Collaborative discussions between pharmacists and general practitioners to optimise patient medication: a qualitative study within a clinical trial.

BACKGROUND: There has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking. AIM: To explore GP and pharmacist views and experiences of in-person, inter-professional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice. DESIGN AND SETTING: A mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands. METHOD: Audio-recordings of IPCDs between GPs and pharmacists, and individual semi-structured interviews exploring their reflections on these discussions. All recordings were transcribed verbatim and analysed thematically. RESULTS: Fourteen practices took part in the process evaluation (Feb 2021- Sept 2023). Seventeen IPCD meetings were audio recorded discussing 30 patients (range of 1-6 patients per meeting). Six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits including: strengthening their working relationship; learning from each other; and gaining in confidence to manage more complex patients. It was often challenging, however, to find time for the IPCDs. CONCLUSION: The model of IPCD studied provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for inter-professional liaison and collaboration, and structured interventions may facilitate improved patient care.

Improving the care of children with GENetic Rare disease: Observational Cohort study (GenROC)-a study protocol.

INTRODUCTION: Around 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality. Often little is known about expected growth and phenotypes in these children. Parents have responded by setting up social media groups to generate data themselves. Given the significant clinical evidence gaps, this research will attempt to identify growth patterns, developmental profiles and phenotypes, providing data on long-term medical and educational outcomes. This will guide clinicians when to investigate, monitor or treat symptoms and when to search for additional or alternative diagnoses. METHODS AND ANALYSIS: This is an observational, multicentre cohort study recruiting between March 2023 and February 2026. Children aged 6 months up to 16 years with a pathogenic or likely pathogenic variant in a specified gene will be eligible. Children will be identified through the National Health Service and via self-recruitment. Parents or carers will complete a questionnaire at baseline and again 1 year after recruitment. The named clinician (in most cases a clinical geneticist) will complete a clinical proforma which will provide data from their most recent clinical assessment. Qualitative interviews will be undertaken with a subset of parents partway through the study. Growth and developmental milestone curves will be generated through the DECIPHER website (https://deciphergenomics.org) where 5 or more children have the same genetic syndrome (at least 10 groups expected). ETHICS AND DISSEMINATION: The results will be presented at national and international conferences concerning the care of children with genetic syndromes. Results will also be submitted for peer review and publication.

A Risk Assessment and Planning Tool to Prevent Sudden Unexpected Death in Infancy: Development and Evaluation of The Baby Sleep Planner.

BACKGROUND: Successful national safer sleep campaigns in the United Kingdom have lowered the death rates from sudden unexpected death in infancy (SUDI) over the past 3 decades, but deaths persist in socioeconomically deprived families. The circumstances of current deaths suggest that improvements in support for some families to follow safer sleep advice more consistently could save lives. OBJECTIVE: This study aimed to develop and evaluate a risk assessment and planning tool designed to improve the uptake of safer sleep advice in families with infants at increased risk of SUDI. METHODS: A co-design approach was used to develop the prototype interface of a web-based tool with 2 parts: an individual SUDI risk assessment at birth and a downloadable plan for safety during times of disruption. The advice contained within the tool is concordant with national guidance from the Lullaby Trust, the United Nations International Children's Emergency Fund (UNICEF), and the National Institute for Health and Care Excellence. User testing of the prototype tool was conducted by inviting health visitors, midwives, and family nurses to use it with families eligible for additional support. Qualitative interviews with health professionals and families allowed for iterative changes to the tool and for insights into its function and influence on parental behavior. RESULTS: A total of 22 health professionals were enrolled in the study, of whom 20 (91%) were interviewed. They reported appreciating the functionality of the tool, which allowed them to identify at-risk families for further support. They felt that the tool improved how they communicated about risks with families. They suggested expanding its use to include relevance in the antenatal period and having versions available in languages other than English. They reported using the tool with 58 families; 20 parents gave consent to be interviewed by the research team about their experiences with the tool. Families were positive about the tool, appreciated the trustworthy information, and felt that it was useful and appropriate and that the plans for specific infant sleeps would be of benefit to them and other family members. CONCLUSIONS: Our tool combines risk assessment and safety planning, both of which have the potential to improve the uptake of lifesaving advice. Refinements to the tool based on these findings have ensured that the tool is ready for further evaluation in a larger study before being rolled out to families with infants at increased risk.

