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Gabapentin is an effective treatment for chronic neuropathic pain but may cause dizziness, drowsiness, and confusion in some older adults. The goal of this study was to assess the association between gabapentin dosing and adverse outcomes by obtaining estimates of the 30-day risk of hospitalization with altered mental status and mortality in older adults (mean age 76 years) in Ontario, Canada initiated on high dose (>600 mg/day; n = 34,159) compared to low dose (≤600 mg/day; n = 76,025) oral gabapentin in routine outpatient care. A population-based, retrospective cohort study assessing new gabapentin use between 2002 to 2014 was conducted. The primary outcome was 30-day hospitalization with an urgent head computed tomography (CT) scan in the absence of evidence of stroke (a proxy for altered mental status). The secondary outcome was 30-day all-cause mortality. The baseline characteristics measured in the two dose groups were similar. Initiation of a high versus low dose of gabapentin was associated with a higher risk of hospitalization with head CT scan (1.27% vs. 1.06%, absolute risk difference 0.21%, adjusted relative risk 1.29 [95% CI 1.14 to 1.46], number needed to treat 477) but not a statistically significant higher risk of mortality (1.25% vs. 1.16%, absolute risk difference of 0.09%, adjusted relative risk of 1.01 [95% CI 0.89 to 1.14]). Overall, the risk of being hospitalized with altered mental status after initiating gabapentin remains low, but may be reduced through the judicious use of gabapentin, use of the lowest dose to control pain, and vigilance for early signs of altered mental status.

Donepezil, rivastigmine and galantamine are popular cholinesterase inhibitors used to manage the symptoms of Alzheimer disease and other dementias; regulatory agencies in several countries warn about a possible risk of rhabdomyolysis with donepezil, based on information from case reports. Our goal was to investigate the 30-day risk of admission to hospital with rhabdomyolysis associated with initiating donepezil versus other cholinesterase inhibitors. We conducted a retrospective cohort study in Ontario, Canada, from 2002 to 2017. Participants were adults aged 66 years or older with a newly dispensed prescription for donepezil compared with rivastigmine or galantamine. The primary outcome was hospital admission with rhabdomyolysis (assessed using hospital diagnostic codes) within 30 days of a new prescription of a cholinesterase inhibitor. Odds ratios were estimated using logistic regression, with inverse probability of treatment weights calculated from propensity scores. The average age in our 2 groups was 81.1 years, and 61.4% of our population was female. Donepezil was associated with a higher risk of hospital admission with rhabdomyolysis compared with rivastigmine or galantamine (88 events in 152 300 patients [0.06%] v. 16 events in 68 053 patients [0.02%]; weighted odds ratio of 2.21, 95% confidence interval [CI] 1.52–3.22). Most hospital admissions with rhabdomyolysis after donepezil use were not severe, and no patient was treated with acute dialysis or mechanical ventilation. Initiating donepezil is associated with a higher 30-day risk of admission to hospital with rhabdomyolysis compared with initiating rivastigmine or galantamine. The proportion of patients who develop severe rhabdomyolysis within 30 days of initiating donepezil is very low.

Background Palato-pharyngo-laryngeal myoclonus, a variant of palatal myoclonus, is characterized by involuntary rhythmic movements of palatal, pharyngeal, and laryngeal muscles. Symptomatic palatal myoclonus is classically associated with hypertrophic olivary degeneration on MRI imaging due to a lesion in the triangle of Guillain-Mollaret. Case presentation We report a case of palato-pharyngo-laryngeal myoclonus in a patient post-cerebellar hemorrhagic stroke who presented with recurrent retrograde migration of his gastrojejunostomy feeding tubes. Treatment with either divalproex sodium or gabapentin resulted in a significant decrease in his gastrointestinal symptoms and no further episodes of gastrojejunostomy tube migration. Conclusions This case study indicates that the movement disorder associated with hypertrophic olivary degeneration may involve the gastrointestinal system. Anticonvulsants, such as gabapentin and divalproex sodium, may reduce the severity of gastrointestinal symptoms in cases associated with hypertrophic olivary degeneration. The anatomy of the Guillain-Mollaret triangle and the pathophysiology of hypertrophic olivary degeneration are reviewed.

