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To describe the features of HIV-associated chronic lung disease (CLD) in older children and adolescents living with HIV and to examine the clinical factors associated with CLD. This is a post hoc analysis of baseline data from the BREATHE clinical trial (ClinicalTrials.gov, NCT02426112).Children and adolescents aged 6-19 years were screened for CLD (defined as a FEV1 z-score-1 with no reversibility post-bronchodilation with salbutamol) at two HIV clinics in Harare, Zimbabwe, and Blantyre, Malawi. Eligible participants with CLD (cases) were enrolled, together with a control group without CLD [frequency-matched by age group and duration on antiretroviral therapy (ART)] in a 4:1 allocation ratio. A clinical history and examination were undertaken. The association between CLD and a priori-defined demographic and clinical covariates was investigated using multivariable logistic regression.Of the 1585 participants screened, 419 (32%) had a FEV1 z-score-1, of whom 347 were enrolled as cases [median age 15.3 years (IQR 12.7-17.7); 48.9% female] and 74 with FEV1 z-score0 as controls [median age 15.6 years (IQR 12.1-18.2); 62.2% female]. Among cases, current respiratory symptoms including cough and shortness of breath were reported infrequently (9.3% and 1.8%, respectively). However, 152 (43.8%) of cases had a respiratory rate above the 90th centile for their age. Wasting and taking second-line ART were independently associated with CLD.The presence of CLD indicates the need to address additional treatment support for youth living with HIV, alongside ART provision, to ensure a healthier adulthood.Décrire les caractéristiques de la maladie pulmonaire chronique (MPC) associée au VIH chez les enfants plus âgés et les adolescents vivant avec le VIH et examiner les facteurs cliniques associés à la MPC. Il s'agit d'une analyse post-hoc des données de référence de l'essai clinique BREATHE (ClinicalTrials.gov, NCT02426112 ). MÉTHODES: Les enfants et adolescents âgés de 6 à 19 ans ont été dépistés pour la MPC (défini comme un score z FEV1-1 sans réversibilité post-bronchodilatation avec du salbutamol) dans deux cliniques VIH à Harare, au Zimbabwe et à Blantyre, au Malawi. Les participants éligibles atteints de MPC (cas) ont été inscrits, ainsi qu'un groupe témoin sans MPC (fréquence appariée par groupe d'âge et durée sous ART) dans un rapport d'allocation de 4:1. Une histoire clinique et un examen ont été entrepris. L'association entre la MPC et les covariables démographiques et cliniques définies a priori a été étudiée en utilisant une régression logistique multivariable. RÉSULTATS: Sur les 1.585 participants dépistés, 419 (32%) avaient un score z FEV 1-1, dont 347 étaient inscrits comme cas (âge médian 15,3 ans [IQR 12,7 -17,7]; 48,9% de sexe féminin), et 74 avec un score z FEV10 comme témoins (âge médian 15,6 ans [IQR 12,1 -18,2]; 62,2% de sexe féminin). Parmi les cas, les symptômes respiratoires en cours, y compris la toux et l'essoufflement, n’ont pas été rapportés fréquemment (9,3% et 1,8%, respectivement). Cependant, 152 (43,8%) des cas avaient une fréquence respiratoire supérieure au 90La présence de MPC indique la nécessité d’un soutien thérapeutique supplémentaire aux jeunes vivant avec le VIH, à côté de à la fourniture de l’ART, pour assurer un âge adulte en meilleure santé.

ObjectiveHIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD.DesignCase--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility.MethodsCryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD.ResultsBiomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association.ConclusionHCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.

In a cross-sectional study of 296 children and adolescents from Zimbabwe living with perinatal human immunodeficiency virus, individuals with the top tertile of cytomegalovirus-specific immunoglobulin G titer had an increased odds of chronic lung disease (odds ratio, 3.33; 95% confidence interval, 1.37–8.85; P = .010).

