Search Results (241)

Background/Objectives: Hypovitaminosis-D is a highly prevalent condition worldwide, associated with adverse skeletal and extra-skeletal outcomes. Increasing demand for serum 25-hydroxyvitamin D (25(OH)D) testing points toward the need for simple tools to identify individuals at risk and optimize laboratory use. We aimed to develop and validate a clinical risk score for predicting hypovitaminosis-D based on easily assessable risk factors. Methods: This cross-sectional study included 1408 adults aged ≥50 years (1286 women and 122 men) attending centers across Italy dedicated to osteoporosis and metabolic bone diseases. Demographic, clinical, lifestyle, and dietary data were collected through a standardized questionnaire. Overall, 1147 subjects (81.5%) were receiving cholecalciferol supplementation. Univariable and multivariable logistic regression analyses identified predictors of 25(OH)D < 20 ng/mL (primary outcome) and <30 ng/mL. Risk scores were derived from models and internally validated. Discriminative ability was assessed using ROC curves, and calibration was conducted by comparing predicted and observed probabilities. Results: The median age was 67 years, and 91.3% were female. Median 25(OH)D was 33.2 ng/mL; 9.8% had levels < 20 ng/mL. Independent predictors of hypovitaminosis-D (25(OH)D < 20 ng/mL) included higher body mass index, residence in Northern Italy, reduced summer sun exposure, sunscreen use, cardiovascular disease, glucocorticoid use, absence of cholecalciferol supplementation, and no prior vitamin D use. The score (range 9–18) showed good discrimination (Area under the curve; AUC: 79.1%, 95% CI: 75.3–82.9) and calibration (r = 0.98, p < 0.001). A screening cut-off (10.3–10.7) ensured high sensitivity (87.0–92.7%), while 11.9–12.0 balanced sensitivity (~62%) and specificity (~80%). A second score for 25(OH)D < 30 ng/mL showed moderate discrimination (AUC: 69.6%). Performance remained stable across seasons and in untreated subjects (AUC: 72.7%). Female predominance, widespread vitamin D use, and the absence of external validation or impact analyses limit generalizability. Conclusions: The proposed data-driven clinical risk score may help identify individuals at risk of vitamin D deficiency and support targeted screening strategies, potentially reducing unnecessary testing in routine clinical practice. Full article

Vitamin D is a fat-soluble vitamin, considered a prohormone, that plays a fundamental role in calcium absorption and reabsorption, as well as the modulation of inflammatory response in infectious conditions such as COVID-19. A literature search was conducted in scientific databases and official sources, selecting studies published in the last 10 years in Spanish and English related to vitamin D and COVID-19; studies unrelated to the nutritional approach were excluded to reduce bias and ensure a rigorous and reproducible analysis. It was observed that the probability of contracting COVID-19 increases as the D3 hypovitaminosis prevalence increases. In Mexico, the relevance of vitamin D deficiency or supplementation in this disease has been controversial. Some studies claim that vitamin D supplementation could be a protective factor. According to the National Health Survey in Mexico (Ensanut), the Mexican population has significant deficiencies in this vitamin, contributing to an unfavorable diagnosis, particularly for children and pregnant women, as it is considered a deficiency in the blood when it is below 30 ng/mL and insufficiency when below 20 ng/mL, making these deficiencies important risk factors in the development of COVID-19 severe cases. Nevertheless, the use of vitamin D as an adjuvant agent in the treatment of COVID-19 can represent one of the main options for public health, providing therapeutic properties and health benefits. Full article

