摘要 :
Background : Since the advent of combination antiretroviral therapy (cART), non-AIDS defining malignancies (NADM) have become increasingly important. We examined risk factors for NADM, including immunological, virological and soci...
展开
Background : Since the advent of combination antiretroviral therapy (cART), non-AIDS defining malignancies (NADM) have become increasingly important. We examined risk factors for NADM, including immunological, virological and socio-behavioral characteristics. Methods: We linked the Swiss HIV Cohort Study (SHCS) with cancer registries to identify incident cancers between 1996 and 2012. We analyzed four common NADM: anal, lung, prostate, and liver cancer. We calculated standardized incidence ratios (SIRs) and assessed the effect of time-updated CD4 and CD8 count, CD4/CD8 ratio, and HIV viral load (copies/ml) in Cox regression models. We lagged time-dependent variables for 12, 24, and 36 months and captured cumulative exposures using simple moving averages (SMA). In multivariable models, we also considered HIV transmission group, smoking, and chronic hepatitis B or C infection as potential predictors of NADM incidence. Results. Between 1996 and 2012, 563 HIV-infected individuals developed NADM, including 70 anal, 49 lung, 44 prostate, and 36 liver cancers. Compared with the general population, the SHCS exhibited higher rates of anal (SIR 76.1, 95% Confidence interval (CI) 60.2-96.2), lung (SIR 1.98, 1.50-2.62), and liver cancer (SIR 7.28, 5.25-10.1) but similar rates of prostate cancer (SIR 1.03, 0.76-1.38). Anal cancer was associated with low CD4 cell count, high CD8 cell count, men who have sex with men, and smoking. For lung cancer, the CD8 cell count was the only significant predictor identified among the immunological and virological factors. CD4 cell count, and chronic hepatitis B and C infection were predictive of liver cancer incidence. We found no evidence of any of the immunological factors being associated with prostate cancer. Conclusions: The importance of immunodeficiency (indexed by CD4 count) and immune senescence (indexed by CD8 count) differs across NADM. Immunodeficiency was an important risk factor for anal and liver cancer whereas immune senescence was associated with lung cancer and anal cancer.
收起
摘要 :
Motivated by the need to smooth and to summarize multiple simultaneous time series arising from networks of environmental monitors, we propose a hierarchical wavelet model for which estimation of hyperparameters can be performed b...
展开
Motivated by the need to smooth and to summarize multiple simultaneous time series arising from networks of environmental monitors, we propose a hierarchical wavelet model for which estimation of hyperparameters can be performed by marginal maximum likelihood. The result is an empirical Bayes thresholding procedure whose results improve on those of wavethresh in terms of mean square error. We apply the approach to data from the SensorScope environmental modelling system, and briefly discuss issues that arise concerning variance estimation in this context.
收起
摘要 :
Microarrays have become an important tool for studying the molecular basis of complex disease traits and fundamental biological processes. A common purpose of microarray experiments is the detection of genes that are differentiall...
展开
Microarrays have become an important tool for studying the molecular basis of complex disease traits and fundamental biological processes. A common purpose of microarray experiments is the detection of genes that are differentially expressed under two conditions, such as treatment versus control or wild type versus knockout. We introduce a Laplace mixture model as a long-tailed alternative to the normal distribution when identifying differentially expressed genes in microarray experiments, and provide an extension to asymmetric over- or underexpression. This model permits greater flexibility than models in current use as it has the potential, at least with sufficient data, to accommodate both whole genome and restricted coverage arrays. We also propose likelihood approaches to hyperparameter estimation which are equally applicable in the Normal mixture case. The Laplace model appears to give some improvement in fit to data, though simulation studies show that our method performs similarly to several other statistical approaches to the problem of identification of differential expression.
收起
摘要 :
Background. Decision makers often need to assess the real-world effectiveness of new drugs prelaunch, when phase II/III randomized controlled trials (RCTs) but no other data are available. Objective. To develop a method to predict...
展开
Background. Decision makers often need to assess the real-world effectiveness of new drugs prelaunch, when phase II/III randomized controlled trials (RCTs) but no other data are available. Objective. To develop a method to predict drug effectiveness prelaunch and to apply it in a case study in rheumatoid arthritis (RA). Methods. The approach 1) identifies a market-approved treatment ( S ) currently used in a target population similar to that of the new drug ( N ); 2) quantifies the impact of treatment, prognostic factors, and effect modifiers on clinical outcome; 3) determines the characteristics of patients likely to receive N in routine care; and 4) predicts treatment outcome in simulated patients with these characteristics. Sources of evidence include expert opinion, RCTs, and observational studies. The framework relies on generalized linear models. Results. The case study assessed the effectiveness of tocilizumab (TCZ), a biologic disease-modifying antirheumatic drug (DMARD), combined with conventional DMARDs, compared to conventional DMARDs alone. Rituximab (RTX) combined with conventional DMARDs was identified as treatment S. Individual participant data from 2 RCTs and 2 national registries were analyzed. The model predicted the 6-month changes in the Disease Activity Score 28 (DAS28) accurately: the mean change was -2.101 (standard deviation [SD] = 1.494) in the simulated patients receiving TCZ and conventional DMARDs compared to -1.873 (SD = 1.220) in retrospectively assessed observational data. It was -0.792 (SD = 1.499) in registry patients treated with conventional DMARDs. Conclusion. The approach performed well in the RA case study, but further work is required to better define its strengths and limitations.
