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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. [ABSTRACT FROM AUTHOR]

Ceftolozane‐tazobactam is a new β‐lactam/β‐lactamase inhibitor combination approved by the U.S. Food and Drug Administration in 2019 for the treatment of hospital‐acquired and ventilator‐associated pneumonia. The combination is a particularly potent inhibitor of penicillin‐binding proteins with higher affinity than other β‐lactam agents. Persons with cystic fibrosis (pwCF) often harbour resistant Gram‐negative bacteria in the airways and need antibiotics to prevent declining lung function. To test whether the introduction of ceftolozane‐tazobactam in the period 2015–2020 led to a bacterial population level increase in cephalosporin resistance in a Danish CF population. In vitro, activity of ceftolozane‐tazobactam was evaluated by susceptibility testing of clinical Pseudomonas aeruginosa isolated from pwCF from January 1, 2015, to June 1, 2020. Six thousand three hundred thirty two isolates collected from 210 adult pwCF were included. Thirty pwCF were treated with ceftolozane‐tazobactam at least once. Ceftolozane‐tazobactam exposure did not increase cephalosporin resistance on an individual or population level. However, resistance to ceftolozane‐tazobactam was recorded despite no prior exposure in four pwCF. Compared to ceftazidime, ceftolozane‐tazobactam had a better in vitro activity on P. aeruginosa. The percentage of non‐mucoid P. aeruginosa isolates susceptible to ceftolozane‐tazobactam were higher or equal to 5 other β‐lactams. Ceftolozane‐tazobactam expands the armamentaria against P. aeruginosa with acceptable levels for a selection of drug resistance. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization worldwide. Bed rest with low levels of physical activity is common during periods of hospitalization and leads to functional decline as well as increased risk of complications. The aim of this study is to assess the effect of supervised physical training during hospitalization with CAP compared with standard usual care for CAP on length of hospital stay, risk of readmission, mortality risk, physical capacity, muscle and fat mass, muscle strength, metabolic function, systemic inflammation, health-related quality of life, and physical activity level.Methods: This study is a randomized controlled trial with three parallel experimental arms. Based on a sample size calculation, a total of 210 patients admitted with CAP at Nordsjællands Hospital, Hillerød, Denmark, will be recruited. Patients will be randomly allocated (1:1:1) to either (1) standard usual care, (2) standard usual care combined with in-bed cycling, or (3) standard usual care combined with exercises from a booklet. The primary outcome is differences in length of hospital stay between groups, with secondary outcomes being differences between groups in time to (1) 90-day readmission and (2) 180-day mortality. Further secondary outcomes are differences in changes from baseline between groups in (3) lean mass, (4) fat mass, (5) fat-free mass, (6) physical capacity, (7) health-related quality of life, (8) systemic inflammation, and (9) physical activity level after discharge. Data on length of hospital stay, readmission, and mortality will be collected from patient files, while total lean, fat, and fat-free mass will be quantitated by dual-energy x-ray absorptiometry and bioelectrical impedance analysis. Physical function will be assessed using grip strength, 30-s chair stand tests, and Barthel Index-100. Health-related quality of life will be assessed with the EQ-5D-5L questionnaire. Systemic inflammation will be assessed in blood samples, while accelerometers are used for measuring physical activity.Discussion: If a simple physical training program appears to diminish the impact of critical illness and hospitalization on clinical outcome, mobility, and health-related quality of life, it may lead to novel therapeutic approaches in the treatment of patients hospitalized with CAP.Trial Registration: ClinicalTrials.gov NCT04094636 . Registered on 1 April 2019. [ABSTRACT FROM AUTHOR]

Background: A frequent comorbidity in cystic fibrosis (CF) is CF related diabetes (CFRD) caused by a gradual decline in insulin secretion. The reduction in the anabolic hormone, insulin, might explain the weight loss that precedes onset of CFRD. We investigated the association between muscle and fat mass in relation to glucose tolerance and insulin function. Methods: In a cross-sectional study with CF patients (⩾18 years), we conducted an oral glucose tolerance test and dual energy X-ray absorptiometry scan (DXA). Based on plasma glucose, glucose tolerance was defined as normal (NGT): 1-hour <11.1 mmol/L and 2-hour <7.8 mmol/L, impaired (IGT): 2-hour ⩾7.8 and <11.1 mmol/L or CFRD: 2-hour ⩾11.1 mmol/L. Insulin resistance (HOMA-IR) was derived from fasting levels of plasma glucose and plasma insulin, and fat-free and fat mass index (kg/m2) from DXA. Associations were evaluated using linear regression models adjusted for age, sex, and pancreas insufficiency. Results: Among 79 CF patients with exocrine pancreas insufficiency, impairment of glucose tolerance corresponded to reduced insulin secretion. In the IGT group the fat-free mass index (FFMI) was 1.2 kg/m2 (95% CI: [−2.3, −0.03] kg/m2, P =.044) lower compared to the NGT group. FFMI increased insignificantly by 0.4 kg/m2 (95% CI: [−0.6, 1.5] kg/m2, P =.422) among the insulin-treated CFRD group compared to IGT. Fat mass index (FMI) was not different between groups but tended to decrease with glucose tolerance impairment. For each 100 pmol/L increase in fasting insulin FFMI increased by 1.77 kg/m2 (95% CI: [0.21, 3.33] kg/m2/pmol/L/100) and FMI increased by 6.15 kg/m2 (95% CI: [3.87, 8.44] kg/m2/pmol/L/100). In multivariate analyses, HOMA-IR was positively associated with FFMI (β = 0.5 kg/m2/HOMA-IR, 95% CI: [0.08, 0.92] kg/m2/HOMA-IR, P =.021) and FMI (β = 1.5 kg/m2/HOMA-IR, 95% CI: [0.87, 2.15] kg/m2/HOMA-IR, P <.001). Conclusions: Muscle mass was significantly lower among participants with impaired glucose tolerance (IGT), while muscle mass was normalized among those treated with insulin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Abdominal obesity predict metabolic syndrome parameters at low levels of waist circumference (WC) in Africans. At the same time, the African lipid profile phenotype of low high-density lipoprotein (HDL) cholesterol without concomitant elevated triglyceride levels renders high triglyceride levels detrimental to cardiometabolic health unsuitable for identifying cardiometabolic risk in black African populations. Objectives: We aimed to identify simple clinical measures for cardiometabolic risk based on WC and HDL in an adult Kenyan population in order to determine which of the two predictors had the strongest impact. Methods: We used linear regression analyses to assess the association between the two exposure variables WC and HDL with cardiometabolic risk factors including ultrasound-derived visceral (VAT) and subcutaneous adipose tissue (SAT) accumulation, fasting and 2-h venous glucose, fasting insulin, fasting lipid profile, and blood pressure in adult Kenyans (n = 1 370), and a sub-population with hyperglycaemia (diabetes and pre-diabetes) (n = 196). The same analyses were performed with an interaction between WC and HDL to address potential effect modification. Ultrasound-based, semi-quantitative hepatic steatosis assessment was used as a high-risk measure of cardiometabolic disease. Results: Mean age was 38.2 (SD 10.7) (range 17–68) years, mean body mass index was 22.3 (SD 4.5) (range 13.0–44.8) kg/m2, and 57.8% were women. Cardiometabolic risk was found in the association between both WC and HDL and all outcome variables (p<0.05) except for HDL and SAT, fasting and 2-h venous glucose. Additive cardiometabolic risk (WC and HDL interaction) was found for SAT, low-density lipoprotein cholesterol, and triglycerides. No differences in the association between WC and HDL and the outcome variables were found when comparing the full study population and the hyperglycaemia sub-population. Increase in WC and HDL were both associated with hepatic steatosis (OR 1.09, p<0.001, and OR 0.46, p = 0.031, respectively). Conclusion: In adult Kenyans, increasing WC identified more cardiometabolic risk factors compared to HDL. [ABSTRACT FROM AUTHOR]

