Vitamin D in patients with COVID-19: is there a room for it?

Vitamin-D receptors are found in a variety of cells with the potential to regulate many cellular functions. Higher COVID-19 severity has been reported in individuals, which are known to have lower vitamin-D levels. The relation between vitamin-D and COVID-19 has been analysed with a number of studies but only few met high standards. Studies revealed discordant findings. There is no data from interventional trials clearly indicating that vitamin-D supplementation may prevent against COVID-19. An increasing number of observational studies put forward the preventive feature of adequate vitamin-D status for COVID-19 mortality. Yet, there are again conflicting findings. This narrative review summarizes the current evidence and provides a practical advice to lessen the impact of COVID-19 by ensuring recommended vitamin-D intakes. This approach would not be harmful, but potentially useful. Vitamin-D is safe especially if it does not exceed the upper-tolerable-limit. Daily doses are recommended over the weekly or monthly higher doses. Mega-doses are not recommended because of its potential to lead adverse events. The target level of vitamin-D is proposed above 30 ng/mL in majority of the studies. Nonetheless, one should consider that the benefit is foreseen to be small, and some time (months) may be needed for such effect.

Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe.

Introduction: Certain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe. Methods: Serum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory. Results: Median levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769). Discussion: The data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.

Evaluation of Clinical Practice Guidelines on Fall Prevention and Management for Older Adults: A Systematic Review.

Importance: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking. Objectives: To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. Evidence Review: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. Findings: Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations. Conclusions and Relevance: This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.

Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission.

Selenium (Se) and zinc (Zn) are essential trace elements needed for appropriate immune system responses, cell signalling and anti-viral defence. A cross-sectional observational study was conducted at two hospitals in Ghent, Belgium, to investigate whether Se and/or Zn deficiency upon hospital admission correlates to disease severity and mortality risk in COVID-19 patients with or without co-morbidities. Trace element concentrations along with additional biomarkers were determined in serum or plasma and associated to disease severity and outcome. An insufficient Se and/or Zn status upon hospital admission was associated with a higher mortality rate and a more severe disease course in the entire study group, especially in the senior population. In comparison to healthy European adults, the patients displayed strongly depressed total Se (mean ± SD: 59.2 ± 20.6 vs. 84.4 ± 23.4 µg L-1) and SELENOP (mean ± SD: 2.2 ± 1.9 vs. 4.3 ± 1.0 mg L-1) concentrations at hospital admission. Particularly strong associations were observed for death risk of cancer, diabetes and chronic cardiac disease patients with low Se status, and of diabetes and obese patients with Zn deficiency. A composite biomarker based on serum or plasma Se, SELENOP and Zn at hospital admission proved to be a reliable tool to predict severe COVID-19 course and death, or mild disease course. We conclude that trace element assessment at hospital admission may contribute to a better stratification of patients with COVID-19 and other similar infectious diseases, support clinical care, therapeutic interventions and adjuvant supplementation needs, and may prove of particular relevance for patients with relevant comorbidities.

Toward a geriatric approach to patients with advanced age and cardiovascular diseases: position statement of the EuGMS Special Interest Group on Cardiovascular Medicine.

Cardiovascular diseases (CVD) are highly prevalent in older adults and represent a major geriatric health-care concern. Management of CVD in older patients may be challenging due to specific geriatric issues, such as frailty and multi-morbidity, which may influence patients' outcomes. In this clinical context, diagnostic and therapeutic strategies should target those outcomes that have higher priority in geriatric health care, including disability prevention and quality of life. Older adults with CVD should be offered a reasonably optimized treatment, customized to the individual's frailty level and functional status. Yet, most clinical trials excluded comorbid and frail patients and evidence to support CVD management in this vulnerable population is lacking. Therefore, a geriatric approach is needed in cardiovascular medicine, characterized by a holistic, patient-centered perspective focusing on functional status and quality of life. With a view to promote the geriatric approach in the management of older patients with CVD, the EuGMS Special Interest Group (SIG) on Cardiovascular Medicine was founded in 2018, consisting of a network of geriatricians with an extensive expertise in geriatric cardiovascular medicine. The present position paper aims to present the Cardiovascular SIG and illustrate its main purposes and action programs.

Pharmacological Interventions to Improve Muscle Mass, Muscle Strength and Physical Performance in Older People: An Umbrella Review of Systematic Reviews and Meta-analyses.

