Standard versus fractionated high-dose cisplatin plus radiation for locally advanced head and neck cancer: Results of the CisFRad (GORTEC 2015-02) randomized phase II trial.

BACKGROUND: Chemoradiotherapy with high-dose cisplatin (HD-Cis: 100 mg/m2 q3w for three cycles) is the standard of care (SOC) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Cumulative delivered dose of cisplatin is prognostic of survival, even beyond 200 mg/m2 but high toxicity compromises its delivery. AIM: Cisplatin fractionation may allow, by decreasing the peak serum concentration, to decrease toxicity. To date, no direct comparison was done of HD-Cis versus fractionated high dose cisplatin (FHD-Cis). METHODS: This is a multi-institutional randomized phase II trial, stratified on postoperative or definitive chemoradiotherapy, comparing HD-Cis to FHD-Cis (25 mg/m2/d d1-4 q3w for 3 cycles) in patients with LA-HNSCC. The primary endpoint was the cumulative delivered cisplatin dose. RESULTS: Between December 2015 and April 2018, 124 patients were randomized. Median cisplatin cumulative delivered dose was 291 mg/m2 (IQR: 251;298) in the FHD-Cis arm and 274 mg/m2 (IQR: 198;295) in the HD-Cis arm (P = 0.054). The proportion of patients receiving a third cycle of cisplatin was higher, with a lower proportion of grade 3-4 acute AEs in the FHD-Cis arm compared to the HD-Cis arm: 81 % vs. 64 % (P = 0.04) and 10 % vs. 17 % (P = 0.002), respectively. With a median follow-up of 48 months (IQR: 41;55), locoregional failure rate, PFS and OS were similar between the two arms. CONCLUSION: Although the primary endpoint was not met, FHD-Cis allowed more cycles of cisplatin to be delivered with lower toxicity, when compared to SOC. FHD-Cis concurrently with RT is a treatment option which deserves further consideration.

Effect of nutritional supplementation on bone mineral density in children with sickle cell disease: protocol for an open-label, randomised controlled clinical trial.

INTRODUCTION: Children with sickle cell disease show a significant decrease in bone mineral density, an increase in resting energy expenditure of more than 15%, a decrease in fat and lean mass as well as a significant increase in protein turnover, particularly in bone tissue. This study aims to evaluate the effectiveness of an increase in food intake on bone mineral density and the clinical and biological complications of paediatric sickle cell disease. METHODS AND ANALYSIS: The study is designed as an open-label randomised controlled clinical trial conducted in the Paediatrics Unit of the Orléans University Hospital Centre. Participants aged 3-16 years will be randomly divided into two groups: the intervention group will receive oral nutritional supplements (pharmacological nutritional hypercaloric products) while the control group will receive age-appropriate and gender-appropriate nutritional intake during 12 months. Total body less head bone mineral density will be measured at the beginning and the end of the trial. A rigorous nutritional follow-up by weekly 24 hours recall dietary assessment and planned contacts every 6 weeks will be carried out throughout the study. A school absenteeism questionnaire, intended to reflect the patient's school productivity, will be completed by participants and parents every 3 months. Blood samples of each patient of both groups will be stocked at the beginning and at the end of the trial, for future biological trial. Clinical and biological complications will be regularly monitored. ETHICS AND DISSEMINATION: The protocol has been approved by the French ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse; approval no: 2-20-092 id9534). Children and their parents will give informed consent to participate in the study before taking part. Results will be disseminated through peer-reviewed journals or international academic conferences. TRIAL REGISTRATION NUMBER: NCT04754711.

Proton pump inhibitors in esophageal atresia: A systematic review and meta-analysis.

Gastroesophageal reflux disease (GERD) is frequent and prolonged in esophageal atresia (EA) pediatric patients requiring routine use of proton pump inhibitors (PPIs). However, there are still controversies on the prophylactic use of PPIs and the efficacy of PPIs on GERD and EA complications in this special condition. The aim of the study is to assess the prophylactic use of PPIs in pediatric patients with EA and its complications. We, therefore, performed a systematic review including all reports on the subject from 1980 to 2022. We conducted meta-analysis of the pooled proportion of PPI-and no PPI groups using random effect model, meta-regression, and estimate heterogeneity by heterogeneity index I2 . Thirty-eight reports on the topic met the criteria selection, representing a cumulative 6044 patients with EA. Prophylactic PPI prescription during the first year of life does not appear to prevent GERD persistence at follow-up and is not associated with a significantly reduced rate of antireflux surgical procedures (ARP). PPIs improve peptic esophagitis and induce remission of eosinophilic esophagitis at a rate of 50%. Their effect on other GERD outcomes is uncertain. Evidence suggests that PPIs do not prevent anastomotic stricture, Barrett's esophagus, or respiratory complications. PPI use in EA can improve peptic and eosinophilic esophagitis but is ineffective on the other EA complications. Side effects of PPIs in EA are almost unknown.

Patterns of Benzodiazepine Use and Excess Risk of All-Cause Mortality in the Elderly: A Nationwide Cohort Study.

