Objective -To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH).Design -Cohort study with logistic regression analysis to combine predictors and treatment modality.Setting -Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries.Participants -Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models.Main outcome measure -Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale.Results -Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a "neuroimaging model," with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort. Conclusion -The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients. IntroductionSubarachnoid haemorrhage from a ruptured intracranial aneurysm (SAH) is a relatively uncommon but severe subtype of stroke that is associated with a sudden dramatic onset in otherwise apparently healthy individuals and often results in poor outcomes. On average, a third of affected individuals do not survive; at least one in five of those who do survive are unable to regain functional independence.1 SAH is unlike the more common ischaemic stroke as it affects younger adults (median age 55) and therefore results in disproportionately many years of lost productive life.1 2 Predicting the outcome of this condition can be challenging given the considerable heterogeneity in the characteristics of affected individuals and their clinical course and variability in morphology of the aneurysm. Reliance on clinical intuition alone might be insufficient for accur...

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; for the Canadian Drug Safety and Effectiveness Research Network (CDSERN) IMPORTANCE Suicide is the tenth leading cause of death in the United States, and its rate has risen by 16% in the past decade. Deliberate self-poisoning is the leading method of attempted suicide. Unlike more violent methods, which are almost universally fatal, survival following self-poisoning is common, providing an opportunity for secondary prevention. However, the long-term risk of suicide following a first episode of self-poisoning is unknown. OBJECTIVE To determine the risk of suicide and mortality from other causes following a first self-poisoning episode. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study using multiple linked health care databases. We identified all individuals with a first self-poisoning episode in Ontario, Canada, from April 1, 2002, through December 31, 2010, and followed up all surviving participants until December 31, 2011, or death, whichever occurred first. For each individual with a deliberate self-poisoning episode, we randomly selected 1 control from the same population with no such history, matched for age (within 3 months), sex, and calendar year. MAIN OUTCOMES AND MEASURES The primary analysis examined the risk of suicide following discharge after self-poisoning. The secondary analyses explored factors associated with suicide and examined the risk of death caused by accidents or any other cause. RESULTS We identified 65 784 patients (18 482 [28.1%] younger than 20 years) who were discharged after a first self-poisoning episode. During a median follow-up of 5.3 years (interquartile range, 3.1-7.6 years), 4176 died, including 976 (23.4%) by suicide. The risk of suicide following self-poisoning was markedly increased relative to controls (hazard ratio, 41.96; 95% CI, 27.75-63.44), corresponding to a suicide rate of 278 vs 7 per 100 000 person-years, respectively. The median time from hospital discharge to completed suicide was 585 days (interquartile range, 147-1301 days). Older age, male sex, multiple intervening self-poisoning episodes, higher socioeconomic status, depression, and recent psychiatric care were strongly associated with suicide. Patients with a self-poisoning episode were also more likely to die because of accidents (hazard ratio, 10.45; 95% CI, 8.10-13.47) and all causes combined (hazard ratio, 5.55; 95% CI, 5.12-6.02). CONCLUSIONS AND RELEVANCE A first self-poisoning episode is a strong predictor of subsequent suicide and premature death. Most suicides occur long after the index poisoning, emphasizing the importance of longitudinal, sustained secondary prevention initiatives.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. 2 0 0 4 2 0 0 5 2 0 0 6 2 0 0 7 2 0 0 8 2 0 0 9 2 0 1 0 2 0 1 1 2 0 1 2 2 0 1 3 2 0 1 4 2 0 1 5 2 0 1 6 2 0 1 7 Other Negational Affirmational The New England Journal of Medicine Downloaded from nejm.org on June 9, 2017. For personal use only. No other uses without permission.

David Juurlink and colleagues evaluated the risk of hospitalization with hypomagnesemia among patients taking proton pump inhibitors. Please see later in the article for the Editors' Summary

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Objective To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death. Design Population based nested case-control study. Setting Ontario, Canada, from 1 April 1994 to 1 January 2012. Participants Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes. Main outcome measure Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index. Results Of 39 879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin. Conclusions In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.

ObjectivesTo evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV).DesignSystematic review and random-effects meta-analysis.MethodsMultiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias.Results19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6–9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients.ConclusionsIntravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen.PROSPERO registration numberCRD42015022041.