PLoS medicine
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Randomized Controlled Trial
Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study.
Sickle cell disease (SCD), a congenital hemolytic anemia that exacts terrible global morbidity and mortality, is driven by polymerization of mutated sickle hemoglobin (HbS) in red blood cells (RBCs). Fetal hemoglobin (HbF) interferes with this polymerization, but HbF is epigenetically silenced from infancy onward by DNA methyltransferase 1 (DNMT1). ⋯ Administration of oral THU-decitabine to patients with SCD was safe in this study and, by targeting DNMT1, upregulated HbF in RBCs. Further studies should investigate clinical benefits and potential harms not identified to date.
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Understanding the past-year prevalence of male-perpetrated intimate partner violence (IPV) and risk factors is essential for building evidence-based prevention and monitoring progress to Sustainable Development Goal (SDG) 5.2, but so far, population-based research on this remains very limited. The objective of this study is to compare the population prevalence rates of past-year male-perpetrated IPV and nonpartner rape from women's and men's reports across 4 countries in Asia and the Pacific. A further objective is to describe the risk factors associated with women's experience of past-year physical or sexual IPV from women's reports and factors driving women's past-year experience of partner violence. ⋯ Past-year IPV indicators based on women's reported experience that were developed to track SDG 5 are probably reasonably reliable but will not always give the same prevalence as may be reported by men. Report validity requires further research. Interviews with men to track past-year nonpartner rape perpetration are feasible and important. The findings suggest a range of factors are associated with past-year physical and/or sexual IPV exposure; of particular interest is the resilience pathway suggested by the structural model, which is highly amenable to intervention and explains why combining economic empowerment of women and gender empowerment/relationship skills training has been successful. This study provides additional rationale for scaling up violence prevention interventions that combine economic and gender empowerment/relationship skills building of women, as well as the value of investing in girls' education with a view to long-term violence reduction.
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Review Meta Analysis
Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.
Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin (GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients. ⋯ Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue.
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India was estimated to have the largest numbers of stillbirths globally in 2015, and the Indian government has adopted a target of <10 stillbirths per 1,000 births by 2030 through the India Newborn Action Plan (INAP). The objective of this study was to use verbal autopsy interviews to examine factors associated with stillbirth in the Indian state of Bihar and make recommendations for the INAP to better inform the setting of priorities and actions to reduce stillbirths. ⋯ To our knowledge, this study is among the few large, population-based assessments of stillbirths using verbal autopsy at the state level in India. These findings provide detailed insight into investigating the possible risk factors for stillbirths, as well as insight into the ground-level changes that are needed within the health system to design and implement effective preventive and intervention policies to reduce the burden of stillbirths. As most of the stillbirths are preventable with high-quality, evidence-based interventions delivered before and during pregnancy and during labour and childbirth, it is imperative that with INAP in place, India aspires to document stillbirths in a systematic and standardised manner to bridge the knowledge gap for appropriate actions to reduce stillbirths. We have made several recommendations based on our study that could further strengthen the INAP approach to improve the quality and quantity of stillbirth data to avoid this needless loss of lives.
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Multicenter Study Observational Study
Evaluation of novel computerized tomography scoring systems in human traumatic brain injury: An observational, multicenter study.
Traumatic brain injury (TBI) is a major contributor to morbidity and mortality. Computerized tomography (CT) scanning of the brain is essential for diagnostic screening of intracranial injuries in need of neurosurgical intervention, but may also provide information concerning patient prognosis and enable baseline risk stratification in clinical trials. Novel CT scoring systems have been developed to improve current prognostic models, including the Stockholm and Helsinki CT scores, but so far have not been extensively validated. The primary aim of this study was to evaluate the Stockholm and Helsinki CT scores for predicting functional outcome, in comparison with the Rotterdam CT score and Marshall CT classification. The secondary aims were to assess which individual components of the CT scores best predict outcome and what additional prognostic value the CT scoring systems contribute to a clinical prognostic model. ⋯ The Stockholm and Helsinki CT scores provide more information on the damage sustained, and give a more accurate outcome prediction, than earlier classification systems. The strong independent predictive value of tSAH may reflect an underrated component of TBI pathophysiology. A change to these newer CT scoring systems may be warranted.