The healthcare system costs of hip fracture care in South Africa.

Despite rapidly ageing populations, data on healthcare costs associated with hip fracture in Sub-Saharan Africa are limited. We estimated high direct medical costs for managing hip fracture within the public healthcare system in SA. These findings should support policy decisions on budgeting and planning of hip fracture services. PURPOSE: We estimated direct healthcare costs of hip fracture (HF) management in the South African (SA) public healthcare system. METHODS: We conducted a micro-costing study to estimate costs per patient treated for HF in five regional public sector hospitals in KwaZulu-Natal (KZN), SA. Two hundred consecutive, consenting patients presenting with a fragility HF were prospectively enrolled. Resources used including staff time, consumables, laboratory investigations, radiographs, operating theatre time, surgical implants, medicines, and inpatient days were collected from presentation to discharge. Counts of resources used were multiplied by unit costs, estimated from the KZN Department of Health hospital fees manual 2019/2020, in local currency (South African Rand, ZAR), and converted to 2020 US$ prices. Generalized linear models estimated total covariate-adjusted costs and cost predictors. RESULTS: The mean unadjusted cost for HF management was US$6935 (95% CI; US$6401-7620) [ZAR114,179 (95% CI; ZAR105,468-125,335)]. The major cost driver was orthopaedics/surgical ward costs US$5904 (95% CI; 5408-6535), contributing to 85% of total cost. The covariate-adjusted cost for HF management was US$6922 (95% CI; US$6743-7118) [ZAR113,976 (95% CI; ZAR111,031-117,197)]. After covariate adjustment, total costs were higher in patients operated under general anaesthesia [US$7251 (95% CI; US$6506-7901)] compared to surgery under spinal anaesthesia US$6880 (95% CI; US$6685-7092) and no surgery US$7032 (95% CI; US$6454-7651). CONCLUSION: Healthcare costs following a HF are high relative to the gross domestic product per capita and per capita spending on health in SA. As the population ages, this significant economic burden to the health system will increase.

Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Cloacal and surface temperatures of tom turkeys exposed to different rearing temperature regimes during the first 12 weeks of growth.

Years of genetic selection have caused an increase in growth rate and market body mass in agricultural poultry species compared to earlier genetic strains, potentially altering their physiological requirements. The objective of this study was to expose Hybrid Converter tom turkeys on a weekly basis to the recommended rearing temperature regime (TCON: control) or 4°C below the recommended standard (TTRT: treatment) to determine their thermal responses. Once per week for 12 weeks, 12 turkeys were individually exposed to either TCON or TTRT for a 2-h period. Surface temperatures of the breast (TBREAST), wing (TWING), drumstick (TDRUM), head (THEAD), and shank (TSHANK) were measured at 20-min intervals using an infrared camera, while a thermal data logger measured the skin surface temperature under the wing (TLOGGER) at 30-s intervals. The cloacal temperature (TCORE) was measured using a medical thermometer at the start and end of the exposure period. Regardless of exposure temperature, the TBREAST (TCON: P<0.001 and TTRT: P<0.001), TWING (TCON: P<0.001 and TTRT: P<0.001), and TDRUM (TCON: P<0.001 and TTRT: P<0.001) decreased from weeks 4 to 6 and remained constant from weeks 1 to 3 and 8 to 12. THEAD was elevated in week 2 (TCON: P<0.001) or week 3 (TTRT: P<0.001), TSHANK increased slightly during week 3 for both TCON (P<0.001) and TTRT (P<0.001), and TLOGGER (TCON: P<0.001 and TTRT: P=0.001) and TCORE (TCON: P<0.001 and TTRT: P<0.001) were lower during the first week. Thereafter, THEAD, TSHANK, TLOGGER, and TCORE remained constant. Exposure to TTRT resulted in lower TBREAST, TWING, and TDRUM compared to TCON. Generally, THEAD, TSHANK, TLOGGER, and TCORE were not affected by the different exposure temperatures. The data demonstrated that the degree of thermal response expressed is dependent on the location of measurement, age, and exposure temperature.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

BACKGROUND: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. METHODS: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). CONCLUSIONS: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Accelerating P300-based neurofeedback training for attention enhancement using iterative learning control: a randomised controlled trial.

