Blood cultures remain the gold standard for detecting bacteremia despite their limitations. The current practice of blood culture collection is still inefficient with low yields. Limited focus has ...been given to the association between timing of specimen collection at different time points during admission and their yield.
We carried out a retrospective observational study by analyzing all 3,890 sets of cultures collected from the 1,962 admitted patients over the seven-month period of this study. We compared the blood culture yield between the early group (≤24 hours after admission) and the late group (> 24 hours of admission). We also investigated the effect of prehospital oral antibiotics and pre-analytical time on the first cultures in the emergency department. Epidemiology and efficiency of blood cultures were studied for each medical specialty.
In total, 3,349(86.1%) blood cultures were negative and 541(13.9%) were positive for one or more microorganisms. After correcting for contamination, the overall yield was 290 (7.5%). The early group (n = 1,490) yielded significantly more true-positive cultures (10.1% versus 5.8%, P<0.001) than the late group (n = 2,400). The emergency department had a significantly higher yield than general wards, 11.2% versus 5.7% (p<0.001). Prehospital oral antibiotic use and pre-analytical time did not affect the yield of first cultures at the emergency department (p = 0.735 and 0.816 respectively). The number of tests needed to obtain one true-positive culture varied between departments, ranging from 7 to 45.
This study showed that blood cultures are inefficient in detecting bacteremia. Cultures collected during 24 hours after admission yielded more positive results than those collected later. Significant variations in blood culture epidemiology and efficiency per specialty suggest that guidelines should be reevaluated. Future studies should aim at improving blood culture yield, implementing educational programs to reduce contamination and cost-effective application of modern molecular diagnostic technologies.
Background
Transanal total mesorectal excision (TaTME) provides an excellent view of the resection margins for rectal cancer from below, but is challenging due to few anatomical landmarks. During ...implementation of this technique, patient safety and optimal outcomes need to be ensured. The aim of this study was to evaluate the learning curve of TaTME in patients with rectal cancer in order to optimize future training programs.
Methods
All consecutive patients after TaTME for rectal cancer between February 2012 and January 2017 were included in a single-center database. Influence of surgical experience on major postoperative complications, leakage rate and operating time was evaluated using cumulative sum charts and the splitting model. Correction for potential case-mix differences was performed.
Results
Over a period of 60 months, a total of 138 patients were included in this study. Adjusted for case-mix, improvement in postoperative outcomes was clearly seen after the first 40 patients, showing a decrease in major postoperative complications from 47.5 to 17.5% and leakage rate from 27.5 to 5%. Mean operating time (42 min) and conversion rate (from 10% to zero) was lower after transition to a two-team approach, but neither endpoint decreased with experience. Readmission and reoperation rates were not influenced by surgical experience.
Conclusions
The learning curve of TaTME affected major (surgical) postoperative complications for the first 40 patients. A two-team approach decreased operative time and conversion rate. When implementing this new technique, a thorough teaching and supervisory program is recommended to shorten the learning curve and improve the clinical outcomes of the first patients.
Phosphoglucomutase 1 (PGM1) is a key enzyme for the regulation of energy metabolism from glycogen and glycolysis, as it catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate. ...PGM1 deficiency is an autosomal recessive disorder characterized by a highly heterogenous clinical spectrum, including hypoglycemia, cleft palate, liver dysfunction, growth delay, exercise intolerance, and dilated cardiomyopathy. Abnormal protein glycosylation has been observed in this disease. Oral supplementation with D-galactose efficiently restores protein glycosylation by replenishing the lacking pool of UDP-galactose, and rescues some symptoms, such as hypoglycemia, hepatopathy, and growth delay. However, D-galactose effects on skeletal muscle and heart symptoms remain unclear. In this study, we established an in vitro muscle model for PGM1 deficiency to investigate the role of PGM1 and the effect of D-galactose on nucleotide sugars and energy metabolism. Genome-editing of C2C12 myoblasts via CRISPR/Cas9 resulted in
(mouse homologue of human
, according to updated nomenclature) knockout clones, which showed impaired maturation to myotubes. No difference was found for steady-state levels of nucleotide sugars, while dynamic flux analysis based on
C6-galactose suggested a block in the use of galactose for energy production in knockout myoblasts. Subsequent analyses revealed a lower basal respiration and mitochondrial ATP production capacity in the knockout myoblasts and myotubes, which were not restored by D-galactose. In conclusion, an in vitro mouse muscle cell model has been established to study the muscle-specific metabolic mechanisms in PGM1 deficiency, which suggested that galactose was unable to restore the reduced energy production capacity.
