The burden of secrecy in the management of multimorbidity in older people living with HIV aged 70 and over.

The secrecy surrounding HIV continues to be a major concern for older people living with HIV (OPWH) despite their long-term experience of HIV and the presence of other chronic diseases. Our study aims to highlight how the secrecy surrounding HIV can affect the management of the other conditions. The results of this socio-anthropological sub-study of the ANRS EP66 SEPTAVIH study, which assesses frailty in OPWH, are based on in-depth interviews conducted with 20 OPWH with multimorbidities aged 70 years and over and 9 caregivers. Based on a cross-sectional thematic analysis, this study shows that HIV infection differs from other chronic diseases due to the secrecy and stigma associated with HIV. These specific issues associated with HIV complicate the lives of OPWH, depriving them of support from loved ones and forcing them to exclude their general practitioner from their care system. This then causes OPWH with multiple chronic diseases to become socially vulnerable and isolated. Interventions that support the sharing of information on HIV among OPWH and also among caregivers need to be identified as a matter of urgency in order to improve the lives and management of OPWH with multimorbidities.Trial Registration: ClinicalTrials.gov identifier: NCT03958786.

Increased incidence of pathogenic variants in ATM in the context of testing for breast and ovarian cancer predisposition.

Pathogenic Variants (PV) in major cancer predisposition genes are only identified in approximately 10% of patients with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Next Generation Sequencing (NGS) leads to the characterization of incidental variants in genes other than those known to be associated with HBOC syndrome. The aim of this study was to determine if such incidental PV were specific to a phenotype. The detection rates of HBOC-associated and incidental PV in 1812 patients who underwent genetic testing were compared with rates in control groups FLOSSIES and ExAC. The rates of incidental PV in the PALB2, ATM and CHEK2 genes were significantly increased in the HBOC group compared to controls with, respective odds ratios of 15.2 (95% CI = 5.6-47.6), 9.6 (95% CI = 4.8-19.6) and 2.7 (95% CI = 1.3-5.5). Unsupervised Hierarchical Clustering on Principle Components characterized 3 clusters: by HBOC (P = 0.01); by ExAC and FLOSSIES (P = 0.01 and 0.02 respectively); and by HBOC, ExAC and FLOSSIES (P = 0.01, 0.04 and 0.04 respectively). Interestingly, PALB2 and ATM were grouped in the same statistical cluster defined by the HBOC group, whereas CHEK2 was in a different cluster. We identified co-occurrences of PV in ATM and BRCA genes and confirmed the Manchester Scoring System as a reliable PV predictor tool for BRCA genes but not for ATM or PALB2. This study demonstrates that ATM PV, and to a lesser extent CHEK2 PV, are associated with HBOC syndrome. The co-occurrence of ATM PV with BRCA PV suggests that such ATM variants are not sufficient alone to induce cancer, supporting a multigenism hypothesis.

PROSPECT guidelines for video-assisted thoracoscopic surgery: a systematic review and procedure-specific postoperative pain management recommendations.

Video-assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and reduced postoperative pain compared with thoracotomy. However, analgesic regimens for video-assisted thoracoscopic surgery vary significantly. The goal of this systematic review was to evaluate the available literature and develop recommendations for optimal pain management after video-assisted thoracoscopic surgery. A systematic review was undertaken using procedure-specific postoperative pain management (PROSPECT) methodology. Randomised controlled trials published in the English language, between January 2010 and January 2021 assessing the effect of analgesic, anaesthetic or surgical interventions were identified. We retrieved 1070 studies of which 69 randomised controlled trials and two reviews met inclusion criteria. We recommend the administration of basic analgesia including paracetamol and non-steroidal anti-inflammatory drugs or cyclo-oxygenase-2-specific inhibitors pre-operatively or intra-operatively and continued postoperatively. Intra-operative intravenous dexmedetomidine infusion may be used, specifically when basic analgesia and regional analgesic techniques could not be given. In addition, a paravertebral block or erector spinae plane block is recommended as a first-choice option. A serratus anterior plane block could also be administered as a second-choice option. Opioids should be reserved as rescue analgesics in the postoperative period.

Anti-Müllerian hormone: A function beyond the Müllerian structures.