BACKGROUND: Sarcopenia, defined as the pathological decline in muscle mass, muscle strength and physical performance with aging, has become one of the geriatric giants because of its increasing prevalence and devastating health effects. The Belgian Society of Gerontology and Geriatrics (BSGG) is currently developing evidence-based guidelines for the prevention and therapy of sarcopenia for use in broad clinical practice. This systematic review summarizes the results of the Working Group on Pharmacology. OBJECTIVE: Our objective was to provide an evidence-based overview of the possible pharmacological interventions for sarcopenia with a focus on interventions that have already been studied in systematic reviews or meta-analyses. METHODS: We conducted a systematic umbrella review. Using the electronic databases PubMed and Web of Science, we identified systematic reviews and meta-analyses that assessed the effect of pharmacological interventions on criteria for sarcopenia in subjects aged ≥ 65 years. Study selection, quality assessment and data extraction were performed by two independent reviewers. RESULTS: We identified seven systematic reviews or meta-analyses, encompassing ten pharmacological interventions: vitamin D, combined estrogen-progesterone, dehydroepiandrosterone, growth hormone, growth hormone-releasing hormone, combined testosterone-growth hormone, insulin-like growth factor-1, pioglitazone, testosterone and angiotensin-converting enzyme inhibitors. Importantly, very few systematic reviews or meta-analyses clearly mentioned baseline sarcopenia status. Therefore, our recommendations are generalised to older people, without specifying whether the muscle effect is more effective in healthy, pre-sarcopenic or sarcopenic older people. Vitamin D had a significant effect on muscle strength and physical performance, especially in women with low baseline values (< 25 nmol/l). Adverse events were rare. Testosterone had a strong effect on muscle mass and a modest to minimal effect on muscle strength and physical performance, respectively, when supplementing men with low serum levels (< 200-300 ng/dl). The adverse events were rare and mild. Insufficient evidence was available to recommend other pharmacological interventions. CONCLUSION: Only vitamin D, especially in older women, and testosterone in older men with clinical muscle weakness and low testosterone serum levels can be justified in daily clinical practice to improve muscle mass, muscle strength and/or physical performance.

Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.

Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily ß-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (P<0·001) and gastrocnemius (P=0·001) muscle. To conclude, the body creatine pool declined over a 3-month vegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

Systematic review of systematic reviews of non-pharmacological interventions to treat behavioural disturbances in older patients with dementia. The SENATOR-OnTop series.

OBJECTIVE: To provide an overview of non-pharmacological interventions for behavioural and psychological symptoms in dementia (BPSD). DESIGN: Systematic overview of reviews. DATA SOURCES: PubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL and PsycINFO (2009-March 2015). ELIGIBILITY CRITERIA: Systematic reviews (SRs) that included at least one comparative study evaluating any non-pharmacological intervention, to treat BPSD. DATA EXTRACTION: Eligible studies were selected and data extracted independently by 2 reviewers.The AMSTAR checklist was used to assess the quality of the SRs. DATA ANALYSIS: Extracted data were synthesised using a narrative approach. RESULTS: 38 SRs and 129 primary studies were identified, comprising the following categories of non-pharmacological interventions: (1) sensory stimulation interventions (25 SRs, 66 primary studies) that encompassed: shiatsu and acupressure, aromatherapy, massage/touch therapy, light therapy, sensory garden and horticultural activities, music/dance therapy, dance therapy, snoezelen multisensory stimulation therapy, transcutaneous electrical nerve stimulation; (2) cognitive/emotion-oriented interventions (13 SRs; 26 primary studies) that included cognitive stimulation, reminiscence therapy, validation therapy, simulated presence therapy; (3) behaviour management techniques (6 SRs; 22 primary studies); (4) Multicomponent interventions (3 SR; four primary studies); (5) other therapies (5 SRs, 15 primary studies) comprising exercise therapy, animal-assisted therapy, special care unit and dining room environment-based interventions. CONCLUSIONS: A large number of non-pharmacological interventions for BPSD were identified. The majority of the studies had great variation in how the same type of intervention was defined and applied, the follow-up duration, the type of outcome measured, usually with modest sample size. Overall, music therapy and behavioural management techniques were effective for reducing BPSD.

Effects of Histidine and ß-alanine Supplementation on Human Muscle Carnosine Storage.

PURPOSE: Carnosine is a dipeptide composed of ß-alanine and L-histidine and is present in skeletal muscle. Chronic oral ß-alanine supplementation can induce muscle carnosine loading and is therefore seen as the rate-limiting factor for carnosine synthesis. However, the effect of L-histidine supplementation on carnosine levels in humans is never established. This study aims to investigate whether 1) L-histidine supplementation can induce muscle carnosine loading and 2) combined supplementation of both amino acids is more efficient than ß-alanine supplementation alone. METHODS: Fifteen male and 15 female participants were equally divided in three groups. Each group was supplemented with either pure ß-alanine (BA) (6 g·d), L-histidine (HIS) (3.5 g·d), or both amino acids (BA + HIS). Before (D0), after 12 d (D12), and after 23 d (D23) of supplementation, carnosine content was evaluated in soleus and gastrocnemius medialis muscles by H-MRS, and venous blood samples were collected. Muscle biopsies were taken at D0 and D23 from the vastus lateralis. Plasma and muscle metabolites (ß-alanine, histidine, and carnosine) were measured by high-performance liquid chromatography. RESULTS: Both BA and BA + HIS groups showed increased carnosine concentrations in all investigated muscles, with no difference between these groups. By contrast, carnosine levels in the HIS group remained unaltered. Histidine levels were significantly decreased in plasma (-30.6%) and muscle (-31.6%) of the BA group, and this was prevented when ß-alanine and L-histidine were supplemented simultaneously. CONCLUSION: We confirm that ß-alanine, and not L-histidine, is the rate-limiting precursor for carnosine synthesis in human skeletal muscle. Yet, although L-histidine is not rate limiting, its availability is not unlimited and gradually declines upon chronic ß-alanine supplementation. The significance of this decline still needs to be determined, but may affect physiological processes such as protein synthesis.