INTRODUCTION: Despite the risks associated with their use, benzodiazepines remain used more widely than wisely. In this context, a better understanding of how their patterns of use can be associated with an increased risk of death appears essential. Indeed, the studies that investigated this association so far are inconsistent and question the influence of potential biases. OBJECTIVE: The objective of this study was to investigate the association of various patterns of benzodiazepine use with all-cause mortality. METHODS: A nationwide cohort of non-prevalent benzodiazepine users aged ≥ 65 years was identified using French healthcare insurance system claims databases. Exposure to benzodiazepines considered short-term, chronic (defined as a cumulated ≥ 6-month period over the previous 12 months), ongoing, and discontinued use. Using a Cox model, adjusted hazard ratios for all-cause mortality were estimated according to benzodiazepine patterns of use; exposure and confounders were treated as time-dependent variables. RESULTS: In the cohort of 54,958 individuals aged ≥ 65 years, adjusted hazard ratios for all-cause mortality and benzodiazepines were 2.26 (95% confidence interval 1.96-2.61) for short-term use, 3.86 (3.04-4.90) for chronic use-discontinued, and 3.05 (2.17-4.29) for chronic use-ongoing. At age 80 years, these were 1.62 (1.48-1.79), 2.00 (1.82-2.19) and 1.13 (1.02-1.26), respectively. Adjusted hazard ratios show similar decreases with age for all patterns of benzodiazepine use. CONCLUSIONS: These findings confirm the existence of an excess risk of mortality associated with benzodiazepine use and provide pattern- and age-specific estimates. Higher risks were observed for patients aged < 80 years, short-term use, or chronic use recently interrupted. If the two latter can relate to an indication bias, the associations found for ongoing chronic use and short-term use conversely support a potential causal hypothesis.

Projections of prevalence, lifetime risk, and life expectancy of Parkinson's disease (2010-2030) in France.

BACKGROUND: Previous studies on the number of Parkinson's disease (PD) patients in the future based on projections of population size underestimated PD burden because they did not take into account the improvement of life expectancy over time. OBJECTIVE: The objective of this study was to assess PD progression from 2010 to 2030 in France in terms of prevalent patient numbers, prevalence rates, lifetime risk, and life expectancy with PD, accounting for projections of overall mortality and increased risk of death of PD patients. METHODS: To provide projections of PD burden, we applied a multistate approach considering age and calendar time to incidence and prevalence rates of PD (France 2010) based on drug claims and national demographic data. RESULTS: The number of PD patients will increase by ∼65% between 2010 (n = 155,000) and 2030 (n ∼ 260,000), mainly for individuals older than 65 years; the prevalence rate of PD after age 45 will increase from 0.59% in 2010 to ∼0.80% in 2030. We project an extension of ∼3 years of the life expectancy of PD patients at 65 years between 2010 (women, 14.8 years; men, 13.0 years) and 2030 (women, 17.8 years; men, 16.1 years), and a relative increase of about 10% of the lifetime risk of PD at 45 years between 2010 (women, 5.5%; men, 6.0%) and 2030 (women, 6.3%; men, 7.4%). CONCLUSIONS: The number of PD patients is predicted to grow substantially in future years as a consequence of population aging and life expectancy improvement. The assessment of the future PD burden is an important step for planning resources needed for patient care in aging societies. © 2018 International Parkinson and Movement Disorder Society.

Impact of intervention targeting risk factors on chronic disease burden.

The aging of the population is accompanied by a sharp rise of chronic disease prevalences, such as dementia. These diseases generally cannot be prevented or cured and persist over time, with a progressive deterioration of health, requiring specific care. To reduce the burden of these diseases, it is appropriate to propose interventions targeting disease risk factors, but the association between most of these risk factors and mortality makes it difficult to anticipate the potential impact of such interventions. A method was previously proposed to estimate changes in disease prevalence following an intervention targeting subjects at a given age where the incidence of the disease is supposed to be null. Here, we propose a general framework to make projections for life expectancies with and without the disease, the age at onset, and the lifelong probability of the disease, and to evaluate the consequences of preventive interventions targeting risk factors on these various measures of disease burden. The methodology takes into account the mortality trend over calendar time and age in both healthy and diseased subjects, and the change in mortality due to the intervention. The method is applied to make projections for dementia in 2030 according to several scenarios of public health interventions.

Projections of health indicators for chronic disease under a semi-Markov assumption.

Chronic diseases are a growing public health problem due to the population aging. Their economic, social and demographic burden will worsen in years to come. Up to now, the method used to provide projections and assess the future disease burden makes a non-homogeneous Markov assumption in an illness-death model. Both age and calendar year have been taken into account in all parameter estimations, but the time spent with the disease was not considered. This work develops the method with a semi-Markov assumption to model mortality among the diseased and considering the time spent with the disease. The method is applied to estimate several health indicators for dementia in France in 2030. We find that mortality among the individuals with dementia depends on age, calendar year and disease duration, and it is greater for men than for women at all ages. The projections for 2030 suggest a 27% increase of the number of dementia cases. The model proposed in this work has flexible assumptions that make it adaptable to provide projections for various diseases.