HMG-CoA reductase inhibitors (statins) use and risk of non-Hodgkin lymphoma in HIV-positive persons

Objective: Experimental studies suggested that HMG-CoA reductase inhibitors ('statins') may have antilymphoma properties. We investigated whether statin use is associated with reduced risk of non-Hodgkin lymphoma (NHL) in HIV-positive persons. Design: A nested case-control study was conducted among HIV-positive members of Kaiser Permanente California, a large managed care organization. Methods: Cases were incident HIVþ NHL diagnosed from 1996 to 2008. Controls were HIV-positive members without NHL matched 5 : 1 to cases by age, sex, race, index year and known duration of HIV infection. Data were collected from Kaiser Permanente's electronic medical records. Conditional logistic regression was used to examine the effect of statin use on HIV þ NHL risk, adjusting for potential confounders (matching factors, prior clinical AIDS diagnosis, antiretroviral use, baseline CD4 cell count, and history of selected co-morbidity) and use of nonstatin lipid-lowering therapy (LLT). Results: A total of 259 cases and 1295 controls were included. Eight percent of the cases and 14% of the controls had a history of statin use. Statin use was associated with lower risk of HIV þ NHL; hazard ratio and 95% confidence intervals for ever use, less than 12, and at least 12 months cumulative use was 0.55 (0.31-0.95), 0.64 (0.31-1.28), and 0.50 (0.23-1.10), respectively. P value for trend for duration of statin use was 0.08. No association between nonstatin LLT use and risk of NHL was observed

Differences in COVID-19 testing and adverse outcomes by race, ethnicity, sex, and health system setting in a large diverse US cohort

Background Racial/ethnic disparities during the first six months of the COVID-19 pandemic led to differences in COVID-19 testing and adverse outcomes. We examine differences in testing and adverse outcomes by race/ethnicity and sex across a geographically diverse and system-based COVID-19 cohort collaboration. Methods Observational study among adults (≥18 years) within six US cohorts from March 1, 2020 to August 31, 2020 using data from electronic health record and patient reporting. Race/ethnicity and sex as risk factors were primary exposures, with health system type (integrated health system, academic health system, or interval cohort) as secondary. Proportions measured SARS-CoV-2 testing and positivity; attributed hospitalization and death related to COVID-19. Relative risk ratios (RR) with 95% confidence intervals quantified associations between exposures and main outcomes. Results 5,958,908 patients were included. Hispanic patients had the highest proportions of SARS-CoV-2 testing (16%) and positivity (18%), while Asian/Pacific Islander patients had the lowest portions tested (11%) and White patients had the lowest positivity rates (5%). Men had a lower likelihood of testing (RR = 0.90 [0.89–0.90]) and a higher positivity risk (RR = 1.16 [1.14–1.18]) compared to women. Black patients were more likely to have COVID-19-related hospitalizations (RR = 1.36 [1.28–1.44]) and death (RR = 1.17 [1.03–1.32]) compared with White patients. Men were more likely to be hospitalized (RR = 1.30 [1.16–1.22]) or die (RR = 1.70 [1.53–1.89]) compared to women. These racial/ethnic and sex differences were reflected in both health system types. Conclusions This study supports evidence of disparities by race/ethnicity and sex during the COVID-19 pandemic that persisted even in healthcare settings with reduced barriers to accessing care. Further research is needed to understand and prevent the drivers that resulted in higher burdens of morbidity among certain Black patients and men

Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. METHODS: Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). RESULTS: Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). CONCLUSIONS: Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-Analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = \uc3\ua2 '0.24 to \uc3\ua2 '0.73; P < 1.49 \uc3\u97 10 \uc3\ua2 '4), and lower thickness in the precentral gyri bilaterally (d = \uc3\ua2 '0.34 to \uc3\ua2 '0.52; P < 4.31 \uc3\u97 10 \uc3\ua2 '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = \uc3\ua2 '1.73 to \uc3\ua2 '1.91, P < 1.4 \uc3\u97 10 \uc3\ua2 '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = \uc3\ua2 '0.36 to \uc3\ua2 '0.52; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = \uc3\ua2 '0.29 to \uc3\ua2 '0.54; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = \uc3\ua2 '0.27 to \uc3\ua2 '0.51; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < \uc3\ua2 '0.0018; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed

Mental and Physical Quality of Life by Age Groups in People Living With HIV.

Quality of life (QoL) is relevant to people living with HIV (PLWH) with increased life expectancy because of antiretroviral therapy. Our cross-sectional study examined associations between sociodemographic, HIV-related and psychological variables, and QoL, overall and by age. PLWH (n = 614) completed questionnaires at enrollment in an alcohol treatment study. QoL was assessed by the 12-item Short Form Survey, which includes physical and mental domains. Linear regression models evaluated the association of age and other factors with mental and physical QoL. PLWH younger than 50 years (n = 310) reported poorer mental QoL but better physical QoL compared to older PLWH (n = 304). Poorer mental QoL was associated with substance use, depression, and anxiety. Poorer physical QoL was associated with depression and history of injection drug use. We identified age-group differences in QoL for this primary care-based sample. Health care providers can use our findings to guide patient-centered care

Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer.

