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Background Effective integration of evidence and youth perspectives into policy is crucial for supporting the future health and well-being of young people. The aim of this project was to translate evidence from the Access 3 project to support development of a new state policy on youth health and well-being within New South Wales (NSW), Australia. Ensuring the active contribution of young people within policy development was a key objective of the knowledge translation (KT) process. Methods The KT activity consisted of a 1-day facilitated forum with 64 purposively sampled stakeholders. Participants included eight young people, 14 policy-makers, 15 academics, 22 clinicians or managers from NSW health services, four general practitioners and one mental health service worker. Research to be translated came from the synthesized findings of the NSW Access 3 project. The design of the forum included stakeholder presentations and group workshops, guided by the 2003 Lavis et al. KT framework that was improved by the Grimshaw et al. KT framework in 2012. Members of the Access 3 research team took on the role of knowledge brokers throughout the KT process. Participant satisfaction with the workshop was evaluated using a brief self-report survey. Policy uptake was determined through examination of the subsequent NSW Youth Health Framework 2017–2024. Results A total of 25 policy recommendations were established through the workshop, and these were grouped into six themes that broadly aligned with the synthesized findings from the Access 3 project. The six policy themes were (1) technology solutions, (2) integrated care and investment to build capacity, (3) adolescent health checks, (4) workforce, (5) youth participation and (6) youth health indicators. Forum members were asked to vote on the importance of individual recommendations. These policy recommendations were subsequently presented to the NSW Ministry of Health, with some evidence of policy uptake identified. The majority of participants rated the forum positively. Conclusions The utilization of KT theories and active youth engagement led to the successful translation of research evidence and youth perspectives into NSW youth health policy. Future research should examine the implementation of policy arising from these KT efforts.

© 2019 The Authors Objective: To quantify barriers to healthcare for young people (12–24 years) and identify socio-demographic correlates and predictors. Methods: This cross-sectional survey targeted young people living in New South Wales, Australia, with oversampling of marginalised groups. Principles Component Analysis (PCA) identified clusters of barriers. Ordinal regression identified predictors of each barrier cluster. Results: A total of 1,416 young people completed surveys. Participants with chronic conditions and increasing psychological distress reported a greater number of barriers. Of 11 potential barriers to visiting a health service, cost was most common (45.8%). The PCA identified three clusters: structural barriers (61.3%), attitudinal barriers (44.1%) and barriers relating to emerging autonomy (33.8%). Conclusions: Barriers to healthcare reported by young people are multi-dimensional and have changed over time. Structural barriers, especially cost, are the most prominent among young people. Approaches to overcome structural barriers need to be addressed to better support marginalised young people's healthcare access. Implications for public health: Understanding predictors of different barrier types can inform more targeted approaches to improving access. Equitable access to healthcare is a priority for early diagnosis and treatment in young people, especially reducing out of pocket costs.

Background: The aim of this study was to measure young people&rsquo, s health status and explore associations between health status and belonging to one or more socio-culturally marginalised group. Methods: part of the Access 3 project, this cross-sectional survey of young people aged 12&ndash, 24 years living in New South Wales, Australia, oversampled young people from one or more of the following groups: Aboriginal and or Torres Strait Islander, living in rural and remote areas, homeless, refugee, and/or, sexuality and/or gender diverse. This paper reports on findings pertaining to health status, presence of chronic health conditions, psychological distress, and wellbeing measures. Results: 1416 participants completed the survey, 897 (63.3%) belonged to at least one marginalised group, 574 (40.5%) to one, 281 (19.8%) to two and 42 (3.0%) to three or four groups. Belonging to more marginalised groups was significantly associated with having more chronic health conditions (p = 0.001), a greater likelihood of high psychological distress (p = 0.001) and of illness or injury related absence from school or work (p &lt, 0.05). Conclusions: increasing marginalisation is associated with decreasing health status. Using an intersectional lens can to be a useful way to understand disadvantage for young people belonging to multiple marginalised groups.

