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Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial

Por: Simpson · S. A. · Evans · R. A. · Gilbert · H. R. · Branson · A. · Barber · S. · McIntosh · E. · Ahmed · Z. · Dean · S. G. · Doherty · P. J. · Gardiner · N. · Greaves · C. · Daw · P. · Ibbotson · T. · Jani · B. · Jolly · K. · Mair · F. · Ormandy · P. · Smith · S. · Singh · S. J. · Taylor · R.
Introduction

Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes.

Methods and analysis

A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention.

Ethics and dissemination

The trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public.

Trial registration number

ISRCTN68786622.

Protocol version

2.0 (16 May 2023).

Perception and views about individualising antibiotic duration for respiratory tract infections when patients feel better: a qualitative study with primary care professionals

Por: Moragas · A. · Uguet · P. · Cots · J. M. · Boada · A. · Bjerrum · L. · Llor · C.
Background

Evidence shows a high rate of unnecessary antibiotic prescriptions for respiratory tract infections (RTIs) in primary care. There is increasing evidence showing that shorter courses for RTIs are safe and help in reducing antimicrobial resistance (AMR). Stopping antibiotics earlier, as soon as patients feel better, rather than completing antibiotic courses, may help reduce unnecessary exposure to antibiotics and AMR.

Objectives

The aim of this study was to explore the perceptions and views of primary care healthcare professionals about customising antibiotic duration for RTIs by asking patients to stop the antibiotic course when they feel better.

Design

Qualitative research.

Setting and participants

A total of 21 qualitative interviews with primary care professionals (experts and non-experts in AMR) were conducted from June to September 2023. Data were audiorecorded, transcribed and analysed thematically.

Results

Overall, experts seemed more amenable to tailoring the antibiotic duration for RTIs when patients feel better. They also found the dogma of ‘completing the course’ to be obsolete, as evidence is changing and reducing the duration might lead to less AMR, but claimed that evidence that this strategy is as beneficial and safe as fixed courses was unambiguous. Non-experts, however, believed the dogma of completing the course. Clinicians expressed mixed views on what feeling better might mean, supporting a shared decision-making approach when appropriate. Participants claimed good communication to professionals and patients, but were sceptical about the risk of medicalisation when asking patients to contact clinicians again for a check-up visit.

Conclusions

Clinicians reported positive and negative views about individualising antibiotic courses for RTIs, but, in general, experts supported a customised antibiotic duration as soon as patients feel better. The information provided by this qualitative study will allow improving the performance of a large randomised clinical trial aimed at evaluating if this strategy is safe and beneficial.

Incidence, pathogens and antimicrobial resistance of blood and cerebrospinal fluid isolates from a tertiary neonatal unit in South Africa: A 10 year retrospective review

by Reenu Thomas, Claude Ondongo-Ezhet, Nini Motsoaledi, Mike Sharland, Michelle Clements, Sithembiso Velaphi

Objective

To determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa.

Methods

Single-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1st January 2010 to 31st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available.

Results

There were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.6[95%CI, 0.5–0.7];p = Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%[95%CI,4.2%-5.3%];pStaphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%[95%CI,-3.5%–2%],pCandida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated.

Conclusions

There has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized.

Random forest classification as a tool in epidemiological modelling: Identification of farm-specific characteristics relevant for the occurrence of <i>Fasciola hepatica</i> on German dairy farms

by Andreas W. Oehm, Yury Zablotski, Amely Campe, Martina Hoedemaker, Christina Strube, Andrea Springer, Daniela Jordan, Gabriela Knubben-Schweizer

