR 4.52, 95% CI 3.29–6.20) and those who live in British Columbia (OR 2.56, 95% CI 1.49–4.42) were more likely to report cost-related nonadherence. Predicted rates of cost-related nonadherence ranged from 3.6% (95% CI 2.4–4.5) among people with insurance and high household incomes to 35.6% (95% CI 26.1%–44.9%) among people with no insurance and low household incomes. Interpretation: About 1 in 10 Canadians who receive a prescription report cost-related nonadherence. The variability in insurance coverage for prescription medications appears to be a key reason behind this phenomenon.

Inappropriate prescribing before and after nursing home admission

OBJECTIVES: To compare the prevalence of inappropriate prescribing before and after nursing home admission and to determine which patient and physician characteristics are associated with inappropriate prescribing in the nursing home setting.

Opioid Dose and Risk of Road Trauma in Canada: A Population-Based Study

BACKGROUND Use of opioids may predispose drivers to road trauma, yet the effect of opioid dose on this association is unknown. METHODS We conducted a population-based nested case-control study of patients aged 18 to 64 years who received at least 1 publicly funded prescription for an opioid from April 1, 2003, through March 31, 2011. Cases were defined as having an emergency department visit related to road trauma. Patients without road trauma served as a control group matched to cases by age, sex, index year, prior road trauma, and a disease risk index. We compared the risk of road trauma among patients treated with doses of opioids ranging from very low to very high (<20 to ≥200 morphine equivalents daily). In a subgroup analysis, we stratified our analysis by driver status. RESULTS Among 549 878 eligible adults, we identified 5300 cases with road trauma and matched an equal number of controls. Multivariate adjustment yielded no significant association between escalating opioid dose and odds of road trauma (adjusted odds ratio ranged between 1.00 and 1.09). However, a significant association between opioid dose and road trauma was observed among drivers. Compared with very low opioid doses, drivers prescribed low doses had a 21% increased odds of road trauma (adjusted odds ratio, 1.21 [95% CI, 1.02-1.42]); those prescribed moderate doses, 29% increased odds (1.29 [1.06-1.57]); those prescribed high doses, 42% increased odds (1.42 [1.15-1.76]); and those prescribed very high doses, 23% increased odds (1.23 [1.02-1.49]). CONCLUSIONS Among drivers prescribed opioids, a significant relationship exists between drug dose and risk of road trauma. This association is distinct and does not appear with passengers, pedestrians, and others injured in road trauma.

The burden of premature opioid-related mortality

Background and Aims The burden of premature mortality due to opioid-related death has not been fully characterized. We calculated temporal trends in the proportion of deaths attributable to opioids and estimated years of potential life lost (YLL) due to opioid-related mortality in Ontario, Canada. Design Cross-sectional study. Setting Ontario, Canada. Participants Individuals who died of opioid-related causes between January 1991 and December 2010. Measurements We used the Registered Persons Database and data abstracted from the Office of the Chief Coroner to measure annual rates of opioid-related mortality. The proportion of all deaths related to opioids was determined by age group in each of 1992, 2001 and 2010. The YLL due to opioid-related mortality were estimated, applying the life expectancy estimates for the Ontario population. Findings We reviewed 5935 opioid-related deaths in Ontario between 1991 and 2010. The overall rate of opioid-related mortality increased by 242% between 1991 (12.2 per 1 000 000 Ontarians) and 2010 (41.6 per 1 000 000 Ontarians; P < 0.0001). Similarly, the annual YLL due to premature opioid-related death increased threefold, from 7006 years (1.3 years per 1000 population) in 1992 to 21 927 years (3.3 years per 1000 population) in 2010. The proportion of deaths attributable to opioids increased significantly over time within each age group (P < 0.05). By 2010, nearly one of every eight deaths (12.1%) among individuals aged 25–34 years was opioid-related. Conclusions Rates of opioid-related deaths are increasing rapidly in Ontario, Canada, and are concentrated among the young, leading to a substantial burden of disease.

