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Protein electrophoresis was carried out on 102,000 samples from the patients of a district general hospital over 10 years, and a monoclonal protein was detected in 730 cases; of these, 114 could be classified as B cell malignancies and 261 as monoclonal gammopathy of undefined significance (MGUS). The various clinical and laboratory features of monoclonal gammopathy were examined with respect to distinguishing the malignant conditions from MGUS at first presentation. [ABSTRACT FROM PUBLISHER]

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency.

Preterm birth (PTB) is the leading cause of infant mortality globally. Research has focused on developing predictive models for PTB without prioritizing cost-effective interventions. Physical activity and sleep present unique opportunities for interventions in low- and middle-income populations (LMICs). However, objective measurement of physical activity and sleep remains challenging and self-reported metrics suffer from low-resolution and accuracy. In this study, we use physical activity data collected using a wearable device comprising over 181,944 h of data across N = 1083 patients. Using a new state-of-the art deep learning time-series classification architecture, we develop a 'clock' of healthy dynamics during pregnancy by using gestational age (GA) as a surrogate for progression of pregnancy. We also develop novel interpretability algorithms that integrate unsupervised clustering, model error analysis, feature attribution, and automated actigraphy analysis, allowing for model interpretation with respect to sleep, activity, and clinical variables. Our model performs significantly better than 7 other machine learning and AI methods for modeling the progression of pregnancy. We found that deviations from a normal 'clock' of physical activity and sleep changes during pregnancy are strongly associated with pregnancy outcomes. When our model underestimates GA, there are 0.52 fewer preterm births than expected (P = 1.01e - 67, permutation test) and when our model overestimates GA, there are 1.44 times (P = 2.82e - 39, permutation test) more preterm births than expected. Model error is negatively correlated with interdaily stability (P = 0.043, Spearman's), indicating that our model assigns a more advanced GA when an individual's daily rhythms are less precise. Supporting this, our model attributes higher importance to sleep periods in predicting higher-than-actual GA, relative to lower-than-actual GA (P = 1.01e - 21, Mann-Whitney U). Combining prediction and interpretability allows us to signal when activity behaviors alter the likelihood of preterm birth and advocates for the development of clinical decision support through passive monitoring and exercise habit and sleep recommendations, which can be easily implemented in LMICs., (© 2023. The Author(s).)

Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 presynaptic proteins revealed near-complete separation between primates and mice involving synaptic pruning, cellular energy, lipid metabolism, and neurotransmission. In addition, our analysis revealed a strong overlap between the presynaptic composition of human and macaque in the cerebral cortex and neostriatum. Our unique approach illuminates species- and region-specific variation in presynapse molecular composition., (© 2023. Springer Nature Limited.)

(1) Background: to retrospectively evaluate safety and efficacy of combined microwave ablation (MWA) and bilateral expandable titanium SpineJack (SJ) implants followed by vertebroplasty (VP) for the treatment of painful thoracolumbar pathological vertebral compression fracture. (2) Methods: from July 2017 to October 2022, twenty-eight patients (13 women and 15 men; mean age 68 ± 11 years) with a history of primary neoplasm and thirty-six painful vertebral metastases with vertebral compression fracture underwent combined MWA and bilateral expandable titanium SpineJack implants with vertebroplasty. We analyzed safety through complications rate, and efficacy through vertebral height restoration and pain decrease, evaluated using a visual analogue scale (VAS), and Functional Mobility Scale (FMS), and local tumor control. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI at 6 months after the procedure. (3) Results: Technical success rate was 100%. No procedure-related major complications or death occurred. Vertebral height restoration was observed in 22 levels (58%), with a mean anterior height restoration of 2.6 mm ± 0.6 and a mean middle height restoration of 4.4 mm ± 0.6 ( p < 0.001). Mean VAS score of pain evaluation on the day before treatment was 6.3 ± 1.5 (range 4-9). At the 6-month evaluation, the median VAS score for pain was 0.4 ± 0.6 (range 0-2) with a mean reduction of 93.65% (6.8 ± 0.7 vs. 0.4 ± 0.6; p < 0.000) compared with baseline evaluation. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI was performed at 6 months after the procedure, showing no local recurrence, implant displacement, or new fractures in the treated site. (4) Conclusions: combined microwave ablation and bilateral expandable titanium SpineJack implants with vertebroplasty is a safe and effective procedure for the treatment of pathological compressive vertebral fractures. The vertebral stabilization achieved early and persistent pain relief, increasing patient mobility, improving recovery of walking capacity, and providing local tumor control.

