Heather J. Prior

Use of proton pump inhibitors and risk of osteoporosis-related fractures.

Background: The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures. Methods: We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years. Results: We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16–3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02–2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68–12.29, p = 0.002). Interpretation: Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.

Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults

Background: Regulatory bodies worldwide, including Health Canada, have issued warnings about prescribing antidepressants to children and adolescents. We sought to determine whether the Health Canada warning had the desired effects on prescribing patterns and outcomes and whether it had any unintended health consequences. Methods: We examined data from prescription and health care databases representing more than 265 000 children, adolescents and young adults annually to determine changes in the rates of antidepressant prescription, use of health services and outcomes in these populations in the 9 years before and the 2 years after the Health Canada warning. We also examined the data for unintended changes in these rates among patients with anxiety disorders. We used young adults as the comparison group because they were not targeted by the warning. Results: Following the warning, the rate of antidepressant prescriptions decreased among children and adolescents (relative risk [RR] 0.86, 95% confidence interval [CI] 0.81–0.91) and among young adults (RR 0.90, 95% CI 0.86–0.93). Ambulatory visits because of depression decreased among children and adolescents (RR 0.90, 95% CI 0.85–0.96) and young adults (RR 0.91, 95% CI 0.87–0.96). The rate of completed suicides among children and adolescents rose significantly after the warning (RR 1.25, 95% CI 1.08–1.44; annual rate per 1000 = 0.04 before and 0.15 after the warning). There was no equivalent change in the rate of completed suicides among young adults (RR 1.01, 95% CI 0.93–1.10; annual rate per 1000 = 0.15 before and 0.22 after the warning). Among patients with an anxiety disorder, the prescription rates did not change among children and adolescents, except for a decrease in the use of selective serotonin reuptake inhibitors other than fluoxetine, but the rates among young adults changed similar to the pattern of changes in the overall prescribing of antidepressants. There was also a significant decrease in the rate of physician visits because of anxiety disorders among young adults after the warning. Interpretation: Health advisories and warnings issued by regulatory bodies may have unintended consequences on the provision of care, delivery of health services and clinical outcomes. Further efforts are required to ensure that health warnings do not result in unexpected harm.

Fracture risk from psychotropic medications: a population-based analysis.

Background: Selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and antipsychotics have each been associated with an increased risk of fracture in older individuals. The aim of this study was to better define the magnitude of fracture risk with psychotropic medications and to determine whether a dose-effect relationship exists. Methods: Population-based administrative databases were used to examine psychotropic medication exposure and fractures in persons aged 50 years and older in Manitoba between 1996 and 2004. Persons with osteoporotic fractures (vertebral, wrist, or hip [n = 15,792]) were compared with controls (3 controls for each case matched for age, sex, ethnicity, and comordibity [n = 47,289]). Medications examined included antidepressants (SSRIs vs other monoamines), antipsychotics, lithium, and benzodiazepines. Results: Selective serotonin reuptake inhibitors were associated with the highest adjusted odds of osteoporotic fractures (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.32-1.59). Other monoamine antidepressants (OR = 1.15; 95% CI, 1.07-1.24) and benzodiazepines (OR = 1.10; 95% CI, 1.04-1.16) were also associated with greater fracture risk, although the relationship was weaker. Lithium was associated with lower fracture risk (OR = 0.63; 95% CI, 0.43-0.93), whereas the relationship with antipsychotics was not significant in the models that adjusted for diagnoses. A dose-effect relationship was seen with SSRIs and benzodiazepines. Conclusions: This study provides novel insight into the relationship between fractures and psychotropic medications in the elderly. Selective serotonin reuptake inhibitors seem to have a greater risk than other psychotropic classes, and higher doses may further increase that risk. Lithium seems to be protective against fractures.

Association of Antiepileptic Drugs With Nontraumatic Fractures: A Population-Based Analysis

OBJECTIVE To explore the relationship between antiepileptic drug (AED) use and nontraumatic fractures in those aged 50 years and older. DESIGN Retrospective matched cohort study. PARTICIPANTS A total of 15,792 persons, identified through the Population Health Research Data Repository from Manitoba, Canada, with nontraumatic fractures of the wrist, hip, and vertebra occurring between 1996 and 2004. Each patient was matched for age, sex, ethnicity, and comorbidity with up to 3 controls (n = 47,289). INTERVENTIONS Prior AED use (carbamazepine, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproic acid, and vigabatrin) was determined from pharmacy data in the repository. Odds ratios (OR) for fracture from AED exposure were adjusted for sociodemographic and comorbidity factors known to affect fracture risk. RESULTS A significant increase in fracture risk was found for most of the AEDs being investigated (carbamazepine, clonazepam, gabapentin, phenobarbital, and phenytoin). The adjusted ORs ranged from 1.24 (95% confidence interval [CI], 1.05-1.47) for clonazepam to 1.91 (95% CI, 1.58-2.30) for phenytoin. The only AED not associated with increased fracture risk was valproic acid (adjusted OR, 1.10; 95% CI, 0.70-1.72). CONCLUSIONS Most AEDs were associated with an increased risk of nontraumatic fractures in individuals aged 50 years or older. Further studies are warranted to assess the risk of nontraumatic fractures with the newer AEDs and to determine the efficacy of osteoprotective medications in this population.