Objective: Vitamin D deficiency is a global concern, but its prevalence in critically ill patients in high-sunlight tropical regions is limited. This study evaluated the prevalence of vitamin D deficiency in intensive care unit (ICU) patients in southern Taiwan and identified which variables correlate with deficiency and in-hospital mortality. Methods: We prospectively enrolled 221 critically ill patients, categorizing them by serum 25(OH)D levels as follows: Group A (sufficient, ≥30 ng/mL), Group B (insufficient, 20.0–29.9 ng/mL), and Group C (deficient, ≤19.9 ng/mL). Clinical variables, laboratory parameters, and outcomes were analyzed. Results: Despite the tropical climate, 33.5% of patients were vitamin D-deficient, and 47.1% were insufficient. Group C patients were significantly younger than other groups (p = 0.049). Significant differences between Groups C and A were observed in ICU length of stay (p = 0.036) and total hospital stay (p = 0.004). Multivariable analysis confirmed that only younger age (OR 0.968, p = 0.008) and low albumin level (OR 0.171, p < 0.001) were independently associated with vitamin D deficiency. Only serum albumin (p = 0.001) and C-reactive protein (CRP) levels (p = 0.015) were significantly associated with in-hospital mortality. Conclusions: Vitamin D deficiency is highly prevalent among critically ill patients in southern Taiwan, challenging the assumption that tropical ultraviolet exposure is naturally protective. Younger age and hypoalbuminemia are independent predictors of vitamin D deficiency. However, vitamin D levels were not independently associated with in-hospital mortality, which was instead predicted by albumin and CRP levels. These findings highlight a high rate of hypovitaminosis D in ICU but do not support its role as an independent predictor of mortality. Full article

Background: Adolescence represents an essential stage of life for the prevention of metabolic changes associated with diseases, especially cardiovascular diseases. Objectives: The objectives of this study were to identify nutritional status and associate it with metabolic alterations in adolescent girls. Methods: We conducted a cross-sectional study that included adolescent 10–14-year-old girls from public schools. The research was undertaken with 79 girls. Results: We identified that over half of the girls were sedentary, excessively exposed to screens, physically inactive, and did not practice physical activities in sunlight. The menarche age was significantly lower in girls with overweight and obesity. Most girls skipped breakfast (53.1%) and watched television (84.8%). We observed a high percentage of adolescents with overweight (65.7%), hypovitaminosis D (78.4%) and high levels of triglycerides (69.6%). We did not find an association between hypovitaminosis D and some recorded metabolic parameters (glycemia, glycated hemoglobin, insulin, total cholesterol, HDL-c, LDL-c and triglycerides). However, insulin levels, HOMA-IR, HDL-c, and systolic blood pressure were significantly associated with overweight and obesity, and our results may reflect the characteristics of the study sample and suggest that obese children may already exhibit early signs and risk factors for these chronic diseases during childhood, consistent with national and international data. Conclusions: The identification of metabolic alterations, nutritional status and lifestyle enables early and directed interventions, which may lead to the present and future cardiometabolic health improvements relative to adolescents. Full article

Introduction: Hypocalcemia represents a major cause of seizures in children in the absence of fever or infections. Hypovitaminosis D, usually associated with a lack of proper prophylactic regimens, can trigger those events. This case series aims to highlight two cases of hypocalcemic seizures in infants, attributed to severe vitamin D deficiency, with the aim of raising awareness regarding the importance of vitamin D prophylaxis. A narrative review of the literature is also provided, which highlights similar reported cases. Methods: We hereby report two cases of male infants (aged 4 months and 5 months) who presented to the emergency department of a tertiary pediatric center with seizures in the absence of fever or infections. Diagnostic work-ups revealed low levels of total serum calcium and ionic calcium deficiency. The cause of the hypocalcemia turned out to be severe vitamin D deficiency in both cases, caused by complete absence of vitamin D supplements since birth and during maternal pregnancy. In both cases, combined oral calcium and vitamin D supplementation led to complete resolution of symptoms and restoration of normal calcium levels. A comprehensive review of the literature is also provided, which focuses on pediatric studies and case reports that analyzed the prevalence, particularities, and outcomes of hypocalcemic seizures related to vitamin D deficiency. Articles including subjects with congenital or endocrine disorders that could have caused hypocalcemia were ruled out. Results: After accessing the full-length form of each article and applying the inclusion and exclusion criteria, 27 articles were included, namely 14 studies and 13 case reports. Hypocalcemic seizures caused by vitamin D deficiency are more common in infants, are usually linked to maternal hypovitaminosis D, and have a higher prevalence in developing countries. Most of the case reports depicting hypocalcemic seizures were distinguished through very low vitamin D levels. Conclusions: These case series emphasize the importance of vitamin D supplementation for the prevention of hypocalcemia, which constitutes a major metabolic cause of seizures in infancy. Nevertheless, maternal vitamin D supplementation during pregnancy is the only factor that can ensure the presence of satisfactory deposits in the newborn and prevent hypovitaminosis D-related complications. Full article