Preterm birth (PTB) is the leading cause of death in children under five, yet comprehensive studies are hindered by its multiple complex etiologies. Epidemiological associations between PTB and maternal characteristics have been previously described. This work used multiomic profiling and multivariate modeling to investigate the biological signatures of these characteristics. Maternal covariates were collected during pregnancy from 13,841 pregnant women across five sites. Plasma samples from 231 participants were analyzed to generate proteomic, metabolomic, and lipidomic datasets. Machine learning models showed robust performance for the prediction of PTB (AUROC = 0.70), time-to-delivery ( r = 0.65), maternal age ( r = 0.59), gravidity ( r = 0.56), and BMI ( r = 0.81). Time-to-delivery biological correlates included fetal-associated proteins (e.g., ALPP, AFP, and PGF) and immune proteins (e.g., PD-L1, CCL28, and LIFR). Maternal age negatively correlated with collagen COL9A1, gravidity with endothelial NOS and inflammatory chemokine CXCL13, and BMI with leptin and structural protein FABP4. These results provide an integrated view of epidemiological factors associated with PTB and identify biological signatures of clinical covariates affecting this disease.

Psychosocial and stress-related factors (PSFs), defined as internal or external stimuli that induce biological changes, are potentially modifiable factors and accessible targets for interventions that are associated with adverse pregnancy outcomes (APOs). Although individual APOs have been shown to be connected to PSFs, they are biologically interconnected, relatively infrequent, and therefore challenging to model. In this context, multi-task machine learning (MML) is an ideal tool for exploring the interconnectedness of APOs on the one hand and building on joint combinatorial outcomes to increase predictive power on the other hand. Additionally, by integrating single cell immunological profiling of underlying biological processes, the effects of stress-based therapeutics may be measurable, facilitating the development of precision medicine approaches., Objectives: The primary objectives were to jointly model multiple APOs and their connection to stress early in pregnancy, and to explore the underlying biology to guide development of accessible and measurable interventions., Materials and Methods: In a prospective cohort study, PSFs were assessed during the first trimester with an extensive self-filled questionnaire for 200 women. We used MML to simultaneously model, and predict APOs (severe preeclampsia, superimposed preeclampsia, gestational diabetes and early gestational age) as well as several risk factors (BMI, diabetes, hypertension) for these patients based on PSFs. Strongly interrelated stressors were categorized to identify potential therapeutic targets. Furthermore, for a subset of 14 women, we modeled the connection of PSFs to the maternal immune system to APOs by building corresponding ML models based on an extensive single cell immune dataset generated by mass cytometry time of flight (CyTOF)., Results: Jointly modeling APOs in a MML setting significantly increased modeling capabilities and yielded a highly predictive integrated model of APOs underscoring their interconnectedness. Most APOs were associated with mental health, life stress, and perceived health risks. Biologically, stressors were associated with specific immune characteristics revolving around CD4/CD8 T cells. Immune characteristics predicted based on stress were in turn found to be associated with APOs., Conclusions: Elucidating connections among stress, multiple APOs simultaneously, and immune characteristics has the potential to facilitate the implementation of ML-based, individualized, integrative models of pregnancy in clinical decision making. The modifiable nature of stressors may enable the development of accessible interventions, with success tracked through immune characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Becker, Dai, Chang, Feyaerts, Stelzer, Zhang, Berson, Saarunya, De Francesco, Espinosa, Kim, Marić, Mataraso, Payrovnaziri, Phongpreecha, Ravindra, Shome, Tan, Thuraiappah, Xue, Mayo, Quaintance, Laborde, King, Dhabhar, Gotlib, Wong, Angst, Shaw, Stevenson, Gaudilliere and Aghaeepour.)

