BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

These data indicate that for seriously ill hospitalized patients with advanced chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, recommended clinical prediction criteria are not effective in identifying a population with a survival prognosis of 6 months or less.

OBJECTIVE:To characterize the dying experience of patients with cancer over the last 6 months of life. STUDY DESIGN A retrospective analysis of the last 6 months of life among patients with colon cancer and nonsmall cell lung cancer enrolled in a prospective cohort study from

OBJECTIVE: To characterize chronic obstructive pulmonary disease (COPD) over patients' last 6 months of life. STUDY DESIGN: A retrospective analysis of a prospective cohort from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). SETTING:Hospitalization for exacerbation of COPD at five US teaching hospitals. PARTICIPANTS: COPD patients who died within 1 year (n = 416) among 1016 enrolled. METHODS: Interview and medical record data were organized into time windows beginning with death and ending 6 months earlier. OUTCOME MEASURES: Days in hospital, prognosis, illness severity, function, symptoms, patients' preferences, and impacts on families. RESULTS: One-year survival was 59%, 39% had 2 3 comorbidities, and 15 to 25% of the patients' last 6 months were in hospitals. Exacerbation etiologies included respiratory infection (47%) and cardiac problems (30%). Better quality of life predicted longer survival (ARR: 0.36; 95% CI, 0.19-0.87) as did heart failure etiology of exacerbation (ARR: 0.57; CI, 0.40,0.82). Estimates of survival by physicians and by prognostic model were well calibrated, although patients with the worst prognoses survived longer than predicted. Patients' estimates of prognosis were poorly calibrated. One-quarter of patients had serious pain throughout, and two-thirds had serious dyspnea. Patients' illnesses had a major impact on more than 25% of families. Patients' preferences for Do-Not-Resuscitate orders increased from 40% at 3 to 6 months before death to 77% within 1 month of From the 'Center to Improve Care of the Dying, The George Washington University, Washington, DC; tDivision of Allergy, Pulmonary, and Critical Care, death; their decisions not to use mechanical ventilation increased from 12 to 31%, and their preferences for resuscitation decreased from 52 to 23%. CONCLUSIONS: Patients with advanced COPD often die within 1 year and have substantial comorbidities and symptoms. Adequate description anchors improved care. J Am Geriatr SOC 48:S91-S100,2000. ~~~ hronic obstructive pulmonary disease (COPD) is the C fourth leading cause of death in the United States, with about 110,000 deaths annually.' COPD affects approximately 15 million people in the United state^,^,^ and its prevalence and mortality rates are in~reasing.~-~ COPD is slowly progressive and disabling, with quality of life and ability to perform activities of daily living often compromised for many years as a result of the severe dyspnea and deterioration of exercise ~a p a c i t y .~ For patients with advanced COPD, exacerbations are common and often lead to hospitalization, intubation, and mechanical ventilation. Hospitalization represents the largest component of the cost of care for COPD patient^.'^^ US medical care expenditures for COPD exceed 14.5 billion dollars annually." Despite the substantial health and economic burden of COPD on our society, little information in the literature details the experiences of patients dying with this illness.Clinical experience and research indi...