The Effect of HIV Treatment Interruption on Subsequent Immunological Response.

Recovery of CD4-positive T lymphocyte count after initiation of antiretroviral therapy (ART) has been thoroughly examined among people with human immunodeficiency virus infection. However, immunological response after restart of ART following care interruption is less well studied. We compared CD4 cell-count trends before disengagement from care and after ART reinitiation. Data were obtained from the East Africa International Epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration (2001-2011; n = 62,534). CD4 cell-count trends before disengagement, during disengagement, and after ART reinitiation were simultaneously estimated through a linear mixed model with 2 subject-specific knots placed at the times of disengagement and treatment reinitiation. We also estimated CD4 trends conditional on the baseline CD4 value. A total of 10,961 patients returned to care after disengagement from care, with the median gap in care being 2.7 (interquartile range, 2.1-5.4) months. Our model showed that CD4 cell-count increases after ART reinitiation were much slower than those before disengagement. Assuming that disengagement from care occurred 12 months after ART initiation and a 3-month treatment gap, CD4 counts measured at 3 years since ART initiation would be lower by 36.5 cells/µL than those obtained under no disengagement. Given that poorer CD4 restoration is associated with increased mortality/morbidity, specific interventions targeted at better retention in care are urgently required.

Issues with the expected information matrix of linear mixed models provided by popular statistical packages under missingness at random dropout.

Likelihood-based methods ignoring missingness at random (MAR) produce consistent estimates provided that the whole likelihood model is correct. However, the expected information matrix (EIM) depends on the missingness mechanism. It has been shown that calculating the EIM by considering the missing data pattern as fixed (naive EIM) is incorrect under MAR, but the observed information matrix (OIM) is valid under any MAR missingness mechanism. In longitudinal studies, linear mixed models (LMMs) are routinely applied, often without any reference to missingness. However, most popular statistical packages currently provide precision measures for the fixed effects by inverting only the corresponding submatrix of the OIM (naive OIM), which is effectively equivalent to the naive EIM. In this paper, we analytically derive the correct form of the EIM of LMMs under MAR dropout to compare its differences with the naive EIM, which clarifies why the naive EIM fails under MAR. The asymptotic coverage rate of the naive EIM is numerically calculated for two parameters (population slope and slope difference between two groups) under various dropout mechanisms. The naive EIM can severely underestimate the true variance, especially when the degree of MAR dropout is high. Similar trends emerge under misspecified covariance structure, where, even the full OIM may lead to incorrect inferences and sandwich/bootstrap estimators are generally required. Results from simulation studies and application to real data led to similar conclusions. In LMMs, the full OIM should be preferred to the naive EIM/OIM, though if misspecified covariance structure is suspected, robust estimators should be used.

The sphenoidal emissary foramina prevalence: a meta-analysis of 6,369 subjects.

PURPOSE: To estimate the prevalence of the sphenoidal emissary foramina (SEF), and the effect of possible moderators on it. METHODS: A systematic online literature search was conducted. The pooled prevalence with 95% confidence intervals was estimated. Outlier and influential analyses were performed. The presence of small-study effect and publication bias were evaluated. Moderator analyses were executed to investigate the effect of the specimens' continent of origin, type of study (dried skull or imaging), probing for the evaluation of SEF patency (conduction and instruments used), side dominance (bilateral or unilateral), morphometric data [SEF diameter, distances SEF-Foramen ovale (FO) and SEF-Foramen spinosum (FS)], and the methodology used for the morphometric measurements (caliper, DICOM Viewer, and image analysis software) on the estimated prevalence. RESULTS: In total, 6,460 subjects from 26 studies were included in the meta-analysis. The overall SEF prevalence was estimated as 38.1%. The heterogeneity was high and statistically significant. No indications of publication bias and small-study effect were identified. The conducted subgroup analyses did not yield statistically significant differences in the SEF prevalence between groups, except of the type of side dominance. Both results of the univariable and multivariable regression analyses showed the association of the unilateral dominance with a decrease in the reported SEF prevalence. CONCLUSION: The identification of more unilateral than bilateral foramina in a given cohort is associated with a decrease in the reported crude SEF prevalence. Laterality-specific estimates should be established for a precisive estimation of the emissary foramina prevalence.