Fasciola hepatica is an internal parasite of both human and veterinary relevance. In order to control fasciolosis, a multitude of attempts to predict the risk of infection such as risk maps or forecasting models have been developed. These attempts mainly focused on the influence of geo-climatic and meteorological features. Predicting bovine fasciolosis on farm level taking into account farm-specific settings yet remains challenging. In the present study, a new methodology for this purpose, a data-driven machine learning approach using a random forest classification algorithm was applied to a cross-sectional data set of farm characteristics, management regimes, and farmer aspects within two structurally different dairying regions in Germany in order to identify factors relevant for the occurrence of F. hepatica that could predict farm-level bulk tank milk positivity. The resulting models identified farm-specific key aspects in regard to the presence of F. hepatica. In study region North, farm-level production parameters (farm-level milk yield, farm-level milk fat, farm-level milk protein), leg hygiene, body condition (prevalence of overconditioned and underconditioned cows, respectively) and pasture access were identified as features relevant in regard to farm-level F. hepatica positivity. In study region South, pasture access together with farm-level lameness prevalence, farm-level prevalence of hock lesions, herd size, parity, and farm-level milk fat appeared to be important covariates. The stratification of the analysis by study region allows for the extrapolation of the results to similar settings of dairy husbandry. The local, region-specific modelling of F. hepatica presence in this work contributes to the understanding of on-farm aspects of F. hepatica appearance. The applied technique represents a novel approach in this context to model epidemiological data on fasciolosis which allows for the identification of farms at risk and together with additional findings in regard to the epidemiology of fasciolosis, can facilitate risk assessment and deepen our understanding of on-farm drivers of the occurrence of F. hepatica.

New methodology to assess the excess burden of antibiotic resistance using country-specific parameters: a case study regarding E. coli urinary tract infections

Por: Godijk · N. G. · McDonald · S. A. · Altorf-van der Kuil · W. · Schoffelen · A. F. · Franz · E. · Bootsma · M. C. J.
Objectives

Antimicrobial resistant (AMR) infections are a major public health problem and the burden on population level is not yet clear. We developed a method to calculate the excess burden of resistance which uses country-specific parameter estimates and surveillance data to compare the mortality and morbidity due to resistant infection against a counterfactual (the expected burden if infection was antimicrobial susceptible). We illustrate this approach by estimating the excess burden for AMR (defined as having tested positive for extended-spectrum beta-lactamases) urinary tract infections (UTIs) caused by E. coli in the Netherlands in 2018, which has a relatively low prevalence of AMR E. coli, and in Italy in 2016, which has a relatively high prevalence.

Design

Excess burden was estimated using the incidence-based disability-adjusted life-years (DALYs) measure. Incidence of AMR E. coli UTI in the Netherlands was derived from ISIS-AR, a national surveillance system that includes tested healthcare and community isolates, and the incidence in Italy was estimated using data reported in the literature. A systematic literature review was conducted to find country-specific parameter estimates for disability duration, risks of progression to bacteraemia and mortality.

Results

The annual excess burden of AMR E. coli UTI was estimated at 3.89 and 99.27 DALY/100 0000 population and 39 and 2786 excess deaths for the Netherlands and Italy, respectively.

Conclusions

For the first time, we use country-specific and pathogen-specific parameters to estimate the excess burden of resistant infections. Given the large difference in excess burden due to resistance estimated for Italy and for the Netherlands, we emphasise the importance of using country-specific parameters describing the incidence and disease progression following AMR and susceptible infections that are pathogen specific, and unfortunately currently difficult to locate.

Cohort profile: evaluation of immune response and household transmission of SARS-CoV-2 in Costa Rica: the RESPIRA study

Por: Loria · V. · Aparicio · A. · Hildesheim · A. · Cortes · B. · Barrientos · G. · Retana · D. · Sun · K. · Ocampo · R. · Prevots · D. R. · Zuniga · M. · Waterboer · T. · Wong-McClure · R. · Morera · M. · Butt · J. · Binder · M. · Abdelnour · A. · Calderon · A. · Gail · M. H. · Pfeiffer · R. M.
Purpose

The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19.

Participants

From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence.

Findings to date

Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up.

Future plans

RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024.

Trial registration number

NCT04537338.

The association between cardiopulmonary exercise testing and postoperative outcomes in patients with lung cancer undergoing lung resection surgery: A systematic review and meta-analysis

by Nabeela Arbee-Kalidas, Hlamatsi Jacob Moutlana, Yoshan Moodley, Moses Mogakolodi Kebalepile, Palesa Motshabi Chakane

Background

Exercise capacity should be determined in all patients undergoing lung resection for lung cancer surgery and cardiopulmonary exercise testing (CPET) remains the gold standard. The purpose of this study was to investigate associations between preoperative CPET and postoperative outcomes in patients undergoing lung resection surgery for lung cancer through a review of the existing literature.

Methods

A search was conducted on PubMed, Scopus, Cochrane Library and CINAHL from inception until December 2022. Studies investigating associations between preoperative CPET and postoperative outcomes were included. Risk of bias was assessed using the QUIPS tool. A random effect model meta-analysis was performed. I2 > 40% indicated a high level of heterogeneity.