Implementation of the CHIldren with acute COugh (CHICO) intervention to improve antibiotics management: a qualitative study in primary care.

BACKGROUND: Childhood respiratory tract infections (RTIs) are common and can lead to unnecessary antibiotic use and antimicrobial resistance. The CHIldren with COugh (CHICO) intervention incorporates a clinician-focused algorithm (STARWAVe) to predict future hospitalisation risk, elicitation of carer concerns, and a carer-focused personalised leaflet recording treatment decisions and safety-netting information. AIM: To examine the implementation of the CHICO intervention by primary care clinicians. DESIGN AND SETTING: A qualitative study with primary care clinicians in England taking part in the CHICO randomised controlled trial. METHOD: Interviews explored the CHICO intervention's acceptability and use. Clinicians from a range of practices with high and low antibiotic dispensing rates were recruited. Normalisation process theory underpinned data collection and thematic analysis. RESULTS: Most clinicians liked the intervention because it was quick and easy to use, it helped elicit carer concerns, and reassured clinicians and carers of the appropriateness of treatment decisions. However, clinicians used it as a supportive aid for treatment decisions rather than as a tool for behaviour change. The accompanying advice leaflet helped explain treatment decisions and support self-care. The intervention did not always align with clinicians' usual processes, which could affect use. Increased familiarisation with the algorithm led to reduced intervention use, which was further reduced during the COVID-19 pandemic as a result of changes to practice and remote consultations. CONCLUSION: Clinicians found the CHICO intervention useful to support decision making around antibiotic prescribing and it helped discussions with carers about concerns and treatment decisions. The intervention may need to be adapted to align more with clinicians' consultation flow and remote consultations.

Predicting Prostate Surgery Outcomes from Standard Clinical Assessments of Lower Urinary Tract Symptoms To Derive Prognostic Symptom and Flowmetry Criteria.

BACKGROUND: Assessment of male lower urinary tract symptoms (LUTS) needs to identify predictors of symptom outcomes when interventional treatment is planned. OBJECTIVE: To develop a novel prediction model for prostate surgery outcomes and validate it using a separate patient cohort and derive thresholds for key clinical parameters. DESIGN, SETTING, AND PARTICIPANTS: From the UPSTREAM trial of 820 men seeking treatment for LUTS, analysis of bladder diary (BD), International Prostate Symptom Score (IPSS), IPSS-quality of life, and uroflowmetry data was performed for 176 participants who underwent prostate surgery and provided complete data. For external validation, data from a retrospective database of surgery outcomes in a Japanese urology department (n = 227) were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Symptom improvement was defined as a reduction in total IPSS of ≥3 points. Multiple logistic regression, classification tree analysis, and random forest models were generated, including versions with and without BD data. RESULTS AND LIMITATIONS: Multiple logistic regression without BD data identified age (p = 0.029), total IPSS (p = 0.0016), and maximum flow rate (Qmax; p = 0.066) as predictors of outcomes, with area under the receiver operating characteristic curve (AUC) of 77.1%. Classification tree analysis without BD data gave thresholds of IPSS <16 and Qmax ≥13 ml/s (AUC 75.0%). The random forest model, which included all clinical parameters except BD data, had an AUC of 94.7%. Internal validation using the bootstrap method showed reasonable AUCs (69.6-85.8%). Analyses using BD data marginally improved the model fits. External validation gave comparable AUCs for logistic regression, classification tree analysis, and random forest models (all without BD; 70.9%, 67.3%, and 68.5%, respectively). Limitations include the significant number of men with incomplete baseline data and limited assessments in the external validation cohort. CONCLUSIONS: Outcomes of prostate surgery can be predicted preoperatively using age, total IPSS, and uroflowmetry data, with prognostic thresholds of 16 for IPSS and 13 ml/s for Qmax. PATIENT SUMMARY: This study identified key preoperative factors that can predict outcomes of prostate surgery for bothersome urinary symptoms, including which patients are at risk of a poor outcome.

Maternal vaccination provision in NHS maternity trusts across England.

