Association of C2, a derivative of the radial artery pressure waveform, with new onset of type 2 diabetes mellitus: the MESA study.

BackgroundAlthough microvascular dysfunction is known to result from diabetes, it might also lead to diabetes. Lower values of C2, a derivative of the radial artery pressure waveform, indicate microvascular dysfunction and predict hypertension and cardiovascular disease (CVD). We studied the association of C2 with incident diabetes in subjects free of overt CVD.MethodsAmong multi-ethnic participants (n = 5214), aged 45-84 years with no diabetes, C2 was derived from the radial artery pressure waveform. Incident diabetes (N = 651) was diagnosed as new fasting glucose ≥ 126 mg/dL or antidiabetic medicine over ~ 10 years. The relative incidence density (RID) for incident diabetes per standard deviation (SD) of C2 was studied during ~ 10 years follow-up using four levels of adjustment.ResultsMean C2 at baseline was 4.58 ± 2.85 mL/mmHg × 100. The RID for incident diabetes per SD of C2 was 0.90 (95% CI 0.82-0.99, P = 0.03). After adjustment for demographics plus body size, the corresponding RID was 0.81 (95% CI 0.73-0.89, P < 0.0001); body mass index (BMI) was the dominant covariate here. After adjustment for demographics plus cardiovascular risk factors, the RID was 0.98 (95% CI 0.89, 1.07, P = 0.63). After adjustment for all the parameters in the previous models, the RID was 0.87 (95% CI 0.78, 0.96, P = 0.006).ConclusionsIn a multi-ethnic sample free of overt CVD and diabetes at baseline, C2 predicted incident diabetes after adjustment for demographics, BMI and CVD risk factors. Differences in arterial blood pressure wave morphology may indicate a long-term risk trajectory for diabetes, independently of body size and the classical risk factors

Associations of body composition measures and C2, a marker for small artery elasticity: The MESA.

ObjectiveLower C2, a continuous blood pressure waveform characteristic asserted to represent small artery elasticity, predicts future cardiovascular disease events. It is hypothesized that the paradoxical positive association between body mass index (BMI) and C2 may reflect muscle instead of excess fat.MethodsIn a multi-ethnic, community-living cohort of 1,960 participants, computed tomography scans of the abdomen were used to measure visceral adipose tissue (VAT) and total abdominal muscle tissue (TAMT), and applanation tonometry of the radial arteries was used to assess C2. The period cross-sectional associations between BMI, TAMT, and VAT with C2 were ascertained.ResultsThe mean age was 62 ± 9 years and 51% were male. After adjustments for age, gender, ethnicity, pack years smoking cigarettes, diabetes, hypertension, and total and HDL cholesterol, higher BMI (standardized beta = 0.09, P-value < 0.01) and more TAMT (standardized beta = 0.12, P-value < 0.01) were significantly associated with higher C2. In contrast, more VAT (standardized beta = -0.09, P-value < 0.01) was associated with lower C2.ConclusionsIn multivariable analysis, VAT, in contrast to TAMT and BMI, was associated with less compliant small arteries. Visceral fat may be a better marker for detrimental excess body fat than BMI

Cost-effectiveness of Physical Therapy vs Intra-articular Glucocorticoid Injection for Knee Osteoarthritis: A Secondary Analysis From a Randomized Clinical Trial