Childhood obesity is increasing especially in Latinos and early intervention is essential to prevent later obesity complications. Latino children (n = 201) recruited at two San Francisco hospitals were assessed at birth including infant anthropometrics and feeding practices and followed to age 9 with annual anthropometric assessments. We evaluated the relationship between perinatal risk factors and obesity at age 9 and chronic obesity (obesity at both 5 and 9 years). Higher birthweight [odds ratio (OR) 2.48, 95% confidence interval (CI) 1.06-5.81] and maternal pre-pregnancy body mass index (BMI) (OR 1.09, 95% CI 1.00-1.18) were associated with increased risk for obesity at 9 years. Higher maternal pre-pregnancy BMI (OR 1.10, 95% CI 1.01-1.20) was associated with chronic obesity. Additionally, prenatal depression symptoms were protective (OR 0.33, 95% CI 0.11-0.94) against chronic obesity. We found no association between maternal age and education, exclusive breastfeeding at 4-6 weeks, rapid infant weight gain, and obesity or chronic obesity. Perinatal risk factors for obesity including higher birthweight and maternal pre-pregnancy BMI persisted until age 9, whereas, other variables significant at age 5 in our cohort and other populations including exclusive breastfeeding and rapid infant weight gain were no longer associated with increased risk. [ABSTRACT FROM AUTHOR]

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 8805;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. [ABSTRACT FROM AUTHOR]

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-interactionp < 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. [ABSTRACT FROM PUBLISHER]

Background: Diabetes is increasingly common in TB endemic regions and plays a role as a possible risk factor for increased progression from latent TB infection (LTBI) to active TB disease. Although the pathophysiological mechanisms are not fully understood, the immune system is weakened in diabetes patients and therefore the validity of interferon gamma release assays (IGRA) may be compromised. The aim of the present study was to assess the association between diabetes and Mycobacterium tuberculosis (Mtb) antigen-specific interferon gamma (IFN-γ) release in a TB endemic area among culture-confirmed TB patients and non-TB controls. Methods: Culture-confirmed pulmonary TB patients ( n = 187) and healthy non-TB neighbourhood controls ( n = 190) from Mwanza, Tanzania were tested for the presence of circulating T cells recognizing Mtb antigens using an IGRA. The diabetes status of all participants was assessed using a standard oral glucose tolerance test. The impact of diabetes on the performance of the IGRA was estimated using robust linear and logistic regression. Results: Compared to normal glucose tolerance, diabetes was associated with reduced levels of Mtb-specific IFN-γ. Increasing levels of fasting blood glucose (B − 0.3, 95% confidence interval − 0.6 to − 0.03, p = 0.033) was negatively associated with IFN-γ. Although TB patients had higher specific and lower unspecific mitogen IFN-γ responses compared to non-TB controls, the association between diabetes and IFN-γ did not depend on TB status. Conclusion: Diabetes is associated with lower levels of Mtb antigen-specific IFN-γ, and the validity of IFN- γ tests for LTBI may be questionable in individuals with diabetes. [ABSTRACT FROM AUTHOR]

Objective Strong evidence suggests diabetes may be associated with tuberculosis ( TB) and could influence TB treatment outcomes. We assessed the role of diabetes on sputum culture conversion and mortality among patients undergoing TB treatment. Methods A total of 1250 Tanzanian TB patients were followed prospectively during TB treatment with sputum culture after 2 and 5 months. Survival status was assessed at least 1 year after initiation of treatment. At baseline, all participants underwent testing for diabetes and HIV, and the serum concentration of the acute phase reactant alpha-1 glycoprotein ( AGP) was determined. Results There were no differences between participants with and without diabetes regarding the proportion of positive cultures at 2 (3.8% vs. 5.8%) and 5 (1.3% vs. 0.9%) months ( P > 0.46). However, among patients with a positive TB culture, relatively more patients with diabetes died before the 5-month follow-up. Within the initial 100 days of TB treatment, diabetes was associated with a fivefold increased risk of mortality ( RR 5.09, 95% CI 2.36; 11.02, P < 0.001) among HIV uninfected, and a twofold increase among HIV co-infected patient ( RR 2.33 95% CI 1.20; 4.53, P = 0.012), while diabetes was not associated with long-term mortality. Further adjustment with AGP did not change the estimates. Conclusion Diabetes considerably increases risk of early mortality during TB treatment. The effect may not be explained by increased severity of TB, but could be due to impaired TB treatment response. Research is needed to clarify the mechanism and to assess whether glycaemic control improves survival. [ABSTRACT FROM AUTHOR]

