Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study.

AIMS/HYPOTHESIS: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency. METHODS: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity. RESULTS: Among 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001). CONCLUSIONS/INTERPRETATION: In individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance.

Effect of Exercise Training on Prognosis in Community-acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of standard care (SoC) combined with supervised in-bed cycling (Bed-Cycle) or booklet exercises (Book-Exe) versus SoC in community-acquired pneumonia (CAP). METHODS: In this randomized controlled trial, 186 patients with CAP were assigned to SoC (n = 62), Bed-Cycle (n = 61), or Book-Exe (n = 63). Primary outcome length of stay (LOS) was analyzed with analysis of covariance. Secondary outcomes, 90-day readmission, and 180-day mortality were analyzed with Cox proportional hazard regression and readmission days with negative-binominal regression. RESULTS: LOS was -2% (95% CI: -24 to 25) and -1% (95% CI: -22 to 27) for Bed-Cycle and Book-Exe, compared with SoC. Ninety-day readmission was 35.6% for SoC, 27.6% for Bed-Cycle, and 21.3% for Book-Exe. Adjusted hazard ratio (aHR) for 90-day readmission was 0.63 (95% CI: .33-1.21) and 0.54 (95% CI: .27-1.08) for Bed-Cycle and Book-Exe compared with SoC. aHR for 90-day readmission for combined exercise was 0.59 (95% CI: .33-1.03) compared with SoC. aHR for 180-day mortality was 0.84 (95% CI: .27-2.60) and 0.82 (95% CI: .26-2.55) for Bed-Cycle and Book-Exe compared with SoC. Number of readmission days was 226 for SoC, 161 for Bed-Cycle, and 179 for Book-Exe. Incidence rate ratio for readmission days was 0.73 (95% CI: .48-1.10) and 0.77 (95% CI: .51-1.15) for Bed-Cycle and Book-Exe compared with SoC. CONCLUSIONS: Although supervised exercise training during admission with CAP did not reduce LOS or mortality, this trial suggests its potential to reduce readmission risk and number of readmission days. CLINICAL TRIALS REGISTRATION: NCT04094636.

NatIonal Danish endocarditis stUdieS - Design and objectives of the NIDUS registry.

AIMS: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease. METHODS: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources. CONCLUSIONS AND PERSPECTIVES: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed.

Evaluation of the Danish Colorectal Cancer Screening Program Among People With Cystic Fibrosis.

GOALS: We aimed to evaluate the Danish CRC screening program, estimate colonic neoplasia's prevalence, and assess the utilized BP regimens. BACKGROUND: People with cystic fibrosis (pwCF) have an increased risk of precancerous polyps and colorectal cancer (CRC), with occurrence at an earlier age compared with the general population. Consequently, colonoscopy screening is recommended. PwCF requires specific bowel preparation (BP) regimens to ensure an adequate colonoscopy. STUDY: We conducted a national retrospective cohort study, which included all pwCF eligible for colonoscopy according to international recommendations in 26 months. RESULTS: Among 119 eligible pwCF, 58 completed colonoscopies during the screening period. The screening was omitted in 25% of pwCF. Among the pwCF undergoing colonoscopy screening, precancerous polyps were found in 24% and none with CRC. One patient developed CRC before being offered screening. Risk factors for neoplasia were old age and male sex. The quality of BP was high, even though most pwCF received standard BP. The best quality was found in nonorgan transplanted, pwCF who received modulator treatment and those with no laxatives use. CONCLUSIONS: We detected a high adherence to CRC screening, but also a substantial proportion of pwCF who were not informed about screening recommendations, calling for greater awareness among clinicians. Although lower than previously described, our study revealed high numbers of precancerous polyps and CRC compared with the general population, underlining the need for screening. BP quality remained high, despite frequent use of standard regimens, implicating the need for more individualized regimens before undergoing colonoscopy.

The impact of an oral glucose load on IFN-γ-release in persons infected with Mycobacterium tuberculosis.

