Correlates of Opioid Use Among Ontario Long-Term Care Residents and Variation by Pain Frequency and Intensity: A Cross-sectional Analysis.

BACKGROUND: Chronic non-cancer pain is common among older residents of long-term care (LTC) homes and often poorly recognized and treated. With heightened concerns regarding opioid prescribing in recent years, it is important to examine the current prevalence of opioid use and its association with resident characteristics to help identify those potentially at risk of medication harms as well as suboptimal pain management. OBJECTIVES: The aims were to estimate the prevalence and correlates of opioid use among non-palliative LTC residents and explore variation in opioid prevalence and correlates across strata defined by pain frequency and intensity. METHODS: We conducted a population-based cross-sectional study of all older (aged > 65 years) LTC residents (excluding those with cancer or receiving palliative care) in Ontario, Canada during 2018-2019. Health administrative databases were linked with standardized clinical assessment data to ascertain residents' health and pain characteristics and their opioid and other medication use. Modified Poisson regression models estimated unadjusted and adjusted associations between residents' characteristics and opioid use, overall and across strata capturing pain frequency and intensity. RESULTS: Among 75,020 eligible residents (mean age 85.1 years; 70% female), the prevalence of opioid use was 18.5% and pain was 29.4%. Opioid use ranged from 12.2% for residents with no current pain to 55.7% for those with severe pain. In adjusted models, residents newly admitted to LTC (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI] 0.57-0.62) and with moderate to severe cognitive impairment (aRR = 0.69, 95% CI 0.66-0.72) or dementia (aRR = 0.76, 95% CI 0.74-0.79) were significantly less likely to receive an opioid, whereas residents with select conditions (e.g., arthritis, aRR = 1.37, 95% CI 1.32-1.41) and concurrently using gabapentinoids (aRR = 1.80, 95% CI 1.74-1.86), benzodiazepines (aRR = 1.33, 95% CI 1.28-1.38), or antidepressants (aRR = 1.31, 95% CI 1.27-1.35) were significantly more likely to receive an opioid. The associations observed for residents newly admitted, with dementia, and concurrently using gabapentinoids, benzodiazepines, or antidepressants were largely consistent across all pain strata. CONCLUSIONS: Our findings describe resident sub-groups at potentially higher risk of adverse health outcomes in relation to both opioid use and non-use. LTC clinical and policy changes informed by research are required to ensure the appropriate recognition and management of non-cancer pain in this setting.

Influenza Vaccine Effectiveness Among Patients With Cancer: A Population-Based Study Using Health Administrative and Laboratory Testing Data From Ontario, Canada.

PURPOSE: Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer. PATIENTS AND METHODS: We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time. RESULTS: We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, -5% to 19%) for patients with hematologic malignancies (P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer. CONCLUSION: Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.

Cardiovascular and Neuropsychiatric Events after Varenicline Use for Smoking Cessation.

RATIONALE: Varenicline aids in smoking cessation but has also been associated with serious adverse events. OBJECTIVES: The aim of this study was to determine the risks of cardiovascular and neuropsychiatric events after varenicline receipt in a real-world setting. METHODS: A population-based, self-controlled risk interval study using linked universal health administrative data from the diverse, multicultural population of Ontario, Canada, was conducted. In two separate analyses, new varenicline users between September 1, 2011 and February 15, 2014 were observed from 1 year before to 1 year after varenicline receipt. The relative incidences of cardiovascular and neuropsychiatric hospitalizations and emergency department visits in the 12 weeks after varenicline receipt (the risk interval) compared with the remaining observation period (the control interval) were estimated in two separate fixed-effect conditional Poisson regressions. Sensitivity analyses tested the robustness of the results. MEASUREMENTS AND MAIN RESULTS: Among 56,851 new users of varenicline, 6,317 cardiovascular and 10,041 neuropsychiatric hospitalizations and emergency department visits occurred from 1 year before to 1 year after receipt. The incidence of cardiovascular events was 34% higher in the risk compared with the control interval (relative incidence, 1.34; 95% confidence interval, 1.25-1.44). Findings were consistent in sensitivity analyses, most notably in those without any history of previous cardiovascular disease. The relative incidence of neuropsychiatric events was marginally significant in the primary (relative incidence, 1.06; 95% confidence interval, 1.00-1.13) but not all sensitivity analyses. CONCLUSIONS: Varenicline appears to be associated with an increased risk of cardiovascular but not neuropsychiatric events.

