LORENZO LUCENA PEDROSA (1807-1881). RECUPERANDO UNA FIGURA SEÑERA DE LA SEGUNDA REFORMA ESPAÑOLA

El autor reúne datos conocidos y desconocidos para reconstruir la biografía de Lucena: brillante alumno, después catedrático y rector del seminario diocesano de Córdoba, que por su huida y paso al protestantismo cayó en desgracia ante sus compatriotas. Los historiadores de hoy todavía no han valorado suficientemente sus méritos para con el protestantismo de habla castellana. Se describen sus sucesivos periodos de trabajo en Gibraltar, Liverpool y Oxford, así como sus servicios de traductor y revisor de publicaciones religiosas (la Biblia de Reina y Valera, ed. 1862) a instancias de la Sociedad para Promover el Conocimiento Cristiano (SPCK)

Pain in people living with HIV and its association with healthcare resource use, well-being and functional status

Objective: We describe the prevalence of pain and its associations with healthcare resource utilisation and quality-of-life. Design: The POPPY Study recruited three cohorts: older PLWH (≥50 years, n = 699), younger demographically/lifestyle similar PLWH (<50 years, n = 374) and older demographically/lifestyle similar HIV-negative (≥50 years, n = 304) people from April 2013-February 2016. Methods: Current pain and pain-related healthcare use was collected via a self-reported questionnaire. Logistic regression assessed between-group differences in the prevalence of pain in the past month and current pain after controlling for potential confounders. Associations between current pain and healthcare resource use, reported joint problems, depressive symptoms, quality-of-life and functional status were assessed in PLWH using Mann-Whitney U and Chi-squared tests. Results: Pain in the past month was reported by 473/676 (70.0%) older PLWH, 224/357 (62.7%) younger PLWH and 188/295 (63.7%) older HIV-negative controls (p = 0.03), with current pain reported in 330 (48.8%), 134 (37.5%) and 116 (39.3%), respectively (p = 0.0007). Older PLWH were more likely to experience current pain, even after adjustment for confounders. Of those with pain in the past month, 56/412 (13.6%) had missed days of work or study due to pain, and 520 (59%) had seen a doctor about their pain. PLWH experiencing current painhad more depressive symptoms, poorer quality-of-life on all domains, and greater functional impairment, regardless of age group. Conclusions: Even in the effective ART era, pain remains common in PLWH and has a major impact on quality-of-life and associated healthcare and societal costs. Interventions are required to assist clinicians and PLWH to proactively manage pain

Defining cognitive impairment in people-living-with-HIV: the POPPY study

Background The reported prevalence of cognitive impairment (CI) varies widely in cohorts of people living with HIV (PLWH); this may partly be due to the use of different diagnostic criteria. Agreement between diagnostic criteria of CI, the optimal definition to use, and associations with patient-reported cognitive symptoms have not been fully investigated. Methods Two hundred ninety PLWH aged >50 years and 97 matched negative controls completed a detailed assessment of cognitive function and three questions regarding cognitive symptoms. Age- and education-adjusted test scores (T-scores) determined if subjects met the following definitions of CI: Frascati, global deficit score (GDS) and the multivariate normative comparison (MNC) method. Results PLWH were more likely than controls to meet each definition of CI (ORs were 2.17, 3.12 and 3.64 for Frascati, GDS and MNC, respectively). Agreement of MNC with Frascati and GDS was moderate (Cohen’s k = 0.42 and 0.48, respectively), whereas that between Frascati and GDS was good (k = 0.74). A significant association was found between all the three criteria and reporting of memory loss but not with attention and reasoning problems. The 41 (14 %) PLWH meeting all the three criteria had the lowest median global T-score (36.9) and highest rate of symptom reporting (42 %). Conclusions Different CI criteria show fair diagnostic agreement, likely reflecting their ability to exclude CI in the same group of individuals. Given the lower overall cognitive performance and higher rates of symptom reporting in those meeting all three criteria of CI, further work assessing this as a definition of CI in PLWH is justified

Cohort profile: the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study

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Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIV

Background: People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk. Methods: We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ (relatively low levels of inflammation). Ten-year CVD risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression. Results: Of the 312 participants included (70% living with HIV, median [interquartile range; IQR] age 55 [51–60] years; 82% male; 91% white), 146, 36, and 130 were in the ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ cluster, respectively. The median [IQR] QRISK scores were 9.3% (4.5–14.5) and 10.2% (5.5–16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK (5.8% [1.0–10.7] and 3.1% [0.3–5.8]) scores were higher, respectively, for those in the ‘gut/immune activation’ and ‘neurovascular’ clusters compared to those in the reference cluster. Conclusions: People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV

Defining cognitive impairment in people-living-with-HIV: the POPPY study

Background The reported prevalence of cognitive impairment (CI) varies widely in cohorts of people living with HIV (PLWH); this may partly be due to the use of different diagnostic criteria. Agreement between diagnostic criteria of CI, the optimal definition to use, and associations with patient-reported cognitive symptoms have not been fully investigated. Methods Two hundred ninety PLWH aged >50 years and 97 matched negative controls completed a detailed assessment of cognitive function and three questions regarding cognitive symptoms. Age- and education-adjusted test scores (T-scores) determined if subjects met the following definitions of CI: Frascati, global deficit score (GDS) and the multivariate normative comparison (MNC) method. Results PLWH were more likely than controls to meet each definition of CI (ORs were 2.17, 3.12 and 3.64 for Frascati, GDS and MNC, respectively). Agreement of MNC with Frascati and GDS was moderate (Cohen’s k = 0.42 and 0.48, respectively), whereas that between Frascati and GDS was good (k = 0.74). A significant association was found between all the three criteria and reporting of memory loss but not with attention and reasoning problems. The 41 (14 %) PLWH meeting all the three criteria had the lowest median global T-score (36.9) and highest rate of symptom reporting (42 %). Conclusions Different CI criteria show fair diagnostic agreement, likely reflecting their ability to exclude CI in the same group of individuals. Given the lower overall cognitive performance and higher rates of symptom reporting in those meeting all three criteria of CI, further work assessing this as a definition of CI in PLWH is justified

Sleep health and cognitive function among people with and without HIV: the use of different machine learning approaches

Study objectives We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches. Methods Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in UK/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for socio-demographics. Average and standard deviation (SD) of eleven sleep measures over 7-days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures. Results In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency and wake after sleep onset were not associated with global T-scores according to rank regression (p=0.51, p=0.09, p=0.16, respectively). In contrast, global T-scores associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males). Conclusions Using multivariable analytical approaches, measures of sleep continuity, timing and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in assessment of health and functioning

Changes in multimorbidity burden over a 3–5 year period among people with HIV

Introduction: As people living with HIV age, the increasing burden of multimorbidity poses a significant health challenge. The aims of this study were to identify common patterns of multimorbidity and examine changes in their burden, as well as their associations with risk factors, over a 3–5 year period in people with HIV, enrolled in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study.Methods: Common multimorbidity patterns were identified in POPPY participants with HIV using principal component analysis, based on Somers’ D statistic. Multimorbidity burden scores were calculated for each participant/pattern at study entry/follow-up and were standardised relative to the mean in the sample at baseline (scores &gt;0 thus reflect a greater number of comorbidities relative to the mean). Two multivariable linear regression models were fitted to examine the associations between risk factors and burden z-scores at baseline and change in z-scores over a 3–5 year period.Results: Five patterns were identified among the 1073 POPPY participants with HIV {median age [interquartile range (IQR)], 52 (47–59) years; 85% male and 84% white}: Cardiovascular diseases (CVDs), Sexually transmitted diseases (STDs), Neurometabolic, Cancer and Mental-gastro-joint. The multivariable linear regression showed that older age, behavioural factors (i.e., body mass index (BMI), history of injection drug use, current recreational drug use and sex between men), and HIV-specific factors (i.e., duration since HIV diagnosis and a prior AIDS diagnosis) were associated with higher multimorbidity burden at baseline. However, only three of the factors (age, BMI and duration since HIV diagnosis) were significantly associated with an increase in burden across specific patterns over time.Discussion: Key modifiable and non-modifiable factors contributing to an increase in burden of multimorbidity were identified. Our findings may inform the development of more targeted interventions and guidelines to effectively prevent and manage the rising burden of multimorbidity in people with HIV

Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV

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 (p0.05). 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