Background To support longitudinal research into mood in adolescents we sought to assess the feasibility of collecting mood data via Short Message Service (SMS) over 3 years, and to investigate the relationship between SMS data and self-report measures of depression. Methods Prospective cohort study of young people aged 9 to 14 years at baseline. Participants completed Short Mood and Feelings Questionnaire (SMFQ) and the Youth Self Report Anxious/Depressed ((YSR)/AD) and Withdrawn/Depressed (YSR/WD) scales at baseline and annually for 3 years. In addition, at 3 monthly intervals they responded to an SMS asking them to rate their mood from 0 to 9 (9 highest). Results 277 young people (43% female) completed all four waves of the survey. There was a 87% response rate to requests for SMS Mood ratings. Mean SMS Mood decreased over time for females (p = 0.006) but not males (p = 0.45). We found an inverse association between SMS Mood and the SMFQ, YSR/AD and YSR/WD, scales in females and the SMFQ and YSR/WD scales in males. 45% of participants reported at least one SMS Mood rating score below 5, while 5% reported clusters of low SMS scores. Clusters of low SMS Mood scores were associated with SMFQ scores in the clinical range at 24 (OR = 4.45) and 36 months (OR = 4.72), and YSR/WD in the clinical range at 36 months (OR = 4.61). Conclusions SMS Mood ratings represent a feasible means to augment but not replace assessment of mood obtained using standard instruments.

Context Pubertal adolescents show strong appetites. How this is mediated is unclear, but ghrelin and peptide YY (PYY) play potentially important roles. Objective To measure ghrelin and PYY change in relation to pubertal growth. Design Three-year prospective cohort study. Setting Australian regional community. Participants Eighty healthy adolescents (26 girls; 54 boys) recruited at 10 to 13 years. Main Outcome Measures Fasting circulating total ghrelin, total PYY, IGF-1, insulin, leptin (via radioimmunoassay), estradiol and testosterone (via mass spectrometry), anthropometry, and body composition (via bioelectrical impedance). Results Adolescents exhibited normal developmental change. Mixed models revealed positive associations for ghrelin to age2 (both sexes: P < 0.05), indicating a U-shaped trend over time. Ghrelin was also inversely associated with IGF-1 (both sexes: P < 0.05), leptin in girls (P < 0.01), and insulin in boys (P < 0.05) and negatively correlated with annual height and weight velocity (both sexes: P ≤ 0.01). PYY showed no age-related change in either sex. Neither ghrelin nor PYY were associated with Tanner stage. Weight subgroup analyses showed significant ghrelin associations with age2 in healthy-weight but not overweight and obese adolescents (7 girls; 18 boys). Conclusions Adolescents showed a U-shaped change in ghrelin corresponding to physical and biochemical markers of growth, and no change in PYY. The overweight and obesity subgroup exhibited an apparent loss of the U-shaped ghrelin trend, but this finding may be attributed to greater maturity and its clinical significance is unclear. Further research on weight-related ghrelin and PYY trends at puberty is needed to understand how these peptides influence growth and long-term metabolic risk.

Background Previous research has shown that interdisciplinary ward rounds have the potential to improve team functioning and patient outcomes. Design A convergent parallel multimethod approach to evaluate a hospital interdisciplinary ward round intervention and ward restructure. Setting An acute medical unit in a large tertiary care hospital in regional Australia. Participants Thirty-two clinicians and inpatients aged 15 years and above, with acute episode of care, discharged during the year prior and the year of the intervention. Intervention A daily structured interdisciplinary bedside round combined with a ward restructure. Measurements Qualitative measures included contextual factors and measures of change and experiences of clinicians. Quantitative measures included length of stay (LOS), monthly "calls for clinical review," and cost of care delivery. Results Clinicians reported improved teamwork, communication, and understanding between and within the clinical professions, and between clinicians and patients, after the intervention implementation. There was no statistically significant difference between the intervention and control wards in the change in LOS over time (Wald ?2 = 1.05; degrees of freedom [df] = 1; P = .31), but a statistically significant interaction for cost of stay, with a drop in cost over time, was observed in the intervention group, and an increase was observed in the control wards (Wald ?2 = 6.34; df = 1; P = .012). The medical wards and control wards differed significantly in how the number of monthly "calls for clinical review" changed from prestructured interdisciplinary bedside round (SIBR) to during SIBR (F (1,44) = 12.18; P = .001). Conclusions Multimethod evaluations are necessary to provide insight into the contextual factors that contribute to a successful intervention and improved clinical outcomes.