Frailty and Potentially Inappropriate Medication Use at Nursing Home Transition.

BACKGROUND/OBJECTIVES: To estimate the prevalence of potentially inappropriate medication (PIM) use among older adults with cognitive impairment or dementia prior to and following admission to nursing homes and in relation to frailty. DESIGN: Retrospective cohort study using health administrative databases. SETTING: Ontario, Canada. PARTICIPANTS: 41,351 individuals with cognitive impairment or dementia, aged 66+ years newly admitted to nursing home between 2011 and 2014. MEASUREMENTS: PIMs were defined with 2015 Beers Criteria and included antipsychotics, H2 -receptor antagonists, benzodiazepines, and drugs with strong anticholinergic properties. Medication information was obtained at nursing home admission and in the subsequent 180 days. Multivariable Cox proportional-hazards models were used to assess the impact of frailty status (determined by a 72-item frailty index) on the hazard of starting and discontinuing PIMs. RESULTS: At admission, 44% of residents with cognitive impairment or dementia were on a PIM and prevalence varied by frailty (38.7% non-frail, 42.8% pre-frail, and 48.1% frail, P < .001). Following admission, many residents discontinued PIMs (23.5% for antipsychotics, 49.3% benzodiazepines, 32.2% anticholinergics, and 30.9% H2 -receptor antagonists). However, PIMs were also introduced with 10.9% newly started on antipsychotics, benzodiazepines (10.1%), anticholinergics (6.6%), and H2 -receptor antagonists (1.2%). After adjustment for other characteristics, frail residents had a similar risk of PIM discontinuation as non-frail residents except for anticholinergics (HR = 1.21, 95% CI 1.06-1.39) but were more likely to be newly prescribed benzodiazepines (HR = 1.32, 95% CI 1.20-1.44), antipsychotics (HR = 1.36, 1.23-1.49), and anticholinergics (HR = 1.34, 95% CI 1.20-1.50). CONCLUSION: Many residents with cognitive impairment or dementia enter nursing homes on PIMs. PIMs are more likely to be started in frail individuals following admission. Interventions to support deprescribing of PIMs should be implemented targeting frail individuals during the transition to nursing home.

The Effect of Changes in Cervical Cancer Screening Guidelines on Chlamydia Testing.

PURPOSE: Many chlamydia infections are identified through screening, which is frequently offered to females concomitantly with cervical cancer screening. Recent cervical cancer screening guidelines recommend screening less frequently and starting later. We sought to evaluate the impact of the May 2012 Ontario, Canada, cervical cancer screening guideline change on Papanicolaou (Pap) and chlamydia trachomatis (chlamydia) testing and incidence. METHODS: We extracted population-based physician billing claims data to identify Pap and chlamydia tests and public health surveillance data to identify chlamydia cases. We used interrupted time series analysis of quarterly data spanning 2 years before and after the guideline change and fitted segmented linear regression or rational functions to the outcomes using autoregressive integrated moving average models. Outcomes were stratified by sex and age group. RESULTS: Two years after the guideline change, we observed reduced chlamydia testing in females, with the greatest relative reduction (25.5%) among those aged 15 to 19 years. We also observed decreases in reported chlamydia incidence for females aged 15 to 19 years and 20 to 24 years (relative reductions of 16.8% and 14.4%, respectively). Chlamydia incidence remained the same for males, despite increased chlamydia testing. CONCLUSIONS: Recent cervical cancer screening guideline changes in Ontario were associated with reduced chlamydia testing and reported new cases of chlamydia in females. Females aged 15 to 19 years, who are at high risk for chlamydia if sexually active, and who no longer warrant cervical cancer screening, were disproportionately affected. Females should be tested for chlamydia based on risk, regardless of need for Pap testing.

Relation between primary care physician supply and diabetes care and outcomes: a cross-sectional study.