Preeclampsia is a complex disease of pregnancy whose physiopathology remains unclear. We developed machine-learning models for early prediction of preeclampsia (first 16 weeks of pregnancy) and over gestation by analyzing six omics datasets from a longitudinal cohort of pregnant women. For early pregnancy, a prediction model using nine urine metabolites had the highest accuracy and was validated on an independent cohort (area under the receiver-operating characteristic curve [AUC] = 0.88, 95% confidence interval [CI] [0.76, 0.99] cross-validated; AUC = 0.83, 95% CI [0.62,1] validated). Univariate analysis demonstrated statistical significance of identified metabolites. An integrated multiomics model further improved accuracy (AUC = 0.94). Several biological pathways were identified including tryptophan, caffeine, and arachidonic acid metabolisms. Integration with immune cytometry data suggested novel associations between immune and proteomic dynamics. While further validation in a larger population is necessary, these encouraging results can serve as a basis for a simple, early diagnostic test for preeclampsia., Competing Interests: S.R.Q. is a founder, consultant, and shareholder of Mirvie. M.N.M. is a shareholder of Mirvie. D.A.R. is a shareholder of Blue Willow Biologics, Cantata Bio, Evelo Biosciences, Karius, Proderm IQ, and Second Genome. D.A.R. is an advisor to Cantata Bio and Visby Medical. K.G.S. is paid advisor of Mission Biocapital and Infinant Health; equity holder and paid advisor of Avexegen; and equity holder of mProbe. M.P.S. is a co-founder and scientific advisor of Personalis, SensOmics, Qbio, January AI, Fodsel, Filtricine, Protos, RTHM, Iollo, Marble Therapeutics, and Mirvie, and a scientific advisor of Genapsys, Jupiter, Neuvivo, Swaza, and Mitrix., (© 2022 The Authors.)

Background: Radiofrequency ablation (RFA) and cementoplasty, individually and in concert, has been adopted as palliative interventional strategies to reduce pain caused by bone metastases and prevent skeletal related events. We aim to evaluate the feasibility and safety of a steerable RFA device with an articulating bipolar extensible electrode for the treatment of extraspinal bone metastases. Methods: All data were retrospectively reviewed. All the ablation procedures were performed using a steerable RFA device (STAR, Merit Medical Systems, Inc., South Jordan, UT, USA). The pain was assessed with a VAS score before treatment and at 1-week and 3-, 6-, and 12-month follow-up. The Functional Mobility Scale (FMS) was recorded preoperatively and 1 month after the treatment through a four-point scale (4, bedridden; 3, use of wheelchair; 2, limited painful ambulation; 1, normal ambulation). Technical success was defined as successful intraoperative ablation and cementoplasty without major complications. Results: A statistically significant reduction of the median VAS score before treatment and 1 week after RFA and cementoplasty was observed (p < 0.001). A total of 6/7 patients who used a wheelchair reported normal ambulation 1 month after treatment. All patients with limited painful ambulation reported normal ambulation after the RFA and cementoplasty (p = 0.003). Technical success was achieved in all the combined procedures. Two cement leakages were reported. No local recurrences were observed after 1 year. Conclusions: The combined treatment of RFA with a steerable device and cementoplasty is a safe, feasible, and promising clinical option for the management of painful bone metastases, challenging for morphology and location, resulting in an improvement of the quality of life of patients.

