Marlo Whitehead

Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study.

Objective To assess the risk of systemic adverse events associated with intravitreal injections of vascular endothelial growth factor inhibiting drugs. Design Population based nested case-control study. Setting Ontario, Canada. Participants 91 378 older adults with a history of physician diagnosed retinal disease identified between 1 April 2006 and 31 March 2011. Cases were 1477 patients admitted to hospital for ischaemic stroke, 2229 admitted for an acute myocardial infarction, 1059 admitted or assessed in an emergency department for venous thromboembolism, and 2623 admitted for congestive heart failure. Event-free controls (at a ratio of 5:1) were matched to cases on the basis of year of birth, sex, history of the outcome in the previous 5 years, and diabetes. Main exposure measure Exposure to vascular endothelial growth factor inhibiting drugs identified within 180 days before the index date. Results After adjustment for potential confounders, participants who had ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism were not more likely than control participants to have been exposed to either bevacizumab (adjusted odds ratios of 0.95 (95% confidence interval 0.68 to 1.34) for ischaemic stroke, 1.04 (0.77 to 1.39) for acute myocardial infarction, 0.81 (0.49 to 1.34) for venous thromboembolism, and 1.21 (0.91 to 1.62) for congestive heart failure) or ranibizumab (adjusted odds ratios 0.87 (0.68 to 1.10) for ischaemic stroke, 0.90 (0.72 to 1.11) for acute myocardial infarction, 0.88 (0.67 to 1.16) for venous thromboembolism, and 0.87 (0.70 to 1.07) for congestive heart failure). Similarly, a secondary analysis of exclusive users of bevacizumab or ranibizumab showed no differences in risk between the two drugs (adjusted odds ratios for bevacizumab relative to ranibizumab of 1.03 (0.67 to 1.60) for ischaemic stroke, 1.23 (0.85 to 1.77) for acute myocardial infarction, 0.92 (0.51 to 1.69) for venous thromboembolism, and 1.35 (0.93 to 1.95) for congestive heart failure). These findings were consistent for all but one outcome in subgroup analyses. Conclusions Intravitreal injections of bevacizumab and ranibizumab were not associated with significant risks of ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism.

Stroke Rates after Introduction of Vascular Endothelial Growth Factor Inhibitors for Macular Degeneration: A Time Series Analysis

OBJECTIVE To assess whether stroke rates among patients with retinal disease were influenced by the rapid and sequential uptakes of bevacizumab and ranibizumab for age-related macular degeneration (AMD). DESIGN Population-based, time series analysis using encrypted, linked healthcare databases in Ontario, Canada. PARTICIPANTS We included all patients aged 66 years or older with physician-diagnosed retinal disease in the previous 5 years between 2002 and 2010 (N = 116 388). A secondary analysis evaluated patients who had undergone photodynamic therapy (PDT) within the preceding year (N = 10 059). METHODS We used segmented regression analysis to evaluate changes in the rate of hospitalization for ischemic stroke associated with the introduction of bevacizumab and ranibizumab. The stroke rate was compared across 3 mutually exclusive periods: the period before the availability of bevacizumab or ranibizumab, the period of bevacizumab dominant AMD therapy, and the period of ranibizumab dominant AMD therapy. MAIN OUTCOME MEASURES Hospitalizations for ischemic stroke. RESULTS Among patients with retinal disease, neither the trend nor the level of the stroke time series changed with the uptake of bevacizumab (trend change coefficient -0.0026 stroke hospitalizations/1000 subjects/month [95% confidence interval {CI}, -0.0066 to 0.0014; P = 0.20]; level change coefficient, 0.036 stroke hospitalizations/1000 subjects [95% CI, -0.070 to 0.14; P = 0.51]), or ranibizumab (trend change coefficient: -0.0011 stroke hospitalizations/1000 subjects/month [95% CI, -0.0087 to 0.0065; P = 0.78]; level change coefficient: -0.017 stroke hospitalizations/1000 subjects [95% CI, -0.14 to 0.11; P = 0.79]). Similar results were observed in the analysis restricted to patients with recent PDT and in analyses stratified on age, sex, history of stroke, and history of diabetes. CONCLUSIONS The rapid uptake of vascular endothelial growth factor (VEGF) inhibitors for AMD was not associated with a change in the rate of hospitalization for stroke among Ontario seniors with retinal disease. Furthermore, stroke rates in the bevacizumab and ranibizumab periods were not different. These population-level results complement the findings of a recently published trial comparing bevacizumab and ranibizumab, and may assist clinicians and policy makers as they balance the comparative efficacy, safety, and cost of these 2 closely related treatments.

