Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

La leishmaniasis visceral en la región de Murcia: estudio multicéntrico 1997-2013

ResumenIntroducciónLa prevalencia de la leishmaniasis visceral (LV), una parasitosis endémica en la cuenca mediterránea, puede verse afectada por movimientos migratorios.ObjetivoEl objetivo de este estudio fue analizar los casos de LV valorados en hospitales de la región de Murcia.Material y métodosSe trata de un estudio retrospectivo multicéntrico de los casos de LV diagnosticados y tratados en los diferentes hospitales de nuestra región, que se agruparon en 2 cohortes: períodoA (pA), el comprendido entre los años 1997 y 2005, y períodoB (pB), el transcurrido entre 2006 y 2013.ResultadosSe analizaron 97 casos de LV (75% fueron hombres y la edad media fue de 35 años), 36 en pA y 61 en pB; el 11% de los pacientes procedían de otros países en pA y el 22% en pB (subsaharianos en 10 casos); el 55% tenían algún tipo de inmunosupresión (80% de ellos estaban diagnosticados de infección por VIH). Las manifestaciones más frecuentes fueron: fiebre (85%) y astenia (66%). La duración media de los síntomas antes de la primera consulta fue de 47días, y el tiempo medio transcurrido entre esta primera consulta y la realización de la prueba diagnóstica, de 13días. El hallazgo más común en la exploración física fue la esplenomegalia (89%), mientras que la trombocitopenia fue el hallazgo de laboratorio más constante (78%). El diagnóstico se confirmó con la detección de amastigotes y/o PCR del aspirado medular en el 61% de los casos; en el 39% restante el aspirado fue negativo y fue necesario el estudio de otras muestras (biopsia de médula ósea, ganglio linfático, laringe, colon, parótida y amígdala, PCR en sangre, serología o inmunocromatografía en orina). El tratamiento más usado fue anfotericinaB liposomal (71%), seguida de glucantime (27%) y anfotericinaB complejo lipídico (1%); en un caso no se pudo averiguar el tratamiento administrado. Se objetivaron 16 recidivas, 11 de ellas en pacientes con sida.ConclusionesAun a riesgo de sesgos propios de estudios retrospectivos y a pesar del mejor control de la infección VIH, observamos en nuestra región un aumento en la frecuencia de casos de LV, probablemente favorecido por el aumento del número de inmigrantes.AbstractIntroductionThe prevalence of visceral leishmaniasis (VL), an endemic parasitic infection in the Mediterranean basin, can be affected by migratory movements.ObjectiveTo analyze VL cases evaluated at several hospitals in the Murcia region.MethodsRetrospective, multicentric study of VL cases; patients were grouped into two time periods: periodA (pA: 1997-2005) and periodB (pB: 2006-2013).ResultsA total of 97 VL cases were analyzed (75% men, mean age 35 years), 36 of them in pA and 61 in pB; 11% and 22% of the patients were foreigners in pA and pB, respectively (10 from sub-Saharan Africa); 55% suffered from some type of immunosuppression (80% HIV). The most common clinical manifestations were fever (85%) and asthenia (66%). The mean duration of symptoms before the first medical contact was 47 days and the average time between the first contact and the microbiological confirmation was 13 days. The most common finding on physical examination was splenomegaly (89%), whereas thrombocytopenia was the most frequent laboratory finding (78%). Diagnoses were confirmed by detection of amastigotes and/or PCR of bone marrow aspiration (BMA) in 61%; in the remaining 39% of cases, BMA was negative and additional samples were necessary (bone marrow, lymph node, larynx, colon, parotid and amygdala biopsy, PCR of blood samples, serology or urine antigen detection). The most commonly used treatment was liposomal amphotericinB (71%), followed by glucantime (27%) and amphotericinB lipid complex (1%). A total of 16 recurrent cases (11 in AIDS patients), were observed.ConclusionsAlthough this is a retrospective study and despite better control of HIV infection, we have observed an increase in the frequency of VL cases in our region, which is probably related to migratory flows

La leishmaniasis visceral en la región de Murcia: estudio multicéntrico 1997-2013

Introducción: La prevalencia de la leishmaniasis visceral (LV), una parasitosis endémica en la cuenca mediterránea, puede verse afectada por movimientos migratorios. Objetivo: El objetivo de este estudio fue analizar los casos de LV valorados en hospitales de la región de Murcia. Material y métodos: Se trata de un estudio retrospectivo multicéntrico de los casos de LV diagnosticados y tratados en los diferentes hospitales de nuestra región, que se agruparon en 2 cohortes: período A (pA), el comprendido entre los años 1997 y 2005, y período B (pB), el transcurrido entre 2006 y 2013. Resultados: Se analizaron 97 casos de LV (75% fueron hombres y la edad media fue de 35 años), 36 en pA y 61 en pB; el 11% de los pacientes procedían de otros países en pA y el 22% en pB (subsaharianos en 10 casos); el 55% tenían algún tipo de inmunosupresión (80% de ellos estaban diagnosticados de infección por VIH). Las manifestaciones más frecuentes fueron: fiebre (85%) y astenia (66%). La duración media de los síntomas antes de la primera consulta fue de 47 días, y el tiempo medio transcurrido entre esta primera consulta y la realización de la prueba diagnóstica, de 13 días. El hallazgo más común en la exploración física fue la esplenomegalia (89%), mientras que la trombocitopenia fue el hallazgo de laboratorio más constante (78%). El diagnóstico se confirmó con la detección de amastigotes y/o PCR del aspirado medular en el 61% de los casos; en el 39% restante el aspirado fue negativo y fue necesario el estudio de otras muestras (biopsia de médula ósea, ganglio linfático, laringe, colon, parótida y amígdala, PCR en sangre, serología o inmunocromatografía en orina). El tratamiento más usado fue anfotericina B liposomal (71%), seguida de glucantime (27%) y anfotericina B complejo lipídico (1%); en un caso no se pudo averiguar el tratamiento administrado. Se objetivaron 16 recidivas, 11 de ellas en pacientes con sida. Conclusiones: Aun a riesgo de sesgos propios de estudios retrospectivos y a pesar del mejor control de la infección VIH, observamos en nuestra región un aumento en la frecuencia de casos de LV, probablemente favorecido por el aumento del número de inmigrantes

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research