HIV continuum of care: expanding scope beyond a cross-sectional view to include time analysis: a systematic review.

INTRODUCTION: The continuum of care (CoC) model has been used to describe the main pillars of HIV care. This study aims to systematically review methods and elucidate gaps in the CoC analyses, especially in terms of the timing of the progression through steps, recognized nowadays as a critical parameter for an effective response to the epidemic. METHODS: A PubMed and EMBASE databases search up to December 2019 resulted in 1918 articles, of which 209 were included in this review; 84 studies presented in major HIV conferences were also included. Studies that did not provide explicit definitions, modelling studies and those reporting only on metrics for subpopulations or factors affecting a CoC stage were excluded. Included articles reported results on 1 to 6 CoC stages. RESULTS: Percentage treated and virally suppressed was reported in 78%, percentage diagnosed and retained in care in 58%, percentage linked to care in 54% and PLHIV in 36% of the articles. Information for all stages was provided in 23 studies. Only 6 articles use novel CoC estimates: One presents a dynamic CoC based on multistate analysis techniques, two base their time-to-next-stage estimates on a risk estimation method based on the cumulative incidence function, weighted for confounding and censoring and three studies estimated the HIV infection time based on mathematical modelling. CONCLUSION: A limited number of studies provide elaborated time analyses of the CoC. Although time analyses lack the straightforward interpretation of the cross-sectional CoC, they provide valuable insights for the timely response to the HIV epidemic. A future goal would be to develop a model that retains the simplicity of the cross-sectional CoC but also incorporates timing between stages.

Misspecifying the covariance structure in a linear mixed model under MAR drop-out.

Misspecification of the covariance structure in a linear mixed model (LMM) can lead to biased population parameters' estimates under MAR drop-out. In our motivating example of modeling CD4 cell counts during untreated HIV infection, random intercept and slope LMMs are frequently used. In this article, we evaluate the performance of LMMs with specific covariance structures, in terms of bias in the fixed effects estimates, under specific MAR drop-out mechanisms, and adopt a Bayesian model comparison criterion to discriminate between the examined approaches in real-data applications. We analytically show that using a random intercept and slope structure when the true one is more complex can lead to seriously biased estimates, with the degree of bias depending on the magnitude of the MAR drop-out. Under misspecified covariance structure, we compare in terms of induced bias the approach of adding a fractional Brownian motion (BM) process on top of random intercepts and slopes with the approach of using splines for the random effects. In general, the performance of both approaches was satisfactory, with the BM model leading to smaller bias in most cases. A simulation study is carried out to evaluate the performance of the proposed Bayesian criterion in identifying the model with the correct covariance structure. Overall, the proposed method performs better than the AIC and BIC criteria under our specific simulation setting. The models under consideration are applied to real data from the CASCADE study; the most plausible model is identified by all examined criteria.

HIV-1 molecular transmission clusters in nine European countries and Canada: association with demographic and clinical factors.

BACKGROUND: Knowledge of HIV-1 molecular transmission clusters (MTCs) is important, especially in large-scale datasets, for designing prevention programmes and public health intervention strategies. We used a large-scale HIV-1 sequence dataset from nine European HIV cohorts and one Canadian, to identify MTCs and investigate factors associated with the probability of belonging to MTCs. METHODS: To identify MTCs, we applied maximum likelihood inferences on partial pol sequences from 8955 HIV-positive individuals linked to demographic and clinical data. MTCs were defined using two different criteria: clusters with bootstrap support >75% (phylogenetic confidence criterion) and clusters consisting of sequences from a specific region at a proportion of >75% (geographic criterion) compared to the total number of sequences within the network. Multivariable logistic regression analysis was used to assess factors associated with MTC clustering. RESULTS: Although 3700 (41%) sequences belonged to MTCs, proportions differed substantially by country and subtype, ranging from 7% among UK subtype C sequences to 63% among German subtype B sequences. The probability of belonging to an MTC was independently less likely for women than men (OR = 0.66; P < 0.001), older individuals (OR = 0.79 per 10-year increase in age; P < 0.001) and people of non-white ethnicity (OR = 0.44; P < 0.001 and OR = 0.70; P = 0.002 for black and 'other' versus white, respectively). It was also more likely among men who have sex with men (MSM) than other risk groups (OR = 0.62; P < 0.001 and OR = 0.69; P = 0.002 for people who inject drugs, and sex between men and women, respectively), subtype B (ORs 0.36-0.70 for A, C, CRF01 and CRF02 versus B; all P < 0.05), having a well-estimated date of seroconversion (OR = 1.44; P < 0.001), a later calendar year of sampling (ORs 2.01-2.61 for all post-2002 periods versus pre-2002; all P < 0.01), and being naïve to antiretroviral therapy at sampling (OR = 1.19; P = 0.010). CONCLUSIONS: A high proportion (>40%) of individuals belonged to MTCs. Notably, the HIV epidemic dispersal appears to be driven by subtype B viruses spread within MSM networks. Expansion of regional epidemics seems mainly associated with recent MTCs, rather than the growth of older, established ones. This information is important for designing prevention and public health intervention strategies.

