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Background: Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown. MethodsandFindings: We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43;95% CI 1.06-1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73;95% CI 1.11-2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25;95% CI 0.81-1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54-2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients. Conclusions: PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia., Introduction Proton-pump inhibitors (PPIs) are among the most widely prescribed drugs in the world, with more than 147 million prescriptions dispensed in the United States in 2010 alone [1]. They [...]

Several studies demonstrate that use of commonly prescribed medications is associated with improved survival in various malignancies. Methods of classifying medication use in many of these studies, however, do not account for intermittent or cumulative use. Moreover, there are limited data in kidney cancer. Therefore, we performed a population‐based cohort study utilizing healthcare databases in Ontario, Canada. We identified patients aged ≥65 with an incident diagnosis of kidney cancer between 1997 and 2013 and examined use of nine putative anti‐neoplastic medications using prescription claims. Cox proportional hazard models evaluated the association of medication exposure on cancer‐specific and overall survival. We conducted three separate analyses: the effect of cumulative duration of exposure to the study medications on outcomes, the effect of current exposure (in a binary nature) and the effect of exposure at diagnosis. During the 16‐year study period, we studied 9,124 patients. Increasing cumulative use of angiotensin‐converting enzyme inhibitors, non‐steroidal anti‐inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors were associated with markedly improved cancer‐specific survival; increasing use of NSAIDs was associated with markedly improved overall survival. These results were generally discordant with analyses evaluating the effect of current use and exposure at diagnosis. In conclusion, pharmacoepidemiology studies may be sensitive to the method of analysis; cumulative use analyses may be the most robust as it accounts for intermittent use and supports a dose–outcome relationship. Prospective studies are needed to confirm whether patients diagnosed with kidney cancer should be started on an angiotensin‐converting enzyme inhibitor, NSAID or selective serotonin reuptake inhibitor to improve survival. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Over the past 20 years, the prescribing of opioids has increased dramatically in North America, with parallel increases in opioid addiction, overdose, and associated deaths. We examined whether young children of women prescribed opioids were at increased risk of opioid overdose. METHODS: We conducted a population-based, nested case control study in Ontario, Canada, between 2002 and 2015. We identified children aged ≤10 years, whose mothers received publicly funded prescriptions for an opioid or a nonsteroidal antiinflammatory drug (comparator analgesic) in the preceding year. Cases were children who presented to hospital for or died of opioid overdose. Each case was matched with 4 controls with no opioid overdose. The primary outcome was the risk of opioid overdose. RESULTS: We identified 103 children who presented to the hospital with opioid overdose and matched them with 412 controls. Half of the children with opioid overdose were <2 years old. Compared with controls, children with an opioid overdose were far more likely to have a mother who received a prescription opioid (unadjusted odds ratio, 2.41; 95% confidence interval, 1.68-3.45) and who was prescribed antidepressants. The most commonly implicated overdose opioids were codeine (53.4%), oxycodone (32.0%), and methadone (15.5%). CONCLUSIONS: Young children of mothers prescribed opioids are at a markedly increased risk of overdose. Physicians, pharmacists, and parents should take measures to mitigate the risk of opioid-related harm to children, such as prescribing smaller quantities, emphasizing the importance of secure medication storage, and the prompt disposal of unused opioids. [ABSTRACT FROM AUTHOR]

Background: Eating disorders, specifically anorexia nervosa, bulimia nervosa and eating disorder not otherwise specified, represent a substantial burden to the health care system. Our goal was to estimate the economic burden of patients who received specialized inpatient care for an eating disorder out of country. Method: We conducted a cost-of-illness study evaluating health care costs among patients in Ontario who received specialized inpatient care for an eating disorder out of country from 2003 to 2011, from the public third-party payer perspective. Using linked administrative databases, we estimated net costs of eating disorders for 2 patient groups: those who received specialized inpatient care both out of country and in province (n = 160), and those who received specialized inpatient care out of country only (n = 126). Results: Patients approved for specialized out-of-country inpatient care were mostly girls and young women from high-income, urban neighbourhoods. Total net costs varied annually and were higher for patients treated both out of country and in province (about $11 million before 2007, $6.5 million after) than for those treated out of country alone (about $5 million and $2 million, respectively). The main cost drivers were out-of-country care and physician services. Interpretation: Costs associated with eating disorder care represent a substantial economic burden to the Ontario health care system. Given the high costs of out-of-country care, there may be opportunity to redirect these funds to increase capacity and expertise for eating disorder treatment within Ontario. [ABSTRACT FROM AUTHOR]

