Multi-faceted intervention to improve management of antibiotics for children presenting to primary care with acute cough and respiratory tract infection (CHICO): efficient cluster randomised controlled trial.

OBJECTIVE: To assess whether an easy-to-use multifaceted intervention for children presenting to primary care with respiratory tract infections would reduce antibiotic dispensing, without increasing hospital admissions for respiratory tract infection. DESIGN: Two arm randomised controlled trial clustered by general practice, using routine outcome data, with qualitative and economic evaluations. SETTING: English primary care practices using the EMIS electronic medical record system. PARTICIPANTS: Children aged 0-9 years presenting with respiratory tract infection at 294 general practices, before and during the covid-19 pandemic. INTERVENTION: Elicitation of parental concerns during consultation; a clinician focused prognostic algorithm to identify children at very low, normal, or elevated 30 day risk of hospital admission accompanied by antibiotic prescribing guidance; and a leaflet for carers including safety netting advice. MAIN OUTCOME MEASURES: Rate of dispensed amoxicillin and macrolide antibiotics (superiority comparison) and hospital admissions for respiratory tract infection (non-inferiority comparison) for children aged 0-9 years over 12 months (same age practice list size as denominator). RESULTS: Of 310 practices needed, 294 (95%) were randomised (144 intervention and 150 controls) representing 5% of all registered 0-9 year olds in England. Of these, 12 (4%) subsequently withdrew (six owing to the pandemic). Median intervention use per practice was 70 (by a median of 9 clinicians). No evidence was found that antibiotic dispensing differed between intervention practices (155 (95% confidence interval 138 to 174) items/year/1000 children) and control practices (157 (140 to 176) items/year/1000 children) (rate ratio 1.011, 95% confidence interval 0.992 to 1.029; P=0.25). Pre-specified subgroup analyses suggested reduced dispensing in intervention practices with fewer prescribing nurses, in single site (compared with multisite) practices, and in practices located in areas of lower socioeconomic deprivation, which may warrant future investigation. Pre-specified sensitivity analysis suggested reduced dispensing among older children in the intervention arm (P=0.03). A post hoc sensitivity analysis suggested less dispensing in intervention practices before the pandemic (rate ratio 0.967, 0.946 to 0.989; P=0.003). The rate of hospital admission for respiratory tract infections in the intervention practices (13 (95% confidence interval 10 to 18) admissions/1000 children) was non-inferior compared with control practices (15 (12 to 20) admissions/1000 children) (rate ratio 0.952, 0.905 to 1.003). CONCLUSIONS: This multifaceted antibiotic stewardship intervention for children with respiratory tract infections did not reduce overall antibiotic dispensing or increase respiratory tract infection related hospital admissions. Evidence suggested that in some subgroups and situations (for example, under non-pandemic conditions) the intervention slightly reduced prescribing rates but not in a clinically relevant way. TRIAL REGISTRATION: ISRCTN11405239ISRCTN registry ISRCTN11405239.

A multifaceted intervention to reduce antibiotic prescribing among CHIldren with acute COugh and respiratory tract infection: the CHICO cluster RCT.