Importance: Physical therapy and glucocorticoid injections are initial treatment options for knee osteoarthritis, but available data indicate that most patients receive one or the other, suggesting they may be competing interventions. The initial cost difference for treatment can be substantial, with physical therapy often being more expensive at the outset, and cost-effectiveness analysis can aid patients and clinicians in making decisions. Objective: To investigate the incremental cost-effectiveness between physical therapy and intra-articular glucocorticoid injection as initial treatment strategies for knee osteoarthritis. Design, setting, and participants: This economic evaluation is a secondary analysis of a randomized clinical trial performed from October 1, 2012, to May 4, 2017. Health economists were blinded to study outcomes and treatment allocation. A randomized sample of patients seen in primary care and physical therapy clinics with a radiographically confirmed diagnosis of knee osteoarthritis were evaluated from the clinical trial with 96.2% follow-up at 1 year. Interventions: Physical therapy or glucocorticoid injection. Main outcomes and measures: The main outcome was incremental cost-effectiveness between 2 alternative treatments. Acceptability curves of bootstrapped incremental cost-effectiveness ratios (ICERs) were used to identify the proportion of ICERs under the specific willingness-to-pay level ($50 000-$100 000). Health care system costs (total and knee related) and health-related quality-of-life based on quality-adjusted life-years (QALYs) were obtained. Results: A total of 156 participants (mean [SD] age, 56.1 [8.7] years; 81 [51.9%] male) were randomized 1:1 and followed up for 1 year. Mean (SD) 1-year knee-related medical costs were $2113 ($4224) in the glucocorticoid injection group and $2131 ($1015) in the physical therapy group. The mean difference in QALY significantly favored physical therapy at 1 year (0.076; 95% CI, 0.02-0.126; P = .003). Physical therapy was the more cost-effective intervention, with an ICER of $8103 for knee-related medical costs, with a 99.2$100 000. Conclusions and relevance: A course of physical therapy was cost-effective compared with a course of glucocorticoid injections for patients with knee osteoarthritis. These results suggest that, although the initial cost of delivering physical therapy may be higher than an initial course of glucocorticoid injections, 1-year total knee-related costs are equivalent, and greater improvement in QALYs may justify the initial higher costs. Trial registration: ClinicalTrials.gov Identifier: NCT0142715

Joint tests for quantitative trait loci in experimental crosses

Selective genotyping is common because it can increase the expected correlation between QTL genotype and phenotype and thus increase the statistical power of linkage tests (i.e., regression-based tests). Linkage can also be tested by assessing whether the marginal genotypic distribution conforms to its expectation, a marginal-based test. We developed a class of joint tests that, by constraining intercepts in regression-based analyses, capitalize on the information available in both regression-based and marginal-based tests. We simulated data corresponding to the null hypothesis of no QTL effect and the alternative of some QTL effect at the locus for a backcross and an F2 intercross between inbred strains. Regression-based and marginal-based tests were compared to corresponding joint tests. We studied the effects of random sampling, selective sampling from a single tail of the phenotypic distribution, and selective sampling from both tails of the phenotypic distribution. Joint tests were nearly as powerful as all competing alternatives for random sampling and two-tailed selection under both backcross and F2 intercross situations. Joint tests were generally more powerful for one-tailed selection under both backcross and F2 intercross situations. However, joint tests cannot be recommended for one-tailed selective genotyping if segregation distortion is suspected

A quantitative cross-sectional survey of psychosocial stimulation and counselling interventions at nutritional rehabilitation units in Southern Malawi

Background Inpatient treatment at nutritional rehabilitation units (NRUs) is needed for children who have severe acute malnutrition (SAM) and acute illness, loss of appetite, or severe oedema. World Health Organization guidelines state that nutritional counselling should be done with primary caregivers at NRUs. These recommendations also include psychosocial stimulation interventions to improve developmental outcomes in children with SAM. However, there is limited information about the delivery of these types of interventions for caregivers and children in NRU settings. The primary objective of this research was therefore to obtain data about NRU resources, activities, and protocols relevant to psychosocial stimulation and counselling interventions during inpatient treatment of children with SAM. Methods A cross-sectional survey was administered by interview at all 16 NRUs in seven districts in Southern Malawi. Participants were health workers, nurses, and nutritionists employed at the respective NRUs. Results The response rate was 100% across NRUs. Half of participants said that psychosocial stimulation interventions are conducted at their respective NRUs, yet none of the NRUs have protocols for delivery of these interventions. Furthermore, 7/16 (44%) NRUs have no resources for psychosocial stimulation including play materials. Thirteen of 16 (81%) participants said that they feel this type of intervention is very important and 3/16 (19%) participants said that this somewhat important for children with SAM. All NRUs provide counselling to caregivers about breastfeeding and nutrition; 15/16 (94%) also give counselling about water, sanitation and hygiene. Conclusions Ultimately, results from this survey highlighted that there is a need to invest in comprehensive interventions to improve developmental and nutritional outcomes in these vulnerable children requiring admission to NRUs

A protocol for a proof-of-concept randomized control trial testing increased protein quantity and quality in ready-to-use therapeutic food in improving linear growth among 6-23-month-old children with severe wasting in Malawi

