Nanometa Live: a user-friendly application for real-time metagenomic data analysis and pathogen identification.

SUMMARY: Nanometa Live presents a user-friendly interface designed for real-time metagenomic data analysis and pathogen identification utilizing Oxford Nanopore Technologies' MinION and Flongle flow cells. It offers an efficient workflow and graphical interface for the visualization and interpretation of metagenomic data as it is being generated. Key features include automated BLAST validation, streamlined handling of custom Kraken2 databases, and a simplified graphical user interface for enhanced user experience. Nanometa Live is particularly notable for its capability to run without constant internet or server access once installed, setting it apart from similar tools. It provides a comprehensive view of taxonomic composition and facilitates the detection of user-defined pathogens or other species of interest, catering to both researchers and clinicians. AVAILABILITY AND IMPLEMENTATION: Nanometa Live has been implemented as a local web application using the Dash framework with Snakemake handling the data processing. The source code is freely accessible on the GitHub repository at https://github.com/FOI-Bioinformatics/nanometa_live and it is easily installable using Bioconda. It includes containerization support via Docker and Singularity, ensuring ease of use, reproducibility, and portability.

Testosterone and resistance training improved physical performance and reduced fatigue in frail older men: 1 year follow-up of a randomized clinical trial.

OBJECTIVE: To improve health conditions among hypogonadal men ≥70 years of age using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium, and protein. METHODS: This study is a 1-year follow-up of a double-blind RCT lasting 20 weeks, including 148 older men ≥70 years old with low testosterone levels and mobility problems. During 52 weeks, 4 groups received either testosterone therapy (TU) or progressive resistance training (Training), both (Combo), or no intervention (Controls). Physiotherapists supported the training groups until week 20, while these participants continued trained on their own during weeks 21 to 52. The main outcome measure was the 30-s chair stand test. RESULTS: The following numbers of participants completed the trial: 20 (Combo), 20 (Controls), 24 (TU), and 14 (Training). When examining 30-s chair stand test performance within each group at baseline, and at weeks 4, 20 and 52, only the Combo group improved (p = 0.001, Friedman Test). Compared to controls, only the Combo group experienced reduced fatigue and tiredness (p < 0.05). CONCLUSIONS: Fifty-two weeks of testosterone supplementation combined with progressive resistance training may enhance physical performance, alleviate fatigue, and had no notable detrimental impacts among males aged ≥70 suffering from mobility issues and testosterone insufficiency.Trial registration - Clinical Trials NCT02873559.

Testing Psychological Inoculation to Reduce Reactance to Vaccine-Related Communication.

Research has found that vaccine-promoting messages can elicit state reactance (i.e., negative emotions in response to a perceived threat to behavioral freedom), especially among individuals with high trait reactance (i.e., proneness to experiencing reactance). This can result in a lower willingness to accept vaccines. We investigated whether inoculation against reactance - that is, forewarning individuals about potentially experiencing reactance - can reduce the effects of trait reactance on vaccination willingness. Participants (N = 710) recruited through Facebook were randomly allocated to be either inoculated or not. They were then shown a message promoting a fictitious vaccine, which included either a low, medium, or high threat to freedom. Contrary to research on other health topics, inoculation was ineffective at reducing state reactance toward the vaccination message. Inoculation also did not mitigate the effects of trait reactance on vaccination willingness, and was even counterproductive in some cases. High-reactant individuals were less willing to get vaccinated than low-reactant ones, especially at high freedom threat. Conversely, high freedom threat resulted in increased vaccination willingness among low-reactant individuals. Further research is needed to understand why inoculation against reactance produces different results with vaccination, and to develop communication strategies that mitigate reactance to vaccination campaigns without compromising the positive effects of vaccine recommendations for low-reactant individuals.

The kinetics of SARS-CoV-2 viremia in COVID-19 patients receiving remdesivir.

