Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America.

BACKGROUND: Cardiovascular disease and non-AIDS malignancies have become major causes of death among HIV-infected individuals. The relative impact of lifestyle and HIV-related factors are debated. METHODS: We estimated associations of smoking with mortality more than 1 year after antiretroviral therapy (ART) initiation among HIV-infected individuals enrolled in European and North American cohorts. IDUs were excluded. Causes of death were assigned using standardized procedures. We used abridged life tables to estimate life expectancies. Life-years lost to HIV were estimated by comparison with the French background population. RESULTS: Among 17 995 HIV-infected individuals followed for 79 760 person-years, the proportion of smokers was 60%. The mortality rate ratio (MRR) comparing smokers with nonsmokers was 1.94 [95% confidence interval (95% CI) 1.56-2.41]. The MRRs comparing current and previous smokers with never smokers were 1.70 (95% CI 1.23-2.34) and 0.92 (95% CI 0.64-1.34), respectively. Smokers had substantially higher mortality from cardiovascular disease, non-AIDS malignancies than nonsmokers [MRR 6.28 (95% CI 2.19-18.0) and 2.67 (95% CI 1.60-4.46), respectively]. Among 35-year-old HIV-infected men, the loss of life-years associated with smoking and HIV was 7.9 (95% CI 7.1-8.7) and 5.9 (95% CI 4.9-6.9), respectively. The life expectancy of virally suppressed, never-smokers was 43.5 years (95% CI 41.7-45.3), compared with 44.4 years among 35-year-old men in the background population. Excess MRRs/1000 person-years associated with smoking increased from 0.6 (95% CI -1.3 to 2.6) at age 35 to 43.6 (95% CI 37.9-49.3) at age at least 65 years. CONCLUSION: Well treated HIV-infected individuals may lose more life years through smoking than through HIV. Excess mortality associated with smoking increases markedly with age. Therefore, increases in smoking-related mortality can be expected as the treated HIV-infected population ages. Interventions for smoking cessation should be prioritized

Telephone conversation impairs sustained visual attention via a central bottleneck

Recent research has shown that holding telephone conversations disrupts one's driving ability. We asked whether this effect could be attributed to a visual attention impairment. In Experiment 1, participants conversed on a telephone or listened to a narrative while engaged in multiple object tracking (MOT), a task requiring sustained visual attention. We found that MOT was disrupted in the telephone conversation condition, relative to single-task MOT performance, but that listening to a narrative had no effect. In Experiment 2, we asked which component of conversation might be interfering with MOT performance. We replicated the conversation and single-task conditions of Experiment 1 and added two conditions in which participants heard a sequence of words over a telephone. In the shadowing condition, participants simply repeated each word in the sequence. In the generation condition, participants were asked to generate a new word based on each word in the sequence. Word generation interfered with MOT performance, but shadowing did not. The data indicate that telephone conversation disrupts attention at a central stage, the act of generating verbal stimuli, rather than at a peripheral stage, such as listening or speaking

Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants

Purpose: Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are neurotropic human alphaherpesviruses endemic worldwide. Upon primary infection, both viruses establish lifelong latency in neurons and reactivate intermittently to cause a variety of mild to severe diseases. Acute retinal necrosis (ARN) is a rare, sight-threatening eye disease induced by ocular VZV or HSV infection. The virus and host factors involved in ARN pathogenesis remain incompletely described. We hypothesize an underlying genetic defect in at least part of ARN cases. Methods: We collected blood from 17 patients with HSV-or VZV-induced ARN, isolated DNA and performed Whole Exome Sequencing by Illumina followed by analysis in Varseq with criteria of CADD score &gt; 15 and frequency in GnomAD &lt; 0.1% combined with biological filters. Gene modifications relative to healthy control genomes were filtered according to high quality and read-depth, low frequency, high deleteriousness predictions and biological relevance. Results: We identified a total of 50 potentially disease-causing genetic variants, including missense, frameshift and splice site variants and on in-frame deletion in 16 of the 17 patients. The vast majority of these genes are involved in innate immunity, followed by adaptive immunity, autophagy, and apoptosis; in several instances variants within a given gene or pathway was identified in several patients.Discussion: We propose that the identified variants may contribute to insufficient viral control and increased necrosis ocular disease presentation in the patients and serve as a knowledge base and starting point for the development of improved diagnostic, prophylactic, and therapeutic applications.</p

Development and Validation of a Risk Score for Febrile Neutropenia After Chemotherapy in Patients With Cancer: The FENCE Score

