Enhancing research quality and reporting: why the Journal of Comorbidity is now publishing study protocols

The Journal of Comorbidity was launched in 2011 and has since become established as a high-quality journal that publishes open-access, peer-reviewed articles, with a focus on advancing the clinical management of patients with comorbidity/multimorbidity. To further enhance research quality and reporting of studies in this field, the journal is now offering authors the opportunity to publish a summary of their study protocols – a move designed to generate interest and raise awareness in ongoing clinical research and to enable researchers to detail their methodologies in order that replication by scientific peers is possible

Challenges in economic evaluations in obstetric care : a scoping review and expert opinion

© 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.Peer reviewedPublisher PD

The Journal of Comorbidity affiliates with the Society for Academic Primary Care

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The 5T mouse multiple myeloma model: absence of c-myc oncogene rearrangement in early transplant generations.

Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM), arising spontaneously in the ageing C57BL/KaLwRij mice, was investigated in order to see whether the MM cells contain c-myc abnormalities of the MPC or RIC type. Rearrangement of the c-myc oncogene was found in the bone marrow cells only in 5T2 MM transplantation line in a mouse of the 24th generation and in none of the seven other MM of the 5T series which were of earlier generations. Since the mouse 5T MM resembles the human MM very closely, including the absence of consistent structural c-myc oncogene abnormalities, it can serve as a useful experimental model for studies on the aetiopathogenesis of this disease

Duloxetine in OsteoArthritis (DOA) study: study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty

Introduction Residual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degree of central sensitisation (CS) is associated with poorer postoperative outcomes and residual pain. It is thus hypothesised that preoperative treatment of CS could enhance postoperative outcomes. Duloxetine has been shown to be effective for several chronic pain syndromes, including knee osteoarthritis (OA), in which CS is most likely one of the underlying pain mechanisms. This study aims to evaluate the postoperative effects of preoperative screening and targeted duloxetine treatment of CS on residual pain compared with care-as-usual. Methods and analysis This multicentre, pragmatic, prospective, open-label, randomised controlled trial includes patients with idiopathic hip/knee OA who are on a waiting list for primary THA/TKA. Patients at risk for CS will be randomly allocated to the preoperative duloxetine treatment programme group or the care-as-usual control group. The primary end point is the degree of postoperative pain 6 months after THA/TKA. Secondary end points at multiple time points up to 12 months postoperatively are: pain, neuropathic pain-like symptoms, (pain) sensitisation, pain catastrophising, joint-associated problems, physical activity, health-related quality of life, depressive and anxiety symptoms, and perceived improvement. Data will be analysed on an intention-to-treat basis. Ethics and dissemination The study is approved by the local Medical Ethics Committee (METc 2014/087) and will be conducted according to the principles of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard (GCP), and in compliance with the Medical Research Involving Human Subjects Act (WMO)

Management of prolonged first stage of labour in a low-resource setting: lessons learnt from rural Malawi

Background Caesarean sections without medical indication cause substantial maternal and perinatal ill-health, particularly in low-income countries where surgery is often less safe. In presence of adequate labour monitoring and by appropriate use of evidence-based interventions for prolonged first stage of labour, unnecessary caesarean sections can be avoided. We aim to describe the incidence of prolonged first stage of labour and the use of amniotomy and augmentation with oxytocin in a low-resource setting in Malawi. Methods Retrospective analysis of medical records and partographs of all women who gave birth in 2015 and 2016 in a rural mission hospital in Malawi. Primary outcomes were incidence of prolonged first stage of labour based on partograph tracings, caesarean section indications and utilization of amniotomy and oxytocin augmentation. Results Out of 3246 women who gave birth in the study period, 178 (5.2%) crossed the action line in the first stage of labour, of whom 21 (11.8%) received oxytocin to augment labour. In total, 645 women gave birth by caesarean section, of whom 241 (37.4%) with an indication 'prolonged first stage of labour'. Only 113 (46.9%) of them crossed the action line and in 71/241 (29.5%) membranes were still intact at the start of caesarean section. Excluding the 60 women with prior caesarean sections, 14/181 (7.7%) received oxytocin prior to caesarean section for augmentation of labour. Conclusion The diagnosis prolonged first stage of labour was often made without being evident from labour tracings and two basic obstetric interventions to prevent caesarean section, amniotomy and labour augmentation with oxytocin, were underused.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Single-machine scheduling with stepwise tardiness costs and release times

