Boothdrejer3573

contrasting associations of adiposity with CVD incidence and with mortality. The high mortality risk at low and high BMI levels highlights, if causal, the importance of maintaining normal weight among people with diabetes.

Efpeglenatide is a long-acting glucagon-like peptide-1 receptor agonist being developed to improve glycemic control in type 2 diabetes (T2D). In the BALANCE 205 study (NCT02075281), efpeglenatide significantly reduced body weight versus placebo in patients with obesity, or overweight with comorbidities, and without T2D. These subanalyses explore the efficacy and safety of efpeglenatide in subgroups of patients with pre-diabetes and stratified by body mass index (BMI) or age from the BALANCE study.

The 20-week BALANCE study randomized patients with BMI ≥30 kg/m

or ≥27 kg/m

with comorbidities, and without diabetes, to efpeglenatide 4 mg or 6 mg once weekly, 6 mg or 8 mg once every 2 weeks, or placebo. For these subanalyses, patients were stratified by pre-diabetes status (glycated hemoglobin (HbA

) 5.7%-6.4% (39-46 mmol/mol) or fasting plasma glucose (FPG) 100-125 mg/dL) and by BMI or age < or ≥ median values (34.9 kg/m

and 44 years, respectively) at baseline.

In patients with pre-diabetes at baial effects of efpeglenatide on glycemic control and body weight regardless of pre-diabetes status, age, or BMI at baseline. The effects of efpeglenatide on glycemic control in patients with pre-diabetes suggest it might help reduce the likelihood of at-risk patients developing diabetes.Studies of the epidemiology of heart failure in the general population can inform assessments of disease burden, research, public health policy and health system care delivery. We performed a systematic review of prevalence, incidence and survival for all available population-representative studies to inform the Global Burden of Disease 2020. We examined population-based studies published between 1990 and 2020 using structured review methods and database search strings. Studies were sought in which heart failure was defined by clinical diagnosis using structured criteria such as the Framingham or European Society of Cardiology criteria, with studies using alternate case definitions identified for comparison. Study results were extracted with descriptive characteristics including age range, location and case definition. Search strings identified 42 360 studies over a 30-year period, of which 790 were selected for full-text review and 125 met criteria for inclusion. 45 sources reported estimates of prevalence, 41 of incidence and 58 of mortality. Prevalence ranged from 0.2%, in a Hong Kong study of hospitalised heart failure patients in 1997, to 17.7%, in a US study of Medicare beneficiaries aged 65+ from 2002 to 2013. Collapsed estimates of incidence ranged from 0.1%, in the EPidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine (EPICAL) study of acute heart failure in France among those aged 20-80 years in 1994, to 4.3%, in a US study of Medicare beneficiaries 65+ from 1994 to 2003. One-year heart failure case fatality ranged from 4% to 45% with an average of 33% overall and 24% for studies across all adult ages. Diagnostic criteria, case ascertainment strategy and demographic breakdown varied widely between studies. Prevalence, incidence and survival for heart failure varied widely across countries and studies, reflecting a range of study design. Heart failure remains a high prevalence disease among older adults with a high risk of death at 1 year.

To systematically assess the diagnostic accuracy of rapid point-of-care tests for diagnosis of current SARS-CoV-2 infections in children under real-life conditions.

Systematic review and meta-analysis.

MEDLINE, Embase, Cochrane Database for Systematic Reviews, INAHTA HTA database, preprint servers (via Europe PMC), ClinicalTrials.gov, WHO ICTRP from 1 January 2020 to 7 May 2021; NICE Evidence Search, NICE Guidance, FIND Website from 1 January 2020 to 24 May 2021.

Diagnostic cross-sectional or cohort studies were eligible for inclusion if they had paediatric study participants and compared rapid point-of care tests for diagnosing current SARS-CoV-2 infections with reverse transcription polymerase chain reaction (RT-PCR) as the reference standard. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the risk of bias and the applicability of the included studies. Bivariate meta-analyses with random effects were performed. Variability was assessed by subgroup analyseson uses of these tests in children (eg, self-testing in schools or parents testing their toddlers before kindergarten) have not been addressed in clinical performance studies yet. The observed low diagnostic sensitivity may impact the planned purpose of the broad implementation of testing programmes.

CRD42021236313.

CRD42021236313.

Obstructive sleep apnea (OSA) is diagnosed through polysomnography (PSG) testing and commonly treated with positive airway pressure (PAP). The initial recommended treatment for pediatric OSA is adenotonsillectomy, but when this is contraindicated or ineffective, PAP is the next option. Children followed in our pediatric sleep disorders center who are diagnosed with OSA and meet criteria for therapy are empirically prescribed a PAP device, usually auto-titrating PAP (APAP), to avoid delays in therapy. Titration PSG is performed later to assess adequacy of settings. The aims of this study were to determine how often PSG titration results in changes to empirically prescribed PAP and to assess adherence to therapy before and after PSG titration.