Background Young people have unique social, emotional and developmental needs that require a welcoming and responsive health system, and policies that support their access to health care. Those who are socially or culturally marginalised may face additional challenges in navigating health care, contributing to health inequity. The aim of this study was to understand health system navigation, including the role of technology, for young people belonging to one or more marginalised groups, in order to inform youth health policy in New South Wales, Australia. Methods This qualitative longitudinal study involved 2–4 interviews each over 6 to 12 months with marginalised young people aged 12–24 years living in NSW. The analysis used Nvivo software and grounded theory. Results We interviewed 41 young people at baseline who were living in rural or remote areas, sexuality and/or gender diverse, refugee, homeless, and/or Aboriginal. A retention rate of over 85% was achieved. Nineteen belonged to more than one marginalised group allowing an exploration of intersectionality. General practitioners (family physicians) were the most commonly accessed service throughout the study period. Participants were ambivalent about their healthcare journeys. Qualitative analysis identified five themes:Technology brings opportunities to understand, connect and engage with servicesHealthcare journeys are shaped by decisions weighing up convenience, engagement, effectiveness and affordability.Marginalised young people perceive and experience multiple forms of discrimination leading to forgone care.Multiple marginalisation makes health system navigation more challengingThe impact of health system complexity and fragmentation may be mitigated by system knowledge and navigation support Conclusions The compounding effects of multiple discrimination and access barriers were experienced more strongly for young people belonging to mutiple marginalised groups. We identify several areas for improving clinical practice and policy. Integrating technology and social media into processes that facilitate access and navigation, providing respectful and welcoming services that recognise diversity, improving health literacy and involving professionals in advocacy and navigation support may help to address these issues. Electronic supplementary material The online version of this article (10.1186/s12939-019-0941-2) contains supplementary material, which is available to authorized users.

Background Influenza is a global infectious disease with a large burden of illness and high healthcare costs. Those who experience greater burden of disease include younger and older people, and pregnant women. Although there are known age and sex susceptibilities, little is known about how the interaction of age and sex may affect a population’s vulnerability to infection with different subtypes of influenza virus. Methods Laboratory-confirmed cases of influenza notified between 1 January 2009 and 31 December 2015 obtained from the Australian Government National Notifiable Diseases Surveillance System Influenza Public Data Set were analysed by age, sex and virus subtype. Age standardised notification rates per 100,000 population were calculated separately for females and males and used to generate female-to-male ratios with 95% confidence intervals for influenza A and B, and for virus subtypes A(H1N1)pdm09 and A(H3N2). Results 334,560 notifications for influenza A (all notifications), A(H1N1)pmd09, A(H3N2) and B subtypes from a total of 335,414 influenza notifications were analysed. Male notification rates were significantly higher for the 0 to 4 years old age group regardless of virus type or subtype; and higher for those aged 0 to 14 years and those 85 years and older for influenza types A and B and subtype A(H1N1)pdm09. Female notification rates were significantly higher for A(H1N1)pdm09 in those aged 15 to 54 years, for Type A and sub-type A(H3N2) in those aged 15 to 69 years, and for Influenza B in those aged 20 to 74 years. Conclusions We observed a female dominance in notification rates throughout the adult age groups, which could possibly be related to health seeking behaviours. However, differences in health seeking behaviours cannot explain the variations observed across virus subtypes in the particular age groups with higher female notifications. Depending on their age, females may be more susceptible to certain subtypes of influenza virus. These observations suggest that there is an interaction between age and sex on susceptibility to influenza infection which varies by the subtype of the virus. The inclusion of pregnancy and menopausal status in surveillance data may assist development of targeted public health approaches during the emergence of new subtypes of influenza virus. Targeted vaccination campaigns may need to take into consideration specific age and sex groups who have a greater susceptibility to influenza infection as well as those who experience a greater burden of illness.