BACKGROUND AND OBJECTIVE: To diagnose tuberculosis infection (TBI), whole blood is incubated with M.tuberculosis (Mtb)-specific peptides and the release of interferon-γ (IFN-γ) is measured in IFN-γ-release assays (IGRAs). Hyperglycaemia and fluctuations in blood glucose may modulate IFN-γ-release. Here, we investigated if glucose intake affects IFN-γ-release or IGRA results in IGRAs taken during an oral glucose tolerance test (OGTT). METHODS: Persons with TB disease (TB) or TBI underwent a standard 75-g OGTT at the start and end of treatment for TB or TBI. Blood for the IGRA QuantiFERON-TB Gold Plus (QFT) containing Mtb-specific tubes (TB1 and TB2), a non-specific mitogen tube (MIT) and an empty control tube (NIL) was drawn at sample-timepoints -15 (baseline), 60, 90, 120 and 240 min during the OGTT. Blood glucose was measured in parallel at all timepoints. IFN-γ-release (after subtraction of NIL) at each timepoint was compared with baseline using linear-mixed-model analysis. RESULTS: Twenty-four OGTTs from 14 participants were included in the final analysis. Compared to baseline, IFN-γ-release was increased at sample-timepoint 240 min for TB1; geometric mean (95% confidence interval) 3.0 (1.5-6.2) vs 2.5 (1.4-4.4) IU/mL (p = 0.047), and MIT; 182.6 (103.3-322.9) vs 146.0 (84.0-254.1) IU/mL (p = 0.002). Plasma glucose levels were not associated with IFN-γ-release and the QFT test results were unaffected by the OGTT. CONCLUSION: Ingestion of glucose after a 10-h fast was associated with increased IFN-γ-release after 240 min in the MIT tube. However, there was no association between plasma glucose levels at the QFT sampling timepoint and IFN-γ-release. Furthermore, the QFT test results were not affected by glucose intake. The overall effect of an OGTT and prevailing plasma glucose levels on IFN-γ-release in IGRAs seem limited. TRIAL REGISTRATION: Trial registration ID: NCT04830462 ( https://clinicaltrials.gov/study/NCT04830462 ). Registration date: 05-Apr-2021.

The effect of Mycobacterium tuberculosis treatment on thrombelastography-assessed haemostasis: a prospective cohort study.

BACKGROUND AND OBJECTIVE: Tuberculosis disease (TB) and tuberculosis infection (TBI) have been associated with increased risk of cardiovascular disease which may be connected to infection-related haemostatic changes. It is unknown if treatment of Mycobacterium tuberculosis influences haemostasis. Here, we assessed if TB or TBI treatment affects thrombelastography (TEG)-assessed haemostasis. METHODS: Individuals with TB or TBI were included from a TB outpatient clinic in Copenhagen, Denmark. Patients treated with antithrombotic medication or systemic immunosuppressants were excluded. TEG analysis was performed before and after TB/TBI treatment using the TEG®6s analyser to provide data on the reaction time of clot initiation (R) (min), the speed of clot formation (K) (min) and clot build-up (Angle) (°), maximum clot strength (MA) (mm), and clot breakdown/fibrinolysis (LY30) (%). Differences in TEG were assessed using paired t tests. RESULTS: We included eleven individuals with TB with median [interquartile range] [IQR] age 52 (Liu et al. in Medicine (United States) 95, 2016) years and mean (standard deviation) (SD) body mass index (BMI) 24.7 (6.3) kg/m2 as well as 15 individuals with TBI with median [IQR] age 49 (Wells et al. in Am J Respir Crit Care Med 204:583, 2021) years and BMI 26.0 (3.2) kg/m2. Treatment reduced MA for both TB (64.0 (6.3) vs. 57.9 (5.2) mm, p = 0.016) and TBI (61.3 (4.1) vs. 58.6 (5.0) mm, p = 0.023) whereas R, K, Angle and LY30 were unaffected. CONCLUSION: TEG analysis showed that treatments of TB and TBI were associated with reduced MA which may indicate the existence of cardiovascular benefits from therapy. TRIAL REGISTRATION: Registered at ClinicalTrials.gov 05 April 2021 with registration number NCT04830462.

