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.

Relationship Between Clinician Language and the Success of Behavioral Weight Loss Interventions : A Mixed-Methods Cohort Study.

BACKGROUND: International guidelines recommend that primary care clinicians recognize obesity and offer treatment opportunistically, but there is little evidence on how clinicians can discuss weight and offer treatment in ways that are well received and effective. OBJECTIVE: To examine relationships between language used in the clinical visit and patient weight loss. DESIGN: Mixed-methods cohort study. SETTING: 38 primary care clinics in England participating in the Brief Intervention for Weight Loss trial. PARTICIPANTS: 246 patients with obesity seen by 87 general practitioners randomly sampled from the intervention group of the randomized clinical trial. MEASUREMENTS: Conversation analysis of recorded discussions between 246 patients with obesity and 87 clinicians regarding referral to a 12-week behavioral weight management program offered as part of the randomized clinical trial. Clinicians' interactional approaches were identified and their association with patient weight loss at 12 months (primary outcome) was examined. Secondary outcomes included patients' agreement to attend weight management, attendance, loss of 5% body weight, actions taken to lose weight, and postvisit satisfaction. RESULTS: Three interactional approaches were identified on the basis of clinicians' linguistic and paralinguistic practices: creating a sense of referrals as "good news" related to the opportunity of the referral (n = 62); "bad news," focusing on the harms of obesity (n = 82); or neutral (n = 102). Outcome data were missing from 57 participants, so weighted analyses were done to adjust for missingness. Relative to neutral news, good news was associated with increased agreement to attend the program (adjusted risk difference, 0.25 [95% CI, 0.15 to 0.35]), increased attendance (adjusted risk difference, 0.45 [CI, 0.34 to 0.56]), and weight change (adjusted difference, -3.60 [CI, -6.58 to -0.62]). There was no evidence of differences in mean weight change comparing bad and neutral news, and no evidence of differences in patient satisfaction across all 3 approaches. LIMITATIONS: Data were audio only, so body language and nonverbal cues could not be assessed. There is potential for selection bias and residual confounding. CONCLUSION: When raising the topic of excess weight in clinical visits, presenting weight loss treatment as a positive opportunity is associated with greater uptake of treatment and greater weight loss. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research School for Primary Care Research and the Foundation for the Sociology of Health and Illness.

The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.

BACKGROUND: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. METHODS AND FINDINGS: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. CONCLUSIONS: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

Self-monitoring for improving control of blood pressure in patients with hypertension: a Cochrane intervention review.

BACKGROUND: Hypertension is a major risk factor for cardiovascular events with only a minority of people treated to satisfactory levels. There is an increasing body of literature pertaining to the beneficial effect of self-blood pressure monitoring (SBPM) on blood pressure control in hypertensive patients. It is cost-effective, well tolerated, and has been shown to be a better predictor of end organ damage than traditional office blood pressure monitoring (OBPM). The aim of this Cochrane review is to provide an up-to-date assessment on the effectiveness of self-monitoring in the management of hypertension.Is SBPM more efficacious in reducing blood pressure, compared with OBPM or usual care?Is SBPM with additional supports more efficacious in reducing blood pressure, compared with no additional support?Are there any adverse events associated with SBPM, compared with OBPM or usual care? METHODS: All randomised controlled trials of adult patients with a diagnosis of primary hypertension where the intervention of interest is SBPM will be included. Data extraction, analysis and risk of bias assessment will be carried out by two independent authors. Analysis will be based on intention-to-treat (ITT) data from individual trials. RESULTS: Primary outcome measures include change in mean office systolic and/or diastolic BP, change in mean ambulatory blood pressure, the proportion of patients reaching target BP, and adverse events including mortality or cardiovascular morbidity or related to treatment with antihypertensive agents. DISCUSSION: This review will help to determine if self-monitoring of blood pressure, with or without co-interventions, is effective in lowering blood pressure. Results will be available for conference.

Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.