Objective. Neurofeedback (NFB) training through brain-computer interfacing has demonstrated efficacy in treating neurological deficits and diseases, and enhancing cognitive abilities in healthy individuals. It was previously shown that event-related potential (ERP)-based NFB training using a P300 speller can improve attention in healthy adults by incrementally increasing the difficulty of the spelling task. This study aims to assess the impact of task difficulty adaptation on ERP-based attention training in healthy adults. To achieve this, we introduce a novel adaptation employing iterative learning control (ILC) and compare it against an existing method and a control group with random task difficulty variation.Approach. The study involved 45 healthy participants in a single-blind, three-arm randomised controlled trial. Each group underwent one NFB training session, using different methods to adapt task difficulty in a P300 spelling task: two groups with personalised difficulty adjustments (our proposed ILC and an existing approach) and one group with random difficulty. Cognitive performance was evaluated before and after the training session using a visual spatial attention task and we gathered participant feedback through questionnaires.Main results. All groups demonstrated a significant performance improvement in the spatial attention task post-training, with an average increase of 12.63%. Notably, the group using the proposed iterative learning controller achieved a 22% increase in P300 amplitude during training and a 17% reduction in post-training alpha power, all while significantly accelerating the training process compared to other groups.Significance. Our results suggest that ERP-based NFB training using a P300 speller effectively enhances attention in healthy adults, with significant improvements observed after a single session. Personalised task difficulty adaptation using ILC not only accelerates the training but also enhances ERPs during the training. Accelerating NFB training, while maintaining its effectiveness, is vital for its acceptability by both end-users and clinicians.

[Role of percutaneous coronary intervention in diabetic patients]. / Rôle de la revascularisation coronarienne chez le patient diabétique avec maladie coronarienne stable.

Clinical outcomes after revascularization, both for surgery and percutaneous coronary intervention (PCI), is significantly worse in diabetic patients compared with non-diabetic patients. While in acute coronary syndrome, PCI is favored because of the increased risk of surgery performed during ongoing infarction, in stable patients assessment of clinical factors, such as coronary anatomy and comorbidities should guide decision of the revascularization modality (e.g., surgical, PCI, or conservative). Surgery should be favored in patients with multivessel coronary disease and acceptable surgical risk. Overall, the threshold for surgery compared to PCI should be lower in diabetic patients compared with non-diabetic ones.

Methods for think-aloud interviews in health-related resource-use research: the PECUNIA RUM instrument.

BACKGROUND: The think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent's perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap. METHODS: Methods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A 'before the interview' (including translation, recruitment, training), Part B 'during the interview' (including setting, opening, completing the instrument, open-ended questions, closing), and part C 'after the interview' (including transcription and data analysis, trustworthiness). CONCLUSIONS: This manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.

Infusion of noradrenaline through the proximal line of a migrated central venous catheter.

A 41-year-old, obese, patient was admitted to Accident and Emergency with a history of leg cellulitis. A central line was inserted. Documented aspiration of blood from all lines, central venous pressure trace obtained and correct position noted on the chest X-ray (CXR). The patient became increasingly septic despite antibiotic therapy. He was subsequently commenced on a noradrenaline infusion; however, the blood pressure was unresponsive. On admission to the intensive care unit (ICU), it was noted he had an area of white skin over the right clavicle. The infusions were stopped and a CXR confirmed proximal migration of the line. The central line was re-sited and his noradrenaline recommenced with an improvement in his blood pressure. Acute renal failure developed which required haemofiltration for 24 hours. The condition improved and the patient was discharged from ICU. It took several weeks for his renal function to return to normal, but he was discharged home with no permanent damage.

Proper understanding of recurrent stress urinary incontinence treatment in women (PURSUIT): a randomised controlled trial of endoscopic and surgical treatment.