Tamoxifen Use and Osteoporotic Fracture Risk: A Population-Based Analysis

PURPOSE Although tamoxifen has been shown to increase bone mineral density in clinical trials, it is less clear whether this significantly affects fracture rates. Even fewer data are available on skeletal outcomes when tamoxifen is used outside of the context of a clinical trial. A population-based case-control study was undertaken to determine whether tamoxifen use is associated with osteoporotic fractures in routine clinical practice. PATIENTS AND METHODS Population-based administrative data for the Province of Manitoba, Canada, were examined for tamoxifen use and nontraumatic fracture codes in women 50 years of age or older. Women with osteoporotic fractures (vertebral, wrist or hip; n = 11,096) from 1996 to 2004 were each compared with three controls without fracture, matched for age, ethnicity, and comorbidity (n = 33,209). Tamoxifen use was classified as never, past use, or current use. RESULTS Lower osteoporotic fracture rates were associated with current tamoxifen use (univariate odds ratio [OR] = 0.68; 95% CI, 0.55 to 0.84). After controlling for demographic and medical diagnoses known to affect fracture risk, current use was associated with a significantly reduced overall osteoporotic fracture risk (adjusted OR = 0.68; 95% CI, 0.55 to 0.88) and of hip fractures (adjusted OR = 0.47; 95% CI, 0.28 to 0.77). Neither recent nor remote past tamoxifen use was associated with reduced osteoporotic fracture risk. Breast cancer was not independently associated with osteoporotic fractures (adjusted OR = 0.95; 95% CI, 0.81 to 1.12). CONCLUSION In a population-based case-control study, current tamoxifen use was associated with a substantial reduction in osteoporotic fractures.

Are cervical cancer screening rates different for women with schizophrenia? A Manitoba population-based study

CONTEXT Barriers to cervical cancer screening (Pap tests) may exist for women experiencing schizophrenia. DESIGN This study analyzed healthcare records of all women in the province of Manitoba, Canada to: (a) compare cervical cancer screening rates of women with and without schizophrenia; and (b) determine factors associated with screening uptake. SETTING This study took place in Manitoba, Canada, utilizing anonymized universal administrative data in the Population Health Research Data Repository at the Manitoba Centre for Health Policy. PARTICIPANTS All females aged 18-69 living in Manitoba December 31, 2002, excluding those diagnosed with invasive or in situ cervical cancer in the study period or previous 5 years. MAIN OUTCOME To determine factors associated with Papanicolaou (Pap) test uptake (1+ Pap test in 3 years, 2001/02-2003/04), logistic regression modeling included: diagnosis of schizophrenia, age, region, average household income, continuity of care (COC), presence of major physical comorbidity. Good COC was defined as at least 50% of ambulatory physician visits from the same general/family practitioner within two years. RESULTS Women with schizophrenia (n=3220) were less likely to have a Pap test (58.8% vs. 67.8%, p<.0001) compared to all other women (n=335 294). In the logistic regression, a diagnosis of schizophrenia (aOR=0.70, 95% CI 0.65-0.75); aged 50+, and living in a low-income area or the North decreased likelihood; good continuity of care (aOR 1.88, 95% CI 1.85-1.91) and greater physical comorbidity (1.21, 95% CI 1.04-1.41) increased likelihood. CONCLUSION Women with schizophrenia are less likely to receive appropriate cervical cancer screening. Since good continuity of care by primary care physicians may mitigate this, psychiatrists should consider assisting in ensuring screening uptake.

Does a diagnosis of schizophrenia reduce rates of mammography screening? A Manitoba population-based study

1. IntroductionIt is estimated that mammography screening can reducemortality from breast cancer by 20 –35% for women aged 50 to69years,and20%forwomenaged40through49years( Elmoreetal.;2005;FletcherandElmore2003 ).Forwomenaged50 –69,theCanadian Task Force on the Periodic Health Examination (nowknownastheCanadianTaskForceonPreventiveHealthCare)andthe U.S. Preventive Services Task Force recommend mammo-graphyscreeningevery1 –2years(deGrasseetal.,1999;Ferrinietal.,1996; Ringash and Canadian Task Force on Preventive HealthCare, 2001; US Preventive Services Task Force 2002 ). ManitobasBreastScreeningProgramstatesthatthebestchancesofreducingdeaths from breast cancer arise from screening at least 70% ofManitoba women aged 50 through 69 every two years.According to the Statistics Canada Canadian CommunityHealth Survey [CCHS] 3.1 (Statistics Canada 2005) 72.6% ofwomen aged 50 through 69 years received a mammogram(screening or diagnostic) over a two-year period. Women inManitoba self-reported much lower rates, at 65.6%, with 42.6%

Comparative health care use patterns of people with schizophrenia near the end of life: A population-based study in Manitoba, Canada

