Supporting Self-management Among Young People With Acne Vulgaris Through a Web-Based Behavioral Intervention: Development and Feasibility Randomized Controlled Trial.

BACKGROUND: Acne is a common skin condition that is most prevalent in young people. It can have a substantial impact on the quality of life, which can be minimized with the appropriate use of topical treatments. Nonadherence to topical treatments for acne is common and often leads to treatment failure. OBJECTIVE: The aim of this study is to develop a web-based behavioral intervention to support the self-management of acne and to assess the feasibility of recruitment, retention, and engagement of users with the intervention. METHODS: The intervention was developed iteratively using the LifeGuide software and following the person-based approach for intervention development. The target behavior was appropriate use of topical treatments. Barriers and facilitators identified from the qualitative research and evidence from the wider literature were used to identify techniques to improve and promote their use. Young people with acne aged 14-25 years who had received treatment for acne in the past 6 months were invited to participate through mail-out from primary care practices in the South of England in a parallel, unblinded randomized trial. Participants were automatically randomized using a computer-generated algorithm to usual care or to usual care plus access to the web-based intervention. Usage data was collected, and a series of questionnaires, including the primary outcome measure for skin-specific quality of life (Skindex-16), were collected at baseline and at the 4- and 6-week follow-ups. RESULTS: A total of 1193 participants were invited, and 53 young people with acne were randomized to usual care (27/53, 51%) or usual care plus intervention (26/53, 49%). The response rate for the primary outcome measure (Skindex-16) was 87% at 4 weeks, 6 weeks, and at both time points. The estimate of mean scores between groups (with 95% CI) using linear regression showed a trend in the direction of benefit for the web-based intervention group in the primary outcome measure (Skindex-16) and secondary measures (Patient Health Questionnaire-4 and the Problematic Experiences of Therapy Scale). Intervention usage data showed high uptake of the core module in the usual care plus web-based intervention group, with 88% (23/26) of participants completing the module. Uptake of the optional modules was low, with less than half visiting each (myth-busting quiz: 27%; living with spots or acne: 42%; oral antibiotics: 19%; what are spots or acne: 27%; other treatments: 27%; talking to your general practitioner: 12%). CONCLUSIONS: This study demonstrated the feasibility of delivering a trial of a web-based intervention to support self-management in young people with acne. Additional work is needed before a full definitive trial, including enhancing engagement with the intervention, recruitment, and follow-up rates. TRIAL REGISTRATION: ISRCTN 78626638; https://tinyurl.com/n4wackrw.

Challenges in managing urinary tract infection and the potential of a point-of-care test guided care in primary care: an international qualitative study.

BACKGROUND: Little is known about clinicians' experiences of using a point-of-care test (POCT) to inform management of urinary tract infection (UTI) in general practice. AIM: To explore experiences of using the Flexicult test to inform management of UTI and views on requirements for an optimal POCT to inform successful implementation. DESIGN & SETTING: Telephone interviews with 35 primary care clinicians and healthcare professionals in Wales, England, Spain, and the Netherlands, who had participated in a trial of the Flexicult POCT for UTI based on urine culture. METHOD: Thematic analysis of semi-structured interviews. RESULTS: Most primary care clinicians interviewed agreed on the need for a POCT in UTI management, and that the Flexicult POCT delivered quicker results than laboratory results used in usual care, reassured patients, boosted their confidence in decision-making, and reminded them about antibiotic stewardship. However, clinicians also reported difficulties in interpreting results, limitations on when the Flexicult could be used, and concerns that testing all patients would strain care delivery and prolong patient discomfort when delaying decisions until a non-rapid POCT result was available. An optimal POCT would produce more rapid results, and be reliable and easy to use. Uptake into routine care would be enhanced by: clear guidance on which patients should be tested; training for interpreting 'grey area' results; reiterating that even 'straightforward' cases might be better managed with a test; clear messages about stopping unnecessary antibiotics versus completing a course; and better self-management strategies to accompany implementation of delayed, or non-prescription of, antibiotics. CONCLUSION: Primary care clinicians believe that POCT tests could play a useful role in the management of UTI and gave clear recommendations for successful implementation.

Adding emollient bath additives to standard eczema management for children with eczema: the BATHE RCT.