Whereas prematurity is a major cause of neonatal mortality, morbidity, and lifelong impairment, the degree of prematurity is usually defined by the gestational age (GA) at delivery rather than by neonatal morbidity. Here we propose a multi-task deep neural network model that simultaneously predicts twelve neonatal morbidities, as the basis for a new data-driven approach to define prematurity. Maternal demographics, medical history, obstetrical complications, and prenatal fetal findings were obtained from linked birth certificates and maternal/infant hospitalization records for 11,594,786 livebirths in California from 1991 to 2012. Overall, our model outperformed traditional models to assess prematurity which are based on GA and/or birthweight (area under the precision-recall curve was 0.326 for our model, 0.229 for GA, and 0.156 for small for GA). These findings highlight the potential of using machine learning techniques to predict multiple prematurity phenotypes and inform clinical decisions to prevent, diagnose and treat neonatal morbidities., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Cerebrospinal fluid (CSF) neurofilament light protein (NfL) is a marker of central nervous system neuro-axonal injury. A novel, ultra-sensitive assay can determine plasma NfL. In untreated people-with-HIV (PWH), CSF and plasma NfL are strongly correlated. We aimed to assess this correlation in PWH on suppressive antiretroviral treatment (ART) and lifestyle-similar HIV-negative individuals enrolled into the COmorBidity in Relation to AIDS (COBRA) study. Differences in paired CSF (sandwich ELISA, UmanDiagnostics) and plasma (Simoa digital immunoassay, Quanterix™) NfL between PWH and HIV-negative participants were tested using Wilcoxon's test; associations were assessed using Pearson's correlation. CSF and plasma NfL, standardised to Z-scores, were included as dependent variables in linear regression models to identify factors independently associated with values in PWH and HIV-negative participants. Overall, 132 PWH (all with plasma HIV RNA < 50 copies/mL) and 79 HIV-negative participants were included. Neither CSF (median 570 vs 568 pg/mL, p = 0.37) nor plasma (median 10.7 vs 9.9 pg/mL, p = 0.15) NfL differed significantly between PWH and HIV-negative participants, respectively. CSF and plasma NfL correlated moderately, with no significant difference by HIV status (PWH: rho = 0.52; HIV-negative participants: rho = 0.47, p (interaction) = 0.63). In multivariable regression analysis, higher CSF NfL Z-score was statistically significantly associated with older age and higher CSF protein, and higher plasma NfL Z-score with older age, higher serum creatinine and lower bodyweight. In conclusion, in PWH on ART, the correlation between CSF and plasma NfL is moderate and similar to that observed in lifestyle-similar HIV-negative individuals. Consideration of renal function and bodyweight may be required when utilising plasma NfL., (© 2021. The Author(s).)

Aims: The purpose of this study was to assess the effectiveness of a navigational radiofrequency ablation device with concurrent vertebral augmentation in the treatment of posterior vertebral body metastatic lesions, which are technically difficult to access. Primary outcomes of the study were evaluation of pain palliation and radiologic assessment of local tumor control., Materials and Methods: Thirty-five patients with 41 vertebral spinal metastases involving the posterior vertebral body underwent computed tomography-guided percutaneous targeted radiofrequency ablation, with a navigational radiofrequency ablation device, associated with vertebral augmentation. Twenty-one patients (60%) had 1 or 2 metastatic lesions (Group A) and fourteen (40%) patients had multiple (>2) vertebral lesions (Group B). Changes in pain severity were evaluated by visual analog scale (VAS). Metastatic lesions were evaluated in terms of radiological local control., Results: The procedure was technically successful in all the treated vertebrae. Among the symptomatic patients, the mean VAS score dropped from 5.7 (95% CI 4.9-6.5) before tRFA and to 0.9 (95% CI 0.4-1.3) after tRFA ( p < 0.001). The mean decrease in VAS score between baseline and one week follow up was 4.8 (95% CI 4.2-5.4). VAS decrease over time between one week and one year following radiofrequency ablation was similar, suggesting that pain relief was immediate and durable. Neither patients with 1-2 vertebral metastases, nor those with multiple lesions, showed radiological signs of local progression or recurrence of the tumor in the index vertebrae during a median follow up of 19 months (4-46 months) and 10 months (4-37 months), respectively., Conclusion: Treatment of spinal metastases with a navigational radiofrequency ablation device and vertebral augmentation can be used to obtain local tumor control with immediate and durable pain relief, providing effective treatment in the multimodality management of difficult-to-reach spinal metastases.

Background: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI)., Methods: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4 + count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART., Results: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (p adj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (p adj = 0.048 and p adj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals., Conclusions: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size., Funding: This work was supported by ZonMw (09120011910035) and FP7 Health (305522)., Competing Interests: AP, JV, NK, FW, Md, DD, MB, CS, AW, JP, PR, BB No competing interests declared, (© 2021, Pasternak et al.)

