A Prognostic Model for Critically Ill Children in Locations With Emerging Critical Care Capacity.

OBJECTIVES: To develop a clinical prediction model to risk stratify children admitted to PICUs in locations with limited resources, and compare performance of the model to nine existing pediatric severity scores. DESIGN: Retrospective, single-center, cohort study. SETTING: PICU of a pediatric hospital in Siem Reap, northern Cambodia. PATIENTS: Children between 28 days and 16 years old admitted nonelectively to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory data recorded at the time of PICU admission were collected. The primary outcome was death during PICU admission. One thousand five hundred fifty consecutive nonelective PICU admissions were included, of which 97 died (6.3%). Most existing severity scores achieved comparable discrimination (area under the receiver operating characteristic curves [AUCs], 0.71-0.76) but only three scores demonstrated moderate diagnostic utility for triaging admissions into high- and low-risk groups (positive likelihood ratios [PLRs], 2.65-2.97 and negative likelihood ratios [NLRs], 0.40-0.46). The newly derived model outperformed all existing severity scores (AUC, 0.84; 95% CI, 0.80-0.88; p < 0.001). Using one particular threshold, the model classified 13.0% of admissions as high risk, among which probability of mortality was almost ten-fold greater than admissions triaged as low-risk (PLR, 5.75; 95% CI, 4.57-7.23 and NLR, 0.47; 95% CI, 0.37-0.59). Decision curve analyses indicated that the model would be superior to all existing severity scores and could provide utility across the range of clinically plausible decision thresholds. CONCLUSIONS: Existing pediatric severity scores have limited potential as risk stratification tools in resource-constrained PICUs. If validated, our prediction model would be a readily implementable mechanism to support triage of critically ill children at admission to PICU and could provide value across a variety of contexts where resource prioritization is important.

Correction to: The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort.

The original article [1] contains an omitted grant acknowledgement and affiliation as relates to the contribution of co-author, Rafael Perera-Salazar. As such, the following two amendments should apply to the original article.

Oseltamivir and influenza-related complications in children: a retrospective cohort in primary care.

BACKGROUND: Influenza and influenza-like illness (ILI) place considerable burden on healthcare systems, especially during influenza epidemics and pandemics. During the 2009/10 H1N1 influenza pandemic, UK national guidelines recommended antiviral medications for patients presenting within 72 h of ILI onset. However, it is not clear whether antiviral treatment was associated with reductions in influenza-related complications. METHODS: Our study population consisted of a retrospective cohort of children aged ≤17 years who presented with influenza/ILI at UK primary care practices contributing to the Clinical Practice Research Datalink during the 2009/10 pandemic. We used doubly robust inverse-probability weighted propensity scores and physician prior prescribing instrumental variable methods to estimate the causal effect of oseltamivir prescribing on influenza-related complications. Secondary outcomes were complications requiring intervention, pneumonia, pneumonia or hospitalisation, influenza-related hospitalisation and all-cause hospitalisation. RESULTS: We included 16 162 children, of whom 4028 (24.9%) were prescribed oseltamivir, and 753 (4.7%) had recorded complications. Under propensity score analyses oseltamivir prescriptions were associated with reduced influenza-related complications (risk difference (RD) -0.015, 95% CI -0.022--0.008), complications requiring further intervention, pneumonia, pneumonia or hospitalisation and influenza-related hospitalisation, but not all-cause hospitalisation. Adjusted instrumental variable analyses estimated reduced influenza-related complications (RD -0.032, 95% CI -0.051--0.013), pneumonia or hospitalisation, all-cause and influenza-related hospitalisations. CONCLUSIONS: Based on causal inference analyses of observational data, oseltamivir treatment in children with influenza/ILI was associated with a small but statistically significant reduction in influenza-related complications during an influenza pandemic.

Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial.

BACKGROUND: Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care. METHODS: This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366. FINDINGS: 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups. INTERPRETATION: Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care. FUNDING: National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort.