Results

Thirty-seven studies were included with 6450 patients. Twenty-eight studies had low risk of bias. V˙O2 peak is the oxygen consumption at peak exercise and serves as a marker of cardiopulmonary fitness. Higher estimates of V˙O2 peak, measured and as a percentagege of predicted, showed significant associations with a lower risk of mortality [MD: 3.66, 95% CI: 0.88; 6.43 and MD: 16.49, 95% CI: 6.92; 26.07] and fewer complications [MD: 2.06, 95% CI: 1.12; 3.00 and MD: 9.82, 95% CI: 5.88; 13.76]. Using a previously defined cutoff value of > 15mL/kg/min for V˙O2 peak, showed evidence of decreased odds of mortality [OR: 0.55, 95% CI: 0.28–0.81] and but not decreased odds of postoperative morbidity [OR: 0.82, 95% CI: 0.64–1.00]. There was no relationship between V˙E/V˙CO2 slope, which depicts ventilatory efficiency, with mortality [MD: -9.60, 95% CI: -27.74; 8.54] however, patients without postoperative complications had a lower preoperative V˙E/V˙CO2 [MD: -2.36, 95% CI: -3.01; -1.71]. Exercise load and anaerobic threshold did not correlate with morbidity or mortality. There was significant heterogeneity between studies.

Conclusions

Estimates of cardiopulmonary fitness as evidenced by higher V˙O2 peak, measured and as a percentage of predicted, were associated with decreased morbidity and mortality. A cutoff value of V˙O2 peak > 15mL/kg/min was consistent with improved survival but not with fewer complications. Ventilatory efficiency was associated with decreased postoperative morbidity but not with improved survival. The heterogeneity in literature could be remedied with large scale, prospective, blinded, standardised research to improve preoperative risk stratification in patients with lung cancer scheduled for lung resection surgery.

Attitudes of patients with schizophrenia spectrum or bipolar disorders towards medication self‐management during hospitalisation

Abstract

Background

Medication self-management (MSM) is defined as a person's ability to cope with medication treatment for a chronic condition, along with the associated physical and psychosocial effects that the medication causes in their daily lives. For many patients, it is important to be able to self-manage their medication successfully, as they will often be expected to do after discharge.

Aim

The aim of this study was to describe the willingness and attitudes of patients with schizophrenia spectrum or bipolar disorders regarding MSM during hospital admission. A secondary aim was to identify various factors associated with patient willingness to participate in MSM and to describe their assumptions concerning needs and necessary conditions, as well as their attitudes towards their medication.

Methods

A multicentre, quantitative cross-sectional observational design was used to study the willingness and attitudes of psychiatric patients regarding MSM during hospitalisation. The study adhered to guidelines for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE).

Results

In this study, 84 patients, of which 43 were patients with schizophrenia spectrum disorders and 41 were patients with bipolar disorders, participated. A majority of the patients (81%) were willing to participate in MSM during their hospitalisation. Analysis revealed patients are more willing to MSM if they are younger (r = −.417, p < .001) and a decreasing number of medicines (r = −.373, p = .003). Patients' willingness was positively associated with the extent of support by significant others during and after hospitalisation (Pearson's r = .298, p = .011). Patients were convinced that they would take their medication more correctly if MSM were to be allowed during hospitalisation (65%).

Conclusion

Most of the patients were willing to self-manage their medication during hospitalisation, however, under specific conditions such as being motivated to take their medication correctly and to understand the benefits of their medication.

Relevance to Clinical Practice

From a policy point of view, our study provided useful insights into how patients look at MSM to enable the development of future strategies. Since patients are willing to self-manage their medication during hospitalisation, this may facilitate its implementation.

Patient contribution

Patients were recruited for this study. Participation was voluntary, and signed informed consent was obtained from all participants prior to the questionnaire.

