mPneumonia, an Innovation for Diagnosing and Treating Childhood Pneumonia in Low-Resource Settings: A Feasibility, Usability and Acceptability Study in Ghana.

Pneumonia is the leading cause of infectious disease mortality in children. Currently, health care providers (HCPs) are trained to use World Health Organization Integrated Management of Childhood Illness (IMCI) paper-based protocols and manually assess respiratory rate to diagnose pneumonia in low-resource settings (LRS). However, this approach of relying on clinical signs alone has proven problematic.

Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial.

Objective: Methotrexate is used routinely worldwide for the medical treatment of clinically stable women with a tubal ectopic pregnancy. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicenter randomized controlled trial was to compare success rates of methotrexate against placebo for the conservative treatment of tubal ectopic pregnancy.

Quality of Life in Type 1 Diabetes and Celiac Disease: Role of the Gluten-Free Diet.

Objective: To evaluate quality of life (QoL) and glycemic control in youth with type 1 diabetes (T1D) and celiac disease vs T1D only. We hypothesized that QoL scores would be lower in youth with T1D and celiac disease and those nonadherent to the gluten-free diet (GFD).

Study Design: This case control study included 35 youth with T1D and 35 with T1D  and  celiac disease matched for age, sex, diabetes duration, and hemoglobin A1c level.

Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: A meta-analysis.

Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA.

Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution.

The effect of neoadjuvant chemotherapy and chemoradiotherapy on exercise capacity and outcome following upper gastrointestinal cancer surgery: an observational cohort study.

Background: In 2014 approximately 21,200 patients were diagnosed with oesophageal and gastric cancer in England and Wales, of whom 37 % underwent planned curative treatments. Potentially curative surgical resection is associated with significant morbidity and mortality. For operable locally advanced disease, neoadjuvant chemotherapy (NAC) improves survival over surgery alone.

Effectiveness of a Predictive Algorithm in the Prevention of Exercise-Induced Hypoglycemia in Type 1 Diabetes.

Background: Sensor-augmented pump therapy (SAPT) with a predictive algorithm to suspend insulin delivery has the potential to reduce hypoglycemia, a known obstacle in improving physical activity in patients with type 1 diabetes. The predictive low glucose management (PLGM) system employs a predictive algorithm that suspends basal insulin when hypoglycemia is predicted. The aim of this study was to determine the efficacy of this algorithm in the prevention of exercise-induced hypoglycemia under in-clinic conditions.

Assessment of plasma acylcarnitines before and after weight loss in obese subjects.

Acylcarnitines, fatty acid oxidation (FAO) intermediates, have been implicated in diet-induced insulin resistance and type 2 diabetes mellitus, as increased levels are found in obese insulin resistant humans. Moreover plasma acylcarnitines have been associated with clinical parameters related to glucose metabolism, such as fasting glucose levels and HbA1c. We hypothesized that plasma acylcarnitines would correlate with energy expenditure, insulin sensitivity and other clinical parameters before and during a weight loss intervention.

A qualitative comparison of needles and insulin pump use in children with type 1 diabetes.

Managing type 1 diabetes mellitus is an ongoing and challenging process; we investigated children's experience of different treatment regimens. Interviews with 17 children (7-15 years) at two time points were analysed using the grounded theory approach. Illness phase and treatment regimen shaped how bodily cues were interpreted.

Prevention of Insulin-Induced Hypoglycemia in Type 1 Diabetes with Predictive Low Glucose Management System.

Background: Sensor-augmented pump therapy (SAPT) with algorithms to predict impending low blood glucose and suspend insulin delivery has the potential to reduce hypoglycemia exposure. The aim of this study was to determine whether predictive low glucose management (PLGM) system is effective in preventing insulin-induced hypoglycemia in controlled experiments.

Methods: Two protocols were used to induce hypoglycemia in an in-clinic environment.

Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function.

Introduction: Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life.

Utility of salivary enzyme immunoassays for measuring estradiol and testosterone in adolescents: a pilot study.

Aim: We investigated the utility of enzyme immunoassay kits for measuring low levels of salivary estradiol and testosterone in adolescents and objectively assessed prevalence of blood contamination.

Methods: Endocrine patients provided plasma and saliva for estradiol (females) or testosterone (males) assay. Saliva samples were also tested with a blood contamination kit.

The CORE Service Improvement Programme for mental health crisis resolution teams: study protocol for a cluster-randomised controlled trial.