Detection of SARS-CoV-2 RNA in serum, viremia, has been linked to disease severity and outcome. The kinetics of viremia in patients receiving remdesivir has not been thoroughly studied and could help predict treatment response and outcome. We investigated the kinetics of SARS-CoV-2 viremia and factors associated with baseline viremia, viral clearance and 30-day mortality in patients receiving remdesivir. An observational study including 378 hospitalised patients (median age 67 years, 67% male) sampled with serum SARS-CoV-2 RT-PCR within ± 24 h of initiation of remdesivir treatment. Baseline viremia was present in 206 (54%) patients with a median Ct value of 35.3 (IQR = 33.3-37.1). In patients with baseline viremia, the estimated probability of viral clearance was 72% by day 5. Ct values decreased significantly during remdesivir treatment for viremic patients, indicating an increase in viral load. In total, 44 patients (12%) died within 30 days, and mortality was significantly associated with viremia at baseline (OR = 2.45, p = 0.01) and lack of viral clearance by day 5 (OR = 4.8, p = < 0.01). Viral clearance was not associated with any individual risk factor. Viremia appears to be a prognostic marker before and during remedesivir treatment. The resolution of viremia was similar to patients not receiving remdesivir in other studies, and the decrease in Ct values during treatment questions the antiviral capacity of remdesivir in vivo. Prospective studies are warranted to confirm our findings.

Spillover effects of the COVID-19 pandemic on attitudes to influenza and childhood vaccines.

The current study sought to determine whether public perceptions of other vaccines and diseases than COVID-19 have been impacted by the COVID-19 pandemic. We longitudinally examined whether there had been a change from before the COVID-19 pandemic to during the pandemic in: (a) influenza vaccination behaviour and intentions; (b) the perceived benefit of childhood vaccines and influenza vaccines; (c) the perceived safety of childhood vaccines and influenza vaccines; (d) the perceived severity of measles and influenza; and (e) trust in healthcare professionals in two samples of Finnish adults (N = 205 in Study 1 and N = 197 in Study 2). The findings showed that during the pandemic, more people than before had received or wanted to receive the influenza vaccine. The respondents also believed that influenza was more dangerous during the pandemic and that vaccinations were safer and more beneficial. On the other hand, for childhood vaccines only perceived safety increased. Finally, in one of the studies, people had more confidence in medical professionals during the pandemic than they had before. Together, these findings imply a spillover of the COVID-19 pandemic on how people view other vaccines and illnesses.

The behavioral immune system and vaccination intentions during the coronavirus pandemic.

The behavioral immune system is considered to be a psychological adaptation that decreases the risk of infection. Research suggests that, in the current environment, this system can produce attitudes with negative health consequences, such as increased vaccine hesitancy. In three studies, we investigated whether two facets of the behavioral immune system-germ aversion (i.e., aversion to potential pathogen transmission) and perceived infectability (i.e., perceived susceptibility to disease)-predicted intentions to accept COVID-19 and influenza vaccination during the pandemic. The behavioral immune system mechanisms were measured before the COVID-19 pandemic in one study, and during the pandemic in two. In contrast to previous research, those with higher germ aversion during the pandemic perceived vaccines to be safer and had higher intentions to accept vaccination. Germ aversion before the pandemic was not associated with vaccination intentions. Individuals who perceived themselves as more susceptible to disease were slightly more willing to accept vaccination. We conjecture that high disease threat reverses the relationship between the behavioral immune system response and vaccination. As the associations were weak, individual differences in germ aversion and perceived infectability are of little practical relevance for vaccine uptake.

Unwillingness to engage in behaviors that protect against COVID-19: the role of conspiracy beliefs, trust, and endorsement of complementary and alternative medicine.