收起
摘要 :
Background. Old age is an important risk factor for developing cancer, but few data exist on this association in people with human immunodeficiency virus (HIV, PWH) in sub-Saharan Africa.Methods. The South African HIV Cancer Match...
展开
Background. Old age is an important risk factor for developing cancer, but few data exist on this association in people with human immunodeficiency virus (HIV, PWH) in sub-Saharan Africa.Methods. The South African HIV Cancer Match study is a nationwide cohort of PWH based on a linkage between HIV-related laboratory records from the National Health Laboratory Service and cancer diagnoses from the National Cancer Registry for 2004-2014. We included PWH who had HIV-related tests on separate days. Using natural splines, we modeled cancer incidence rates as a function of age.Results. We included 5 222 827 PWH with 29 580 incident cancer diagnoses—most commonly cervical cancer (n = 7418), Kaposi sarcoma (n = 6380), and breast cancer (n = 2748). In young PWH, the incidence rates for infection-related cancers were substantially higher than for infection-unrelated cancers. At age 40 years, the most frequent cancer was cervical cancer in female and Kaposi sarcoma in male PWH. Thereafter, the rates of infection-unrelated cancers increased steeply, particularly among male PWH, where prostate cancer became the most frequent cancer type at older age. Whereas Kaposi sarcoma rates peaked at 34 years (101/100 000 person-years) in male PWH, cervical cancer remained the most frequent cancer among older female PWH.Conclusions. Infection-related cancers are common in PWH in South Africa, but rates of infection-unrelated cancers overtook those of infection-related cancers after age 54 years in the overall study population. As PWH in South Africa live longer, prevention and early detection of infection-unrelated cancers becomes increasingly important. Meanwhile, control strategies for infection-related cancers, especially cervical cancer, remain essential.
收起
摘要 :
Background Mental disorders can adversely affect HIV treatment outcomes and survival. Data are scarce on premature deaths in people with mental disorders in HIV-positive populations, particularly in low-income and middle-income co...
展开
Background Mental disorders can adversely affect HIV treatment outcomes and survival. Data are scarce on premature deaths in people with mental disorders in HIV-positive populations, particularly in low-income and middle-income countries. In this study, we quantified excess mortality associated with mental disorders in HIV-positive people in South Africa, adjusting for HIV treatment outcomes. Methods For this cohort study, we analysed routinely collected data on HIV-positive adults receiving antiretroviral therapy (ART) in Cape Town, South Africa between Jan 1, 2004, to Dec 31, 2017. Data from three ART programmes were linked with routine medical records on mental health treatment from Jan 1, 2010, to Dec 31, 2017, and mortality surveillance data from the South African National Population Register up to Dec 31, 2017. People living with HIV aged 15 years or older who initiated ART at a programme site were eligible for analysis. We followed up patients from ART initiation or Jan 1, 2010, whichever occurred later, to transfer, death, or Dec 31, 2017. Patients were considered as having a history of mental illness if they had ever received psychiatric medication or been hospitalised for a mental disorder. We calculated adjusted hazard ratios (aHRs) with 95% CIs for associations between history of mental illness, mortality, and HIV treatment outcomes (retention in care with viral load suppression [VLS; viral load 180 days late for a clinic visit at closure of the database]) using Cox proportional hazard regression and multistate models. Results 58?664 patients were followed up for a median of 4·3 years (IQR 2·1–6·4), 2927 (5·0%) of whom had a history of mental illness. After adjustment for age, sex, treatment programme, and year of ART initiation, history of mental illness was associated with increased risk of mortality from all causes (aHR 2·98 [95% CI 2·69–3·30]), natural causes (3·00 [2·69–3·36]), and unnatural causes (2·10 [1·27–3·49]), compared with no history of mental illness. Risk of all-cause mortality in people with a history of mental illness remained increased in multivariable analysis adjusted for age, sex, treatment programme, year of ART initiation, CD4 count and WHO clinical stage at ART initiation, retention in HIV care with or without VLS, and LTFU (2·73 [2·46–3·02]). In our multistate model, adjusted for age, sex, year of ART initiation, cumulative time with NVL, and WHO clinical stage and CD4 cell count at ART initiation, rates of excess all-cause mortality in people with history of mental illness were greatest in patients retained in care with VLS (aHR 3·43 [95% CI 2·83–4·15]), followed by patients retained in care with NVL (2·74 [2·32–3·24]), and smallest in those LTFU (2·12 [1·78–2·53]). History of mental illness was also associated with increased risk of HIV viral rebound (transitioning from VLS to NVL; 1·50 [1·32–1·69]) and LTFU in people with VLS (1·19 [1·06–1·34]). Interpretation Mental illness was associated with substantial excess mortality in HIV-positive adults in Cape Town. Excess mortality among people with a history of mental illness occurred independently of HIV treatment success. Interventions to reduce excess mortality should address the complex physical and mental health-care needs of people living with HIV and mental illness. Funding National Institutes of Health, Swiss National Science Foundation, South African Medical Research Council.
