Multichotomous tests have three or more outcome or risk categories, and can provide richer information and a better fit with clinical decision-making than dichotomous tests. Our objective is to present a fully developed approach to the meta-analysis of multichotomous clinical prediction rules (CPRs) and tests, including meta-analysis of stratum specific likelihood ratios.
We have developed a novel approach to the meta-analysis of likelihood ratios for multichotomous tests that avoids the need to dichotomise outcome categories, and demonstrate its application to a sample CPR. We also review previously reported approaches to the meta-analysis of the area under the receiver operating characteristic curve (AUROCC) and meta-analysis of a measure of calibration (observed:expected) for multichotomous tests or CPRs.
Using data from 10 studies of the Cancer of the Prostate Risk Assessment (CAPRA) risk score for prostate cancer recurrence, we calculated summary estimates of the likelihood ratios for low, moderate and high risk groups of 0.40 (95% CI 0.32 to 0.49), 1.24 (95% CI 0.99 to 1.55) and 4.47 (95% CI 3.21 to 6.23), respectively. Applying the summary estimates of the likelihood ratios for each risk group to the overall prevalence of cancer recurrence in a population allows one to estimate the likelihood of recurrence for each risk group in that population.
An approach to meta-analysis of multichotomous tests or CPRs is presented. A spreadsheet for data preparation and code for R and Stata are provided for other researchers to download and use. Combined with summary estimates of the AUROCC and calibration, this is a comprehensive strategy for meta-analysis of multichotomous tests and CPRs.
Commentary on: Carlton E, Kohne J, Shankar-Hari, et al. Readmission diagnoses after paediatric severe sepsis hospitalisation. Crit Care Med 2019;47:583–90.
Children with coexisting comorbidities when discharged following severe sepsis have a higher rate of readmission as compared with matched hospitalisations for other acute medical conditions. There is a need for internationally agreed evidence-based guidelines/consensus paper to minimise post-sepsis readmissions through identification of potentially preventable factors, appropriate discharge criteria and parental education. More research is required into strategies towards prevention of readmissions following discharge after an episode of severe sepsis in children.
Children with coexisting comorbidities when discharged following severe sepsis have a higher rate of readmission as compared with matched hospitalisations for other acute medical conditions.
There is a need for internationally agreed evidence-based guidelines/consensus paper to minimise post-sepsis readmissions through identification of potentially preventable factors, appropriate discharge criteria and parental education.
More research is required into strategies towards prevention of readmissions following discharge after an episode of severe sepsis in children.
Sepsis is a leading cause of avoidable death across all age groups.
Interstitial lung diseases are characterised by scarring of lung tissue that leads to reduced transfer of oxygen into the blood, decreased exercise capacity and premature death. Ambulatory oxygen therapy may be used to treat exertional oxyhaemoglobin desaturation, but there is little evidence to support its efficacy and there is wide variation in clinical practice. This study aims to compare the clinical efficacy and cost-effectiveness of ambulatory oxygen versus ambulatory air in people with fibrotic interstitial lung disease and exertional desaturation.
A randomised, controlled trial with blinding of participants, clinicians and researchers will be conducted at trial sites in Australia and Sweden. Eligible participants will be randomised 1:1 into two groups. Intervention participants will receive ambulatory oxygen therapy using a portable oxygen concentrator (POC) during daily activities and control participants will use an identical POC modified to deliver air. Outcomes will be assessed at baseline, 3 months and 6 months. The primary outcome is change in physical activity measured by number of steps per day using a physical activity monitor (StepWatch). Secondary outcomes are functional capacity (6-minute walk distance), health-related quality of life (St George Respiratory Questionnaire, EQ-5D-5L and King’s Brief Interstitial Lung Disease Questionnaire), breathlessness (Dyspnoea-12), fatigue (Fatigue Severity Scale), anxiety and depression (Hospital Anxiety and Depression Scale), physical activity level (GENEActive), oxygen saturation in daily life, POC usage, and plasma markers of skeletal muscle metabolism, systematic inflammation and oxidative stress. A cost-effectiveness evaluation will also be undertaken.