BACKGROUND: The presence of additional chronic conditions has a significant impact on the treatment and management of type 2 diabetes (T2DM). Little is known about the patterns of comorbidities in this population. The aims of this study are to quantify comorbidity patterns in people with T2DM, to estimate the prevalence of six chronic conditions in 2027 and to identify clusters of similar conditions. METHODS: We used the Clinical Practice Research Datalink (CPRD) linked with the Index of Multiple Deprivation (IMD) data to identify patients diagnosed with T2DM between 2007 and 2017. 102,394 people met the study inclusion criteria. We calculated the crude and age-standardised prevalence of 18 chronic conditions present at and after the T2DM diagnosis. We analysed longitudinally the 6 most common conditions and forecasted their prevalence in 2027 using linear regression. We used agglomerative hierarchical clustering to identify comorbidity clusters. These analyses were repeated on subgroups stratified by gender and deprivation. RESULTS: More people living in the most deprived areas had ≥ 1 comorbidities present at the time of diagnosis (72% of females; 64% of males) compared to the most affluent areas (67% of females; 59% of males). Depression prevalence increased in all strata and was more common in the most deprived areas. Depression was predicted to affect 33% of females and 15% of males diagnosed with T2DM in 2027. Moderate clustering tendencies were observed, with concordant conditions grouped together and some variations between groups of different demographics. CONCLUSIONS: Comorbidities are common in this population, and high between-patient variability in comorbidity patterns emphasises the need for patient-centred healthcare. Mental health is a growing concern, and there is a need for interventions that target both physical and mental health in this population.

Patient consultation rate and clinical and NHS outcomes: a cross-sectional analysis of English primary care data from 2.7 million patients in 238 practices.

BACKGROUND: Primary care workload is high and increasing in the United Kingdom. We sought to examine the association between rates of primary care consultation and outcomes in England. METHODS: Cross sectional observational study of routine electronic health care records in 283 practices from the Clinical Practice Research Datalink from April 2013 to March 2014. Outcomes included mortality rate, hospital admission rate, Quality and Outcomes Framework (QOF) performance and patient satisfaction. Relationships between consultation rates (with a general practitioner (GP) or nurse) and outcomes were investigated using negative binomial and ordinal logistic regression models. RESULTS: Rates of GP and nurse consultation (per patient person-year) were not associated with mortality or hospital admission rates: mortality incidence rate ratio (IRR) per unit change in GP/ nurse consultation rate = 1.01, 95% CI [0.98 to 1.04]/ 0.97, 95% CI [0.93 to 1.02]; hospital admission IRR per unit change in GP/ nurse consultation rate = 1.02, 95% CI [0.99 to 1.04]/ 0.98, 95% CI [0.94 to 1.032]. Higher rates of nurse but not GP consultation were associated with higher QOF achievement: OR = 1.91, 95% CI [1.39 to 2.62] per unit change in nurse consultation rate vs. OR = 1.04, 95% CI [0.87 to 1.24] per unit change in GP consultation rate. The association between the rates of GP/ nurse consultations and patient satisfaction was mixed. CONCLUSION: There are few associations between primary care consultation rates and outcomes. Previously identified demographic and staffing factors, rather than practice workload, appear to have the strongest relationships with mortality, admissions, performance and satisfaction. Studies with more detailed patient-level data would be required to explore these findings further.

UK medical students' attitudes towards their future careers and general practice: a cross-sectional survey and qualitative analysis of an Oxford cohort.

BACKGROUND: Against the background of the recruitment crisis in general practice, we aimed to determine what United Kingdom (UK) medical students value in their future careers, how they perceive careers in general practice (GP) and what influences them. METHODS: Cross-sectional survey of 280 final and penultimate year medical students at the University of Oxford, with questions relating to career choices, factors of importance when choosing a career and attitudes towards general practice as a career. Quantitative methods included cluster analysis, chi squared tests of independence and logistic regression analysis. Qualitative data were analysed thematically using the Framework method. RESULTS: Response rate was 89% (280/315). 40% of participants said that general practice was an attractive or very attractive career option. Respondents valued job satisfaction, work-life balance and close relationships with patients. However, fewer than 20% of respondents agreed that community-based working was important to them and many (often citing particular GPs they had observed) felt that general practice as currently structured may not be satisfying or fulfilling because of high workload, financial pressures and externally imposed directives. 63% perceived GPs to have lower status than hospital specialties and 49% thought the overall culture of their medical school had negatively influenced their views towards general practice. Some respondents considered that general practice would not be intellectually challenging or compatible with a research career; some appeared to have had limited exposure to academic primary care. CONCLUSIONS: With the caveat that this was a sample from a single medical school, medical students may be put off careers in general practice by three main things: low perceived value of community-based working and low status of general practice (linked to a prevailing medical school culture); observing the pressures under which GPs currently work; and lack of exposure to academic role models and primary care-based research opportunities. To improve recruitment of the next generation of GPs, medical schools must provide high quality placements in general practice, expose students to academic role models and highlight to policymakers the links between the current pressures in UK general practice and the recruitment crisis.