The anti-Müllerian hormone (AMH) is a heterodimeric glycoprotein belonging to the TGFb superfamily implicated in human embryonic development. This hormone was first described as allowing regression of the epithelial embryonic Müllerian structures in males, which would otherwise differentiate into the uterus and fallopian tubes. It activates a signaling pathway mediated by two transmembrane receptors. Binding of AMH to its receptor induces morphological changes leading to the degeneration of Müllerian ducts. Recently, new data has shown the role played by this hormone on structures other than the genital tract. If testicular AMH expression decreases in humans over the course of a lifetime, synthesis may persist in other tissues in adulthood. The mechanisms underlying its production have been unveiled. The aim of this review is to describe the different pathways in which AMH has been identified and plays a pivotal role.

[Self-assessment of healthcare workers regarding the management of trans people in a university hospital]. / Auto-évaluation de professionnels de santé concernant la prise en charge des personnes trans dans un hôpital universitaire.

INTRODUCTION: Trans people face more barriers when seeking healthcare than the cisgender population probably due to a lack of knowledge, education and comfort of healthcare workers. The purpose of this study was to assess the knowledge and comfort felt by healthcare professionals in managing trans people in a French university hospital. METHODS: A self-questionnaire was emailed to healthcare professionals working in departments usually involved in the care of trans people in a French university hospital "not specialized" in medical and surgical gender transition. The questionnaire included demographic questions and Likert scales regarding their knowledge and comfort in taking care of trans people. Responses on the 7-point Likert scales were categorized into "low", "medium" and "high" groups, and responses on the 5-point Likert scales were categorized into "in favour", "neutral" and "against" groups. RESULTS: One hundred and two (29%) healthcare professionals answered the questionnaire. Half worked in surgical departments (urology, plastic surgery, gynecology), 24% worked in medical departments (endocrinology, reproductive medicine, cytogenetics) and 26% worked in psychiatry. The majority (60.3%) rated their level of knowledge as "low" and 39.7% as "medium". Sixteen percent rated their level of comfort in managing trans people as "low", 72.5% as "medium" and 11.5% as "high". A majority (77.5%) were in favor of having the costs of gender transition care covered by the national health insurance system, 16.4% were neutral and 6% were against this idea. Feelings about surgical and hormonal gender transition were overwhelmingly (96.4%) in favour or neutral and 91% were willing to get more training and education to manage trans people. CONCLUSION: The lack of comfort felt by healthcare professionals in university hospital in managing trans people seems to be related to a lack of knowledge and training in that field and not to a disagreement with the need of transgender healthcare. LEVEL OF EVIDENCE: 3.

What do the changing patterns of comorbidity burden in people living with HIV mean for long-term management? Perspectives from European HIV cohorts.

Undoubtedly, comorbidities complicate long-term HIV management and have significant cost implications for healthcare systems. A better understanding of these comorbidities and underlying causes would allow for a more considered and proactive approach to the long-term management of HIV. This review examines cross-sectional analyses of six European cohort studies (Athens Multicenter AIDS Cohort Study, Aquitaine Cohort, EuroSIDA Cohort study, French claims EGB, German InGef Cohort and the Italian Cohort of Individuals, Naïve for Antiretrovirals), which included individuals with HIV followed over a certain period of time. Based on these cohorts, we examined how comorbidities have changed over time; how they compromise HIV management; and how much of a financial burden they impart. These data also provided a framework to explore the major issues of ageing and HIV and the practical implications of managing such issues in real-life practice.

Increased risk of type 2 diabetes in antidepressant users: evidence from a 6-year longitudinal study in the E3N cohort.

AIM: To examine the association between antidepressant medication use and the risk of type 2 diabetes. METHODS: Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire-based follow-up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional-hazard regression models were used, with drug exposure considered as a time-varying parameter. RESULTS: Of the 63 999 women who were free of drug-treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6-year follow-up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non-users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine-type, 'other' or 'mixed' antidepressants had a 1.25-fold (95% CI 0.99, 1.57), 1.66-fold (95% CI 1.12, 2.46), 1.35-fold (95% CI 1.00, 1.84) and 1.82-fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non-users, respectively. CONCLUSION: Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).