BACKGROUND: Childhood eczema is very common. Treatment often includes emollient bath additives, despite there being little evidence of their effectiveness. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of emollient bath additives in the management of childhood eczema. DESIGN: Pragmatic, randomised, open-label, multicentre superiority trial with two parallel groups. SETTING: Ninety-six general practices in Wales, the west of England and southern England. Invitation by personal letter or opportunistically. PARTICIPANTS: Children aged between 12 months and 12 years fulfilling the UK Diagnostic Criteria for Atopic Eczema. Children with inactive or very mild eczema (a score of ≤ 5 on the Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once per week or whose parents/carers were not prepared to accept randomisation. INTERVENTIONS: The intervention group were prescribed bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued standard eczema management, including regular leave-on emollients and topical corticosteroids (TCSs) when required. MAIN OUTCOME MEASURES: The primary outcome was eczema control measured by Patient Oriented Eczema Measure [POEM, 0 (clear) to 28 (severe)] weekly for 16 weeks. The secondary outcomes were eczema severity over 1 year (4-weekly POEM), number of eczema exacerbations, disease-specific quality of life (QoL) (Dermatitis Family Impact Questionnaire), generic QoL (Child Health Utility-9 Dimensions) and type and quantity of topical steroid/calcineurin inhibitors prescribed. Children were randomised (1 : 1) using online software to either bath additives plus standard eczema care or standard eczema care alone, stratified by recruiting centre, and there was open-label blinding. RESULTS: From December 2014 to May 2016, 482 children were randomised: 51% were female, 84% were white and the mean age was 5 years (n = 264 in the intervention group, n = 218 in the control group). Reported adherence to randomised treatment allocation was > 92% in both groups, with 76.7% of participants completing at least 12 (80%) of the first 16 weekly questionnaires for the primary outcome. Baseline POEM score was 9.5 [standard deviation (SD) 5.7] in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. Average POEM score over the first 16 weeks was 7.5 (SD 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group, with no statistically significant difference between the groups. After controlling for baseline severity and confounders (ethnicity, TCS use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% confidence interval -0.27 to 1.10), which is well below the published minimal clinically important difference of 3 points. There was no difference between groups in secondary outcomes or in adverse effects such as redness, stinging or slipping. LIMITATIONS: Simple randomisation resulted in an imbalance in baseline group size, although baseline characteristics were well balanced between groups. CONCLUSION: This trial found no evidence of clinical benefit of including emollient bath additives in the standard management of childhood eczema. FUTURE WORK: Further research is required on optimal regimens of leave-on emollients and the use of emollients as soap substitutes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84102309. FUNDING: This project was funded by the NIHR Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 22, No. 57. See the NIHR Journals Library website for further project information.

Feasibility of weekly participant-reported data collection in a pragmatic randomised controlled trial in primary care: experiences from the BATHE trial (Bath Additives for the Treatment of cHildhood Eczema).

BACKGROUND: Patient-reported outcomes measures in clinical trials ensure that evaluations of effectiveness focus on outcomes that are important to patients. In relapsing-remitting conditions, such as eczema, repeated measurements may allow a more accurate reflection of disease burden and treatment effect than less frequent measurements. We asked parents/carers of children with eczema taking part in a trial of bath emollients to complete weekly questionnaires for 16 weeks. METHODS: The objective of this study was to determine the acceptability and practicality of collecting weekly measures of eczema severity online for 16 weeks in children aged 1 to 11 years as part of the BATHE study. BATHE randomised patients to bath emollients plus standard eczema care or standard eczema care only. The primary outcome was eczema severity, measured by the seven-item Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Acceptability was explored through qualitative interviews with 10 participants. Interviews were audio-recorded, transcribed and analysed thematically. Practicality was assessed by exploring the completeness of the data and keeping a log of any problems. RESULTS: Four hundred and eighty-two participants were recruited to the trial and 429 opted to complete measures online (89.0%). Data were collected online for 83% of time points over the 16-week period and there was no association between socio-demographic characteristics and data completeness. Two hundred and six (48%) completed their weekly data every week for 16 weeks and 341 (79%) completed it at least 80% of the time. The mean number of weeks completed was 13.3 out of 16 (SD 4.2). Interviewees said that they understood the rationale behind weekly collection and some welcomed this as it helped them realise how their child's eczema changed weekly. Whilst some interviewees spoke of weekly questionnaires as onerous, others said that they found them quick and easy. Reminders were welcomed. Parents/carers seemed happy to receive telephone reminders and it was sometimes useful for eliciting problems relating to obtaining trial medication or password problems for online data collection. CONCLUSIONS: Amongst this population, high levels of data completeness suggests that weekly completion of the online questionnaire appears to be acceptable and feasible over a 16-week period. TRIAL REGISTRATION: ISRCTN84102309 . Registered on 9 December 2013.

Emollient bath additives for the treatment of childhood eczema (BATHE): multicentre pragmatic parallel group randomised controlled trial of clinical and cost effectiveness.