Body Mass Index, Outcomes, and Mortality Following Cardiac Surgery in Ontario, Canada

Background The “obesity paradox” reflects an observed relationship between obesity and decreased morbidity and mortality, suggesting improved health outcomes for obese individuals. Studies examining the relationship between high body mass index (BMI) and adverse outcomes after cardiac surgery have reported conflicting results. Methods and Results The study population (N=78 762) was comprised of adult patients who had undergone first-time coronary artery bypass (CABG) or combined CABG/aortic valve replacement (AVR) surgery from April 1, 1998 to October 31, 2011 in Ontario (data from the Institute for Clinical Evaluative Sciences). Perioperative outcomes and 5-year mortality among pre-defined BMI (kg/m2) categories (underweight <20, normal weight 20 to 24.9, overweight 25 to 29.9, obese 30 to 34.9, morbidly obese >34.9) were compared using Bivariate analyses and Cox multivariate regression analysis to investigate multiple confounders on the relationship between BMI and adverse outcomes. A reverse J-shaped curve was found between BMI and mortality with their respective hazard ratios. Independent of confounding variables, 30-day, 1-year, and 5-year survival rates were highest for the obese group of patients (99.1% [95% Confidence Interval {CI}, 98.9 to 99.2], 97.6% [95% CI, 97.3 to 97.8], and 90.0% [95% CI, 89.5 to 90.5], respectively), and perioperative complications lowest. Underweight and morbidly obese patients had higher mortality and incidence of adverse outcomes. Conclusions Overweight and obese patients had lower mortality and adverse perioperative outcomes after cardiac surgery compared with normal weight, underweight, and morbidly obese patients. The “obesity paradox” was confirmed for overweight and moderately obese patients. This may impact health resource planning, shifting the focus to morbidly obese and underweight patients prior to, during, and after cardiac surgery.

Subspecialization in Glaucoma Surgery

PURPOSE To evaluate trends in glaucoma surgery subspecialization. DESIGN Population-based analysis of incisional glaucoma surgery and laser trabeculoplasty practice patterns among all ophthalmologists in Ontario, Canada, from 1995 through 2010. PARTICIPANTS All ophthalmologists in Ontario, Canada, providing universal health care for the provincial population of approximately 12 million. METHODS The province of Ontario provides government-funded universal health care insurance to all citizens through the Ontario Health Insurance Plan (OHIP). Anonymized physician services data were obtained from the OHIP database, which has excellent accuracy for procedure performance. MAIN OUTCOME MEASURES Proportion of ophthalmologists providing incisional glaucoma surgery and laser trabeculoplasty and the distribution of these surgical and laser procedures among ophthalmologists. RESULTS Between 1995 and 2010, the median number of ophthalmologists in Ontario was 427 (35.1 per 1 million population), ranging from 417 to 453 (32.9-40.3 per 1 million population). The percentage of ophthalmologists providing incisional glaucoma surgery dropped from 35% in 1995 to 19% in 2010, a 47% decline. Over the same period, the mean number of incisional glaucoma surgeries performed per surgeon doubled, and the percentage of incisional glaucoma operations provided by high-volume surgeons rose from 23% to 59%. The percentage of ophthalmologists performing laser trabeculoplasty was relatively stable (48% in 1995 to 50% in 2010). CONCLUSIONS Over the past 16 years, the proportion of ophthalmologists providing incisional glaucoma surgery has declined significantly. At the same time, the proportion of incisional glaucoma surgery provided by high-volume glaucoma surgeons has more than doubled. These trends will have important implications for stakeholders from policy makers and hospitals to academic departments and residency education programs.

Exploration of pressure ulcer and related skin problems across the spectrum of health care settings in Ontario using administrative data

This is a prospective cohort study using population‐level administrative data to describe the scope of pressure ulcers in terms of its prevalence, incidence risk, associating factors and the extent to which best practices were applied across a spectrum of health care settings. The data for this study includes the information of Ontario residents who were admitted to acute care, home care, long term care or continuing care and whose health care data is contained in the resident assessment instrument‐minimum data set (RAI‐MDS) and the health outcomes for better information and care (HOBIC) database from 2010 to 2013. The analysis included 203 035 unique patients. The overall prevalence of pressure ulcers was approximately 13% and highest in the complex continuing care setting. Over 25% of pressure ulcers in long‐term care developed one week after discharge from acute care hospitalisation. Individuals with cardiovascular disease, dementia, bed mobility problems, bowel incontinence, end‐stage diseases, daily pain, weight loss and shortness of breath were more likely to develop pressure ulcers. While there were a number of evidence‐based interventions implemented to treat pressure ulcers, only half of the patients received nutritional interventions.