Objectives: To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH)., Methods: Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders., Results: Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p<0.01)], independently of ABC concentrations. Associations of ABC PK parameters with global and domain z-scores were non-significant after adjustment for confounders and 3TC concentrations (all p's>0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores., Conclusions: Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance., Competing Interests: F.P. has received grants from Gilead, ViiV and Janssen and personal fees from Gilead, ViiV and MSD. C.S. has received funding from Gilead Sciences, ViiV Healthcare, and Janssen-Cilag for membership of data safety and monitoring boards, advisory boards, and speaker panels and preparation of educational materials. A.W. has received honoraria or research grants from VIiV Healthcare, Gilead Sciences, BMS, Merck and Co. and Janssen. M.B. has received speaker fees from Gilead, MSD/Merck and Janssen, advisory fees from ViiV, Gilead and MSD/Merck, honoraria from Gilead for speakers’ bureau and a travel grant from Gilead, and has been the principal investigator in clinical trials sponsored by Gilead, ViiV, Mylan, Janssen and Bristol-Meyers Squibb. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: The aim of this study was to evaluate the agreement between self-reported sleep measures and insomnia with objectively measured sleep parameters in people with HIV (PWH) and HIV-negative individuals., Design: A cross-sectional analysis of PWH and lifestyle-similar HIV-negative individuals., Methods: Self-reported measures included time spent in bed, sleep onset latency and a validated insomnia questionnaire. Objective measures were assessed via 7-days/nights of actigraphy data to determine average and intra-individual variability of several sleep measures (including time spent in bed and onset latency). Spearman's correlation coefficient and Cohen's κ were used to assess the agreement between self-reported and actigraphy-assessed measures. Associations between insomnia and actigraphy-assessed sleep parameters were evaluated using partial least-square discriminant analysis (PLS-DA)., Results: We found fair correlation between self-reported and actigraphy-assessed time spent in bed in 342 PWH (rs = 0.46) and 119 HIV-negative individuals (rs = 0.48). Among PWH, the correlation did not differ by age, education, depressive symptoms and self-reported insomnia (all P > 0.05), but was stronger in men (P = 0.05) and in those with a BMI of at least 25 kg/m2 (P < 0.001). Agreement between self-reported and actigraphy-assessed sleep onset latency was poor in both PWH (κ = 0.002, P = 0.49) and HIV-negative individuals (κ = 0.009, P = 0.65). According to PLS-DA, self-reported insomnia most strongly correlated with intra-individual variability of sleep duration, movement index and efficiency., Conclusion: We report poor-to-fair agreement between self-reported and actigraphy-assessed sleep measures in PWH. Insomnia symptoms correlated with regularity of sleep duration, quality and efficiency. These findings highlight the importance of both patient-reported and objective measures of daily sleep variation, for better understanding sleep disorders in PWH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA)., Methods: Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires., Results: We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2-12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia., Conclusions: Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)

Motivation: People with HIV on successful antiretroviral therapy show signs of premature aging and are reported to have higher rates of age-associated comorbidities. HIV-associated immune dysfunction and inflammation have been suggested to contribute to this age advancement and increased risk of comorbidities., Method: Partial least squares regression (PLSR) was used to explore associations between biological age advancement and immunological changes in the T cell and monocyte compartment in people with HIV (n=40), comparable HIV-negative individuals (n=40) participating in the Comorbidity in Relation to AIDS (COBRA) cohort, and blood donors (n=35)., Results: We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. Interestingly, a unique monocyte and T cell immune phenotypic profile predictive for age advancement was found within each group. An inflammatory monocyte immune phenotypic profile associated with age advancement in HIV-negative individuals, while the monocyte profile in blood donors and people with HIV was more reflective of loss of function. The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. In people with HIV, age advancement was related to changes in the CD4 + T cell compartment and more reflective of immune recovery after cART treatment., Impact: The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. While the monocyte and T cell immune phenotypic profile within the HIV-negative individuals reflected those observed in the combined three groups, a distinct profile related to immune dysfunction, was observed within blood donors and people with HIV. These data suggest that varying exposures to lifestyle and infection-related factors may be associated with specific changes in the innate and adaptive immune system, that all contribute to age advancement., (Copyright © 2020 De Francesco, Sabin, Reiss and Kootstra.)