OBJECTIVES: To determine the clinical effectiveness and cost effectiveness of including emollient bath additives in the management of eczema in children. DESIGN: Pragmatic randomised open label superiority trial with two parallel groups. SETTING: 96 general practices in Wales and western and southern England. PARTICIPANTS: 483 children aged 1 to 11 years, fulfilling UK diagnostic criteria for atopic dermatitis. Children with very mild eczema and children who bathed less than once weekly were excluded. INTERVENTIONS: Participants in the intervention group were prescribed emollient bath additives by their usual clinical team to be used regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued with standard eczema management, including leave-on emollients, and caregivers were given standardised advice on how to wash participants. MAIN OUTCOME MEASURES: The primary outcome was eczema control measured by the patient oriented eczema measure (POEM, scores 0-7 mild, 8-16 moderate, 17-28 severe) weekly for 16 weeks. Secondary outcomes were eczema severity over one year (monthly POEM score from baseline to 52 weeks), number of eczema exacerbations resulting in primary healthcare consultation, disease specific quality of life (dermatitis family impact), generic quality of life (child health utility-9D), utilisation of resources, and type and quantity of topical corticosteroid or topical calcineurin inhibitors prescribed. RESULTS: 483 children were randomised and one child was withdrawn, leaving 482 children in the trial: 51% were girls (244/482), 84% were of white ethnicity (447/470), and the mean age was 5 years. 96% (461/482) of participants completed at least one post-baseline POEM, so were included in the analysis, and 77% (370/482) completed questionnaires for more than 80% of the time points for the primary outcome (12/16 weekly questionnaires to 16 weeks). The mean baseline POEM score was 9.5 (SD 5.7) in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. The mean POEM score over the 16 week period was 7.5 (SD. 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group. No statistically significant difference was found in weekly POEM scores between groups over 16 weeks. After controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additives group were 0.41 points higher than in the bath additives group (95% confidence interval -0.27 to 1.10), below the published minimal clinically important difference for POEM of 3 points. The groups did not differ in secondary outcomes, economic outcomes, or adverse effects. CONCLUSIONS: This trial found no evidence of clinical benefit from including emollient bath additives in the standard management of eczema in children. Further research is needed into optimal regimens for leave-on emollient and soap substitutes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84102309.

Point-of-care urine culture for managing urinary tract infection in primary care: a randomised controlled trial of clinical and cost-effectiveness.

BACKGROUND: The effectiveness of using point-of-care (POC) urine culture in primary care on appropriate antibiotic use is unknown. AIM: To assess whether use of the Flexicult™ SSI-Urinary Kit, which quantifies bacterial growth and determines antibiotic susceptibility at the point of care, achieves antibiotic use that is more often concordant with laboratory culture results, when compared with standard care. DESIGN AND SETTING: Individually randomised trial of females with uncomplicated urinary tract infection (UTI) in primary care research networks (PCRNs) in England, the Netherlands, Spain, and Wales. METHOD: Multilevel regression compared outcomes between the two groups while controlling for clustering. RESULTS: In total, 329 participants were randomised to POC testing (POCT) and 325 to standard care, and 324 and 319 analysed. Fewer females randomised to the POCT arm than those who received standard care were prescribed antibiotics at the initial consultation (267/324 [82.4%] versus 282/319 [88.4%], odds ratio [OR] 0.56, 95% confidence interval [CI] = 0.35 to 0.88). Clinicians indicated the POCT result changed their management for 190/301 (63.1%). Despite this, there was no statistically significant difference between study arms in antibiotic use that was concordant with laboratory culture results (primary outcome) at day 3 (39.3% POCT versus 44.1% standard care, OR 0.84, 95% CI = 0.58 to 1.20), and there was no evidence of any differences in recovery, patient enablement, UTI recurrences, re-consultation, antibiotic resistance, and hospitalisations at follow-up. POCT culture was not cost-effective. CONCLUSION: Point-of-care urine culture was not effective when used mainly to adjust immediate antibiotic prescriptions. Further research should evaluate use of the test to guide initiation of 'delayed antibiotics'.

Comparison of microbiological diagnosis of urinary tract infection in young children by routine health service laboratories and a research laboratory: Diagnostic cohort study.

OBJECTIVES: To compare the validity of diagnosis of urinary tract infection (UTI) through urine culture between samples processed in routine health service laboratories and those processed in a research laboratory. POPULATION AND METHODS: We conducted a prospective diagnostic cohort study in 4808 acutely ill children aged <5 years attending UK primary health care. UTI, defined as pure/predominant growth ≥105 CFU/mL of a uropathogen (the reference standard), was diagnosed at routine health service laboratories and a central research laboratory by culture of urine samples. We calculated areas under the receiver-operator curve (AUC) for UTI predicted by pre-specified symptoms, signs and dipstick test results (the "index test"), separately according to whether samples were obtained by clean catch or nappy (diaper) pads. RESULTS: 251 (5.2%) and 88 (1.8%) children were classified as UTI positive by health service and research laboratories respectively. Agreement between laboratories was moderate (kappa = 0.36; 95% confidence interval [CI] 0.29, 0.43), and better for clean catch (0.54; 0.45, 0.63) than nappy pad samples (0.20; 0.12, 0.28). In clean catch samples, the AUC was lower for health service laboratories (AUC = 0.75; 95% CI 0.69, 0.80) than the research laboratory (0.86; 0.79, 0.92). Values of AUC were lower in nappy pad samples (0.65 [0.61, 0.70] and 0.79 [0.70, 0.88] for health service and research laboratory positivity, respectively) than clean catch samples. CONCLUSIONS: The agreement of microbiological diagnosis of UTI comparing routine health service laboratories with a research laboratory was moderate for clean catch samples and poor for nappy pad samples and reliability is lower for nappy pad than for clean catch samples. Positive results from the research laboratory appear more likely to reflect real UTIs than those from routine health service laboratories, many of which (particularly from nappy pad samples) could be due to contamination. Health service laboratories should consider adopting procedures used in the research laboratory for paediatric urine samples. Primary care clinicians should try to obtain clean catch samples, even in very young children.