Compared to Caucasians, Chinese achieve a higher blood concentration of statin for a given dose. It remains unknown whether this translates to increased risk of serious statin-associated adverse events amongst Chinese patients. We conducted a population-based retrospective cohort study of older adults (mean age, 74 years) newly prescribed a statin in Ontario, Canada between 2002 and 2013, where 19,033 Chinese (assessed through a validated surname algorithm) were matched (1:3) by propensity score to 57,099 non-Chinese. This study used linked healthcare databases. The follow-up observation period (mean 1.1, maximum 10.8 years) was similar between groups, as were the reasons for censoring the observation period (end of follow-up, death, or statin discontinuation). Forty-seven percent (47%) of Chinese were initiated on a higher than recommended statin dose. Compared to non-Chinese, Chinese ethnicity did not associate with any of the four serious statin-associated adverse events assessed in this study [rhabdomyolysis hazard ratio (HR) 0.61 (95% CI 0.28 to 1.34), incident diabetes HR 1.02 (95% CI 0.80 to 1.30), acute kidney injury HR 0.90 (95% CI 0.72 to 1.13), or all-cause mortality HR 0.88 (95% CI 0.74 to 1.05)]. Similar results were observed in subgroups defined by statin type and dose. We observed no higher risk of serious statin toxicity in Chinese than matched non-Chinese older adults with similar indicators of baseline health. Regulatory agencies should review available data, including findings from our study, to decide if a change in their statin dosing recommendations for people of Chinese ethnicity is warranted.

To characterize the 90-day risk of hospitalization with pneumonia among patients treated with different anti-hypertensive drug classes. Population based cohort study using five linked databases. Individuals over the age of 65 who filled a new outpatient prescription for one of four anti-hypertensive medications: ACE inhibitors (n = 86 775), ARBs (n = 33,953), calcium channel blockers (CCB, n = 34,240), beta blockers (BB, n = 35,331) and thiazide diuretics (n = 64 186). Hospitalization with pneumonia within 90 days of a qualifying prescription. We adjusted for ten a priori selected covariates, including age, sex, diabetes and number of visits to a family doctor. Baseline characteristics of the groups were relatively well matched, except for age, sex, diabetes and frequency of family doctor visits. 128 of the 86 775 patients (0.15%) initiated on an ACE inhibitor and 43 of the 33953 patients (0.13%) of patients initiated on an ARB were hospitalized with pneumonia in the subsequent 90 days. 135 of 64 186 patients (0.21%) initiated on a thiazide, 112 of 35 331 patients (.32%) initiated on a BB, and 89 of 34 240 (0.26%) patients initiated on a CCB achieved the primary outcome. Compared to calcium channel blockers, ACE inhibitors (adjusted OR 0.61, 95% CI 0.46 to 0.81) and ARBs (adjusted OR 0.52, 95% CI 0.36 to 0.76) were associated with a lower risk of pneumonia. No benefit was seen with thiazides (adjusted OR 0.87, 95% CI 0.66 to 1.14) or beta blockers (adjusted OR 1.21, 95% CI 0.91 to 1.60). Initiating medications that block the renin angiotensin system, compared to other anti-hypertensive medications, is associated with a small absolute reduction in the 90 day risk of hospitalization with pneumonia.

Increased rehabilitation intensity, the number of minutes of therapy per day, is associated with improved outcomes. However, it is unclear whether males and females receive the same inpatient stroke rehabilitation intensity. A sub-analysis of a retrospective population-based cohort study of adults (5877 females, 6893 males) with stroke discharged to inpatient rehabilitation between 2017 and 2021 was conducted. The mean rehabilitation intensity was 75.86 min/day for males and 73.33 min/day for females ( p < .0001). Males <80 years of age were more likely to receive higher rehabilitation intensity than females. Future research should explore what factors account for this sex difference. Les hommes bénéficient d’une réadaptation post-AVC plus intense que celle des femmes en Ontario (Canada) . L’augmentation de l’intensité d’une réadaptation, à savoir un nombre accru de minutes de thérapie par jour, est associée à de meilleurs résultats. Cela dit, on ignore si les hommes et les femmes bénéficient de la même intensité de réadaptation à la suite d’une hospitalisation consécutive à un AVC. À cet égard, nous avons effectué une sous-analyse d’une étude de cohorte rétrospective basée sur une population d’adultes (5877 femmes, 6893 hommes) victimes d’un AVC et ayant obtenu un congé de l’hôpital après une réadaptation, et ce, de 2017 à 2021. L’intensité moyenne de la réadaptation était de 75,86 minutes/jour pour les hommes alors qu’elle était de 73,33 minutes/jour pour les femmes ( p < 0,0001). Les hommes âgés de moins de 80 ans étaient aussi plus susceptibles de bénéficier d’une intensité de réadaptation plus élevée que celle des femmes. En cela, les recherches futures devraient explorer les facteurs qui expliquent cette différence entre les sexes.