We previously proposed the term 'opportunistic non‐communicable diseases (NCDs)' to raise awareness of how NCDs thrive in societies with inadequate healthcare services. However, we did not anticipate that within the next year the new coronavirus disease (COVID‐19) would sweep the globe. Lockdowns became the primary strategy for mitigation in most countries. However, the extensive restrictions and allocation of resources towards the containment of the pandemic have likely served as a catalyst of NCDs, especially in populations, societies and individuals already at high risk. We are presenting evidence to qualify two primary factors responsible for the potential impact on the development of NCDs during the COVID‐19 pandemic. The first is disrupted healthcare services including avoidance and postponement of healthcare visits. The second is effects of changing lifestyle and living conditions including isolation, loss of job and income. The accumulated effect of these factors will likely further accelerate the development of NCDs and impair their management, especially in low‐ and middle‐income countries. Insufficient vaccination coverage due to inequality in vaccine distribution and vaccine hesitancy left room for the incubation of immune‐evasive variants that threatened to sustain or reinitiate the pandemic. We believe the concept of opportunistic NCDs and the potential catalytic effect that pandemics may have on the development of NCDs and their management, should be used as further arguments to secure equal vaccine distribution, promote global vaccine acceptance and to speed up and increase investments in primary health care in low‐ and middle‐income countries to cope with the already existing NCD crisis and to prepare for future epidemics. [ABSTRACT FROM AUTHOR]

Objective Diabetes is associated with pulmonary tuberculosis (TB), possibly due to impaired immunity, and diabetes may exacerbate the clinical manifestations of TB. Our aim was to assess the role of diabetes in the clinical manifestations of TB. Methods We studied 1250 patients with pulmonary TB in an urban population in a cross-sectional study in Tanzania. All participants were tested for diabetes and HIV co-infection, and TB culture intensity was assessed. Levels of white blood cells, haemoglobin, acute phase reactants, CD4 count and HIV viral load were measured, and a qualitative morbidity questionnaire was used to identify the prevalence of disease-related symptoms. Results Tuberculosis patients with diabetes had a higher neutrophil count (B 0.5 × 109 cells/l, 95% CI 0.2; 0.9, P = 0.001) than non-diabetic TB patients. Serum C-reactive protein (B 18.8 mg/l, CI 95% 8.2; 29.4, P = 0.001) and alpha-1-acid glycoprotein (B 0.2 g/l, CI 95% 0.03; 0.3, P = 0.02) were similarly higher in patients with diabetes. Diabetes did not affect culture intensity or HIV status, but self-reported fever was three times higher among participants with diabetes than in those without diabetes (OR 2.9, CI 95% 1.5; 5.7, P = 0.002). Conclusion Diabetes is associated with small changes in the manifestations of TB, but may have little clinical significance. [ABSTRACT FROM AUTHOR]

Background: Due to the association between diabetes and pulmonary tuberculosis (TB), diabetes may threaten the control of TB. In a prospective cohort study nested in a nutrition trial, we investigated the role of diabetes on changes in anthropometry, grip strength, and clinical parameters over a five months follow-up period. Methods: Among pulmonary TB patients with known diabetes status, we assessed anthropometry and clinical parameters (e.g. haemoglobin) at baseline and after two and five months of TB treatment. A linear mixed-effects model (repeated measurements) was used to investigate the role of diabetes during recovery. Results: Of 1205 TB patients, the mean (standard deviation) age was 36.6 (13.0) years, 40.9% were females, 48.9% were HIV co-infected, and 16.3% had diabetes. TB patients with diabetes co-morbidity experienced a lower weight gain at two (1.3 kg, CI95% 0.5; 2.0, p = 0.001) and five months (1.0 kg, CI95% 0.3; 1.7, p = 0.007). Similarly, the increase in the level of haemoglobin was lower among TB patients with diabetes co-morbidity after two (Δ 0.6 g/dL, CI95% 0.3; 0.9 p<0.001) and five months (Δ 0.5 g/dL, CI95% 0.2; 0.9 p = 0.004) of TB treatment, respectively. Conclusion: TB patients initiating TB treatment with diabetes co-morbidity experience delayed recovery of body mass and haemoglobin, which are important for the functional recovery from disease. [ABSTRACT FROM AUTHOR]

Background: Diabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent. Methods: A case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants. Results: Among 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p,0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants. Conclusion: Diabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control. [ABSTRACT FROM AUTHOR]

As strategies targeting undernutrition and infections become increasingly successful in low- and middle-income countries (LMICs), a second challenge has appeared, namely premature onset of non-communicable diseases (NCDs). In LMICs, NCDs are often related to exposure to undernutrition and infections. As NCDs strike societies and individuals with impaired resistance or a deficient health (care) state, why not label such diseases 'opportunistic', in analogy with opportunistic infections attacking individuals with HIV? We propose the concept of opportunistic NCDs, hoping that fighting against infections, and for better maternal and child health, is becoming acknowledged as essential for the early prevention of NCDs. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess L‐lactate and D‐lactate in endotracheal aspirate from intubated patients hospitalized at the intensive care unit and explore their use as diagnostic biomarkers for inflammation and lower respiratory tract infections (LRTI). Tracheal aspirates from 91 intubated patients were obtained at time of intubation and sent for microbiological analyses, neutrophil count, and colorimetric lactate measurements. We compared the concentration of lactate from patients with microbiological verified LRTI or clinical/radiological suspicion of LRTI with a control group. In addition, associations between inflammation and the lactate isomers were examined by correlating L‐lactate and D‐lactate with sputum neutrophils and clinical assessments. The concentration of L‐lactate was increased in aspirates with verified or suspected LRTI (p < 0.001) relative to the control group at Day 0. Connections between L‐lactate and inflammation were indicated by the correlation between neutrophils and L‐lactate (p < 0.001). We found no increase in sputum D‐lactate from patients with verified or suspected LRTI relative to the control group and D‐lactate was not correlated with neutrophils. L‐lactate was found to be a potential indicator for inflammation and LRTI at the time of intubation. An association was found between neutrophil count and L‐lactate. Interestingly, the increase of L‐lactate in the control group after intubation may suggest that intubation challenges the host response by inflicting tissue damage or by introducing infectious microbes. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia (CAP) causes a large burden of disease. Due to difficulties in obtaining representative respiratory samples and insensitive standard microbiological methods, the microbiological aetiology of CAP is difficult to ascertain. With a few exceptions, standard-of-care diagnostics are too slow to influence initial decisions on antimicrobial therapy. The management of CAP is therefore largely based on empirical treatment guidelines. Empiric antimicrobial therapy is often initiated in the primary care setting, affecting diagnostic tests based on conventional bacterial culture in hospitalized patients. Implementing rapid molecular testing may improve both the proportion of positive tests and the time it takes to obtain test results. Both measures are important for initiation of pathogen-targeted antibiotics, involving rapid de-escalation or escalation of treatment, which may improve antimicrobial stewardship and potentially patient outcome.Methods: Patients presenting to the emergency department of Haukeland University Hospital (HUH) in Bergen, Norway, will be screened for inclusion into a pragmatic randomised controlled trial (RCT). Eligible patients with a suspicion of CAP will be included and randomised to receive either standard-of-care methods (standard microbiological testing) or standard-of-care methods in addition to testing by the rapid and comprehensive real-time multiplex PCR panel, the BioFire® FilmArray® Pneumonia Panel plus (FAP plus) (bioMérieux S.A., Marcy-l'Etoile, France). The results of the FAP plus will be communicated directly to the treating staff within ~2 h of sampling.Discussion: We will examine if rapid use of FAP plus panel in hospitalized patients with suspected CAP can improve both the time to and the proportion of patients receiving pathogen-directed treatment, thereby shortening the exposure to unnecessary antibiotics and the length of hospital admission, compared to the standard-of-care arm. The pragmatic design together with broad inclusion criteria and a straightforward intervention could make our results generalizable to other similar centres.Trial Registration: ClinicalTrials.gov NCT04660084 . Registered on December 9, 2020. [ABSTRACT FROM AUTHOR]