Evolution of comorbidities in people living with HIV between 2004 and 2014: cross-sectional analyses from ANRS CO3 Aquitaine cohort.

BACKGROUND: The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. METHODS: The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. RESULTS: 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the "high" or "very high" risk groups of the disease risk scores for CKD, CVE and bone fracture score. CONCLUSIONS: Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.

PROSPECT guideline for oncological breast surgery: a systematic review and procedure-specific postoperative pain management recommendations.

Analgesic protocols used to treat pain after breast surgery vary significantly. The aim of this systematic review was to evaluate the available literature on this topic and develop recommendations for optimal pain management after oncological breast surgery. A systematic review using preferred reporting items for systematic reviews and meta-analysis guidance with procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials assessing postoperative pain using analgesic, anaesthetic or surgical interventions were identified. Seven hundred and forty-nine studies were found, of which 53 randomised controlled trials and nine meta-analyses met the inclusion criteria and were included in this review. Quantitative analysis suggests that dexamethasone and gabapentin reduced postoperative pain. The use of paravertebral blocks also reduced postoperative pain scores, analgesia consumption and the incidence of postoperative nausea and vomiting. Intra-operative opioid requirements were documented to be lower when a pectoral nerves block was performed, which also reduced postoperative pain scores and opioid consumption. We recommend basic analgesics (i.e. paracetamol and non-steroidal anti-inflammatory drugs) administered pre-operatively or intra-operatively and continued postoperatively. In addition, pre-operative gabapentin and dexamethasone are also recommended. In major breast surgery, a regional anaesthetic technique such as paravertebral block or pectoral nerves block and/or local anaesthetic wound infiltration may be considered for additional pain relief. Paravertebral block may be continued postoperatively using catheter techniques. Opioids should be reserved as rescue analgesics in the postoperative period. Research is needed to evaluate the role of novel regional analgesic techniques such as erector spinae plane or retrolaminar plane blocks combined with basic analgesics in an enhanced recovery setting.

Determinants of 20-year non-progression to Type 2 diabetes in women at very high risk: the E3N cohort study.

AIMS: To identify the most important determinants associated with not developing Type 2 diabetes in women considered to be at very high risk. METHODS: Between 1995 and 2014, we followed 402 women from the E3N cohort study who were considered to be at very high risk of Type 2 diabetes based on the D.E.S.I.R. score. We then computed a classification and regression tree model to identify, among a large set of risk factors, the top risk factors associated with not having Type 2 diabetes at the end of the follow-up. RESULTS: During follow-up, 117 women (29%) were diagnosed with Type 2 diabetes, while 285 (71%) were still free of the disease in 2014. A low Western dietary pattern score was the top characteristic associated with not developing Type 2 diabetes, as only 20% of the women at very high risk in the E3N study with that characteristic developed Type 2 diabetes (compared with 29% overall). In women with a moderate or high Western dietary pattern score, the most important characteristic associated with not developing Type 2 diabetes was a high total dietary antioxidant capacity, as only 26% of these women ultimately developed Type 2 diabetes. CONCLUSIONS: We showed that the top characteristic associated with not developing Type 2 diabetes, despite being at very high risk, was a healthy diet, characterized by limiting Western dietary habits, but with a high intake of antioxidant-rich foods. This underscores the importance of diet in the prevention of Type 2 diabetes in people at high risk.

Transmission of Type 2 diabetes to sons and daughters: the D.E.S.I.R. cohort.

AIMS: To document the family transmission of Type 2 diabetes to men and women. METHOD: The French D.E.S.I.R. cohort followed men and women over 9 years, with 3-yearly testing for incident Type 2 diabetes. First- and/or second-degree family histories of diabetes were available for 2187 men and 2282 women. Age-adjusted hazard ratios were estimated for various family members and groupings of family members, as well as for a genetic diabetes risk score, based on 65 diabetes-associated loci. RESULTS: Over 9 years, 136 men and 63 women had incident Type 2 diabetes. The hazard ratios for diabetes associated with having a first-degree family member with diabetes (parents, siblings, children) differed between men [1.21 (95% CI 0.80, 1.85)] and women [3.02 (95% CI 1.83, 4.99); Pinteraction =0.006]. The genetic risk score was predictive of diabetes in both men and women, with similar hazard ratios 1.10 (95% CI 1.06, 1.15) and 1.08 (95% CI 1.02, 1.14) respectively, for each additional at-risk allele. In women, the risk associated with having a family member with diabetes persisted after adjusting for the genetic score. CONCLUSION: Women with a family history of diabetes (paternal or maternal) were at risk of developing Type 2 diabetes and this risk was independent of a genetic score; in contrast, for men, there was no association. Diabetes screening and prevention may need to more specifically target women with diabetes in their family, but further studies are required as the number of people with diabetes in this study was small.