Ethical approval has been granted in Australia by Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/42) with governance approval at all Australian sites, and in Sweden (Lund Dnr: 2019-02963). The results will be published in peer-reviewed scientific journals, presented at conferences and disseminated to consumers in publications for lay audiences.
ClinicalTrials.gov Registry (NCT03737409).
Previously improving life expectancy and all-cause mortality in the UK has stalled since the early 2010s. National analyses have demonstrated changes in mortality rates for most age groups and causes of death, and with deprived populations most affected. The aims here were to establish whether similar changes have occurred across different parts of the UK (countries, cities), and to examine cause-specific trends in more detail.
Population-based trend analysis.
Whole populations of countries and selected cities of the UK.
European age-standardised mortality rates (calculated by cause of death, country, city, year (1981–2017), age group, sex and—for all countries and Scottish cities—deprivation quintiles); changes in rates between 5-year periods; summary measures of both relative (relative index of inequality) and absolute (slope index of inequality) inequalities.
Changes in mortality from around 2011/2013 were observed throughout the UK for all adult age groups. For example, all-age female rates decreased by approximately 4%–6% during the 1980s and 1990s, approximately 7%–9% during the 2000s, but by
The study presents further evidence of changing mortality in the UK. The timing, geography and socioeconomic gradients associated with the changes appear to support suggestions that they may result, at least in part, from UK Government ‘austerity’ measures which have disproportionately affected the poorest.
To understand how acute care nurses make decisions about administering “as‐needed” (PRN) psychotropic medications to hospitalised people with dementia (PWD).
Behavioural and psychological symptoms of dementia occur in approximately 75% of PWD admitted to acute care. Despite this, few studies provide insight into the use and prevalence of psychotropic use in acute care.
A qualitative descriptive design was used to explore acute care nurses’ decision‐making about PRN psychotropic medication administration to PWD.
Semi‐structured interviews were conducted with eight nurses from three acute care medical units in a large tertiary hospital in Western Canada. Conventional content analysis was used to develop three themes that reflect nurses’ decision‐making related to administering PRNs to hospitalised PWD. COREQ guidelines were followed.
Three themes of legitimising control, making the patient fit and future telling were developed. Legitimising control involved medicating undesirable behaviours to promote the nurses’ perceptions of safety. Making the patient fit involved maintaining routine and order. Future telling involved pre‐emptively medicating to prevent undesirable behaviours from escalating. Nurses provided little to no mention of assessing for physical causes contributing to behaviours. PRNs were seen as a reasonable alternative to physical restraints and were frequently used. Additionally, organisational and unit routines greatly influenced nurses’ decision‐making.
These findings provide an initial understanding of how nurses make decisions to administer PRN medications to hospitalised older people and may inform prescribing practices. There were novel findings about the lack of assessment prior to PRN administration, and the nurses’ collective response in decision‐making. More research is needed to better understand the complexities of nurses’ decision‐making, to assist in the development of interventions for nursing practice.
Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach.
Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics.
Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases.
There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5–9.5 days. Median presymptomatic infectious period across studies varied over
There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.
The number of inconclusive physical rehabilitation randomised controlled trials for patients with critical illness is increasing. Evidence suggests critical illness patient subgroups may exist that benefit from targeted physical rehabilitation interventions that could improve their recovery trajectory. We aim to identify critical illness patient subgroups that respond to physical rehabilitation and map recovery trajectories according to physical function and quality of life outcomes. Additionally, the utilisation of healthcare resources will be examined for subgroups identified.
This is an individual participant data meta-analysis protocol. A systematic literature review was conducted for randomised controlled trials that delivered additional physical rehabilitation for patients with critical illness during their acute hospital stay, assessed chronic disease burden, with a minimum follow-up period of 3 months measuring performance-based physical function and health-related quality of life outcomes. From 2178 records retrieved in the systematic literature review, four eligible trials were identified by two independent reviewers. Principal investigators of eligible trials were invited to contribute their data to this individual participant data meta-analysis. Risk of bias will be assessed (Cochrane risk of bias tool for randomised trials). Participant and trial characteristics, interventions and outcomes data of included studies will be summarised. Meta-analyses will entail a one-stage model, which will account for the heterogeneity across and the clustering between studies. Multiple imputation using chained equations will be used to account for the missing data.
