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Below are the 3 articles selected as suggested reading for this week by McMaster editors.
Please be advised that until the end of August Publications of the Week will be temporarily published in a less frequent, biweekly cycle.
Long-acting opioids for noncancer pain: the risk of death
The prescription of long-acting opioids for noncancer pain, as opposed to prescribing additional nonopioid pain medications, was associated with an increased risk of death (close to 70 additional deaths per 10,000 person-years of treatment).
In this retrospective cohort study, authors reviewed over 22,000 new prescriptions for noncancer pain, including both long-acting opioids (sustained-release morphine, controlled-release oxycodone, transdermal fentanyl, methadone) and control medications (analgesic anticonvulsants [gabapentin, pregabalin, carbamazepine] or low-dose cyclic antidepressants). The risk of death was adjusted by taking into account over 100 potential factors, including demographics, diagnoses related to chronic pain (the most common diagnosis was back pain), use of short-acting opioids and other medications for pain, use of benzodiazepines and other psychotropic medications linked with the risk of overdose death, 23 psychiatric diagnoses, cardiovascular conditions, respiratory diseases, and medical care utilization.
The hazard ratio (HR) for total mortality was 1.64 (95% confidence interval [CI], 1.26-2.12), with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7). This was entirely due to increased risk of out-of-hospital death, with a risk difference of 67.1 per 10,000 person-years, including the additional risk of unintentional overdose (risk difference, ~21 per 10,000 person-years), cardiovascular death (risk difference, ~29 per 10,000 person-years), and respiratory death (7 per 10,000 person-years). The HR during the first 30 days of therapy with long-acting opioids was increased 4-fold, with a risk difference of 200 excess deaths per 10,000 person-years.
Within limitations of an observational cohort study based on an administrative database, those findings should be considered and discussed with patients prior to treatment.
Alteplase in patients with ischemic stroke: balancing benefits and risks
The decision to treat patient with ischemic stroke with alteplase requires a complex and difficult process of balancing potential benefits (increased proportion of patients surviving with excellent function) versus increased risks of early intracerebral hemorrhage, death from such hemorrhage, and possibly death overall. This analysis helps in performing such a balancing act, taking into account time to treatment (better results with earlier treatment) and the severity of original stroke (higher absolute risk of bleeding and risk of death from hemorrhage with increasing stroke severity).
In this individual patient data meta-analysis, treatment with alteplase increased the risk of intracranial hemorrhage from 1.3% to 6.8% and risk of death from such bleeding from 0.4% to 2.7%. In authors' estimates, for each 100 patients with mild stroke (National Institutes of Health Stroke Scale [NIHSS] 0-4) treated early (0 to 3 hours), the number of patients achieving an excellent outcome was increased by 12, compared with increased by 6 among those treated between 3 and 4.5 hours. Among such patients, there was no increase in the number of deaths, and there was a decrease in the number of patients most severely disabled (bedbound; by 6 if treated early, by 1 if treated late). For 100 patients with the most severe stroke at presentation (NIHSS >15), authors estimate that there will be 3 fewer people dying if treated early and 1 more dying if treated late. The number of people with an excellent outcome could be increased among the 100 patients with most severe strokes from 6 to 11 if treated early and from 6 to 8 if treated late.
The article provides a visual aid (Figure 5) facilitating communication of treatment effects to patients and their families.
Arrhythmia recurrence despite ICD in patients with ischemic cardiomyopathy: VT ablation vs escalation of antiarrhythmic drugs
Recurrent ventricular tachycardia (VT) occurs among patients who had an implantable cardioverter-defibrillator (ICD) inserted for ischemic cardiomyopathy. Treatment of such patients involves introduction or escalation of antiarrhythmic therapy (medical group) or catheter ablation (ablation group). Comparing those two treatments, authors observed no difference in mortality with a decreased risk of recurrent VT confined to those not treated at baseline with amiodarone.
The study included over 250 patients who had myocardial infarction, had an ICD inserted, and had an episode of VT during the previous 6 months while treated with an antiarrhythmic drug (class I or III). The combined outcome included death, appropriate discharge of the ICD, and VT storm (defined as 3 episodes of VT within 24 hours). At the time of enrollment, the average time from the last myocardial infarction was >10 years, previous coronary artery bypass graft was performed in >40% of patients, amiodarone was used in slightly over 60% (in most at a dose <300 mg), and the other main antiarrhythmic drug was sotalol. ß-Blockers were used in >90% of the enrolled individuals. Patients treated medically had either amiodarone started, amiodarone dose increased (if the original dose was <300 mg/day), or mexiletine added (if already on amiodarone of at least 300 mg/day). The mean time of observation was 27 months.
The primary combined outcome was less frequent among the ablation group (59% vs 69%; hazard ratio [HR], 0.72) with the risk of death similar (27.3% vs 27.6%; HR, 0.96) and lower risk of VT storm (24% vs 33%; HR, 0.66). In subgroup analysis, this benefit was present among patients receiving amiodarone therapy at baseline (61% vs 77%) but absent among patients not treated originally with amiodarone (55% vs 51%). Pulmonary and hepatic toxicity was more frequent among 127 patients in the medical escalation group (2 deaths from hepatic toxicity and 1 from pulmonary toxicity plus 6 episodes of nonfatal hepatic toxicity).