Longitudinal and time-to-drop-out joint models can lead to seriously biased estimates when the drop-out mechanism is at random.

Missing data are common in longitudinal studies. Likelihood-based methods ignoring the missingness mechanism are unbiased provided missingness is at random (MAR); under not-at-random missingness (MNAR), joint modeling is commonly used, often as part of sensitivity analyses. In our motivating example of modeling CD4 count trajectories during untreated HIV infection, CD4 counts are mainly censored due to treatment initiation, with the nature of this mechanism remaining debatable. Here, we evaluate the bias in the disease progression marker's change over time (slope) of a specific class of joint models, termed shared-random-effects-models (SREMs), under MAR drop-out and propose an alternative SREM model. Our proposed model relates drop-out to both the observed marker's data and the corresponding random effects, in contrast to most SREMs, which assume that the marker and the drop-out processes are independent given the random effects. We analytically calculate the asymptotic bias in two SREMs under specific MAR drop-out mechanisms, showing that the bias in marker's slope increases as the drop-out probability increases. The performance of the proposed model, and other commonly used SREMs, is evaluated under specific MAR and MNAR scenarios through simulation studies. Under MAR, the proposed model yields nearly unbiased slope estimates, whereas the other SREMs yield seriously biased estimates. Under MNAR, the proposed model estimates are approximately unbiased, whereas those from the other SREMs are moderately to heavily biased, depending on the parameterization used. The examined models are also fitted to real data and results are compared/discussed in the light of our analytical and simulation-based findings.

Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection.

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/µl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of 'exhaustion' or 'immune checkpoint' markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches.

Potential adjustment methodology for missing data and reporting delay in the HIV Surveillance System, European Union/European Economic Area, 2015.

Accurate case-based surveillance data remain the key data source for estimating HIV burden and monitoring prevention efforts in Europe. We carried out a literature review and exploratory analysis of surveillance data regarding two crucial issues affecting European surveillance for HIV: missing data and reporting delay. Initial screening showed substantial variability of these data issues, both in time and across countries. In terms of missing data, the CD4+ cell count is the most problematic variable because of the high proportion of missing values. In 20 of 31 countries of the European Union/European Economic Area (EU/EEA), CD4+ counts are systematically missing for all or some years. One of the key challenges related to reporting delays is that countries undertake specific one-off actions in effort to capture previously unreported cases, and that these cases are subsequently reported with excessive delays. Slightly different underlying assumptions and effectively different models may be required for individual countries to adjust for missing data and reporting delays. However, using a similar methodology is recommended to foster harmonisation and to improve the accuracy and usability of HIV surveillance data at national and EU/EEA levels.

A Method to Estimate the Size and Characteristics of HIV-positive Populations Using an Individual-based Stochastic Simulation Model.