Background: Clinical uncertainty in primary care regarding the prognosis of children with respiratory tract infections contributes to the unnecessary use of antibiotics. Improved identification of children at low risk of future hospitalisation might reduce clinical uncertainty. A National Institute for Health and Care Research-funded 5-year programme (RP-PG-0608-10018) was used to develop and feasibility test an intervention. Objectives: The aim of the children with acute cough randomised controlled trial was to reduce antibiotic prescribing among children presenting with acute cough and respiratory tract infection without increasing hospital admission. Design: An efficient, pragmatic open-label, two-arm trial (with embedded qualitative and health economic analyses) using practice-level randomisation using routinely collected data as the primary outcome. Setting: General practitioner practices in England. Participants: General practitioner practices using the Egton Medical Information Systems® patient-record system for children aged 0-9 years presenting with a cough or upper respiratory tract infection. Recruited by Clinical Research Networks and Clinical Commissioning Groups. Intervention: Comprised: (1) elicitation of parental concerns during consultation; (2) a clinician-focused prognostic algorithm to identify children with acute cough and respiratory tract infection at low, average or elevated risk of hospitalisation in the next 30 days accompanied by prescribing guidance, (3) provision of a printout for carers including safety-netting advice. Main outcome measures: Co-primaries using the practice list-size for children aged 0-9 years as the denominator: rate of dispensed amoxicillin and macrolide items at each practice (superiority comparison) from NHS Business Services Authority ePACT2 and rate of hospital admission for respiratory tract infection (non-inferiority comparison) from Clinical Commissioning Groups, both routinely collected over 12 months. Results: Of the 310 practices required, 294 (95%) were recruited (144 intervention and 150 controls) with 336,496 registered 0-9-year-olds (5% of all 0-9-year-old children in England) from 47 Clinical Commissioning Groups. Included practices were slightly larger than those not included, had slightly lower baseline dispensing rates and were located in more deprived areas (reflecting the distribution for practice postcodes nationally). Twelve practices (4%) subsequently withdrew (six related to the pandemic). The median number of times the intervention was used was 70 per practice (by a median of 9 clinicians) over 12 months. There was no evidence that the antibiotic dispensing rate in the intervention practices [0.155 (95% confidence interval 0.135 to 0.179)] differed to controls [0.154 (95% confidence interval 0.130 to 0.182), relative risk= 1.011 (95% confidence interval 0.992 to 1.029); p = 0.253]. There was, overall, a reduction in dispensing levels and intervention usage during the pandemic. The rate of hospitalisation for respiratory tract infection in the intervention practices [0.019 (95% confidence interval 0.014 to 0.026)] compared to the controls [0.021 (95% confidence interval 0.014 to 0.029)] was non-inferior [relative risk = 0.952 (95% confidence interval 0.905 to 1.003)]. The qualitative evaluation found the clinicians liked the intervention, used it as a supportive aid, especially with borderline cases but that it, did not always integrate well within the consultation flow and was used less over time. The economic evaluation found no evidence of a difference in mean National Health Service costs between arms; mean difference -£1999 (95% confidence interval -£6627 to 2630). Conclusions: The intervention was feasible and subjectively useful to practitioners, with no evidence of harm in terms of hospitalisations, but did not impact on antibiotic prescribing rates. Future work and limitations: Although the intervention does not appear to change prescribing behaviour, elements of the approach may be used in the design of future interventions. Trial registration: This trial is registered as ISRCTN11405239 (date assigned 20 April 2018) at www.controlled-trials.com (accessed 5 September 2022). Version 4.0 of the protocol is available at: https://www.journalslibrary.nihr.ac.uk/ (accessed 5 September 2022). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (NIHR award ref: 16/31/98) programme and is published in full in Health Technology Assessment; Vol. 27, No. 32. See the NIHR Funding and Awards website for further award information.

Coughs and colds (also known as respiratory tract infections) are the most common reason that children are taken to family doctors and nurses in primary care. These clinicians are not always sure how best to treat them and often use antibiotics 'just in case'. There are now concerns that clinicians are using antibiotics too often, and that this is increasing the number of resistant bugs (bacteria that cannot be killed by antibiotics). We wanted to see if using a scoring system of symptoms and signs of illness to help clinicians identify children very unlikely to need hospital care as well as listening to parents' concerns and giving them a personalised leaflet with care and safety advice, reduced antibiotic use. We recruited practices rather than patients, so did not need individual patient consent. The two main outcomes were the rate of antibiotics dispensed for children and number of children admitted to hospital for respiratory tract infections, using routinely collected data for 0­9-year-olds. We recruited 294 general practitioner practices, which was 95% of the total needed; 144 were asked to use the intervention and 150 to continue providing usual care (controls); only 12 practices subsequently withdrew (6 related to the pandemic). The average number of times the intervention was used was 70 per practice (by an average of 9 clinicians) over 12 months. There was no evidence that the antibiotic dispensing rate in the intervention practices differed from control practices. Further analyses showed an overall reduction in dispensing levels and intervention usage during the pandemic. The rate of hospitalisation for respiratory tract infection in the intervention practices was similar to the control practices. In the interviews, we found that clinicians liked the intervention and used it as a supportive aid during consultations, especially for borderline cases, rather than a tool to change prescribing behaviour.