Context:Intentional overdose is a leading method of self-harm and suicide, and repeat attempts strongly predict eventual death by suicide. Objectives:To determine the risk of recurrence after a first intentional overdose. Secondary objectives included characterization of the temporal course and potential predictors of repeat overdose, a strong risk factor for death from suicide. Methods:Design: Population-based cohort study. Setting:Ontario, Canada, from 1 April 2002 to 31 March 2013. Participants:All Ontario residents presenting to an emergency department after a first intentional overdose. Main outcome measures:The incidence and timing of recurrent overdose. Results:We followed 81,675 patients discharged from hospital after a first intentional overdose. Overall, 13,903 (17.0%) returned with a repeat overdose after a median interval of 288 (inter-quartile range: 62 to 834) days. Of these, 4493 (5.5%) had multiple repeat episodes. Factors associated with repeat self-poisoning included psychiatric care in the preceding year (adjusted hazard ratio [aHR] 1.55; 95% confidence interval [CI] 1.50 to 1.61), alcohol dependence (aHR 1.41; 95% CI 1.35 to 1.46) and documented depression (aHR 1.39; 95% CI 1.34 to 1.44). Female sex, rural residence, lower socioeconomic status, ingestion of psychoactive drugs and younger age were also weakly associated with repeat overdose. Discussion:Hospital presentation for repetition of intentional overdose is common, with recurrent episodes often far removed from the first. While several factors predict overdose repetition, none is particularly strong. Conclusion:Secondary prevention initiatives should be implemented for all individuals who present to the emergency department and survive intentional overdose. [ABSTRACT FROM AUTHOR]

Background: Maternal placental syndromes are associated with adverse fetal outcomes and maternal cardiovascular disease. However, whether HIV infection increases the risk of maternal placental syndromes is unknown. Our objective was to compare the risk of maternal placental syndromes between women living with and without HIV infection in Ontario. Methods: We conducted a population-based study using health administrative data from Ontario. We identified all pregnancies resulting in a live birth between Apr. 1, 2002, and Mar. 31, 2011; we identified women living with HIV using a validated case-finding algorithm. Our primary composite outcome was maternal placental syndromes, defined as a diagnosis of preeclampsia, eclampsia, placental abruption or placental infarction. We used generalized estimating equations with a logit link function to derive adjusted odds ratios (AORs) and 95% confidence intervals (CI) for the association between HIV infection and maternal placental syndromes. Results: Data from 1 132 871 pregnancies were available for analysis; 634 (0.06%) of the pregnancies were in women living with HIV. After multivariable adjustment, we found no difference in the risk of maternal placental syndromes between women living with HIV and those without HIV infection (5.8% v. 5.6%; AOR 0.85 [95% CI 0.59-1.21]). An increased risk of maternal placental syndromes was associated with pre-existing diabetes (AOR 1.47 [95% CI 1.39-1.54]), pre-existing hypertension (AOR 4.28 [95% CI 4.15-4.42]) and chronic kidney disease (AOR 1.83 [95% CI 1.61-2.08]). Interpretation: Women with HIV are not at increased risk of maternal placental syndromes. Our results underscore the importance of optimizing the management of comorbid illness associated with maternal placental syndromes during the prenatal period for all women, irrespective of HIV status. [ABSTRACT FROM AUTHOR]