Chlorthalidone Versus Hydrochlorothiazide for the Treatment of Hypertension in Older Adults: A Population-Based Cohort Study

BACKGROUND Some evidence suggests that chlorthalidone may be superior to hydrochlorothiazide for the treatment of hypertension. OBJECTIVE To compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide in older adults. DESIGN Propensity score-matched observational cohort study with up to 5 years of follow-up. SETTING Ontario, Canada. PATIENTS All individuals aged 66 years or older who were newly treated with chlorthalidone or hydrochlorothiazide and were not hospitalized for heart failure, stroke, or myocardial infarction in the prior year were eligible for inclusion. Each chlorthalidone recipient was matched to up to 2 hydrochlorothiazide recipients on the basis of age, sex, year of treatment initiation, and propensity score. MEASUREMENTS The primary outcome was a composite of death or hospitalization for heart failure, stroke, or myocardial infarction. Safety outcomes included hospitalization with hypokalemia or hyponatremia. RESULTS A total of 29 873 patients were studied. During follow-up, chlorthalidone recipients (n = 10 384) experienced the primary outcome at a rate of 3.2 events per 100 person-years of follow-up, and hydrochlorothiazide recipients experienced 3.4 events per 100 person-years of follow-up (adjusted hazard ratio, 0.93 [95% CI, 0.81 to 1.06]). Patients treated with chlorthalidone were more likely to be hospitalized with hypokalemia (adjusted hazard ratio, 3.06 [CI, 2.04 to 4.58]) or hyponatremia (adjusted hazard ratio, 1.68 [CI, 1.24 to 2.28]). In 9 post hoc analyses comparing patients initially prescribed 12.5, 25, or 50 mg of chlorthalidone per day with those prescribed 12.5, 25, or 50 mg of hydrochlorothiazide per day, the former were more likely to be hospitalized with hypokalemia for all 6 comparisons in which a statistically significant association was found. The results of other effectiveness and safety outcomes were also consistent with those of the main analysis. LIMITATION Unmeasured differences in baseline characteristics or physician treatment approaches or an insufficiently large sample may have limited the ability to detect small differences in the comparative effectiveness of the drugs. CONCLUSION As typically prescribed, chlorthalidone in older adults was not associated with fewer adverse cardiovascular events or deaths than hydrochlorothiazide. However, it was associated with a greater incidence of electrolyte abnormalities, particularly hypokalemia. PRIMARY FUNDING SOURCE Ontario Ministry of Health and Long-Term Care.

Effect of a Postdischarge Virtual Ward on Readmission or Death for High-Risk Patients: A Randomized Clinical Trial

IMPORTANCE Hospital readmissions are common and costly, and no single intervention or bundle of interventions has reliably reduced readmissions. Virtual wards, which use elements of hospital care in the community, have the potential to reduce readmissions, but have not yet been rigorously evaluated. OBJECTIVE To determine whether a virtual ward-a model of care that uses some of the systems of a hospital ward to provide interprofessional care for community-dwelling patients-can reduce the risk of readmission in patients at high risk of readmission or death when being discharged from hospital. DESIGN, SETTING, AND PATIENTS High-risk adult hospital discharge patients in Toronto were randomly assigned to either the virtual ward or usual care. A total of 1923 patients were randomized during the course of the study: 960 to the usual care group and 963 to the virtual ward group. The first patient was enrolled on June 29, 2010, and follow-up was completed on June 2, 2014. INTERVENTIONS Patients assigned to the virtual ward received care coordination plus direct care provision (via a combination of telephone, home visits, or clinic visits) from an interprofessional team for several weeks after hospital discharge. The interprofessional team met daily at a central site to design and implement individualized management plans. Patients assigned to usual care typically received a typed, structured discharge summary, prescription for new medications if indicated, counseling from the resident physician, arrangements for home care as needed, and recommendations, appointments, or both for follow-up care with physicians as indicated. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of hospital readmission or death within 30 days of discharge. Secondary outcomes included nursing home admission and emergency department visits, each of the components of the primary outcome at 30 days, as well as each of the outcomes (including the composite primary outcome) at 90 days, 6 months, and 1 year. RESULTS There were no statistically significant between-group differences in the primary or secondary outcomes at 30 or 90 days, 6 months, or 1 year. The primary outcome occurred in 203 of 959 (21.2%) of the virtual ward patients and 235 of 956 (24.6%) of the usual care patients (absolute difference, 3.4%; 95% CI, -0.3% to 7.2%; P = .09). There were no statistically significant interactions to indicate that the virtual ward model of care was more or less effective in any of the prespecified subgroups. CONCLUSIONS AND RELEVANCE In a diverse group of high-risk patients being discharged from the hospital, we found no statistically significant effect of a virtual ward model of care on readmissions or death at either 30 days or 90 days, 6 months, or 1 year after hospital discharge. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01108172.