BACKGROUND: Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer. METHODS AND FINDINGS: We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors. CONCLUSIONS: Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.

The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations.

BACKGROUND: We aimed to understand the time period of cancer diagnosis and the cancer types detected in primary care patients with unexpected weight loss (UWL) to inform cancer guidelines. METHODS: This retrospective matched cohort study used cancer registry linked electronic health records from the UK's Clinical Practice Research Datalink from between 2000 and 2014. Univariable and multivariable time-to-event analyses examined the association between UWL, and all cancers combined, cancer site and stage. RESULTS: In all, 63,973 patients had UWL recorded, of whom 1375 (2.2%) were diagnosed with cancer within 2 years (days-to-diagnosis: mean 181; median 80). Men with UWL (HR 3.28 (2.88-3.73)) and women (1.87 (1.68-2.08)) were more likely than comparators to be diagnosed with cancer within 3 months. The association was greatest in men aged ≥50 years and women ≥70 years. The commonest cancers were pancreas, cancer of unknown primary, gastro-oesophageal, lymphoma, hepatobiliary, lung, bowel and renal-tract. The majority were late-stage, but there was some evidence of association with stage II and stage III cancers. In the 3-24 months after presenting with UWL, cancer diagnosis was less likely than in comparators. CONCLUSION: UWL recorded in primary care is associated with a broad range of cancer sites of early and late-stage.

Factors associated with the prescribing of high-dose opioids in primary care: a systematic review and meta-analysis.

BACKGROUND: The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care. METHODS: We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNTH) calculation on factors when applicable. RESULTS: We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I2 = 0%, NNTH 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care. CONCLUSIONS: High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed. STUDY REGISTRATION: PROSPERO, CRD42018088057.

Biomarkers for diagnosing serious bacterial infections in older outpatients: a systematic review.

BACKGROUND: The value of biomarkers for diagnosing bacterial infections in older outpatients is uncertain and limited official guidance exists for clinicians in this area. The aim of this review is to critically appraise and evaluate biomarkers for diagnosing bacterial infections in older adults (aged 65 years and above). METHODS: We searched Medline, Embase, Web of Science and the Cochrane Library, from inception to January 2018. We included studies assessing the diagnostic accuracy of blood, urinary, and salivary biomarkers in diagnosing bacterial infections in older adults. The QUADAS-2 tool was used to assess study quality. RESULTS: We identified 11 eligible studies of moderate quality (11,034 participants) including 51 biomarkers at varying thresholds for diagnosing bacterial infections. An elevated Procalcitonin (≥ 0.2 ng/mL) may help diagnose bacteraemia in older adults [+ve LR range 1.50 to 2.60]. A CRP ≥ 50 mg/L only raises the probability of bacteraemia by 5%. A positive urine dipstick aids diagnosis of UTI (+ve LR range 1.23 to 54.90), and absence helps rule out UTI (-ve LR range 0.06 to 0.46). An elevated white blood cell count is unhelpful in diagnosing intra-abdominal infections (+ve LR range 0.75 to 2.62), but may aid differentiation of bacterial infection from other acute illness (+ve LR range 2.14 to 7.12). CONCLUSIONS: The limited available evidence suggests that many diagnostic tests useful in younger patients, do not help to diagnose bacterial infections in older adults. Further evidence from high quality studies is urgently needed to guide clinical practice. Until then, symptoms and signs remain the mainstay of diagnosis in community based populations.

Physician Support of Smoking Cessation After Diagnosis of Lung, Bladder, or Upper Aerodigestive Tract Cancer.

