Reducing the duration of antibiotic therapy in surgical patients through a specific nationwide antimicrobial stewardship program. A prospective, interventional cohort study

Anti-Bacterial Agents; Surgical Wound Infection; Infection ControlAgentes Antibacterianos; Infección de Heridas Quirúrgicas; Control de la infecciónAgents antibacterians; Infecció de la ferida quirúrgica; Control de la infeccióBackground: Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to reduce the duration of treatments in surgical patients to <7 days. Methods: Prospective cohort study evaluating surgical patients receiving antibiotics ≥7 days in 32 hospitals. Indication for treatment, quality of source control, type of recommendations issued, and adherence to the recommendations were analysed. Temporal trends in the percentages of patients with treatment >7 days were evaluated using a linear regression model and Pearson's correlation coefficients. Results: A total of 32 499 patients were included. Of these, 13.7% had treatments ≥7 days. In all, 3912 stewardship interventions were performed, primarily in general surgery (90.7%) and urology (8.1%). The main types of infection were intra-abdominal (73.4%), skin/soft tissues (9.8%) and urinary (9.2%). The septic focus was considered controlled in 59.9% of cases. Out of 5458 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (21.7%), metronidazole (11.2%), amoxicillin/clavulanate (10.3%), meropenem (10.7%), ceftriaxone (9.3%) and ciprofloxacin (6.7%). The main recommendations issued were: treatment discontinuation (35.0%), maintenance (40.0%) or de-escalation (15.5%), and the overall adherence rate was 91.5%. With adequate source control, the most frequent recommendation was to terminate treatment (51.2%). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (Pc=-0.69;P < 0.001). Conclusions: This stewardship programme reduced the duration of treatments in surgical departments. Preference was given to general surgery services, intra-abdominal infection, and beta-lactam antibiotics, including carbapenems. Adherence to the issued recommendations was high

Early functional and morphological muscle adaptations during short-term inertial-squat training

Purpose: To assess early changes in muscle function and hypertrophy, measured as increases in muscle cross-sectional areas (CSAs) and total volume, over a 4 weeks inertial resistance training (RT) program. Methods: Ten young RT-naive volunteers (age 23.4 4.1 years) underwent 10 training sessions (2-3 per week) consisting of five sets of 10 flywheel squats (moment of inertia 900 kg cm2). Magnetic resonance imaging (MRI) scans of both thighs were performed before (PRE), and after 2 (IN) and 4 (POST) weeks of training to compute individual muscle volumes and regional CSAs. Scans were performed after 96 h of recovery after training sessions, to avoid any influence of acute muscle swelling. PRE and POST regional muscle activation was assessed using muscle functional MRI (mfMRI) scans. Concentric (CON) and eccentric (ECC) squat force and power, as well as maximal voluntary isometric contraction force (MVIC) of knee extensors and flexors, were measured in every training session. Results: Significant quadriceps hypertrophy was detected during (IN: 5.5% 1.9%) and after (POST: 8.6% 3.6%) the training program. Increases in squat force (CON: 32% 15%, ECC: 31 15%) and power (CON: 51% 30%, ECC: 48% 27%) were observed over the training program. Knee extensor MVIC significantly increased 28% 17% after training, but no changes were seen in knee flexor MVIC. No correlation was found between regional muscular activation in the first session and the % of increase in regional CSAs (r = -0.043, P = 0.164). Conclusion: This study reports the earliest onset of whole-muscle hypertrophy documented to date. The process initiates early and continues in response to RT, contributing to initial increases in force. The results call into question the reliability of mfMRI as a tool for predicting the potential hypertrophic effects of a given strengthening exercise

Spatiotemporal characteristics of motor actions by blind long jump athletes

Background Blind people depend on spatial and temporal representations to perform activities of daily living and compete in sport. Objective The aim of this study is to determine the spatiotemporal characteristics of long jumps performed by blind athletes and compare findings with those reported for sighted athletes. Methods We analysed a sample of 12 male athletes competing in the F11 Long Jump Finals at the Paralympic Games in London 2012. Performances were recorded using four high-speed cameras, and speeds were measured using a radar speed gun. The images were processed using validated image analysis software. Results The long jump run-up is shorter in blind athletes than in sighted athletes. We observed statistically significant differences for body centre of mass velocity and an increase in speed over the last three strides prior to take-off, contrasting with reports for sighted athletes and athletes with less severe visual impairment, who maintain or reduce their speed during the last stride. Stride length for the last three strides was the only spatial characteristic that was not significantly associated with effective jump distance. Blind long jumpers extend rather than shorten their last stride. Contact time with the take-off board is longer than that reported for sighted athletes. Conclusion The actions of blind long jumpers, unlike those without disabilities, do not vary their leg actions during the final runway approach for optimal placement on the take-off board