CONTEXT The rate of health care and palliative care utilization for patients with schizophrenia near the end-of-life is currently unknown. OBJECTIVE Compare rate of health care services, including palliative care, used in the last 6-24months of life for patients with and without schizophrenia. DESIGN Using the de-identified administrative data Repository at the Manitoba Centre for Health Policy; a matched cohort study between 1995/96 and 2007/08,comparing healthcare services utilized six months to two years prior to death of all (de-identified) decedents with a diagnosis of schizophrenia >10years to decedents without a schizophrenia diagnosis. SETTING province of Manitoba, Canada (population 1.235 million). PARTICIPANTS Schizophrenia definition: ICD-9-CM 295, or ICD-10-CA code of F20, F21, F23.2, F25 in hospital or physician files, over a 12-year period 1987-1998, in the 12years prior to death for each individual. Decedents were matched (1:3) on age, sex, geography and date of death ±2months. MAIN OUTCOME MEASURES Health service utilization rates within six-months to two years prior to death. RESULTS In the last six months of life, compared to their matched cohort: decedents with schizophrenia had higher rates (52.1% vs. 24.4%, p<.00001) and number of days (89.2 vs. 40.3days, p<.0001) residing in a nursing home; had higher ambulatory visit rates to general practitioners (6.4 vs. 5.5 visits per person, p<.0001), higher rate of visits to psychiatrists (0.53 vs. 0.07 visits per person) and lower rates of seeing other specialists. They were less likely to have opioid analgesia (aRR=0.7157, p-value=0.0006) or to receive palliative care (aOR=0.48, 95% CI 0.41-0.57). CONCLUSION End-of-life care is lacking for patients with schizophrenia. Compared to their matched cohort, these patients were much more likely to die in nursing homes, less likely to see specialists (other than psychiatrists), less likely to be prescribed analgesics, and less likely to receive palliative care.

Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early-Onset Type 2 Diabetes in Canadian First Nations and Non–First Nations Offspring

OBJECTIVE Type 2 diabetes is increasing in children worldwide, with Canadian First Nations (FN) children disproportionally affected. The prevalence of gestational diabetes mellitus (GDM) also is increasing. The objective of this study was to evaluate the impact of GDM exposure in utero and FN status on the subsequent risk of type 2 diabetes in offspring in the first 30 years of life. RESEARCH DESIGN AND METHODS In this population-based historical prospective cohort study, we used administrative databases linked to a clinical database to explore the independent association and interaction between GDM and FN status on the subsequent development of type 2 diabetes in offspring. RESULTS Among 321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN status were independently associated with subsequent risk of type 2 diabetes in offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44–3.76; P < 0.0001] vs. 4.86 [95% CI 4.08–5.79; P < 0.0001], respectively). No interaction between GDM and FN status on type 2 diabetes risk was observed. FN status had a stronger impact on the development of type 2 diabetes in offspring than GDM. CONCLUSIONS GDM is an important modifiable risk factor for type 2 diabetes, and its prevention may reduce the prevalence of subsequent type 2 diabetes in offspring. This study adds unique and rigorous evidence to the global public health debate about the impact of GDM on the long-term health of offspring.

Breastfeeding Initiation Associated With Reduced Incidence of Diabetes in Mothers and Offspring

OBJECTIVE: To examine associations between breastfeeding initiation and subsequent diabetes among First Nations (indigenous people in Canada who are not Métis or Inuit) and non–First Nations mothers and their offspring with and without gestational diabetes mellitus (GDM). METHODS: This retrospective database study included 334,553 deliveries (1987–2011) in Manitoba with up to 24 years of follow-up for diabetes using population-based databases. Information of breastfeeding initiation before hospital discharge was obtained from hospital abstracts recorded by nurses in postpartum wards. Cox proportional hazard models were applied to examine the association between breastfeeding initiation and risk of diabetes in mothers and their offspring. RESULTS: Breastfeeding initiation was recorded in 83% of non–First Nations mothers and 56% of First Nations mothers (P<.001). Breastfeeding initiation was associated with a reduced risk of incident (later developed) diabetes in non–First Nations mothers without GDM (hazard ratio [HR] 0.73 [or −27% of risk], 95% confidence interval [CI] 0.68–0.79), non–First Nations mothers with GDM (HR 0.78 or −22% of risk, CI 0.69–0.89), First Nations mothers without GDM (HR 0.89 or −11% of risk, CI 0.81–0.98), and First Nations mothers with GDM (HR 0.82 or −18% of risk, CI 0.73–0.92) with 24 years of follow-up or less. With 24 years of follow-up or less, breastfeeding initiation was associated with a 17% lower risk of youth-onset type 2 diabetes in offspring (HR 0.83, CI 0.69–0.99, P=.038). The association between breastfeeding initiation and subsequent diabetes in mothers and offspring was independent of family income, rural residence, First Nations status, GDM, parity, gestational hypertension, and age of the mother. CONCLUSION: Breastfeeding initiation is associated with a reduced risk of diabetes among women and their offspring in Manitoba. The results suggest that breastfeeding might be a potentially modifiable factor to reduce the risk of diabetes in both First Nations and non–First Nations women and children.