Improving the Diagnosis and Treatment of Urinary Tract Infection in Young Children in Primary Care: Results from the DUTY Prospective Diagnostic Cohort Study.

PURPOSE: Up to 50% of urinary tract infections (UTIs) in young children are missed in primary care. Urine culture is essential for diagnosis, but urine collection is often difficult. Our aim was to derive and internally validate a 2-step clinical rule using (1) symptoms and signs to select children for urine collection; and (2) symptoms, signs, and dipstick testing to guide antibiotic treatment. METHODS: We recruited acutely unwell children aged under 5 years from 233 primary care sites across England and Wales. Index tests were parent-reported symptoms, clinician-reported signs, urine dipstick results, and clinician opinion of UTI likelihood (clinical diagnosis before dipstick and culture). The reference standard was microbiologically confirmed UTI cultured from a clean-catch urine sample. We calculated sensitivity, specificity, and area under the receiver operator characteristic (AUROC) curve of coefficient-based (graded severity) and points-based (dichotomized) symptom/sign logistic regression models, and we then internally validated the AUROC using bootstrapping. RESULTS: Three thousand thirty-six children provided urine samples, and culture results were available for 2,740 (90%). Of these results, 60 (2.2%) were positive: the clinical diagnosis was 46.6% sensitive, with an AUROC of 0.77. Previous UTI, increasing pain/crying on passing urine, increasingly smelly urine, absence of severe cough, increasing clinician impression of severe illness, abdominal tenderness on examination, and normal findings on ear examination were associated with UTI. The validated coefficient- and points-based model AUROCs were 0.87 and 0.86, respectively, increasing to 0.90 and 0.90, respectively, by adding dipstick nitrites, leukocytes, and blood. CONCLUSIONS: A clinical rule based on symptoms and signs is superior to clinician diagnosis and performs well for identifying young children for noninvasive urine sampling. Dipstick results add further diagnostic value for empiric antibiotic treatment.

The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness.

BACKGROUND: It is not clear which young children presenting acutely unwell to primary care should be investigated for urinary tract infection (UTI) and whether or not dipstick testing should be used to inform antibiotic treatment. OBJECTIVES: To develop algorithms to accurately identify pre-school children in whom urine should be obtained; assess whether or not dipstick urinalysis provides additional diagnostic information; and model algorithm cost-effectiveness. DESIGN: Multicentre, prospective diagnostic cohort study. SETTING AND PARTICIPANTS: Children < 5 years old presenting to primary care with an acute illness and/or new urinary symptoms. METHODS: One hundred and seven clinical characteristics (index tests) were recorded from the child's past medical history, symptoms, physical examination signs and urine dipstick test. Prior to dipstick results clinician opinion of UTI likelihood ('clinical diagnosis') and urine sampling and treatment intentions ('clinical judgement') were recorded. All index tests were measured blind to the reference standard, defined as a pure or predominant uropathogen cultured at ≥ 10(5) colony-forming units (CFU)/ml in a single research laboratory. Urine was collected by clean catch (preferred) or nappy pad. Index tests were sequentially evaluated in two groups, stratified by urine collection method: parent-reported symptoms with clinician-reported signs, and urine dipstick results. Diagnostic accuracy was quantified using area under receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) and bootstrap-validated AUROC, and compared with the 'clinician diagnosis' AUROC. Decision-analytic models were used to identify optimal urine sampling strategy compared with 'clinical judgement'. RESULTS: A total of 7163 children were recruited, of whom 50% were female and 49% were < 2 years old. Culture results were available for 5017 (70%); 2740 children provided clean-catch samples, 94% of whom were ≥ 2 years old, with 2.2% meeting the UTI definition. Among these, 'clinical diagnosis' correctly identified 46.6% of positive cultures, with 94.7% specificity and an AUROC of 0.77 (95% CI 0.71 to 0.83). Four symptoms, three signs and three dipstick results were independently associated with UTI with an AUROC (95% CI; bootstrap-validated AUROC) of 0.89 (0.85 to 0.95; validated 0.88) for symptoms and signs, increasing to 0.93 (0.90 to 0.97; validated 0.90) with dipstick results. Nappy pad samples were provided from the other 2277 children, of whom 82% were < 2 years old and 1.3% met the UTI definition. 'Clinical diagnosis' correctly identified 13.3% positive cultures, with 98.5% specificity and an AUROC of 0.63 (95% CI 0.53 to 0.72). Four symptoms and two dipstick results were independently associated with UTI, with an AUROC of 0.81 (0.72 to 0.90; validated 0.78) for symptoms, increasing to 0.87 (0.80 to 0.94; validated 0.82) with the dipstick findings. A high specificity threshold for the clean-catch model was more accurate and less costly than, and as effective as, clinical judgement. The additional diagnostic utility of dipstick testing was offset by its costs. The cost-effectiveness of the nappy pad model was not clear-cut. CONCLUSIONS: Clinicians should prioritise the use of clean-catch sampling as symptoms and signs can cost-effectively improve the identification of UTI in young children where clean catch is possible. Dipstick testing can improve targeting of antibiotic treatment, but at a higher cost than waiting for a laboratory result. Future research is needed to distinguish pathogens from contaminants, assess the impact of the clean-catch algorithm on patient outcomes, and the cost-effectiveness of presumptive versus dipstick versus laboratory-guided antibiotic treatment. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Nappy pad urine samples for investigation and treatment of UTI in young children: the 'DUTY' prospective diagnostic cohort study.