Kinematic characteristics of the long jump approach run in paralympic-level male limb-deficients

The purpose of this study was to define the variables typifying the long jump approach run phase in paralympic-level male amputees. The sample comprised of the eleven (4 transtibial, 5 transfemoral and 2 single below-the-knee amputees). The parameters analysed were: official distance, toe-to-board distance, effective distance, stride contact time, stride flight time, total stride time, stride length, stride frequency, stride velocity, horizontal velocity, vertical velocity, resultant velocity, height of body center of mass, take-off stride angle, relative differences in stride length and relative differences in stride frequency. The findings of the study revealed that 77.8% of the para-athletes perform the take-off with the leg supported by the prosthesis. Horizontal velocity during the last three strides before take-off has been shown to have a high correlation with the official jump distance: 3rd last (r=0.65, p<0.05), 2nd last (r=0.69, p<0.05) and last (r=0.67, p<0.05) strides. Stride length and stride frequency patterns for the 3rd, 2nd and last strides were as follows: medium-long-short and high-low-high. Horizontal velocity at the last stride is higher compared to the preceding two. The findings of the study support the notion that a wide range of similarities exist in the running patterns and factors correlating with jumping distance between Paralympic amputee athletes and able-bodied high-level athletes

Early Functional and Morphological Muscle Adaptations During Short-Term Inertial-Squat Training

Purpose: To assess early changes in muscle function and hypertrophy, measured as increases in muscle cross-sectional areas (CSAs) and total volume, over a 4 weeks inertial resistance training (RT) program.Methods: Ten young RT-naive volunteers (age 23.4 ± 4.1 years) underwent 10 training sessions (2–3 per week) consisting of five sets of 10 flywheel squats (moment of inertia 900 kg⋅cm2). Magnetic resonance imaging (MRI) scans of both thighs were performed before (PRE), and after 2 (IN) and 4 (POST) weeks of training to compute individual muscle volumes and regional CSAs. Scans were performed after ≥96 h of recovery after training sessions, to avoid any influence of acute muscle swelling. PRE and POST regional muscle activation was assessed using muscle functional MRI (mfMRI) scans. Concentric (CON) and eccentric (ECC) squat force and power, as well as maximal voluntary isometric contraction force (MVIC) of knee extensors and flexors, were measured in every training session.Results: Significant quadriceps hypertrophy was detected during (IN: 5.5% ± 1.9%) and after (POST: 8.6% ± 3.6%) the training program. Increases in squat force (CON: 32% ± 15%, ECC: 31 ± 15%) and power (CON: 51% ± 30%, ECC: 48% ± 27%) were observed over the training program. Knee extensor MVIC significantly increased 28% ± 17% after training, but no changes were seen in knee flexor MVIC. No correlation was found between regional muscular activation in the first session and the % of increase in regional CSAs (r = -0.043, P = 0.164).Conclusion: This study reports the earliest onset of whole-muscle hypertrophy documented to date. The process initiates early and continues in response to RT, contributing to initial increases in force. The results call into question the reliability of mfMRI as a tool for predicting the potential hypertrophic effects of a given strengthening exercise

Time course and association of functional and biochemical markers in severe semitendinosus damage following intensive eccentric leg curls: differences between and within subjects