Brain imaging in children with neonatal cholestatic liver disease: A systematic review.

AIM: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development. METHODS: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools. RESULTS: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation. CONCLUSION: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment.

Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study.

BACKGROUND AND AIMS: In the Partial Oral Treatment of Endocarditis (POET) trial, stabilized patients with left-sided infective endocarditis (IE) were randomized to oral step-down antibiotic therapy (PO) or conventional continued intravenous antibiotic treatment (IV), showing non-inferiority after 6 months. In this study, the first guideline-driven clinical implementation of the oral step-down POET regimen was examined. METHODS: Patients with IE, caused by Staphylococcus aureus, Enterococcus faecalis, Streptococcus spp. or coagulase-negative staphylococci diagnosed between May 2019 and December 2020 were possible candidates for initiation of oral step-down antibiotic therapy, at the discretion of the treating physician. The composite primary outcome in patients finalizing antibiotic treatment consisted of embolic events, unplanned cardiac surgery, relapse of bacteraemia and all-cause mortality within 6 months. RESULTS: A total of 562 patients [median age 74 years (IQR, interquartile range, 65-80), 70% males] with IE were possible candidates; PO was given to 240 (43%) patients and IV to 322 (57%) patients. More patients in the IV group had IE caused by S. aureus, or had an intra-cardiac abscess, or a pacemaker and more were surgically treated. The primary outcome occurred in 30 (13%) patients in the PO group and in 59 (18%) patients in the IV group (P = .051); in the PO group, 20 (8%) patients died vs. 46 (14%) patients in the IV group (P = .024). PO-treated patients had a shorter median length of stay [PO 24 days (IQR 17-36) vs. IV 43 days (IQR 32-51), P < .001]. CONCLUSIONS: After clinical implementation of the POET regimen almost half of the possible candidates with IE received oral step-down antibiotic therapy. Patients in the IV group had more serious risk factors for negative outcomes. At 6-month follow-up, there was a numerically but not statistically significant difference towards a lower incidence of the primary outcome, a lower incidence of all-cause mortality and a reduced length of stay in the PO group. Due to the observational design of the study, the lower mortality may to some extent reflect selection bias and unmeasured confounding. Clinical implementation of PO regimens seemed feasible and safe.

Bacterial biofilms predominate in both acute and chronic human lung infections.

BACKGROUND: A basic paradigm of human infection is that acute bacterial disease is caused by fast growing planktonic bacteria while chronic infections are caused by slow-growing, aggregated bacteria, a phenomenon known as a biofilm. For lung infections, this paradigm has been thought to be supported by observations of how bacteria proliferate in well-established growth media in the laboratory-the gold standard of microbiology. OBJECTIVE: To investigate the bacterial architecture in sputum from patients with acute and chronic lung infections. METHODS: Advanced imaging technology was used for quantification and direct comparison of infection types on fresh sputum samples, thereby directly testing the acute versus chronic paradigm. RESULTS: In this study, we compared the bacterial lifestyle (planktonic or biofilm), growth rate and inflammatory response of bacteria in freshly collected sputum (n=43) from patient groups presenting with acute or chronic lung infections. We found that both acute and chronic lung infections are dominated by biofilms (aggregates of bacteria within an extracellular matrix), although planktonic cells were observed in both sample types. Bacteria grew faster in sputum from acute infections, but these fast-growing bacteria were enriched in biofilms similar to the architecture thought to be reserved for chronic infections. Cellular inflammation in the lungs was also similar across patient groups, but systemic inflammatory markers were only elevated in acute infections. CONCLUSIONS: Our findings indicate that the current paradigm of equating planktonic with acute and biofilm with chronic infection needs to be revisited as the difference lies primarily in metabolic rates, not bacterial architecture.

Body composition, physical capacity, and immuno-metabolic profile in community-acquired pneumonia caused by COVID-19, influenza, and bacteria: a prospective cohort study.