Introduction: Ready-to-use therapeutic foods (RUTFs) have successfully promoted recovery from severe wasting and increased treatment coverage. However, RUTFs do not sufficiently improve linear growth, leaving many survivors of severe wasting at risk of persistent stunting, which is associated with high mortality risk, poor child development and non-communicable diseases in adulthood. High protein quantity and quality can stimulate linear growth. Aim: The trial aims to assess whether higher-protein-RUTF leads to higher concentrations of markers of linear growth compared to standard RUTF among 6–23 months old children with severe wasting. Methods: We designed a higher protein quantity and quality RUTF for a proof-of-concept (PoC) double-blind randomized controlled trial. Outcomes: The primary outcome is a change in insulin-like growth factor-1 (IGF-1), a hormone positively associated with linear growth after four weeks of treatment. Secondary outcomes include changes in ponderal and linear growth and in body composition from baseline to eight weeks later; plasma amino acid profile at four weeks; acceptability and safety. Implications: These findings will help in informing the potential impact of increased protein in RUTF on linear growth when treating severe wasting towards conducting a larger clinical trial. Trial registration: The trial has been registered on clinicaltrial.gov (NCT05737472)

Dysglycemia in Children with Severe Acute Malnutrition: A Systematic Review and Meta-Analysis.

Dysglycemia is a common complication of severe acute malnutrition (SAM) in children. Its prevalence and impact on short- and long-term outcomes are not well described. This systematic review was undertaken to review the available evidence on dysglycemia (either hypo- or hyperglycemia) in hospitalized children with SAM. The 2 primary objectives of this systematic review were to understand the prevalence of hypoglycemia and hyperglycemia in children with SAM. A secondary objective was to understand the relation between dysglycemia and clinical outcomes like mortality in children with SAM. MEDLINE was searched with terms related to children, SAM, and dysglycemia. A meta-analysis of proportions was completed to determine the hypoglycemia prevalence and a standard meta-analysis was done to determine the relation between hypoglycemia and mortality. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 2148 articles were identified in the database search of which 16 met the inclusion criteria for the systematic review based on screening done by multiple reviewers. The overall prevalence of hypoglycemia in SAM across studies based on the meta-analysis of proportions was 9% (95% CI: 7%, 12%; I2 = 92%). Meta-analysis results showed that hypoglycemia was associated with a higher chance of mortality during hospitalization in children with SAM (OR: 4.29; 95% CI: 3.04, 6.05; I2 = 0%). According to the GRADE evaluation, the certainty of the evidence for the prevalence of hypoglycemia was low and for hyperglycemia was very low. For the relation between hypoglycemia and mortality, the certainty of the evidence was moderate. A meta-analysis was not carried out for the prevalence of hyperglycemia due to the wide range of definitions used for across studies, but the prevalence ranged from 2% to 38% in the literature. This systematic review highlights the need for further work in this area to include serial glucose measurements to understand the clinical importance of dysglycemia during hospitalization in children with SAM

Association of C2, a derivative of the radial artery pressure waveform, with new onset of type 2 diabetes mellitus: the MESA study

Background Although microvascular dysfunction is known to result from diabetes, it might also lead to diabetes. Lower values of C2, a derivative of the radial artery pressure waveform, indicate microvascular dysfunction and predict hypertension and cardiovascular disease (CVD). We studied the association of C2 with incident diabetes in subjects free of overt CVD. Methods Among multi-ethnic participants (n = 5214), aged 45–84 years with no diabetes, C2 was derived from the radial artery pressure waveform. Incident diabetes (N = 651) was diagnosed as new fasting glucose ≥ 126 mg/dL or antidiabetic medicine over ~ 10 years. The relative incidence density (RID) for incident diabetes per standard deviation (SD) of C2 was studied during ~ 10 years follow-up using four levels of adjustment. Results Mean C2 at baseline was 4.58 ± 2.85 mL/mmHg × 100. The RID for incident diabetes per SD of C2 was 0.90 (95% CI 0.82–0.99, P = 0.03). After adjustment for demographics plus body size, the corresponding RID was 0.81 (95% CI 0.73–0.89, P < 0.0001); body mass index (BMI) was the dominant covariate here. After adjustment for demographics plus cardiovascular risk factors, the RID was 0.98 (95% CI 0.89, 1.07, P = 0.63). After adjustment for all the parameters in the previous models, the RID was 0.87 (95% CI 0.78, 0.96, P = 0.006). Conclusions In a multi-ethnic sample free of overt CVD and diabetes at baseline, C2 predicted incident diabetes after adjustment for demographics, BMI and CVD risk factors. Differences in arterial blood pressure wave morphology may indicate a long-term risk trajectory for diabetes, independently of body size and the classical risk factors