Integrase strand transfer inhibitor (INSTI) related changes in BMI and risk of diabetes: a prospective study from the RESPOND cohort consortium.

BACKGROUND: With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, this study explored the relationship between INSTI/non-INSTI regimens, BMI changes, and DM risk. METHODS: RESPOND participants were included if they had CD4, HIV RNA, and ≥ 2 BMI measurements during follow up. Those with prior DM were excluded. DM was defined as a random blood glucose ≥ 11·1 mmol/L, HbA1c ≥ 6·5%/48 mmol/mol, use of antidiabetic medication, or site reported clinical diagnosis. Poisson regression assessed the association between natural log (ln) of time-updated BMI, current INSTI/non-INSTI, and their interactions, on DM risk. RESULTS: Among 20,865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (IQR 37-52), with a median BMI of 24 kg/m2 (IQR 22-26). There were 785 DM diagnoses with a crude rate of 0·73 (95%CI 0·68-0·78)/100 PYFU. Ln(BMI) was strongly associated with DM (adjusted incidence rate ratio (aIRR) 16·54 per log increase, 95%CI 11·33-24·13; p<0·001). Current INSTI use associated with increased DM risk (IRR 1·58, 95%CI 1·37-1·82; p<0·001) in univariate analyses, only partially attenuated when adjusted for variables including ln(BMI) (aIRR 1·48, 95%CI 1·29-1·71; p<0·001). There was no interaction between ln(BMI), INSTI and non-INSTI use, and DM (p=0·130). CONCLUSIONS: In RESPOND, compared with non-INSTIs, current use of INSTIs was associated with an increased DM risk, which partially attenuated when adjusted for BMI changes and other variables.

Cognitive impairment and therapeutic response in resistant depression.

OBJECTIVES: Therapeutic response in depression is a major challenge since more than one third of patients are not in remission after two attempts of antidepressant treatment and will present a treatment-resistant depression. In order to better adapt therapeutic strategies for treatment-resistant patients, predictive indicators and markers of therapeutic response still need to be identified. In parallel, patients with depression exhibit disturbances in cognitive functioning. This study aims to describe and compare cognitive performances collected at inclusion of patients presenting treatment-resistant depression who will be responders at 6 months to those of non-responders, and to evaluate the predictive value of cognitive indicators on clinical therapeutic response at 6 months after a therapeutic modification. METHODS: Observational study. Patients were evaluated at the clinical (HDRS and BDI-II) and cognitive levels using standardized tools assessing memory, executive functions, attention, and social cognition, prior to a change in antidepressant treatment. Six months after inclusion, they were reassessed and classified into two groups based on the presence or absence of therapeutic response, defined by a 50% improvement on HDRS and BDI-II. The cognitive scores collected at inclusion were then compared. Additionally, univariate logistic regression models were used. RESULTS: Thirty patients were included in this study. Only 13 could be evaluated at 6 months. Among these patients, four had responded to the new treatment while nine were non-responders. Both groups of patients presented deviant cognitive performances compared to norms on tests evaluating executive functions and attention. Statistical analyses did not reveal any difference between the cognitive performances of responders and non-responders at 6 months. Regression analyses showed no association between cognitive scores and therapeutic response at 6 months. CONCLUSION: Executive functioning plays a significant role in treatment-resistant depression. In order to improve the understanding and identification of subtypes of depression, cognitive indicators should be systematically integrated into future research.

A Comprehensive Insight into the Economic Profile of People Receiving Metabolic and Bariatric Surgery Use in France.

BACKGROUND: The use of metabolic and bariatric surgery (MBS) is not uniformly distributed within the population, even if it is governed by established guidelines. This disparity seems to be associated, among other factors, with the economic profile of people receiving this surgery. OBJECTIVES: We investigated the disparities in the use of MBS with respect to the socio-economic level in France based on socio-economic status (SES). MATERIALS AND METHODS: A descriptive observational study was conducted to compare the population of individuals with obesity who underwent MBS (MBS group) with individuals with obesity with no history of MBS (obese group). Data were extracted from the French National Hospital discharge database ("Programme De Médicalisation des Systèmes d'Information," PMSI). Socio-economic status (SES) was assessed through the French Deprivation Index (FDep). RESULTS: The use of MBS was significantly lower in patients having a higher SES compared to those having a lower one. There was no statistically significant difference in the use of MBS between individuals within the 4th and 5th SES quintiles compared to those in the 2nd and 3rd quintiles. No difference was found in the specific MBS procedures used depending on the SES. The obesity level was significantly lower in patients from the 1st and 3rd SES quintiles compared to the patients having a lower SES. CONCLUSION: Our study provides valuable insights into the complex interrelationships between the use of MBS, patients' SES, and obesity levels according to the FDep. These findings underscore the importance of developing targeted interventions to address disparities in the use of bariatric care.

Intranasal dexmedetomidine for sedation in ABR testing in children: No pain, big gain!

OBJECTIVES: Obtaining perfect immobility or sleep in children undergoing ABR auditory brainstem response) testing can be challenging. We examined the effectiveness and safety of intranasal dexmedetomidine for sedation of children undergoing ABR testing. MATERIAL AND METHODS: We included prospectively all patients aged from 1 to 15 years for whom sedation for ABR testing was required, between July 2018 and November 2021. We administered an initial dose of 2.5 µg/kg intranasal dexmedetomidine with a repeat dose of 1 µg/kg if needed 30 min later. Collected data included success rate of sedation, sedation onset and recovery times and incidence of side effects. RESULTS: ABR testing was undertaken successfully in 57 of the 59 patients, giving a total success rate of 96,6 %. (95 % confidence interval 88.5 %-99.1 %). The median time to onset of sleep was 32 ± 18.3 min. The median duration of sedation recovery time was 48 ± 24.7 min. We recorded the adverse effects. Thirty-one patients experienced bradycardia and 28 patients experienced hypotension, all of which resolved without intervention. CONCLUSION: Intranasal dexmedetomidine is an effective, safe, simple of use and noninvasive method for sedation in children. It could have a major role in auditory brainstem response testing, specially in the case of non-cooperative children. REGISTRATION NUMBER OF THE TRIAL: NCT03530371.