Objective: To determine comorbidity indices in people with HIV (PWH) and lifestyle-similar HIV-negative controls., Design: Cross-sectional analysis of the Pharmacokinetic and clinical Observations in PeoPle over fiftY cohort study in the United Kingdom and Ireland., Methods: The Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index and the Comorbidity Burden Index were compared between older PWH and HIV-negative controls using the Mann-Whitney U test; the magnitude of the difference between groups was quantified using the r effect size., Results: The 699 PWH and 304 HIV-negative controls were predominantly male (87.5% vs. 64.0%), white (86.3% vs. 90.0%) and had median ages of 57 and 58 years, respectively. Among PWH, the median (interquartile range) CD4 T-cell count was 624 (475, 811) cells/μl; 98.7% were on antiretroviral therapy. The median (interquartile range) ECI was 0 (0, 8) and 0 (-3, 1), Charlson Comorbidity Index was 2 (1, 5) and 1 (0, 1) and Comorbidity Burden Index 8.6 (2.2, 16.8) and 5.9 (0.6, 10.8), respectively. While all three indices were significantly higher in PWH than in controls (P < 0.001 for each), the magnitude of the differences between the two groups were small to medium, with effect sizes (95% confidence interval) of 0.21 (0.16, 0.27), 0.38 (0.32, 0.42) and 0.18 (0.11, 0.23), respectively., Conclusion: These three comorbidity indices are higher in PWH compared with HIV-negative controls, although the magnitude of differences between groups were small. Differences in the ECI, reportedly associated with poorer coronavirus disease 2019 outcomes, were driven by more individuals with HIV being within the higher end of the range.

Background: We investigate the association of widespread pain with sleep quality among people with HIV and HIV-negative controls., Setting: UK-based cohort., Methods: Pain information was collected through a pain mannikin identifying affected body sites; pain was classified as widespread if pain was reported in ≥4 of 5 body regions and in ≥7 of 15 body sites, and as regional otherwise. Sleep was assessed a median of 3.2 years later through 7-night actigraphy and through self-reported assessments of sleep quality. Chi-squared tests, Kruskal-Wallis tests, and linear/logistic regression considered associations between pain extent and sleep quality., Results: Of the 414 participants, 74 (17.9%) reported widespread and 189 (45.7%) regional pain. Although there were few clear associations between actigraphy outcomes and pain extent, those with widespread and regional pain consistently reported poorer sleep quality on all self-reported measures than those with no pain. Median (interquartile range) insomnia severity index and Patient-reported Outcomes Measurement Information System (PROMIS) for sleep disturbance and sleep-related impairment scores were 12 (7-16), 55.3 (48.0-58.9), and 57.2 (48.9-61.3), respectively, for those with widespread pain, 8 (4-13), 51.2 (45.5-58.3), and 50.3 (43.6-56.1) for those with regional pain, and 5 (2-9), 47.9 (42.9-54.3), and 45.5 (41.4-50.3) for those with no pain (all P values 0.0001). Associations remained strong after adjustment for HIV status and other confounders, and were reduced but remained significant, after adjustment for depressive symptoms., Conclusions: Widespread pain was not associated with objective measures of sleep but was strongly associated with self-reported assessments of sleep quality in people with HIV.

Aims: To assess associations of comorbidity patterns observed in people living with HIV (PLWH) with risk factors and health outcomes., Methods: Common patters of comorbidities in PLWH participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study were determined using principal component analysis and a severity score for each pattern was derived. Associations between each pattern's severity score and risk factors were assessed using median regression. The independent associations of patterns' severity scores with self-reported physical and mental health (SF-36 summary scores) were assessed using linear regression, with functional impairment (Lawton IADL < 8) and hospitalization in last year using logistic regression and with number of general practitioner visits using Poisson regression., Results: A total of 1073 PLWH were analysed: 85.2% male, median (interquartile range) age 52 (47-59) years, 98% on therapy. Duration of HIV was associated with higher severity in 4/6 of patterns: cardiovascular diseases, mental health problems, metabolic disorders and chest/other infections (all P ≤ 0.001). Prior AIDS was associated with higher severity scores for the same patterns and for the pattern of cancers (P < 0.001). The pattern of cardiovascular diseases was associated with poorer physical health (P = 0.02), higher risk of functional impairment (P = 0.02) and hospitalization (P < 0.001) and with higher number of general practitioner visits (P < 0.001). Severity of mental health (all P < 0.001) and of chest/other infections patterns negatively affected all the five health outcomes., Conclusion: Common patterns of comorbidities seen in PLWH appear to have different risk factors and to differently affect health outcomes. These findings may assist the development of targeted intervention to prevent, treat and manage the increasingly prevalent multimorbidity in PLWH.

Between 2006 and 2017, frailty prevalence decreased in HIV-positive individuals aged 50 years but presented a 3-fold increase among those 75 years of age. This dynamic relationship, defined as the frailty compression ratio, represents the net result of gero-inducing and gero-protective competing forces, described in the cohort.