PURPOSE: Smoking cessation after a diagnosis of lung, bladder, and upper aerodigestive tract cancer appears to improve survival, and support to quit would improve cessation. The aims of this study were to assess how often general practitioners provide active smoking cessation support for these patients and whether physician behavior is influenced by incentive payments. METHODS: Using electronic primary care records from the UK Clinical Practice Research Datalink, 12,393 patients with incident cases of cancer diagnosed between 1999 and 2013 were matched 1 to 1 to patients with incident cases of coronary heart disease (CHD) diagnosed during the same time. We assessed differences in the proportion for whom physicians updated smoking status, advised quitting, and prescribed cessation medications, as well as the proportion of patients who stopped smoking within a year of diagnosis. We further examined whether any differences arose because the physicians were offered incentives to address smoking in patients with CHD and not cancer. RESULTS: At diagnosis, 32.0% of patients with cancer and 18.2% of patients with CHD smoked tobacco. Patients with cancer were less likely than patients with CHD to have their general practitioners update smoking status (OR = 0.18; 95% CI, 0.17-0.19), advise quitting (OR = 0.38; 95% CI, 0.36-0.40), or prescribe medication (OR = 0.67; 95% CI, 0.63-0.73), and they were less likely to have stopped smoking (OR = 0.76; 95% CI, 0.69-0.84). One year later 61.7% of patients with cancer and 55.4% with CHD who were smoking at diagnosis were still smoking. Introducing incentive payments was associated with more frequent interventions, but not for patients with CHD specifically. CONCLUSIONS: General practitioners were less likely to support smoking cessation in patients with cancer than with CHD, and patients with cancer were less likely to stop smoking. This finding is not due to the difference in incentive payments.

Community treatment orders and social outcomes for patients with psychosis: a 48-month follow-up study.

PURPOSE: Community treatment orders (CTOs) are widely used internationally despite a lack of evidence supporting their effectiveness. Most effectiveness studies are relatively short (12-months or less) and focus on clinical symptoms and service data, while a little attention is given to patients' social outcomes and broader welfare. We tested the association between the duration of CTO intervention and patients' long-term social outcomes. METHODS: A sub-sample (n = 114) of community-based patients from the Oxford Community Treatment Order Evaluation Trial (OCTET) were interviewed 48 months after randomisation. Multivariate regression models were used to examine the association between the duration of the CTO intervention and social outcomes as measured by the social network schedule, Objective Social Outcomes Index, Euro-Qol EQ-5D-3L (EQ-5D), and Oxford Capabilities Questionnaire for Mental Health. RESULTS: No significant association was found between the duration of CTO intervention and social network size (IRR = 0.996, p = .63), objective social outcomes (B = -0.003, p = .77), health-related quality of life (B = 0.001, p = .77), and capabilities (B = 0.046, p = .41). There were no between-group differences in social outcomes when outcomes were stratified by original arm of randomisation. Patients had a mean of 10.2 (SD = 5.9) contacts in their social networks, 42% of whom were relatives. CONCLUSIONS: CTO duration was not associated with improvements in patients' social outcomes even over the long term. This study adds to growing concerns about CTO effectiveness and the justification for their continued use.

What does being on a community treatment orders entail? A 3-year follow-up of the OCTET CTO cohort.

PURPOSE: Community Treatment Orders lack evidence of effectiveness. Very little is known about how they are used in practice and over time in terms of what it obliges patients to do and the judicial threshold for remaining on an order. AIMS: To investigate CTO implementation in England in terms of the use of specified conditions, and judicial hearings; whether these change over time, and; the level of continued coercion. METHOD: 36-month observational prospective study of patients on CTO in the OCTET follow-up study. RESULTS: The number of CTO conditions remained stable over time but consolidated around medication adherence and remaining in contact with services. Ten percent of Mental Health Tribunal Hearings and only 1 percent of Hospital Managers Hearings resulted in discharge. Twenty-seven percent of patients experienced more than one CTO episode and eighteen percent remained under compulsion until the end of follow-up. CONCLUSIONS: CTOs seem to be used primarily to oblige patients to take medication and stay in contact with services. There is agreement between clinical and legal judgements about their appropriateness and threshold for use. A pattern of continuous coercion for a significant group of patients raises concerns. If CTOs are to be continued to be imposed, their use should be carefully monitored with further cohort studies with long-term follow-up.