BACKGROUND: The added diagnostic utility of nappy pad urine samples and the proportion that are contaminated is unknown. AIM: To develop a clinical prediction rule for the diagnosis of urinary tract infection (UTI) based on sampling using the nappy pad method. DESIGN AND SETTING: Acutely unwell children <5 years presenting to 233 UK primary care sites. METHOD: Logistic regression to identify independent associations of symptoms, signs, and urine dipstick test results with UTI; diagnostic utility quantified as area under the receiver operator curves (AUROC). Nappy pad rule characteristics, AUROC, and contamination, compared with findings from clean-catch samples. RESULTS: Nappy pad samples were obtained from 3205 children (82% aged <2 years; 48% female), culture results were available for 2277 (71.0%) and 30 (1.3%) had a UTI on culture. Female sex, smelly urine, darker urine, and the absence of nappy rash were independently associated with a UTI, with an internally-validated, coefficient model AUROC of 0.81 (0.87 for clean-catch), which increased to 0.87 (0.90 for clean-catch) with the addition of dipstick results. GPs' 'working diagnosis' had an AUROC 0.63 (95% confidence intervals [CI] = 0.53 to 0.72). A total of 12.2% of nappy pad and 1.8% of clean-catch samples were 'frankly contaminated' (risk ratio 6.66; 95% CI = 4.95 to 8.96; P<0.001). CONCLUSION: Nappy pad urine culture results, with features that can be reported by parents and dipstick tests, can be clinically useful, but are less accurate and more often contaminated compared with clean-catch urine culture.

Empiric antibiotic treatment for urinary tract infection in preschool children: susceptibilities of urine sample isolates.

BACKGROUND: Antibiotic treatment recommendations based on susceptibility data from routinely submitted urine samples may be biased because of variation in sampling, laboratory procedures and inclusion of repeat samples, leading to uncertainty about empirical treatment. OBJECTIVE: To describe and compare susceptibilities of Escherichia coli cultured from routinely submitted samples, with E. coli causing urinary tract infection (UTI) from a cohort of systematically sampled, acutely unwell children. METHODS: Susceptibilities of 1458 E. coli isolates submitted during the course of routine primary care for children <5 years (routine care samples), compared to susceptibilities of 79 E. coli isolates causing UTI from 5107 children <5 years presenting to primary care with an acute illness [systematic sampling: the Diagnosis of Urinary Tract infection in Young children (DUTY) cohort]. RESULTS: The percentage of E. coli sensitive to antibiotics cultured from routinely submitted samples were as follows: amoxicillin 45.1% (95% confidence interval: 42.5-47.7%); co-amoxiclav using the lower systemic break point (BP) 86.6% (84.7-88.3%); cephalexin 95.1% (93.9-96.1%); trimethoprim 74.0% (71.7-76.2%) and nitrofurantoin 98.2% (97.4-98.8%). The percentage of E. coli sensitive to antibiotics cultured from systematically sampled DUTY urines considered to be positive for UTI were as follows: amoxicillin 50.6% (39.8-61.4%); co-amoxiclav using the systemic BP 83.5% (73.9-90.1%); co-amoxiclav using the urinary BP 94.9% (87.7-98.4%); cephalexin 98.7% (93.2-99.8%); trimethoprim 70.9% (60.1-80.0%); nitrofurantoin 100% (95.3-100.0%) and ciprofloxacin 96.2% (89.4-98.7%). CONCLUSION: Escherichia coli susceptibilities from routine and systematically obtained samples were similar. Most UTIs in preschool children remain susceptible to nitrofurantoin, co-amoxiclav and cephalexin.

Bath additives for the treatment of childhood eczema (BATHE): protocol for multicentre parallel group randomised trial.