Clarithromycin overcomes stromal cell-mediated drug resistance against proteasome inhibitors in myeloma cells via autophagy flux blockage leading to high NOXA expression

by Shota Moriya, Hiromi Kazama, Hirotsugu Hino, Naoharu Takano, Masaki Hiramoto, Shin Aizawa, Keisuke Miyazawa

We previously reported that macrolide antibiotics, such as clarithromycin (CAM), blocked autophagy flux, and simultaneous proteasome and autophagy inhibition by bortezomib (BTZ) plus CAM resulted in enhanced apoptosis induction in multiple myeloma (MM) cells via increased endoplasmic reticulum (ER) stress loading. However, in actual therapeutic settings, cell adhesion-mediated drug resistance between bone marrow stromal cells (BMSC) and MM cells has been known to be a barrier to treatment. To investigate whether CAM could enhance BTZ-induced cytotoxicity in MM cells under direct cell adhesion with BMSC, we established a co-culture system of EGFP-labeled MM cells with BMSC. The cytotoxic effect of BTZ on MM cells was diminished by its interaction with BMSC; however, the attenuated cytotoxicity was recovered by the co-administration of CAM, which upregulates ER stress loading and NOXA expression. Knockout of NOXA in MM cells canceled the enhanced cell death by CAM, indicating that NOXA is a key molecule for cell death induction by the co-administration of CAM. Since NOXA is degraded by autophagy as well as proteasomes, blocking autophagy with CAM resulted in the sustained upregulation of NOXA in MM cells co-cultured with BMSC in the presence of BTZ. Our data suggest that BMSC-associated BTZ resistance is mediated by the attenuation of ER stress loading. However, the addition of CAM overcomes BMSC-associated resistance via upregulation of NOXA by concomitantly blocking autophagy-mediated NOXA degradation and transcriptional activation of NOXA by ER stress loading.

Associations of production characteristics with the on-farm presence of <i>Fasciola hepatica</i> in dairy cows vary across production levels and indicate differences between breeds

by Andreas W. Oehm, Yury Zablotski, Martina Hoedemaker, Amely Campe, Christina Strube, Daniela Jordan, Andrea Springer, Markus Klawitter, Gabriela Knubben-Schweizer

Fasciola hepatica is one of the economically most important endoparasites in cattle production. The aim of the present work was to evaluate the relevance of production level on the associations of on-farm presence of F. hepatica with farm-level milk yield, milk fat, and milk protein in Holstein cows, a specialised dairy breed, and in Simmental cows, a dual purpose breed. Furthermore, we investigated whether differential associations were present depending on breed. Data from 560 dairy farms across Germany housing 93,672 cows were analysed. The presence of F. hepatica antibodies was determined via ELISA on bulk tank milk samples. Quantile regression was applied to model the median difference in milk yield, milk fat, and milk protein depending on the interaction of breed and fluke occurrence. Whereas a reduction in milk yield (-1,206 kg, p F. hepatica positive German Holstein farms, only milk fat (-33.8 kg, p = 0.01) and milk protein (-22.6 kg, p = 0.03) were affected on F. hepatica positive German Simmental farms. Subsequently, production traits were modelled within each of the two breeds for low, medium, and high producing farms in the presence of F. hepatica antibodies and of confounders. On Holstein farms, the presence of F. hepatica seropositivity was associated with lower production, while on German Simmental farms such an association was less evident. This work demonstrates that production level is relevant when assessing the associations between the exposure to F. hepatica with production characteristics. Moreover, both models indicate a breed dependence. This could point towards a differential F. hepatica resilience of specialised dairy breeds in comparison with dual purpose breeds.

A prospective study to analyse the concentration of octenidine in hand wounds after disinfection by LC–MS/MS

Abstract

Toxic reactions can appear after pressurised flushing of soft tissue with octenidine (OCT) containing disinfectants. Their use for surgical disinfection could complicate the diagnosis of possible contamination. In patients with open lacerations of their hand's subcutaneous tissue samples were taken before and after surgical disinfection with Octenisept® and analysed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). In 16 out of 20 tissue samples, OCT was detected after disinfection (lower limit of quantification (LLOQ)=10 pg/mL/mg). The concentration of OCT was below the LLOQ, estimation of mean of 0.6 pg/mL/mg (0.22–0.98 pg/mL/mg, 95%-CI) before disinfection and mean of 179.4 pg/mL/mg (13.35–432.0 pg/mL/mg, 95%-CI) after disinfection. This study shows that the disinfection of open wounds with Octenisept® leads to a quantifiable concentration of OCT in open wounds. In cases of suspected OCT-mediated toxic reaction, the use of antiseptics containing OCT should be avoided.

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