Recall of patients on community treatment orders over three years in the OCTET CTO cohort.

BACKGROUND: Randomised studies consistently show that Community Treatment Orders (CTOs) do not have the intended effect of preventing relapse and readmissions of patients with severe and enduring mental illness. Critics suggest this in part can be explained by RCTs studying newly introduced CTO regimes and that patients therefore were not brought back to hospital for short-term observations ('recall') as frequently as intended. Our purpose was (i) to test the hypothesis that CTO practice as regards recall of patients to hospital in England and Wales was as rigorous under the OCTET trial period as in current routine use and (ii) to investigate the reasons for and outcomes of recalls and whether this changed over time. METHOD: Thirty six-month observational prospective study of 198 patients in the OCTET Follow-up Study. RESULTS: Forty percent of patients were recalled, 19 % more than once. This is in line with current national use. Deterioration in clinical condition was the most common reason for recalls (49 %), and 68 % of recalls resulted in revocation of the order (i.e., retention in hospital under compulsion). This pattern remained stable over time. CONCLUSION: The use of recall cannot explain why RCTs have not confirmed any benefits from CTOs, and their continued use should be reconsidered. TRIAL REGISTRATION: The OCTET Trial was retrospectively registered on 12 November 2009 ( ISRCTN73110773 ).

GPs' adherence to guidelines for structured assessments of stroke survivors in the community and care homes.

BACKGROUND: Clinical practice guidelines recommend that stroke survivors' needs be assessed at regular intervals after stroke. The extent to which GPs comply with national guidance particularly for patients in care homes who have greatest clinical complexity is unknown. OBJECTIVES: This study aimed to establish the current clinical practice in the UK of needs assessment by GPs for stroke survivors after hospital discharge for acute stroke. METHODS: Cross-sectional online survey of current practice of GPs, using the national doctors.net network. RESULTS: The survey was completed by 300 GPs who had on average been working for 14 years. The structured assessment of stroke survivors' needs was not offered by 31% of GPs, with no significant difference for level of provision in community or care home settings. The outputs of reviews were added to patients' notes by 89% of GPs and used to change management by 57%. Only half the GPs reported integrating the information obtained into care plans and only a quarter of GPs had a protocol for follow-up of identified needs. Analysis of free-text comments indicated that patients in some care homes may receive more regular and structured reviews. CONCLUSIONS: This survey suggests that at least one-third of GPs provide no formal review of the needs of stroke patients and that in only a minority are identified needs addressed in a structured way. Standardization is required for what is included in reviews and how needs are being identified and met.

Use of Cognitive and Behavioral Strategies During a Weight Loss Program: A Secondary Analysis of the Doctor Referral of Overweight People to Low-Energy Total Diet Replacement Treatment (DROPLET) Trial.