Background
Caesarean section (CS) rates are rising globally. Long‐term adverse outcomes after CS might be reduced when the optimal uterine closure technique becomes evident.
Objective
To determine ...the effect of uterine closure techniques after CS on maternal and ultrasound outcomes.
Search strategy
Literature search in electronic databases.
Selection criteria
Randomised controlled trials (RCTs) or prospective cohort studies that evaluated uterine closure techniques and reported on ultrasound findings, perioperative or long‐term outcomes.
Data collection and analysis
Twenty studies (15 053 women) were included in our meta‐analyses for various outcomes. We calculated pooled risk ratios (RR) and weighted mean differences (WMD) with 95% CI through random‐effect analysis.
Main results
Residual myometrium thickness (RMT), reported in eight studies (508 women), decreased by 1.26 mm after single‐ compared with double‐layer closure (95% CI −1.93 to −0.58), particularly when locked sutures were used. Healing ratio RMT/adjacent myometrium thickness (AMT) decreased after single‐layer closure (WMD −7.74%, 95% CI −13.31 to −2.17), particularly in the case of locked sutures. Niche prevalence increased (RR 1.71, 95% CI 1.11–2.62) when the decidua was excluded. Dysmenorrhea occurred more often in the single‐layer group (RR 1.23, 95% CI 1.01–1.48), whereas incidence of uterine rupture was similar (RR 1.91, 95% CI 0.63–5.74).
Conclusion
Double‐layer unlocked sutures are preferable to single‐layer locked sutures regarding RMT, healing ratio and dysmenorrhoea. Excluding the decidua seems to result in higher niche prevalence. As thin residual myometrium or niches may serve as intermediates for gynaecological and reproductive outcomes, future studies should focus on these outcomes.
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#Uterineclosuretechniques after #caesarean affect #longtermoutcomes.
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#Uterineclosuretechniques after #caesarean affect #longtermoutcomes.
The most important reason for childhood cancer treatment failure in low-income countries is treatment abandonment.
The aim of this study was to explore reasons for childhood cancer treatment ...abandonment and assess the clinical condition of these children.
This was a descriptive study using semistructured questionnaires. Home visits were conducted to interview families of childhood cancer patients, diagnosed between January 2007 and January 2009, who had abandoned treatment at the Moi Teaching and Referral Hospital (MTRH).
Between January 2007 and January 2009, 222 children were newly diagnosed with a malignancy at MTRH. Treatment outcome was documented in 180 patients. Of these 180 patients, 98 (54%) children abandoned treatment. From December 2011 until August 2012, 53 (54%) of the 98 families were contacted. Due to lack of contact information, 45 families were untraceable. From 53 contacted families, 46 (87%) families agreed to be interviewed. Reasons for abandonment were reported by 26 families, and they were diverse. Most common reasons were financial difficulties (46%), inadequate access to health insurance (27%) and transportation difficulties (23%). Most patients (72%) abandoned treatment after the first 3 months had been completed. Of the 46 children who abandoned treatment, 9 (20%) were still alive: 6 (67%) of these children looked healthy and 3 (33%) ill. The remaining 37 (80%) children had passed away.
Prevention of childhood cancer treatment abandonment requires improved access to health insurance, financial or transportation support, proper parental education, psychosocial guidance and ameliorated communication skills of healthcare providers.
Positron emission tomography (PET) imaging of macrophages using the translocator protein (TSPO) tracer (R)-11CPK11195 has shown the promise to image rheumatoid arthritis (RA). To further improve TSPO ...PET for RA imaging, second generation TSPO tracers 11CDPA-713 and 18FDPA-714 have recently been evaluated pre-clinically showing better imaging characteristics.
