Predictive Value of Skeletal Muscle Mass in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients Treated With Immune Checkpoint Inhibitors

Background Reduced muscle mass has been associated with increased treatment complications in several tumor types. We evaluated the impact of skeletal muscle index (SMI) on prognosis and immune-related adverse events (IrAEs) in a cohort of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoints inhibitors (ICI). Methods A single-institutional, retrospective study was performed including 61 consecutive patients of R/M HNSCC diagnosed between July 2015 and December 2018. SMI was quantified using a CT scan at L3 to evaluate body composition. Median baseline SMI was used to dichotomize patients in low and high SMI. Kaplan-Meier estimations were used to detect overall survival (OS) and progression-free survival (PFS). Toxicity was recorded using Common Terminology Criteria for Adverse Event v4.3. Results Patients were 52 men (85.2%) with mean of age 57.7 years (SD 9.62), mainly oral cavity (n = 21; 34.4%). Low SMI was an independent factor for OS in the univariate (HR, 2.06; 95% CI, 1.14-3.73, p = 0.017) and multivariate Cox analyses (HR, 2.99; 95% CI, 1.29-6.94; p = 0.011). PFS was also reduced in patients with low SMI (PFS HR, 1.84; 95% CI, 1.08-3.12; p = 0.025). IrAEs occurred in 29 (47.5%) patients. There was no association between low SMI and IrAEs at any grade (OR, 0.56; 95% CI, 0.20-1.54; p = 0.261). However, grades 3 to 4 IrAEs were developed in seven patients of whom three had low SMI. Conclusions Low SMI before ICI treatment in R/M HNSCC patients had a negative impact on OS and PFS. Further prospective research is needed to confirm the role of body composition as a predictive biomarker in ICI treatment

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: Study protocol for the SAFO trial

Introduction Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (=18 years) with isolation of MSSA from at least one blood culture =72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

ThresholdROC: optimum threshold estimation tools for continuous diagnostic tests in R

We introduce an R package that estimates decision thresholds in diagnostic settings with a continuous marker and two or three underlying states. The package implements parametric and non-parametric estimation methods based on minimizing an overall cost function, as well as confidence interval estimation approaches to account for the sampling variability of the cut-off. Further features of the package include sample size determination and estimation of diagnostic accuracy measures. We used randomly generated data and two real datasets to illustrate the capabilities and characteristics of the package

ThresholdROC: optimum threshold estimation tools for continuous diagnostic tests in R

We introduce an R package that estimates decision thresholds in diagnostic settings with a continuous marker and two or three underlying states. The package implements parametric and non-parametric estimation methods based on minimizing an overall cost function, as well as confidence interval estimation approaches to account for the sampling variability of the cut-off. Further features of the package include sample size determination and estimation of diagnostic accuracy measures. We used randomly generated data and two real datasets to illustrate the capabilities and characteristics of the package

Citizens' perceptions of the presence and health risks of synthetic chemicals in food: results of an online survey in Spain

Objective: To explore factors influencing perceptions and viewpoints on the responsibility for the presence of toxic substances in food, on enforcement of laws and regulations that control human exposure to toxic substances in food, and on the effectiveness of such regulations. Methods: An online survey was completed by 740 individuals from several parts of Spain (median age, 47 years; 67% were women; 70% had completed university studies). Results: Over 87% of respondents said that it was possible that throughout their lives they could have accumulated in their body toxic substances potentially dangerous to their health. The attribution of the responsibility for toxic substances in food to a larger number of social groups was more frequent among respondents who consulted information about the problem more often (odds ratio [OR]: 1.92), who correctly identified factors that increase the likelihood of toxic substances in food being harmful to human health (OR: 2.86), who better knew the health problems that may be caused by such substances (OR: 2.48), and who recognised more food groups that tend to have concentrations of toxic substances potentially harmful to health (OR: 2.92) (all p values <0.001). Women were 65% less likely than men to answer that regulations on toxic substances in food are effective (p < 0.001); and so were participants who identified more food groups with potentially toxic concentrations. Conclusions: Among study participants there was a widespread scepticism and distrust towards the enforcement and effectiveness of laws and regulations that in Spain aim to control human exposure to toxic substances in food

Infectious diseases experts as part of the antibiotic stewardship team in primary care: protocol for a cluster-randomised blinded study (IDASP)

Introduction: Antibiotic overuse is directly related to antibiotic resistance, and primary care is one of the main reasons for this overuse. This study aims to demonstrate that including experts on infectious diseases (ID) within the antimicrobial stewardship (AMS) programme team in primary care settings achieves higher reductions in overall antibiotic consumption and increases the quality of prescription. Methods and analysis: A multicentre, cluster-randomised, blinded clinical trial will be conducted between 2021 and 2023. Six primary care centres will be randomly assigned to an advanced or a standard AMS programme. The advanced AMS programme will consist of a standard AMS programme combined with the possibility that general practitioners (GP) will discuss patients' therapies with ID experts telephonically during working days and biweekly meetings. The main endpoint will be overall antibiotic consumption, defined as daily defined dose per 1000 inhabitants per day (DHD). Secondary end-points will be: (1) unnecessary antibiotic prescriptions in patients diagnosed with upper respiratory tract or urinary tract infection, (2) adequacy of antibiotic prescription, (3) reattendance to GP or emergency room within 30 days after the initial GP visit and (4) hospital admissions for any reason within 30 days after the GP visit. Two secondary endpoints (unnecessary antibiotic therapy and adequacy of therapy) will be evaluated by blinded investigators.We will select three clusters (centres) per arm (coverage of 147 644 inhabitants) which will allow the rejection of the null hypothesis of equal consumption with a power of 80%, assuming a moderate intracluster correlation of 0.2, an intracluster variance of 4 and a mean difference of 1 DHD. The type I error will be set at 5%