Objective To investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe. Methods Children (0–19 years) and adults (>19 years) starting ART between 2013 and 2015 were followed for a median of 2.8 and 2.7 years, respectively. The incidence rates of virological failure (VF), low-level viraemia (LLV), and viral blips were assessed and the predictors of viraemia were determined using logistic and parametric survival regression analyses. Results A total of 630 individuals initiated ART, and 19.7% of children and 5.6% of adults did not achieve viral suppression by 12 months. Younger age and CD4 count ≤200 cells/mm3 at baseline were associated with not being virally suppressed at 12 months in adults. Among those who achieved viral suppression during the follow-up period, the incidence of VF was higher in children (4.0/100 person-years vs. 0.4/100 person-years in adults; p < 0.001), as was the incidence of LLV (1.9/100 person-years vs. 0.3/100 person-years in adults; p = 0.03). The incidence rate of blips was 10.9 per 100 person-years in children and 4.0 per 100 person-years in adults. Conclusions Children are less likely to reach viral suppression and are at higher risk of viraemia while on ART than adults. The significance of LLV and blips needs further study. © 2018 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Objective: HIV disrupts host defense mechanisms and maintains chronic inflammation in the lung. Nitric oxide is a marker of lung inflammation and can be measured in the exhaled air. We investigated the relationship between exhaled nitric oxide (eNO), HIV status and airway abnormalities in perinatally HIV-infected children aged 6–19 years. Design: A cross-sectional study. Methods: HIV-infected individuals on antiretroviral therapy and HIV-uninfected children with no active tuberculosis (TB) or acute respiratory tract infection were recruited from a public hospital in Harare, Zimbabwe. Clinical history was collected and eNO testing and spirometry was performed. The association between eNO and explanatory variables (HIV, FEV1 z-score, CD4+ cell count, viral load, history of TB) was investigated using linear regression analysis adjusted for age, sex and time of eNO testing. Results: In total, 222 HIV-infected and 97 HIV-uninfected participants were included. Among HIV-infected participants, 57 (25.7%) had a history of past TB; 56 (25.2%) had airway obstruction, but no prior TB. HIV status was associated with lower eNO level [mean ratio 0.79 (95% confidence interval, 95% CI 0.65–0.97), P = 0.03]. Within the HIV-infected group, history of past TB was associated with lower eNO levels after controlling for age, sex and time of eNO testing [0.79 (95% CI 0.67–0.94), P = 0.007]. Conclusion: HIV infection and history of TB were associated with lower eNO levels. eNO levels may be a marker of HIV and TB-induced alteration in pulmonary physiology; further studies focused on potential causes for lower eNO levels in HIV and TB are warranted. Copyright 2019 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Background Human immunodeficiency virus (HIV) infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV-infected children. We investigated composition of gut microbiota in HIV-infected and -uninfected children and assessed associations between gut microbiota and patient characteristics. Methods In a cross-sectional study, rectal swabs were collected from 177 HIV-infected and 103 HIV-uninfected controls. Gut microbial composition was explored using 16S ribosomal ribonucleic acid sequencing. Results Human immunodeficiency virus-infected children had significantly lower alpha-diversity and higher beta-diversity compared to HIV-uninfected. No association was observed between microbiome diversity and CD4+ T-cell count, HIV viral load, or HIV-associated chronic lung disease. We found enriched levels of Corynebacterium (P < .01), Finegoldia (P < .01), and Anaerococcus (P < .01) in HIV-infected participants and enrichment of Enterobacteriaceae (P = .02) in participants with low CD4+ counts (