BACKGROUND: Higher primary care physician supply is associated with lower mortality due to heart disease, cancer and stroke, but its relation to diabetes care and outcomes is unknown. We examined the association between primary care physician supply and evidence-based testing and hospital visits for people with diabetes in naturally occurring multispecialty physician networks in Ontario, Canada. METHODS: We conducted a cross-sectional analysis between Apr. 1, 2009, and Mar. 31, 2011, using linked administrative data. We included all Ontario residents over 40 years of age with a diagnosis of diabetes before Apr. 1, 2007, who were alive on Apr. 1, 2009 (N = 712 681). We tested the association between physician supply and outcomes at the network level using separate Poisson regression models for urban and nonurban physician networks. We accounted for clustering at the physician and network level and adjusted for patient characteristics. RESULTS: Patients in physician networks with a high supply of primary care physicians were more likely to receive the optimal number of evidence-based tests for diabetes than patients in networks with low primary care physician supply (urban relative risk [RR] 1.06, 95% confidence interval [CI] 1.04-1.07; nonurban RR 1.17, 95% CI 1.14-1.21) but were no different regarding emergency department visits (urban RR 1.05, 95% CI 0.94-1.17; nonurban RR 0.96, 95% CI 0.85-1.08) or hospital admissions for diabetes complications (urban RR 1.01, 95% CI 0.89-1.14; nonurban RR 0.91, 95% CI 0.77-1.07). INTERPRETATION: Having more primary care physicians per capita is associated with better diabetes care but not with reduced hospital visits in this setting. Further research to understand this relation and how it varies by setting is important for resource planning.

Trends in relative survival in patients with a diagnosis of hepatocellular carcinoma in Ontario: a population-based retrospective cohort study.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is increasing and survival rates are poor. Our objectives were to estimate the relative survival over time in patients with HCC in Ontario and to examine potential factors associated with excess mortality risk. METHODS: We performed a population-based retrospective cohort analysis involving patients with a diagnosis of HCC in Ontario between 1990 and 2009 using data extracted from the Ontario Cancer Registry. Relative survival was estimated by controlling for background mortality using expected mortality from Ontario life tables. A generalized linear model was used to estimate the excess mortality risk for important factors. RESULTS: A total of 5645 patients had HCC diagnosed during the study period; 4412 (78.2%) of these patients were male. Improvements in 1-year relative survival were observed across all age groups over time: the highest was among those patients less than 60 years of age who had a diagnosis of HCC during 2005-2009, with 1-year survival exceeding 50% for both sexes. However, the overall 5-year relative survival did not exceed 28%. The excess mortality risk decreased with increased years of follow-up, recent diagnosis, and curative or noncurative treatments for HCC, whereas excess mortality risk increased with age. INTERPRETATION: Although improving, the prognosis for HCC remains poor. Our findings highlight the importance of effective prevention and treatment for HCC to reduce the burden of disease and improve health care systems.

Improved Survival in Patients with Viral Hepatitis-Induced Hepatocellular Carcinoma Undergoing Recommended Abdominal Ultrasound Surveillance in Ontario: A Population-Based Retrospective Cohort Study.

The optimal schedule for ultrasonographic surveillance of patients with viral hepatitis for the detection of hepatocellular carcinoma (HCC) remains unclear owing to a lack of reliable studies. We examined the timing of ultrasonography in patients with viral hepatitis-induced HCC and its impact on survival and mortality risk while determining predictors of receiving surveillance before HCC diagnosis. A population-based retrospective cohort analysis of patients with viral hepatitis-induced HCC in Ontario between 2000 and 2010 was performed using data from the Ontario Cancer Registry linked health administrative data. HCC surveillance for 2 years preceding diagnosis was assigned as: i) ≥ 2 abdominal ultrasound screens annually; ii) 1 screen annually; iii) inconsistent screening; and iv) no screening. Survival rates were estimated using the Kaplan-Meier method and parametric models to correct for lead-time bias. Associations between HCC surveillance and the risk of mortality after diagnosis were examined using proportional-hazards regression adjusting for confounding factors. Overall, 1,483 patients with viral hepatitis-induced HCC were identified during the study period; 20.2% received ≥ 1 ultrasound screen annually (routine surveillance) for the 2 years preceding diagnosis. The 5-year survival of those receiving routine surveillance was 31.93% (95% CI: 25.77-38.24%) and 31.84% (95% CI: 25.69-38.14%) when corrected for lead-time bias (HCC sojourn time 70 days and 140 days, respectively). This is contrasted with 20.67% (95% CI: 16.86-24.74%) 5-year survival in those who did not undergo screening. In the fully adjusted model, compared to unscreened patients, routine surveillance was associated with a lower mortality risk and a hazard ratio of 0.76 (95% CI: 0.64-0.91) and 0.81 (95% CI: 0.68-0.97), corrected for the respective lead-time bias. Our findings suggest that routine ultrasonography in patients with viral hepatitis is associated with improved survival and reduced mortality risk in a population-based setting. The data emphasizes the importance of surveillance for timely intervention in HCC-diagnosed patients.