We study a scheduling problem that belongs to the yard operations component of the railroad planning problems, namely the hump sequencing problem. The scheduling problem is characterized as a single-machine problem with stepwise tardiness cost objectives. This is a new scheduling criterion which is also relevant in the context of traditional machine scheduling problems. We produce complexity results that characterize some cases of the problem as pseudo-polynomially solvable. For the difficult-to-solve cases of the problem, we develop mathematical programming formulations, and propose heuristic algorithms. We test the formulations and heuristic algorithms on randomly generated single-machine scheduling problems and real-life datasets for the hump sequencing problem. Our experiments show promising results for both sets of problems

No Difference in Recovery of Patient-Reported Outcome and Range of Motion between Cruciate Retaining and Posterior Stabilized Total Knee Arthroplasty:A Double-Blind Randomized Controlled Trial

Both from the perspective of the individual and from a socioeconomic point of view (e.g., return to work), it is important to have an insight into the potential differences in recovery between posterior cruciate ligament retaining (PCR) and posterior stabilized (PS) total knee arthroplasty (TKA) implants. The primary aim of this study was to compare the speed of recovery of patient-reported outcome between patients with a PCR and PS TKA during the first postoperative year. The secondary aim was to compare the effect on range of motion (ROM). In a randomized, double-blind, controlled, single-center trial, 120 adults diagnosed with osteoarthritis of the knee were randomized into either the PCR or PS group. Primary outcome was speed of recovery of patient-reported pain and function, measured with the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), with a follow-up of 1year. Main secondary outcome measure was ROM. A generalized estimating equations (GEE) analysis was used to assess whether there was a difference over time between groups (" p -value for interaction"). Between 2008 and 2011, 59 participants received a PCR TKA (mean age, 70.3 years [SD=7.7]; mean body mass index [BMI], 30.5kg/m (2) [SD=5.4]) and 55 participants a PS TKA (mean age, 73.5 years [SD=7.0]; mean BMI, 29.2kg/m (2) [SD=4.4]). Six patients (two PCR and four PS) were excluded because of early drop-out, so 114 patients (95%) were available for analysis. In between group difference for total WOMAC score was -1.3 (95% confidence interval [CI]: -5.6 to 3.1); p -value for interaction was 0.698. For ROM, in between group difference was 1.1 (95% CI: -2.6 to 4.7); p -value for interaction was 0.379. These results demonstrated that there are no differences in speed of recovery of WOMAC or ROM during the first postoperative year after PCR or PS TKA

Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis

Objective: Corticosteroids are used in sepsis treatment to benefit outcome. However, discussion remains on which patients will benefit from treatment. Inter-individual variations in cortisol sensitivity, mediated through the glucocorticoid receptor, might play a role in the observed differences. Our aim was to study changes in mRNA levels of three glucocorticoid receptor splice variants in neutrophils of children with sepsis. Patients and design: Twenty-three children admitted to the pediatric intensive care unit with sepsis or septic shock were included. Neutrophils were isolated at days 0, 3 and 7, and after recovery (>3 months). mRNA levels of the glucocorticoid receptor splice variants GR-α (determining most of the cortisol effect), GR-P (increasing GR-α effect) and GR-β (inhibitor of GR-α) were measured quantitatively. Main results: Neutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-α and GR-P splice variants on day 0 compared to after recovery. GR-α and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-β mRNA levels did not change significantly during sepsis. GR expression was negatively correlated to interleukin-6 (a measure of disease severity, r = -0.60, P = 0.009). Conclusions: Children with sepsis or septic shock showed a transient depression of glucocorticoid receptor mRNA in their neutrophils. This feature may represent a tissue-specific adaptation during sepsis leading to increased cortisol resistance of neutrophils. Our study adds to understanding the mechanism of cortisol sensitivity in immune cells. Future treatment strategies, aiming at timing and tissue specific regulation of glucocorticoids, might benefit patients with sepsis or septic shock