INTRODUCTION: Bath emollients are widely prescribed for childhood eczema, yet evidence of their benefits over direct application of emollients is lacking. Objectives To determine the clinical and cost-effectiveness of adding bath emollient to the standard management of eczema in children DESIGN: Pragmatic open 2-armed parallel group randomised controlled trial. SETTING: General practitioner (GP) practices in England and Wales. PARTICIPANTS: Children aged over 12 months and less than 12 years with eczema, excluding inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale). INTERVENTIONS: Children will be randomised to either bath emollients plus standard eczema care or standard eczema care only. OUTCOME MEASURES: Primary outcome is long-term eczema severity, measured by the Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Secondary outcomes include: number of eczema exacerbations resulting in healthcare consultations over 1 year; eczema severity over 1 year; disease-specific and generic quality of life; medication use and healthcare resource use; cost-effectiveness. Aiming to detect a mean difference between groups of 2.0 (SD 7.0) in weekly POEM scores over 16 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up, gives a total sample size of 423 children. We will use repeated measures analysis of covariance, or a mixed model, to analyse weekly POEM scores. We will control for possible confounders, including baseline eczema severity and child's age. Cost-effectiveness analysis will be carried out from a National Health Service (NHS) perspective. ETHICS AND DISSEMINATION: This protocol was approved by Newcastle and North Tyneside 1 NRES committee 14/NE/0098. Follow-up will be completed in 2017. Findings will be disseminated to participants and carers, the public, dermatology and primary care journals, guideline developers and decision-makers. TRIAL REGISTRATION NUMBER: ISRCTN84102309.

Childhood urinary tract infection in primary care: a prospective observational study of prevalence, diagnosis, treatment, and recovery.

BACKGROUND: The prevalence of targeted and serendipitous treatment for, and associated recovery from, urinary tract infection (UTI) in pre-school children is unknown. AIM: To determine the frequency and suspicion of UTI in children who are acutely ill, along with details of antibiotic prescribing, its appropriateness, and whether that appropriateness impacted on symptom improvement and recovery. DESIGN AND SETTING: Prospective observational cohort study in primary care sites in urban and rural areas in England and Wales. METHOD: Systematic urine sampling from children aged <5 years presenting in primary care with acute illness with culture in NHS laboratories. RESULTS: Of 6079 children's urine samples, 339 (5.6%) met laboratory criteria for UTI and 162 (47.9%) were prescribed antibiotics at the initial consultation. In total, 576/7101 (8.1%) children were suspected of having a UTI prior to urine sampling, including 107 of the 338 with a UTI (clinician sensitivity 31.7%). Children with a laboratory-diagnosed UTI were more likely to be prescribed antibiotics when UTI was clinically suspected than when it was not (86.0% versus 30.3%, P<0.001). Of 231 children with unsuspected UTI, 70 (30.3%) received serendipitous antibiotics (that is, antibiotics prescribed for a different reason). Overall, 176 (52.1%) children with confirmed UTI did not receive any initial antibiotic. Organism sensitivity to the prescribed antibiotic was higher when UTI was suspected than when treated serendipitously (77.1% versus 26.0%; P<0.001). Children with UTI prescribed appropriate antibiotics at the initial consultation improved a little sooner than those with a UTI who were not prescribed appropriate antibiotics initially (3.5 days versus 4.0 days; P = 0.005). CONCLUSION: Over half of children with UTI on culture were not prescribed antibiotics at first presentation. Serendipitous UTI treatment was relatively common, but often inappropriate to the organism's sensitivity. Methods for improved targeting of antibiotic treatment in children who are acutely unwell are urgently needed.

Point of care testing for urinary tract infection in primary care (POETIC): protocol for a randomised controlled trial of the clinical and cost effectiveness of FLEXICULT™ informed management of uncomplicated UTI in primary care.

BACKGROUND: Urinary tract infections (UTI) are the most frequent bacterial infection affecting women and account for about 15% of antibiotics prescribed in primary care. However, some women with a UTI are not prescribed antibiotics or are prescribed the wrong antibiotics, while many women who do not have a microbiologically confirmed UTI are prescribed antibiotics. Inappropriate antibiotic prescribing unnecessarily increases the risk of side effects and the development of antibiotic resistance, and wastes resources. METHODS/DESIGN: 614 adult female patients will be recruited from four primary care research networks (Wales, England, Spain, the Netherlands) and individually randomised to either POCT guided care or the guideline-informed 'standard care' arm. Urine and stool samples (where possible) will be obtained at presentation (day 1) and two weeks later for microbiological analysis. All participants will be followed up on the course of their illness and their quality of life, using a 2 week self-completed symptom diary. At 3 months, a primary care notes review will be conducted for evidence of further evidence of treatment failures, recurrence, complications, hospitalisations and health service costs. DISCUSSION: Although the Flexicult™ POCT is used in some countries in routine primary care, it's clinical and cost effectiveness has never been evaluated in a randomised clinical trial. If shown to be effective, the use of this POCT could benefit individual sufferers and provide evidence for health care authorities to develop evidence based policies to combat the spread and impact of the unprecedented rise of infections caused by antibiotic resistant bacteria in Europe. TRIAL REGISTRATION NUMBER: ISRCTN65200697 (Registered 10 September 2013).

Validating the prediction of lower urinary tract infection in primary care: sensitivity and specificity of urinary dipsticks and clinical scores in women.