Understanding the effect of contraceptives on the development of precancerous lesions of the cervix and cervical cancer may provide information that is valuable to women in contraceptive decision-making. The purpose of this study was to evaluate the association between recent intrauterine device (IUD) use (by type) and cervical intraepithelial neoplasia 2, 3, adenocarcinoma in situ or cancer (CIN2+ or CIN3+). Case-control study of 17,559 women age 18-49 with incident CIN2+ cases and 5:1 age-matched, incidence-density selected controls (N=87,378) who were members of Kaiser Permanente Northern California Healthcare System from 1996 to 2014. Recent IUD use, within 18 months prior to index, was the exposure of interest. We identified 1,657 IUD users among the cases and 7,925 IUD users among controls. After adjusting for sexually transmitted infection testing, smoking, HPV vaccination, hormonal contraceptive use, parity, race and number of outpatient healthcare system visits, IUD use was associated with an increased rate of CIN2+ [rate ratio (RR) 1.12, 95% confidence interval (1.05-1.18), p&lt;0.001] but not CIN3+ [RR 1.02 (0.93-1.11), p=0.71]. Levonorgestrel-IUD use was associated with an increased rate of CIN2+ [RR 1.18 (1.08-1.30), p&lt;0.001] but not CIN3+ [RR 1.05 (0.91-1.21), p=0.48]. Copper-IUD use was not associated with CIN2+ [RR 0.88 (0.75-1.04), p=0.13] or CIN3+ [RR 0.81 (0.64-1.02), p=0.07]. Recent IUD use had variable weak associations with CIN2+ but was not associated with increased risk of CIN3+. Recent levonorgestrel-IUD use may be associated with CIN2, a lesion with a high rate of regression, but not CIN3, which is considered a true pre-cancerous lesion. The observed association between levonorgestrel-IUDs and CIN2+ was modest but warrants further investigation. It may have clinical importance for contraceptive counseling if this finding is shown to be consistent across other studies and other populations

Comparison of dementia incidence and prevalence between individuals with and without HIV infection in primary care from 2000 to 2016.

OBJECTIVE: To compare dementia incidence and prevalence after age 50 years by HIV status. DESIGN: Observational cohort, 2000-2016. METHODS: People with HIV (PWH) on antiretroviral therapy (ART) and demographically similar people without HIV (PWoH), all aged 50 years and older, were identified from Kaiser Permanente healthcare systems in Northern California, Southern California, and Mid-Atlantic States (Maryland, Virginia, Washington DC). Dementia diagnoses were obtained from electronic health records. Incidence and prevalence of dementia, overall and by time period (i.e. 2000-2002, 2003-2004, …, 2015-2016), were calculated using Poisson regression. Trends were examined using Joinpoint regression. Rate ratios were used to compare dementia by HIV status with adjustment for sociodemographics, substance use, and clinical factors. RESULTS: The study included 13 296 PWH and 155 354 PWoH (at baseline: for both, mean age = 54 years, 89% men; for PWH, 80% with HIV RNA &lt;200 copies/ml). From 2000 to 2016, overall incidence of dementia was higher among PWH [adjusted incidence rate ratio (aIRR) = 1.80, 95% confidence interval (CI) = 1.60-2.04]. Dementia incidence decreased among both PWH and PWoH (-8.0 and -3.1% per period, respectively) but remained higher among PWH in the most recent time period, 2015-2016 (aIRR = 1.58, 95% CI = 1.18-2.12). The overall prevalence of dementia from 2000 to 2016 was higher among PWH [adjusted prevalence ratio (aPR) = 1.86, 95% CI = 1.70-2.04] and was also higher among PWH in 2015-2016 (aPR = 1.75, 95% CI = 1.56-1.97). CONCLUSION: Reductions in dementia incidence are encouraging and may reflect ART improvement, but PWH are still more likely to have dementia than PWoH. Monitoring the burden of dementia among PWH is important as this population ages

Antiretroviral Therapy Adherence and Use of an Electronic Shared Medical Record Among People Living with HIV

Electronic shared medical records (SMR) are emerging healthcare technologies that allow patients to engage in their healthcare by communicating with providers, refilling prescriptions, scheduling appointments, and viewing portions of medical records. We conducted a pre-post cohort study of HIV-positive adults who used and did not use SMR in two integrated healthcare systems. We compared the difference in antiretroviral refill adherence between SMR users and age- and sex-frequency matched non-users from the 12-month period prior to SMR useto the 12-month period starting 6 months after initiation of SMR use. High adherence was maintained among SMR users (change = -0.11 %) but declined among non-users (change = -2.05 %; p = 0.003). Among SMR users, there was a steady improvement in adherence as monthly frequency of SMR use increased (p = 0.009). SMR use, particularly more frequent use, is associated with maintaining high adherence and non-use is associated with declines in adherence over time among patients with access to these online services