Clinical workload in UK primary care: a retrospective analysis of 100 million consultations in England, 2007-14.

BACKGROUND: Primary care is the main source of health care in many health systems, including the UK National Health Service (NHS), but few objective data exist for the volume and nature of primary care activity. With rising concerns that NHS primary care workload has increased substantially, we aimed to assess the direct clinical workload of general practitioners (GPs) and practice nurses in primary care in the UK. METHODS: We did a retrospective analysis of GP and nurse consultations of non-temporary patients registered at 398 English general practices between April, 2007, and March, 2014. We used data from electronic health records routinely entered in the Clinical Practice Research Datalink, and linked CPRD data to national datasets. Trends in age-standardised and sex-standardised consultation rates were modelled with joinpoint regression analysis. FINDINGS: The dataset comprised 101,818,352 consultations and 20,626,297 person-years of observation. The crude annual consultation rate per person increased by 10·51%, from 4·67 in 2007-08, to 5·16 in 2013-14. Consultation rates were highest in infants (age 0-4 years) and elderly people (≥85 years), and were higher for female patients than for male patients of all ages. The greatest increases in age-standardised and sex-standardised rates were in GPs, with a rise of 12·36% per 10,000 person-years, compared with 0·9% for practice nurses. GP telephone consultation rates doubled, compared with a 5·20% rise in surgery consultations, which accounted for 90% of all consultations. The mean duration of GP surgery consultations increased by 6·7%, from 8·65 min (95% CI 8·64-8·65) to 9·22 min (9·22-9·23), and overall workload increased by 16%. INTERPRETATION: Our findings show a substantial increase in practice consultation rates, average consultation duration, and total patient-facing clinical workload in English general practice. These results suggest that English primary care as currently delivered could be reaching saturation point. Notably, our data only explore direct clinical workload and not indirect activities and professional duties, which have probably also increased. This and additional research questions, including the outcomes of workload changes on other sectors of health care, need urgent answers for primary care provision internationally. FUNDING: Department of Health Policy Research Programme.

Telemonitoring and/or self-monitoring of blood pressure in hypertension (TASMINH4): protocol for a randomised controlled trial.

BACKGROUND: Self-monitoring of hypertension is associated with lower systolic blood pressure (SBP). However, evidence for the use of self-monitoring to titrate antihypertensive medication by physicians is equivocal. Furthermore, there is some evidence for the efficacy of telemonitoring in the management of hypertension but it is not clear what this adds over and above self-monitoring. This trial aims to evaluate whether GP led antihypertensive titration using self-monitoring results in lower SBP compared to usual care and whether telemonitoring adds anything to self-monitoring alone. METHODS/DESIGN: This will be a pragmatic primary care based, unblinded, randomised controlled trial of self-monitoring of BP with or without telemonitoring compared to usual care. Eligible patients will have poorly controlled hypertension (>140/90 mmHg) and will be recruited from primary care. Participants will be individually randomised to either usual care, self-monitoring alone, or self-monitoring with telemonitoring. The primary outcome of the trial will be difference in clinic SBP between intervention and control groups at 12 months adjusted for baseline SBP, gender, BP target and practice. At least 1110 patients will be sufficient to detect a difference in SBP between self-monitoring with or without telemonitoring and usual care of 5 mmHg with 90% power with an adjusted alpha of 0.017 (2-sided) to adjust for all three pairwise comparisons. Other outcomes will include adherence of anti-hypertensive medication, lifestyle behaviours, health-related quality of life, and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative sub study will gain insights into the views, experiences and decision making processes of patients and health care professionals focusing on the acceptability of self-monitoring and telemonitoring in the routine management of hypertension. DISCUSSION: The results of the trial will be directly applicable to primary care in the UK. If successful, self-monitoring of BP in people with hypertension would be applicable to hundreds of thousands of individuals in the UK. TRIAL REGISTRATION: ISRCTN 83571366 . Registered 17 July 2014.

External validation of clinical severity scores to guide referral of paediatric acute respiratory infections in resource-limited primary care settings.

