Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy: a systematic review using individual patient data.

PURPOSE: We conducted a systematic review and individual patient data (IPD) meta-analysis to examine the utility of cystatin C for evaluation of glomerular function in children with cancer. METHODS: Eligible studies evaluated the accuracy of cystatin C for detecting poor renal function in children undergoing chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies shared IPD. We calculated the correlation between log cystatin C and GFR stratified by study and measure of cystatin C. We dichotomized the reference standard at GFR 80 ml/min/1.73m2 and stratified cystatin C at 1 mg/l, to calculate sensitivity and specificity in each study and according to age group (0-4, 5-12, and ≥ 13 years). In sensitivity analyses, we investigated different GFR and cystatin C cut points. We used logistic regression to estimate the association of impaired renal function with log cystatin C and quantified diagnostic accuracy using the area under the ROC curve (AUC). RESULTS: Six studies, which used different test and reference standard thresholds, suggested that cystatin C has the potential to monitor renal function in children undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children) showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%), although use of a GFR cut point of < 60 ml/min/1.73m2 (data only available from two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic accuracy appeared to decrease with age. CONCLUSIONS: Cystatin C has better diagnostic accuracy than creatinine as a test for glomerular dysfunction in young people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for it to replace current reference standards for predicting clinically relevant impairments that may alter dosing of important nephrotoxic agents.

Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review.

To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with localised prostate cancer in receipt of surgery, radiotherapy or active surveillance and reported symptomatic and quality-of-life (QoL) data from 6 to 60 months after treatment were eligible. Data were extracted by one reviewer and checked by another. In all, 64 studies (80 treatment cohorts) were included. Most were single treatment cohorts from the USA or Europe. Radiotherapy was the most common treatment (40 cohorts, including 31 brachytherapy cohorts) followed by prostatectomy (39 cohorts), with only one active surveillance cohort. Most frequently measured symptoms were urinary, followed by sexual, and bowel; QoL was assessed in only 17 cohorts. Most studies used validated measures, although poor data reporting and differences between studies meant that it was not possible to pool data. Data on the precise impact of short-term symptomatic and QoL outcomes after treatment for localised prostate cancer are of insufficient quality for clear guidance to men about the risks to these aspects of their lives. It is important that future studies focus on collecting core outcomes through validated measures and comply with reporting guidelines, so that clear and accurate information can be derived for men considering screening or treatment for prostate cancer.

Inclusive approaches to involvement of community groups in health research: the co-produced CHICO guidance.

BACKGROUND: Racially marginalised groups are underserved in healthcare and underrepresented in health research. Patient and public involvement and engagement (PPIE) is established as the method to ensure equity in health research. However, methods traditionally employed in PPIE can lead to the exclusion of some communities and exacerbation of existing inequalities, highlighting the need to develop inclusive processes for more inclusive community involvement in health research. We aimed to produce guidance to promote good practice for inclusive involvement of racially marginalised community groups in health research via public and community involvement and engagement. METHODS: The CHecklist for Inclusive COmmunity involvement in health research (CHICO) was co-produced by researchers and three Bristol-based community organisations: Dhek Bhal, My Friday Coffee Morning-Barton Hill, and Malcolm X Elders. After initial conversations and link building with community leaders to develop relationships, researchers attended at least three meetings with each community group to discuss preferred approaches to involvement. Each community group had a different format, and discussions were open and tailored to fit the groups preferences. The meetings were held in the community groups' usual meeting venue. Notes from meetings were reviewed by researchers to identify key themes, which were used to inform the creation of a draft illustration which was then taken back to the community groups for refinement and used to inform the development of written guidance and the final illustration. RESULTS: Checklist items were structured into three stages: (1) building relationships, (2) reciprocal relationships and (3) practicalities. Stage 1 highlights the importance of building trust with the community group over time through regular visits to community venues and talking to people informally to understand the history of the group, their preferences and needs, and topics that are likely to be of interest to them. Stage 2 focusses on maintaining a reciprocal relationship and understanding how to best to give back to the community. Stage 3 provides guidance on the practicalities of designing and running inclusive community-based involvement activities, including consideration of the venue, format, communication-style, language requirements, social activities, and provision of food. CONCLUSIONS: Our co-produced checklist can guide researchers in how to involve people from different ethnicities in health research that is relevant to their community.