BACKGROUND: Vaccinations for seasonal influenza and pertussis have been recommended for pregnant women in England since 2010 and 2012, respectively. Uptake rates are suboptimal with large regional variations. To improve uptake, from 2016 onwards maternity trusts were commissioned to offer pertussis (and other) vaccinations in addition to these being available in primary care. Since 2021, Covid-19 vaccination has also been recommended for pregnant women. Overall maternal vaccination rates are routinely available, but not the relative provision by maternity trusts. We aimed to describe the national picture of maternity trust provision of maternal vaccinations, including how the maternity trust vaccination programme has progressed. METHODS: Cross-sectional survey plus comparisons with 2017-18 figures for maternity trust provision of pertussis vaccination, and with UKHSA data for total pertussis vaccination. RESULTS: Twelve NHS commissioners participated (from 13/06/22 to 31/03/23) providing data for 120 (of a total 124) maternity trusts across England. All 120 (100%) trusts were commissioned to deliver influenza, and 107 (89%) to deliver pertussis vaccinations, though not all actually administered the vaccines; 29% offered Covid-19 vaccinations. For 2021-22 we found a mean of 25% (range 0-81.3%) women were vaccinated for pertussis (a large increase compared with previous estimates for 2017-18); and 11% (range 0-74.2%) for influenza, via their maternity trust. Commissioners reported a negative impact of the pandemic on routine vaccination provision. There was indication of efficiency by vaccinating women attending for other appointments. There are diverse mechanisms for reporting pertussis and influenza vaccinations administered at maternity trusts back to primary care, which may be inefficient for maternity staff workload and accuracy of data transfer (especially for pertussis). CONCLUSION: A high proportion of maternity trusts provide both pertussis and influenza vaccinations, despite a negative impact of the pandemic. Reasons for large between-trust variation in vaccination rates should be explored to improve uptake and equity.

Changes in background characteristics and risk factors among SIDS infants in England: cohort comparisons from 1993 to 2020.

OBJECTIVES: Using the National Child Mortality Database, this work aims to investigate background characteristics and risk factors in the sleeping environment associated with sudden infant death syndrome (SIDS) and compare the prevalence with previous English SIDS case-control studies. DESIGN: Cohort of SIDS in 2020 compared with a combined analysis of two case-control studies conducted in 1993-1996 and 2003-2006. SETTING: England, UK PARTICIPANTS: 138 SIDS deaths in 2020 compared with 402 SIDS deaths and 1387 age-equivalent surviving controls, combined from previous studies. RESULTS: The increased vulnerability of SIDS infants identified in previous studies has become more marked. The infants who died in 2020 were younger (median=66 days (IQR: 34-118) vs 86 days (IQR: 52-148), p=0.003) with an increased prevalence of low birth weight (30.5% vs 21.6%, p=0.04) and preterm births (29.6% vs 19.3%, p=0.012). The excess of socioeconomically deprived families, male infants and high levels of maternal smoking during pregnancy were still evident. Among recent deaths, fewer infants were put down or found on their side; however, there was no significant change in the proportion of infants who were put down (15.6% vs 14.6%, p=0.81) and found prone (40.4% vs 35.3%, p=0.37), despite population wide risk reduction advice over three decades. The proportional increase observed in 2003-2006 of half the deaths occurring while sleeping next to an adult was maintained in 2020, and for the vast majority (90%), this was in hazardous circumstances (adult had consumed alcohol, smoked, slept on a sofa, or the infant was premature or low birth weight and less than 3 months old). More deaths also occurred when there was a disruption in infant care routine compared with previous observations (52.6% vs 20.7%, p<0.001). CONCLUSIONS: A more targeted approach is needed with vulnerable families emphasising the importance of sleeping infants on their back and proactive planning infant sleep when there are disruptions to the normal routine, in particular to avoid hazardous co-sleeping.

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.

Vision function in children 10 years after grade 3 or 4 intraventricular haemorrhage with ventricular dilation: A masked prospective study.

