Effectiveness of different local actions to control vitamin D prescription in Italy.

INTRODUCTION: In the last decade, the significant expenditure and consumption increase of vitamin D in Italy led some regions to adopt strategies to improve prescribing appropriateness and contain expenditure. MATERIALS AND METHODS: Using the statistical analysis method of interrupted time series for consumption and expenditure of cholecalciferol, different types of interventions adopted in four Italian regions and their efficacy were evaluated. RESULTS: Molise achieved the best results by adopting a health professionals' education program in addition to a prescriber-sanction system. Emilia-Romagna also opted for a medical education strategy, but the results were less relevant due to the lack of penalties. Lazio obtained a slowdown in consumption growth by targeting on the utilization of lower-cost per defined daily dose (DDD) packs and adopting a therapeutic plan. Sardinia showed a decrease in expenditure by adopting a target threshold of lower-cost formulation. CONCLUSION: The reimbursement of the lowest-cost packs within the National Health Service (NHS) undoubtedly influences spending trend, but it does not solve prescriptive inappropriateness.

Assessment, treatment and prevention of vitamin D deficiency.

Vitamin D deficiency is prevalent among various groups in the UK, and can result from insufficient sunlight exposure and dietary intake. There is a population-wide recommendation of 10 micrograms (400 international units) of vitamin D per day, with a daily supplement advised. However, supplement use is often suboptimal, compounding the risk of deficiency. Long-term vitamin D deficiency can cause rickets in children and osteomalacia or osteoporosis in adults. Therefore, it is important that nurses recognise which groups are at increased risk of vitamin D deficiency and understand how to assess people's vitamin D status. Nurses also need to be able to support the prevention and treatment of low vitamin D levels, which typically involves supplementation and lifestyle changes.

Hypoparathyroidism-related health care utilization and expenditure during the first postoperative year after total thyroidectomy for cancer: a comprehensive national cohort study.

Objectives: Hypoparathyroidism is the most common complication of total thyroidectomy for cancer, and requires calcium and/or vitamin D supplementation for an unpredictable period of time. The additional cost associated with this complication has not hitherto been assessed. The aim of this study was to assess the economic burden of postoperative hypoparathyroidism after total thyroidectomy for cancer in France. Methods: Based on the French national cancer cohort, which extracts data from the French National Health Data System (SNDS), all adult patients who underwent a total thyroidectomy for cancer in France between 2011 and 2015 were identified, and their healthcare resource use during the first postoperative year was compared according to whether they were treated postoperatively with calcium and/or vitamin D or not. Univariate and multivariate cost analyses were performed with the non-parametric Wilcoxon test and generalized linear model (gamma distribution and log link), respectively. Results: Among the 31,175 patients analyzed (75% female, median age: 52y), 13,247 (42%) started calcium and/or vitamin D supplementation within the first postoperative month, and 2,855 patients (9.1%) were still treated at 1 year. Over the first postoperative year, mean overall and specific health expenditures were significantly higher for treated patients than for untreated patients: €7,233 vs €6,934 per patient (p<0.0001) and €478.6 vs €332.7 per patient (p<0.0001), respectively. After adjusting for age, gender, Charlson Comorbidity index, ecological deprivation index, types of thyroid resection, lymph node dissection and complications, year and region, the incremental cost of overall health care utilization was €142 (p<0.004). Conclusion: Our study found a significant additional cost in respect of health expenditures for patients who had hypoparathyroidism after thyroidectomy for cancer, over the first postoperative year. Five-year follow-up is planned to assess the impact of more severe long-term complications on costs.

Is vitamin D supplementation program in Iranian schools effective in reducing adolescent depressive symptoms? Cost effectiveness study.