In Denmark, tuberculous meningitis is rare. Central nervous system (CNS) involvement with Mycobacterium bovis is even rarer and has only been seen three times since 1992. We present a case of M. bovis meningitis in a previously healthy young Nigerian-born male, who had been exposed to unpasteurized dairy products in Nigeria but had no known contact with larger mammals. Before the development of meningitis, the patient had several contacts with the health system due to fever and non-specific symptoms. Finally, upon hospital admission, the patient was diagnosed with M. tuberculosis complex meningitis and treated empirically. After 13 days he was discharged without neurological sequelae. Later, the culture revealed M. bovis and treatment was adjusted accordingly. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre‐emptive treatment of lung disease and other CF‐related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high‐dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side‐effects and costs. [ABSTRACT FROM AUTHOR]

Objective: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of β-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 β-cell dysfunction and insulin resistance which was categorised as follows: normal β-cell function and insulin sensitivity, isolated β-cell dysfunction, isolated insulin resistance, and combined β-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 β-cell dysfunction and insulin resistance with outcome measures.Results: β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated β-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 β-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 β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance, respectively.Conclusions: β-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. [ABSTRACT FROM AUTHOR]

Bacterial aerobic respiration may determine the outcome of antibiotic treatment in experimental settings, but the clinical relevance of bacterial aerobic respiration for the outcome of antibiotic treatment has not been tested. Therefore, we hypothesized that bacterial aerobic respiration is higher in sputum from patients with acute lower respiratory tract infections (aLRTI), than in sputum from patients with chronic LRTI (cLRTI), where the bacteria persist despite antibiotic treatment. The bacterial aerobic respiration was determined according to the dynamics of the oxygen (O2) concentration in sputum from aLRTI patients (n = 52). This result was evaluated by comparison to previously published data from patients with cLRTI. O2 consumption resulting in anoxic zones was more frequent in sputum with detected bacterial pathogens. The bacterial aerobic respiration in aLRTI sputum approximated 55% of the total O2 consumption, which was significantly higher than previously published for cLRTI. The bacterial aerobic respiration in sputum was higher in aLRTI patients than previously seen in cLRTI patients, indicating the presence of bacteria with a sensitive physiology in aLRTI. These variations in bacterial physiology between aLRTI patients and cLRTI patients may contribute the huge difference in treatment success between the two patient groups. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is commonly used to guide community-acquired pneumonia (CAP) treatment. A positive association between admission glucose and CRP levels has been observed in patients with CAP. The associations between prediabetes, unknown diabetes, acute-on-chronic hyperglycaemia, and CRP levels, and between admission CRP levels and insulin resistance (IR) in CAP, remain unexplored. This study investigated the associations firstly between chronic, acute, and acute-on-chronic hyperglycaemia and CRP levels, and secondly between admission CRP levels and IR in CAP. In a prospective cohort study of adults with CAP, the associations between chronic, acute, and acute-on-chronic hyperglycaemia (admission glucose minus HbA1c-derived average glucose) and CRP levels until admission day 3 were modelled with repeated-measures linear mixed models. IR was estimated with the homeostasis model assessment of IR (HOMA-IR). The association between admission CRP levels and HOMA-IR was modelled with linear regression. In 540 patients, no association between chronic, acute, or acute-on-chronic hyperglycaemia and CRP levels was found. In 266 patients, every 50 mg/L increase in admission CRP was associated with a 7% (95% CI 1–14%) higher HOMA-IR. In conclusion, our findings imply that hyperglycaemia does not influence CRP levels in patients with CAP, although admission CRP levels were positively associated with IR. [ABSTRACT FROM AUTHOR]

• Hemoglobin A1c (HbA1c) declined after initiating elexacaftor/tezacaftor/ivacaftor. • HbA1c declined irrespective of age, sex, and baseline glucose tolerance status. • Insulin use was unchanged after initiation with elexacaftor/tezacaftor/ivacaftor. • In those with diabetes, continuous glucose monitoring measures were also unaltered. Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI. We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment. Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters. In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article related to height as an anticipation marker for survival during a tuberculosis treatment.

Background: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania. Methods: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes. Results: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25–3.03; OGTT: RRR = 1.90, 95% CI 0.96–3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93–4.34; OGTT: RRR = 1.61, 95% CI 1.22–2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT. Conclusions: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes. [ABSTRACT FROM AUTHOR]

The article presents a study which examined whether traditional Western population risk factors for diabetes are effective in identifying individuals with diabetes among urban Tanzanians. The study was authorized by the Medical Research Coordinating Committee of the National Institute for Medical Research in Tanzania. In the study, diabetes was diagnosed by using the standard oral glucose tolerance test (OGTT).

