Spinal 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.
We 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.
In 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.
Among 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 .).
Background
Population‐based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most ...common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5‐year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population‐Based Cancer Registries (PBCRs) in India.
Methods
In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer‐II approach, respectively.
Results
The 5‐year age‐standardized relative survival (95% confidence interval CI) of patients with breast cancer was 66.4% (95% CI, 65.5%–67.3%). Mizoram (74.9%; 95% CI, 68.1%–80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%–74.9%), Kollam (71.5%; 95% CI, 69.2%–73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%–71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%–68.6%). The 5‐year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively.
Conclusions
The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.
In the largest analysis of population‐based cancer survival to date covering 17,331 female breast cancers from 11 cancer registries in India, disparities in survival indicate that comprehensive breast cancer control strategies should be implemented across the country.
In Israel, gates, fences, and walls encircle public spaces while guards scrutinize, inspect, and interrogate. With a population constantly aware of the possibility of suicide bombings, Israel is ...defined by its culture of security.Security and Suspicionis a closely drawn ethnographic study of the way Israeli Jews experience security in their everyday lives.
Observing security concerns through an anthropological lens, Juliana Ochs investigates the relationship between perceptions of danger and the political strategies of the state. Ochs argues that everyday security practices create exceptional states of civilian alertness that perpetuate-rather than mitigate-national fear and ongoing violence. In Israeli cities, customers entering gated urban cafés open their handbags for armed security guards and parents circumnavigate feared neighborhoods to deliver their children safely to school. Suspicious objects appear to be everywhere, as Israelis internalize the state's vigilance for signs of potential suicide bombers. Fear and suspicion not only permeate political rhetoric, writes Ochs, but also condition how people see, the way they move, and the way they relate to Palestinians. Ochs reveals that in Israel everyday practices of security-in the home, on commutes to work, or in cafés and restaurants-are as much a part of conflict as soldiers and military checkpoints.
Based on intensive fieldwork in Israel during the second intifada,Security and Suspicioncharts a new approach to issues of security while contributing to our appreciation of the subtle dynamics of the Israeli-Palestinian conflict. This book offers a way to understand why security propagates the very fears and suspicions it is supposed to reduce.
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