Validation of infant immunization billing codes in administrative data.

Ontario has a single payer provincial health insurance program. Administrative data may provide a potentially robust source of information for post-marketing vaccine studies. Vaccine-specific immunization billing codes were introduced in 2011. Our objective was to validate Ontario's universal health care administrative datasets to assess infant immunization status. Electronic medical record data from the Electronic Medical Record Administrative data Linked Database (EMRALD) was used as the reference standard to calculate performance characteristics of the Ontario Health Insurance Plan (OHIP) database vaccine-specific and general immunization codes for 4 primary infant immunizations: diphtheria, tetanus, acellular pertussis, inactivated polio, Haemophilus influenzae type B (DTaP-IPV-Hib) combination vaccine, pneumococcal conjugate vaccine, measles, mumps, rubella (MMR) vaccine, and meningococcal conjugate serogroup C vaccine. OHIP billing claims had specificity ranging from 81% to 92%, sensitivity 70% to 83%, positive predictive value (PPV) 97% to 99%, and negative predictive value (NPV) 13% to 46% for identifying the various specific vaccines in administrative data. For cohorts vaccinated in the new code introduction phase, using both the vaccine-specific and general codes had higher sensitivity than the vaccine-specific codes alone. In conclusion, immunization billing claims from administrative data in Ontario had high specificity and PPV, moderate sensitivity, and low NPV. This study identifies some of the applications of utilizing administrative data for post-marketing vaccine studies. However, limitations of these data decrease their utility for measuring vaccine coverage and effectiveness. Therefore, the establishment of a comprehensive and linkable immunization registry should be a provincial priority.

Increased risk of mycobacterial infections associated with anti-rheumatic medications.

RATIONALE: Anti-tumour necrosis factor (TNF) agents and other anti-rheumatic medications increase the risk of TB in rheumatoid arthritis (RA). Whether they increase the risk of infections with nontuberculous mycobacteria (NTM) is uncertain. OBJECTIVES: To determine the effect of anti-TNF therapy and other anti-rheumatic drugs on the risk of NTM disease and TB in older patients with RA. METHODS: Population-based nested case-control study among Ontario seniors aged ≥67 years with RA who were prescribed at least one anti-rheumatic medication between 2001 and 2011. We identified cases of TB and NTM disease microbiologically and identified drug exposures using linked prescription drug claims. We estimated ORs using conditional logistic regression, controlling for several potential confounders. MEASUREMENTS AND MAIN RESULTS: Among 56 269 older adults with RA, we identified 37 cases of TB and 211 cases of NTM disease; each case was matched to up to 10 controls. Individuals with TB or NTM disease were both more likely to be using anti-TNF therapy (compared with non-use); adjusted ORs (95% CIs) were 5.04 (1.27 to 20.0) and 2.19 (1.10 to 4.37), respectively. Exposure to leflunomide and other anti-rheumatic drugs with high immunosuppressing potential also were associated with both TB and NTM disease, while oral corticosteroids and hydroxychloroquine were associated with NTM disease. CONCLUSIONS: Anti-TNF use is associated with increased risk of both TB and NTM disease, but appears to be a relatively greater risk for TB. Several other anti-rheumatic drugs were also associated with mycobacterial infections.

Health care costs associated with hepatocellular carcinoma: a population-based study.