PURPOSE: We aimed to assess the cost-effectiveness of the vitamin D supplementation program in Iranian adolescents reducing adolescent depressive Symptoms. METHODS: In the current cost-effectiveness analysis, the viewpoint of Iran's Ministry of Health was selected. The target population was 1,519,762 Iranian high school students (733,657 girls and 786,105 boys). The total costs of the vitamin D supplementations program were based on the reports of the Nutrition Improvement Office of Iran's Ministry of Health and were adjusted to 2018. The variable of Quality-Adjusted Life Years (QALYs) was considered a suitable variable for estimating the effectiveness of vitamin D supplementation. We chose one year as the time horizon. A decision tree model was constructed in TreeAge Pro. The results of the cost-effectiveness analysis were reported in term of the Incremental Cost-Effectiveness Ratio (ICER). RESULTS: The results of our study showed that the estimated cost per QALY gained of the vitamin D supplementation program is equal to 1528.6676 $, which indicates that vitamin D supplementation in adolescents(11-18Y) is a cost-effective and a dominant strategy in preventing depression through the cost-saving and QALYs increment compared to the no intervention. Sensitivity analysis showed that the possible variations in vitamin D supplement costs could not alter the results, and vitamin D supplementation may be a predominant and cost-effective strategy to prevent adulthood depression with a 100% probability. CONCLUSION: The national program of vitamin D supplementation among Iranian adolescents was a cost-efficient strategy reducing adolescent depressive Symptoms through the cost-saving and QALYs increment compared to the no intervention.

Preoperative vitamin D supplementation is a cost-effective intervention in arthroscopic rotator cuff repair.

BACKGROUND: This study investigates the potential role of preoperative 25(OH)D supplementation as a cost-effective strategy to decrease revision rotator cuff repair (RCR) rates and lower the total health care burden from patients undergoing primary arthroscopic RCR. Previous literature has emphasized the importance of vitamin D on bone health maintenance, soft tissue healing, and outcomes in RCR. Inadequate preoperative vitamin D levels may increase revision RCR rates following primary arthroscopic RCR. Although 25(OH)D deficiency is common in RCR patients, serum screening is not routinely performed. METHODS: A cost-estimation model was developed to determine the cost-effectiveness of both preoperative selective and nonselective 25(OH)D supplementation in RCR patients in order to reduce revision RCR rates. Prevalence and surgical cost data were obtained from published literature through systematic reviews. Cost of serum 25(OH)D assay and supplementation were obtained from public-use data. Mean and lower and upper bounds of 1-year cost savings were calculated for both the selective and nonselective supplementation scenarios. RESULTS: Preoperative 25(OH)D screening and subsequent selective 25(OH)D supplementation was calculated to result in a mean cost savings of $6,099,341 (range: -$2,993,000 to $15,191,683) per 250,000 primary arthroscopic RCR cases. Nonselective 25(OH)D supplementation of all arthroscopic RCR patients was calculated to result in a mean cost savings of $11,584,742 (range: $2,492,401-$20,677,085) per 250,000 primary arthroscopic RCR cases. Univariate adjustment projects that selective supplementation is a cost-effective strategy in clinical contexts where the cost of revision RCR exceeds $14,824.69 and prevalence of 25(OH)D deficiency exceeds 6.67%. Additionally, nonselective supplementation is a cost-effective strategy in clinical scenarios where revision RCR cost is ≥$4216.06 and prevalence of 25(OH)D deficiency is ≥1.93%. CONCLUSIONS: This cost-predictive model promotes the role of preoperative 25(OH)D supplementation as a cost-effective mechanism to reduce revision RCR rates and lower the overall health care burden from arthroscopic RCR. Nonselective supplementation appears to be more cost-effective than selective supplementation, likely due to the lower cost of 25(OH)D supplementation compared to serum assays.

Vitamin D supplementation for children with mild to moderate asthma: an economic evaluation.

INTRODUCTION: A large proportion of asthma patients remain uncontrolled despite using inhaled corticosteroids. Some add-on therapies such as vitamin D supplements have been recommended for this subgroup of patients. The purpose of this study was to assess the cost-utility of vitamin D supplementation in children with mild to moderate persistent asthma in Colombia. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. The model was analyzed probabilistically, and a value of information (VOI) analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS: The mean incremental cost of vitamin D supplementation versus no supplementation is USD $44.60. The mean incremental benefit of vitamin D supplementation versus no supplementation is 0.05 QALY. This position of absolute dominance (vitamin D supplementation has lower costs and higher QALYs than no supplementation) is unnecessary to estimate the incremental cost-effectiveness ratio. Our base-case results were robust to variations in all assumptions and parameters. CONCLUSION: Add-on therapy with vitamin D supplementation is a cost-effective strategy for patients between 6 and 17 years of age with mild to moderate asthma in Colombia.