BACKGROUND: Dipsticks are one of the most commonly used near-patient tests in primary care, but few clinical or dipstick algorithms have been rigorously developed. AIM: To confirm whether previously documented clinical and dipstick variables and algorithms predict laboratory diagnosis of urinary tract infection (UTI). DESIGN OF STUDY: Validation study. SETTING: Primary care. METHOD: A total of 434 adult females with suspected lower UTI had bacteriuria assessed using the European Urinalysis Guidelines. RESULTS: Sixty-six per cent of patients had confirmed UTI. The predictive values of nitrite, leucocyte esterase (+ or greater), and blood (haemolysed trace or greater) were confirmed (independent multivariate odds ratios = 5.6, 3.5, and 2.1 respectively). The previously developed dipstick rule--based on presence of nitrite, or both leucocytes and blood-- was moderately sensitive (75%) but less specific (66%; positive predictive value [PPV] 81%, negative predictive value [NPV] 57%). Predictive values were improved by varying the cut-off point: NPV was 76% for all three dipstick results being negative; the PPV was 92% for having nitrite and either blood or leucocyte esterase. Urine offensive smell was not found to be predictive in this sample; for a clinical score using the remaining three predictive clinical features (urine cloudiness, dysuria, and nocturia), NPV was 67% for none of the features, and PPV was 82% for three features. CONCLUSION: A clinical score is of limited value in increasing diagnostic precision. Dipstick results can modestly improve diagnostic precision but poorly rule out infection. Clinicians need strategies to take account of poor NPVs.

Cost effectiveness of management strategies for urinary tract infections: results from randomised controlled trial.

OBJECTIVE: To assess the cost effectiveness of different management strategies for urinary tract infections. DESIGN: Cost effectiveness analysis alongside a randomised controlled trial with a one month follow-up. SETTING: Primary care. PARTICIPANTS: 309 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection. INTERVENTIONS: Patients were randomised to five basic management approaches: empirical antibiotics, empirical delayed (by 48 hours) antibiotics, or targeted antibiotics based on either a high symptom score (two or more of urine cloudiness, smell, nocturia, dysuria), dipstick results (nitrite or leucocytes and blood), or receipt of a positive result on midstream urine analysis. MAIN OUTCOME MEASURE: Duration of symptoms and cost of care. RESULTS: Management with targeted antibiotics with midstream urine analysis was more costly over the period of one month. Costs for the midstream urine analysis and dipstick management groups were pound37 and pound35, respectively; these compared with pound31 for immediate antibiotics. Cost effectiveness acceptability curves suggested that if avoiding a day of moderately bad symptoms was valued at less than pound10, then immediate antibiotics is likely to be the most cost effective strategy. For values over pound10, targeted antibiotics with dipstick testing becomes the most cost effective strategy, though because of the uncertainty we can never be more than 70% certain that this strategy truly is the most cost effective. CONCLUSION: Dipstick testing with targeted antibiotics is likely to be cost effective if the value of saving a day of moderately bad symptoms is pound10 or more, but caution is required given the considerable uncertainty surrounding the estimates.

Effect of antibiotic prescribing strategies and an information leaflet on longer-term reconsultation for acute lower respiratory tract infection.

BACKGROUND: Limited evidence suggests that delayed prescribing may influence future consultation behaviour. AIM: To assess the effects of antibiotic prescribing strategy on reconsultation in the year following presentation with acute lower respiratory tract infection (LRTI). DESIGN OF STUDY: Balanced factorial randomised trial. SETTING: Primary care. METHOD: Eight hundred and seven subjects, aged>or=3 years, had acute illness presenting with cough as the main symptom, plus at least one symptom or sign from sputum, chest pain, dyspnoea or wheeze. The subjects were randomised to one of three prescribing strategies (antibiotics, delayed antibiotic, no antibiotic) and a leaflet. Prior antibiotic use and reconsultation were assessed by medical record review. RESULTS: Patients who had been prescribed antibiotic for cough in the previous 2 years were much more likely to reconsult (incidence rate ratio [IRR]=2.55, 95% confidence interval [CI]=1.62 to 4.01) and use of a delayed prescription strategy is associated with reduced reconsultation in this group. In those with prior antibiotic exposure, there was a 34% reduction in consultation rate in the no antibiotic group (IRR=0.66, 0.30 to 1.44, P=0.295) and a 78% reduction for the delayed antibiotic group (IRR=0.22, 0.10 to 0.49, P<0.001) when compared with those given immediate antibiotics. This effect was not observed in patients who had not been prescribed antibiotics in the previous 2 years; there was no reduction in consultations in the no antibiotic group (IRR=1.23, 0.79 to 1.92, P=0.358) or the delayed antibiotic group (1.19, 0.78 to 1.80, P=0.426). There was an increase in consultation rate with an information leaflet (IRR=1.27, 0.86 to 1.87, P=0.229). Past attendance with cough, or past attendance with other respiratory illness and smoking, also predicted reconsultation with cough. CONCLUSION: Delayed antibiotic prescribing for LRTI appears effective in modifying reconsultation behaviour, particularly in those with a prior history of antibiotic prescription for LRTI.

Predicting the duration of symptoms in lower respiratory tract infection.