Health research needs to be for everyone. For this to happen, people from all backgrounds need to be involved. However, people from ethnic minority backgrounds are often not involved in the design of health research. We wanted to find out how researchers and community groups can work together to make the research process more inclusive. Researchers worked with three community groups in Bristol. These were South Asian, African Caribbean and (majority) Somali community groups. One researcher talked with community leaders to find out if the interests of the research unit was relevant to community members and to understand how each group would prefer to work. Following this, at least three meetings were held with each group. After these meetings, we looked at what was talked about. We suggest that researchers involving community groups in health research follow three key steps. Step 1 is making relationships and covers the importance of building trust with the community. This should be through talking with community leaders and regular visits to the group to get to know members before asking for input. Step 2 is about how to best to give back to the community. This is important to make sure that relationships are fair. Step 3 is about how to design and run activities. This includes thinking about the venue, language needs, social activities, and providing food. Our suggestions can help researchers and community groups to work together on health research. We have made an illustration of our findings for sharing.

Prehabilitation for frail patients undergoing total hip or knee replacement: protocol for the Joint PREP feasibility randomised controlled trial.

BACKGROUND: Approximately, 8% of community-based adults aged ≥ 50 years in England are frail. Frailty has been found to be associated with poorer outcomes after joint replacement. Targeting frailty preoperatively via exercise and protein supplementation has the potential to improve outcomes for people undergoing joint replacement. Prior to proceeding with a randomised controlled trial (RCT), a feasibility study is necessary to address key uncertainties and explore how to optimise trial design and delivery. METHODS: The Joint PRehabilitation with Exercise and Protein (Joint PREP) study is a feasibility study for a multicentre, two-arm, parallel group, pragmatic, RCT to evaluate the clinical and cost-effectiveness of prehabilitation for frail patients undergoing total hip or knee replacement. Sixty people who are ≥ 65 years of age, frail according to the self-reported Groningen Frailty Indicator, and scheduled to undergo total hip or knee replacement at 2-3 hospitals in England and Wales will be recruited and randomly allocated on a 1:1 ratio to the intervention or usual care group. The usual care group will receive the standard care at their hospital. The intervention group will be given a daily protein supplement and will be asked to follow a home-based, tailored daily exercise programme for 12 weeks before their operation, in addition to usual care. Participants will be supported through six follow-up calls from a physiotherapist during the 12-week intervention period. Study questionnaires will be administered at baseline and 12 weeks after randomisation. Embedded qualitative research with patients will explore their experiences of participating, reasons for nonparticipation, and/or reasons for withdrawal or treatment discontinuation. Primary feasibility outcomes will be eligibility and recruitment rates, adherence to the intervention, and acceptability of the trial and the intervention. DISCUSSION: This study will generate important data regarding the feasibility of a RCT to evaluate a prehabilitation intervention for frail patients undergoing total hip and knee replacement. A future phase-3 RCT will determine if preoperative exercise and protein supplementation improve the recovery of frail patients after primary joint replacement. TRIAL REGISTRATION: ISRCTN11121506, registered 29 September 2022.

Development of evidence-based guidelines for the treatment and management of periprosthetic hip infection.

Periprosthetic hip-joint infection is a multifaceted and highly detrimental outcome for patients and clinicians. The incidence of prosthetic joint infection reported within two years of primary hip arthroplasty ranges from 0.8% to 2.1%. Costs of treatment are over five-times greater in people with periprosthetic hip joint infection than in those with no infection. Currently, there are no national evidence-based guidelines for treatment and management of this condition to guide clinical practice or to inform clinical study design. The aim of this study is to develop guidelines based on evidence from the six-year INFection and ORthopaedic Management (INFORM) research programme. We used a consensus process consisting of an evidence review to generate items for the guidelines and online consensus questionnaire and virtual face-to-face consensus meeting to draft the guidelines. The consensus panel comprised 21 clinical experts in orthopaedics, primary care, rehabilitation, and healthcare commissioning. The final output from the consensus process was a 14-item guideline. The guidelines make recommendations regarding increased vigilance and monitoring of those at increased risk of infection; diagnosis including strategies to ensure the early recognition of prosthetic infection and referral to orthopaedic teams; treatment, including early use of DAIR and revision strategies; and postoperative management including appropriate physical and psychological support and antibiotic strategies. We believe the implementation of the INFORM guidelines will inform treatment protocols and clinical pathways to improve the treatment and management of periprosthetic hip infection.

