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Background. Understanding the predictors of mortality in individuals with human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfection can be useful in management of these patients. Methods. We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) for these analyses. Multivariate Cox-regression models were used to determine predictors of mortality. Results. Among 8,039 HIV infected veterans, 5251 (65.3%) had HCV coinfection. The all-cause mortality rate was 74.1 (70.4–77.9) per 1000 person-years (PY) among veterans with HIV/HCV coinfection and 39.8 (36.3–43.6) per 1000 PY for veterans with HIV monoinfection. The multivariable adjusted hazard ratio (95% confidence interval) of all-cause mortality for HCV infection was 1.58 (1.36–1.84). Positive predictors of mortality included decompensated liver disease (2.33 (1.98–2.74)), coronary artery disease (1.74 (1.32–2.28)), chronic kidney disease (1.62 (1.36–1.92)), and anemia (1.58 (1.31–1.89)). Factors associated with reduced mortality included HCV treatment (0.41 (0.27–0.63)) and higher CD4 count (0.90 (0.87–0.93) per 100 cells/μL higher count). Data were insufficient to make informative analyses of the role of HCV virologic response. Conclusion. HCV coinfection was associated with substantial increased risk of mortality among HIV infected veterans. HCV treatment was associated with significantly lower risk of mortality.

New Findings What is the central question of this study? We aimed to investigate the effects of the cyclo‐oxygenase (COX) inhibitor indomethacin on resistance vessel function in young and older adults and to test the hypothesis that indomethacin will attenuate forearm vascular conductance during reactive hyperaemia. What is the main finding and its importance? Older adults demonstrated an attenuated vasodilator response to ischaemia after COX inhibition compared with their younger counterparts. This suggests that older adults do not compensate for the vascular changes induced by an acute dose of indomethacin. Long‐term use of indomethacin may increase vascular resistance and reduce the response to acute haemodynamic stress in older adults. The risk for potential adverse cardiovascular consequences of COX inhibition should be considered. We have previously shown that non‐selective cyclo‐oxygenase inhibition, via indomethacin, unfavourably increased central blood pressure in older adults, with little effect in young adults. In addition, the vasoactive prostaglandins have been shown to contribute to both peripheral vasodilator responses and large artery function; however, there is little information available in older adults and conflicting reports in young adults on the extent to which resistance vessel function is influenced by indomethacin. Thus, we tested the hypothesis that cyclo‐oxygenase inhibition using indomethacin would attenuate forearm vascular conductance during reactive hyperaemia in older adults compared with young adults. Forearm blood flow responses to 5 min of forearm ischaemia were measured in 26 healthy adults (13 young, 25 ± 5 years old; and 13 older, 65 ± 6 years old), using venous occlusion plethysmography before and after indomethacin. Baseline forearm blood flow and vascular conductance were not different between groups during either trial, and there were no age‐related differences prior to cyclo‐oxygenase inhibition. Peak forearm vascular conductance and blood flow were similar between groups before indomethacin, but lower in older adults after indomethacin compared with young adults (27 ± 4 versus 41 ± 4 ml (100 ml)−1 min−1 (100 mmHg)−1, P = 0.02; and 23 ± 3 versus 33 ± 3 ml (100 ml)−1 min−1, P = 0.02, respectively). These results, in conjunction with our previous findings in large arteries, suggest that ageing alters the effect of cyclo‐oxygenase inhibition on vascular responses, and specifically, the resistance vessel responses underlying reactive hyperaemia.

Key Points Patients living in low SES neighborhoods had worse survival after DLBCL. Disparity was most striking in younger (non-Medicare) patients and after the introduction of rituximab.

Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9–100%), and the mean specificity was 98.0% (87.5–100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.