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.

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.

Efficacy and safety of a novel triple combination cream compared to Kligman's trio for melasma: A 24-week double-blind prospective randomized controlled trial.

BACKGROUND: Kligman's trio (KT), combining hydroquinone, retinoic acid and corticosteroid, is considered as the gold standard treatment of melasma. Its efficacy has never been matched before, but it is tempered by frequent adverse effects. OBJECTIVE: To assess the efficacy and tolerance of a New Trio (NT) combination with isobutylamido-thiazolyl-resorcinol, retinoic acid and cortosteroid compared to KT. METHODS: We conducted a 24-week monocentric trial, randomized, double-blind, controlled versus KT, with 40 melasma patients. NT and KT were applied for 12 weeks and associated with the same sunscreen applied for 24 weeks. The primary endpoint was the modified Melasma Area Severity Index (mMASI) at 12 weeks. Patient quality of life was investigated using MelasQoL. RESULTS: After 12 weeks, KT and NT groups both demonstrated a significant improvement in mMASI, respectively -2.84 (SE 0.69, p < 0.0002) and -4.33 (SE 0.71, p < 0.0001). The mean difference between the two groups was -1.49 (IC 95% -3.52 to 0.54, p = 0.14). MelasQoL improvement was -6.66 (SE 3.29, p = 0.0515) with KT and -12.57 (SE 3.29, p = 0.0006) with NT. CONCLUSION: The NT combination appears to be an effective treatment option for treating melasma and could be considered as a well-tolerated alternative to KT.

Effectiveness of Geniculate Artery Embolization for Chronic Pain after Total Knee Replacement-A Pilot Study.

PURPOSE: To evaluate the efficacy and safety of embolization of hyperemic synovial tissue for the treatment of persistent pain after total knee arthroplasty (TKA). MATERIALS AND METHODS: Twelve patients with persistent pain after TKA were enrolled in this prospective, single-center pilot study. Genicular artery embolization (GAE) was performed using 75-µm spherical particles. The patients were assessed using a 100-point Visual Analog Scale (VAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline and 3 and 6 months thereafter. Adverse events were recorded at all time points. RESULTS: A mean of 1.8 ± 0.8 abnormal hyperemic genicular arteries were identified and embolized, with a median volume of diluted embolic material of 4.3 mL in all 12 (100%) patients. The mean VAS score on walking improved from 73 ± 16 at baseline to 38 ± 35 at the 6-month follow-up (P < .05). The mean KOOS pain score improved from 43.6 ± 15.5 at baseline to 64.6 ± 27.1 at the 6-month follow-up (P < .05). At the 6-month follow-up, 55% and 73% of the patients attained a minimal clinically important change in pain and quality of life, respectively. Self-limited skin discoloration occurred in 5 (42%) patients. The VAS score increased by more than 20 immediately after embolization in 4 (30%) patients, who required analgesic treatment for 1 week. CONCLUSION: GAE is a safe method of treating persistent pain after TKA that demonstrates potential efficacy at 12 months.

Hidradenitis suppurativa and social disadvantage: A nationwide administrative data study of the French hospitalized population.

BACKGROUND: A lower socioeconomical status (SES) has been reported in patients suffering from hidradenitis suppurative (HS). However, limitations in the available studies prevent drawing definitive conclusions. OBJECTIVES: The objective of this study was to assess the SES of HS patients using a specific SES indicator, the French DEPrivation index (FDep), specifically designed and validated for the French population. METHODS: This cross-sectional cohort study compared the HS hospitalized population with the general hospitalized population without HS. Data were extracted from the French national hospital discharge database, an exhaustive database on all reimbursed hospital stay in the country with a rolling 10-year history (2012-2021). We included all patients aged 7-75 years with at least one stay in a French hospital. A 1:40 propensity score matching, adjusted for age, sex, smoking status and obesity, was performed to create 2 groups of comparable patients. Subgroup analysis was done in the minor (7-17 years) and major (25-75 years) populations independently. RESULTS: In the overall population, we identified 33,880 patients with HS and 24,445,337 patients without HS. After propensity score matching, logistic regression showed a significant association between HS and social disadvantage. There is a 22.5% increased risk of developing HS for individuals being in quintile 5 (the most disadvantaged quintile) versus quintile 1 (the least disadvantaged quintile) (p < 0.0001). After propensity score matching, the logistic regression showed no association between HS and social disadvantage in the 7-17 subgroup. In this minor population, an association between HS and social disadvantage was observed when propensity score matching was performed on age and sex only. CONCLUSIONS: We demonstrate a significant association between HS and low SES in the adult population. In children between 7 and 17, low SES was associated with obesity and tobacco consumption, but not with HS when the populations were matched on these confounding factors.

Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study.

BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Bariatric surgery reduces the risk of pancreatic cancer in individuals with obesity before the age of 50 years: A nationwide administrative data study in France.

BACKGROUND: Obesity is a well-established risk factor for pancreatic cancer. Bariatric surgery has demonstrated superior results in terms of weight loss and obesity-related comorbidities compared to medical and behavioral treatments. The aim of this study is to evaluate the effect of bariatric surgery on pancreatic cancer incidence in individuals with obesity. METHOD: Individuals with a diagnosis of obesity were retrieved from the French national hospital discharge database. We conducted a cohort study comparing the risk to develop pancreatic cancer in individuals with obesity with and without history of bariatric surgery; the inverse probability of treatment weighting (IPTW) method was performed to assess the uncertainty around the results. Moreover, a subgroup analysis according to age at the time of bariatric surgery was performed to study its impact on the risk of pancreatic cancer. Finally, possible differences depending on the type of bariatric procedure (sleeve gastrectomy vs Roux-en-Y gastric bypass) were also explored. RESULTS: 160,129 (Bariatric Surgery group) and 1,263,804 (control group) patients with 5.2 ± 1.9 and 6.0 ± 1.9 years of follow-up respectively were included. A significant reduced risk to develop pancreatic cancer during follow-up was identified for the bariatric surgery group in the overall population (HR: 0.567). However, this reduced risk was only observed in the 18-50 years group. These results were furtherly confirmed after IPTW analysis. No difference was found between different bariatric procedures. CONCLUSION: Bariatric surgery has a protective effect against pancreatic cancer in the 18-50 years population. High-quality prospective studies are needed to confirm these results.

Clinical and Economic Impact of Bariatric Surgery Post Liver Transplantation: a Nationwide, Population-Based Retrospective Study.

PURPOSE: Prevalence of obesity in liver transplant recipients is increasing with the overall epidemic augmentation of severe obesity, the effects of immunosuppressive drugs, and lifestyle changes which are responsible for de novo obesity development or aggravation of pre-existing obesity. The aim of this study is to analyze the differences in overall mortality, re-hospitalization rate, and hospitalization-related costs between patients undergoing bariatric surgery after liver transplantation and patients undergoing bariatric surgery alone. MATERIALS AND METHODS: Twenty patients with history of liver transplantation who underwent bariatric surgery were analyzed from the French National Hospital Discharge Database. Overall mortality, re-hospitalization rate, length of stay for bariatric procedure, and the costs of bariatric surgery hospitalization and eventual re-hospitalizations were compared to a group of 360,846 patients who underwent bariatric surgery alone from 2010 to 2019. Furthermore, a 1:1 propensity score matching analysis was conducted. RESULTS: Patients with a history of liver transplantation showed an increased risk of overall mortality (HR: 7.66, p = 0.0047) and increased costs of hospitalization for bariatric surgery (8250 ± 4822€ vs 5583 ± 3398€, p = 0.0005). No differences in length of stay, re-hospitalization rate, and costs were found after multivariate analysis. After propensity score matching analysis, a significant increased cost of hospitalization (8250 ± 4822€ vs 6086 ± 1813€, p = 0.0195) still resulted for the liver transplantation group. CONCLUSION: Bariatric surgery represents the best treatment for obesity and its related associated medical problems. Our study highlights an increased risk of overall all-cause mortality and increased costs of hospitalization in this population compared to patients undergoing bariatric surgery alone.