It is important not only to collect epidemiologic data on HIV but to also fully utilize such information to understand the epidemic over time and to help inform and monitor the impact of policies and interventions. We describe and apply a novel method to estimate the size and characteristics of HIV-positive populations. The method was applied to data on men who have sex with men living in the UK and to a pseudo dataset to assess performance for different data availability. The individual-based simulation model was calibrated using an approximate Bayesian computation-based approach. In 2013, 48,310 (90% plausibility range: 39,900-45,560) men who have sex with men were estimated to be living with HIV in the UK, of whom 10,400 (6,160-17,350) were undiagnosed. There were an estimated 3,210 (1,730-5,350) infections per year on average between 2010 and 2013. Sixty-two percent of the total HIV-positive population are thought to have viral load <500 copies/ml. In the pseudo-epidemic example, HIV estimates have narrower plausibility ranges and are closer to the true number, the greater the data availability to calibrate the model. We demonstrate that our method can be applied to settings with less data, however plausibility ranges for estimates will be wider to reflect greater uncertainty of the data used to fit the model.

Right-Sided Aortic Arch: A Computed Tomography Angiography Investigation, A Systematic Review with Meta-Analysis.

Background/Objectives: The right-sided aortic arch (RAA) is an uncommon variation of the aortic arch (AA), characterized by the aorta crossing over the right main bronchus. In the RAA, the descending aorta can be found on either the right or left side of the spine. The current study comprises a comprehensive retrospective computed tomography angiography (CTA) investigation into the prevalence of the RAA within the Greek population. Additionally, we will conduct a systematic review and meta-analysis to elucidate both common and rare morphological variants of the RAA. This research is significant as it sheds light on the prevalence and characteristics of the RAA in a specific population, providing valuable insights for clinical practice. Methods: Two hundred CTAs were meticulously investigated for the presence of a RAA. In addition, the PubMed, Google Scholar, and Scopus online databases were thoroughly searched for studies referring to the AA morphology. The R programming language and RStudio were used for the pooled prevalence meta-analysis, while several subgroup analyses were conducted. Results: Original study: A unique case of 200 CTAs (0.5%) was identified with an uncommon morphology. The following branches emanated from the RAA under the sequence: the right subclavian artery (RSA), the right common carotid artery (RCCA), the left common carotid artery (LCCA), and the left vertebral artery (LVA) in common origin with the aberrant left subclavian artery (ALSA). The ALSA originated from a diverticulum (of Kommerell) and followed a retroesophageal course. Systematic Review and Meta-Analysis: Sixty-two studies (72,187 total cases) met the inclusion criteria. The pooled prevalence of the RAA with a mirror-image morphology was estimated at 0.07%, and the RAA with an ALSA was estimated at <0.01%. Conclusions: AA anomalies, specifically the RAA, raise clinical interest due to their coexistence with developmental heart anomalies and possible interventional complications. Congenital heart anomalies, such as the Tetralogy of Fallot and patent foramen ovale, coexisted with RAA mirror-image morphology.

Prisoners' perceptions and satisfaction with telepsychiatry services in Greece.

Telepsychiatry is an effective tool to support and provide mental health services to prison inmates. In Greece, telepsychiatry was formally applied in two correctional facilities in 2018. The objective of this study was to compare inmates' perceptions and satisfaction with telepsychiatry versus face-to-face consultation. The sample consisted of 100 male inmates with a multicultural background and prior experience with both methods of services provision. The data were obtained through a Demographic Data Questionnaire, a Participant Satisfaction Questionnaire to assess satisfaction with face-to-face psychiatric services, and another Participant Satisfaction Questionnaire to assess satisfaction with telepsychiatric services. The results have shown a higher level of satisfaction with telepsychiatry compared to face-to-face care. Statistically significant improvements (all p-values <0.001) were noted in: waiting times, support for relapse prevention, follow up, quality of mental health care, quality of care in the management of psychiatric problems and related medication, behaviour of psychiatrists, duration of the assessment, sense of comfort, and confidentiality. Telepsychiatry has proved to be an acceptable way of approaching and supporting inmates in Greece, with most of the participants expressing high acceptance, satisfaction, and preference rates. Implications for additional research and further development of telepsychiatry are discussed.

Prisoners' Perceptions and Satisfaction with Telepsychiatry Services in Greece and the Effects of Its Use on the Coercion of Mental Healthcare.