BACKGROUND: Different pathogens can cause community-acquired pneumonia (CAP); however, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has re-emphasized the vital role of respiratory viruses as a cause of CAP. The aim was to explore differences in metabolic profile, body composition, physical capacity, and inflammation between patients hospitalized with CAP caused by different etiology. METHODS: A prospective study of Danish patients hospitalized with CAP caused by SARS-CoV-2, influenza, or bacteria. Fat (FM) and fat-free mass (FFM) were assessed with bioelectrical impedance analysis. Physical activity and capacity were assessed using questionnaires and handgrip strength. Plasma (p)-glucose, p-lipids, hemoglobin A1c (HbA1c), p-adiponectin, and cytokines were measured. RESULTS: Among 164 patients with CAP, etiology did not affect admission levels of glucose, HbA1c, adiponectin, or lipids. Overall, 15.2% had known diabetes, 6.1% had undiagnosed diabetes, 51.3% had pre-diabetes, 81% had hyperglycemia, and 60% had low HDL-cholesterol, with no difference between groups. Body mass index, FM, and FFM were similar between groups, with 73% of the patients being characterized with abdominal obesity, although waist circumference was lower in patients with COVID-19. Physical capacity was similar between groups. More than 80% had low handgrip strength and low physical activity levels. Compared to patients with influenza, patients with COVID-19 had increased levels of interferon (IFN)-γ (mean difference (MD) 4.14; 95% CI 1.36-12.58; p = 0.008), interleukin (IL)-4 (MD 1.82; 95% CI 1.12-2.97; p = 0.012), IL-5 (MD 2.22; 95% CI 1.09-4.52; p = 0.024), and IL-6 (MD 2.41; 95% CI 1.02-5.68; p = 0.044) and increased IFN-γ (MD 6.10; 95% CI 2.53-14.71; p < 0.001) and IL-10 (MD 2.68; 95% CI 1.53-4.69; p < 0.001) compared to patients with bacterial CAP, but no difference in IL-1ß, tumor necrosis factor-α, IL-8, IL-18, IL-12p70, C-reactive protein, and adiponectin. CONCLUSION: Despite higher inflammatory response in patients with COVID-19, metabolic profile, body composition, and physical capacity were similar to patients with influenza and bacterial CAP.

Predictors of glucose metabolism and blood pressure among Ethiopian individuals with HIV/AIDS after one-year of antiretroviral therapy.

OBJECTIVE: Better understanding of glucose metabolism in patients with HIV after initiating antiretroviral therapy (ART) is important to target treatment and follow-up for diabetes risk and other non-communicable diseases in resource-limited settings. The aim of this study was to assess the changes and predictors of glucose metabolism and blood pressure among patients with HIV on ART for 12 months. METHODS: One-year follow-up of Ethiopian patients with HIV after initiation of ART was done. Outcomes were changes in fasting plasma glucose (FPG), and 30-minute (30mPG) and 2-hour plasma glucose (2hPG) after oral glucose tolerance test, glycated haemoglobin (HbA1c), fasting plasma insulin (p-insulin), homeostatic model assessment index for insulin resistance (HOMA-IR) and blood pressure.   RESULTS: The mean age was 33 years, and the majority were women. During the first 12 months, levels of all plasma glucose parameters decreased, while p-insulin (10B 3.1; 95% CI2.4, 4.0), HOMA-IR (10B 3.1; 95% CI2.3, 4.0) and systolic blood pressure (B 4.0; 95% CI2.5, 5.5) increased. Fat-free mass at baseline predicted higher increments in p-insulin, HOMA-IR and blood pressure; whereas, fat mass predicted higher increment in HbA1c. CONCLUSIONS: Among Ethiopian patients with HIV, blood pressure and insulin increased, and all glucose parameters declined during 12-month of ART. Only longer-term follow-up will tell us whether insulin increase is due to insulin resistance or from recovering ß-cells.

ß-cell dysfunction and insulin resistance in relation to pre-diabetes and diabetes among adults in north-western Tanzania: a cross-sectional study.

