Abstract Background and Aims The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct acting antivirals (DAA) is unclear. Our aim was to examine the risk and ...determinants of HCC in patients cured with DAA. Methods We conducted a retrospective cohort study of HCV patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between 1/1/2015 and 12/31/2015. We calculated the annual incidence rates for HCC by SVR. We used Cox regression models to compare the risk of HCC in patients with vs . those without SVR and to identify factors associated with incident HCC among patients with SVR. We reviewed a sample of HCC patients for tumor size and stage at diagnosis. Results Among 22,500 patients treated with DAA (19,518 with SVR; 2,982 without SVR), the mean (SD) age was 61.6 (6.1) year, and 39.0% had cirrhosis. There were 271 new cases of HCC, including 183 in patients with SVR. Compared to patients without SVR, those with SVR had a significantly reduced risk of HCC (0.90 vs. 3.45 HCC/100 PY; adjusted hazard ratio HR, 0.28, 95% CI=0.22–0.36). Patients with cirrhosis had the highest annual incidence of HCC after SVR (1.82 vs. 0.34/100 PY in patients without cirrhosis; adjusted HR, 4.73. 95% CI, 3.34-6.68). Most (>44.8%) HCC were classified as stage I. Maximum size of the largest lesion was ≤5 cm in over 75% of cases. Conclusions Among patients treated with DAA, SVR was associated with a considerable reduction in the risk of HCC. We did not find any evidence to suggest that DAAs promote HCC. However, in patients with SVR, the absolute HCC risk remained high in patients with established cirrhosis. These patients should be considered for ongoing HCC surveillance.
To describe the history, clinical findings, and possible etiologies of ophthalmic findings discovered in 7 astronauts after long-duration space flight, and document vision changes in approximately ...300 additional astronauts.
Retrospective, observational examination of ophthalmic findings in 7 astronauts and analysis of postflight questionnaires regarding in-flight vision changes in approximately 300 additional astronauts.
Seven astronauts with ophthalmic anomalies upon return from long-duration space missions to the International Space Station and 300 additional astronauts who completed postflight questionnaires regarding in-flight vision changes.
Before and after long-duration space flight, all 7 subjects underwent complete eye examinations, including cycloplegic and/or manifest refraction and fundus photography. Six underwent postmission optical coherence tomography (OCT) and magnetic resonance imaging (MRI); 4 had lumbar punctures (LP). Approximately 300 astronauts were queried regarding visual changes during space missions.
Refractive change, fundus photograph examination, retina OCT, orbital MRI, LP opening pressures, and examination of visual acuity data.
After 6 months of space flight, 7 astronauts had ophthalmic findings, consisting of disc edema in 5, globe flattening in 5, choroidal folds in 5, cotton wool spots (CWS) in 3, nerve fiber layer thickening by OCT in 6, and decreased near vision in 6 astronauts. Five of 7 with near vision complaints had a hyperopic shift ≥+0.50 diopters (D) between pre/postmission spherical equivalent refraction in 1 or both eyes (range, +0.50 to +1.75 D). These 5 showed globe flattening on MRI. Lumbar punctures performed in the 4 with disc edema documented opening pressures of 22, 21, 28, and 28.5 cm H(2)O performed 60, 19, 12, and 57 days postmission, respectively. The 300 postflight questionnaires documented that approximately 29% and 60% of astronauts on short and long-duration missions, respectively, experienced a degradation in distant and near visual acuity. Some of these vision changes remain unresolved years after flight.
We hypothesize that the optic nerve and ocular changes we describe may result from cephalad fluid shifts brought about by prolonged microgravity exposure. The findings we report may represent parts of a spectrum of ocular and cerebral responses to extended microgravity exposure.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
A comprehensive classification system for preterm birth requires expanded gestational boundaries that recognize the early origins of preterm parturition and emphasize fetal maturity over fetal age. ...Exclusion of stillbirths, pregnancy terminations, and multifetal gestations prevents comprehensive consideration of the potential causes and presentations of preterm birth. Any step in parturition (cervical softening and ripening, decidual-membrane activation, and/or myometrial contractions) may initiate preterm parturition, and should be recorded for every preterm birth, as should the condition of the mother, fetus, newborn, and placenta, before a phenotype is assigned.