BACKGROUND: Prisoners are often associated with mental health and substance use disorders. Coercive measures are widely used in prison settings. The objective of this study was to compare inmates' perceptions and satisfaction with telepsychiatry versus face-to-face consultation and the effects of telepsychiatry on the use of coercive measures. The sample consisted of 100 male inmates from various backgrounds who had experienced both approaches of services (face to face and telepsychiatry). METHOD: The data were obtained through an interview where the individuals completed a Demographic Data Questionnaire, a Participant Satisfaction Questionnaire to assess satisfaction with face-to-face psychiatric services, and a Participant Satisfaction Questionnaire to assess their satisfaction with services offered via telepsychiatry. Additionally, calculations of time spent waiting for a face-to-face psychiatric evaluation and time spent in handcuffs and in confined spaces were made before and after the introduction of telepsychiatry. RESULTS: Statistically significant improvements (all p-values < 0.001) were noted in waiting times, support for relapse prevention, follow up, quality of mental health care, quality of care in the management of psychiatric problems and related medication, behavior of psychiatrists, duration of the assessment, sense of comfort, and confidentiality. Telepsychiatry led to the elimination of time spent in handcuffs and in confined spaces (transport vehicles). CONCLUSION: According to the results of this study, telepsychiatry is an acceptable method of service delivery in correctional facilities and was associated with a reduction of coercive practices.

Estimation of Improvements in Mortality in Spectrum Among Adults With HIV Receiving Antiretroviral Therapy in High-Income Countries.

INTRODUCTION: Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates. METHODS: The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts. RESULTS: In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates. DISCUSSION: Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.

Care interruptions and mortality among adults in Europe and North America: a collaborative analysis of cohort studies.

OBJECTIVE: Interruptions in care of people with HIV (PWH) on antiretroviral therapy (ART) are associated with adverse outcomes, but most studies have relied on composite outcomes. We investigated whether mortality risk following care interruptions differed from mortality risk after first starting ART. DESIGN: Collaboration of 18 European and North American HIV observational cohort studies of adults with HIV starting ART between 2004-2019. METHODS: Care interruptions were defined as gaps in contact of ≥365 days, with a subsequent return to care (distinct from loss to follow-up), or ≥270 days and ≥545 days in sensitivity analyses. Follow-up time was allocated to no/pre-interruption or post-interruption follow-up groups. We used Cox regression to compare hazards of mortality between care interruption groups, adjusting for time-updated demographic and clinical characteristics and biomarkers upon ART initiation or re-initiation of care. RESULTS: Of 89197 PWH, 83.4% were male and median age at ART start was 39 years (interquartile range [IQR]: 31-48). 8654 PWH (9.7%) had ≥1 care interruption; 10913 episodes of follow-up following a care interruption were included. There were 6104 deaths in 536,334 person-years, a crude mortality rate of 11.4 (95%CI: 11.1-11.7) per 1000 person-years. The adjusted mortality hazard ratio (HR) for the post-interruption group was 1.72 (95%CI: 1.57-1.88) compared with the no/pre-interruption group. Results were robust to sensitivity analyses assuming ≥270-day (HR 1.49, 95%CI: 1.40-1.60) and ≥545-day (HR 1.67, 95%CI: 1.48-1.88) interruptions. CONCLUSIONS: Mortality was higher among PWH reinitiating care following an interruption, compared with when PWH initially start ART, indicating the importance of uninterrupted care.

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.

Impact of HIV-1 subtype on CD4 count at HIV seroconversion, rate of decline, and viral load set point in European seroconverter cohorts.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype may influence disease progression. We compared CD4 lymphocyte cell count levels at seroconversion, decline rates and viral load set point in individuals infected with different HIV-1 subtypes. METHODS: We used data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration, restricted to those infected since 1996, aged ≥15 years, and applied mixed effects models for CD4 cell count decline and median regression for viral load set point (mean level 6-24 months from seroconversion). RESULTS: The analysis included 3364 seroconverters with known HIV-1 subtypes. Compared with subtype B, CD4 at seroconversion was significantly higher for subtype CRF01 and lower for subtype C. Subsequent CD4 decline was significantly slower for subtypes A and CRF02 and marginally slower for subtype C compared with B. Mean CD4 loss at 2 years of seroconversion for white men exposed through sex between men, aged 30-39 years, having seroconverted since 2006, enrolled within 6 months of seroconversion, and without acute infection was 88, 142, 100, 130, 103, and 167 cells/µL for subtypes A, B, C, CRF01_AE, CRF02_AG, and G, respectively. In adjusted analysis, median viral load set point and time to clinical AIDS/death did not differ significantly by subtype, although all subtypes, except C, tended to have lower levels compared with B. CONCLUSIONS: HIV-1 subtype significantly influences seroconversion CD4 cell levels and decline rates but not viral load set point. These findings may be helpful to HIV-positive individuals and their attending physicians in understanding disease progression.