OBJECTIVE: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of ß-cell dysfunction and insulin resistance on pre-diabetes and diabetes. METHODS: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of ß-cell dysfunction and insulin resistance which was categorised as follows: normal ß-cell function and insulin sensitivity, isolated ß-cell dysfunction, isolated insulin resistance, and combined ß-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of ß-cell dysfunction and insulin resistance with outcome measures. RESULTS: ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated ß-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined ß-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance, respectively. CONCLUSIONS: ß-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: cross-sectional study in North-Western Tanzania.

BACKGROUND: Although the burden of impaired renal function is rising in sub-Saharan Africa (SSA), little is known about correlates of impaired renal function in the region. We determined factors associated with estimated glomerular filtration rate (eGFR) and impaired renal function in HIV-infected and HIV-uninfected adults. METHODS: We undertook cross-sectional analysis of data from 1947 adults at enrolment for a cohort study on diabetes and associated complications in HIV patients in Mwanza, north-western Tanzania. A structured questionnaire was used to collect data on sociodemography, smoking, alcohol, physical activity, antiretroviral therapy (ART) and anthropometry. We measured blood pressure, tested blood samples for creatinine, glucose and HIV, and performed Kato Katz for Schistosoma mansoni. Correlates of eGFR (mL/min/1.73 m2) and impaired renal function (eGFR< 60 mL/min/1.73 m2) were determined using linear regression and logistic regression, respectively. RESULTS: 655 (34%) participants were HIV-uninfected, 956 (49%) were ART-naive HIV-infected and 336 (17%) were HIV-infected adults on ART. The mean age was 41 years (SD12) and majority (59%) were females. Overall, the mean eGFR was 113.6 mL/min/1.73 m2 but 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naive HIV-infected and 129.5 mL/min/1.73 m2 in HIV-infected ART-experienced adults, and respective prevalence of impaired renal function was 7.0, 5.7, 8.1 and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol drinking, higher body mass index and diabetes mellitus. Anaemia was associated with 1.9 (95% Confidence Interval (CI):1.2, 2.7, p = 0.001) higher odds of impaired renal function compared to no anaemia and this effect was modified by HIV status (p value 0.02 for interaction). CONCLUSION: Impaired renal function is prevalent in this middle-aged study population. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults and those with high socioeconomic status. Interventions targeting modifiable risk factors such as alcohol and weight reduction are warranted.

HIV and metabolic syndrome in an Ethiopian population.

BACKGROUND: The global prevalence of metabolic syndrome (MS) is increasing due to lifestyle changes. Studies have found that MS is associated with human immunodeficiency virus (HIV) and antiretroviral treatment (ART), but controversies still exist on associations between HIV and MS. AIMS: To assess associations between HIV and MS among ART-naïve HIV positive individuals compared to HIV negative individuals. SUBJECTS AND METHODS: A cross-sectional study among ART-naïve HIV positive and HIV negative individuals recruited from HIV treatment and testing facilities in Ethiopia. Information was collected on components of MS: waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), blood pressure and fasting plasma glucose (FPG). Data were analysed using logistic and linear regression stratified by sex and adjusted for age, wealth and education. RESULTS: Data from 329 HIV positive and 100 HIV negative individuals were included. HIV positive status was associated with higher odds of MS in women (OR: 3.56, 95%CI: 1.25; 10.15) (n = 292), but not in men (OR: 0.98, 95%CI: 0.22; 4.30) (n = 137), interaction: p= .11. Associations between HIV and components of MS were strongest for HDL-C among women and for FPG among men. The most prevalent components of MS in HIV positive individuals were elevated triglycerides, reduced HDL-C and elevated FPG. CONCLUSIONS: HIV was associated with MS among ART-naïve women, suggesting that MS should be evaluated before initiating ART and monitored during treatment to identify those at risk of developing diabetes and cardiovascular disease (CVD).

Physical activity level among children recovering from severe acute malnutrition.