Cost-effectiveness analysis of adding omega-3 or vitamin D supplementation to standard therapy in treating painful crises of pediatric sickle cell disease patients.

OBJECTIVE: Painful crises represents a predominant complication of sickle cell disease (SCD). The only approved treatments for painful crises in many countries are hydroxyurea plus potent analgesics. Our earlier clinical trial concluded that omega-3 and vitamin D had a potential therapeutic impact on painful crises. However, there is limited research evaluating their therapeutic applications and cost-effectiveness. This paper aims at comparing the cost-effectiveness of omega-3 and vitamin D supplementation to the standard therapy in treating painful crises among children with SCD. PATIENTS AND METHODS: Cost-effectiveness analyses of daily supplementation of omega-3 and vitamin D were performed. The economic evaluation was based on data derived from a prospective 10-month randomized clinical trial (n = 165 patients; 15 patients dropped). 50 patients were recruited into the omega-3 + standard therapy group (hydroxyurea and folic acid daily with ibuprofen as needed), 50 patients into the vitamin D + standard therapy group, and 50 patients receiving standard therapy alone served as a control group. Outcome measures from the randomized clinical trial were used to determine incremental effectiveness. Cost estimates were calculated from the healthcare payer's perspective. The analysis considered the improvement in various outcome measures and are presented here as percent change from baseline to determine the incremental effectiveness and the incremental cost for the treatment of both interventions. RESULTS: Adding omega-3 or vitamin D to the standard therapy was more cost-effective than standard treatment alone. Vitamin D was a cheaper but less cost-effective alternative for most outcomes between the two treatments, including LDL-C and HDL-C. It was also more cost-effective but less clinically effective in reducing vaso-occlusive crisis episodes and pain severity. Omega-3 supplementation was significantly more cost-effective than vitamin D supplementation and the standard treatment for those measures. CONCLUSIONS: The present study showed that using vitamin D and omega-3 as add-on treatments for a painful crisis in pediatric sickle cell disease could have overall cost-saving and clinical benefits. However, further studies with a longer treatment duration are needed to establish more significant effects of the interventions for better policy and clinical decision-making.

Vitamin D Supplementation in the Assessment of Cardiovascular Risk Factors in Overweight and Obese Children.

Background: Childhood obesity is associated with cardiovascular-disease (CVD) risk factors, an unfavorable lipid profile and reduced levels of 25(OH)D. The aim of our study is to evaluate whether vitamin D supplementation may play a role in the assessment of the CVD risk factors in overweight/obese children and adolescents. Methods: We performed a retrospective observational study involving children (9−15 years of age) with a known diagnosis of overweight or obesity (BMI > 25) and decreased levels of 25(OH)D (<25 ng/mL), who underwent oral vitamin D supplementation (100,000 UI, one vial/month) for six months. The anthropometric parameters, 25(OH)D, serum lipids and ALT levels were measured at the beginning (T0) and after 6 months (T1). Results: Of the 58 patients recruited, 45 had an increase in the serum 25(OH)D levels after supplementation. Vitamin D supplementation was associated with a decrease in the serum levels of the total cholesterol (p = 0.009), LDL-C (p = 0.005) and ALT (p = 0.005), and an increase in HDL-C (p = 0.03). These results were confirmed when the correction for the body mass index (BMI) was applied. Conclusions: The favorable effect of vitamin D supplementation on the total cholesterol, LDL-C, HDL-C and ALT could transform these values into modifiable risk factors starting in early childhood, with beneficial effects on long-term health.

Electronic health record data use in the assessment of quality indicators for glucocorticoid osteoporosis screening in systemic lupus erythematosus.