Summary Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric ...symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD. Methods We did a randomised, parallel group, double-blind, placebo-controlled trial of 20 mg memantine taken orally daily for 26 weeks in patients with FTD. Participants met Neary criteria for behavioural variant FTD (bvFTD) or semantic dementia and had characteristic brain atrophy. Use of acetylcholinesterase inhibitors was prohibited. Individuals were randomly assigned to receive either memantine or matched placebo tablets (1:1) in blocks of two and four patients. All patients and study personnel were masked to treatment assignment. Primary endpoints were the change in total NPI score and clinical global impression of change (CGIC) score after 26 weeks and were analysed by intention to treat. This study is registered with Clinicaltrials.gov , number NCT00545974. Findings Of 100 patients screened, 81 were randomly assigned to receive memantine (39 patients) or placebo (42 patients). Five (6%) patients discontinued, and 76 completed the 26-week treatment. Enrolment numbers were lower than planned because of many patients’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI −3·9 to 8·3, p=0·47) or CGIC (mean difference 0·0, −0·4 to 0·4, p=0·90) after 26 weeks of treatment. Memantine was generally well tolerated; however, patients in the memantine group had more frequent cognitive adverse events (six patients) than those in the placebo group (one). Interpretation Memantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD. Funding Forest Research Institute.
In 2009, the Global Alliance to Prevent Prematurity and Stillbirth Conference charged the authors to propose a new comprehensive, consistent, and uniform classification system for preterm birth. This ...first article reviews issues related to measurement of gestational age, clinical vs etiologic phenotypes, inclusion vs exclusion of multifetal and stillborn infants, and separation vs combination of pathways to preterm birth. The second article proposes answers to the questions raised here, and the third demonstrates how the proposed system might work in practice.
The preterm birth syndrome: a prototype phenotypic classification Villar, Jose, MD, MSc, MPH, FRCOG; Papageorghiou, Aris T., MBChB, MRCOG; Knight, Hannah E., MSc ...
American journal of obstetrics and gynecology,
02/2012, Letnik:
206, Številka:
2
Journal Article
Recenzirano
Preterm birth is a syndrome with many causes and phenotypes. We propose a classification that is based on clinical phenotypes that are defined by ≥1 characteristics of the mother, the fetus, the ...placenta, the signs of parturition, and the pathway to delivery. Risk factors and mode of delivery are not included. There are 5 components in a preterm birth phenotype: (1) maternal conditions that are present before presentation for delivery, (2) fetal conditions that are present before presentation for delivery, (3) placental pathologic conditions, (4) signs of the initiation of parturition, and (5) the pathway to delivery. This system does not force any preterm birth into a predefined phenotype and allows all relevant conditions to become part of the phenotype. Needed data can be collected from the medical records to classify every preterm birth. The classification system will improve understanding of the cause and improve surveillance across populations.
In recent years, translational research with various animal models has been helpful to answer basic questions about the effect of antenatal inflammation on maturation and development of the fetal ...lung and immune system. The fetal lung and immune systems are very plastic and their development can be conditioned and influenced by both endogenous and/or exogenous factors. Antenatal inflammation can induce pulmonary inflammation, leading to lung injury and remodeling in the fetal lung. Exposure to antenatal inflammation can induce interleukin-1α production, which enhances surfactant protein and lipid synthesis thereby promoting lung maturation. Interleukin-1α is therefore a candidate for the link between lung inflammation and lung maturation, preventing respiratory distress syndrome in preterm infants. Antenatal inflammation can, however, cause structural changes in the fetal lung and affect the expression of growth factors, such as transforming growth factor-beta, connective tissue growth factor, fibroblast growth factor-10, or bone morphogenetic protein-4, which are essential for branching morphogenesis. These alterations cause alveolar and microvascular simplification resembling the histology of bronchopulmonary dysplasia. Antenatal inflammation may also affect neonatal outcome by modulating the responsiveness of the immune system. Lipopolysaccharide-tolerance (endotoxin hyporesponsiveness/immunoparalysis), induced by exposure to inflammation in utero, may prevent fetal lung damage, but increases susceptibility to postnatal infections. Moreover, prenatal exposure to inflammation appears to be a predisposition for the development of adverse neonatal outcomes, like bronchopulmonary dysplasia, if the preterm infant is exposed to a second postnatal hit, such as mechanical ventilation oxygen exposure, infections, or steroids.