Background: Vitamin D is a key regulator of skeletal homeostasis, and hypovitaminosis D is highly prevalent among postmenopausal women, who are at increased risk of osteoporosis, sarcopenia, and related complications. Accurate assessment of serum 25-hydroxyvitamin D [25(OH)D] is therefore essential. However, substantial variability exists among analytical methods, particularly between automated chemiluminescent immunoassays (CLIA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), the latter considered the reference technique. This study aimed to compare four analytical methods, three CLIA platforms, and LC-MS/MS for measuring circulating 25(OH)D levels in a cohort of menopausal and postmenopausal women. Methods: A total of 425 serum samples from menopausal and postmenopausal women representing the real-world distribution of vitamin D levels in this population were analyzed using three automated CLIA systems and LC-MS/MS. Method comparison, agreement, precision through quality control assessment, total error, and sigma were evaluated. Results: The evaluated CLIA platforms (Abbott, Snibe, and Siemens) showed strong correlation with LC-MS/MS, with r = 0.919, r = 0.978, and r = 0.879. Furthermore, all assays showed excellent precision (CV < 5%), with good-to-acceptable total error (TE) and Sigma-metric performance. Conclusions: In conclusion, these findings demonstrate that while CLIA platforms offer a reliable and precise alternative for routine clinical use, these findings underscore the importance of method selection and result interpretation in the clinical assessment of vitamin D status in postmenopausal women. Furthermore, it highlights the ongoing need to minimize inter-assay variability and ensure consistent vitamin D assessment. Full article

Background/Objectives: Vitamin D deficiency and insufficiency represent a widespread problem in the majority of Central Asian countries, attributable to the geographical location of the region, urbanization, and dietary patterns of the population. Given that vitamin D not only participates in the regulation of calcium and phosphate metabolism but also exerts pleiotropic effects on various organs and systems, its insufficiency and deficiency are associated with a broad spectrum of pathological conditions, ranging from asymptomatic manifestations to severe clinical symptoms, including the development of autoimmune diseases, metabolic disorders, cardiovascular, gynecological and reproductive, and rheumatological conditions. The development of national and interdisciplinary guidelines addressing the diagnosis, prevention of insufficiency, and correction of vitamin D deficiency in the countries of Central Asia represents an important step toward the establishment of effective preventive programs and treatment strategies, which may contribute to a reduction in the prevalence of diseases associated with vitamin D deficiency. The aim of the present work is to formulate a resolution capturing the conclusions and recommendations derived from an interdisciplinary expert discussion. Methods: An Expert Council meeting with the participation of specialists in endocrinology, obstetrics and gynecology, rheumatology, clinical pharmacology, and other medical disciplines from Central Asian and European countries was conducted in Almaty (Kazakhstan) on 18 June 2025. During this meeting, the pleiotropic action of vitamin D was extensively discussed basing on RCTs and observational studies. Results: Following the Expert Council meeting, current international clinical guidelines, scientific research data, and relevant epidemiological evidence were reviewed, leading to the formulation of a resolution that reflects the agreed-upon recommendations for the prevention of vitamin D insufficiency and the correction of vitamin D deficiency across different age groups according to baseline vitamin D metabolite levels. Conclusions: The expert discussion emphasized the need for unified interdisciplinary approaches to the diagnosis, correction, and prevention of vitamin D deficiency in the countries of Central Asia. The proposed recommendations may serve as a foundation for the development of national clinical protocols and the implementation of effective preventive and therapeutic strategies in the countries of Central Asia. Full article