BACKGROUND: We investigated if people's response to the official recommendations during the COVID-19 pandemic is associated with conspiracy beliefs related to COVID-19, a distrust in the sources providing information on COVID-19, and an endorsement of complementary and alternative medicine (CAM). METHODS: The sample consisted of 1325 Finnish adults who filled out an online survey marketed on Facebook. Structural regression analysis was used to investigate whether: 1) conspiracy beliefs, a distrust in information sources, and endorsement of CAM predict people's response to the non-pharmaceutical interventions (NPIs) implemented by the government during the COVID-19 pandemic, and 2) conspiracy beliefs, a distrust in information sources, and endorsement of CAM are related to people's willingness to take a COVID-19 vaccine. RESULTS: Individuals with more conspiracy beliefs and a lower trust in information sources were less likely to have a positive response to the NPIs. Individuals with less trust in information sources and more endorsement of CAM were more unwilling to take a COVID-19 vaccine. Distrust in information sources was the strongest and most consistent predictor in all models. Our analyses also revealed that some of the people who respond negatively to the NPIs also have a lower likelihood to take the vaccine. This association was partly related to a lower trust in information sources. CONCLUSIONS: Distrusting the establishment to provide accurate information, believing in conspiracy theories, and endorsing treatments and substances that are not part of conventional medicine, are all associated with a more negative response to the official guidelines during COVID-19. How people respond to the guidelines, however, is more strongly and consistently related to the degree of trust they feel in the information sources, than to their tendency to hold conspiracy beliefs or endorse CAM. These findings highlight the need for governments and health authorities to create communication strategies that build public trust.

Fearing the disease or the vaccine: The case of COVID-19.

As studies indicate that people perceive COVID-19 as a threatening disease, the demand for a vaccine against the disease could be expected to be high. Vaccine safety concerns might nevertheless outweigh the perceived disease risks when an individual decides whether or not to accept the vaccine. We investigated the role of perceived risk of COVID-19 (i.e., perceived likelihood of infection, perceived disease severity, and disease-related worry) and perceived safety of a prospective vaccine against COVID-19 in predicting intentions to accept a COVID-19 vaccine. Three Finnish samples were surveyed: 825 parents of small children, 205 individuals living in an area with suboptimal vaccination coverage, and 1325 Facebook users nationwide. As points of reference, we compared the perceptions of COVID-19 to those of influenza and measles. COVID-19 was perceived as a threatening disease-more so than influenza and measles. The strongest predictor of COVID-19 vaccination intentions was trusting the safety of the potential vaccine. Those perceiving COVID-19 as a severe disease were also slightly more intent on taking a COVID-19 vaccine. Informing the public about the safety of a forthcoming COVID-19 vaccine should be the focus for health authorities aiming to achieve a high vaccine uptake.

MeningiSSS: A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis.

BACKGROUND: Knowing the individual child's risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors. METHODS: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure. RESULTS: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores' results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson-Todd Scale (AUC = 0.79) was all associated with death. CONCLUSIONS: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.

Cost-effectiveness of ustekinumab in moderate to severe Crohn's disease in Sweden.

BACKGROUND: Human monoclonal antibody ustekinumab is a novel Crohn's disease (CD) treatment blocking pro-inflammatory cytokines interleukin-12 and 23. The study's objective was to assess cost-effectiveness of ustekinumab in moderate to severely active CD in Sweden. METHODS: A cost-effectiveness model with an induction phase decision-tree structure and a maintenance phase Markov cohort structure was constructed. CD was represented by five health-states: remission, mild, moderate-severe, surgery and death. Ustekinumab was compared to adalimumab in patients who had failed conventional care, some of which had tried TNF-alpha-inhibitor(s) without experiencing treatment failure or side effects ("conventional care failure population") and to vedolizumab in patients previously failing TNF-alpha-inhibitor treatment. Discontinuation probabilities, utilities and ustekinumab induction efficacy were sourced from phase-III trials. Maintenance and comparator efficacy came from network-meta and treatment-sequence analyses. Resource use and unit costs were derived from literature and validated by clinical experts. The analysis had a societal perspective, a life-time time-horizon, and 2-year treatment duration. The results robustness was tested in univariate and probabilistic sensitivity analyses. Cost-effectiveness was estimated using quality-adjusted life-years (QALYs). RESULTS: Ustekinumab dominated adalimumab in conventional care failure population (costs: - €6984, QALYs: + 0.232). In TNF-alpha-inhibitor failure population ustekinumab accrued 0.133 more QALYs than vedolizumab, yielding a €30,282 incremental cost-effectiveness ratio. Results were sensitive to decreasing the time horizon and increased treatment duration. At Swedish reference willingness-to-pay of €63,000 (SEK 600,000), ustekinumab had 94% probability of being cost-effective versus adalimumab, and 72% versus vedolizumab. CONCLUSIONS: Results indicate ustekinumab dominates adalimumab in conventional care failure population, and is cost-effective versus vedolizumab in TNF-alpha-inhibitor failure population.