OBJECTIVE: To determine whether electronic health record (EHR) data components could be identified and used to assess bone health quality indicators in patients with systemic lupus erythematosus as a foundation for population health management. METHODS: We identified patients in our EHR system who had diagnosis codes for lupus from 2012 to 2017 and characterized them based on the frequency and dosage of prescribed glucocorticoid medications. The medical records of patients who received repeated high-dose glucocorticoid orders were further reviewed for osteoporosis, osteoporotic fractures, receipt of appropriate preventive screening, and orders for protective medications based on established quality indicators. Descriptive statistics were calculated to summarize results. RESULTS: We identified 617 patients with a lupus diagnosis; 414 received glucocorticoid prescriptions, 189 received chronic, high-dose; and 83 received chronic, low-dose prescription orders. Of those with chronic high-dose glucocorticoid prescriptions, 14% had an osteoporosis diagnosis, 3% had an osteoporotic fracture, 51% received a prescription for calcium/vitamin D, 43% had bone mineral density screening orders, 20% received a spine radiograph order, 29% had a documented T-score, 12% received a prescription for osteoporosis medication, and 6% had a documented osteoporosis screening. We were able to identify data elements in the EHR for all nine components of the osteoporosis management quality indicator. CONCLUSIONS: It is possible to identify data in the EHR for all attributes of the quality indicator for osteoporosis in lupus patients who receive chronic high-dose glucocorticoids. However, missing data and need to extract data from text-based notes may make development of population management tools challenging.

Assessment of calcium and vitamin D medications adherence in patients with hypoparathyroidism after thyroidectomy.

In this study, we found that patients with hypoparathyroidism had a problem with calcium medication compliance, and this problem increased with the duration of the disease. We also showed that patients are concerned about the possible side effects of drugs. INTRODUCTION: In this study, we aimed to evaluate adherence to active vitamin D and calcium replacement in patients with post-surgical hypoparathyroidism. METHODS: To elucidate the medication adherence, we performed a questionnaire survey using the six-item "Medication adherence questionnaire"(MAQ). The first, second, and sixth questions reflect the motivation status of the patients whereas the third, fourth, and fifth questions reflect the knowledge about the medication that is received. The responses are scored and patients are classified regarding their motivation to and knowledge about the particular drug. RESULTS: Totally, 64 patients (male: 12/female: 52; mean age 48.6±11.6 years) who had post-operative hypoparathyroidism were included in our study. Median disease durance was 60 months (min-max: 12-295 months). We found that motivation score of calcium usage was significantly lower compared to vitamin D usage (p<0.001). The calcium motivation score was reversely correlated with disease duration (r= -0.256 and p=0.046). The most common worry about calcium usage was nephrotoxicity, and the most common worries about calcitriol treatment were kidney damage and polyuria. One-third of the patients were taking oral calcium and calcitriol less than the recommended dose. CONCLUSION: One-third of patients lack motivation to use calcium whereas half of the patients experiences anxiety about drug-related side effects. This is a preliminary study showing that vital calcium and active vitamin D intake may be interrupted due to side effect anxiety.

Risk Analysis of Denosumab-Induced Hypocalcemia in Bone Metastasis Treatment: Renal Dysfunction Is Not a Risk Factor for Its Incidence in a Strict Denosumab Administration Management System with Calcium/Vitamin D Supplementation.

We have reported that a strict denosumab administration management system with oral calcium/vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for ≥grade 2 hypocalcemia incidence have been identified in denosumab-treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age ≥65 years (odds ratio, 95% confidence interval: 2.57, 1.11-5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71-8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of all-grade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.

Challenges and Opportunities for Osteoporosis Care During the COVID-19 Pandemic.

PURPOSE: The coronavirus disease 2019 (COVID-19) has both directly and indirectly affected osteoporosis diagnosis and treatment throughout the world. METHODS: This mini-review summarizes the available evidence regarding the effects of COVID-19, its treatment, and the consequences of the pandemic itself on bone health. Additionally, we review evidence and expert recommendations regarding putative effects of osteoporosis medications on COVID-19 outcomes and vaccine efficacy and summarize recommendations for continuation of osteoporosis treatment during the pandemic. RESULTS: The use of standard screening procedures to assess for osteoporosis and fracture risk declined dramatically early in the pandemic, while rates of fragility fractures were largely unchanged. COVID-19, its treatments, and public health measures to prevent viral spread are each likely to negatively affect bone health. Osteoporosis treatments are not known to increase risk of adverse events from COVID-19, and preclinical data suggest possible beneficial effects of some therapies. Vitamin D deficiency is clearly associated with adverse outcomes from COVID-19, but it remains unclear whether vitamin D supplementation may improve outcomes. Osteoporosis treatment should be continued whenever possible, and recommendations for substituting therapies, if required, are available. CONCLUSION: The COVID-19 pandemic has decreased screening and disrupted treatment for osteoporosis. Osteoporosis medications are safe and effective during the pandemic and should be continued whenever possible. Further studies are needed to fully understand the impact of the COVID-19 pandemic on long-term bone health.