Background: Post-thyroxine treatment of thyroid dysfunction remains a clinical concern, especially in Middle Eastern populations. Methods: This descriptive cross-sectional study was conducted in 2023 at King Fahad Hospital, Hufof, Kingdom of Saudi Arabia. Of the 237 patients treated with L-thyroxine (L-T4) for hypothyroidism, 163 patients, almost exclusively females (152 females, 11 males), met the inclusion criteria and were enrolled. Thyroid hormones, lipid profiles, and 25-hydroxyvitamin D (25OH-D) were measured using standard laboratory assays. Results: Only 57% of patients achieved euthyroid status following L-T4 treatment, while 12.3% developed post-thyroxine-treatment (PTT) hyperthyroidism, and 30.7% developed PTT hypothyroidism. Older age was significantly associated with dysthyroidism (p = 0.018), whereas obesity (p = 0.937) and vitamin D levels (p = 0.982) were not. Total cholesterol (TC) and LDLc positively correlated with TSH levels, while elevated triglycerides (TGs) were significantly associated with PTT hyperthyroidism. The two dysthyroid subgroups were comparable across all non-thyroid parameters, including age, BMI, 25(OH)D levels, and lipid fractions. However, free T4 was significantly higher in PTT hyperthyroidism (p < 0.001); free T3 showed a trend toward higher levels in PTT hyperthyroidism (p = 0.052); and TSH was significantly higher in PTT hypothyroidism (p < 0.001). Conclusions: The proportions of patients with PTT hypo- and hyperthyroidism are aligned with international observations. Furthermore, the age was significantly associated with dysthyroidism, and dyslipidemia is the most consistent biochemical correlate of suboptimal thyroid status; however, the associations of PTT dysthyroidism with hypovitaminosis D and BMI were not noticed in this setting. Full article

Background/Objectives: Despite its beneficial effect on the healing of bone fractures and in the treatment of osteoporosis, there is still a lack of evidence on the impact of clinical outcomes after a total joint arthroplasty (TJA). This review aims to establish the role of vitamin D in clinical outcomes after a total knee arthroplasty (TKA). Methods: In this review, PubMed, Scopus and Web of Science databases were cross-checked by two reviewers independently. The inclusion criteria were original human studies published in English from 2014 to 2024. For identification-relevant studies, the search terms used were as follows: “Vitamin D” and “total knee arthroplasty” or “total knee replacement” or “total joint arthroplasty” or “total joint replacement”. Case reports, letters and expert consensuses were excluded from the analysis. Finally, 19 studies were included in this review. Results: A literature review shows that vitamin D may have an impact on patients treated for osteoarthritis (OA) of the knee with a significant prevalence of hypovitaminosis in orthopedic patients. The influence was observed for periprosthetic joint infections: PJI patients have significantly lower vitamin D levels than primary ones. Also, a greater incidence of revision knee surgery due to PJIs in the deficient group compared to the non-deficient group at a one-year follow-up was found, of up to a 2-fold increase. This affects the clinical outcome with a lower Knee Society Score (KSS) functional score in the vitamin D-deficient group. Conclusions: The current data suggest that the vitamin D metabolism pathway and its implications in orthopedic patients, especially those treated with TKA surgery, may be a significant factor that improves clinical and functional outcomes. A possible relation between a low preoperative concentration of vitamin D and its impact on the outcomes, such as the length of the hospital stay, implant survival, and risk of complications, is needed to support these findings in multicenter, prospective studies and randomized controlled trials. Full article

Background/Objectives: Anemia of inflammation (AI) is a prevalent condition linked to systemic inflammation in several chronic diseases, including chronic liver diseases. Hypovitaminosis D is frequently identified in patients with chronic diseases, and its pathogenic role in anemia is currently under investigation. The aim of this study was to prospectively investigate changes in hemoglobin concentration and inflammatory markers in vitamin D-deficient/-insufficient patients with decompensated cirrhosis after initiating vitamin D supplementation, in addition to the supplementation of other micronutrients if needed. Methods: Patients with cirrhosis discharged from decompensation were assessed at baseline and 3 months after vitamin D supplementation. Laboratory parameters of red cell series, nutrition, and micronutrients were assessed in both visits, together with markers of systemic inflammation. Results: Thirty-nine patients were included in the study, of whom 33 completed the 3-month evaluation and were analyzed [age: 62.7 ± 10.7 years; gender: n = 29 (87.9%) males; Charlson index: 5.9 ± 1.6; Model for End-Stage Liver Disease (MELD): 12.4 ± 4.5; baseline hemoglobin (Hb): 11.7 ± 1.8 g/dL (anemia n = 24 (72.7%)); mean 25-hydroxyvitamin D (25OHD) plasma level: 15.5 ± 8.6 µg/L]. A significant increase in plasma 25OHD (40.1 ± 17.8, p < 0.001) and in Hb (12.4 ± 2.0, p = 0.01) was observed at 3 months with a decrease in the prevalence of anemia (n = 17, p = 0.015) and of Interleukin 6 in plasma levels [IL-6, 10.7 (5.8–23.3) vs. 6.5 (4.1–11.8), p = 0.016]. A greater rise in hemoglobin was correlated with higher plasma IL-6 concentration at baseline. Milder anemia and indexes of hypoferremia at baseline, along with optimal renal function and plasma levels of 25OHD at 3 months, were linked to resolution of anemia. Conclusions: Treating vitamin D deficiency together with other micronutrient deficits is associated with inflammation amelioration and improvement in anemia in patients with cirrhosis following discharge from acute decompensation. This paper supports the potential role of vitamin D in the management of anemia in patients with decompensated cirrhosis by modulating systemic inflammation. Full article