AIM: We examined children 10 to 11 years after grade 3 or 4 intraventricular haemorrhage and ventricular dilation (IVHVD) and investigated whether the grade of IVHVD affected their visual outcome. We explored associations between visual outcomes with cognitive outcomes and extra support at school. METHOD: The visual examinations were part of a 10-year follow-up study for children in a randomized trial. Testers followed a protocol and were masked to whether the child had experienced grade 3 or grade 4 IVHVD and all other data. RESULTS: Thirty-two children were tested: 24 were male and mean (standard deviation) age was 10 years 5 months (1 year 2 months); range 8 years 9 months to 12 years 9 months. All had at least one visual impairment. The median (interquartile range) number of impairments per child was six (six to nine) for children who experienced a grade 4 IVHVD compared with three (two to four) for children who experienced a grade 3 IVHVD (p = 0.003). Each extra vision impairment per child was associated with increased educational support at school, after adjustment for developmental age equivalence (odds ratio = 1.7 [95% confidence interval 1.1-2.6], p = 0.015). INTERPRETATION: Children who experience grade 3 or 4 IVHVD have a high level of visual morbidity at age 10 to 11 years. These children may have unmet visual needs and their outcomes might improve if these needs could be addressed. WHAT THIS PAPER ADDS: Parent-reported questionnaire responses underestimated directly assessed visual morbidity. Grade 4 intraventricular haemorrhage and ventricular dilatation (IVHVD) was followed by more vision impairments than grade 3 IVHVD. Simple tests of visual perceptual skills correlated with the neuropsychology tests. Children with supranuclear eye movement disorders were more likely to be receiving extra help at school. Each additional visual impairment increased the likelihood of extra educational support.

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.

Can primary care research be conducted more efficiently using routinely reported practice-level data: a cluster randomised controlled trial conducted in England?

OBJECTIVES: Conducting randomised controlled trials (RCTs) in primary care is challenging; recruiting patients during time-limited or remote consultations can increase selection bias and physical access to patients' notes is costly and time-consuming. We investigated barriers and facilitators to running a more efficient design. DESIGN: An RCT aiming to reduce antibiotic prescribing among children presenting with acute cough and a respiratory tract infection (RTI) with a clinician-focused intervention, embedded at the practice level. By using aggregate level, routinely collected data for the coprimary outcomes, we removed the need to recruit individual participants. SETTING: Primary care. PARTICIPANTS: Baseline data from general practitioner practices and interviews with individuals from Clinical Research Networks (CRNs) in England who helped recruit practices and Clinical Commission Groups (CCGs) who collected outcome data. INTERVENTION: The intervention included: (1) explicit elicitation of parental concerns, (2) a prognostic algorithm to identify children at low risk of hospitalisation and (3) provision of a printout for carers including safety-netting advice. COPRIMARY OUTCOMES: For 0-9 years old-(1) Dispensing data for amoxicillin and macrolide antibiotics and (2) hospital admission rate for RTI. RESULTS: We recruited 294 of the intended 310 practices (95%) representing 336 496 registered 0-9 years old (5% of all 0-9 years old children). Included practices were slightly larger, had slightly lower baseline prescribing rates and were located in more deprived areas reflecting the national distribution. Engagement with CCGs and their understanding of their role in this research was variable. Engagement with CRNs and installation of the intervention was straight-forward although the impact of updates to practice IT systems and lack of familiarity required extended support in some practices. Data on the coprimary outcomes were almost 100%. CONCLUSIONS: The infrastructure for trials at the practice level using routinely collected data for primary outcomes is viable in England and should be promoted for primary care research where appropriate. TRIAL REGISTRATION NUMBER: ISRCTN11405239.

Prognostic value of upper respiratory tract microbes in children presenting to primary care with respiratory infections: A prospective cohort study.