Strabismus surgical subspecialization: a population-based analysis.

IMPORTANCE The growing complexity of medical and surgical care has resulted in increasing subspecialization. To date, data have been lacking regarding the degree to which subspecialization has affected the provision of strabismus surgical services. This gap is important to address given the implications for health care human resources planning and educational programs. OBJECTIVE To investigate the effect of subspecialization on the provision of strabismus surgery services. DESIGN, SETTING, AND PARTICIPANTS Population-based study in Ontario, Canada, which provides universal health care coverage to the provincial population. Participants included all ophthalmologists in Ontario and the provincial population of approximately 12 million persons from January 1, 1994, through December 31, 2011. MAIN OUTCOMES AND MEASURES Surgeon-level rates of strabismus surgery. RESULTS From January 1, 1994, through December 31, 2011, the percentage of ophthalmologists who provided strabismus surgery decreased from 37.7% (156 of 414 surgeons) to 12.5% (54 of 432 surgeons; difference, 25.2%; 95% CI, 19.3%-30.9%; P < .001), a 66.8% decline from the baseline level. Of ophthalmologists who provided strabismus surgery during the same period, the mean number of strabismus procedures per surgeon grew from 16.2 to 55.3 per year, a 241.4% increase (95% CI, 20.4%-461.6%; P < .001). These trends occurred at all career stages. CONCLUSIONS AND RELEVANCE Strabismus surgery has evolved into a subspecialized field of ophthalmology during the past 15 years. These findings may have important implications for health care professionals and health care system leaders, including the need to account for subspecialization in physician human resources decisions to ensure access to quality strabismus surgery across regions. Furthermore, residency education programs and their governing organizations may need to account for strabismus subspecialization when designing curriculum and accreditation requirements.

Adverse Gastrointestinal Events with Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors: Nested Case–Control Study

BackgroundIntravenous administration of vascular endothelial growth factor (VEGF)-inhibiting drugs is associated with adverse gastrointestinal (GI) events. Clinical trials of VEGF inhibitors used for the treatment of retinal diseases have suggested higher risks of adverse GI events among patients treated with bevacizumab. However, population-based studies have been lacking.ObjectiveOur objective was to assess risks for GI adverse events associated with intravitreal injections of VEGF-inhibiting drugs.MethodsWe conducted a population-based, nested case–control study of 114,427 older adults in Ontario, Canada, with retinal disease identified between 1 November 2005 and 30 April 2011. Of these, 3,582 cases were admitted to hospital or assessed in an emergency department for GI adverse events. Controls were matched to cases on the basis of age, sex, and outcome history.ResultsPatients experiencing adverse events were equally as likely as matched controls to have been exposed to bevacizumab or ranibizumab. Adjusted odds ratios for bevacizumab were 1.05 (95 % confidence interval [CI] 0.69–1.61) for upper GI ulceration, 1.29 (95 % CI 0.86–1.96) for diverticular disease, 1.49 (95 % CI 0.84–2.63) for pancreatitis, 0.82 (95 % CI 0.53–1.29) for cholelithiasis, and 1.45 (95 % CI 0.67–3.12) for cholecystitis. For ranibizumab they were 1.25 (95 % CI 0.88–1.77) for upper GI ulceration, 1.12 (95 % CI 0.83–1.52) for diverticular disease, 0.85 (95 % CI 0.51–1.40) for pancreatitis, 0.77 (95 % CI 0.53–1.11) for cholelithiasis, and 0.83 (95 % CI 0.44–1.56) for cholecystitis. Results were similar when the analysis was restricted to patients only exposed to a single type of VEGF inhibitor.ConclusionsIn this population-based study, intravitreal injections of bevacizumab and ranibizumab were not associated with increased risks of adverse GI events.