Health-related quality of life across all stages of autosomal dominant polycystic kidney disease.

BACKGROUND: A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease. METHODS: A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients. RESULTS: Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5. CONCLUSIONS: Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered.

Real-world costs of autosomal dominant polycystic kidney disease in the Nordics.

BACKGROUND: There is limited real-world data on the economic burden of patients with autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to estimate the annual direct and indirect costs of patients with ADPKD by severity of the disease: chronic kidney disease (CKD) stages 1-3; CKD stages 4-5; transplant recipients; and maintenance dialysis patients. METHODS: A retrospective study of ADPKD patients was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Data on medical resource utilisation were extracted from medical charts and patients were asked to complete a self-administered questionnaire. RESULTS: A total of 266 patients were contacted, 243 (91%) of whom provided consent to participate in the study. Results showed that the economic burden of ADPKD was substantial at all levels of the disease. Lost wages due to reduced productivity were large in absolute terms across all disease strata. Mean total annual costs were highest in dialysis patients, driven by maintenance dialysis care, while the use of immunosuppressants was the main cost component for transplant care. Costs were twice as high in patients with CKD stages 4-5 compared to CKD stages 1-3. CONCLUSIONS: Costs associated with ADPKD are significant and the progression of the disease is associated with an increased frequency and intensity of medical resource utilisation. Interventions that can slow the progression of the disease have the potential to lead to substantial reductions in costs for the treatment of ADPKD.

Atomically Resolved Structural and Chemical Investigation of Single MXene Sheets.

The properties of two-dimensional (2D) materials depend strongly on the chemical and electrochemical activity of their surfaces. MXene, one of the most recent additions to 2D materials, shows great promise as an energy storage material. In the present investigation, the chemical and structural properties of individual Ti3C2 MXene sheets with associated surface groups are investigated at the atomic level by aberration corrected STEM-EELS. The MXene sheets are shown to exhibit a nonuniform coverage of O-based surface groups which locally affect the chemistry. Additionally, native point defects which are proposed to affect the local surface chemistry, such as oxidized titanium adatoms (TiOx), are identified and found to be mobile.

COVID-19 and influenza vaccine-hesitancy subgroups.

Health communicators are faced with the challenge that people can hesitate vaccines for different reasons. Our aim was to identify and describe the qualities of distinct COVID-19 and influenza vaccine-hesitancy subgroups to facilitate the development of tailored vaccine-hesitancy communication. In two studies, we used agglomerative hierarchical cluster analysis to identify COVID-19 (N = 554) and influenza (N = 539) vaccine-hesitancy subgroups in the general population based on nine vaccine hesitancy-related variables (intent to get vaccinated, perceived vaccine safety, perceived vaccine efficacy, perceived disease threat, perceived vaccination responsibility, perceived vaccination convenience, distrust in authorities, conspiracy mentality, and reliance on anecdotal testimonies). We identified and described six distinct COVID-19 vaccine-hesitancy subgroups (the Vaccination Positive, the Ambivalent, the Fearing Skeptic, the Unconvinced, the Constrained Skeptic, and the Vaccination Opponent), and three influenza vaccine-hesitancy subgroups (the Vaccination Positive, the Complacent, and the Vaccination Opponent), with different levels of hesitancy. We discuss the implications of the results for health communicators. Our results shed light on the (dis)similarities between people who hesitate COVID-19 and influenza vaccines and suggest that there is greater variety in hesitancy concerning COVID-19 vaccinations than influenza vaccinations. These findings can be used to design and test tailored vaccination messages.

