Hepatitis C virus (HCV) genotype is an important criteria in determining duration of therapy and predictor of sustained virologic response (SVR) to pegylated interferon (PEG IFN) and ribavirin (RBV) ...therapy. Optimal duration of therapy for patients with HCV genotype 6 is not known. We conducted a multicenter, open‐label randomized controlled trial of patients with HCV genotype 6 at five gastroenterology clinics in the western U.S. Patients were stratified by viral load and histologic stage and assigned to receive PEG IFN‐α2a 180 μg subcutaneously weekly and weight‐based oral RBV 800 to 1,200 mg daily for 24 or 48 weeks. Primary outcome measurement was SVR rate by intention‐to‐treat analysis. From February 2005 to October 2007 a total of 60 patients (age 51 ± 10 years, 47% male, log HCVRNA 6.3 ± 1.1 IU/mL) were enrolled: 27 patients to 24 weeks and 33 patients to 48 weeks of therapy. In the 24‐week and 48‐week groups, 96% and 97% achieved early virologic response (P = 0.90); 89% versus 94% achieved end of therapy virologic response (P = 0.48). SVR was achieved in 70% versus 79% of patients assigned to 24 weeks versus 48 weeks (P = 0.45). Rapid virologic response (RVR) was a significant predictor of SVR in the 48‐week group and trending towards significance in the 24‐week group: 82% and 83% of those with RVR achieved SVR versus 33% and 29% for the 24‐week and 48‐week groups, respectively (P = 0.07 and P = 0.02). Conclusion: There was no significant difference in SVR rates in patients with HCV genotype 6 treated with PEG IFN‐α2a and RBV for 24 versus 48 weeks. (HEPATOLOGY 2010;52:1573‐1580)
Studies of the human microbiome share both technical and conceptual similarities with genome-wide association studies and genetic epidemiology. However, the microbiome has many features that differ ...from genomes, such as its temporal and spatial variability, highly distinct genetic architecture and person-to-person variation. Moreover, there are various potential mechanisms by which distinct aspects of the human microbiome can relate to health outcomes. Recent advances, including next-generation sequencing and the proliferation of multi-omic data types, have enabled the exploration of the mechanisms that connect microbial communities to human health. Here, we review the ways in which features of the microbiome at various body sites can influence health outcomes, and we describe emerging opportunities and future directions for advanced microbiome epidemiology.
Type 2 diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). However, it is unknown whether T2D duration or additional metabolic comorbidities further contribute to HCC risk. From the ...Nurses' Health Study (NHS), 120,826 women were enrolled in 1980, and from the Health Professionals Follow‐up Study (HPFS), 50,284 men were enrolled in 1986 and followed through 2012. Physician‐diagnosed T2D was ascertained at baseline and updated biennially. Cox proportional hazards regression models were used to calculate age‐ and multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HCC. Over 32 years of follow‐up (4,488,410 person‐years), we documented 112 cases of HCC (69 women, 43 men). T2D was associated with an increased HCC risk (multivariable HR, 4.59; 95% CI, 2.98‐7.07), as was an increasing T2D duration (Ptrend < 0.001). Compared to nondiabetics, the multivariable HRs for HCC were 2.96 (95% CI, 1.57‐5.60) for 0‐<2 years; 6.08 (95% CI, 2.96‐12.50) for 2‐<10 years; and 7.52 (95% CI, 3.88‐14.58) for ≥10 years. Increasing number of metabolic comorbidities (T2D, obesity, hypertension, and dyslipidemia) was associated with increased HCC risk (Ptrend < 0.001); compared to individuals without metabolic comorbidity, those with four metabolic comorbidities had an 8.1‐fold increased HCC risk (95% CI, 2.48‐26.7). In T2D, neither insulin use nor oral hypoglycemic use was significantly associated with HCC risk (HR, 2.04 95% CI, 0.69‐6.09 and HR, 1.45 95% CI, 0.69‐3.07, respectively). Conclusion: T2D is independently associated with increased risk for HCC in two prospective cohorts of U.S. men and women. This risk is enhanced with prolonged diabetes duration and with comorbid metabolic conditions, suggesting the importance of insulin resistance in the pathogenesis of HCC. (Hepatology 2018;67:1797‐1806)
Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B ...deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking.
In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile.