Background: As an alternative to hospital admission, crisis resolution teams (CRTs) provide intensive home treatment to people experiencing mental health crises. Trial evidence supports the effectiveness of the CRT model, but research suggests that the anticipated reductions in inpatient admissions and increased user satisfaction with acute care have been less than hoped for following the scaling up of CRTs nationally in England, as mandated by the National Health Service (NHS) Plan in 2000. The organisation and service delivery of the CRTs vary substantially.

Mild cold effects on hunger, food intake, satiety and skin temperature in humans.

Background: Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake.

Objective: To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography.

Methods: We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality.

A double blind community-based randomized trial of amoxicillin versus placebo for fast breathing pneumonia in children aged 2-59 months in Karachi, Pakistan (RETAPP).

Background: Fast breathing pneumonia is characterized by tachypnoea in the absence of danger signs and is mostly viral in etiology. Current guidelines recommend antibiotic therapy for all children with fast breathing pneumonia in resource limited settings, presuming that most pneumonia is bacterial. High quality clinical trial evidence to challenge or support the continued use of antibiotics, as recommended by the World Health Organization is lacking.

Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type.

Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH.

Methods: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details.

Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial.

Background: The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study.

Review and evaluation of penalised regression methods for risk prediction in low-dimensional data with few events.

Risk prediction models are used to predict a clinical outcome for patients using a set of predictors. We focus on predicting low-dimensional binary outcomes typically arising in epidemiology, health services and public health research where logistic regression is commonly used. When the number of events is small compared with the number of regression coefficients, model overfitting can be a serious problem.

Premorbid function, comorbidity, and frailty predict outcomes after ruptured abdominal aortic aneurysm repair.

Objective: Strategies to improve outcomes for patients with ruptured abdominal aortic aneurysm (rAAA) are becoming more evident. The aging population, however, continues to make the decision to intervene often difficult, especially given that traditional risk models do not reflect issues of aging and frailty. This study aimed to integrate measures of function alongside comorbidity- and frailty-specific factors to determine outcome.

Sample size calculation for a stepped wedge trial.

Background: Stepped wedge trials (SWTs) can be considered as a variant of a clustered randomised trial, although in many ways they embed additional complications from the point of view of statistical design and analysis. While the literature is rich for standard parallel or clustered randomised clinical trials (CRTs), it is much less so for SWTs. The specific features of SWTs need to be addressed properly in the sample size calculations to ensure valid estimates of the intervention effect.

How to develop a more accurate risk prediction model when there are few events.

When the number of events is low relative to the number of predictors, standard regression could produce overfitted risk models that make inaccurate predictions. Use of penalised regression may improve the accuracy of risk prediction

A note on obtaining correct marginal predictions from a random intercepts model for binary outcomes.

Background: Clustered data with binary outcomes are often analysed using random intercepts models or generalised estimating equations (GEE) resulting in cluster-specific or 'population-average' inference, respectively.

Methods: When a random effects model is fitted to clustered data, predictions may be produced for a member of an existing cluster by using estimates of the fixed effects (regression coefficients) and the random effect for the cluster (conditional risk calculation), or for a member of a new cluster (marginal risk calculation). We focus on the second.

The Clinical Relevance of Microbleeds in Stroke study (CROMIS-2): rationale, design, and methods.

Background And Rationale: The increasing use of oral anticoagulants, mostly to prevent ischemic stroke due to atrial fibrillation in an ageing population, has been associated with a fivefold increased incidence of oral anticoagulant-associated intracerebral hemorrhage: a rare, serious, and unpredictable complication. We hypothesize that cerebral microbleeds and other markers of cerebral small vessel disease on magnetic resonance imaging, and genetic polymorphisms (e.g.

Are multiple primary outcomes analysed appropriately in randomised controlled trials? A review.

Objectives: To review how multiple primary outcomes are currently considered in the analysis of randomised controlled trials. We briefly describe the methods available to safeguard the inferences and to raise awareness of the potential problems caused by multiple outcomes.

Methods/design: We reviewed randomised controlled trials (RCTs) in neurology and psychiatry disease areas, as these frequently analyse multiple outcomes.

Incidence and Outcomes of Severe Renal Impairment Following Ruptured Abdominal Aortic Aneurysm Repair.

Introduction: Acute kidney injury (AKI) following ruptured abdominal aortic aneurysm (rAAA) repair is common and multifactorial. A standard definition of AKI after endovascular repair (EVAR), the Aneurysm Renal Injury Score (ARISe), has been proposed to facilitate standardised reporting and thus improve understanding of this issue.

Methods: Data were collected retrospectively on AKI in a prospectively maintained database of all patients treated for rAAA in a single tertiary referral centre since the availability of routine out of hours emergency EVAR.