Accurate and reliable guidelines for referral of children from resource-limited primary care settings are lacking. We identified three practicable paediatric severity scores (the Liverpool quick Sequential Organ Failure Assessment (LqSOFA), the quick Pediatric Logistic Organ Dysfunction-2, and the modified Systemic Inflammatory Response Syndrome) and externally validated their performance in young children presenting with acute respiratory infections (ARIs) to a primary care clinic located within a refugee camp on the Thailand-Myanmar border. This secondary analysis of data from a longitudinal birth cohort study consisted of 3010 ARI presentations in children aged ≤ 24 months. The primary outcome was receipt of supplemental oxygen. We externally validated the discrimination, calibration, and net-benefit of the scores, and quantified gains in performance that might be expected if they were deployed as simple clinical prediction models, and updated to include nutritional status and respiratory distress. 104/3,010 (3.5%) presentations met the primary outcome. The LqSOFA score demonstrated the best discrimination (AUC 0.84; 95% CI 0.79-0.89) and achieved a sensitivity and specificity > 0.80. Converting the scores into clinical prediction models improved performance, resulting in ~ 20% fewer unnecessary referrals and ~ 30-50% fewer children incorrectly managed in the community. The LqSOFA score is a promising triage tool for young children presenting with ARIs in resource-limited primary care settings. Where feasible, deploying the score as a simple clinical prediction model might enable more accurate and nuanced risk stratification, increasing applicability across a wider range of contexts.

Therapist-assisted online psychological therapies differing in trauma focus for post-traumatic stress disorder (STOP-PTSD): a UK-based, single-blind, randomised controlled trial.

BACKGROUND: Many patients are currently unable to access psychological treatments for post-traumatic stress disorder (PTSD), and it is unclear which types of therapist-assisted internet-based treatments work best. We aimed to investigate whether a novel internet-delivered cognitive therapy for PTSD (iCT-PTSD), which implements all procedures of a first-line, trauma-focused intervention recommended by the UK National Institute for Health and Care Excellence (NICE) for PTSD, is superior to internet-delivered stress management therapy for PTSD (iStress-PTSD), a comprehensive cognitive behavioural treatment programme focusing on a wide range of coping skills. METHODS: We did a single-blind, randomised controlled trial in three locations in the UK. Participants (≥18 years) were recruited from UK National Health Service (NHS) Improving Access to Psychological Therapies (IAPT) services or by self-referral and met DSM-5 criteria for PTSD to single or multiple events. Participants were randomly allocated by a computer programme (3:3:1) to iCT-PTSD, iStress-PTSD, or a 3-month waiting list with usual NHS care, after which patients who still met PTSD criteria were randomly allocated (1:1) to iCT-PTSD or iStress-PTSD. Randomisation was stratified by location, duration of PTSD (<18 months or ≥18 months), and severity of PTSD symptoms (high vs low). iCT-PTSD and iStress-PTSD were delivered online with therapist support by messages and short weekly phone calls over the first 12 weeks (weekly treatment phase), and three phone calls over the next 3 months (booster phase). The primary outcome was the severity of PTSD symptoms at 13 weeks after random assignment, measured by self-report on the PTSD Checklist for DSM-5 (PCL-5), and analysed by intention-to-treat. Safety was assessed in all participants who started treatment. Process analyses investigated acceptability and compliance with treatment, and candidate moderators and mediators of outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN16806208. FINDINGS: Of the 217 participants, 158 (73%) self-reported as female, 57 (26%) as male, and two (1%) as other; 170 (78%) were White British, 20 (9%) were other White, six (3%) were Asian, ten (5%) were Black, eight (4%) had a mixed ethnic background, and three (1%) had other ethnic backgrounds. Mean age was 36·36 years (SD 12·11; range 18-71 years). 52 (24%) participants met self-reported criteria for ICD-11 complex PTSD. Fewer than 10% of participants dropped out of each treatment group. iCT-PTSD was superior to iStress-PTSD in reducing PTSD symptoms, showing an adjusted difference on the PCL-5 of -4·92 (95% CI -8·92 to -0·92; p=0·016; standardised effect size d=0·38 [0·07 to 0·69]) for immediate allocations and -5·82 (-9·59 to -2·04; p=0·0027; d=0·44 [0·15 to 0·72]) for all treatment allocations. Both treatments were superior to the waiting list for PCL-5 at 13 weeks (d=1·67 [1·23 to 2·10] for iCT-PTSD and 1·29 [0·85 to 1·72] for iStress-PTSD). The advantages in outcome for iCT-PTSD were greater for participants with high dissociation or complex PTSD symptoms, and mediation analyses showed both treatments worked by changing negative meanings of the trauma, unhelpful coping, and flashback memories. No serious adverse events were reported. INTERPRETATION: Trauma-focused iCT-PTSD is effective and acceptable to patients with PTSD, and superior to a non-trauma-focused cognitive behavioural stress management therapy, suggesting that iCT-PTSD is an effective way of delivering the contents of CT-PTSD, one of the NICE-recommended first-line treatments for PTSD, while reducing therapist time compared with face-to-face therapy. FUNDING: Wellcome Trust, UK National Institute for Health and Care Research Oxford Health Biomedical Research Centre.