The article discusses a case-control study conducted in Mwanza, Tanzania to examine prevention of development of Tuberculosis (TB) by using Bacillus Calmette-Guerin (BCG) vaccines. It reports that multivariable conditional logistic regression model was used to analyze association between several factors including TB, BCG vaccination and HIV. The study concluded that the vaccine provides overall protection against risk of developing active TB irrespective of HIV status in adults.

Supplemental Digital Content is Available in the Text. Background: Higher nocturnal heart rate and lower nocturnal heart rate variability (HRV) is associated with increased cardiovascular disease mortality. Longitudinal studies on nocturnal HRV in people living with HIV (PLWH) are lacking. Methods: We conducted a 1-year prospective cohort study of adult PLWH and HIV-uninfected community controls in northwestern Tanzania. At enrollment, we collected data on cardiovascular risk factors and tested blood samples for hemoglobin, insulin, CD4 cell count, and C-reactive protein. We measured nocturnal HRV and heart rate at baseline and first-year follow-up. Mixed effect linear regression was used to determine predictors of lower HRV. Results: Of the 111 enrolled participants (74 PLWH and 37 HIV-uninfected adults), 57.7% were female and the median age was 40 years. Over 1 year of follow-up, the average nocturnal heart rate was 4.5 beats/minute higher in PLWH (P = 0.006). In the fully adjusted model (with age, sex, nocturnal heart rate, and diabetes), average nocturnal HRV was 10.5 milliseconds lower in PLWH compared with HIV-uninfected adults (P = 0.03). Unlike with nocturnal heart rate, nocturnal HRV did not improve after 1 year of ART in PLWH or HIV-uninfected adults (fully adjusted change = −2.5 milliseconds, P = 0.45). Lower educational attainment, lesser pancreatic β-cell function, and anemia were associated with higher HRV. Conclusions: Nocturnal parasympathetic nervous system function was persistently lower in PLWH compared with HIV-uninfected adults even after antiretroviral therapy initiation. Improving nocturnal autonomic nervous system function could be a target for cardiovascular disease prevention in PLWH. [ABSTRACT FROM AUTHOR]

Background With improved prognosis of CF, comorbidities including chronic kidney disease (CKD) are becoming increasingly important. Identification of those at highest CKD risk is hence a priority. Methods In this cross-sectional study, adults with CF attending the Copenhagen CF Centre at Rigshospitalet with ≥ 2 measurements of serum creatinine from 2013 to 2015 were included. Data was obtained from an electronic CF database, which contains anonymised clinical and laboratory data on all individuals attending the clinic. CKD was defined as a confirmed (≥ 3 months apart) estimated glomerular filtration rate ≤ 60 mL/min/1.73m 2 . Results Of 181 individuals, the CKD prevalence was 2.7% and increased to 11% after inclusion of lung transplanted patients. Individuals with CKD were generally older (median 39 (IQR, 36–45) vs. 31 (IQR, 24–39) years; p < 0.001), diabetic (86% vs. 41%, p < 0.001), with longer median duration of chronic pulmonary infection (28.3 (20.0–35.8) vs. 20.0 (9.9–34.7) years; p = 0.008) and with longer intravenous aminoglycosides use (606 (IQR, 455–917) vs. 273 (IQR, 91–826) days, p = 0.005). Conclusions The CKD prevalence is high and related to age, diabetes, chronic infection, transplantation and aminoglycosides use. These observations call for longitudinal studies investigating CKD predictors in adults with CF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD. Methods: An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline. Discussion: Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD. Trial registration: ClinicalTrials.gov NCT04873856. Registered on May 3, 2021. [ABSTRACT FROM AUTHOR]

Background and Objectives: Mola (Amblypharyngodon mola) is a nutrient-rich, small fish found in ponds and rice fields in Bangladesh. The aim of the present intervention was to assess the effect of mola consumption on iron status in children with marginal vitamin A status.Methods and Study Design: Bangladeshi children (n=196), aged 3-7 years, with marginal vitamin A status were randomly allocated to one of three intervention groups served different fish curries: mola curry (experimental group); rui (Labeo rohita) curry with added retinyl palmitate (positive control group); or rui curry (negative control group). The intervention meals were served 6 days/week for 9 weeks. The experimental and positive control meals were designed to contain similar amounts of retinol activity equivalents per portion. The mola curry contained four times more iron compared to the rui curries due to different iron content in the two fish species. Haemoglobin, ferritin, serum transferrin receptor and Creactive protein were measured at screening and endpoint.Results: In the experimental group receiving mola, serum transferrin receptor concentration declined 0.73 mg/L (95% CI 0.17, 1.28, p=0.01) compared to the positive control group, while there were no differences between groups in ferritin or haemoglobin.Conclusions: Consumption of mola instead of rui has potentially an effect on iron status in children with marginal vitamin A status, seen as a decrease in serum transferrin receptor concentration. [ABSTRACT FROM AUTHOR]

Background: Impaired functional status is a risk factor for hospitalization in patients with community-acquired pneumonia (CAP). The aim was to determine the influence of functional status and physical activity level on severe outcomes, including length of stay, admission to the intensive care unit (ICU), readmission, and mortality in patients with CAP. Methods: A prospective cohort study among patients hospitalized with CAP. Functional status was assessed with the Barthel index and grip strength, and physical activity level was assessed using the international physical activity questionnaire. Linear regression was used to assess the association with length of stay, and logistic regression was used to assess the risk of severe outcomes. Results: Among 355 patients admitted with CAP, 18% had a low Barthel index (<80), 45% had a low grip strength, and 75% had a low physical activity level. Low Barthel index was associated with increased risk of ICU admission (OR 3.6, 95% CI 1.2–10.9), longer length of stay (27.9%, 95% CI 2.3–59.7%), readmission within 30, 90, and 180 days (OR 2.1–2.4, p < 0.05), and mortality within 90 and 180 days (OR 4.2–5.0, p < 0.05). Low grip strength was associated with increased risk of 90 days readmission (OR 1.6, 95% CI 1.0–2.6, p < 0.05) and mortality within 30, 90, and 180 days (OR 2.6–3.2, p < 0.05). Low physical activity level was associated with increased risk of readmission within 90 and 180 days (OR 1.8–2.1, p < 0.05) and mortality within 30, 90, and 180 days (OR 3.3–5.5, p < 0.05). Conclusions: Impaired functional status and low physical activity level were associated with a longer length of stay and increased risk of ICU admission, readmission, and mortality in patients hospitalized with CAP. Routine assessment of functional status and physical activity level in clinical care could enable early identification of individuals with excess risk for a poor prognosis. Trial registration: ClinicalTrials.gov, NCT03795662. [ABSTRACT FROM AUTHOR]