Background: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with the risk of several chronic and acute diseases. However, updated data on vitamin D status in Mediterranean countries, including Italy, remain limited, hindering effective public health strategies. Objective: To assess serum 25(OH)D levels and their seasonal variation in healthy blood donors aged 18–65 years living in Northern Italy and not taking vitamin D supplements. Given the latitude and the high levels of environmental pollution, cutaneous vitamin D synthesis may be impaired in this population. Recent Italian guidelines on supplementation emphasize the need for updated data on the prevalence of hypovitaminosis D and seasonal variation in endogenous vitamin D synthesis. Methods: In this exploratory retrospective cross-sectional study, 534 blood donors (268 men and 266 women) attending the Transfusion Medicine Unit of the Verona University Hospital were enrolled between April 2016 and May 2018. Serum 25(OH)D concentrations were analyzed by season. Clinical, lifestyle, pharmacological and dietary characteristics were also collected. Results: Among healthy, normal-weight individuals, the prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/L) was low and limited to one-two months per year. Overweight and obesity significantly reduced the likelihood of achieving adequate 25(OH)D levels through cutaneous synthesis for several months. Mean 25(OH)D concentrations were higher than those previously reported in the same area, while seasonal variation remained preserved. Conclusions: In a relatively small non-supplemented population of blood donors living in a high polluted urban area of Northern Italy, seasonal vitamin D synthesis seems to be preserved. These updated data show higher 25(OH)D levels compared to past findings. Although these data certainly warrant further validation through a national survey involving other regions of Italy and in not selected population, they appear to be in line with the SIOMMMS recommendations against indiscriminate serum 25(OH)D testing and against routine supplementation for healthy normal-weight individuals under 70 years. Full article

Survivors of childhood leukemia are at increased risk of long-term skeletal complications, including reduced bone mineral density (BMD). Vitamin D deficiency and genetic variations in the vitamin D receptor (VDR) gene are important factors influencing bone health, yet their combined effects remain insufficiently studied, particularly in North African populations. This case-control study included 130 survivors of childhood acute lymphoblastic leukemia (ALL) in remission (age range: 5–26 years) and 110 age- and sex-matched healthy controls recruited from Beni Messous Hospital. BMD was assessed at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry and expressed as z-scores. Serum 25-hydroxyvitamin D levels were measured, and VDR polymorphisms (FokI, ApaI, and BsmI) were analyzed using PCR-RFLP. Hypovitaminosis D was observed in 43.85% of patients at diagnosis and 23.07% after remission. Survivors had significantly lower BMD compared with controls at both the lumbar spine (z-score: −4.26 ± 0.75 vs. 0 ± 1, p < 0.001) and femoral neck (−3.78 ± 0.45 vs. 0 ± 1, p < 0.001). Reduced BMD for age was identified in 30% of patients. Variant genotypes TT (FokI), AA (BsmI), and CC (ApaI) were more frequent in patients and were associated with lower BMD (p < 0.0001). These findings suggest that hypovitaminosis D and VDR polymorphisms may be associated with bone health in survivors of childhood leukemia. The coexistence of these factors may contribute to interindividual variability in BMD. Full article