A clinical proof of concept study to evaluate 11CDPA-713 and 18FDPA-714 to visualize arthritis in RA patients.
RA patients (n = 13) with at least two active hand joints were included. PET/CT scans of the hands were obtained after injection of 18FDPA-714, 11CDPA-713 and/or (R)-11CPK11195 (max. 2 tracers pp). Standardized uptake values (SUVs) and target-to-background (T/B) ratios were determined. Imaging data of the 3 different tracers were compared by pooled post-hoc testing, and by a head to head comparison.
Clinically active arthritis was present in 110 hand joints (2-17 pp). Arthritic joints were visualized with both 11CDPA-713 and 18FDPA-714. Visual tracer uptake corresponded with clinical signs of arthritis in 80% of the joints. Mean absolute uptake in PET-positive joints was significantly higher for 11CDPA-713 than for 18FDPA-714, the latter being not significantly different from (R)-11CPK11195 uptake. Background uptake was lower for both DPA tracers compared with that of (R)-11CPK11195. Higher absolute uptake and lower background resulted in two-fold higher T/B ratios for 11CDPA-713.
11CDPA-713 and 18FDPA-714 visualize arthritic joints in active RA patients and most optimal arthritis imaging results were obtained for 11CDPA-713. Second generation TSPO macrophage PET provides new opportunities for both early diagnosis and therapy monitoring of RA.
Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism ...spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design.
We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants' natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials.
These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level.
EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .
Smith-Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Often, patients with SMS are ...diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the effectiveness of methylphenidate (MPH), the first-line pharmacological treatment for ADHD, in patients with SMS is unclear. Our objective is to examine the effectiveness of MPH for ADHD symptoms in individuals with SMS, proposing an alternative trial design as traditional randomized controlled trials are complex in these rare and heterogeneous patient populations. We will initiate an N-of-1 series of double-blind randomized and placebo-controlled multiple crossover trials in six patients aged greater than or equai to 6 years with a genetically confirmed SMS diagnosis and a multidisciplinary established ADHD diagnosis, according to a power analysis based on a summary measures analysis of the treatment effect. Each N-of-1 trial consists of a baseline period, dose titration phase, three cycles each including randomized intervention, placebo and washout periods, and follow-up. The intervention includes twice daily MPH (doses based on age and body weight). The primary outcome measure will be the subscale hyperactivity/inattention of the Strengths and Difficulties Questionnaire (SDQ), rated daily. Secondary outcome measures are the shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index, Goal Attainment Scaling (GAS), and the personal questionnaire (PQ). Statistical analysis will include a mixed model analysis. All subjects will receive an assessment of their individual treatment effect and data will be aggregated to investigate the effectiveness of MPH for ADHD in SMS at a population level. This study will provide information on the effectiveness of MPH for ADHD in SMS, incorporating personalized outcome measures. This protocol presents the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder, providing a much-needed bridge between science and practice to optimize evidence-based and personalized care.
Abstract It is estimated that by 2050 more than one in five people will be aged 65 or over. In this age group, falls are one of the most serious life-threatening events that can occur. Their ...automatic detection would help reduce the time of arrival of medical attention, thus reducing the mortality rate and in turn promoting independent living. This study evaluated a variety of existing and novel fall-detection algorithms for a waist-mounted accelerometer based system. In total, 21 algorithms of varying degrees of complexity were tested against a comprehensive data-set recorded from 10 young healthy volunteers performing 240 falls and 120 activities of daily living (ADL) and 10 elderly healthy volunteers performing 240 scripted ADL and 52.4 waking hours of continuous unscripted normal ADL. Results show that using an algorithm that employs thresholds in velocity, impact and posture (velocity+impact+posture) achieves 100% specificity and sensitivity with a false-positive rate of less than 1 false-positive (0.6 false-positives) per day of waking hours. This algorithm is the most suitable method of fall-detection, when tested using continuous unscripted activities performed by elderly healthy volunteers, which is the target environment for a fall-detection device.
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