Background: Bed rest with limited physical activity is common during admission. The aim was to determine the association between daily step count and physical activity levels during and after admission with community-acquired pneumonia (CAP) and the risk of readmission and mortality. Methods: A prospective cohort study of 166 patients admitted with CAP. Step count and physical activity were assessed with accelerometers during and after admission and were categorised as sedentary, light, or moderate-vigorous physical activity. Linear regression was used to assess the association between step count and length of stay. Logistic regression was used to assess the association between step count, physical activity level, and risk of readmission and mortality. Results: Patients admitted with CAP were sedentary, light physically active, and moderate-to-vigorous physically active 96.4%, 2.6%, and 0.9% of their time, respectively, with 1356 steps/d. For every 500-step increase in daily step count on day 1, the length of stay was reduced by 6.6%. For every 500-step increase in daily step count during admission, in-hospital and 30-day mortality was reduced. Increased light and moderate-to-vigorous physical activity during admission were associated with reduced risk of in-hospital and 30-day mortality. After discharge, patients increased their daily step count to 2654 steps/d and spent more time performing light and moderate-to-vigorous physical activity. For every 500-step increase in daily step count after discharge, the risk of readmission was reduced. Higher moderate-to-vigorous physical activity after discharge was associated with a reduced risk of readmission. Conclusions: Increased physical activity during admission was associated with a reduced length of stay and risk of mortality, whereas increased physical activity after discharge was associated with a reduced risk of readmission in patients with CAP. Interventions focusing on increasing physical activity levels should be prioritised to improve the prognosis of patients admitted with CAP. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic was met with strict containment measures. We hypothesized that societal infection control measures would impact the number of hospital admissions for respiratory tract infections, as well as, the spectrum of pathogens detected in patients with suspected community acquired pneumonia (CAP).Methods: This study is based on aggregated surveillance data from electronic health records of patients admitted to the hospitals in Bergen Hospital Trust from January 2017 through June 2021, as well as, two prospective studies of patients with suspected CAP conducted prior to and during the COVID-19 pandemic (pre-COVID cohort versus COVID cohort, respectively). In the prospective cohorts, microbiological detections were ascertained by comprehensive PCR-testing in lower respiratory tract specimens. Mann-Whitney's U test was used to analyse continuous variables. Fisher's exact test was used for analysing categorical data. The number of admissions before and during the outbreak of SARS-CoV-2 was compared using two-sample t-tests on logarithmic transformed values.Results: Admissions for respiratory tract infections declined after the outbreak of SARS-CoV-2 (p < 0.001). The pre-COVID and the COVID cohorts comprised 96 and 80 patients, respectively. The proportion of viruses detected in the COVID cohort was significantly lower compared with the pre-COVID cohort [21% vs 36%, difference of 14%, 95% CI 4% to 26%; p = 0.012], and the proportion of bacterial- and viral co-detections was less than half in the COVID cohort compared with the pre-COVID cohort (19% vs 45%, difference of 26%, 95% CI 13% to 41%; p < 0.001). The proportion of bacteria detected was similar (p = 0.162), however, a difference in the bacterial spectrum was observed in the two cohorts. Haemophilus influenzae was the most frequent bacterial detection in both cohorts, followed by Streptococcus pneumoniae in the pre-COVID and Staphylococcus aureus in the COVID cohort.Conclusion: During the first year of the COVID-19 pandemic, the number of admissions with pneumonia and the microbiological detections in patients with suspected CAP, differed from the preceding year. This suggests that infection control measures related to COVID-19 restrictions have an overall and specific impact on respiratory tract infections, beyond reducing the spread of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID‐19. Few studies have investigated regulators of iron metabolism in the context of COVID‐19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community‐acquired pneumonia (CAP) caused by SARS‐CoV‐2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross‐sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C‐reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS‐CoV‐2 with 143.8 (100.7–180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1–125.4) and 53.5 (25.2–125.8) ng/mL, respectively. The median ferritin level was more than 2‐fold higher in patients with SARS‐CoV‐2 compared with the other etiologies (p < 0.001). Patients with SARS‐CoV‐2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS‐CoV‐2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Blood glucose levels exceeding 8 mM are shown to increase glucose levels in airway surface in cystic fibrosis (CF). Moreover, high levels of endobronchial glucose are proposed to increase the growth of common CF bacteria and feed the neutrophil‐driven inflammation. In the infected airways, glucose may be metabolized by glycolysis to lactate by both bacteria and neutrophils. Therefore, we aimed to investigate whether increased blood glucose may fuel the glycolytic pathways of the lung inflammation by determining sputum glucose and lactate during an oral glucose tolerance test (OGTT). Sputum from 27 CF patients was collected during an OGTT. Sputum was collected at fasting and one and two hours following the intake of 75 g of glucose. Only participants able to expectorate more than one sputum sample were included. Glucose levels in venous blood and lactate and glucose content in sputum were analyzed using a regular blood gas analyzer. We collected 62 sputum samples: 20 at baseline, 22 after 1 h, and 20 after 2 h. Lactate and glucose were detectable in 30 (48.4%) and 43 (69.4%) sputum samples, respectively. The sputum lactate increased significantly at 2 h in the OGTT (p = 0.024), but sputum glucose was not changed. As expected, plasma glucose level significantly increased during the OGTT (p < 0.001). In CF patients, sputum lactate increased during an OGTT, while the sputum glucose did not reflect the increased plasma glucose. The increase in sputum lactate suggests that glucose spills over from plasma to sputum where glucose may enhance the inflammation by fueling the anaerobic metabolism in neutrophils or bacteria. [ABSTRACT FROM AUTHOR]