BackgroundThe integration of digital technology into everyday lives of young people has become widespread. It is not known whether and how technology influences barriers and facilitators to healthcare, and whether and how young people navigate between face-to-face and virtual healthcare. To provide new knowledge essential to policy and practice, we designed a study that would explore health system access and navigation in the digital age. The study objectives are to: (1) describe experiences of young people accessing and navigating the health system in New South Wales (NSW), Australia; (2) identify barriers and facilitators to healthcare for young people and how these vary between groups; (3) describe health system inefficiencies, particularly for young people who are marginalised; (4) provide policy-relevant knowledge translation of the research data.Methods and analysisThis mixed methods study has four parts, including: (1) a cross-sectional survey of young people (12–24 years) residing in NSW, Australia; (2) a longitudinal, qualitative study of a subsample of marginalised young people (defined as young people who: identify as Aboriginal and/or Torres Strait Islander; are experiencing homelessness; identify as sexuality and/or gender diverse; are of refugee or vulnerable migrant background; and/or live in rural or remote NSW); (3) interviews with professionals; (4) a knowledge translation forum.Ethics and disseminationEthics approvals were sought and granted. Data collection commenced in March 2016 and will continue until June 2017. This study will gather practice and policy-relevant intelligence about contemporary experiences of young people and health services, with a unique focus on five different groups of marginalised young people, documenting their experiences over time.Access 3will explore navigation around all levels of the health system, determine whether digital technology is integrated into this, and if so how, and will translate findings into policy-relevant recommendations.

Chin Moi Chow,1 Shi Ngar Wong,1 Mirim Shin,1 Rebecca G Maddox,2 Kristy-Lee Feilds,3 Karen Paxton,4 Catherine Hawke,4 Philip Hazell,3 Katharine Steinbeck5 1Discipline of Exercise and Sport Science, Faculty of Health Sciences, 2Sydney Medical School, 3Discipline of Psychiatry, 4School of Rural Health, 5Discipline of Paediatrics and Child Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia Abstract: Actigraphy is increasingly used for sleep monitoring. However, there is a lack of standardized methodology for data processing and analysis, which often makes between study comparisons difficult, if not impossible, and thus open to flawed interpretation. This study evaluated a manual method for detection of the rest interval in actigraph data collected with Actiwatch 2. The rest interval (time in bed), defined as the bedtime and rise time and set by proprietary software, is an essential requirement for the estimation of sleep indices. This study manually and systematically detected the rest interval of 187 nights of recording from seven healthy males and three females, aged 13.5±0.7 (mean ± standard deviation) years. Data were analyzed for agreement between software default algorithm and manual scoring. Inter-rater reliability in manual scoring was also tested between two scorers. Data showed consistency between default settings and manual scorers for bedtime and rise time, but only moderate agreement for the rest interval duration and poor agreement for activity level at bedtime and rise time. Manual detection of rest intervals between scorers showed a high degree of agreement for all parameters (intraclass correlations range 0.864 to 0.995). The findings demonstrate that the default algorithm on occasions was unable to detect rest intervals or set the exact interval. Participant issues and inter-scorer issues also made difficult the detection of rest intervals. These findings have led to a manual detection protocol to define bedtime and rise time, supplemented with an event diary. Keywords: actigraph recording, activity level, light level

Background: Adolescent recruitment into longitudinal health studies is challenging. The aim of this paper is to report the detailed process and costs of recruiting young adolescents and their families into an intensive longitudinal study of the effects of puberty hormones on health, behaviour and wellbeing in early adolescence, based in regional/rural Australia. Methods: Participants were recruited using a saturation strategy of targeted methods (including school visits and community events) and non-targeted recruitment approaches (including print and electronic media advertising, and social media). Direct (face-to-face contact with the public) and indirect (behind-the-scenes preparatory activities) researcher hours were calculated for each of the recruitment strategies. Results: The study recruited 342 adolescent participants and a parent/guardian over two years. School and community-based recruitment required 6.2 and 6.0 researcher hours per activity, respectively. Direct researcher hours were primarily spent on delivering presentations and connecting with community members at community events. The majority of indirect hours were spent preparing and assembling information packs for distribution to students and parents during school visits. Non-targeted recruitment strategies using media advertising were the most frequently used methods. Researchers were estimated to have spent less than one hour for each media activity. In 27 months, an estimated $250,000 was spent on recruitment activities and resources. A combination of methods was used to recruit young adolescents and their families into a longitudinal health study. Conclusions: The financial costs and researcher time committed to this study highlight the labour-intensive nature of recruitment. The data presented are useful for researchers planning longitudinal studies in adolescents.

