Search

Introduction: Flow cytometry (FCM) is widely used in the diagnosis of mature B‐cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B‐cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. Methods: Cases with a final diagnosis of DLBCL that were analysed by eight‐colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. Results: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B‐cell (GCB) and non‐GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine‐needle aspirates, or between samples from nodal compared to extranodal tissue. Conclusion: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight‐colour analysis, FCM fails to detect numerous cases of DLBCL. [ABSTRACT FROM AUTHOR]

Introduction: In 2015, the World Health Organization recommended that all HIV-infected individuals consider ART initiation as soon as possible after diagnosis. Sex differences in choice of initial ART regimen, indications for switching, time to switching and choice of second-line regimens have not been well described. The aims of this study were to describe first-line ART and CD4 count at ART initiation by sex, calendar year and region, and to analyse time to change or interruption in first-line ART, according to sex in each region. Methods: Participating cohorts included: Southern, East and West Africa (IeDEA-Africa), North America (NA-ACCORD), Caribbean, Central/South America (CCASAnet) and Asia-Pacific including Australia (IeDEA Asia-Pacific). The primary outcomes analysed for each region and according to sex were choice of initial ART, time to switching and time to discontinuation of the first-line regimen. Results and Discussion: The combined cohort data set comprised of 715,252 participants across seven regions from low- to high-income settings. The median CD4 count at treatment initiation was lower in men compared with women in nearly all regions and time periods. Women from North America and Southern Africa were more likely to switch ART compared to men (p < 0.001) with approximately 90% of women reporting a major change after 10 years in North America. Overall, after 8 years on ART, >50% of HIV- positive men and women from Southern Africa, East Africa, South and Central America remained on their original regimen. Men were more likely to have a treatment interruption compared with women in low- and middle-income countries from the Asia/Pacific region (p < 0.001) as were men from Southern Africa (p < 0.001). Greater than 75% of men and women did not report a treatment interruption after 10 years on ART from all regions except North America and Southern Africa. Conclusions: There are regional variations in the ART regimen commenced at baseline and rates of major change and treatment interruption according to sex. Some of this is likely to reflect changes in local and international antiretroviral guideline recommendations but other sex-specific factors such as pregnancy may contribute to these differences. Keywords: cohort studies; gender; treatment; women; sex; HIV, 1 | INTRODUCTION Over the past decade, HIV treatment guidelines have changed, with the CD[4.sup.+] count threshold for initiating antiretroviral therapy (ART) gradually increasing from less than 350 cells/[micro]L in [...]

Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study. Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders. Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25]). Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions. Keywords: Cardiovascular disease; gender; cardiovascular disease interventions; cohort studies; HIV; women; myocardial infarction; stroke, 1 | INTRODUCTION HIV-positive individuals are known to be at increased risk of cardiovascular disease (CVD) compared to the general population [1,2], partly due to an increased prevalence of some [...]

Introduction: Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretrovira regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries.Methods: The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring >0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements >400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed.Results: Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution.Conclusions: The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries.Keywords: ART; substitution; Asian countries; clinical failure; virological failure; effectiveness, 1 | INTRODUCTIONCombination antiretroviral treatments (cART) have been widely available in Asia since 2003 [1]. However, most Asian HIV clinics have limited resources and are able to prescribe regimens based [...]

Background Mendelian randomization (MR) studies are susceptible to metadata errors (e.g. incorrect specification of the effect allele column) and other analytical issues that can introduce substantial bias into analyses. We developed a quality control (QC) pipeline for the Fatty Acids in Cancer Mendelian Randomization Collaboration (FAMRC) that can be used to identify and correct for such errors. Methods We collated summary association statistics from fatty acid and cancer genome-wide association studies (GWAS) and subjected the collated data to a comprehensive QC pipeline. We identified metadata errors through comparison of study-specific statistics to external reference data sets (the National Human Genome Research Institute-European Bioinformatics Institute GWAS catalogue and 1000 genome super populations) and other analytical issues through comparison of reported to expected genetic effect sizes. Comparisons were based on three sets of genetic variants: (i) GWAS hits for fatty acids, (ii) GWAS hits for cancer and (iii) a 1000 genomes reference set. Results We collated summary data from 6 fatty acid and 54 cancer GWAS. Metadata errors and analytical issues with the potential to introduce substantial bias were identified in seven studies (11.6%). After resolving metadata errors and analytical issues, we created a data set of 219 842 genetic associations with 90 cancer types, generated in analyses of 566 665 cancer cases and 1 622 374 controls. Conclusions In this large MR collaboration, 11.6% of included studies were affected by a substantial metadata error or analytical issue. By increasing the integrity of collated summary data prior to their analysis, our protocol can be used to increase the reliability of downstream MR analyses. Our pipeline is available to other researchers via the CheckSumStats package (https://github.com/MRCIEU/CheckSumStats). [ABSTRACT FROM AUTHOR]