Association between Antidepressants and Fall-Related Injuries among Long-Term Care Residents

OBJECTIVES Antidepressants are associated with an increased risk of falls although little is known of the comparative risks of different types of antidepressants or individuals who are at greatest risk for falls. We examined the association between new use of antidepressants and fall-related injuries among older adults in long-term care (LTC). DESIGN, SETTING, PARTICIPANTS This was a matched, retrospective cohort study involving LTC residents in Ontario, Canada, from 2008 to 2014. New users of antidepressants were matched to non-users of antidepressants. MEASUREMENTS The primary outcome was any fall resulting in an emergency department (ED) visit or hospitalization within 90 days after exposure. Secondary outcomes included hip fractures, wrist fractures, and falls reported in LTC. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval associated with antidepressants and outcomes. RESULTS New users of any antidepressant had an increased risk of ED visits or hospitalization for falls within 90 days when compared with individuals not receiving antidepressants (5.2% versus 2.8%; adjusted OR: 1.9, 95% CI: 1.7-2.2). Antidepressants were also associated with an increased risk of all secondary outcomes. The increased risk of fall-related injuries was evident among selective-serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, trazodone, and across multiple patient subgroups. CONCLUSIONS New use of antidepressants is associated with significantly increased risk of falls and fall-related injuries among LTC residents across different patient subgroups and antidepressant classes. The potential risk of fall-related outcomes should be carefully considered when initiating antidepressants among older adults in LTC.

Clinic-Based Glaucoma Care in the Era of Surgical Subspecialization

PURPOSE To evaluate the impact of surgeon practice profile on clinic-based glaucoma care. DESIGN Population-based study of glaucoma care patterns in Ontario, Canada from 2000-2010. METHODS Using comprehensive physician services data from the Ontario Health Insurance Plan database, ophthalmologists were divided into 5 surgical practice subgroups. The role of each subgroup in the provision of glaucoma care was evaluated. Consultations and office visits were used to assess nonsurgical care, while laser trabeculoplasty procedures were used to assess clinic-based procedural care. RESULTS Between 2000 and 2010, the population rate of glaucoma consultations and follow-up visits provided by ophthalmologists who do not perform incisional glaucoma surgery increased at average annual rates of 1.6% (P < .0002) and 3.3% (P < .0001), respectively. In contrast, no significant growth in the rate of glaucoma consultations or follow-up visits provided by glaucoma surgeons was observed (0.8%/year [P = .2] for consultations; 0.2%/year [P = .6] for follow-up visits). Between 2000 and 2010, the rate of laser trabeculoplasty procedures provided by ophthalmologists who do not perform incisional glaucoma surgery increased 19.3% annually (P < .0001), while growth among glaucoma surgeons was more modest (annual growth of 9.2% [P = .0002]). CONCLUSIONS While subspecialization is a growing reality in most areas of medicine, we found that the provision of clinic-based glaucoma care remains dependent on ophthalmologists who do not perform incisional glaucoma surgery. With increasing focus on integrated care, these findings will have important implications for residency education programs and their accrediting bodies and will inform decisions of health care policymakers, hospitals, and academic departments.

Mental Health Services Use Trends in Canadian Veterans: A Population-Based Retrospective Cohort Study in Ontario:

Objective: A substantial evidence base in the peer-reviewed literature exists investigating mental illness in the military, but relatively less is documented about mental illness in veterans. This study uses provincial, administrative data to study the use of mental health services by Canadian veterans in Ontario. Method: This was a retrospective cohort study of Canadian Armed Forces and Royal Canadian Mounted Police veterans who were released between 1990 and 2013 and resided in Ontario. Mental health–related primary care physician, psychiatrist, emergency department (ED) visits, and psychiatric hospitalisations were counted. Repeated measures were presented in 5-year intervals, stratified by age at release. Results: The cohort included 23,818 veterans. In the first 5 years following entry into the health care system, 28.9% of veterans had ≥1 mental health–related primary care physician visit, 5.8% visited a psychiatrist at least once, and 2.4% received acute mental health services at an ED. The use of mental health services was consistent over time. Almost 8% of veterans aged 30 to 39 years saw a psychiatrist in the first 5 years after release, compared to 3.5% of veterans aged ≥50 years at release. The youngest veterans at release (<30 years) were the most frequent users of ED services for a mental health–related reason (5.1% had at least 1 ED visit). Conclusion: Understanding how veterans use the health care system for mental health problems is an important step to ensuring needs are met during the transition to civilian life.