We sought to discover adolescents’ thoughts about participation in longitudinal research and identify recruitment and retention strategies that were meaningful to them. We conducted seven focus groups with 10–15-year-olds in two large rural centers in New South Wales, Australia, and all focus groups were digitally recorded, transcribed, and analyzed. Adolescents discussed factors salient to their involvement in focus groups, as well as factors that may influence involvement in a longitudinal study. At the outset of the focus groups, adolescents had a positive view of “research,” but were reluctant to engage in research that involved biologic samples. Effective recruitment of adolescents requires an appreciation of motivators, and time and resources to extend potential participants’ understanding. Supported by Sydney Medical School Foundation.

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.

Background/Aims The longitudinal relationships of within-individual hormone and anthropometric changes during puberty have not ever been fully described. The objectives of this study were to demonstrate that 3 monthly urine collection was feasible in young adolescents and to utilise liquid chromatography-tandem mass spectrometry assay methods for serum and urine testosterone (T), estradiol (E2) and luteinizing hormone (LH) in adolescents by relating temporal changes in urine and serum hormones over 12 months to standard measures of pubertal development. Methods A community sample of 104 adolescents (57 female) was studied over 12 months with annual anthropometric assessment, blood sampling and self-rated Tanner staging and urine collected every 3 months. Serum and urine sex steroids (T, E2) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LH by immunoassay. Results A high proportion (92%) of scheduled samples were obtained with low attrition rate of 6.7% over the 12 months. Urine hormone measurements correlated cross-sectionally and longitudinally with age, anthropometry and Tanner stage. Conclusion We have developed a feasible and valid sampling methodology and measurements for puberty hormones in urine, which allows a sampling frequency by which individual pubertal progression in adolescents can be described in depth.

Mood disorders and health risk behaviors increase in adolescence. Puberty is considered to contribute to these events. However, the precise impact of pubertal hormone changes to the emergence of mood disorders and risk behaviors is relatively unclear. It is important that inappropriate attribution is not made. Our aim was to determine what is known about the effect of endogenous estradiol on human adolescent girls’ mood and behavior. The databases searched were MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Pre-MEDLINE, Web of Science, and Scopus for all dates to October 2014. For inclusion, contemporaneous hormone and mood or behavioral assessment was required. Data were extracted following a template created by the authors. Fourteen studies met our inclusion criteria. There was some consistency in findings for mood and estradiol levels, with associations between estradiol and depression and emotional tone and risk taking. Results were less consistent for studies assessing other mood and behavioural outcomes. Most studies were cross-sectional in design; assay methodologies used in older studies may lack the precision to detect early pubertal hormone levels. Conclusion: Three longitudinal and several cross-sectional studies indicate potential associations between estradiol and certain mood or affective states, especially depression and mood variability though there are insufficient data to confirm that the rise in estradiol during puberty is causative. We believe that it is important for health professionals to take care when attributing adolescent psychopathology to puberty hormones, as the current data supporting these assertions are limited. Australian National Health and Medical Research Council (NHMRC)

Background Adolescence is characterized by marked psychosocial, behavioural and biological changes and represents a critical life transition through which adult health and well-being are established. Substantial research confirms the role of psycho-social and environmental influences on this transition, but objective research examining the role of puberty hormones, testosterone in males and oestradiol in females (as biomarkers of puberty) on adolescent events is lacking. Neither has the tempo of puberty, the time from onset to completion of puberty within an individual been studied, nor the interaction between age of onset and tempo. This study has been designed to provide evidence on the relationship between reproductive hormones and the tempo of their rise to adult levels, and adolescent behaviour, health and wellbeing. Methods/Design The ARCHER study is a multidisciplinary, prospective, longitudinal cohort study in 400 adolescents to be conducted in two centres in regional Australia in the State of New South Wales. The overall aim is to determine how changes over time in puberty hormones independently affect the study endpoints which describe universal and risk behaviours, mental health and physical status in adolescents. Recruitment will commence in school grades 5, 6 and 7 (10–12 years of age). Data collection includes participant and parent questionnaires, anthropometry, blood and urine collection and geocoding. Data analysis will include testing the reliability and validity of the chosen measures of puberty for subsequent statistical modeling to assess the impact over time of tempo and onset of puberty (and their interaction) and mean-level repeated measures analyses to explore for significant upward and downward shifts on target outcomes as a function of main effects. Discussion The strengths of this study include enrollment starting in the earliest stages of puberty, the use of frequent urine samples in addition to annual blood samples to measure puberty hormones, and the simultaneous use of parental questionnaires.

