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Background Some antibiotic agents, including cotrimoxazole, inhibit the metabolism of warfarin sodium and possibly increase the risk of hemorrhage. We examined the risk of upper gastrointestinal (UGI) tract hemorrhage in older patients receiving warfarin in combination with antibiotics commonly used to treat urinary tract infection, with a focus on cotrimoxazole. Methods This population-based, nested case-control study using health care databases in Ontario, Canada, between April 1, 1997, and March 31, 2007, identified residents 66 years or older who were continuously treated with warfarin. Cases were hospitalized with UGI tract hemorrhage. For each case, we selected up to 10 age- and sex-matched control subjects. We calculated adjusted odds ratios (aORs) for exposure to cotrimoxazole, amoxicillin trihydrate, ampicillin trihydrate, ciprofloxacin hydrochloride, nitrofurantoin, and norfloxacin within 14 days before the UGI tract hemorrhage. Results We identified 134 637 patients receiving warfarin, of whom 2151 cases were hospitalized for UGI tract hemorrhage. Cases were almost 4 times more likely than controls to have recently received cotrimoxazole (aOR, 3.84; 95% confidence interval [CI], 2.33-6.33). Treatment with ciprofloxacin was also associated with increased risk (aOR, 1.94; 95% CI, 1.28-2.95), but no significant association was observed with amoxicillin or ampicillin (1.37; 0.92-2.05), nitrofurantoin (1.40; 0.71-2.75), or norfloxacin (0.38; 0.12-1.26). Compared with amoxicillin or ampicillin, cotrimoxazole prescription was associated with an almost 3-fold risk (ratio of ORs, 2.80; 95% CI, 1.48-5.32). Conclusions Among older patients receiving warfarin, cotrimoxazole is associated with a significantly higher risk of UGI tract hemorrhage than other commonly used antibiotics. Whenever possible, clinicians should prescribe alternative antibiotics in patients receiving warfarin.

The prescribing cascade model involves the misinterpretation of an adverse reaction to 1 drug and the subsequent, potentially inappropriate prescription of a second drug. We present a new example of the prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs used to manage urinary incontinence.A population-based retrospective cohort study was carried out in Ontario, Canada. Participants included 44,884 older adults with dementia (20,491 were dispensed a cholinesterase inhibitor and 24,393 were not), enrolled between June 1, 1999, and March 31, 2002. Subjects were observed until they received an anticholinergic drug, stopped the cholinesterase inhibitor treatment, died, or the study period ended (March 31, 2003). The main outcome measure was receipt of an anticholinergic drug to manage urinary incontinence.After adjusting for potential confounding factors, we observed that older adults with dementia who were dispensed cholinesterase inhibitors had an increased risk of subsequently receiving an anticholinergic drug (4.5% vs 3.1%; P.001; adjusted hazard ratio, 1.55; 95% confidence interval, 1.39-1.72), relative to those not receiving cholinesterase inhibitors. This finding was consistent in a series of subgroup analyses.Use of cholinesterase inhibitors is associated with an increased risk of receiving an anticholinergic drug to manage urinary incontinence. The use of an anticholinergic drug in this setting may represent a clinically important prescribing cascade. Clinicians should consider the possible contributing role of cholinesterase inhibitors in new-onset or worsening urinary incontinence and the potential risk of coprescribing cholinesterase inhibitors and anticholinergic drugs to patients with dementia.

Background Initiating antihypertensive drugs in the elderly has been associated with an immediate increased risk of falls. However, it is unknown whether initiation of antihypertensive drugs (eg, thiazide diuretics, angiotensin II converting–enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, or β-adrenergic blockers) is associated with an immediate increased risk of hip fractures. Methods A population-based, self-controlled case series design using health care administrative databases identifying patients initiating an antihypertensive drug in Ontario, Canada. A cohort of newly treated hypertensive elderly patients was linked to the occurrence of hip fractures from April 1, 2000, to March 31, 2009, to create exposed cases. The risk period was the first 45 days following antihypertensive therapy initiation with control periods before and after treatment in a 450-day observation period. The outcome measure was the first occurrence for a proximal femoral fracture during the risk period. The analysis determined the relative incidence (incidence rate ratio), defined as the hip fracture rate in the risk period compared with control periods. Results Among the 301 591 newly treated hypertensive community-dwelling elderly patients, 1463 hip fractures were identified during the observation period. Hypertensive elderly persons who began receiving an antihypertensive drug had a 43% increased risk of having a hip fracture during the first 45 days following treatment initiation relative to the control periods (incidence rate ratio, 1.43; 95% CI, 1.19-1.72). Conclusions Antihypertensive drugs were associated with an immediate increased hip fracture risk during the initiation of treatment in hypertensive community-dwelling elderly patients. Caution is advised when initiating antihypertensive drugs in the elderly.