Abstract Objective Increases in postpartum hemorrhage have been reported from several countries. We assessed temporal trends in postpartum hemorrhage and severe postpartum hemorrhage in Canada ...between 2003 and 2010. Methods We carried out a population-based cohort study of all hospital deliveries in Canada (excluding Quebec) from 2003 to 2010 (n = 2 193 425), using data from the Canadian Institute for Health Information. Postpartum hemorrhage was defined as a blood loss of ≥ 500 mL following vaginal delivery or ≥ 1000 mL following Caesarean section, or as noted by the care provider. Severe postpartum hemorrhage was defined as postpartum hemorrhage plus blood transfusion, hysterectomy, or other procedures to control bleeding (including uterine suturing or ligation/embolization of pelvic arteries). Temporal trends were assessed using the chi-square test for trend, relative risks, and logistic regression. Results Postpartum hemorrhage increased by 22% (95% CI 20% to 25%) from 5.1% in 2003 to 6.2% in 2010 ( P < 0.001), driven by a 29% increase (95% CI 26% to 33%) in atonic postpartum hemorrhage (3.9% in 2003 vs. 5.0% in 2010, P < 0.001). Postpartum hemorrhage with blood transfusion increased from 36.7 to 50.4 per 10 000 deliveries ( P < 0.001), while postpartum hemorrhage with hysterectomy increased from 4.9 to 5.8 per 10 000 deliveries ( P < 0.01). Postpartum hemorrhage with uterine suturing, or ligation/embolization of pelvic arteries, increased from 4.1 to 10.7 per 10 000 deliveries ( P < 0.001). These increases occurred in most provinces and territories, and could not be explained by changes in maternal, fetal, and obstetric factors. Conclusion Rates of postpartum hemorrhage and severe postpartum hemorrhage continued to increase in Canada between 2003 and 2010.
Abstract Objectives Insomnia is a significant public health concern known to particularly impact women and the veteran population; however, rates of insomnia disorder among women veterans are not ...known. Method Women veterans who had received health care at VA Greater Los Angeles Healthcare System between 2008 and 2010 and resided within 25 miles of the facility were sent a postal survey assessing sleep, demographics, and other related patient characteristics. Results A total of 660 women (43.1% of potential responders) returned the postal survey and provided sufficient information for insomnia diagnosis. On average, women reported 6.2 hours of sleep per night. The prevalence of insomnia, determined according to diagnostic criteria from the International Classification of Sleep Disorders-2, was 52.3%. Women with insomnia reported more severely disturbed sleep, and more pain, menopausal symptoms, stress/worries, and nightmares compared with women without insomnia. There was a quadratic relationship between age and insomnia with women in their mid-40s, most likely to have insomnia. Conclusions This survey study found that insomnia symptoms were endorsed by more than one-half of the women veterans in this sample of VA users, highlighting the critical need for enhanced clinical identification and intervention. Further research is needed to establish national rates of insomnia among women veterans and to improve access to evidence-based treatment of insomnia disorder.
Objective The purpose of this study was to examine the association between labor induction and gestational age–specific severe maternal morbidity. Study Design Our study was restricted to women who ...delivered singletons at 37-42 weeks' gestation who had no pregnancy complications from 2003-2010 (n = 1,601,253) in Canada (excluding Quebec). Using a pregnancies-at-risk approach, the week-specific rates of specific morbidity after induction were contrasted with rates among ongoing pregnancies. Logistic regression was used to adjust for confounders. Results Induction increased the rate of postpartum hemorrhage that required blood transfusion at 38 weeks' gestation (adjusted rate ratio, 1.28; 95% confidence interval, 1.11–1.49) and 39 weeks' gestation (adjusted rate ratio, 1.21; 95% confidence interval, 1.06–1.38). Induction was also associated with higher rates of pueperal sepsis at 38 and 39 weeks' gestation and venous thromboembolism at 38 weeks' gestation. The absolute increase in morbidity rates was small; the number needed to harm was large (eg, 1270 for postpartum hemorrhage with blood transfusion at 38 weeks' gestation). Conclusion Among women without pregnancy complications, induction at earlier term is associated with higher rates of specific severe maternal morbidity, although absolute risks are low.
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