BACKGROUND: The association between upper respiratory tract microbial positivity and illness prognosis in children is unclear. This impedes clinical decision-making and means the utility of upper respiratory tract microbial point-of-care tests remains unknown. We investigated for relationships between pharyngeal microbes and symptom severity in children with suspected respiratory tract infection (RTI). METHODS: Baseline characteristics and pharyngeal swabs were collected from 2,296 children presenting to 58 general practices in Bristol, UK with acute cough and suspected RTI between 2011-2013. Post-consultation, parents recorded the severity of six RTI symptoms on a 0-6 scale daily for ≤28 days. We used multivariable hurdle regression, adjusting for clinical characteristics, antibiotics and other microbes, to investigate associations between respiratory microbes and mean symptom severity on days 2-4 post-presentation. RESULTS: Overall, 1,317 (57%) children with complete baseline, microbiological and symptom data were included. Baseline characteristics were similar in included participants and those lacking microbiological data. At least one virus was detected in 869 (66%) children, and at least one bacterium in 783 (60%). Compared to children with no virus detected (mean symptom severity score 1.52), adjusted mean symptom severity was 0.26 points higher in those testing positive for at least one virus (95% CI 0.15 to 0.38, p<0.001); and was also higher in those with detected Influenza B (0.44, 0.15 to 0.72, p = 0.003); RSV (0.41, 0.20 to 0.60, p<0.001); and Influenza A (0.25, -0.01 to 0.51, p = 0.059). Children positive for Enterovirus had a lower adjusted mean symptom severity (-0.24, -0.43 to -0.05, p = 0.013). Children with detected Bordetella pertussis (0.40, 0.00 to 0.79, p = 0.049) and those with detected Moraxella catarrhalis (-0.76, -1.06 to -0.45, p<0.001) respectively had higher and lower mean symptom severity compared to children without these bacteria. CONCLUSIONS: There is a potential role for upper respiratory tract microbiological point-of-care tests in determining the prognosis of childhood RTIs.

Use of the International Consultation on Incontinence Questionnaires Bladder Diary in Men Seeking therapy for Lower Urinary Tract Symptoms.

BACKGROUND: Completion rates and correspondence to other measures need to be established for the International Consultation on Incontinence Questionnaire (ICIQ) bladder diary (ICIQ-BD) in the assessment of male lower urinary tract symptoms (LUTS). OBJECTIVE: To evaluate ICIQ-BD completion rates, frequency, volume, and sensation reporting for men. DESIGN, SETTING, AND PARTICIPANTS: Baseline data from the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM) randomised controlled trial evaluating 820 men at 26 UK hospitals, looking at the ICIQ-BD, uroflowmetry, International Prostate Symptom Score, and ICIQ symptom score for male LUTS (ICIQ-MLUTS), were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The ICIQ-BD, IPSS, ICIQ-MLUTS, and uroflowmetry data at baseline obtained from UPSTREAM were assessed. Correlations were analysed by Pearson's correlation coefficient, and comparison between groups were performed using paired or unpaired t tests or Tukey's test. All statistical tests were two sided and the strength of evidence was presented using p values. RESULTS AND LIMITATIONS: Of the participants, 25.0% (205/820) provided complete voiding and bedtime information for 3 d, 41.2% (338/820) omitted bedtime information, and the remainder omitted some or all voiding information. Median values (minimum - maximum) of 24-h, daytime, and night-time frequencies were 9.7 (3.3-24.0), 7.7 (3.3-22.7), and 1.7 (0.0-5.7), respectively. The mean voided volume per micturition for day and night times were 175.8 ± 74.2 and 264.4 ± 150.7 ml (p < 0.001), respectively. For fully completed diaries, day- and night-time frequency showed a weak-to-moderate correlation with symptom score questionnaires. More severe nocturia was generally reported in symptom scores than in the ICIQ-BD. In patients with high bother for increased daytime frequency (symptom), the mean daytime frequency (ICIQ-BD) was 9.6 ± 3.2 versus 7.6 ± 2.2 for low bother (p < 0.001). High bother for nocturia showed night-time frequency of 2.3 ± 1.2 versus 1.5 ± 1.1 for low bother (p < 0.001). For fully and partially completed diaries, ICIQ-BD sensation scores correlated weakly with symptom scores. Voided volumes from the bladder diary and uroflowmetry correlated weakly. CONCLUSIONS: Two-thirds of men (543/820) fully completed voiding information in the ICIQ-BD, but many omitted bedtime information, limiting the ability to quantify nocturia and diagnose nocturnal polyuria. PATIENT SUMMARY: Most men with urinary symptoms complete a bladder diary fully but may fail to indicate bedtimes. Extra information from a diary helps support symptom questionnaires to explain a patient's urinary habits.

Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP): Protocol for a multicentre cluster randomised trial comparing a complex intervention for medication optimization against usual care.