Defining the role of host biomarkers in the diagnosis and prognosis of the severity of childhood pneumonia: a prospective cohort study.

Reliable tools to inform outpatient management of childhood pneumonia in resource-limited settings are needed. We investigated the value added by biomarkers of the host infection response to the performance of the Liverpool quick Sequential Organ Failure Assessment score (LqSOFA), for triage of children presenting with pneumonia to a primary care clinic in a refugee camp on the Thailand-Myanmar border. 900 consecutive presentations of children aged ≤ 24 months meeting WHO pneumonia criteria were included. The primary outcome was receipt of supplemental oxygen. We compared discrimination of a clinical risk score (LqSOFA) to markers of endothelial injury (Ang-1, Ang-2, sFlt-1), immune activation (CHI3L1, IP-10, IL-1ra, IL-6, IL-8, IL-10, sTNFR-1, sTREM-1), and inflammation (CRP, PCT), and quantified the net benefit of including biomarkers alongside LqSOFA. We evaluated the differential contribution of LqSOFA and host biomarkers to the diagnosis and prognosis of pneumonia severity. 49/900 (5.4%) presentations met the primary outcome. Discrimination of LqSOFA and Ang-2, the best performing biomarker, were comparable (AUC 0.82 [95% CI 0.76-0.88] and 0.81 [95% CI 0.74-0.87] respectively). Combining Ang-2 with LqSOFA improved discrimination (AUC 0.91; 95% CI 0.87-0.94; p < 0.001), and resulted in greater net benefit, with 10-30% fewer children who required oxygen supplementation incorrectly identified as safe for community-based management. Ang-2 had greater prognostic utility than LqSOFA to identify children requiring supplemental oxygen later in their illness course. Combining Ang-2 and LqSOFA could guide referrals of childhood pneumonia from resource-limited community settings. Further work on test development and integration into patient triage is required.

Understanding the Impact of a New Approach to the Safeguarding of Children at Risk: An Evaluation Protocol.

Introduction: Child Safeguarding Services intervene in situations where a child is at risk of serious emotional or physical harm. The response will vary according to the level of risk, but in serious cases, a child may need to be removed from danger and cared for by foster parents either temporarily or permanently. The number of children being taken into care has increased markedly in recent years in the United Kingdom. Oxfordshire County Council (OCC) is implementing a new approach to the welfare of children (Family Solutions Plus; FSP) in which the focus is to support the whole family and ideally reduce the need for foster care.In this paper, we describe a proposed programme of evaluation to examine the impact of FSP on the time children are in contact with services, the nature of the support provided, experience of children and families, the experience of staff, and longer term outcomes for children, particularly whether they remain within the family or need to be cared for outside the home. Methods and analysis: A mixed methods approach will be taken in an observational retrospective study of children's social care services. Quantitative research will include descriptive analysis on data routinely collected by OCC, examining the effect on time spent in services, outcomes for children and how these outcomes are mediated by family characteristics and circumstances. Qualitative research will be carried out using individual interviews and focus groups with children, families and staff in the teams providing family safeguarding services to capture their experiences with the new model. Ethics and dissemination: This project has been registered with the OCC as a service evaluation. The qualitative studies will seek ethical approval from Oxford University Ethics Committee. A local data sharing agreement will govern the transfer of quantitative data. Results will be disseminated through newsletters, community forums, professional publications and conference presentations to national and international audiences.

Framework for the impact analysis and implementation of Clinical Prediction Rules (CPRs).