The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression.

OBJECTIVE: To test the hypothesis that the baseline clinico-pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10-year median follow-up were different from those of men with stable disease (n = 1409). PATIENTS AND METHODS: We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models. RESULTS: The findings showed that 34% of participants (n = 505) had intermediate- or high-risk PCa, and 66% (n = 973) had low-risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low- and intermediate-/high-risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65-69 vs 50-64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins. CONCLUSIONS: We demonstrate that one-third of the ProtecT cohort consists of people with intermediate-/high-risk disease, and the outcomes data at an average of 10 years' follow-up are generalizable beyond men with low-risk PCa.

Active surveillance for low-risk prostate cancer.

Active surveillance (AS) is an important management strategy for men diagnosed with low-risk prostate cancer (PCa). The need for AS is increasing due to the awareness that many PCa are identified that show a low growth potential and therefore are likely to remain clinically asymptomatic during the lifetime of an individual. Currently there is no good method to prevent the overdiagnosis of indolent cancers upfront. During the last decade, several studies on AS around the world have made observations that feed the discussion on how to select and monitor these patients, how to proceed with the research to develop a better and more precise clinical definition of indolent cancers and how to manage men under AS clinically. Furthermore, patients' perspectives have become clearer, and quality of life studies give direction to the practical approach and care for patients and partners. This paper reflects the consensus on the state of the art and the future direction of AS, based on the Inside Track Conference "Active Surveillance for low risk prostate cancer" (Chairmen: C.H. Bangma, NL, and L. Klotz, CA; Co-Chairmen: L.J. Denis, BE, and C. Parker, UK; Scientific Coordinators: M. J. Roobol, NL, and E.W. Steyerberg, NL), organized by the European School of Oncology in collaboration with Europa Uomo in Rotterdam, the Netherlands in January 2012. Topics for discussion were the optimisation of patient selection based on indolent disease definition, the incorporation of therapeutic agents into AS programs, the optimisation of patient care, and the application of emerging technologies and biomarkers.

Measuring the psychosocial impact of population-based prostate-specific antigen testing for prostate cancer in the UK.

OBJECTIVE: To evaluate the psychosocial impact of participation in a population-based prostate-specific antigen (PSA) testing programme, akin to screening, and to explore the relationship between urinary symptoms reported before PSA testing and the response to the subsequent PSA result. PATIENTS AND METHODS: This prospective questionnaire study was nested within the case-finding component of the ProtecT (prostate testing for cancer and treatment) feasibility study (ISRCTN20141297). Men aged 50-69 years from 18 general practices in three cities in the UK completed the Hospital Anxiety and Depression Scale (HADS), the Short Form-12 (SF-12) Health Survey, and the International Continence Society 'male' (ICSmale) questionnaires before giving consent for a PSA test in a community clinic (baseline). Men with an 'abnormal' PSA result returned for further investigation (including biopsy) and repeated these questionnaires before biopsy. RESULTS: At baseline, study participants had similar levels of anxiety and depression to the general male population. There was no increase in the HADS scores, or reduction in the SF-12 mental health component summary score, on attendance at the biopsy clinic after receiving an 'abnormal' PSA result. Urinary symptoms were associated with levels of anxiety and depression before receiving a PSA result (baseline), but were not associated with anxiety and depression at biopsy independently of baseline scores. Therefore changes in anxiety or depression at biopsy did not appear to differ between those with and without urinary symptoms. CONCLUSIONS: This study confirms the findings of other studies that the deleterious effects of receiving an abnormal PSA result during population screening are not identified by generic health-status questionnaires. Comparisons with outcomes of studies measuring cancer-specific distress and using qualitative research methods raise the question of whether a prostate cancer screening-specific instrument is required. However, a standardized measure of anxiety identified differences at baseline between those who did and did not report urinary symptoms. These findings suggest that it might be advisable to better inform men undergoing PSA testing about the uncertain relationship between urinary symptoms and prostate cancer, to minimize baseline levels of psychological distress.