收起
摘要 :
ObjectiveTo compare cancer treatment and all-cause mortality between HIV-positive and HIV-negative cervical cancer patients in South Africa.MethodsWe assessed cancer treatment and all-cause mortality in HIV-positive and HIV-negati...
展开
ObjectiveTo compare cancer treatment and all-cause mortality between HIV-positive and HIV-negative cervical cancer patients in South Africa.MethodsWe assessed cancer treatment and all-cause mortality in HIV-positive and HIV-negative cervical cancer patients who received cancer treatment within 180?days of diagnosis using reimbursement claims data from a private medical insurance scheme in South Africa between 01/2011 and 07/2020. We assessed treatment provision using logistic regression and factors associated with all-cause mortality using Cox regression. We assigned missing values for histology and ethnicity using multiple imputation.ResultsOf 483 included women, 136 (28?%) were HIV-positive at cancer diagnosis (median age: 45.7?years), and 347 (72?%) were HIV-negative (median age: 54.1?years). Among 285 patients with available ICD-O-3 morphology claims codes, the proportion with cervical adenocarcinoma was substantially lower in HIV-positive (4?%) than in HIV-negative patients (26?%). Most HIV-positive patients (67?%) were on antiretroviral therapy at cancer diagnosis. HIV-positive patients were more likely to receive radiotherapy (adjusted odds ratio [aOR] 1.90, 95?% confidence interval [CI] 1.05–3.45) or chemotherapy (aOR 2.02, 95?%CI 0.92–4.43) and less likely to undergo surgery (aOR 0.53, 95?%CI 0.31–0.90) than HIV-negative patients. HIV-positive patients were at a higher risk of death from all causes than HIV-negative patients (adjusted hazard ratio 1.52, 95?%CI 1.06–2.19). Other factors associated with higher all-cause mortality included age?>?60?years and metastases at diagnosis.ConclusionsHIV-positive cervical cancer patients in South Africa had higher all-cause mortality than HIV-negative patients which could be explained by differences in tumour progression, clinical care, and HIV-specific mortality.
收起
摘要 :
Introduction In many countries, mortality due to suicide is higher among people living with HIV than in the general population. We aimed to analyse trends in suicide mortality before and after the introduction of triple combinatio...
展开
Introduction In many countries, mortality due to suicide is higher among people living with HIV than in the general population. We aimed to analyse trends in suicide mortality before and after the introduction of triple combination antiretroviral therapy (cART), and to identify risk factors associated with death from suicide in Switzerland. Methods We analysed data from the Swiss HIV Cohort Study from the pre‐cART (1988‐1995), earlier cART (1996‐2008) and later cART (2009‐2017) eras. We used multivariable Cox regression to assess risk factors for death due to suicide in the ART era and computed standardized mortality ratios (SMRs) to compare mortality rates due to suicide among persons living with HIV with the general population living in Switzerland, using data from the Swiss National Cohort. Results and Discussion We included 20,136 persons living with HIV, of whom 204 (1.0%) died by suicide. In men, SMRs for suicide declined from 12.9 (95% CI 10.4‐16.0) in the pre‐cART era to 2.4 (95% CI 1.2‐5.1) in the earlier cART and 3.1 (95% CI 2.3‐4.3) in the later cART era. In women, the corresponding ratios declined from 14.2 (95% CI 7.9‐25.7) to 10.2 (3.8‐27.1) and to 3.3 (95% CI 1.5‐7.4). Factors associated with death due to suicide included gender (adjusted hazard ratio 0.58 (95% CI 0.38‐0.87) comparing women with men), nationality (1.95 (95% CI 1.34‐2.83) comparing Swiss with other), Centers for Disease Control and Prevention clinical stage (0.33 (95% CI 0.24‐0.46) comparing stage A with C), transmission group (2.64 (95% CI 1.71‐4.09) for injection drug use and 2.10 (95% CI 1.36‐3.24) for sex between men compared to other), and mental health (2.32 (95% CI 1.71‐3.14) for a history of psychiatric treatment vs. no history). There was no association with age. Conclusions Suicide rates have decreased substantially among people living with HIV in the last three decades but have remained about three times higher than in the general population since the introduction of cART. Continued emphasis on suicide prevention among men and women living with HIV is important.
收起
原文获取