Objective Clarithromycin strongly inhibits enzyme cytochrome P450 3A4, preventing the metabolism of some other drugs, while azithromycin is a weak inhibitor. Accordingly, blood concentrations of other drugs increase with clarithromycin coprescription leading to adverse events. These macrolide antibiotics also differ on other properties that may impact outcomes. In this study, we compared outcomes in two groups of macrolide antibiotic users in the absence of potentially interacting drugs. Design Population-based retrospective cohort study. Setting Ontario, Canada, from 2003 to 2010. Patients Patients (mean 74 years) prescribed clarithromycin (n=52 251) or azithromycin (referent group, n=46 618). Main outcomes The primary outcomes were hospital admission within 30 days of a new antibiotic prescription with any of the 12 conditions examined separately (acute kidney injury, acute myocardial infarction, neuroimaging (proxy for delirium), hypotension, syncope, hyperkalaemia, hyponatraemia, hyperglycaemia, arrhythmia, ischaemic stroke, gastrointestinal bleeding and sepsis). The secondary outcome was mortality. Results The baseline characteristics of the two groups, including patient demographics, comorbid conditions, infection type and prescribing physician specialty, were nearly identical. The median daily dose was 1000 mg for clarithromycin and 300 mg for azithromycin and the median duration of dispensing antibiotics was 10 and 5 days, respectively. There was no difference between the groups in the risk of hospitalisation for any condition studied (relative risk ranged from 0.67 to 1.23). Compared with azithromycin, clarithromycin was associated with a slightly higher risk of all-cause mortality (0.46% vs 0.37%, relative risk 1.25, 95% CI 1.03 to 1.52). Conclusions Clarithromycin can be used to assess drug interactions in population-based studies with azithromycin serving as a control group. However, any differences in mortality observed between the two antibiotic groups in the setting of other drug use may be partially attributable to factors beyond the inhibition of drug metabolising enzymes and transporters, as the difference for this outcome was significant.

Background Large, population-based administrative healthcare databases can be used to identify patients with chronic kidney disease (CKD) when serum creatinine laboratory results are unavailable. We examined the validity of algorithms that used combined hospital encounter and physician claims database codes for the detection of CKD in Ontario, Canada. Methods We accrued 123,499 patients over the age of 65 from 2007 to 2010. All patients had a baseline serum creatinine value to estimate glomerular filtration rate (eGFR). We developed an algorithm of physician claims and hospital encounter codes to search administrative databases for the presence of CKD. We determined the sensitivity, specificity, positive and negative predictive values of this algorithm to detect our primary threshold of CKD, an eGFR <45 mL/min per 1.73 m 2 (15.4% of patients). We also assessed serum creatinine and eGFR values in patients with and without CKD codes (algorithm positive and negative, respectively). Results Our algorithm required evidence of at least one of eleven CKD codes and 7.7% of patients were algorithm positive. The sensitivity was 32.7% [95% confidence interval: (95% CI): 32.0 to 33.3%]. Sensitivity was lower in women compared to men (25.7 vs. 43.7%; p <0.001) and in the oldest age category (over 80 vs. 66 to 80; 28.4 vs. 37.6 %; p < 0.001). All specificities were over 94%. The positive and negative predictive values were 65.4% (95% CI: 64.4 to 66.3%) and 88.8% (95% CI: 88.6 to 89.0%), respectively. In algorithm positive patients, the median [interquartile range (IQR)] baseline serum creatinine value was 135 μmol/L (106 to 179 μmol/L) compared to 82 μmol/L (69 to 98 μmol/L) for algorithm negative patients. Corresponding eGFR values were 38 mL/min per 1.73 m 2 (26 to 51 mL/min per 1.73 m 2 ) vs. 69 mL/min per 1.73 m 2 (56 to 82 mL/min per 1.73 m 2 ), respectively. Conclusions Patients with CKD as identified by our database algorithm had distinctly higher baseline serum creatinine values and lower eGFR values than those without such codes. However, because of limited sensitivity, the prevalence of CKD was underestimated.