This individual participant data meta-analysis does not require ethical review as anonymised participant data will be used and no new data collected. Additionally, eligible trials were granted approval by institutional review boards or research ethics committees and informed consent was provided for participants. Data sharing agreements are in place permitting contribution of data. The study findings will be disseminated at conferences and through peer-reviewed publications.
To identify factors influencing the provision, utilisation and sustainability of midwifery units (MUs) in England.
Case studies, using individual interviews and focus groups, in six National Health Service (NHS) Trust maternity services in England.
NHS maternity services in different geographical areas of England Maternity care staff and service users from six NHS Trusts: two Trusts where more than 20% of all women gave birth in MUs, two Trusts where less than 10% of all women gave birth in MUs and two Trusts without MUs. Obstetric, midwifery and neonatal clinical leaders, managers, service user representatives and commissioners were individually interviewed (n=57). Twenty-six focus groups were undertaken with midwives (n=60) and service users (n=52).
Factors influencing MU use.
The study findings identify several barriers to the uptake of MUs. Within a context of a history of obstetric-led provision and lack of decision-maker awareness of the clinical and economic evidence, most Trust managers and clinicians do not regard their MU provision as being as important as their obstetric unit (OU) provision. Therefore, it does not get embedded as an equal and parallel component in the Trust’s overall maternity package of care. The analysis illuminates how implementation of complex interventions in health services is influenced by a range of factors including the medicalisation of childbirth, perceived financial constraints, adequate leadership and institutional norms protecting the status quo.
There are significant obstacles to MUs reaching their full potential, especially free-standing midwifery units. These include the lack of commitment by providers to embed MUs as an essential service provision alongside their OUs, an absence of leadership to drive through these changes and the capacity and willingness of providers to address women’s information needs. If these remain unaddressed, childbearing women’s access to MUs will continue to be restricted.
Depression is a common and debilitating condition. In Australia, general practitioners (GPs) are the key providers of depression care. However, available evidence suggests that case finding for depression in primary care is poor. This study will examine whether a systematic approach to screening for depression and assessing patient preferences for depression care improves depression outcomes among primary care patients.
A cluster randomised controlled design will be used with general practice clinics randomly assigned to either the intervention (n=12) or usual care group (n=12). Patients who are aged 18 and older, presenting for general practice care, will be eligible to participate. Eighty-three participants will be recruited at each clinic. Participants will be asked to complete a baseline survey administered on a touch screen computer at their GP clinic, and then a follow-up survey at 3, 6 and 12 months. Those attending usual care practices will receive standard care. GPs at intervention practices will complete an online Clinical e-Audit, and will be provided with provider and patient-directed resources for depression care. Patients recruited at intervention practices who score 10 or above on the Patient Health Questionnaire-9 will have feedback regarding their depression screening results and preferences for care provided to their GP. The primary analysis will compare the number of cases of depression between the intervention and control groups.
The study has been approved by the University of Newcastle Human Research Ethics Committee, and registered with Human Research Ethics Committees of the University of Wollongong, Monash University and University of New South Wales. Results will be disseminated through peer-reviewed journal publications and conference presentations.
The health workforce is an integral component of the healthcare system. Comprehensive, high-quality data on the health workforce are essential to identifying gaps in health service provision, as well as informing future health workforce and health services planning, and health policy. While many data sources are used in Australia for these purposes, the quality of the data sources with respect to relevance, accessibility and accuracy is not clear.
This scoping review aims to identify and appraise publicly available data sources describing the Australian health workforce. The review will include any data source (eg, registry, administrative database and survey) or document reporting a data source (eg, journal article, report) on the Australian health workforce, which is publicly available and describes the characteristics of the workforce. The search will be conducted in 10 bibliographic databases and the grey literature using an iterative process. Screening of titles and abstracts will be undertaken by two investigators, independently, using Covidence software. Any disagreement between investigators will be resolved by a third investigator. Documents/data sources identified as potentially eligible will be retrieved in full text and reviewed following the same process. Data will be extracted using a customised data extraction tool. A customised appraisal tool will be used to assess the relevance, accessibility and accuracy of included data sources.