UNLABELLED: Although the burden of hepatocellular carcinoma (HCC) is an escalating public health problem, it has not been rigorously estimated within a Canadian context. We conducted a population-based study using Ontario Cancer Registry linked administrative data. The mean net costs of care due to HCC were estimated using a phase of care approach and generalized estimating equations. Using an incidence approach, the mean net costs of care were applied to survival probabilities of HCC patients to estimate 5-year net costs of care and extrapolated to the Canadian population of newly diagnosed HCC patients in 2009. During 2002-2008, 2,341 HCC cases were identified in Ontario. The mean (95% confidence interval [CI]) net costs of HCC care per 30 patient-days (2010 US dollars) were $3,204 ($2,863-$3,545) in the initial phase, $2,055 ($1,734-$2,375) in the continuing care phase, and $7,776 ($5,889-$9,663) in the terminal phase. The mean (95% CI) 5-year net cost of care was $77,509 ($60,410-$94,607) and the 5-year aggregate net cost of care was $106 million ($83-$130 million) (undiscounted). The net costs of patients receiving liver transplantation only and those undergoing surgical resection only were highest in the terminal phase. The net cost of patients receiving radiofrequency ablation as the only treatment was relatively low in the initial phase, and there were no significant differences in the continuing and terminal phases. CONCLUSION: Our findings suggest that costs attributable to HCC are significant in Canada and expected to increase. Our findings of phase-specific cost estimates by resource categories and type of treatment provide information for future cost-effectiveness analysis of potential innovative interventions, resource allocation, and health care budgeting, and public health policy to improve the health of the population.

The impact of infection on population health: results of the Ontario burden of infectious diseases study.

BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Influence of socioeconomic status on survival of hepatocellular carcinoma in the Ontario population; a population-based study, 1990-2009.

BACKGROUND: Research has shown that people from higher socioeconomic status (SES) have better hepatocellular carcinoma (HCC) survival outcomes, although no such research has been carried out in Canada. We aimed to assess if an association between SES and HCC survival existed in the Canadian context. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based cohort study linking HCC cases identified in the Ontario Cancer Registry between 1990 and 2009 to administrative and hospital data. Logistic regression and chi-squared tests were used to evaluate associations between SES (income quintile) and covariates. The Kaplan-Meier method was used to estimate survival. Sequential analysis of the proportional-hazards models were used to determine the association between SES and HCC survival controlling for potential prognostic covariates. During the period 1990-2009, 5,481 cases of HCC were identified. A significant association was found between SES and curative treatment (p = 0.0003), but no association was found between SES and non-curative treatment (p = 0.064), palliative treatment (p = 0.680), or ultrasound screening (p = 0.615). The median survival for the lowest SES was 8.5 months, compared to 8.8 months for the highest SES group. The age- and sex-adjusted proportional-hazards model showed statistically significant difference in HCC survival among the SES groups, with hazard ratio 0.905 (95% confidence intervals 0.821, 0.998) when comparing highest to lowest SES group. Further adjustments indicated that potentially curative treatment was the likely explanation for the association between SES and HCC survival. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that a 10% HCC survival advantage exists for the higher SES groups. This association between SES and HCC survival is most likely a reflection of lack of access to care for low SES groups, revealing inequities in the Canadian healthcare system.

Adherence to breast and ovarian cancer screening recommendations for female relatives from the Ontario site of the Breast Cancer Family Registry.

This study compares adherence to breast and ovarian cancer screening recommendations among a population cohort of women at familial risk of breast and/or ovarian cancer. This cross-sectional study included 1039 first-degree female relatives without breast cancer identified from the Ontario site of the Breast Cancer Family Registry. We compared breast and ovarian cancer screening behaviors, using a telephone-administered questionnaire among three groups of women defined by their familial risk (high, moderate, and low) of breast and/or ovarian cancer. Associations between screening behaviors and familial risk were assessed using multinomial regression models adjusted by familial clustering. Women, 40-49 years of age, at moderate or high familial risk were significantly more likely to have had a screening mammogram within the past 12 months [odds ratio (OR): 2.80; 95% confidence interval (CI): 1.40-5.58], and women of less than 50 years of age were more likely to have a clinical breast examination (OR: 1.84; 95% CI: 1.02-3.31) compared with women at low familial risk. Compared with women at low or moderate familial risk, women at high familial risk were significantly more likely to have ever had a genetic test for the BRCA 1/2 genes (OR: 2.67; 95% CI: 1.76-4.05). Although the overall level of adherence among high-risk women is suboptimal in the community, women at a higher familial risk are adhering more often to cancer screening recommendations than women at a lower familial risk.