Clinical Prediction Rules (CPRs) are tools that quantify the contribution of symptoms, clinical signs and available diagnostic tests, and in doing so stratify patients according to the probability of having a target outcome or need for a specified treatment. Most focus on the derivation stage with only a minority progressing to validation and very few undergoing impact analysis. Impact analysis studies remain the most efficient way of assessing whether incorporating CPRs into a decision making process improves patient care. However there is a lack of clear methodology for the design of high quality impact analysis studies.We have developed a sequential four-phased framework based on the literature and the collective experience of our international working group to help researchers identify and overcome the specific challenges in designing and conducting an impact analysis of a CPR.There is a need to shift emphasis from deriving new CPRs to validating and implementing existing CPRs. The proposed framework provides a structured approach to this topical and complex area of research.

Frequency of Renal Monitoring - Creatinine and Cystatin C (FORM-2C): an observational cohort study of patients with reduced eGFR in primary care.

BACKGROUND: Monitoring is the mainstay of chronic kidney disease management in primary care; however, there is little evidence about the best way to do this. AIM: To compare the effectiveness of estimated glomerular filtration rate (eGFR) derived from serum creatinine and serum cystatin C to predict renal function decline among those with a recent eGFR of 30-89 ml/min/1.73 m2. DESIGN AND SETTING: Observational cohort study in UK primary care. METHOD: Serum creatinine and serum cystatin C were both measured at seven study visits over 2 years in 750 patients aged ≥18 years with an eGFR of 30-89 ml/min/1.73 m2 within the previous year. The primary outcome was change in eGFR derived from serum creatinine or serum cystatin C between 6 and 24 months. RESULTS: Average change in eGFR was 0.51 ml/min/1.73 m2/year when estimated by serum creatinine and -2.35 ml/min/1.73 m2/year when estimated by serum cystatin C. The c-statistic for predicting renal decline using serum creatininederived eGFR was 0.495 (95% confidence interval [CI] = 0.471 to 0.519). The equivalent c-statistic using serum cystatin C-derived eGFR was 0.497 (95% CI = 0.468 to 0.525). Similar results were obtained when restricting analyses to those aged ≥75 or <75 years, or with eGFR ≥60 ml/min/1.73 m2. In those with eGFR <60 ml/min/1.73 m2, serum cystatin C-derived eGFR was more predictive than serum creatinine-derived eGFR for future decline in kidney function. CONCLUSION: In the primary analysis neither eGFR estimated from serum creatinine nor from serum cystatin C predicted future change in kidney function, partly due to small changes during 2 years. In some secondary analyses there was a suggestion that serum cystatin C was a more useful biomarker to estimate eGFR, especially in those with a baseline eGFR <60 ml/min/1.73 m2.

A randomised controlled trial of therapist-assisted online psychological therapies for posttraumatic stress disorder (STOP-PTSD): trial protocol.

BACKGROUND: Over the last few decades, effective psychological treatments for posttraumatic stress disorder (PTSD) have been developed, but many patients are currently unable to access these treatments. There is initial evidence that therapist-assisted internet-based psychological treatments are effective for PTSD and may help increase access, but it remains unclear which of these treatments work best and are most acceptable to patients. This randomised controlled trial will compare a trauma-focussed and a nontrauma-focussed therapist-assisted cognitive behavioural Internet treatment for PTSD: Internet-delivered cognitive therapy for PTSD (iCT-PTSD) and internet-delivered stress management therapy (iStress-PTSD). METHODS/DESIGN: The study is a single-blind, randomised controlled trial comparing iCT-PTSD, iStress-PTSD and a 13-week wait-list condition, with an embedded process study. Assessors of treatment outcome will be blinded to trial arm. Two hundred and seventeen participants who meet DSM-5 criteria for PTSD will be randomly allocated by a computer programme to iCT-PTSD, iStress-PTSD or wait-list at a 3:3:1 ratio. The primary assessment point is at 13 weeks, and further assessments are taken at 6, 26, 39 and 65 weeks. The primary outcome measure is the severity of PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5). Secondary measures of PTSD symptoms are the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the Impact of Event Scale-Revised (IES-R). Other symptoms and well-being will be assessed with the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Scale (GAD-7), WHO (Five) Well-Being Index, Work and Social Adjustment Scale (WSAS), Endicott Quality of Life Scale (QoL), and Insomnia Sleep Index (ISI). Health economics analyses will consider quality of life, productivity, health resource utilisation, employment status and state benefits, and treatment delivery costs. Process analyses will investigate candidate mediators and moderators of outcome. Patient experience will be assessed by interview and questionnaire. DISCUSSION: This study will be the first to compare the efficacy of a trauma-focussed and nontrauma-focussed therapist-assisted online cognitive behavioural treatment for people with posttraumatic stress disorder. TRIAL REGISTRATION: ISRCTN16806208. Registered prospectively on 5 January 2018.