The scoping review is a secondary analysis of existing, publicly available data sources and does not require ethics approval. The findings of this scoping review will further our understanding of the quality and availability of data sources used for health workforce and health services planning in Australia. The results will be submitted for publication in peer-reviewed journals and presented at conferences targeted at health workforce and public health topics.
Care of patients with motor neuron disease (MND) in a specialist, multidisciplinary clinic is associated with improved survival, but access is not universal. We wanted to pilot and establish the feasibility of a definitive trial of a novel telehealth system (Telehealth in Motor neuron disease, TiM) in patients with MND.
An 18-month, single-centre, mixed-methods, randomised, controlled pilot and feasibility study.
TiM telehealth plus usual care versus usual care.
A specialist MND care centre in the UK.
Patients with MND and their primary informal carers.
Recruitment, retention and data collection rates, clinical outcomes including participant quality of life and anxiety and depression.
Recruitment achieved the target of 40 patients and 37 carers. Participant characteristics reflected those attending the specialist clinic and included those with severe disability and those with limited experience of technology. Retention and data collection was good. Eighty per cent of patients and 82% of carer participants reported outcome measures were completed at 6 months. Using a longitudinal analysis with repeated measures of quality of life (QoL), a sample size of 131 per arm is recommended in a definitive trial. The methods and intervention were acceptable to participants who were highly motivated to participate to research. The low burden of participation and accessibility of the intervention meant barriers to participation were minimal. However, the study highlighted difficulties assessing the associated costs of the intervention, the challenge of recruitment in such a rare disease and the difficulties of producing rigorous evidence of impact in such a complex intervention.
A definitive trial of TiM is feasible but challenging. The complexity of the intervention and heterogeneity of the patient population means that a randomised controlled trial may not be the best way to evaluate the further development and implementation of the TiM.
To evaluate the processes involved in using a novel digitally enabled healthcare system (telehealth in motor neuron disease (TiM)) in people living with motor neuron disease (MND) and their informal carers. We examined TiM implementation, potential mechanisms of impact and contextual factors that might influence TiM implementation or impact.
An 18-month, single-centre process evaluation within a randomised, pilot and feasibility study.
TiM plus usual care versus usual care alone.
A specialist UK MND care centre.
40 patients with MND and 37 primary informal carers.
Patient, carer and staff outcomes and experiences using semistructured interviews. Descriptive data on implementation and use of TiM.
The TiM was acceptable and accessible to patients, carers and staff. Intervention uptake and adherence were good: 14 (70%) patients completed a TiM session at least fortnightly. Barriers to TiM use (such as technology experience and disability) were overcome with well-designed technology and face-to-face training. Reported potential benefits of TiM included improved communication and care coordination, reassurance, identification of complications and the potential for TiM to be an alternative or addition to clinic. Benefits depended on patients’ current level of needs or disability. The main challenges were the large number of alerts that were generated by TiM, how the clinicians responded to these alerts and the mismatch between patient/carer expectations and nurses actions. This could be improved by better communication systems and adjusting the alerts algorithm.
TiM has the potential to facilitate access to specialist care, but further iterative developments to the intervention and process evaluations of the TiM in different services are required.
Children with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD.
This is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3–15 years of age), 70 TD participants (3–15 years) and 35 children with idiopathic ASD (7–15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child’s behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria.
This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.
This study compares two vs six weeks of topical antimicrobial therapy with Cadexomer Iodine in patients with diabetic foot ulcers (DFUs) complicated by chronic biofilm infections. Patients with non‐healing DFUs with suspected chronic biofilm infections were eligible for enrolment. Patients were randomised to receive either two or six weeks of treatment with topical Cadexomer Iodine. Tissue biopsies from the ulcers were obtained pre‐and‐post treatment and underwent DNA sequencing and real‐time quantitative polymerase chain reaction (PCR) to determine the total microbial load, community composition, and diversity of bacteria. Scanning electron microscopy confirmed biofilm in all 18 ulcers with suspected chronic biofilm infections. Cadexomer Iodine resulted in 14 of 18 (78%) samples achieving a mean 0.5 log10 reduction in microbial load. Regardless of treatment duration, there was no statistical difference in the reduction of total microbial loads. No difference in the rate of wound healing in the two groups was seen at 6 weeks. Cadexomer Iodine reduces the total microbial load in DFUs with chronic biofilm infections and affects microbial community composition and diversity. All ulcers in both groups showed an initial reduction in wound size with application of Cadexomer Iodine, which might reflect its effect on biofilms.