Aims: The aim was to report the prevalence of diabetes status in patients hospitalized with COVID-19 and assess the association between the glucometabolic status at admission and 90-day mortality.Methods: Consecutive patients hospitalized with COVID-19 were included in the study. All participants included had an HbA1c measurement 60 days prior to or within 7 days after admission. We studied the association between diabetes status, the glycemic gap (difference between admission and habitual status), admission plasma-glucose, and mortality using Cox proportional hazards regression.Results: Of 674 patients included, 114 (17%) had normal glucose level, 287 (43%) had pre-diabetes, 74 (11%) had new-onset, and 199 (30%) had diagnosed diabetes. No association between diabetes status, plasma-glucose at admission, and mortality was found. Compared to the 2nd quartile (reference) of glycemic-gap, those with the highest glycemic gap had increased mortality (3rd (HR 2.38 [1.29-4.38], p = 0.005) and 4th quartile (HR 2.48 [1.37-4.52], p = 0.002).Conclusion: Abnormal glucose metabolism was highly prevalent among patients hospitalized with COVID-19. Diabetes status per se or admission plasma-glucose was not associated with a poorer outcome. However, a high glycemic gap was associated with increased risk of mortality, suggesting that, irrespective of diabetes status, glycemic stress serves as an important prognostic marker for mortality. [ABSTRACT FROM AUTHOR]

This study aimed to investigate sickle cell trait (SCT) associations with physical activity, markers of insulin secretion and resistance, and glucose among people living with HIV infection (PLWH), both antiretroviral therapy (ART) naive and experienced, and HIV‐uninfected adults. This was a cross‐sectional study conducted in Mwanza, Northwestern Tanzania. We used data of 668 participants attained from two sub‐studies of CICADA study. Mean age was 40 (SD 11.5) years, 402 (61.7%) were females and 157 (24.1%) had SCT. PLWH were 422 (64.7%), of these, 80 (18.9%) were on ART. People with SCT had higher risk of having an isolated β‐cell dysfunction compared to those without SCT (RRR = 1.82, CI: 1.10, 3.01, p = 0.02). People with SCT but without HIV infection had lower average acceleration on the trunk longitudinal axis (ACCx) and higher level of self‐reported physical activity. 30 min oral glucose tolerance test among PLWH on ART was higher in those with SCT compared to those without SCT. People with SCT are at higher risk of having β‐cell dysfunction and those with SCT on ART are at more risk of developing diabetes. Future studies to investigate the interaction between SCT and HIV/ART on risk of diabetes should be considered. [ABSTRACT FROM AUTHOR]

Objectives: Data on the role of helminths on diabetes in Africa are limited. We investigated whether Schistosoma and geohelminth infections are associated with β-cell function and insulin resistance among adults. Methods: A cross-sectional study was conducted among adults during 2016–2017. Demography, Schistosoma and geohelminth infections, HIV and insulin data were collected. Insulin during an oral glucose tolerance test (fasting, 30, and 120-min), overall insulin secretion index, insulinogenic index, HOMA-β, and HOMA-IR were main outcome measures for β-cell function and insulin resistance, respectively. Generalized estimating equations and generalized linear models assessed the association of Schistosoma and geohelminth infections with outcome measures separately by HIV status. Outcomes were presented as marginal means with 95% CI. Results: Data were obtained for 1718 participants. Schistosoma infection was associated with higher 30-min insulin (24.2 mU/L, 95% CI: 6.9, 41.6) and overall insulin secretion index (13.3 pmol/L/mmol/L; 3.7, 22.9) among HIV-uninfected participants but with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-12.0 mU/L; -18.9, -5.1), and HOMA-IR (-0.3 mmol/L; -0.6, -0.05) among HIV-infected participants not yet on antiretroviral therapy (ART). Among HIV-infected participants not on ART, geohelminth infection was associated with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-9.1 mU/L; -17.3, -1.0), HOMA-β (-8.9 mU/L)/(mmol/L; -15.3, -2.6) and overall insulin release index (-5.1 pmol/L/mmol/L; -10.3, 0.02), although this was marginally significant. There was no association among those on ART. Conclusions: Schistosoma infection was associated with higher β-cell function among HIV-uninfected participants whereas Schistosoma and geohelminth infections were associated with reduced β-cell function among HIV-infected participants not on ART. [ABSTRACT FROM AUTHOR]

Introduction: In the HIV-infected individuals, physical activity improves physical strength, quality of life and reduces the risk of developing non-communicable diseases. In Sub-Saharan Africa, HIV-infected patients report being less active compared to HIV-uninfected individuals. We assessed the levels and correlates of objectively measured physical activity and capacity among HIV-infected antiretroviral therapy (ART)-naive individuals compared to HIV-uninfected individuals in Mwanza, Tanzania. Method: We conducted a cross-sectional study among newly diagnosed HIV-infected ART-naive individuals and HIV-uninfected individuals frequency-matched for age and sex. Socio-demographic data, anthropometrics, CD4 counts, haemoglobin level, and C-reactive protein (CRP) were collected. Physical activity energy expenditure (PAEE) was assessed as measure of physical activity whereas sleeping heart rate (SHR) and grip strength were assessed as measures of physical capacity. Multivariable linear regression was used to assess the correlates associated with physical activity and capacity. Results: A total of 272 HIV-infected and 119 HIV-uninfected individuals, mean age 39 years and 60% women participated in the study. Compared to HIV-uninfected individuals, HIV-infected had poorer physical activity and capacity: lower PAEE (-7.3 kj/kg/day, 95% CI: -11.2, -3.3), elevated SHR (7.7 beats/min, 95%CI: 10.1, 5.3) and reduced grip strength (-4.7 kg, 95%CI: -6.8, -2.8). In HIV-infected individuals, low body mass index, moderate-severe anaemia, low CD4 counts and high CRP were associated with lower physical activity and capacity. In HIV-uninfected individuals, abdominal obesity and moderate anaemia were associated with lower physical activity and capacity. Conclusion: HIV-infected participants had lower levels of physical activity and capacity than HIV-uninfected participants. Correlates of physical activity and capacity differed by HIV status. Management of HIV and related conditions needs to be provided effectively in health care facilities. Interventions promoting physical activity in these populations will be of importance to improve their health and reduce the risk of non-communicable diseases. [ABSTRACT FROM AUTHOR]