BACKGROUND: Acute lower respiratory tract infection (LRTI) presenting in primary care has a long natural history. Antibiotic treatment makes little or no difference to the duration of cough. Limited information is currently available regarding predictors of illness duration. AIM: To determine predictors of illness duration in acute LRTI in primary care. DESIGN OF STUDY: Secondary analysis of trial data to identify independent predictors of illness severity and duration. SETTING: Primary care. METHOD: Eight-hundred and seven patients aged 3 years and over with acute illness (21 days or less) presenting with cough as the main symptom plus at least one symptom or sign from sputum, chest pain, dyspnoea, or wheeze were recruited to the study. Main outcomes were duration of symptoms (rated at least a slight problem) and more severe symptoms (rated at least moderately bad). RESULTS: The average duration of cough (rated at least a slight problem) was 11.7 days and was shorter among children (duration -1.72 days; 95% confidence interval [CI] = -3.02 to -0.41) or in individuals with a history of fever (-1.22 days; 95% CI = -0.18 to 2.27). The duration of cough was longer among those with restricted activities on the day they saw the doctor (+0.69 days for each point of a 7-point scale). The duration of more severe symptoms was longer in those with a longer duration of symptoms prior to consultation, with a more severe cough on the day of seeing the doctor, and restriction of activities on the day of seeing the doctor. CONCLUSION: Illness duration may be predicted from a limited number of clinical symptoms and from prior history. These findings should be subjected to validation in a separate population. To minimise expectation about rapid resolution of illness, adults who have restricted activities could be advised that they are likely to experience symptoms for longer.

Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis: a randomized controlled trial.

CONTEXT: Acute sinusitis is a common clinical problem that usually results in a prescription for antibiotics but the role of antibiotics is debated. Anti-inflammatory drugs such as topical steroids may be beneficial but are underresearched. OBJECTIVE: To determine the effectiveness of amoxicillin and topical budesonide in acute maxillary sinusitis. DESIGN, SETTING, AND PATIENTS: A double-blind, randomized, placebo-controlled factorial trial of 240 adults (aged > or =16 years) with acute nonrecurrent sinusitis (had > or =2 diagnostic criteria: purulent rhinorrhea with unilateral predominance, local pain with unilateral predominance, purulent rhinorrhea bilateral, presence of pus in the nasal cavity) at 58 family practices (74 family physicians) between November 2001 and November 2005. Patients were randomized to 1 of 4 treatment groups: antibiotic and nasal steroid; placebo antibiotic and nasal steroid; antibiotic and placebo nasal steroid; placebo antibiotic and placebo nasal steroid. INTERVENTION: A dose of 500 mg of amoxicillin 3 times per day for 7 days and 200 mug of budesonide in each nostril once per day for 10 days. MAIN OUTCOME MEASURES: Proportion clinically cured at day 10 using patient symptom diaries and the duration and severity of symptoms. RESULTS: The proportions of patients with symptoms lasting 10 or more days were 29 of 100 (29%) for amoxicillin vs 36 of 107 (33.6%) for no amoxicillin (adjusted odds ratio, 0.99; 95% confidence interval, 0.57-1.73). The proportions of patients with symptoms lasting 10 or more days were 32 of 102 (31.4%) for topical budesonide vs 33 of 105 (31.4%) for no budesonide (adjusted odds ratio, 0.93; 95% confidence interval, 0.54-1.62). Secondary analysis suggested that nasal steroids were significantly more effective in patients with less severe symptoms at baseline. CONCLUSION: Neither an antibiotic nor a topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN60825437.

Developing clinical rules to predict urinary tract infection in primary care settings: sensitivity and specificity of near patient tests (dipsticks) and clinical scores.

BACKGROUND: Suspected urinary tract infection (UTI) is one of the most common presentations in primary care. Systematic reviews have not documented any adequately powered studies in primary care that assess independent predictors of laboratory diagnosis. AIM: To estimate independent clinical and dipstick predictors of infection and to develop clinical decision rules. DESIGN OF STUDY: Validation study of clinical and dipstick findings compared with laboratory testing. SETTING: General practices in the south of England. METHOD: Laboratory diagnosis of 427 women with suspected UTI was assessed using European urinalysis guidelines. Independent clinical and dipstick predictors of diagnosis were estimated. RESULTS: UTI was confirmed in 62.5% of women with suspected UTI. Only nitrite, leucocyte esterase (+ or greater), and blood (haemolysed trace or greater) independently predicted diagnosis (adjusted odds ratios 6.36, 4.52, 2.23 respectively). A dipstick decision rule, based on having nitrite, or both leucocytes and blood, was moderately sensitive (77%) and specific (70%); positive predictive value (PPV) was 81% and negative predictive value (NPV) was 65%. Predictive values were improved by varying the cut-off point: NPV was 73% for all three dipstick results being negative, and PPV was 92% for having nitrite and either blood or leucocyte esterase. A clinical decision rule, based on having two of the following: urine cloudiness, offensive smell, and dysuria and/or nocturia of moderate severity, was less sensitive (65%) (specificity 69%; PPV 77%, NPV 54%). NPV was 71% for none of the four clinical features, and the PPV was 84% for three or more features. CONCLUSIONS: Simple decision rules could improve targeting of investigation and treatment. Strategies to use such rules need to take into account limited negative predictive value, which is lower than expected from previous research.