To identify priority interventions for the prevention and reduction of work stress and burnout in hospital doctors through analysis of (1) doctors’ experiences of work stress and burnout and (2) their preferences with respect to interventions.
Qualitative design using semistructured interviews analysed with deductive thematic analysis.
Hospitals in Ireland.
32 hospital doctors (16 practising consultants and 16 doctors in training) from a range of specialties, career stages, hospital types and locations.
Practical, system-focused interventions were found to be most needed. Challenges with basic entitlements, that is, accessing statutory leave, knowing in advance when leave can be taken and being adequately covered when on leave were identified as requiring urgent attention. Other priority interventions identified were the integration of psychological support in the everyday working environment, time and training for clinical line managers to perform key management activities such as debriefing and education interventions which highlight work stress risks and care pathways, teach self-care and train doctors in how to support one another.
Hospital doctors are feeling the effects of greater demand and fewer resources. What they most urgently need is adequate staffing levels, access to statutory leave and adequate cover when on leave. Doctors do not receive the support they need from their clinical line managers, who lack the skills and time to excel as people managers. Organisations should focus on developing clinical management skills across the system. The culture of medicine needs to change from stigmatisation and competitiveness to compassion and collaboration. Organisations, medical schools and professional bodies can steer this change through education.
Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is characterised by recurring episodes of complete or partial upper airway collapse during sleep. Persistent OSAHS is associated with long-term consequences, such as growth failure, cardiovascular and neurocognitive problems in children. Different from the aetiology of OSAHS in adults, the most common cause of paediatric OSAHS is adenotonsillar hypertrophy. Adenotonsillectomy (AT) has been recommended as the first-line treatment of paediatric OSAHS. Several studies have suggested that retarded growth caused by OSAHS can improve after AT during the prepubertal period. This review will systematically search and summarise the available evidence on the effects of AT on children’s growth.
We will conduct electronic searches in MEDLINE (via PubMed), Embase, Google Scholar and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) or cohort studies that included a control group. Additional records will be searched by checking the references included in the selected studies and relevant reviews. At least two authors will undertake selection of studies and data extraction independently and in duplicate. The Cochrane Risk of Bias tool and Risk Of Bias In Non-randomised Studies—of Interventions will be used to assess the risk of bias of RCT and cohort studies, respectively. A random-effects model will be used for meta-analyses. Data synthesis and other analyses will be carried out using the RevMan V.5.3 software. The Grades of Recommendation, Assessment, Development and Evaluation will be used to assess the quality of the supporting evidence behind each main comparison.
There is no ethical issue in this systematic review given that we will only include published studies. The results will be disseminated via peer-reviewed publications and social networks.
The aim of this study was to develop an observational metric that could be used to assess the performance of a practitioner in completing an acute surgical wound‐dressing procedure using aseptic non‐touch technique (ANTT). A team of clinicians, academics, and researchers came together to develop an observational metric using an iterative six‐stage process, culminating in a Delphi panel meeting. A scoping review of the literature provided a background empirical perspective relating to wound‐dressing procedure performance. Video recordings of acute surgical wound‐dressing procedures performed by nurses in clinical (n = 11) and simulated (n = 3) settings were viewed repeatedly and were iteratively deconstructed by the metric development group. This facilitated the identification of the discrete component steps, potential errors, and sentinel (serious) errors, which characterise a wound dressing procedure and formed part of the observational metric. The ANTT wound‐dressing observational metric was stress tested for clarity, the ability to be scored, and interrater reliability, calculated during a further phase of video analysis. The metric was then subjected to a process of cyclical evaluation by a Delphi panel (n = 21) to obtain face and content validity of the metric. The Delphi panel deliberation verified the face and content validity of the metric. The final metric has three phases, 31 individual steps, 18 errors, and 27 sentinel errors. The metric is a tool that identifies the standard to be attained in the performance of acute surgical wound dressings. It can be used as both an adjunct to an educational programme and as a tool to assess a practitioner's performance of a wound‐dressing procedure in both simulated and clinical practice contexts.