PURPOSE Reports of bupropion misuse have increased since it was first reported in 2002. The purpose of this study was to explore trends in bupropion prescribing suggestive of misuse or diversion in Ontario, Canada. METHODS A serial cross-sectional study was conducted of Ontarians aged younger than 65 years who received prescriptions under Ontario's public drug program from April 1, 2000, to March 31, 2013. We determined the number of potentially inappropriate prescriptions in each quarter, defined as early refills dispensed within 50% of the duration of the preceding prescription, as well as potentially duplicitous prescriptions, defined as similarly early refills originating from a different prescriber and different pharmacy. We replicated these analyses for citalopram and sertraline, antidepressants not known to be prone to abuse. RESULTS We identified 1,780,802 prescriptions for bupropion, 3,402,462 for citalopram, and 1,775,285 for sertraline. Rates of early refills for bupropion declined during the study from 4.8% to 3.1%. In the final quarter, rates of early refills for bupropion were more common than for citalopram (3.1% vs 2.2%) (P <.001) but not for sertraline (3.1% vs 2.9%) (P = .16). Potentially duplicitous prescriptions for bupropion increased dramatically, from <0.05% of all prescriptions in early 2000 to 0.47% in early 2013 and by the final quarter were more common than both citalopram (0.11%) and sertraline (0.12%) (P <.001). CONCLUSIONS Although no marked differences were seen for early refills of bupropion relative to its comparators, potentially duplicitous prescriptions have increased dramatically in Ontario, suggesting growing misuse of the drug. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) cause interstitial nephritis and are an underappreciated cause of acute kidney injury. We examined the risk of acute kidney injury and acute interstitial nephritis in a large population of older patients receiving PPIs. Methods: We conducted a population-based study involving Ontario residents aged 66 years and older who initiated PPI therapy between Apr. 1, 2002, and Nov. 30, 2011. We used propensity score matching to establish a highly comparable reference group of control patients. The primary outcome was hospital admission with acute kidney injury within 120 days, and a secondary analysis examined acute interstitial nephritis. We used Cox proportional hazards regression to adjust for differences between groups. Results: We studied 290 592 individuals who commenced PPI therapy and an equal number of matched controls. The rates of acute kidney injury (13.49 v. 5.46 per 1000 person-years, respectively; hazard ratio [HR] 2.52, 95% CI 2.27 to 2.79) and acute interstitial nephritis (0.32 versus 0.11 per 1000 person-years; HR 3.00, 95% CI 1.47 to 6.14) were higher among patients given PPIs than among controls. Interpretation: In our study population of older adults, those who started PPI therapy had an increased risk of acute kidney injury and acute interstitial nephritis. These are potentially reversible conditions that may not be readily attributed to drug treatment. Clinicians should appreciate the risk of acute interstitial nephritis during treatment with PPIs, monitor patients appropriately and discourage the indiscriminate use of these drugs. [ABSTRACT FROM AUTHOR]

CONTEXTE: Le dabigatran etexiiate est un promédicament dont l'absorption intestinale est empêchée par la P-glycoprotéine et qui est métabolisé en sa forme active, le dabigatran, par une carboxyesté- rase. Contrairement aux autres statines, la simvastatine et la lovasta- tine sont de puissants inhibiteurs de la P-glycoprotéine et de la carboxyestérase et peuvent soit accroître le risque d'hémorragie avec le dabigatran etexiiate soit réduire son efficacité. MÉTHODES : Nous avons mené deux études de cas-témoins emboîtées basées sur une population ontarienne de personnes âgées de 66 ans et plus qui ont commencé le dabigatran etexi- late entre le 1er mai 2012 et le 31 mars 2014. Les patients avec AVC ischémique formaient les cas de la première étude et les patients avec hémorragie grave formaient les cas de la deuxième étude. Chaque cas a été jumelé à jusqu'à quatre témoins en fonction de l'âge et du sexe. Tous les cas et témoins ont reçu une statine unique dans les 60 jours précédant la date de référence. Nous avons déterminé la relation entre chaque résultat et la prise de simvastatine ou de lovastatine comparativement à d'autres statines. RÉSULTATS : Des 45 991 patients qui prenaient le dabigatran etexi- late, nous avons relevé 397 cas avec AVC ischémique et 1117 cas avec hémorragie grave. Après le rajustement multivarié, la prise de simvastatine ou de lovastatine n'a pas été associée au risque accru d'AVC (rapport de cotes ajusté [RC], 1,33, intervalle de confiance [IC] à 95%, 0,88 à 2,01). En revanche, la prise de simvastatine et de lovastatine était associée à un risque plus élevé d'hémorragie grave (RC ajusté, 1,46, IC à 95%, 1,17 à 1,82). INTERPRÉTATION: Chez les patients qui recevaient le dabigatran etexiiate, la simvastatine et la lovastatine étaient associées à un risque plus élevé d'hémorragie grave par rapport à d'autres statines. Il est préférable d'envisager d'autres statines pour ces patients. [ABSTRACT FROM AUTHOR]