Examining the effectiveness of zinc treatment in children admitted with diarrhoea in Kenya's public hospitals: an observational comparative effectiveness study.

BACKGROUND: Kenyan paediatric treatment protocols recommend the use of zinc supplement for all children with diarrhoea. However, there is limited evidence of benefit for young children aged 1-5 months and those who are well-nourished. We examine effectiveness of zinc supplementation for children admitted with diarrhoea to Kenya's public hospitals with different nutritional and age categories. This is to determine whether the current policy where zinc is prescribed for all children with diarrhoea is appropriate. METHODS: We explore the effect of zinc treatment on time to discharge for children aged 1-5 and 6-59 months and amongst those classified as either severely - moderately under-nourished or well-nourished. To overcome the challenges associated with non-random allocation of treatments and missing data in these observational data, we use propensity score methods and multiple imputation to minimize bias. RESULTS: The analysis included 1645 (1-5 months) and 11 546 (6-59 months) children respectively. The estimated sub-distribution hazard ratios for being discharged in the zinc group vs the non-zinc group were 1.25 (95% confidence interval (CI) = 1.07, 1.46) and 1.17 (95% CI = 1.10, 1.24) in these respective age categories. Zinc treatment was associated with shorter time to discharge in both well and under-nourished children. CONCLUSION: Zinc treatment, in general, was associated with shorter time to discharge. In the absence of significant adverse effects, these data support the continued use of zinc for admissions with diarrhoea including those aged 1-5 months and in those who are well-nourished.

Schedules for Self-monitoring Blood Pressure: A Systematic Review.

BACKGROUND: Self-monitoring of blood pressure better predicts prognosis than clinic measurement, is popular with patients, and endorsed in hypertension guidelines. However, there is uncertainty over the optimal self-monitoring schedule. We therefore aimed to determine the optimum schedule to predict future cardiovascular events and determine "true" underlying blood pressure. METHODS: Six electronic databases were searched from November 2009 (updating a National Institute for Health and Care Excellence [NICE] systematic review) to April 2017. Studies that compared aspects of self-monitoring schedules to either prognosis or reliability/reproducibility in hypertensive adults were included. Data on study and population characteristics, self-monitoring regime, and outcomes were extracted by 2 reviewers independently. RESULTS: From 5,164 unique articles identified, 25 met the inclusion criteria. Twelve studies were included from the original NICE review, making a total of 37 studies. Increasing the number of days of measurement improved prognostic power: 72%-91% of the theoretical maximum predictive value (asymptotic maximum hazard ratio) was reached by 3 days and 86%-96% by 7 days. Increasing beyond 3 days of measurement did not result in better correlation with ambulatory monitoring. There was no convincing evidence that the timing or number of readings per day had an effect, or that ignoring the first day's measurement was necessary. CONCLUSIONS: Home blood pressure should be measured for 3 days, increased to 7 only when mean blood pressure is close to a diagnostic or treatment threshold. Other aspects of a monitoring schedule can be flexible to facilitate patient uptake of and adherence with self-monitoring.

Handling missing data in propensity score estimation in comparative effectiveness evaluations: a systematic review.

AIM: Even though systematic reviews have examined how aspects of propensity score methods are used, none has reviewed how the challenge of missing data is addressed with these methods. This review therefore describes how missing data are addressed with propensity score methods in observational comparative effectiveness studies. METHODS: Published articles on observational comparative effectiveness studies were extracted from MEDLINE and EMBASE databases. RESULTS: Our search yielded 167 eligible articles. Majority of these studies (114; 68%) conducted complete case analysis with only 53 of them stating this in the methods. Only 16 articles reported use of multiple imputation. CONCLUSION: Few researchers use correct methods for handling missing data or reported missing data methodology which may lead to reporting biased findings.