The incidence of colorectal cancer (CRC) has increased among Norwegian women, and is among the highest in the world. In order to understand this increase, country specific dietary exposures have been investigated. The aim of this study was to quantify the association between consumption of brown cheese, a common bread topping in Norway, and colorectal, colon, and rectal cancer in the prospective Norwegian Women and Cancer (NOWAC) Study. Data on brown cheese consumption and adjustment factors was available for 82 527 women. During a mean of 14.6 years of follow-up (1.2 million person-years), there were 1360 cases of colorectal cancer (907 colon; 453 rectal). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for colorectal, colon, and rectal cancer sites. We modelled restricted cubic splines with 4 knots, to assess a possible non-linear relationship between brown cheese intake and the investigated cancer sites. In the age-adjusted model, consumption of more than 2 slices (>16 grams) of brown cheese per day was associated with 13% reduced risk of colon cancer (95% CI 4%-21%) compared to women who did not consume brown cheese. The multivariable-adjusted model, however, showed no association between brown cheese consumption and the risk of colorectal, colon, or rectal cancer (colorectal: HR = 0.93, 95% CI 0.76–1.13, p-trend 0.37; colon: HR = 0.83, 95% CI 0.65–1.06; p-trend = 0.10; rectal: HR = 1.16, 95% CI 0.84–1.1.61, p-trend = 0.41). In this large, prospective cohort study of women, consumption of brown cheese was suggestively protective against colon cancer. However, adjustment attenuated the inverse risk association. Brown cheese consumption was not associated with rectal cancer, or colorectal cancer overall.

Introduction: Rheumatoid arthritis (RA) is the most common chronic systemic autoimmune disease. Chronic and severe course, early disability, social disadaptation as well as the high incidence of psychological problems require the development of an integrated approach to etiopathogenesis, diagnostics, management as well as rehabilitation and preventive care. Theory: We have developed a synergetic bio-psycho-socio-spiritual concept of ontogenesis that is represented by a four-dimensional model consisting of vectors of somato- and psycho-, socio- and animogenesis. Animogenesis is a term that integrates understanding of soul and spirit and represents the central fourth part of the proposed ontogenetic model. The vectors are interrelated and determine transit zones with a central part containing conscience – the highest level of self-regulation and reflection of reality accumulating spiritual-moral potential. Results: We propose a synergetic concept for RA development with identified there prenosological stages: predisposition - arthritic family, latent - arthritic diathesis, initial - prearthritic state and three nosological stages: onset, chronic phase and outcomes. Based on the concept we have developed a multidisciplinary program of care for patients with RA, which includes four sections/blocks: medical, psychological, spiritual-moral and social. Preventive measures are implemented in the first three prenosological stages, treatment and rehabilitation - in the three nosological stages, constituting a single multidisciplinary protocol of care for RA patients. The protocol is realized by a team composed of a rheumatologist, psychotherapist, clinical psychologist, social worker and bioethics specialist. Discussions: The model presupposes a multidisciplinary and integral approach to complex psychosomatic cause-effect relationships in the course of the disease. The proposed methodology makes it possible to formulate clinical, psychological, social and moral diagnoses resulting in a synergetic functional diagnosis. Conclusions: Synergetic bio-psycho-socio-spiritual concept of the disease and a multidisciplinary program of care enable to establish personalized protocols for patients with RA, improve management and control the progression of the disease. Lessons learned: The developed framework for RA allows to mobilize new resources and launch effective mechanisms of therapeutic and preventive care. Limitations: The study focuses mainly on the methodological approach and further practical evaluation of proposed program is required. Suggestions for future research: The program of integrated care will be realized and evaluated in a large cohort of patients with RA. Based on synergetic methodology, a multidisciplinary program of care may be developed and implemented for other chronic disorders.

Det er registrert data fra BREATHE prosjektet som er gjennomført i samarbeid med en rekke forskere på 6-19 år HIV-smittede personer i Zimbabwe. Jeg har basert analysene på disse dataene, der jeg har kartlagt antropometrisk status blant disse barna i datainnsamlingstidspunktet. Funnene viser at det er lave forekomster av stunting, undervekt og lav BMI blant barn som ikke er smittet med HIV. Prevalensen stiger for de som har HIV-infeksjon og ytterliggere for de som i tillegg har HIV-assosiert kronisk lungesykdom. Mannlig kjønn og kortere tid for antiretroviral behandling (ART) er assosiert med høyere forekomst av stunting og lav BMI. Sosiodemografisk - og økonomisk bakgrunn, i tillegg til ernæringsskreening er ikke samlet inn data på.