OBJECTIVE: To assess the level and predictors of physical activity at discharge among children recovering from severe acute malnutrition (SAM). METHODS: We conducted a prospective study among 69 children 6-59 months of age admitted with SAM for nutritional rehabilitation at Mulago National Referral Hospital, Uganda. Using hip-mounted triaxial accelerometers, we measured physical activity expressed as counts per minute (cpm) during the last three days of hospital treatment. As potential predictors, we assessed clinical and background characteristics, duration to transition phase and duration of hospitalisation, serum C-reactive protein and whole-blood docosahexaenoic acid (DHA). Multiple linear regression analyses were used to identify predictors of physical activity. RESULTS: The median (IQR) age was 15.5 (12.6; 20.5) months. At discharge, the mean (SD) movement was 285 (126) cpm. Physical activity was 43 (19; 67) cpm higher for each unit increase in weight-for-height z-score (WHZ) and 72 (36; 108) cpm higher for each centimetre increase in MUAC. Whole-blood DHA on admission was also a positive predictor of physical activity, whereas duration to transition phase and duration of hospitalisation were both negative predictors. CONCLUSION: The level of physical activity at discharge among children treated for SAM was low. WHZ, MUAC and DHA on admission were positive predictors of physical activity, whereas duration of stabilisation and hospitalisation was negative predictors of physical activity. These results suggest that assessment of physical activity may be used as a marker of recovery.

Undiagnosed Diabetes Mellitus in Community-Acquired Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diabetes mellitus is an important risk factor for community-acquired pneumonia, whereas the prevalence of undiagnosed diabetes mellitus and prediabetes in patients with community-acquired pneumonia is largely unknown. We aimed to determine the prevalence of prediabetes, undiagnosed diabetes mellitus, and risk factors associated with undiagnosed diabetes mellitus in a large European community-acquired pneumonia cohort. METHODS: This was a multicenter prospective cohort study of hospitals and private practices in Germany and Austria encompassing 1961 adults with community-acquired pneumonia included in the German Community-Acquired Pneumonia Competence Network (CAPNETZ) study between 2007 and 2014. The prevalence of undiagnosed diabetes mellitus and prediabetes was estimated based on hemoglobin A1c measurements. Logistic regression was used to assess risk factors for undiagnosed diabetes mellitus. RESULTS: Fifteen percent of patients had known diabetes mellitus. Among patients without known diabetes mellitus, 5.0% had undiagnosed diabetes mellitus and 37.5% had prediabetes. Male sex (odds ratio [OR], 2.45 [95% confidence interval {CI}, 1.35-4.45]), body mass index ≥25 kg/m2 (OR, 2.64 [95% CI, 1.48-4.72]), and hyperglycemia at admission (6-11 mM: OR, 2.93 [95% CI, 1.54-5.60] and ≥11 mM: OR, 44.76 [95% CI, 17.58-113.98]) were associated with undiagnosed diabetes mellitus. Patients with undiagnosed diabetes mellitus had a higher 180-day mortality rate compared to patients without diabetes mellitus (12.1% vs 3.8%, respectively; P = .001). CONCLUSIONS: Undiagnosed diabetes mellitus was prevalent among community-acquired pneumonia. Male sex, overweight, and hyperglycemia at admission were associated with undiagnosed diabetes mellitus. The long-term mortality among patients with undiagnosed diabetes mellitus was high compared to patients without diabetes mellitus.

Correlates of Physical Activity among Young Children with Moderate Acute Malnutrition.