Introduction: Polypharmacy is increasingly common, and associated with undesirable consequences. Polypharmacy management necessitates balancing therapeutic benefits and risks, and varying clinical and patient priorities. Current guidance for managing polypharmacy is not supported by high quality evidence. The aim of the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial is to evaluate the effectiveness of an intervention to optimise medication use for patients with polypharmacy in a general practice setting. Methods: This trial will use a multicentre, open-label, cluster-randomised controlled approach, with two parallel groups. Practices will be randomised to a complex intervention comprising structured medication review (including interprofessional GP/pharmacist treatment planning and patient-facing review) supported by performance feedback, financial incentivisation, clinician training and clinical informatics (intervention), or usual care (control). Patients with polypharmacy and triggering potentially inappropriate prescribing (PIP) indicators will be recruited in each practice using a computerised search of health records. 37 practices will recruit 50 patients, and review them over a 26-week intervention delivery period. The primary outcome is the mean number of PIP indicators triggered per patient at 26 weeks follow-up, determined objectively from coded GP electronic health records. Secondary outcomes will include patient reported outcome measures, and health and care service use. The main intention-to-treat analysis will use linear mixed effects regression to compare number of PIP indicators triggered at 26 weeks post-review between groups, adjusted for baseline (pre-randomisation) values. A nested process evaluation will explore implementation of the intervention in primary care. Ethics and dissemination: The protocol and associated study materials have been approved by the Wales REC 6, NHS Research Ethics Committee (REC reference 19/WA/0090), host institution and Health Research Authority. Research outputs will be published in peer-reviewed journals and relevant conferences, and additionally disseminated to patients and the public, clinicians, commissioners and policy makers. ISRCTN Registration: 90146150 (28/03/2019).

Child mortality in England during the COVID-19 pandemic.

OBJECTIVES: Using the National Child Mortality Database (NCMD), this work aims to investigate and quantify the characteristics of children dying of COVID-19, and to identify any changes in rate of childhood mortality during the pandemic. DESIGN: We compared the characteristics of the children who died in 2020, split by SARS-CoV-2 status. A negative binomial regression model was used to compare mortality rates in lockdown (23 March-28 June), with those children who died in the preceding period (6 January-22 March), as well as a comparable period in 2019. SETTING: England. PARTICIPANTS: Children (0-17 years). MAIN OUTCOME MEASURES: Characteristics and number of the children who died in 2020, split by SARS-CoV-2 status. RESULTS: 1550 deaths of children between 6th of January and 28 June 2020 were notified to the NCMD; 437 of the deaths were linked to SARS-CoV-2 virology records, 25 (5.7%) had a positive PCR result. PCR-positive children were less likely to be white (37.5% vs 69.4%, p=0.003) and were older (12.2 vs 0.7 years, p<0.0006) compared with child deaths without evidence of the virus. All-cause mortality rates were similar during lockdown compared with both the period before lockdown in 2020 (rate ratio (RR) 0.93 (0.84 to 1.02)) and a similar period in 2019 (RR 1.02 (0.92 to 1.13)). CONCLUSIONS: There is little to suggest that there has been excess mortality during the period of lockdown. The apparent higher frequency of SARS-CoV-2-positive tests among children from black, Asian and minority ethnic groups is consistent with findings in adults. Ongoing surveillance is essential as the pandemic continues.

Prostate Surgery for Men with Lower Urinary Tract Symptoms: Do We Need Urodynamics to Find the Right Candidates? Exploratory Findings from the UPSTREAM Trial.

BACKGROUND: Identifying men whose lower urinary tract symptoms (LUTS) may benefit from surgery is challenging. OBJECTIVE: To identify routine diagnostic and urodynamic measures associated with treatment decision-making, and outcome, in exploratory analyses of the UPSTREAM trial. DESIGN, SETTING, AND PARTICIPANTS: A randomised controlled trial was conducted including 820 men, considering surgery for LUTS, across 26 hospitals in England (ISCTRN56164274). INTERVENTION: Men were randomised to a routine care (RC) diagnostic pathway (n = 393) or a pathway that included urodynamics (UDS) in addition to RC (n = 427). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Men underwent uroflowmetry and completed symptom questionnaires, at baseline and 18 mo after randomisation. Regression models identified baseline clinical and symptom measures that predicted recommendation for surgery and/or surgical outcome (measured by the International Prostate Symptom Score [IPSS]). We explored the association between UDS and surgical outcome in subgroups defined by routine measures. RESULTS AND LIMITATIONS: The recommendation for surgery could be predicted successfully in the RC and UDS groups (area under the receiver operating characteristic curve 0.78), with maximum flow rate (Qmax) and age predictors in both groups. Surgery was more beneficial in those with higher symptom scores (eg, IPSS >16), age <74 yr, Qmax <9.8 ml/s, bladder outlet obstruction index >47.6, and bladder contractility index >123.0. In the UDS group, urodynamic measures were more strongly predictive of surgical outcome for those with Qmax >15, although patient-reported outcomes were also more predictive in this subgroup. CONCLUSIONS: Treatment decisions were informed with UDS, when available, but without evidence of change in the decisions reached. Despite the small group sizes, exploratory analyses suggest that selective use of UDS could detect obstructive pathology, missed by routine measures, in certain subgroups. PATIENT SUMMARY: Baseline clinical and symptom measurements were able to predict treatment decisions. The addition of urodynamic test results, while useful, did not generally lead to better surgical decisions and outcomes over routine tests alone.

Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Drugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease. METHODS: In this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012-003641-15), and is completed. FINDINGS: Between July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was -2·29 mL (95% CI -6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group. INTERPRETATION: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods. FUNDING: Efficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research).

Ca2+ transients in ICC-MY define the basis for the dominance of the corpus in gastric pacemaking.

Myenteric interstitial cells of Cajal (ICC-MY) generate and actively propagate electrical slow waves in the stomach. Slow wave generation and propagation are altered in gastric motor disorders, such as gastroparesis, and the mechanism for the gradient in slow wave frequency that facilitates proximal to distal propagation of slow waves and normal gastric peristalsis is poorly understood.  Slow waves depend upon Ca2+-activated Cl- channels (encoded by Ano1). We characterized Ca2+ signaling in ICC-MY in situ using mice engineered to have cell-specific expression of GCaMP6f in ICC. Ca2+ signaling differed in ICC-MY in corpus and antrum. Localized Ca2+ transients were generated from multiple firing sites and were organized into Ca2+ transient clusters (CTCs). Ca2+ transient refractory periods occurred upon cessation of CTCs, but a relatively higher frequency of Ca2+ transients persisted during the inter-CTC interval in corpus than in antrum ICC-MY. The onset of Ca2+ transients after the refractory period was associated with initiation of the next CTC. Thus, CTCs were initiated at higher frequencies in corpus than in antrum ICC-MY. Initiation and propagation of CTCs (and electrical slow waves) depends upon T-type Ca2+ channels, and durations of CTCs relied upon L-type Ca2+ channels. The durations of CTCs mirrored the durations of slow waves. CTCs and Ca2+ transients between CTCs resulted from release of Ca2+ from intracellular stores and were maintained, in part, by store-operated Ca2+ entry. Our data suggest that Ca2+ release and activation of Ano1 channels both initiate and contribute to the plateau phase of slow waves.

Improving engagement with services to prevent Sudden Unexpected Death in Infancy (SUDI) in families with children at risk of significant harm: A systematic review of evidence.

This paper reports part of a wider systematic review commissioned by the English National Safeguarding Panel on Sudden Unexpected Death in Infancy (SUDI). The wider review covered three areas: interventions to improve safer sleep practices in high-risk families, interventions to improve engagement with services and decision making by parents at high risk of SUDI about infant sleep environments. Here, we report the qualitative and quantitative studies reviewed under the engagement strand. Parental engagement is understood to be a multidimensional task for health and social care professionals comprising attitudinal, relational and behavioural components. Following a PROSPERO registered systematic review synthesizing the three strands outlined, 28 papers were found to be relevant in the review of interventions to improve engagement with services in families with children at risk of significant harm through abuse or neglect. No studies were found that specifically focused on engagement of families at high risk for SUDI, so these wider engagement studies were included. The different types of intervention reported in the included studies are described under two broad themes: Enablers (including parental motivation and working with families) and Barriers. Given the focus in the studies on interventions that support parental engagement, the Enablers theme is more extensive than the Barriers reported although all studies noted well-understood barriers. The evidence underpinning these interventions and approaches are reviewed in this paper. We conclude that effective engagement is facilitated by experienced professionals given time to develop supportive non-judgemental relationships with families in their homes, working long-term, linking with communities and other services. While these conclusions have been drawn from wider studies aimed at reducing child maltreatment, we emphasize lessons to be drawn for SUDI prevention work with families with children at risk of significant harm.