Four-week omega-3 polyunsaturated fatty acids supplementation for liver left lateral section volume reduction in individuals with morbid obesity undergoing bariatric surgery: A double blind, multicenter, randomized placebo-controlled trial.

BACKGROUND: Liver steatosis in morbidly obese individuals undergoing bariatric surgery increases liver volume and may complicate the surgical procedure. This study aimed to assess whether a 4-week supplementation with omega-3 polyunsaturated fatty acids (PUFA) is effective in reducing liver left lateral section (LLLS) volume. PATIENTS AND METHODS: This randomized controlled trial included morbidly obese individuals with metabolic syndrome undergoing bariatric surgery at 3 French bariatric centers between 2017 and 2020. The experimental group had a 4-week preoperative supplementation with omega-3 PUFA, whereas the control group had only placebo. The primary outcome was the reduction of the LLLS volume measured with Magnetic Resonance Imaging (MRI). RESULTS: 42 patients were randomized and 37 completed the study (19 in the experimental group and 18 in the placebo group). The mean LLLS volume decreased of 3.3% (±9.6) in the experimental group vs 1.0% (±18.3) in the placebo group, indicating that omega-3 PUFA were not effective in reducing the LLLS volume compared to the placebo (p = 0.3741). Omega-3 PUFA supplementation was not effective in reducing total liver volume, liver steatosis, rate of liver injuries during surgery and operative time. CONCLUSION: A 4-week preoperative supplementation with omega-3 PUFA was not effective in reducing LLLS volume in morbidly obese individuals undergoing bariatric surgery.

Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium.

OBJECTIVE: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. RESULTS: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND.

Clinical and Economic Impact of Previous Bariatric Surgery on Liver Transplantation: a Nationwide, Population-Based Retrospective Study.

PURPOSE: The present study aims to determine the impact of previous bariatric surgery (BS) on the length of hospital stay; the incidence of mortality, re-transplantation, and re-hospitalization after LT; and the related economic costs, through the analysis of the French National Health Insurance Information System. MATERIALS AND METHODS: All patients aged > 18 years who underwent LT in France in the period from 2010 to 2019 were included. Thirty-nine patients with a history of BS (study group) were compared with 1798 obese patients without previous BS (control group). RESULTS: At the time of LT, patients with a history of BS were significantly younger than those of the control group and had lower Charlson comorbidity index. Female sex was significantly more represented in the study group. No significant differences were detected between the two groups regarding the postoperative mortality rate after LT (10.3% in the study group versus 8.0% in the control group), long-term mortality (0.038 versus 0.029 person-year of follow-up, respectively), re-transplantation (adjusted hazard ratio (HR) = 2.15, p = 0.2437), re-hospitalization (adjusted analysis, IRR = 0.93, p = 0.7517), and costs of LT hospitalization (73,515 € in the study group versus 65,878 € in the control group). After 1:2 propensity score matching, the duration of the LT hospital stay was significantly longer in the study group (58.3 versus 33.4 days, p = 0.0172). CONCLUSION: No significant differences were detected between patients with previous BS versus obese patients without history of BS undergoing LT concerning the rates of mortality, re-LT, re-hospitalization after LT, and costs of hospitalization and re-hospitalizations.

Health-related quality of life of food-allergic children compared with healthy controls and other diseases.

