The effect of antiretroviral therapy on liver disease among adults with HIV and hepatitis C coinfection

In the era of antiretroviral therapy (ART), liver disease has emerged as an important cause of death among persons with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. The objective of this study was to estimate the burden of liver disease and evaluate determinants of liver fibrosis and necroinflammatory activity among HIV/HCV coinfected patients receiving ART. We studied 112 randomly selected and 98 referred HCV-infected patients undergoing care in the Johns Hopkins University HIV clinic. Liver disease was characterized clinically and histologically. Of the 210 individuals studied--64% of whom had received ART within 2 years of liver disease assessment--33% had no fibrosis (F0), and 26% had bridging fibrosis or cirrhosis (> or =F3). The median necroinflammatory activity score was 3 (range, 0-9 of 18). ART was not associated with fibrosis; however, significantly less hepatic necroinflammatory activity was observed among persons who had received highly active antiretroviral therapy longer (P = .02) and more effectively (defined by HIV RNA suppression; P < .01). Twelve percent of individuals had previous ART-associated liver enzyme elevations (grades 3-4), but liver fibrosis was not more severe if the liver enzyme elevation resolved. On the other hand, liver fibrosis was more severe in persons with persistent liver enzyme elevations (grades 1-4). In conclusion, despite widespread exposure to ART and documented instances of ART-related hepatitis, we found no evidence that ART caused serious histological liver disease. Recognition of bridging fibrosis and cirrhosis in some but not most patients underscores the importance of identifying and treating liver disease in HIV/HCV coinfected persons.     

De novo fragment assembly with short mate-paired reads: Does the read length matter?

Increasing read length is currently viewed as the crucial condition for fragment assembly with next-generation sequencing technologies. However, introducing mate-paired reads (separated by a gap of length, GapLength) opens a possibility to transform short mate-pairs into long mate-reads of length ≈ GapLength, and thus raises the question as to whether the read length (as opposed to GapLength) even matters. We describe a new tool, EULER-USR, for assembling mate-paired short reads and use it to analyze the question of whether the read length matters. We further complement the ongoing experimental efforts to maximize read length by a new computational approach for increasing the effective read length. While the common practice is to trim the error-prone tails of the reads, we present an approach that substitutes trimming with error correction using repeat graphs. An important and counterintuitive implication of this result is that one may extend sequencing reactions that degrade with length “past their prime” to where the error rate grows above what is normally acceptable for fragment assembly.     

Cardiac Index Declines During Long‐Term Left Ventricular Device Support

To investigate longitudinal trends in valvular and ventricular function with long‐term left ventricular assist device (LVAD) therapy, we analyzed hemodynamic and echocardiographic data of patients with at least 2 years of continuous LVAD support. All 130 patients who underwent HeartMate II implantation at our institution between 2005 and 2012 were reviewed. Twenty patients had hemodynamic and echocardiographic evaluations in both the early (0–6 months) and late (2–3 years) postoperative period. Patients on inotropic therapy or temporary mechanical support were excluded. The average times of early and late hemodynamic evaluations were 59 ± 41 days and 889 ± 160 days, respectively. Cardiac index (CI) declined by an average of 0.4 L/min/m² (P = 0.04) with concomitant increase in pulmonary capillary wedge pressure (PCWP; P = 0.02). The right atrial pressure to PCWP (RAP:PCWP) ratio decreased during LVAD support suggesting improvement in right ventricular function. While there was an increase in degree of aortic insufficiency (AI) at the late follow‐up period (P = 0.008), dichotomization by median decline in CI (?0.4 L/min/m²) indicated no difference in prevalence of AI among the groups. CI declined in patients with HeartMate II after 2 years of continuous support. An increase in preload and afterload was observed in those with the greatest decline in CI.     

The online case-crossover study is a novel approach to study triggers for recurrent disease flares

OBJECTIVES: To evaluate the feasibility of conducting an online case-crossover study of triggers for recurrent disease flares. METHODS: We conducted an online case-crossover study of triggers for recurrent flares using gout as a paradigm. We constructed a Web site and recruited individuals with history of gout via the Internet. We confirmed gout diagnosis by reviewing each subject's medical records. We collected via the Internet exposure information during the intercritical period using a scheduled Control-period Questionnaire, and prior to recurrent gout attacks using a Hazard-period Questionnaire. RESULTS: Over 10 months we recruited 197 subjects with a history of gout from 41 states and the District of Columbia. We obtained medical records from 172 subjects. All participants had experienced at least one recurrent attack and filled out required questionnaires. The median time between the date of an attack and the date of logging on to the Web site was 2 days. The incidence rate of recurrent gout attacks was 1.03 per person-year. Longer disease duration and presence of comorbidities appeared to increase the risk of recurrent flares. CONCLUSION: The results of this study demonstrate that a case-crossover study can be successfully conducted through the Internet. This approach has broad applicability to other diseases typified by recurrent attacks.     