Quantitative and qualitative analysis of breakfast nutritional composition in French schoolchildren aged 9-11 years.

BACKGROUND: The present study aimed to analyse the nutritional quality of childrens' breakfasts using data collected during a cross-sectional observational study on the prevalence of urinary osmolality in 529 French children aged 9-11 years. METHODS: Total nutrient intake, mean adequacy ratio (MAR), energy density and solid energy density were calculated from breakfast food and fluid nutritional composition. To identify the main qualitative breakfast patterns, each breakfast item was categorised into 15 solid and liquid food categories and a principal component analysis followed by a cluster analysis was performed. RESULTS: Only 9.8% included skipped breakfast. Breakfast provided, on average, 22.9% of the recommended daily energy intake and 24.7% of the mean adequacy ratio of 23 key nutrients. Four breakfast patterns were identified: 'Sweets breakfast' (40.0% of children), 'Traditional French breakfast' (27.2%), 'Ready-to-eat cereal (RTEC) + milk' (18.1%) and 'Dairy and juice breakfast' (9.5%). Nutritionally, the 'RTEC + milk' pattern was the most advantageous. Flavoured milk was the most frequently consumed food (50.5%) and the major component of the 'Traditional French breakfast'. CONCLUSIONS: Although breakfast provided a substantial contribution to a range of nutrients, opportunity for improvement, particularly to less nutrient breakfast patterns, should not be overlooked.

[Cutaneous lesions during hot-tub hypersensitivity pneumonitis: Pseudomonas folliculitis ?] / Lésions cutanées au cours d'une pneumopathie d'hypersensibilité aux bains bouillonnants : folliculites à Pseudomonas ?

BACKGROUND: Interstitial lung disease, cutaneous rash and elevated serum angiotensin converting enzyme (ACE) may suggest diagnoses other than sarcoidosis. PATIENTS AND METHODS: A 58-year-old man had presented dyspnoea for 2 years with increased angiotensin-converting enzyme, as well as an interstitial syndrome and micronodules. The possibility of sarcoidosis was raised. Systemic corticosteroids resulted in improvement of the dyspnoea although it recurred on dose reduction. We noted fluctuating eczematous macules of the limbs with a histology of aspecific folliculitis. The identification of Mycobacterium avium complex (MAC) in the bronchoalveolar wash prompted us to initiate antimycobacterial therapy, but this was to no avail. Review of the CT-scan and questioning of the patient (daily use of a Jacuzzi for 7 years) resulted in diagnosis of hypersensitivity pneumonitis due to MAC. The cutaneous lesions were taken to indicate "hot tub folliculitis". Discontinuation of hot-tub use and a short course of oral corticosteroids resulted in healing within 4 months, with no recurrence at 2 years. DISCUSSION: HTL is a form of hypersensitivity pneumonitis due to the presence of MAC in the water of Jacuzzis. This condition regresses spontaneously without treatment on discontinuation of Jacuzzi use. Hot-tub folliculitis due to Pseudomonas aeruginosa (PA) presents as macules and papules on covered skin areas (swimsuit) within 48hours of bathing and often declines within 2 weeks. CONCLUSION: Our case is original as regards the concomitant lung and cutaneous involvement associated with Jacuzzi use, with an immunoallergic mechanism for the MAC and probably an infectious mechanism for the PA.

CRISPR-on system for the activation of the endogenous human INS gene.