BACKGROUND: Women with stress urinary incontinence (SUI) experience urine leakage with physical activity. Currently, the interventional treatments for SUI are surgical, or endoscopic bulking injection(s). However, these procedures are not always successful, and symptoms can persist or come back after treatment, categorised as recurrent SUI. There are longstanding symptoms and distress associated with a failed primary treatment, and currently, there is no consensus on how best to treat women with recurrent, or persistent, SUI. METHODS: A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the UK, randomising 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. The aim of the trial is to determine whether surgical treatment is superior to endoscopic bulking injections in terms of symptom severity at 1 year after randomisation. This primary outcome will be measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients' and clinicians' views and experiences of the interventions. DISCUSSION: There is a lack of high-quality, randomised, scientific evidence for which treatment is best for women presenting with recurrent SUI. The PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) registry ISRCTN12201059. Registered on 09 January 2020.

The use of crisis medication in the management of terminal haemorrhage due to incurable cancer: a qualitative study.

BACKGROUND: Terminal haemorrhage is a rare but devastating event that may occur in certain advanced cancers. The focus of management involves administration of 'crisis medicine' with the intention of relieving patient distress through sedative doses of anxiolytics or opioids. This practice, whilst widely accepted, is based on limited evidence and has never been formally evaluated. AIM: To evaluate the utility of crisis medication in the management of terminal haemorrhage, through the experiences of nurses who had personally managed such events. METHOD: Semi-structured interviews exploring the experiences of palliative care and head and neck oncology nurses were recorded, transcribed verbatim and analysed using interpretative phenomenological analysis. Saturation of themes occurred after interviewing 11 nurses with cumulative experience of managing 37 terminal haemorrhages. RESULTS: Participants reported crisis medication to have little, if any, role in the management of terminal haemorrhage, which was such a rapid event that patients died before it could be administered. As many events had not been predicted, anticipatory prescribing of crisis medication did not always occur. Staying with and supporting the patient, and using dark-coloured towels to camouflage blood were reported to be of more practical use. A focus on accessing crisis medicines had often been to the detriment of these simple yet beneficial measures. CONCLUSION: Anticipatory prescribing of crisis medication rarely benefits the patient and may unintentionally detract from nursing care. Guidelines on the management of terminal haemorrhage should reconsider the emphasis on crisis medication and focus on non-pharmacological approaches to this invariably fatal event.

[Transcatheter aortic valve implantations in 2011: the interventional cardiologist]. / Remplacement valvulaire aortique percutané en 2011: re point de vue du cardiologue interventionnel.

Since the first transcatheter aortic valve implantation 9 years ago, constant technological progress and simplification of the procedure have been observed. For two devices in particular (Edwards SAPIEN valve and CoreValve), considerable clinical experience has been gained, with over 17,000 implantations each. The safety and efficacy of this technique have recently been confirmed in the randomized trial Partner. Consequently, the end of 2010 saw the TAVI (Transcatheter aortic valve implantation) become the standard-of-care for selected patients deemed inoperable on the basis of age or co-morbidities and now is an acceptable alternative to surgery in selected high-risk operable patients. However, the selection of patients and the technique used (trans-arterial or trans-apical) require a multidisciplinary approach which remains essential for procedural success.

[Transradial approach for coronary angiography and angioplasty: the gold standard]. / Les coronarographies et les angioplasties coronaires par voie radiale: l'approche de choix?

Transradial approach in interventional cardiology is performed heterogenously around the world. Nevertheless, this technique allows to decrease access site complications and major bleeding, and increases patient's comfort. All patient subgroups beneficiate from this approach, especially in the case of acute coronary syndromes in which the bleeding risk is the highest, in relation to aggressive anticoagulation and platelet antiaggregation treatment. Transradial approach requires a longer learning curve than transfemoral approach due to specific technical challenges that are often overcome with experience. Because of its clear benefits, transradial access should become the gold standard approach for coronary diagnostic and interventional procedures.