Introduction Longitudinal studies of adolescents must be ‘adolescent-friendly’, to collect data and to encourage maintenance in the study cohort. Text messaging may offer a feasible means to do both. Methods Adolescents in the Adolescent Rural Cohort, Hormones and Health, Education, Environments and Relationships (ARCHER) study (n=342) are sent automated text messages every 3 months, prompting biological specimen collection. Results A total of 99.2% of participants (or their parents) owned a mobile phone, of which 89.1% of participants responded to text messages and 97.3% of intended urine samples were collected. The average time to provide a urine sample after prompting correlated with time to reply to Short Message Service (SMS). Conclusions This study shows SMS can be used effectively in longitudinal research involving adolescents and is feasible and useful as a reminder tool for regular biological specimen collection. Australian National Health and Medical Research Council

Objective: To assess the impact of different management strategies in urinary tract infections.\ud \ud Design: Randomised controlled trial.\ud \ud Setting: Primary care.\ud \ud Participants: 309 non-pregnant women aged 18-70 presenting with suspected urinary tract infection.\ud \ud Intervention: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed (by 48 hours) antibiotics; or targeted antibiotics based on a symptom score (two or more of urine cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or both leucocytes and blood), or a positive result on midstream urine analysis. Self help advice was controlled in each group.\ud \ud Main outcome measures: Symptom severity (days 2 to 4) and duration, and use of antibiotics.\ud \ud Results: Patients had 3.5 days of moderately bad symptoms if they took antibiotics immediately. There were no significant differences in duration or severity of symptoms (mean frequency of symptoms on a 0 to 6 scale: immediate antibiotics 2.15, midstream urine 2.08, dipstick 1.74, symptom score 1.77, delayed antibiotics 2.11; likelihood ratio test for the five groups P=0.177). There were differences in antibiotic use (immediate antibiotics 97%, midstream urine 81%, dipstick 80%, symptom score 90%, delayed antibiotics 77%; P=0.011) and in sending midstream urine samples (immediate antibiotics 23%, midstream urine 89%, dipstick 36%, symptom score 33%, delayed antibiotics 15%; P

Objective: To assess the natural course and the important predictors of severe symptoms in urinary tract infection and the effect of antibiotics and antibiotic resistance.\ud \ud Design: Observational study.\ud \ud Setting: Primary care.\ud \ud Participants: 839 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection.\ud \ud Main outcome measure: Duration and severity of symptoms.\ud \ud Results: 684 women provided some information on symptoms; 511 had both laboratory results and complete symptom diaries. For women with infections sensitive to antibiotics, severe symptoms, rated as a moderately bad problem or worse, lasted 3.32 days on average. After adjustment for other predictors, moderately bad symptoms lasted 56% longer (incidence rate ratio 1.56, 95% confidence interval 1.22 to 1.99, P