Background/Objectives: Population aging has been accompanied by increased institutionalization of older adults and a high prevalence of vitamin D deficiency in this group. Although the literature suggests a possible relationship between vitamin D and cognition, findings remain inconsistent, particularly in institutional settings. This cross-sectional study aimed to investigate factors associated with vitamin D deficiency in institutionalized older adults, emphasizing the role of vitamin D supplementation and length of institutionalization, as well as to evaluate the association between serum vitamin D levels, cognitive decline, and dementia. Methods: A total of 104 older adults living in different long-term care institutions (LTCFs) in the city of Pelotas, RS, Brazil, were evaluated. Sociodemographic, clinical, and nutritional data were collected via interviews and medical record review. Serum 25-hydroxyvitamin D levels were categorized according to the Institute of Medicine cutoffs (<20 ng/mL and ≥20 ng/mL). Cognitive decline was assessed using the Mini-Mental State Examination, and dementia was evaluated with the Clinical Dementia Rating scale. Analyses included bivariate tests and binary logistic regression. Results: A high prevalence of vitamin D deficiency (52.9%), cognitive decline (83.6%), and questionable or mild dementia (79.4%) was observed. In multivariate analysis, vitamin D supplementation remained independently associated with vitamin D deficiency, whereas no significant association was observed between vitamin D levels and cognitive decline or dementia. Conclusions: Vitamin D deficiency in institutionalized older adults is predominantly associated with contextual and care-related factors rather than cognitive impairment, highlighting the importance of systematic nutritional monitoring and vitamin D supplementation strategies in institutional settings. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute the most common underlying cause of chronic kidney disease in pediatric populations. Maternal hypovitaminosis D links to mesoderm-related birth defects, leading to our hypothesis that maternal vitamin D deficiency (VDD) impairs renal development (a mesoderm-derived process) and induces offspring CAKUT. To investigate whether a low-vitamin D level can cause CAKUT, we used vitamin D-free diets to induce a maternal vitamin D deficiency mice model. The maternal vitamin D deficiency (VDD) mice models and normal vitamin D status (CON) were successfully established by administering a vitamin D-free or vitamin D-sufficient diet for 4 weeks prior to pregnancy. The overall incidence of CAKUT was significantly increased in VDD neonatal mice (19.4% vs. 2.44%; p = 0.0006), with a higher incidence of early duplicated budding in E11.5. E11.5 ureteric bud tissue revealed significantly increased activity of Gdnf-Ret-p-Erk1/2 signaling in the VDD group. In vivo intervention with the p-Erk1/2 antagonist U0126 in the pregnant VDD mice model at E10.5 improved CAKUT occurrence in offspring with p-Erk1/2 expression decreasing toward normal levels. Early metanephric ureteric bud H3K4me3 CUT&TAG analysis at E12.5 revealed chromatin activation patterns, which revealed that the downregulation of Hnf1β promoter region peaks was accompanied by reduced Hnf1β expression, and Robo2 promoter region peak was upregulated with increased Robo2 expression in the VDD group. Maternal vitamin D deficiency in mice significantly increased offspring CAKUT incidence. This phenotype was mediated by enhanced Gdnf-Ret-p-Erk1/2 signaling and reversed by p-Erk1/2 inhibition, with VDD inducing epigenetic remodeling of Hnf1β and Robo2 promoters. Full article

An inverse correlation between serum vitamin D levels and hidradenitis suppurativa (HS) severity is frequently reported, yet the causal nature and direction of this association remain unresolved. A systematic review was conducted following PRISMA guidelines, identifying 12 relevant studies. A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method was subsequently performed using genetic instruments for vitamin D from the UK Biobank (n = 417,580) and HS summary statistics from FinnGen (n = 1420). The systematic review confirmed a high prevalence of vitamin D deficiency (<20 ng mL⁻¹) among HS patients (weighted mean 17.90 ng mL⁻¹) and identified inverse correlations between vitamin D levels and disease severity, active lesions, and C-reactive protein (CRP), while supplementation improved clinical outcomes. A null MR estimate consistent with the absence of a detectable average linear causal effect of lifelong genetically predicted 25(OH)D levels on HS risk in the analyzed population was observed. Sensitivity analyses yielded consistent null results with no significant horizontal pleiotropy. The results suggest that hypovitaminosis D is likely a marker of the systemic inflammatory state rather than a direct causative factor. The observed clinical benefits of vitamin D supplementation warrant further interventional studies to define its potential therapeutic role. Full article