Association of the belief in conspiracy narratives with vaccination status and recommendation behaviours of German physicians.

Vaccine hesitancy has been identified as one of the top ten threats to global health by the World Health Organization (WHO). The belief in conspiracy narratives is repeatedly discussed as a major driver of vaccine hesitancy among the general population. However, there is a lack of research investigating the role of the belief in conspiracy narratives in vaccination decisions and recommendation behaviours of physicians. This is particularly relevant as physicians are one of the major and trusted sources of information for patients' vaccination decisions. This study therefore investigated the association between believing in COVID-19-related conspiracy narratives and physicians' own COVID-19 vaccination status and their recommendation behavior for COVID-19 and other vaccines (e.g., HPV or flu). In a cross-sectional survey among German physicians (N = 602, April 2022) two conspiracy narratives were assessed, stating that the coronavirus is a hoax or that it is human-made. Additional control variables included trust in health institutions, the rejection of complementary and alternative medicine (CAM), the 5C psychological antecedents of vaccination (confidence, complacency, constraints, calculation, and collective responsibility) and demographic variables. Hierarchical regressions indicated that greater belief in the conspiracy narrative claiming that the coronavirus is a hoax was associated with lower COVID-19 vaccination uptake and fewer COVID-19 vaccination recommendations among physicians. The results for recommendation behavior remain robust even when controlling for other variables. Contrary to our assumption, believing that the coronavirus is human-made was not related to vaccination status nor vaccine recommendation behavior. In conclusion, believing in conspiracy narratives that question the existence and thus also the danger of the virus is an important independent predictor of vaccine hesitancy among physicians that should be addressed in future public health interventions.

Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.

Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies.

Importance: Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid ß (Aß)-positive patients without an advanced stage of tau pathology who are most likely to benefit from these therapies. Blood-based biomarkers might reduce the need to use cerebrospinal fluid (CSF) or positron emission tomography (PET) for this. Objective: To evaluate plasma biomarkers for identifying Aß positivity and stage of tau accumulation. Design, Setting, and Participants: The cohort study (BioFINDER-2) was a prospective memory-clinic and population-based study. Participants with cognitive concerns were recruited from 2017 to 2022 and divided into a training set (80% of the data) and test set (20%). Exposure: Baseline values for plasma phosphorylated tau 181 (p-tau181), p-tau217, p-tau231, N-terminal tau, glial fibrillary acidic protein, and neurofilament light chain. Main Outcomes and Measures: Performance to classify participants by Aß status (defined by Aß-PET or CSF Aß42/40) and tau status (tau PET). Number of hypothetically saved PET scans in a plasma biomarker-guided workflow. Results: Of a total 912 participants, there were 499 males (54.7%) and 413 females (45.3%), and the mean (SD) age was 71.1 (8.49) years. Among the biomarkers, plasma p-tau217 was most strongly associated with Aß positivity (test-set area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI, 0.90-0.97). A 2-cut-point procedure was evaluated, where only participants with ambiguous plasma p-tau217 values (17.1% of the participants in the test set) underwent CSF or PET to assign definitive Aß status. This procedure had an overall sensitivity of 0.94 (95% CI, 0.90-0.98) and a specificity of 0.86 (95% CI, 0.77-0.95). Next, plasma biomarkers were used to differentiate low-intermediate vs high tau-PET load among Aß-positive participants. Plasma p-tau217 again performed best, with the test AUC = 0.92 (95% CI, 0.86-0.97), without significant improvement when adding any of the other plasma biomarkers. At a false-negative rate less than 10%, the use of plasma p-tau217 could avoid 56.9% of tau-PET scans needed to identify high tau PET among Aß-positive participants. The results were validated in an independent cohort (n = 118). Conclusions and Relevance: This study found that algorithms using plasma p-tau217 can accurately identify most Aß-positive individuals, including those likely to have a high tau load who would require confirmatory tau-PET imaging. Plasma p-tau217 measurements may substantially reduce the number of invasive and costly confirmatory tests required to identify individuals who would likely benefit from antiamyloid therapies.

Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling.

The pathophysiology underlying various manifestations of cerebral small vessel disease (cSVD) remains obscure. Using cerebrospinal fluid proximity extension assays and co-expression network analysis of 2,943 proteins, we found common and distinct proteomic signatures between white matter lesions (WML), microbleeds and infarcts measured in 856 living patients, and validated WML-associated proteins in three additional datasets. Proteins indicative of extracellular matrix dysregulation and vascular remodeling, including ELN, POSTN, CCN2 and MMP12 were elevated across all cSVD manifestations, with MMP12 emerging as an early cSVD indicator. cSVD-associated proteins formed a co-abundance network linked to metabolism and enriched in endothelial and arterial smooth muscle cells, showing elevated levels at early disease manifestations. Later disease stages involved changes in microglial proteins, associated with longitudinal WML progression, and changes in neuronal proteins mediating WML-associated cognitive decline. These findings provide an atlas of novel cSVD biomarkers and a promising roadmap for the next generation of cSVD therapeutics.

Beneficial effects of exercise, testosterone, vitamin D, calcium and protein in older men-A randomized clinical trial.

BACKGROUND: Due to increasing older populations worldwide, injuries, disabilities and deaths caused by falls among the elderly represent a growing human and societal problem. We aimed to improve health among men of at least 70 years of age with low-normal to low testosterone and mobility problems by using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium and protein. METHODS: This was a single-centre, randomized, placebo-controlled, double-blind trial with 148 older men with a median age of 77 (73-81) years, testosterone levels at median 8 (5-9) nmol/L (full range from 1.1 to 12.9 nmol/L) and mobility problems, recruited at University Hospital of Copenhagen, Herlev Hospital, Denmark. Participants were randomized into four arms for 20 weeks: (1) TU therapy (n = 37); (2) progressive resistance training with supplements of calcium, vitamin D and protein (n = 36); (3) both interventions combined (n = 36); or (4) no intervention (n = 39). The main outcome measure was the 30-s chair stand test, due to test performance correlating with the risk of serious fall injuries and lower extremity muscle strength. Outcome measurements were performed at baseline and after 20 weeks. RESULTS: After the intervention, the combination group receiving progressive resistance training, TU and supplements achieved a median score of 13 (11-15) compared to the control group at 10 (0-14) in the 30-s chair stand test (P = 0.003). This median improvement of 3.0 was clinically important. Compared to the control group, participants in the combination group also increased quality of life (P < 0.05) and reduced both tiredness (P < 0.05) and leg fat (P < 0.05) and had higher variability in the RR interval (P < 0.01). The group receiving TU reduced gynoid and leg fat compared to the control group (both P < 0.05). Blood tests improved for several variables, especially in the combination group. There was no statistically significant increase in adverse effects from either the supplements or training. CONCLUSIONS: In men ≥70 years old with low-normal to low testosterone and mobility problems, supplements of testosterone, calcium, vitamin D and protein combined with progressive resistance training improved 30-s chair stand test performance, muscle strength and quality of life. Both tiredness and leg fat were reduced, and RR interval variability was increased. Significant adverse effects were not observed.