Objectives: to estimate clinical and dipstick predictors of infection and develop and test clinical scores; to compare management using clinical and dipstick scores with commonly used alternative strategies; to estimate the cost-effectiveness of each strategy; and to understand the natural history of urinary tract infection (UTI) and women's concerns about its presentation and management. Design: there were six studies: (1) validation development for diagnostic clinical and dipstick scores; (2) validation of the scores developed; (3) observation of the natural history of UTI; (4) randomised controlled trial (RCT) of scores developed in study 1; (5) economic analysis of the RCT; (6) qualitative study of patients in the RCT. Setting: primary care. Participants: women aged 17-70 with suspected UTI. Interventions: patients were randomised to five management approaches: empirical antibiotics; empirical delayed antibiotics; target antibiotics based on a higher symptom score; target antibiotics based on dipstick results; or target antibiotics based on a positive mid-stream specimen of urine (MSU). Main outcome measures: antibiotic use, use of MSUs, rates of reconsultation and duration, and severity of symptoms. Results: (1) 62.5% of women had confirmed UTI. Only nitrite, leucocyte esterase and blood independently predicted diagnosis of UTI. A dipstick rule--based on having nitrite or both leucocytes and blood--was moderately sensitive (77%) and specific (70%) [positive predictive value (PPV) 81%, negative predictive value (NPV) 65%]. A clinical rule--based on having two of urine cloudiness, offensive smell, reported moderately severe dysuria, moderately severe nocturia--was less sensitive (65%) (specificity 69%, PPV 77%, NPV 54%). (2) 66% of women had confirmed UTI. The predictive values of nitrite, leucocyte esterase and blood were confirmed. The dipstick rule was moderately sensitive (75%) but less specific (66%) (PPV 81%, NPV 57%). (3) Symptoms rated as moderately bad or worse lasted 3.25 days on average for infections sensitive to antibiotics; resistant infections lasted 56% longer, infections not treated with antibiotics 62% longer and symptoms associated with urethral syndrome 33% longer. Symptom duration was shorter if the doctor was perceived to be positive about prognosis, and longer with frequent somatic symptoms, previous history of cystitis, urinary frequency and more severe symptoms at baseline. (4) 66% of the MSU group had laboratory-confirmed UTI. Women suffered 3.5 days of moderately bad symptoms if they took antibiotics immediately but 4.8 days if they delayed taking antibiotics for 48 hours. Taking bicarbonate or cranberry juice had no effect. (5) The MSU group was more costly over 1 month but not over 1 year. Cost-effectiveness acceptability curves showed that for a value per day of moderately bad symptoms of over 10 pounds, the dipstick strategy is most likely to be cost-effective. (6) Fear of spread to the kidneys, blood in the urine, and the impact of symptoms on vocational and leisure activities were important triggers for seeking help. When patients are asked to delay taking antibiotics the uncomfortable and worrying journey from 'person to patient' needs to be acknowledged and the rationale behind delaying the antibiotics made clear. Conclusions: to achieve good symptom control and reduce antibiotic use clinicians should either offer a 48-hour delayed antibiotic prescription to be used at the patient's discretion or target antibiotic treatment by dipsticks (positive nitrite or positive leucocytes and blood) with the offer of a delayed prescription if dipstick results are negative.