Glycaemic status influences the nature and severity of coronary artery disease.

AIMS/HYPOTHESIS: We sought to understand the relationships between glycaemic status and both severity and progression of coronary artery disease (CAD), the leading cause of death in diabetes. METHODS: Baseline fasting blood glucose (FBG) and HbA1c (%)were measured in 426 patients with known or suspected stable CAD, who underwent coronary artery intravascular ultrasound(IVUS) at baseline and after a mean follow-up period of 664 days (range 257 to 961). The patients were categorised as normoglycaemic (n=226, 53%), or as having impaired fasting glucose (n=118, 28%) or diabetes (n=82, 19%). RESULTS: The maximum percentage coronary atheroma area at baseline was greater in diabetic patients (73.33+/-8.86%) than in those with normoglycaemia (69.08+/-10.43%; p=0.001) and impaired fasting glucose (69.32+/-9.59%; p=0.0031). In averaged IVUS measurements of the 30-mm target segment(n=332 participants), change in percentage atheroma area during follow-up was also greater in the diabetes (1.86+/-3.90%) than in other groups (0.28+/-3.32% and 0.56+/-2.96%,p=0.0047 global). FBG correlated with maximum percentage atheroma area at baseline (r=0.17; p=0.0003). HbA1c also correlated with maximum percentage atheroma area at baseline (r=0.26; p=0.0001) and with change in maximum plaque area (r=0.16; p=0.016). A similar pattern of results occurred with plaque volume. The relationships between diabetes or HbA1c and both IVUS measurements of plaque burden and remodelling persisted after adjustment. CONCLUSIONS/INTERPRETATION: Fasting blood glucose, HbA1c and the presence of diabetes are associated with the severity and progression of coronary atherosclerosis. These observations support the hypothesis that better glycaemic control may favourably influence CAD in patients with abnormal glucose tolerance or diabetes.

Epidemiology and pathophysiology of cancer-associated thrombosis.

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. First recognised by Bouillard in 1823 and later described by Trousseau in 1844, multiple studies have since provided considerable evidence for a clinical association between VTE and cancer. Across all cancers, the risk for VTE is elevated 7-fold; in certain malignancies, the risk for VTE may be increased up to 28-fold. Venous thromboembolism is the second leading cause of death in patients with cancer; among survivors, complications commonly include recurrent VTE and post-thrombotic syndrome, and (more rarely) chronic thromboembolic pulmonary hypertension, which are costly, and have a profound impact on the patient's quality of life. Tumour cells can activate blood coagulation through multiple mechanisms, including production of procoagulant, fibrinolytic, and proaggregating activities, release of proinflammatory and proangiogenic cytokines, and interacting directly with host vascular and blood cells (e.g., endothelial cells, leukocytes, and platelets) through adhesion molecules. Increasing evidence suggests that elements of the haemostatic system also have a direct role in eliciting or enhancing angiogenesis, cell survival, and metastasis. Despite the problem posed by VTE in the setting of cancer, it is evident that a significant number of oncologists do not recognise the link between cancer, its treatment, and thrombogenesis. On 22 May 2009, a group of UK-based physicians met in London, UK, to evaluate recent data on cancer thrombosis. This article (1 of 4) briefly reviews key data on the epidemiology and pathophysiology of VTE as a context for a discussion and consensus statement developed by meeting attendees, on the implications of this information for UK clinical practice.

[Paravalvular leak following surgical valve replacement: is there a role for percutaneous paravalvular leak reduction?]. / Fuite paravalvulaire après chirurgie cardiaque: quelle place pour l'approche percutanée?

After valve replacement, significant paravalvular leaks (PVL) may develop in up to 12.5% of the cases. Signs and symptoms include congestive heart failure and/or haemolysis and therefore may require reintervention. Redo valve surgery is considered the therapy of choice for symptomatic patients, either by valve replacement or leak repair. Considering the risk of morbidity and mortality associated with a surgical reintervention and the high post-surgical recurrence of PVL, the endovascular treatment represents an attractive alternative to surgery for high risk patients. The percutaneous approach aims at PVL reduction by implantation of certain occluder devices. The procedure is technically feasible in 60 to 90% of the cases according to different series. Technical success is associated with clinical improvement in 50 to 80% of the cases.