Economic Impact of Integrated Care Models for Patients with Chronic Diseases: A Systematic Review.

OBJECTIVES: To assess the costs and potential financial benefits of integrated care models for patients with chronic diseases, that is, type 2 diabetes mellitus, schizophrenia, and multiple sclerosis, respectively. METHODS: A systematic search of the literature was performed using EMBASE, MEDLINE, and Web of Science. Studies that conducted a cost analysis, considered at least two components of the chronic care model, and compared integrated care with standard care were included. RESULTS: Out of 575 articles, 26 were included. Most studies examined integrated care models for type 2 diabetes mellitus (n = 18) and to a lesser extent for schizophrenia (n = 6) and multiple sclerosis (n = 2). Across the three disease groups, the incremental cost per patient per year ranged from - €3860 to + €613.91 (x¯ = - €533.61 ± €902.96). The incremental cost for type 2 diabetes mellitus ranged from - €1507.49 to + €299.20 (x¯ = - €518.22 ± + €604.75), for schizophrenia from - €3860 to + €613.91 (x¯ = - €677.21 ± + €1624.35), and for multiple sclerosis from - €822 to + €339.43 (x¯ = - €241.29 ± + €821.26). Most of the studies (22 of 26 [84.6%]) reported a positive economic impact of integrated care models: for type 2 diabetes mellitus (16 of 18 [88.9%]), schizophrenia (4 of 6 [66.7%]), and multiple sclerosis (1 of 2 [50%]). CONCLUSIONS: In this systematic literature review, predominantly positive economic impacts of integrated care models for patients with chronic diseases were found.

The geriatric management of frailty as paradigm of "The end of the disease era".

The sustainability of healthcare systems worldwide is threatened by the absolute and relative increase in the number of older persons. The traditional models of care (largely based on a disease-centered approach) are inadequate for a clinical world dominated by older individuals with multiple (chronic) comorbidities and mutually interacting syndromes. There is the need to shift the center of the medical intervention from the disease to the biological age of the individual. Thus, multiple medical specialties have started looking with some interest at concepts of geriatric medicine in order to better face the increased complexity (due to age-related conditions) of their average patient. In this scenario, special interest has been given to frailty, a condition characterized by the reduction of the individual's homeostatic reserves and increased vulnerability to stressors. Frailty may indeed represent the fulcrum to lever for reshaping the healthcare systems in order to make them more responsive to new clinical needs. However, the dissemination of the frailty concept across medical specialties requires a parallel and careful consideration around the currently undervalued role of geriatricians in our daily practice.

Fiber Typing of the Erector Spinae and Multifidus Muscles in Healthy Controls and Back Pain Patients: A Systematic Literature Review.

OBJECTIVE: Understanding the changes in muscle fiber typing is relevant in the context of muscle disorders because it provides information on the metabolic profile and functional capacity. The aim of this study was to systematically review the literature comparing muscle fiber typing in the back muscles of healthy subjects with low back pain (LBP) patients. METHODS: Predefined keywords regarding muscle fiber typing and back muscles were combined in PubMed and Web of Science electronic search engines from inception to August 2014. Full-text articles were independently screened by 2 independent, blinded researchers. Full texts fulfilling the predefined inclusion criteria were assessed on risk of bias by 2 independent researchers, and relative data were extracted. Data were not pooled because of heterogeneity in biopsy locations and population. RESULTS: From the 214 articles that were identified, 18 met the inclusion criteria. These articles evaluated the muscle fiber type distribution or proportional fiber type area between muscles, muscle layers, men, and women or healthy subjects and LBP patients. Regarding muscle fiber type distribution, findings in healthy subjects and LBP patients show no or inconclusive evidence for intermuscular and interindividual differentiation. Studies evaluating the proportional fiber type area also suggest little intermuscular differentiation but provide plausible evidence that the proportional area occupied by type I fibers is higher in women compared to men. The evidence for differentiation based on the presence of low back pain is conflicting. CONCLUSION: This study found that the evidence regarding muscle fiber typing in back muscles is either inconclusive or shows little differences. The most plausible evidence exists for differentiation in proportional fiber type area depending on sex.