Objectives To determine whether microalbuminuria is an independent prognostic factor for the development of diabetic complications and whether improved glycaemic or blood pressure control has a greater influence on the development of diabetic complications in those with microalbuminuria than in those with normoalbuminuria. Data sources Electronic databases up until January 2002. Review methods A protocol for peer review by an external expert panel was prepared that included selection criteria for data extraction and required two independent reviewers to undertake article selection and review. Completeness was assessed using hand-searching of major journals. Random effects meta-analysis was used to obtain combined estimates of relative risk (RR). Funnel plots, trim and fill methods and meta-regression were used to assess publication bias and sources of heterogeneity. Results In patients with type 1 or type 2 DM and microalbuminuria there is a RR of all-cause mortality of 1.8 [95% confidence interval (CI) 1.5 to 2.1] and 1.9 (95% CI 1.7 to 2.1) respectively. Similar RRs were found for other mortality end-points, with age of cohort being inversely related to the RR in type 2 DM. In patients with type 1 DM, there is evidence that microalbuminuria or raised albumin excretion rate has only weak, if any, independent prognostic significance for the incidence of retinopathy and no evidence that it predicts progression of retinopathy, although strong evidence exists for the independent prognostic significance of microalbuminuria or raised albumin excretion rate for the development of proliferative retinopathy (crude RR of 4.1, 95% CI 1.8 to 9.4). For type 2 DM, there is no evidence of any independent prognostic significance for the incidence of retinopathy and little, if any, prognostic relationship between microalbuminuria and the progression of retinopathy or development of proliferative retinopathy. In patients with type 1 DM and microalbuminuria there is an RR of developing end-stage renal disease (ESRD) of 4.8 (95% CI 3.0 to 7.5) and a higher RR (7.5, 95% CI 5.4 to 10.5) of developing clinical proteinuria, with a significantly greater fall in glomerular filtration rate (GFR) in patients with microalbuminuria. In patients with type 2 DM, similar RRs were observed: 3.6 (95% CI 1.6 to 8.4) for developing ESRD and 7.5 (95% CI 5.2 to 10.9) for developing clinical proteinuria, with a significantly greater decline in GFR in the microalbuminuria group of 1.7 (95% CI 0.1 to 3.2) ml per minute per year compared with those who were normoalbuminuric. In adults with type 1 or type 2 DM and microalbuminuria at baseline, the numbers progressing to clinical proteinuria (19% and 24%, respectively) and those regressing to normoalbuminuria (26% and 18%, respectively) did not differ significantly. In children with type 1 DM, regression (44%) was significantly more frequent than progression (15%). In patients with type 1 or type 2 DM and microalbuminuria, there is scarce evidence as to whether improved glycaemic control has any effect on the incidence of cardiovascular disease (CVD), the incidence or progression of retinopathy, or the development of renal complications. However, among patients not stratified by albuminuria, improved glycaemic control benefits retinal and renal complications and may benefit CVD. In the effects of angiotensin-converting enzyme (ACE) inhibitors on GFR in normotensive microalbuminuric patients with type 1 DM, there was no evidence of a consistent treatment effect. There is strong evidence from 11 trials in normotensive type 1 patients with microalbuminuria of a beneficial effect of ACE inhibitor treatment on the risk of developing clinical proteinuria and on the risk of regression to normoalbuminuria. Patients with type 2 DM and microalbuminuria, whether hypertensive or not, may obtain additional cardiovascular benefit from an ACE inhibitor and there may be a beneficial effect on the development of retinopathy in normotensive patients irrespective of albuminuria. There is limited evidence that treatment of hypertensive microalbuminuric type 2 diabetic patients with blockers of the renin--angiotensin system is associated with preserved GFR, but also evidence of no differences in GFR in comparisons with other antihypertensive agents. The data on GFR in normotensive cohorts are inconclusive. In normotensive type 2 patients with microalbuminuria there is evidence from three trials (all enalapril) of a reduction in risk of developing clinical proteinuria; in hypertensive patients there is evidence from one placebo-controlled trial (irbesartan) of a reduction in this risk. Intensive compared with moderate blood pressure control did not affect the rate of progression of microalbuminuria to clinical proteinuria in the one available study. There is inconclusive evidence from four trials of any difference in the proportions of hypertensive patients progressing from microalbuminuria to clinical proteinuria when ACE inhibitors are compared with other antihypertensive agents, and in one trial regression was two-fold higher with lisinopril than with nifedipine. Conclusions The most pronounced benefits of glycaemic control identified in this review are on retinal and renal complications in both normoalbuminuric and microalbuminuric patients considered together, with little or no evidence of any greater benefit in those with microalbuminuria. Hence, microalbuminuric status may be a false boundary when considering the benefits of glycaemic control. Classification of a person as normoalbuminuric must not serve to suggest that they will derive less benefit from optimal glycaemic control than a person who is microalbuminuric. All hypertensive patients benefit from blood pressure lowering and there is little evidence of additional benefit in those with microalbuminuria. Antihypertensive therapy with an ACE inhibitor in normotensive patients with microalbuminuria is beneficial. Monitoring microalbuminuria does not have a proven role in modulating antihypertensive therapy while the patient remains hypertensive. Recommendations for microalbuminuria research include: determining rate and predictors of development and factors involved in regression; carrying out economic evaluations of different screening strategies; investigating the effects of screening on patients; standardising screening tests to enable use of common reference ranges; evaluating the effects of lipid-lowering therapy; and using to modulate antihypertensive therapy.

OBJECTIVE: To determine the extent to which mutations in the mannose binding protein gene predispose to childhood infection. DESIGN: Clinical details and genotype of mannose binding protein determined in consecutive children attending a paediatric department. SETTING: Inner city hospital paediatric service in London. SUBJECTS: 617 children attending hospital between October 1993 and August 1995. MAIN OUTCOME MEASURE: Infection as the cause for attendance or admission in relation to mutations in the mannose binding protein gene. RESULTS: The prevalence of mutations in the mannose binding protein gene in children with infection (146/345) was about twice that in children without infection (64/272) (P < 0.0001). Increased susceptibility to infection was found in both heterozygotic and homozygotic children. 13 out of 17 children homozygotic for variant alleles presented with strikingly severe infections, including 6 with septicaemia. CONCLUSIONS: The findings suggest that mutations in the mannose binding protein gene are an important risk factor for infections in children. Screening for such mutations should be included in the investigation of severe or frequent infections.