A retrospective medical records review was completed for children diagnosed with OSA, prescribed PAP, and had a titration PSG within a 5-y consecutive period of 2008-2012. Demographic data, type of device, pressure settings, and adherence downloads were reviewed. Adheen. Adherence was not increased following the titration PSG. Changes in therapy did not result in increased adherence. Titration PSGs may optimize empirically prescribed settings.

There are several tests recommended by the American Thoracic Society (ATS) to evaluate for airway hyper-responsiveness (AHR), one of which is methacholine challenge testing (MCT). Few studies have examined the correlation of baseline spirometry to predict AHR in MCT, especially in the younger, relatively healthy military population under clinical evaluation for symptoms of exertional dyspnea. The study aim was to retrospectively correlate baseline spirometry values with MCT responsiveness.

This study is a retrospective review of all MCT performed at Brooke Army Medical Center/Wilford Hall Medical Center over a 12-y period; all completed studies were obtained from electronic databases. The following parameters were analyzed from the studies baseline FEV

, FVC, FEV

/FVC, mid-expiratory flow (FEV

), FEV

/FVC. Studies were categorized based on baseline obstruction, restriction, FEF

lower limit of normal, and response to bronchodilator testing (if completed); these values were compared based on methachol% predicted showed a positive correlation with underlying AHR. In patients with exertional dyspnea and normal baseline spirometry, the use of the FEF

may be a useful surrogate measurement to predict reactivity during MCT and consideration for additional testing or treatment.

The analysis of baseline spirometry prior to MCT proved useful in the evaluation of exertional dyspnea in a military population. The presence of airways obstruction (FEV1/FVC less then lower limit of the normal range) followed by a reduction in FEV25-75% less then 70% predicted showed a positive correlation with underlying AHR. In patients with exertional dyspnea and normal baseline spirometry, the use of the FEF25-75% may be a useful surrogate measurement to predict reactivity during MCT and consideration for additional testing or treatment.Chemotherapy can impede cancer progression and is a well-demonstrated component of curative care for some patients with nonmetastatic cancer. However, cancer often relapses in high-risk patients due to acquired chemoresistance and progression to an incurable metastatic stage. There is building evidence from mouse models suggesting a possible stimulatory effect of chemotherapy on metastasis. While clinical trial data from patients with cancer supports the benefits of chemotherapy, the potential adverse effects of chemotherapeutics in a yet unidentified subset of patients are important to consider. In a study by Haj-Shomaly and colleagues, the interaction between the immune system and extracellular matrix remodeling is investigated for its role in the process. The study sheds light on the role of lysyl oxidase secreted by CD8+ T cells in priming the lung microenvironment for metastatic cell seeding, which may represent a targetable axis to further enhance the efficacy of chemotherapy agents.See related article by Haj-Shomaly et al., p. 278.Low oxygen concentrations (hypoxia) are detrimental to most species on Earth; thus, cells have evolved with adaptations allowing them to withstand transient hypoxia. As with other survival pathways, cancer cells have co-opted these mechanisms to keep up with the metabolic demands of rapid growth and proliferation in harsh tumor microenvironments. The most well-studied oxygen response pathway involves hypoxia-inducible factors (HIF) and their regulation by the von Hippel-Lindau protein (pVHL) and the prolyl hydroxylases (PHD1-3). This study from Zhong and colleagues, published in Cancer Research in 1999, was the first to show increased HIF1α expression in several cancer types and in metastases, suggesting a role for HIFs in disease progression. Since publication, significant progress has been made in the understanding of tumor hypoxia responses and efforts to target this pathway as a therapeutic strategy for patients with cancer are underway.See related article by Zhong and colleagues, Cancer Res 1999;595830-5.

To present a comprehensive review of the association between measures of body weight, waist, and fat, and different ratios of these measures, and the risk of type 2 diabetes.

Systematic review and dose-response meta-analysis of cohort studies.

PubMed, Scopus, and Web of Science up to 1 May 2021.

Cohort studies looking at the association between general or central adiposity and body fat content and the risk of type 2 diabetes in the general adult population were included. Two of the authors extracted the data in duplicate. Random effects dose-response meta-analyses were performed to estimate the degree of the associations. Curvilinear associations were modelled with a one stage weighted mixed effects meta-analysis.

216 cohort studies with 2.3 million individuals with type 2 diabetes among 26 million participants were identified. Relative risks were 1.72 (95% confidence interval 1.65 to 1.81; n=182 studies) for an increase in body mass index of 5 units, 1.61 (1.52 to 1.70; n=78) for a 10 cm larger waimass, although the number of studies was small.

A higher body mass index was associated with a greater risk of developing type 2 diabetes. A larger waist circumference, independent of overall adiposity, was strongly and linearly associated with the risk of type 2 diabetes.

PROSPERO CRD42021255338.

PROSPERO CRD42021255338.