Absence of linkage or association for osteoarthritis with the vitamin D receptor/type II collagen locus: the Framingham Osteoarthritis Study

OBJECTIVE: Studies have suggested that polymorphisms or mutations either in the COL2A1 or VDR gene. both on chromosome 12q, are associated with the occurrence of osteoarthritis (OA).We examined linkage and association between the VDR/COL2A1 locus and hand/knee OA in the Framingham Osteoarthritis Study (FOS). METHODS: Hand and knee joints were characterized radiographically in the FOS. An overall score for OA using the standard Kellgren and Lawrence grading scheme was determined, as well as scores for individual features of OA including osteophytes and joint space narrowing. For linkage studies, polymorphic microsatellite markers near the VDR-COL2AI genes on chromosome 12 were tested in a collection of 296 of the largest Framingham Heart Study families and the results analyzed using variance component linkage (SOLAR). For association studies, we characterized the allele status of a subset of subjects at the BsmI site of the VDR gene. RESULTS: Overall, we found no linkage or association between OA and the COL2A1/VDR locus for either knee or hand OA, nor did we find an association or linkage between COL2AI or VDR with any individual radiographic features of OA. CONCLUSION: Despite studies suggesting associations of OA with both COL2A1 and VDR loci, our results suggest that mutations at the COL2A1/VDR locus do not play an important role as a cause of common OA in the population at large.     

Latent tuberculosis infection among undergraduate medical students in Rio de Janeiro State, Brazil.

SETTING: Five medical schools in three cities with different tuberculosis (TB) incidence rates in Rio de Janeiro State, Brazil. OBJECTIVE: To estimate prevalence of and associated factors for latent tuberculosis infection (LTBI) among medical students. DESIGN: A cross-sectional survey was conducted among undergraduate students in pre-clinical, early and late clinical years from schools in cities with low (28/100,000), intermediate (63/100,000) and high (114/100,000) TB incidence rates. Information on socio-demographic profile, previous BCG vaccination, potential TB exposure, co-morbidity and use of respiratory protective masks was obtained. A tuberculin skin test (TST) was performed using the Mantoux technique by an experienced professional. A positive TST, defined as induration > or = 10 mm, was considered LTBI. RESULTS: LTBI prevalence was 6.9% (95%CI 5.4-8.6). In multivariate analysis, male sex (adjusted odds ratio [aOR] 1.8; 95% CI 1.1-3.0), late clinical years (aOR 1.9; 95% CI 1.01-3.5), intermediate TB incidence (aOR 4.3; 95% CI 1.3-14.6) and high TB incidence in the city of medical school (aOR 5.1; 95% CI 1.6-16.8) were significantly associated with LTBI. CONCLUSIONS: The higher prevalence of LTBI in late clinical years suggests that medical students are at increased risk for nosocomial Mycobacterium tuberculosis infection. The implementation of a TB control program may be necessary in medical schools, particularly in cities with higher TB incidence.     

Randomized clinical trials and recent patterns in the use of statins

BACKGROUND: Three landmark trials involving 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) were published between 1994 and 1996 (the Scandinavian Simvastatin Survival Study [4S], the West of Scotland Coronary Prevention Study, and the Cholesterol and Recurrent Events trial). These trials provided evidence that lipid-lowering therapy decreases cardiovascular events, including mortality. Whether these recent data caused a shift toward statin use has not been evaluated. METHODS: Data from the National Ambulatory Medical Care Survey in 1980, 1981, 1985, and 1989 through 1998 were used. We analyzed 5053 visits by patients taking lipid-lowering medications to office-based physicians selected by stratified random sampling. The main outcome measure was use of specific lipid-lowering medications, including statins. RESULTS: In 1980 resins and niacin were the most commonly used lipid-lowering medications. By 1985 rising use of fibrates caused reductions in niacin use and resin use. By 1989 statins replaced fibrates as the most heavily used medications. Statin use climbed continuously thereafter, accounting for 90% of visits by patients treated for hypercholesterolemia in 1998. In time series analyses, increases in overall statin use were temporally unrelated to the publication of clinical trials, although the 4S trial may have contributed to a shift from older statins to simvastatin. For patients receiving lipid-lowering therapy in 1993 to 1998, statin use was significantly more likely for female patients, white patients, and patients visiting cardiologists. CONCLUSIONS: Although the market for lipid-lowering medications is dominated by statins, the rise in statins predated the recent clinical trials supporting their use.