Rikke Krogh-Madsen

Aims: The role of prior wasting malnutrition (PM) in determining insulin sensitivity and secretion in low‐ and middle‐income countries (LMICs) remains unclear. We investigated associations of insulin indices with PM and whether these were modified by current body mass index (BMI). Methods: Participants were enrolled from child and adult cohorts in Zambia, Tanzania, India and the Philippines with previously documented PM or no prior wasting malnutrition (NPM). Plasma glucose, insulin and C‐peptide were measured during an oral glucose tolerance test. Static (HOMA2 %S, HOMA2 %B) and dynamic (Matsuda index, insulinogenic index, disposition index) insulin indices were calculated. Adjusted linear regression models compared indices between PM and NPM groups. Results: In 2172 participants analysed, those with PM had lower current BMI. Children with PM had reduced insulin sensitivity (Matsuda index 20%–24% lower in PM vs. NPM). Adults with PM in early life (36–37 years before) many of whom had high adult BMI, also exhibited lower insulin sensitivity after adjustment for current BMI (Matsuda Index 18% lower in PM vs. NPM). Adults with more recent PM (3–17 years previously), many of whom remained underweight, had low insulin secretion (HOMA2 %B 10%–20% lower in PM vs. NPM) but greater insulin sensitivity associated with their lower BMI (Matsuda index 21%–47% higher in PM vs. NPM). Insulin secretion generally compensated for insulin sensitivity differences, maintaining comparable disposition index and diabetes and prediabetes prevalence between PM and NPM groups. Conclusions: PM affects glucose metabolism differently according to current BMI. Remaining underweight is associated with low insulin secretion and weight gain following PM is linked to reduced insulin sensitivity. Our results further inform understanding of the relative roles of reduced insulin secretion and sensitivity in diabetes pathogenesis in LMICs.

Background: Physical inactivity contributes to functional decline and is associated with increased risk of adverse outcomes in patients hospitalized with community-acquired pneumonia (CAP). Exercise programs applied during acute hospitalization may mitigate these effects, particularly in older adults. This study aimed to evaluate the effect of standard care versus supervised in-bed cycling or booklet-exercise, including resistance and endurance exercises, on functional ability, body composition, and physical activity level in patients hospitalized with CAP. Methods: In this randomized controlled trial, 178 patients hospitalized with CAP were allocated to standard care ( n = 59), in-bed cycling ( n = 58), or booklet-exercise ( n = 61). Functional ability was assessed using grip strength, the 30-second sit-to-stand, and the Barthel index. Body composition was measured with bioelectrical impedance analysis, and physical activity was monitored using accelerometers. Outcomes were evaluated from admission to 3-month post-discharge using linear mixed-effect models. Results: Baseline measures were comparable across groups. At 3 months post-discharge, participants performing in-bed cycling showed a significant improvement in the Barthel index compared to standard care (mean difference: 4.15 points, 95% ΔCI: 0.26–8.04, P = 0.037), while no difference was observed for participants in the booklet-exercise group. There was no effect of the exercise interventions on changes in grip strength, 30-sec sit-to-stand performance, fat mass index, fat-free mass index, or daily step count. Conclusion: Supervised exercise training during hospitalization improved functional ability in patients with CAP 3 months post-discharge. However, the short duration of hospitalization may limit the overall impact of in-hospital exercise interventions, highlighting the need for continued post-discharge exercise strategies to support functional recovery and independence in patients with CAP.

Background: A deficient vitamin D status is linked to increased risk of community-acquired pneumonia (CAP) and both short- and long-term mortality. Given small sizes of previous studies and lack of adjustment for key confounders, we aimed to investigate the association between vitamin D status (sufficient, insufficiency, or deficiency) and mortality risk in adults hospitalized with CAP. Methods: This study, nested within the Surviving Pneumonia Study at Copenhagen University Hospital—North Zealand, Denmark, included adults hospitalized with CAP between 2019 and 2022. Vitamin D status was assessed using serum 25(OH)D concentrations, categorizing participants as sufficient (≥50 nmol/L), insufficient (25–<50 nmol/L), or deficient (<25 nmol/L). Logistic regression was used to assess mortality risk. Covariates included age, sex, Charlson comorbidity index, CURB-65, smoking history, and BMI. Results: Among 514 participants, 29 (5.6%) and 130 (25.3%) had deficient and insufficient vitamin D status, respectively. Participants with deficient vitamin D status were younger, and more than 50% were current smokers. Vitamin D deficiency was associated with higher 90-day (OR: 3.50, 95% CI 1.01; 12.21) and 180-day (OR: 3.27, 95% CI 1.04; 10.25) mortality risk compared with participants with sufficient vitamin D status, while no difference was observed between the sufficient and insufficient group. No differences were observed for in-hospital or 30-day mortality. Conclusions: Participants with deficient vitamin D status were younger and faced higher mortality risk despite milder disease at admission. Given that vitamin D deficiency may relate to poorer health habits and low levels of other micronutrients, trials on tailored micronutrient supplementation during acute conditions like CAP could be considered.

In patients previously hospitalised for COVID‐19, a 12‐week high‐intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functional capacity at 12‐month follow‐up. In this investigator‐blinded, randomised controlled trial, 12 weeks of a supervised HIIT scheme (4 × 4 min, three times a week) was compared to standard care (control) in patients recently discharged from hospital due to COVID‐19. At inclusion and at 12‐month follow‐up, LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), while pulmonary diffusing capacity for carbon monoxide ( D _LCOc , secondary outcome) was examined by the single‐breath method. Symptom severity and functional status were examined by the Post‐COVID‐19 Functional Scale (PCFS) and King's Brief Interstitial Lung Disease (KBILD) questionnaire score. Of the 28 patients assessed at baseline, 22 completed cMRI at 12‐month follow‐up (12.4 ± 0.6 months after inclusion). LVM was maintained in the HIIT but not the standard care group, with a mean between‐group difference of 9.68 [95% CI: 1.72, 17.64] g ( P = 0.0182). There was no differences in change from baseline to 12‐month follow‐up between groups in D _LCOc % predicted (−2.45 [−11.25, 6.34]%; P = 0.578). PCFS and KBILD improved similarly in the two groups. In individuals previously hospitalised for COVID‐19, a 12‐week supervised HIIT scheme resulted in a preserved LVM at 12‐month follow‐up but did not affect pulmonary diffusing capacity or symptom severity.

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.

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.

Undernutrition is associated with increased mortality after hospitalization with community-acquired pneumonia (CAP), whereas obesity is associated with decreased mortality in most studies. We aimed to determine whether undernutrition and obesity are associated with increased risk of re-hospitalization and post-discharge mortality after hospitalization. This study was nested within the Surviving Pneumonia cohort, which is a prospective cohort of adults hospitalized with CAP. Patients were categorized as undernourished, well-nourished, overweight, or obese. Undernutrition was based on diagnostic criteria by the European Society for Clinical Nutrition and Metabolism. Risk of mortality was investigated using multivariate logistic regression and re-hospitalization with competing risk Cox regression where death was the competing event. Compared to well-nourished patients, undernourished patients had a higher risk of 90-day (OR 3.0, 95% CI 1.0; 21.4) mortality, but a similar 30-day and 180-day mortality risk. Obese patients had a similar re-hospitalization and mortality risk as well-nourished patients. In conclusion, among patients with CAP, undernutrition was associated with increased risk of mortality. Undernourished patients are high-risk patients, and our results indicate that in-hospital screening of undernutrition should be implemented to identify patients at mortality risk. Studies are required to investigate whether nutritional therapy after hospitalization with CAP would improve survival.

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 (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.

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.