Underweight is common among tuberculosis (TB) patients. However, there is little information on determinants of body composition at TB treatment initiation in high-TB-burdened countries. This study aimed to determine factors associated with body composition at commencement of TB treatment in Mwanza, Tanzania. A cross-sectional study was conducted from 2007 to 2008 among newly diagnosed TB patients. Fat and fat-free mass were determined using a deuterium dilution technique and fat and fat-free mass indices were computed. Correlates were assessed using multiple regression analysis. A total of 201 pulmonary TB patients were recruited; of these, 37.8% (76) were female, 51.7% (104) were HIV infected, 65.3% (126) had sputum-positive TB, and 24.4% (49) were current smokers. In multiple regressions analysis, males had a 2.2-kg/m² [(95% Cl = 1.6, 2.9); P < 0.00011 lower fat mass index but 1.5 kg/m² [(95% Cl = 0.9, 2.0); P < 0.00011 higher fat-free mass index compared with females. Sputum-positive TB was associated with a lower fat mass index among HIV-uninfected patients [-1.4 kg (95% Cl = -2.5, -0.4); P= 0.006] but not among HIV-infected patients (P-interaction = 0.09). Current smokers had a 0.7-kg/m² [(95% Cl = 0.02, 1.5); P = 0.045] lower fat mass index, but smoking did not affect fat-free mass. High socioeconomic status (SES) was associated with higher fat as well as fat-free mass. HIV infection, cluster of differentiation 4 count, and antiretroviral therapy were not correlates. Sex, smoking, and SES were associated with body composition of TB patients at treatment commencement. Prospective studies are needed to determine the role of these factors on weight gain, functional recovery, and survival during and after treatment. [ABSTRACT FROM AUTHOR]

Introduction: One third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls. Methods: The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI. Results: 245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10B 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test. Conclusion: LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies. [ABSTRACT FROM AUTHOR]

Undernutrition is common among tuberculosis (TB) patients. The objective of this study was to assess the effect of multi- micronutrient supplementation during TB treatment on weight, body composition, and handgrip strength. A total of 865 patients with smear-positive IPTB+) or-negative IPTB-) pulmonary TB were randomly allocated to receive a daily biscuit with or without multi-micronutrients for 60 d during the intensive phase of TB treatment. Weight, arm fat area, arm muscle area, and handgrip strength were assessed at baseline and after 2 and 5 mo. At 2 mo, the multi-micronutrient supplementation led to a higher handgrip gain (1.22 kg; 95% CI = 0.50, 1.94; P= 0.0011 but had no effects on other outcomes. The effects of multi- micronutrient supplementation were modified by HIV infection (P-interaction = 0.002). Among HIV- patients, multi- micronutrient supplementation increased weight gain by 590 g (95% Cl = -40, 1210; P = 0.07) and handgrip strength by 1.6 kg (95% Cl = 0.78, 2.47; P< 0.0011, whereas among HIV+ patients, it reduced weight gain by 1440 g (95% Cl = 290, 2590; P= 0.0021 and had no effect on handgrip strength 10.07 kg; 95% Cl = -1.30, 1.46; P= 0.91). The reduced weight gain among HIV+ patients receiving multi-micronutrient supplementation seemed to be explained by a higher proportion of patients reporting fever. At 5 mo, the effects on weight were sustained, whereas there was no effect on handgrip strength. In conclusion, multi- micronutrient supplementation given as a biscuit is beneficial among HIV- PTB patients and may be recommended to TB programs. More research is needed to develop an effective supplement for HIV+ PTB patients. [ABSTRACT FROM AUTHOR]

Background: The prevalence of latent tuberculosis infection (LTBI) is vastly higher than that of tuberculosis (TB) disease and this enormous reservoir of individuals with LTBI impacts the global TB control strategy. Adolescents are at greatest risk of TB infection and are thus an ideal target population for a potential effective TB vaccine to be added to the current BCG programme as it could reduce the number of latent infections and consequently the number of adults with TB disease. However, LTBI rates are often unknown for this population. This study aims to estimate the magnitude of LTBI and to determine if Tanzanian adolescents would be a good population for a prevention of TB infection trial. Methods: This was a descriptive cross-sectional study that recruited 193 adolescents aged 12 and 16 years from government schools and directly from the community in Mwanza Region, Tanzania. Socio-demographic characteristics were collected for all enrolled participants. Blood was drawn and tested using QuantiFERON-TB Gold In-Tube (QFT-GIT), and Early Secretory Antigenic Target-6–Free Interferon-gamma Release Assay (ESAT-6 free IGRA). Concordance between QFT-GIT and ESAT-6 free IGRA was evaluated using the McNemar's test. Results: Overall estimates of LTBI prevalence were 19.2% [95%CI, 14.1; 25.2] and 18.6% [95%CI, 13.6; 24.6] as measured by QFT-GIT IGRA and ESAT-6 free IGRA, respectively. The 16-year-old cohort had a higher LTBI prevalence (23.7% [95%CI, 16.1; 32.9]) as compared to 12-year-old cohort (14.6% [95%CI, 8.6; 22.7]) as measured by QFT-GIT IGRA. When measured by ESAT-6 Free IGRA, LTBI prevalence was 24.7% (95%CI, 16.9; 34.0) for the 16-year-old cohort and 12.5% (95%CI, 7.0; 20.3) among the 12-year-old cohort. According to both tests the prevalence of TB infection and the corresponding annual risk of tuberculosis infection (ARTI) and force of infection were high and increased with age. Of all enrolled participants, 97.4% had concordant results for QFT-GIT IGRA and ESAT-6 free IGRA (p = 0.65). Conclusions: The prevalence of LTBI and the associated ARTI and force of infection among adolescents is high and increases with age in Mwanza Region. There was a high concordance between the QFT-GIT and the novel ESAT-6 free IGRA assays. These findings suggest Mwanza is a promising area to conduct novel TB vaccine research prevention of infection (POI) studies targeting adolescents. [ABSTRACT FROM AUTHOR]

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 β‐cells. [ABSTRACT FROM AUTHOR]

Introduction: Hemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders. Methods: Blood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT). Results: The mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26, P < 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+ AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM. Conclusions: HbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency. [ABSTRACT FROM AUTHOR]

Background: Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated. Methods: We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose. Results: No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02). Conclusions: In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum. [ABSTRACT FROM AUTHOR]