The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liver-specific organic anion–transporting polypeptides (OATP1B1 and OATP1B3). We studied whether concurrent use of clarithromycin and a statin not metabolized by CYP3A4 was associated with an increased frequency of serious adverse events. Using large health care databases, we studied a population-based cohort of older adults (mean age 74 years) who were taking a statin not metabolized by CYP3A4 (rosuvastatin [76% of prescriptions], pravastatin [21%] or fluvastatin [3%]) between 2002 and 2013 and were newly prescribed clarithromycin (n = 51 523) or azithromycin (n = 52 518), the latter an antibiotic that inhibits neither CYP3A4 nor OATP1B1 and OATP1B3. Outcomes were hospital admission with a diagnostic code for rhabdomyolysis, acute kidney injury or hyperkalemia, and all-cause mortality. All outcomes were assessed within 30 days after co-prescription. Compared with the control group, patients co-prescribed clarithromycin and a statin not metabolized by CYP3A4 were at increased risk of hospital admission with acute kidney injury (adjusted relative risk [RR] 1.65, 95% confidence interval [CI] 1.31 to 2.09), admission with hyperkalemia (adjusted RR 2.17, 95% CI 1.22 to 3.86) and all-cause mortality (adjusted RR 1.43, 95% CI 1.15 to 1.76). The adjusted RR for admission with rhabdomyolysis was 2.27 (95% CI 0.86 to 5.96). The absolute increase in risk for each outcome was small and likely below 1%, even after we considered the insensitivity of some hospital database codes. Among older adults taking a statin not metabolized by CYP3A4, co-prescription of clarithromycin versus azithromycin was associated with a modest but statistically significant increase in the 30-day absolute risk of adverse outcomes.

Objective To evaluate the validity of the International Classification of Diseases, 10th Revision (ICD-10) diagnosis code for hyponatraemia (E87.1) in two settings: at presentation to the emergency department and at hospital admission. Design Population-based retrospective validation study. Setting Twelve hospitals in Southwestern Ontario, Canada, from 2003 to 2010. Participants Patients aged 66 years and older with serum sodium laboratory measurements at presentation to the emergency department (n=64 581) and at hospital admission (n=64 499). Main outcome measures Sensitivity, specificity, positive predictive value and negative predictive value comparing various ICD-10 diagnostic coding algorithms for hyponatraemia to serum sodium laboratory measurements (reference standard). Median serum sodium values comparing patients who were code positive and code negative for hyponatraemia. Results The sensitivity of hyponatraemia (defined by a serum sodium ≤132 mmol/l) for the best-performing ICD-10 coding algorithm was 7.5% at presentation to the emergency department (95% CI 7.0% to 8.2%) and 10.6% at hospital admission (95% CI 9.9% to 11.2%). Both specificities were greater than 99%. In the two settings, the positive predictive values were 96.4% (95% CI 94.6% to 97.6%) and 82.3% (95% CI 80.0% to 84.4%), while the negative predictive values were 89.2% (95% CI 89.0% to 89.5%) and 87.1% (95% CI 86.8% to 87.4%). In patients who were code positive for hyponatraemia, the median (IQR) serum sodium measurements were 123 (119–126) mmol/l and 125 (120–130) mmol/l in the two settings. In code negative patients, the measurements were 138 (136–140) mmol/l and 137 (135–139) mmol/l. Conclusions The ICD-10 diagnostic code for hyponatraemia differentiates between two groups of patients with distinct serum sodium measurements at both presentation to the emergency department and at hospital admission. However, these codes underestimate the true incidence of hyponatraemia due to low sensitivity.