Hospice-at-home nurses' experiences of caring for patients.

BACKGROUND: The demand for hospice-at-home (HH) nurses is increasing due to an ageing global population and many people preferring to die at home. Therefore, the retention of existing HH nurses is vital. AIMS: This paper explores HH nurses' experiences of caring for dying patients to discover the factors that enable them to maintain their enthusiasm for their work, and cope with the challenges of working in a patient's home. METHODS: This qualitative study consisted of multiple unstructured interviews with 16 HH nurses conducted in England. FINDINGS: The interviews show that HH nurses: use a broad range of coping mechanisms; encounter intense, complex, unpredictable and ethically unclear challenges; identify a need for more support; and love their job. CONCLUSION: In order for nurses to continue to enjoy their job, extra support to incorporate protected time for debriefing at the end of an HH nurse's shift is needed. Nurses also need training to develop positive coping skills, external supervision on a one-to-one basis as needed, and have their value demonstrated, by their employers and managers recognising and acknowledging them. These factors are likely to facilitate in the retention of employment of HH nurses.

Feasibility cluster randomised controlled trial of a within-consultation intervention to reduce antibiotic prescribing for children presenting to primary care with acute respiratory tract infection and cough.

OBJECTIVE: To investigate recruitment and retention, data collection methods and the acceptability of a 'within-consultation' complex intervention designed to reduce antibiotic prescribing. DESIGN: Primary care feasibility cluster randomised controlled trial. SETTING: 32 general practices in South West England recruiting children from October 2014 to April 2015. PARTICIPANTS: Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI). INTERVENTION: A web-based clinician-focussed clinical rule to predict risk of future hospitalisation and a printed leaflet with individualised child health information for carers, safety-netting advice and a treatment decision record. CONTROLS: Usual practice, with clinicians recording data on symptoms, signs and treatment decisions. RESULTS: Of 542 children invited, 501 (92.4%) consented to participate, a month ahead of schedule. Antibiotic prescribing data were collected for all children, follow-up data for 495 (98.8%) and the National Health Service resource use data for 494 (98.6%). The overall antibiotic prescribing rates for children's RTIs were 25% and 15.8% (p=0.018) in intervention and control groups, respectively. We found evidence of postrandomisation differential recruitment: the number of children recruited to the intervention arm was higher (292 vs 209); over half were recruited by prescribing nurses compared with less than a third in the control arm; children in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03) and appeared to be more unwell than those in the control arm with higher respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews with clinicians confirmed preferential recruitment of less unwell children to the trial, more so in the control arm. CONCLUSION: Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records. TRIAL REGISTRATION NUMBER: ISRCTN 23547970 UKCRN STUDY ID: 16891.

How well do health professionals interpret diagnostic information? A systematic review.

OBJECTIVE: To evaluate whether clinicians differ in how they evaluate and interpret diagnostic test information. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE and PsycINFO from inception to September 2013; bibliographies of retrieved studies, experts and citation search of key included studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Primary studies that provided information on the accuracy of any diagnostic test (eg, sensitivity, specificity, likelihood ratios) to health professionals and that reported outcomes relating to their understanding of information on or implications of test accuracy. RESULTS: We included 24 studies. 6 assessed ability to define accuracy metrics: health professionals were less likely to identify the correct definition of likelihood ratios than of sensitivity and specificity. -25 studies assessed Bayesian reasoning. Most assessed the influence of a positive test result on the probability of disease: they generally found health professionals' estimation of post-test probability to be poor, with a tendency to overestimation. 3 studies found that approaches based on likelihood ratios resulted in more accurate estimates of post-test probability than approaches based on estimates of sensitivity and specificity alone, while 3 found less accurate estimates. 5 studies found that presenting natural frequencies rather than probabilities improved post-test probability estimation and speed of calculations. CONCLUSIONS: Commonly used measures of test accuracy are poorly understood by health professionals. Reporting test accuracy using natural frequencies and visual aids may facilitate improved understanding and better estimation of the post-test probability of disease.