BACKGROUND: Achieving a sustained energy deficit is essential for weight loss, but the cognitive and behavioral strategies that support this goal are unclear. OBJECTIVE: The goal of this study was to investigate the number and type of cognitive and behavioral strategies used by participants who were enrolled in a 1-year weight loss trial and to explore associations between strategies and magnitude of weight loss at 3 months and 1 year. DESIGN: The study is a secondary post-hoc exploratory analysis of data collected as part of the Doctor Referral of Overweight People to Low-Energy total diet replacement Treatment (DROPLET), a randomized controlled trial conducted in general practices in England, United Kingdom, between January 2016 and August 2017. PARTICIPANTS/SETTING: This study involved 164 participants from both intervention and control groups of the DROPLET trial who completed the Oxford Food and Behaviours (OxFAB) questionnaire to assess the use of 115 strategies grouped into 21 domains used to manage their weight. INTERVENTIONS: Participants were randomized to either a behavioral weight loss program involving 8 weeks total diet replacement (TDR) and 4 weeks of food reintroduction or a program delivered by a medical practice nurse over a 3-month period (usual care [UC]). MAIN OUTCOME MEASURES: Weight was objectively measured at baseline, 3 months, and 1 year. Cognitive and behavioral strategies used to support weight loss were assessed using the OxFAB questionnaire at 3 months. STATISTICAL ANALYSIS PERFORMED: Exploratory factor analysis was used to generate data-driven patterns of strategy use, and a linear mixed-effects model was used to examine associations between use of these patterns and weight change. RESULTS: No evidence was found of a difference in the number of strategies (mean difference, 2.41; 95% confidence interval [CI], -0.83, 5.65) or the number of domains used (mean difference, -0.23; 95% CI, -0.69, 0.23) between the TDR group and the UC group. The number of strategies was not associated with weight loss at either 3 months (-0.02 kg; 95% CI, -0.11, 0.06) or 1 year (-0.05 kg; 95% CI, -0.14, 0.02). Similarly, the number of domains used was not associated with weight loss at 3 months (-0.02 kg; 95% CI, -0.53, 0.49) or 1 year (-0.07 kg; 95% CI, -0.60, 0.46). Factor analysis identified four coherent patterns of strategy use, identified as Physical Activity, Motivation, Planned Eating, and Food Purchasing patterns. Greater use of strategies in the Food Purchasing (-2.6 kg; 95% CI, -4.42, -0.71) and Planned Eating patterns (-3.20 kg; 95% CI, -4.94, -1.46) was associated with greater weight loss at 1 year. CONCLUSIONS: The number of cognitive and behavioral strategies or domains used does not appear to influence weight loss, but the types of strategy appear of greater importance. Supporting people to adopt strategies linked to planned eating and food purchasing may aid long-term weight loss.

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.

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.

Point-of-care prognostication in moderate Covid-19: Analytical validation and prognostic accuracy of a soluble urokinase plasminogen activator receptor (suPAR) rapid test.

The soluble urokinase plasminogen activator receptor (suPAR) has been proposed as a biomarker for risk stratification of patients presenting with acute infections. However, most studies evaluating suPAR have used platform-based assays, the accuracy of which may differ from point-of-care tests capable of informing timely triage in settings without established laboratory capacity. Using samples and data collected during a prospective cohort study of 425 patients presenting with moderate Covid-19 to two hospitals in India, we evaluated the analytical performance and prognostic accuracy of a commercially-available rapid diagnostic test (RDT) for suPAR, using an enzyme-linked immunosorbent assay (ELISA) as the reference standard. Our hypothesis was that the suPAR RDT might be useful for triage of patients presenting with moderate Covid-19 irrespective of its analytical performance when compared with the reference test. Although agreement between the two tests was limited (bias = -2.46 ng/mL [95% CI = -2.65 to -2.27 ng/mL]), prognostic accuracy to predict supplemental oxygen requirement was comparable, whether suPAR was used alone (area under the receiver operating characteristic curve [AUC] of RDT = 0.73 [95% CI = 0.68 to 0.79] vs. AUC of ELISA = 0.70 [95% CI = 0.63 to 0.76]; p = 0.12) or as part of a published multivariable prediction model (AUC of RDT-based model = 0.74 [95% CI = 0.66 to 0.83] vs. AUC of ELISA-based model = 0.72 [95% CI = 0.64 to 0.81]; p = 0.78). Lack of agreement between the RDT and ELISA in our cohort warrants further investigation and highlights the importance of assessing candidate point-of-care tests to ensure management algorithms reflect the assay that will ultimately be used to inform patient care. Availability of a quantitative point-of-care test for suPAR opens the door to suPAR-guided risk stratification of patients with Covid-19 and other acute infections in settings with limited laboratory capacity.

Predicting the risk of acute kidney injury in primary care: derivation and validation of STRATIFY-AKI.

BACKGROUND: Antihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks. AIM: To develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment. DESIGN AND SETTING: Observational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England. METHOD: People aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD (n = 1 772 618), using a Fine-Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum (n = 3 805 322). RESULTS: The mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk. CONCLUSION: This clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case.