Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4

Background: The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liverspecific 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. Methods: 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 allcause mortality. All outcomes were assessed within 30 days after co-prescription. Results: 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. Interpretation: 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

Statin safety in chinese: A population-based study of older adults

Background 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 statinassociated adverse events amongst Chinese patients. Methods 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. Findings 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. Conclusions 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

Effectiveness of nail bed repair in children with or without replacing the fingernail : NINJA multicentre randomized clinical trial

Background Surgery for nail bed injuries in children is common. One of the key surgical decisions is whether to replace the nail plate following nail bed repair. The aim of this RCT was to assess the clinical effectiveness and cost-effectiveness of nail bed repair with fingernail replacement/substitution compared with repair without fingernail replacement. Methods A two-arm 1 : 1 parallel-group open multicentre superiority RCT was performed across 20 secondary-care hospitals in the UK. The co-primary outcomes were surgical-site infection at around 7 days after surgery and cosmetic appearance summary score at a minimum of 4 months. Results Some 451 children presenting with a suspected nail bed injury were recruited between July 2018 and July 2019; 224 were allocated to the nail-discarded arm, and 227 to the nail-replaced arm. There was no difference in the number of surgical-site infections at around 7 days between the two interventions or in cosmetic appearance. The mean total healthcare cost over the 4 months after surgery was €84 (95 per cent c.i. 34 to 140) lower for the nail-discarded arm than the nail-replaced arm (P < 0.001). Conclusion After nail bed repair, discarding the fingernail was associated with similar rates of infection and cosmesis ratings as replacement of the finger nail, but was cost saving

sj-docx-1-wso-10.1177_17474930231215005 – Supplemental material for The association between inpatient rehabilitation intensity and outcomes after stroke in Ontario, Canada

Supplemental material, sj-docx-1-wso-10.1177_17474930231215005 for The association between inpatient rehabilitation intensity and outcomes after stroke in Ontario, Canada by Shannon L MacDonald, Elizabeth Linkewich, Mark Bayley, Irene JH Jeong, Jiming Fang and Jamie L Fleet in International Journal of Stroke</p

Detecting chronic kidney disease in population-based administrative databases using an algorithm of hospital encounter and physician claim codes

Abstract 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 m2 (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 m2 (26 to 51 mL/min per 1.73 m2) vs. 69 mL/min per 1.73 m2 (56 to 82 mL/min per 1.73 m2), 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

Risk of hospitalization for community acquired pneumonia with renin-angiotensin blockade in elderly patients: a population-based study.

OBJECTIVE: To characterize the 90-day risk of hospitalization with pneumonia among patients treated with different anti-hypertensive drug classes. DESIGN: Population based cohort study using five linked databases. PARTICIPANTS: 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). PRIMARY OUTCOME: 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. RESULTS: 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). CONCLUSION: 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

Gabapentin dose and the 30-day risk of altered mental status in older adults: A retrospective population-based study

<div><p>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.</p></div

Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney disease: a retrospective population-based study

Abstract Background Many older patients have chronic kidney disease (CKD), and a lower dose of anti-depressants paroxetine, mirtazapine and venlafaxine is recommended in patients with CKD to prevent drug accumulation from reduced elimination. Using information available in large population-based healthcare administrative databases, we conducted this study to determine if ignoring the recommendation and prescribing a higher versus lower dose of anti-depressants associates with a higher risk of adverse events. Methods We conducted a population-based cohort study to describe the 30-day risk of delirium in older adults who initiated a higher vs. lower dose of these three anti-depressants in routine care. We defined delirium using the best proxy available in our data sources - hospitalization with an urgent head computed tomography (CT) scan. We determined if CKD status modified the association between anti-depressant dose and outcome, and examined the secondary outcome of 30 day all-cause mortality. We used multivariable logistic regression analyses to estimate adjusted odds ratios (relative risk (RR)) and 95% confidence intervals. Results We identified adults (mean age 75) in Ontario who started a new study anti-depressant at a higher dose (n = 36,651; 31%) or lower dose (n = 81,160; 69%). Initiating a higher vs. lower dose was not associated with an increased risk of hospitalization with head CT (1.09% vs. 1.27% (adjusted RR 0.90; 95% CI, 0.80 to 1.02), but was associated with a lower risk of all-cause mortality (0.76% vs. 0.97% RR 0.82; 95% CI, 0.71 to 0.95). Neither of these relative risks were modified by the presence of CKD (p = 0.16, 0.68, respectively). Conclusions We did not observe an increase in two adverse outcomes when study anti-depressants were initiated at a higher dose in elderly patients with moderate CKD. Contrary to our hypothesis, the 30-day risk of mortality was lower when a higher versus lower dose of anti-depressant was initiated in these patients, a finding which requires corroboration and further study

Gabapentin dosing recommendations in popular drug prescribing references.

<p>Gabapentin dosing recommendations in popular drug prescribing references.</p