Validation of NoSAS score for the screening of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder (SBD) characterized by the repetitive collapse of the upper airway during sleep. The aim of the present study was to validate the Neck circumference, Obesity, Snoring, Age, Sex (NoSAS) score in a sample population and to compare its validity for OSA screening, with that of the Berlin questionnaire, STOP-BANG questionnaire and Epworth Sleepiness Scale (ESS). A retrospective analysis was conducted on individuals, aged 18 to 80 years, who reported symptoms indicating SBD and were examined with full-night polysomnography (PSG) at a sleep center. Demographics, anthropometric parameters, comorbidities, ESS, STOP-BANG questionnaire, Berlin questionnaire and PSG data were obtained from the recorded data of the patients. The NoSAS score was determined using the recorded data. A total of 347 participants were enrolled in the study. The NoSAS scores identified individuals with OSA, with an area under the curve (AUC) of 0.774. The NoSAS score performed significantly better than the Berlin questionnaire (AUC 0.617) and the ESS (AUC 0.642), and similarly to STOP-BANG (AUC 0.777) for OSA screening. Using a NoSAS score >7 to predict OSA, the sensitivity and specificity were 85.6 and 50%, respectively; using the STOP-BANG questionnaire, for a score >2, the values were 98.32 and 22% respectively; using the Berlin questionnaire for >1 positive categories, the values were 93.6 and 20%, and using the ESS, for a score >10, the values were 30.3% and 72%, respectively. On the whole, the present study demonstrates that the NoSAS score is a simple, efficient and easy method for screening OSA in the clinical setting. The NoSAS score performs significantly more efficiently than the Berlin questionnaire and ESS, and similarly to STOP-BANG questionnaire for OSA screening.

The impact of meteorological factors on involuntary admission in Attica, Greece.

Few studies in the literature have examined the effect of meteorological factors, especially temperature, on psychiatric hospitalization and even less on their association with involuntary admission. This study aimed to investigate the potential association of meteorological factors with the involuntary psychiatric hospitalization in the region of Attica, Greece. The research was conducted at the Psychiatric Hospital of Attica "Dafni". This was a retrospective time series study of 8 consecutive years of data (2010 to 2017) and included 6887 involuntarily hospitalized patients. Data on daily meteorological parameters were provided from the National Observatory of Athens. Statistical analysis was based on Poisson or negative binomial regression models with adjusted standard errors. Analyses were initially based on univariable models for each meteorological factor separately. All meteorological factors were taken into account through factor analysis and then, through cluster analysis, an objective grouping of days with similar weather type was performed. The resulting types of days were examined for their effect on the daily number of involuntary hospitalizations. Increases in maximum temperature, in average wind speed and in minimum atmospheric pressure values were associated with an increase in the average number of involuntary hospitalizations per day. Increase of the maximum temperature above 23 °C at lag 6 days before admission did not affect significantly the frequency of involuntary hospitalizations. Low temperature and average relative humidity above 60% levels had a protective effect. The predominant day type at lag 1 to 5 days before admission showed the strongest correlation with the daily number of involuntary hospitalizations. The cold season day type, with lower temperatures and a small diurnal temperature range, northerly winds of moderate speed, high atmospheric pressure and almost no precipitation, was associated with the lowest frequency of involuntary hospitalizations, whereas the warm season day type, with low daily temperature and small daily temperature range during the warm season, high values of relative humidity and daily precipitation, moderate wind speed/gust and atmospheric pressure, was associated with the highest. As climate change increases the frequency of extreme weather events, it is necessary to develop a different organizational and administrative culture of mental health services.