The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval CI, -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group.
Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).
The burnout syndrome is characterized by emotional exhaustion, depersonalization, and reduced personal achievement. Uncertainty exists about the prevalence of burnout among medical and surgical ...residents. Associations between burnout and gender, age, specialty, and geographical location of training are unclear. In this meta-analysis, we aimed to quantitatively summarize the global prevalence rates of burnout among residents, by specialty and its contributing factors. We searched PubMed, PsycINFO, Embase, and Web of Science to identify studies that examined the prevalence of burnout among residents from various specialties and countries. The primary outcome assessed was the aggregate prevalence of burnout among all residents. The random effects model was used to calculate the aggregate prevalence, and heterogeneity was assessed by I
statistic and Cochran's Q statistic. We also performed meta-regression and subgroup analysis. The aggregate prevalence of burnout was 51.0% (95% CI: 45.0-57.0%, I
= 97%) in 22,778 residents. Meta-regression found that the mean age (β = 0.34, 95% CI: 0.28-0.40,
< 0.001) and the proportion of males (β = 0.4, 95% CI = 0.10-0.69,
= 0.009) were significant moderators. Subgroup analysis by specialty showed that radiology (77.16%, 95% CI: 5.99-99.45), neurology (71.93%, 95% CI: 65.78-77.39), and general surgery (58.39%, 95% CI: 45.72-70.04) were the top three specialties with the highest prevalence of burnout. In contrast, psychiatry (42.05%, 95% CI: 33.09-51.58), oncology (38.36%, 95% CI: 32.69-44.37), and family medicine (35.97%, 95% CI: 13.89-66.18) had the lowest prevalence of burnout. Subgroup analysis also found that the prevalence of burnout in several Asian countries was 57.18% (95% CI: 45.8-67.85); in several European countries it was 27.72% (95% CI: 17.4-41.11) and in North America it was 51.64% (46.96-56.28). Our findings suggest a high prevalence of burnout among medical and surgical residents. Older and male residents suffered more than their respective counterparts.
Attributes and predictors of long COVID Sudre, Carole H; Murray, Benjamin; Varsavsky, Thomas ...
Nature medicine,
04/2021, Letnik:
27, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a ...protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app
. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.
Given the continued burden of COVID-19 worldwide, there is a high unmet need for data on the effect of social distancing and face mask use to mitigate the risk of COVID-19. We examined the ...association of community-level social distancing measures and individual face mask use with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported 'always' use of face mask was associated with a 62% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. Despite mass vaccination campaigns in many parts of the world, continued efforts at social distancing and face mask use remain critically important in reducing the spread of COVID-19.
A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans ...in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 and subsequent avian outbreaks in 2001 and 2002. These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.
Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown.
To assess the relationship between lipophilic or ...hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis.
Prospective propensity score (PS)-matched cohort.
Swedish registers, 2005 to 2013.
A PS-matched cohort of 16 668 adults (8334 who initiated statin use 6554 lipophilic and 1780 hydrophilic and 8334 nonusers) among 63 279 eligible adults.
Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs).
Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference RD, -4.8 percentage points 95% CI, -6.2 to -3.3 percentage points; adjusted subdistribution hazard ratio aHR, 0.56 CI, 0.41 to 0.79) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points CI, -2.6 to 0.4 percentage points; aHR, 0.95 CI, 0.86 to 1.08). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points CI, -7.6 to -4.2 percentage points; aHR, 0.41 CI, 0.32 to 0.61), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points CI, -9.6 to -6.2 percentage points) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points CI, -6.0 to -3.0 percentage points) statin users.
Lack of lipid, fibrosis, or HCC surveillance data.
In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC.
None.
Microbiome studies of inflammatory bowel diseases (IBD) have achieved a scale for meta-analysis of dysbioses among populations. To enable microbial community meta-analyses generally, we develop ...MMUPHin for normalization, statistical meta-analysis, and population structure discovery using microbial taxonomic and functional profiles. Applying it to ten IBD cohorts, we identify consistent associations, including novel taxa such as Acinetobacter and Turicibacter, and additional exposure and interaction effects. A single gradient of dysbiosis severity is favored over discrete types to summarize IBD microbiome population structure. These results provide a benchmark for characterization of IBD and a framework for meta-analysis of any microbial communities.
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