Insufficient Assessment and Treatment of Vitamin D in the Medical Management of Adolescents with Anorexia Nervosa.

PURPOSE: Suboptimal vitamin D levels are implicated in low bone mineral density, a common medical complication of anorexia nervosa. This study aimed to examine the frequency of vitamin D assessment and treatment for adolescents with anorexia nervosa in outpatient medical management. DESIGN AND METHODS: Retrospective chart review was used to examine 179 adolescents (M age = 15.5 years, SD = 2.2), newly diagnosed with anorexia nervosa at a tertiary care medical center in the United States between January 2000 and July 2016. RESULTS: Only 16% of patients (n = 29) received serum vitamin D assessments following diagnosis, of whom 52% had suboptimal vitamin D levels (n = 15). Only three patients with suboptimal vitamin D were advised to begin supplementation. No patients in our sample were encouraged to begin prophylactic vitamin D supplementation. CONCLUSIONS/PRACTICE IMPLICATIONS: Findings from this study highlight the critical need for widespread care team education about vitamin D assessment and treatment in the medical management of adolescents with anorexia nervosa, particularly in light of the potentially serious consequences of bone mineral density.

Quality assessment of traditional and conventional medicine clinical practice guidelines for osteoporosis.

ABSTRACT: Numerous studies have reported the variable quality of clinical practice guidelines (CPGs) across various domains. The aim of this study was to systematically assess the quality, methodology, and consistency of recently developed traditional and conventional medicine CPGs that focus on the management of osteoporosis and provide helpful recommendations for patients with osteoporosis.From June 2020 to July 2020, CPGs with osteoporosis targeting any age were systematically retrieved. All CPGs of traditional and conventional medicine related to the assessment and diagnosis, management, and clinical therapeutic and pharmacological recommendations with osteoporosis were eligible for inclusion in this study. The excluded documents included guidelines without recommendations, secondary publications derived from CPGs, consensus statements, or consensus conferences based on the opinion of panelists, systematic reviews, editorials, clinical trials, and single-author documents. The quality of CPGs was independently examined by three assessors using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. AGREE II consists of 6 domains; scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. Consequently, selected CPGs were graded as recommended (A), recommended with modifications (B), or not recommended (C), and the specific treatments and preventive recommendations in the CPGs were summarized.The quality of the 15 CPGs assessed varied across the AGREE II domains. The overall quality ranged from 3.0 to 6.0 out of 7. The domain that had the highest scores were "clarity of presentation," with a mean value of 69.0% (range 46%-83%); "editorial independence" had the lowest score of 30.2% (range 0%-75%). The conventional CPGs focused on pharmacological treatments, calcium and vitamin D intake, and prevention, while the traditional CPGs consistently emphasized on herbal medicine and non-pharmaceutical treatment and management.Further development of CPGs will require improvement in domains where low item scores have been obtained in the quality assessment in this present study. Further research is needed on alternative modalities for osteoporosis, especially complementary approaches, and higher quality CPGs are needed to facilitate evidence-based clinical practice.

A pulse survey: assessment and management of bone loss in spinal cord injury.

STUDY DESIGN: An online survey OBJECTIVES: To describe current clinical practices regarding osteoporosis assessment and management in people with Spinal Cord Injury (SCI) and compare them to recommended diagnostic tests and interventions. SETTING: An international collaboration surveying professionals working in SCI Medicine. METHODS: Online cross-sectional survey regarding clinical practice trends in the assessment and treatment of osteoporosis in people with SCI. Assessment of whether discrete professional characteristics influenced practices and if those practices were consistent with recommendations from professional organizations. RESULTS: Eighty-two professionals working in SCI Medicine completed the survey. Respondents were equally likely to test for bone loss during the post-acute phase (between 4- and 18-months post injury) and after low impact fracture (41.46% and 42.68%, respectively) and more likely to test during the chronic phase (51.22%). The majority of respondents (n = 56, 70%) assessed bone density with DXA at the hip, and many (48.78%, n = 40) prescribed simultaneous mobilization, vitamin D and calcium to prevent bone loss in the acute, post-acute and chronic phases. A number of evaluations and interventions were inconsistent with best practice recommendations. CONCLUSIONS: Given that reported practices for detection and treatment of osteoporosis in SCI are inconsistent and not data-driven, there is need for dissemination and adoption of existing clinical practice guidelines.