Bariatric surgery reduces the incidence of hidradenitis suppurativa in individuals with obesity: results of a nationwide administrative data study in France.

BACKGROUND: Hidradenitis suppurativa (HS) is a systemic inflammatory condition associated with obesity, metabolic syndrome, and environmental factors. Bariatric surgery (BS) is effective in reducing weight and resolving obesity-related medical problems. OBJECTIVES: The aim of this case-control study is to evaluate the effects of BS on the occurrence and recurrence of HS in individuals with obesity. SETTING: Nationwide administrative data study using the French national discharge database. METHODS: We compared 297,776 individuals with obesity and without a history of HS who underwent BS (BS group) with 2,735,930 individuals with obesity who did not receive BS (control group) to assess the incidence of de novo HS. From the same database, we compared hospitalization rates for HS recurrence between 310 individuals with obesity and HS who had BS (HS_BS group) and 3875 individuals with obesity who did not have BS (HS_control group). Propensity score matching using the nearest-neighbor method was implemented to create comparable patient groups. RESULTS: Individuals with obesity and without a history of HS who received BS exhibited a significantly reduced risk of developing de novo HS (RR = .736 [.639; .847]). Among patients with a history of HS, those who underwent BS had a nonsignificantly reduced risk of HS recurrence (RR = .676 [.369; 1.238]) compared with those who did not. CONCLUSION: BS reduces the risk of developing de novo HS and seems to have a protective effect on its recurrence in individuals with obesity, although the latter effect was not statistically significant.

What are the prevalence and risk factors associated with wire syndrome in dental students? A cross-sectional study.

INTRODUCTION: Wire syndrome (WS) refers to dental displacements that can be described as aberrant, inaccurate, unexplained, or excessive, on teeth still contained by an intact bonded retainer, without detachment or fracture, leading to evolving dental and periodontal, aesthetic and/or functional consequences. The objective of this study was to define the prevalence rate of mandibular WS and the associated risk factors. METHODS: Participants were dental students who had undergone orthodontic treatment and were wearing an intact fixed mandibular retainer. They completed a 20-item questionnaire, after which an extraoral and intraoral clinical examination was conducted. Participants were assigned to either the non-wire syndrome group or the wire syndrome group by two independent practitioners. Univariate and multivariate logistic regression models were used to investigate potential risk factors. RESULTS: A total of 59 students (23.4years±1.7years) were included. Among these, 9 students presented with mandibular WS, resulting in a prevalence rate of 15.25% (95% CI: 6.08%-24.43%). Univariate analysis revealed a significant association between a deep labio-mental fold, a concave profile, and a multi-strand round wire, and an excess risk of WS. The odds ratios were 16.5 (95% CI: 1.9-146.8, P=0.01), 6.4 (95% CI: 1.0-41.0, P=0.05), and 9.0 (95% CI: 1.7-48.7, P=0.01), respectively. Multivariate analysis confirmed these significant associations, except for the concave profile. CONCLUSIONS: The prevalence rate of wire syndrome was 15.25%. Two risk factors associated with WS were identified: a deep labio-mental fold and a multi-strand round wire retainer.

Integrating artificial intelligence into lung cancer screening: a randomised controlled trial protocol.

INTRODUCTION: Lung cancer (LC) is the most common cause of cancer-related deaths worldwide. Its early detection can be achieved with a CT scan. Two large randomised trials proved the efficacy of low-dose CT (LDCT)-based lung cancer screening (LCS) in high-risk populations. The decrease in specific mortality is 20%-25%.Nonetheless, implementing LCS on a large scale faces obstacles due to the low number of thoracic radiologists and CT scans available for the eligible population and the high frequency of false-positive screening results and the long period of indeterminacy of nodules that can reach up to 24 months, which is a source of prolonged anxiety and multiple costly examinations with possible side effects.Deep learning, an artificial intelligence solution has shown promising results in retrospective trials detecting lung nodules and characterising them. However, until now no prospective studies have demonstrated their importance in a real-life setting. METHODS AND ANALYSIS: This open-label randomised controlled study focuses on LCS for patients aged 50-80 years, who smoked more than 20 pack-years, whether active or quit smoking less than 15 years ago. Its objective is to determine whether assisting a multidisciplinary team (MDT) with a 3D convolutional network-based analysis of screening chest CT scans accelerates the definitive classification of nodules into malignant or benign. 2722 patients will be included with the aim to demonstrate a 3-month reduction in the delay between lung nodule detection and its definitive classification into benign or malignant. ETHICS AND DISSEMINATION: The sponsor of this study is the University Hospital of Nice. The study was approved for France by the ethical committee CPP (Comités de Protection des Personnes) Sud-Ouest et outre-mer III (No. 2022-A01543-40) and the Agence Nationale du Medicament et des produits de Santé (Ministry of Health) in December 2023. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations. TRIAL REGISTRATION NUMBER: NCT05704920.

Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving integrase strand-transfer inhibitors, tenofovir alafenamide, or both compared with other contemporary antiretroviral regimens: a multicentre, prospective observational study from the RESPOND consortium cohorts.

BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. METHODS: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. FINDINGS: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction=0·46 for hypertension; pinteraction=0·31 for dyslipidaemia). INTERPRETATION: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.