COVID-19 confessions: a qualitative exploration of healthcare workers experiences of working with COVID-19.

OBJECTIVES: To gain insight into the experiences and concerns of front-line National Health Service (NHS) workers while caring for patients with COVID-19. DESIGN: Qualitative analysis of data collected through an anonymous website (www.covidconfidential) provided a repository of uncensored COVID-19 experiences of front-line NHS workers, accessed via a link advertised on the Twitter feed of two high profile medical tweeters and their retweets. SETTING: Community of NHS workers who accessed this social media. PARTICIPANTS: 54 healthcare workers, including doctors, nurses and physiotherapists, accessed the website and left a 'story'. RESULTS: Stories ranged from 1 word to 10 min in length. Thematic analysis identified common themes, with a central aspect being the experience and psychological consequence of trauma. Specific themes were: (1) the shock of the virus, (2) staff sacrifice and dedication, (3) collateral damage ranging from personal health concerns to the long-term impact on, and care of, discharged patients and (4) a hierarchy of power and inequality within the healthcare system. CONCLUSIONS: COVID-19 confidential gave an outlet for unprompted and uncensored stories of healthcare workers in the context of COVID-19. In addition to personal experiences of trauma, there were perceptions that many operational difficulties stemmed from inequalities of power between management and front-line workers. Learning from these experiences will reduce staff distress and improve patient care in the face of further waves of the pandemic.

Measuring functional limitations after venous thromboembolism: Optimization of the Post-VTE Functional Status (PVFS) Scale.

INTRODUCTION: We recently proposed a scale for assessment of patient-relevant functional limitations following an episode of venous thromboembolism (VTE). Further development of this post-VTE functional status (PVFS) scale is still needed. METHODS: Guided by the input of VTE experts and patients, we refined the PVFS scale and its accompanying manual, and attempted to acquire broad consensus on its use. RESULTS: A Delphi analysis was performed involving 53 international VTE experts with diverse scientific and clinical backgrounds. In this process, the number of scale grades of the originally proposed PVFS scale was reduced and descriptions of the grades were improved. After these changes, a consensus was reached on the number/definitions of the grades, and method/timing of the scale assessment. The relevance and potential impact of the scale was confirmed in three focus groups totaling 18 VTE patients, who suggested additional changes to the manual, but not to the scale itself. Using the improved manual, the κ-statistics between PVFS scale self-reporting and its assessment via the structured interview was 0.75 (95%CI 0.58-1.0), and 1.0 (95%CI 0.83-1.0) between independent raters of the recorded interview of 16 focus groups members. CONCLUSION: We improved the PVFS scale and demonstrated broad consensus on its relevance, optimal grades, and methods of assessing among international VTE experts and patients. The interobserver agreement of scale grade assignment was shown to be good-to-excellent. The PVFS scale may become an important outcome measure of functional impairment for quality of patient care and in future VTE trials.

Essential yeast protein with unexpected similarity to subunits of mammalian cleavage and polyadenylation specificity factor (CPSF).

The 3' ends of most eukaryotic messenger RNAs are generated by internal cleavage and polyadenylation. In mammals, there is a strict dependence of both reactions on the sequence AAUAAA, which occurs upstream of polyadenylation [poly(A)] sites and which is recognized by CPSF. In contrast, cis-acting signals for yeast 3'-end generation are highly divergent from those of mammals, suggesting that trans-acting factors other than poly(A) polymerase would not be conserved. The essential yeast protein Brr5/Ysh1 shows sequence similarity to subunits of mammalian CPSF and is required for 3'-end processing in vivo and in vitro. These results demonstrate a structural and functional conservation of the yeast and mammalian 3'-end processing machineries despite a lack of conservation of the cis sequences.