Purpose: To investigate the extent and evolution of hamstring muscle damage caused by an intensive bout of eccentric leg curls (ELCs) by (1) assessing the time course and association of different indirect markers of muscle damage such as changes in the force-generating capacity (FGC), functional magnetic resonance (fMRI), and serum muscle enzyme levels and (2) analyzing differences in the degree of hamstring muscle damage between and within subjects (limb-to-limb comparison). Methods: Thirteen male participants performed six sets of 10 repetitions of an ELC with each leg. Before and at regular intervals over 7 days after the exercise, FGC was measured with maximal isometric voluntary contraction (MVC). Serum enzyme levels, fMRI transverse relaxation time (T2) and perceived muscle soreness were also assessed and compared against the FGC. Results: Two groups of subjects were identified according to the extent of hamstring muscle damage based on decreased FGC and increased serum enzyme levels: high responders (n = 10, severe muscle damage) and moderate responders (n = 3, moderate muscle damage). In the high responders, fMRI T2 analysis revealed that the semitendinosus (ST) muscle suffered severe damage in the three regions measured (proximal, middle, and distal). The biceps femoris short head (BFsh) muscle was also damaged and there were significant differences in the FGC within subjects in the high responders. Conclusion: FGC and serum enzyme levels measured in 10 of the subjects from the sample were consistent with severe muscle damage. However, the results showed a wide range of peak MVC reductions, reflecting different degrees of damage between subjects (high and moderate responders). fMRI analysis confirmed that the ST was the hamstring muscle most damaged by ELCs, with uniform T2 changes across all the measured sections of this muscle. During intensive ELCs, the ST muscle could suffer an anomalous recruitment pattern due to fatigue and damage, placing an excessive load on the BFsh and causing it to perform a synergistic compensation that leads to structural damage. Finally, T2 and MVC values did not correlate for the leg with the smaller FGC decrease in the hamstring muscles, suggesting that long-lasting increases in T2 signals after FGC markers have returned to baseline values might indicate an adaptive process rather than damage

Level of hamstrings damage depending on force-generating capacity and creatine kinase activity

The aim of the present study was to categorize the eccentric exercise-induced hamstrings damage by using easy measurable markers such as force-generating capacity and serum creatine kinase activityPeer ReviewedPostprint (published version

Epigenome-wide association study in peripheral tissues highlights DNA methylation profiles associated with episodic memory performance in humans

The decline in episodic memory (EM) performance is a hallmark of cognitive aging and an early clinical sign in Alzheimer&rsquo;s disease (AD). In this study, we conducted an epigenome-wide association study (EWAS) using DNA methylation (DNAm) profiles from buccal and blood samples for cross-sectional (n = 1019) and longitudinal changes in EM performance (n = 626; average follow-up time 5.4 years) collected under the auspices of the Lifebrain consortium project. The mean age of participants with cross-sectional data was 69 &plusmn; 11 years (30&ndash;90 years), with 50% being females. We identified 21 loci showing suggestive evidence of association (p &lt; 1 &times; 10&minus;5) with either or both EM phenotypes. Among these were SNCA, SEPW1 (both cross-sectional EM), ITPK1 (longitudinal EM), and APBA2 (both EM traits), which have been linked to AD or Parkinson&rsquo;s disease (PD) in previous work. While the EM phenotypes were nominally significantly (p &lt; 0.05) associated with poly-epigenetic scores (PESs) using EWASs on general cognitive function, none remained significant after correction for multiple testing. Likewise, estimating the degree of &ldquo;epigenetic age acceleration&rdquo; did not reveal significant associations with either of the two tested EM phenotypes. In summary, our study highlights several interesting candidate loci in which differential DNAm patterns in peripheral tissue are associated with EM performance in humans

Reducing the duration of antibiotic therapy in surgical patients through a specific nationwide antimicrobial stewardship program. A prospective, interventional cohort study

Background: Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to reduce the duration of treatments in surgical patients to 7 days were evaluated using a linear regression model and Pearson's correlation coefficients. Results: A total of 32,499 patients were included. Of these, 13.7% had treatments ≥7 days. In all, 3,912 stewardship interventions were performed, primarily in general surgery (90.7%) and urology (8.1%). The main types of infection were intra-abdominal (73.4%), skin/soft tissues (9.8%) and urinary (9.2%). The septic focus was considered controlled in 59.9% of cases. Out of 5,458 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (21.7%), metronidazole (11.2%), amoxicillin/clavulanate (10.3%), meropenem (10.7%), ceftriaxone (9.3%) and ciprofloxacin (6.7%). The main recommendations issued were: treatment discontinuation (35.0%), maintenance (40.0%) or de-escalation (15.5%), and the overall adherence rate was 91.5%. With adequate source control, the most frequent recommendation was to terminate treatment (51.2%). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (Pc=-0.69;p<0.001). Conclusions: This stewardship programme reduced the duration of treatments in surgical departments. Preference was given to general surgery services, intra-abdominal infection, and beta-lactam antibiotics, including carbapenems. Adherence to the issued recommendations was high

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