Background: Febrile neutropenia (FN) after chemotherapy causes a high burden of morbidity and mortality. We aimed to develop and validate a risk score to predict FN in the first cycle of chemotherapy. Methods: We included patients with solid cancers and diffuse large B-cell lymphomas at Rigshospitalet, University of Copenhagen, 2010-2016. Predictors of FN were analyzed using Poisson regression and random split-sampling. Results: Among 6294 patients in the derivation cohort, 360 developed FN. Female sex, older age, cancer type, disease stage, low albumin, elevated bilirubin, low creatinine clearance, infection before chemotherapy, and number of and type of chemotherapy drugs predicted FN. Compared with those at low risk (n = 2520, 40.0%), the incidence rate ratio of developing FN was 4.8 (95% confidence interval [CI] = 2.9 to 8.1), 8.7 (95% CI = 5.3 to 14.1) and 24.0 (95% CI = 15.2 to 38.0) in the intermediate (n = 1294, 20.6%), high (n = 1249, 19.8%) and very high (n = 1231, 19.6%) risk groups, respectively, corresponding to a number needed to treat with granulocyte colony-stimulating factors to avoid one FN event in the first cycle of 284, 60, 34 and 14. The discriminatory ability (Harrell's C-statistic = 0.80, 95% CI = 0.78 to 0.82) was similar in the validation cohort (n = 3163) (0.79, 95% CI = 0.75 to 0.82). Conclusion: We developed and internally validated a risk score for FN in the first cycle of chemotherapy. The FENCE score is available online and provides good differentiation of risk groups

Incidence Rates and Risk Factors of Clostridioides difficile Infection in Solid Organ and Hematopoietic Stem Cell Transplant Recipients

BACKGROUND: Transplant recipients are an immunologically vulnerable patient group and are at elevated risk of Clostridioides difficile infection (CDI) compared with other hospitalized populations. However, risk factors for CDI post-transplant are not fully understood. // METHODS: Adults undergoing solid organ (SOT) and hematopoietic stem cell transplant (HSCT) from January 2010 to February 2017 at Rigshospitalet, University of Copenhagen, Denmark, were retrospectively included. Using nationwide data capture of all CDI cases, the incidence and risk factors of CDI were assessed. // RESULTS: A total of 1687 patients underwent SOT or HSCT (1114 and 573, respectively), with a median follow-up time (interquartile range) of 1.95 (0.52–4.11) years. CDI was diagnosed in 15% (164) and 20% (114) of the SOT and HSCT recipients, respectively. CDI rates were highest in the 30 days post-transplant for both SOT and HSCT (adjusted incidence rate ratio [aIRR], 6.64; 95% confidence interval [CI], 4.37–10.10; and aIRR, 2.85; 95% CI, 1.83–4.43, respectively, compared with 31–180 days). For SOT recipients, pretransplant CDI and liver and lung transplant were associated with a higher risk of CDI in the first 30 days post-transplant, whereas age and liver transplant were risk factors in the later period. Among HSCT recipients, myeloablative conditioning and a higher Charlson Comorbidity Index were associated with a higher risk of CDI in the early period but not in the late period. // CONCLUSIONS: Using nationwide data, we show a high incidence of CDI among transplant recipients. Importantly, we also find that risk factors can vary relative to time post-transplant

Impact of Plasmodium falciparum infection on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon

BACKGROUND: Improving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies. METHODS: A prospective observational study over a two-year period to assess the burden of anaemia and its relationship to Plasmodium falciparum infection and age was conducted in 8,195 febrile Gabonese children. RESULTS: The proportion of children with anaemia was 83.6% (n = 6830), higher in children between the ages of six and 23 months. Those under three years old were more likely to develop moderate to severe anaemia (68%). The prevalence of malaria was 42.7% and P. falciparum infection was more frequent in children aged 36-47 months (54.5%). The proportion of anaemic children increased with parasite density (p 60%), but was unrelated to P. falciparum parasitaemia. CONCLUSION: Malaria is one of the main risk factors for childhood anaemia which represents a public health problem in Gabon. The risk of severe malarial anaemia increases up the age of three years. Efforts to improve strategies for controlling anaemia and malaria are needed

Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark

BACKGROUND: Characteristics and care of intensive care unit (ICU) patients with COVID‐19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID‐19 admitted to Danish ICUs in the first wave with those admitted later. METHODS: Among all Danish ICU patients with COVID‐19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. RESULTS: Among all hospitalised patients with COVID‐19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID‐19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. CONCLUSIONS: After the first wave of COVID‐19 in Denmark, a lower proportion of hospitalised patients with COVID‐19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level