A propensity-score-matched analysis of laparoscopic vs open surgery for rectal cancer in a population-based study

Aim: the oncological risk/benefit trade-off for laparoscopy in rectal cancer is controversial. Our aim was to compare laparoscopic vs open surgery for resection of rectal cancer, using unselected data from the public healthcare system of Catalonia. Methods: this was a multicentre retrospective cohort study of all patients who had surgery with curative intent for primary rectal cancer at Catalonian public hospitals from 2011 to 2012. We obtained follow-up data for up to 5 years. To minimize the differences between the two groups, we performed propensity score matching on baseline patient characteristics. We used multivariate Cox proportional hazards regression analyses to assess locoregional relapse at 2 years and death at 2 and 5 years. Results: of 1513 patients with Stage I-III rectal cancer, 933 (61.7%) had laparoscopy (conversion rate 13.2%). After applying our propensity score matching strategy (2:1), 842 laparoscopy patients were matched to 517 open surgery patients. Multivariate Cox analysis of death at 2 years [hazard ratio (HR) 0.65, 95% CI 0.48, 0.87; P = 0.004] and 5 years (HR 0.61, 95% CI 0.5, 0.75; P < 0.001) and of local relapse at 2 years (HR 0.44, 95% CI 0.27, 0.72; P = 0.001) showed laparoscopy to be an independent protective factor compared with open surgery. Cconclusions: laparoscopy results in lower locoregional relapse and long-term mortality in rectal cancer in unselected patients with all-risk groups included. Studies using long-term follow-up of cohorts and unselected data can provide information on clinically relevant outcomes to supplement randomized controlled trials

A propensity-score-matched analysis of laparoscopic vs open surgery for rectal cancer in a population-based study

Aim: the oncological risk/benefit trade-off for laparoscopy in rectal cancer is controversial. Our aim was to compare laparoscopic vs open surgery for resection of rectal cancer, using unselected data from the public healthcare system of Catalonia. Methods: this was a multicentre retrospective cohort study of all patients who had surgery with curative intent for primary rectal cancer at Catalonian public hospitals from 2011 to 2012. We obtained follow-up data for up to 5 years. To minimize the differences between the two groups, we performed propensity score matching on baseline patient characteristics. We used multivariate Cox proportional hazards regression analyses to assess locoregional relapse at 2 years and death at 2 and 5 years. Results: of 1513 patients with Stage I-III rectal cancer, 933 (61.7%) had laparoscopy (conversion rate 13.2%). After applying our propensity score matching strategy (2:1), 842 laparoscopy patients were matched to 517 open surgery patients. Multivariate Cox analysis of death at 2 years [hazard ratio (HR) 0.65, 95% CI 0.48, 0.87; P = 0.004] and 5 years (HR 0.61, 95% CI 0.5, 0.75; P < 0.001) and of local relapse at 2 years (HR 0.44, 95% CI 0.27, 0.72; P = 0.001) showed laparoscopy to be an independent protective factor compared with open surgery. Cconclusions: laparoscopy results in lower locoregional relapse and long-term mortality in rectal cancer in unselected patients with all-risk groups included. Studies using long-term follow-up of cohorts and unselected data can provide information on clinically relevant outcomes to supplement randomized controlled trials

A propensity-score-matched analysis of laparoscopic vs open surgery for rectal cancer in a population-based study

Aim: the oncological risk/benefit trade-off for laparoscopy in rectal cancer is controversial. Our aim was to compare laparoscopic vs open surgery for resection of rectal cancer, using unselected data from the public healthcare system of Catalonia. Methods: this was a multicentre retrospective cohort study of all patients who had surgery with curative intent for primary rectal cancer at Catalonian public hospitals from 2011 to 2012. We obtained follow-up data for up to 5 years. To minimize the differences between the two groups, we performed propensity score matching on baseline patient characteristics. We used multivariate Cox proportional hazards regression analyses to assess locoregional relapse at 2 years and death at 2 and 5 years. Results: of 1513 patients with Stage I-III rectal cancer, 933 (61.7%) had laparoscopy (conversion rate 13.2%). After applying our propensity score matching strategy (2:1), 842 laparoscopy patients were matched to 517 open surgery patients. Multivariate Cox analysis of death at 2 years [hazard ratio (HR) 0.65, 95% CI 0.48, 0.87; P = 0.004] and 5 years (HR 0.61, 95% CI 0.5, 0.75; P < 0.001) and of local relapse at 2 years (HR 0.44, 95% CI 0.27, 0.72; P = 0.001) showed laparoscopy to be an independent protective factor compared with open surgery. Cconclusions: laparoscopy results in lower locoregional relapse and long-term mortality in rectal cancer in unselected patients with all-risk groups included. Studies using long-term follow-up of cohorts and unselected data can provide information on clinically relevant outcomes to supplement randomized controlled trials

One Health: la reflexión, un aspecto clave para pasar a la acción

El enfoque One Health aboga por un modelo basado en conservar y promover los activos generadores de salud en su sentido más amplio (salud humana, salud animal, salud ambiental y salud de los ecosistemas). Su sencillez conceptual contrasta con la gran dificultad que supone trasladar este enfoque a la realidad de forma efectiva. Podemos identificar numerosos factores que contribuyen a esta dificultad, pero en esencia todos ellos tienen un origen común: la visión que actualmente prevalece en todos los niveles de la sociedad acerca del significado del término saludPeer reviewe