Background: Transitions between health care settings represent vulnerable periods for medical error. Discontinuation of long-term medication use may occur during discharge from the hospital to the community. Methods: We performed a population-based, cohort study using administrative records from Ontario, Canada, between April 1, 1997, and September 30, 2002. We studied all residents 66 years and older with continuous use of warfarin, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), or-blocker ophthalmic drops for 1 or more years. Those who had an overnight hospitalization for selected elective surgical procedures were compared with 2 control groups: one that had an ambulatory procedure and one that had no procedures. All groups were assessed for the outcome of failure to renew the prescription within 6 months. Results: Rates of drug treatment discontinuation after overnight hospitalizations, after ambulatory procedures, and after no procedures were 11.4%, 7.5%, and 4.8%, respectively, in the warfarin group; 4.0%, 3.9%, and 3.9%, respectively, in the statin group; and 8.4%, 8.9%, and 7.9%, respectively, in the ophthalmic drops group. The adjusted odds ratio (OR) was 2.6 (95% confidence interval [CI], 2.0-3.4) for discontinuation of warfarin therapy after overnight hospitalizations and 1.6 (95% CI, 1.4-1.7) after ambulatory procedures. In contrast, there was no increased risk of discontinuing treatment with either statins (OR for overnight hospitalization, 1.0 [95% CI, 0.9-1.2]; OR for ambulatory procedure, 1.0 [95% CI 1.0-1.1]) or ophthalmic drops (OR for overnight hospitalization, 1.0 [95% CI, 0.8-1.5]; OR for ambulatory procedure, 1.1 [95% CI, 1.0-1.2]). Conclusions: Patients prescribed long-term therapy with warfarin were at risk for potentially unintended medication discontinuation after elective procedures. Patients prescribed statins or -blocker ophthalmic drops were not at increased risk. Arch Intern Med. 2006;166:2525-2531

Background Recent debate has emerged regarding the cardiovascular safety of selective cyclooxygenase 2 inhibitors and the possible cardioprotective effect of naproxen sodium. We compared the rates of acute myocardial infarction (AMI) among elderly patients dispensed selective cyclooxygenase 2 inhibitors, naproxen, and nonselective nonnaproxen nonsteroidal anti-inflammatory drugs (NSAIDs). Methods We conducted a population-based retrospective cohort study using administrative health care data from Ontario, Canada, from April 1, 1998, to March 31, 2001. We identified NSAID-naive cohorts of subjects aged 66 years and older in whom treatment was initiated with celecoxib (n = 15 271), rofecoxib (n = 12 156), naproxen (n = 5669), and nonnaproxen nonselective NSAIDs (n = 33 868), along with a randomly selected control cohort not exposed to NSAIDs (n = 100 000). Multivariate Cox proportional hazards models were used to compare AMI rates between study drug groups while controlling for potential confounders. Results Relative to control subjects, the multivariate model showed no significant differences in AMI risk for new users of celecoxib (adjusted rate ratio [aRR], 0.9; 95% confidence interval [CI], 0.7-1.2), rofecoxib (aRR, 1.0; 95% CI, 0.8-1.4), naproxen (aRR, 1.0; 95% CI, 0.6-1.7), or nonnaproxen nonselective NSAIDs (aRR, 1.2; 95% CI, 0.9-1.4). Conclusions The findings of this observational study suggest no increase in the short-term risk of AMI among users of selective cyclooxygenase 2 inhibitors as commonly used in clinical practice. Furthermore, the findings do not support a short-term reduced risk of AMI with naproxen.