Advances in the field of epigenetics have allowed the design of new therapeutic strategies to address complex diseases such as type 1 diabetes (T1D). Clustered regularly interspaced short palindromic repeats (CRISPR)-on is a novel and powerful RNA-guided transcriptional activator system that can turn on specific gene expression; however, it remains unclear whether this system can be widely used or whether its use will be restricted depending on cell types, methylation promoter statuses or the capacity to modulate chromatin state. Our results revealed that the CRISPR-on system fused with transcriptional activators (dCas9-VP160) activated endogenous human INS, which is a silenced gene with a fully methylated promoter. Similarly, we observed a synergistic effect on gene activation when multiple single guide RNAs were used, and the transcriptional activation was maintained until day 21. Regarding the epigenetic profile, the targeted promoter gene did not exhibit alteration in its methylation status but rather exhibited altered levels of H3K9ac following treatment. Importantly, we showed that dCas9-VP160 acts on patients' cells in vitro, particularly the fibroblasts of patients with T1D.

Safety of zidovudine dose reduction in treatment-naïve HIV infected patients. A randomized controlled study (MiniZID).

BACKGROUND: Since September 2014, zidovudine (ZDV)-based therapy for HIV has been the preferred second-line WHO regimen in Cameroon, but its use is limited by the risk of anaemia at standard dosage. We assessed the safety of a reduced vs. standard dose of ZDV to decrease the risk of anaemia in treatment-naïve, HIV-infected individuals. METHODS: In a prospective, randomized, open-label trial in an HIV clinic in Cameroon, 142 eligible adults (CD4 count < 350 cells/µL) were randomized to receive 24 weeks of a regimen comprising lamivudine plus nevirapine with either a reduced (400 mg) or standard dose (600 mg) of ZDV. The primary endpoint was the proportion of participants with new/worsening anaemia. RESULTS: Median age was 35 years; 58.5% were women; median body mass index was 23.2 kg/m(2) . At baseline, median haemoglobin was 11.6 g/dL, median CD4 cell count was 163 cells/µL, and median plasma HIV-1 RNA load was 5.4 log10 copies/mL. The proportion of participants with new/worsening anaemia was 37.5% (400 mg ZDV) and 32.9% (600 mg ZDV) (P = 0.563). Ten patients with severe anaemia required a switch from ZDV to tenofovir (11.4% in standard-dose arm vs. 2.8% in low-dose arm; P = 0.054). At 24 weeks, there was no significant difference between treatment groups, including median CD4 T-cell count increases. CONCLUSIONS: No significant difference was observed in the overall rate of anaemia between HIV-infected individuals starting a ZDV-based treatment according to a standard- or reduced-dose regimen. Severe anaemia and treatment switches related to study drug, however, were more frequent with 600 mg than 400 mg ZDV.

Multifaceted bench comparative evaluation of latest intensive care unit ventilators.

BACKGROUND: Independent bench studies using specific ventilation scenarios allow testing of the performance of ventilators in conditions similar to clinical settings. The aims of this study were to determine the accuracy of the latest generation ventilators to deliver chosen parameters in various typical conditions and to provide clinicians with a comprehensive report on their performance. METHODS: Thirteen modern intensive care unit ventilators were evaluated on the ASL5000 test lung with and without leakage for: (i) accuracy to deliver exact tidal volume (VT) and PEEP in assist-control ventilation (ACV); (ii) performance of trigger and pressurization in pressure support ventilation (PSV); and (iii) quality of non-invasive ventilation algorithms. RESULTS: In ACV, only six ventilators delivered an accurate VT and nine an accurate PEEP. Eleven devices failed to compensate VT and four the PEEP in leakage conditions. Inspiratory delays differed significantly among ventilators in invasive PSV (range 75-149 ms, P=0.03) and non-invasive PSV (range 78-165 ms, P<0.001). The percentage of the ideal curve (concomitantly evaluating the pressurization speed and the levels of pressure reached) also differed significantly (range 57-86% for invasive PSV, P=0.04; and 60-90% for non-invasive PSV, P<0.001). Non-invasive ventilation algorithms efficiently prevented the decrease in pressurization capacities and PEEP levels induced by leaks in, respectively, 10 and 12 out of the 13 ventilators. CONCLUSIONS: We observed real heterogeneity of performance amongst the latest generation of intensive care unit ventilators. Although non-invasive ventilation algorithms appear to maintain adequate pressurization efficiently in the case of leakage, basic functions, such as delivered VT in ACV and pressurization in PSV, are often less reliable than the values displayed by the device suggest.