BACKGROUND: Food allergy is a potentially life-threatening disease, affecting up to 10% of the pediatric population. OBJECTIVE: The aim of our study was to assess the health-related quality of life (HRQL) of food-allergic patients compared with the general population and patients with other chronic diseases with dietary or allergic burden, in a cross-sectional study. METHODS: We recruited patients aged 8-17 years diagnosed with food allergy and matched healthy controls recruited in schools. We also included patients with asthma, inflammatory bowel disease, celiac disease, diabetes, obesity, and eating disorders. We used the CHQ-CF87 questionnaire for generic HRQL assessment. Food allergy HRQL was also assessed using specific questionnaires: Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM). RESULTS: One hundred and thirty-five food-allergic children, 255 children with chronic diseases, and 463 healthy controls were included in the analyses. Food-allergic patients had a better HRQL than healthy controls in the Behavior (BE), Bodily Pain (BP), Family Activities (FA), and Mental Health (MH) domains and a worse HRQL in the General Health Perception (GH) domain (p = .048). Food-allergic patients exhibited a better HRQL than patients affected by other chronic diseases, notably diabetes. Although an epinephrine autoinjector had been prescribed to 87.4% of the food-allergic children, only 54.2% of them carried it at all times. CONCLUSION: Food-allergic patients display overall good HRQL compared with the general population and those with other diseases with daily symptoms and treatments, in line with recent improvements in food allergy management.

HeaLED: Assessment of skin healing under light-emitting diode (LED) exposure-A randomized controlled study versus placebo.

BACKGROUND: Light-emitting diodes (LEDs) in the visible or near-infrared spectrum have been reported to promote wound healing. However, despite being frequently proposed in daily clinical practice, the efficacy of photobiomodulation treatment after a laser procedure relies on very limited clinical data. OBJECTIVE: To compare the relative efficacy of LED versus placebo treatment in decreasing erythema and transepidermal water loss (TEWL) after a fractional CO2 session. METHODS: We conducted an open prospective intraindividual randomized controlled study with 10 healthy volunteers. An ablative fractional laser was performed on the seven forearm areas. Three consecutive daily sessions of LED (590, 630, and 850 nm [two tested irradiances each] and placebo) were applied after randomization. Physical measures (colorimetry, TEWL), photography, and clinical evaluation were performed on Days 1, 2, 3, 7, and 21. The main criterion of evaluation was the variation of parameter a* (erythema) at 72 hours for each LED parameter compared to placebo treatment. RESULTS: No significant differences in the variation of the parameter a* or any of the other studied parameters were found for the different LEDs compared to the placebo area. CONCLUSION: Photobiomodulation failed to improve healing after laser ablation compared to placebo.

Quick-Wee versus bladder stimulation to collect midstream urine from precontinent infants under 1 year of age: a study protocol for a randomised controlled trial (ES.Stimquick.U).

INTRODUCTION: Urinary tract infections occur in around 1%-4% of boys and 3%-8% of girls under 2 years old. Diagnosis is difficult because of non-specific symptoms and the risk of urine analysis contamination depending on the sampling method used for precontinent infants. The American Academy of Pediatrics recommend transurethral catheterisation and suprapubic aspiration because of a low contamination rate but these techniques are invasive. On the other hand, while the National Institute for Health and Care Excellence advocate clean catch urine for its minimal invasiveness and acceptable contamination rate, it is difficult to accomplish in precontinent infants. Two recent methods have been described: the Quick-Wee method by Kaufman et al (suprapubic stimulation with cold saline-soaked gauze); and bladder stimulation by Herreros et al then by Tran et al (pubic tapping alternating with lumbar massage). This study aims to compare the effectiveness in collecting midstream urine by bladder stimulation vs the Quick-Wee method in infants under 1 year, before walking. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial of 230 infants under 1 year and before walking who need urine analysis, conducted in four paediatric emergency departments in France. Patients will be randomised into two groups: bladder stimulation and Quick-Wee method.The primary endpoint will be the success rate of voiding at least 2 mL of urine in less than 5 min.Secondary outcomes are the time to collect at least 2 mL of urine, comfort, quality of urine and the risk factors associated with failure of the two techniques. ETHICS AND DISSEMINATION: The study protocol was approved by the French national ethic committee (consultative committee of the protection of persons). The results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical Trials Registry - NCT04587999. DATE AND PROTOCOL VERSION IDENTIFIER: October 2020, V.1.

Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium.

BACKGROUND: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. METHODS: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. RESULTS: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per µL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively). INTERPRETATION: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. 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 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 and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences.

Methotrexate treatment in hand osteoarthritis refractory to usual treatments: A randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To examine the effect of methotrexate (MTX) on pain and structural progression in symptomatic erosive hand osteoarthritis (HOA). METHODS: This 1-year prospective, single-centre, randomised, double-blind, placebo-controlled study (www.ClinicalTrial.gov, NCT01068405) followed up patients with symptomatic erosive HOA. Patients were randomised into two groups based on the drug that was administered: 10 mg methotrexate (MTX) per week or a placebo. The primary endpoint was the change in pain (determined using a visual analogue scale [VAS]) from baseline to 3 months. The secondary endpoints were pain VAS score at 12 months, clinical features (pain VAS score and function), radiographic features (the anatomical radiographic Verbruggen-Veys [VV] score and Gent University Score System), and magnetic resonance imaging (MRI) at 12 months. RESULTS: Sixty-four patients with HOA were randomised into either the placebo or MTX group. At 3 months, there was no significant difference in the mean decrease in the pain VAS score (mm) (MTX: 21.1 [standard deviation, 27.4], placebo: 11.7 [24.3]; p = 0.2). At 12 months, according to the VV score, erosive joints progressed significantly more to a remodelling phase in the MTX group than in the placebo group (27% vs 15%; p = 0.03). Joints with space loss appeared to be eroding less in the MTX group compared to the placebo group (8% vs 29%; p = 0.2). Synovitis on MRI at baseline could be associated with the erosive structural evolution of non-erosive joints (p = 0.02). CONCLUSIONS: Weekly doses of 10-mg MTX showed no superiority over the placebo in terms of pain relief at 3 or 12 months. CLINICAL TRIAL REGISTRATION NUMBER: This study was registered at www.ClinicalTrial.gov (NCT01068405).

Occipital Nerve Stimulation for Refractory Chronic Cluster Headache: A Cost-Effectiveness Study.

INTRODUCTION: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. MATERIALS AND METHODS: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second. RESULTS: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261). DISCUSSION: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. CONCLUSION: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.

Impact of smoking on femorotibial and hip osteoarthritis progression: 3-year follow-up data from the KHOALA cohort.

OBJECTIVES: To evaluate the clinical and structural impact of smoking on knee and hip osteoarthritis at baseline and after 3years. METHODS: Observational data on the progressive effects of smoking at baseline and after 3years were collected from The Knee and Hip Osteoarthritis Long-Term Assessment cohort comprising a French population of patients aged 40-75years with symptomatic lower limb osteoarthritis. Clinical (the Western Ontario and McMaster Universities Arthritis Index and Harris scores) and structural (radiography for osteophyte detection and joint-space narrowing assessment) were conducted. The tobacco usage categories were 'never smoker', 'former smoker', and 'current smoker'. RESULTS: Of the 873 subjects included, 215 (25%) were former smokers and 119 (14%) were current smokers. Multivariate analyses revealed that former and current smokers had fewer knee osteophytes in the medial compartment at baseline (odds ratio [OR]=0.64 [0.41-0.99] and 0.63 [0.36-1.11], respectively), lower osteophyte development in the lateral condyle after 3years (OR=011 [0.03-0.45] and 0.15 [0.03-0.97]), and lower osteophyte development in the lateral tibial plateau after 3years (OR=0.22 [0.06-0.75] and 0.68 [0.14-3.35]). Higher tobacco consumption and longer duration of consumption were significantly associated with fewer knee osteophytes at baseline and lower osteophyte development at 3years. CONCLUSION: Although cigarette smoking did not influence knee function, pain, or the need for replacement surgery, current and former smokers developed fewer osteophytes. This relationship may be linked to the quantity and duration of consumption. Our results provide further insight into the smoking-related pathophysiology of osteoarthritis.