OBJECTIVE: To assess the levels of physical activity among young children with moderate acute malnutrition and to identify clinical, biochemical, anthropometric, and sociodemographic correlates of physical activity. STUDY DESIGN: In a cross-sectional study, 1609 children aged 6-23 months wore a triaxial accelerometer (ActiGraph GT3x+; ActiGraph, Pensacola, Florida) for 6 consecutive days, from which total physical activity were determined. Data on morbidity were collected based by history and physical examination, and serum C-reactive protein and α1-acid glycoprotein were measured. RESULTS: A total of 1544 (96%) children had physical activity measured, of whom 1498 (97%) completed 6 consecutive days of physical activity recording with a daily median wear time of 24 hours. The mean (±SD) total physical activity was 707 (±180) vector magnitude counts per minute (cpm). Age was negatively correlated with physical activity; compared with children below 12 months of age, those 12-17 months of age, and 18-23 months of age had 51 (95% CI, 26; 75) and 106 (95% CI, 71; 141) cpm lower physical activity, respectively. Fever and malaria were associated with 49 (95% CI, 27; 70) and 44 (95% CI, 27; 61) cpm lower activity, respectively. Elevated serum C-reactive protein and α1-acid glycoprotein were both negative correlates of physical activity, and hemoglobin was a positive correlate. CONCLUSIONS: Physical activity declines with age in children with moderate acute malnutrition and is also inversely related to infection and inflammatory status. Future studies are needed to ascertain cause and effect of these associations. TRIAL REGISTRATION: Controlled-Trials.com: ISRCTN42569496.

Cardiovascular risk factors in rural Kenyans are associated with differential age gradients, but not modified by sex or ethnicity.

BACKGROUND: The relationship between metabolic disease and the non-modifiable risk factors sex, age and ethnicity in Africans is not well-established. AIM: This study aimed to describe sex, age and ethnicity differences in blood pressure (BP) and lipid status in rural Kenyans. SUBJECTS AND METHODS: A cross-sectional study was undertaken among rural Kenyans. BP and pulse rate (PR) were measured while sitting and fasting blood samples were taken for analysis of standard lipid profile. Standard anthropometric measurements were collected. Physical activity energy expenditure was obtained objectively and lifestyle data were obtained using questionnaires. RESULTS: In total, 1139 individuals (61.0% women) participated aged 17-68 years. Age was positively associated with BP and plasma cholesterol levels. Sitting PR was negatively associated with age in women only (sex-interaction p < 0.001). Ethnicity did not modify any of the age-associations with haemodynamic or lipid outcomes. Differences in intercept between women and men were found in all parameters except for diastolic BP (p = 0.154), with men having lower HDL-C but higher values in all other cardiovascular risk factors. CONCLUSION: BP and plasma cholesterol levels increase with age at a similar gradient in men and women, but absolute levels of the majority of the risk factors were higher in men.

Nutritional supplementation increases rifampin exposure among tuberculosis patients coinfected with HIV.

Nutritional supplementation to tuberculosis (TB) patients has been associated with increased weight and reduced mortality, but its effect on the pharmacokinetics of first-line anti-TB drugs is unknown. A cohort of 100 TB patients (58 men; median age, 35 [interquartile range {IQR}, 29 to 40] years, and median body mass index [BMI], 18.8 [17.3 to 19.9] kg/m(2)) were randomized to receive nutritional supplementation during the intensive phase of TB treatment. Rifampin plasma concentrations were determined after 1 week and 2 months of treatment. The effects of nutritional supplementation, HIV, time on treatment, body weight, and SLCO1B1 rs4149032 genotype were examined using a population pharmacokinetic model. The model adjusted for body size via allometric scaling, accounted for clearance autoinduction, and detected an increase in bioavailability (+14%) for the patients in the continuation phase. HIV coinfection in patients not receiving the supplementation was found to decrease bioavailability by 21.8%, with a median maximum concentration of drug in serum (Cmax) and area under the concentration-time curve from 0 to 24 h (AUC0-24) of 5.6 µg/ml and 28.6 µg · h/ml, respectively. HIV-coinfected patients on nutritional supplementation achieved higher Cmax and AUC0-24 values of 6.4 µg/ml and 31.6 µg · h/ml, respectively, and only 13.3% bioavailability reduction. No effect of the SLCO1B1 rs4149032 genotype was observed. In conclusion, nutritional supplementation during the first 2 months of TB treatment reduces the decrease in rifampin exposure observed in HIV-coinfected patients but does not affect exposure in HIV-uninfected patients. If confirmed in other studies, the use of defined nutritional supplementation in HIV-coinfected TB patients should be considered in TB control programs. (This study has the controlled trial registration number ISRCTN 16552219.).