Burosumabe para o tratamento de hipofosfatemia ligada ao cromossomo X em adultos e crianças / Burosumabe for or treatment of hypophosphatemia linked to or chromosome X in adults and infants

CONTEXTO: A hipofosfatemia ligada ao cromossomo X (HLX) é considerada uma doença ultrarrara, cronicamente debilitante e deformante. É uma doença causada por mutações no gene regulador do fosfato com homologia às endopeptidases do cromossomo X (PHEX), que leva a perda de função do mesmo, gerando erros na detecção de fosfato e aumento dos níveis de fator de crescimento de fibroblastos 23 (FGF23). Os maiores achados clínicos na XLH são hipofosfatemia, retardo no crescimento, raquitismo e/ou osteomalácia. Anormalidades esqueléticassão sinais precoces de HLX. Fraturas, perdas auditivas, problemas dentários e osteomalácia podem aparecer além da perda de qualidade de vida associada. O tratamento convencional é realizado com administração de fosfato e vitamina D. Esta não é uma terapia com alvo no mecanismo fisiopatológico da doença, resumindo-se à tentativa de minorar a hipofosfatemia e o excesso de hormônio da paratireoide. A reposição oral de fosfato e vitamina D são insuficientes para atender aos objetivos do tratamento, não logrando alterar a densidade mineral óssea da coluna e quadril em adultos e estão associados a efeitos adversos importantes. Considera-se a possibilidade de inibição da atividade do FGF23 como uma medida terapêutica única para doenças hipofosfatêmicas causadas pelo excesso de FGF23. O burosumabe é um anticorpo monoclonal, sendo o primeiro medicamento desenvolvido para inibir a FGF23 e com isso aumentar a reabsorção de fosfato do rim, para que pela produção de vitamina D, melhore a absorção intestinal de cálcio e fosfato reduzindo os danos causados pela HLX. Agências internacionais aprovaram seu uso inicialmente nas populações pediátricas, em que o benefício clínico na melhora da HLX está mais estabelecido. Alguns países ampliaram o uso para a população adulta. TECNOLOGIA: burosumabe (CRYSVITA®). PERGUNTA: O uso de burosumabe para o tratamento da hipofosfatemia ligada ao cromossomo X é eficaz e seguro quando comparado ao tratamento com fosfato e vitamina D ou placebo? EVIDÊNCIAS CIENTÍFICAS: Em revisão sistemática da literatura, o demandante selecionou seis estudos clínicos que avaliaram o uso do burosumabe no tratamento da HLX. Três destes foram realizados em pacientes pediátricos e três em pacientes adultos. Há algumas limitações inerentes aos estudos de fase 2 e 3 selecionados. Os resultados apresentados demostram benefícios clínicos especialmente na melhora do raquitismo em crianças, da mobilidade e crescimento com tratamento com burosumabe em relação ao tratamento com fosfato e vitamina D. O estudo de Imel, et al., 2019 mostrou melhora do Escore Radiographic Global Impression of Change (RGI-C) ­ global ­ diferença média dos mínimos quadrados em 40 semanas: 1,1 (IC95% 0,8 ­ 1,5; ; p <0,0001) favorecendo o tratamento com burosumabe. O estudo de Carpenter et al., 2018, avaliou o mesmo escore em 40 semanas e obteve os seguintes resultados de acordo com a posologia: burosumabe, duas vezes por mês (+1,66 ± 0,09); burosumabe, uma vez por mês (+1,47 ± 0,14); burosumabe, todos os pacientes (+1,56 ± 0,08). Ao avaliar a gravidade do raquitismo pelo escore Thatcher, a diferença média dos mínimos quadrados em 40 semanas de acordo com a posologia foi: burosumabe, duas vezes por mês: -1,06 ± 0,11; p< 0,0001; burosumabe, uma vez por mês: -0,73 ± 0,10; p<0,0001 1; burosumabe, todos os pacientes: -0,89 ± 0,0,07. Em adultos também houve benefícios com o uso do medicamento, porém menos consistentes que na população pediátrica. Insogna et al., 2018, avaliaram a cura completa de fraturas ativas ou pseudofraturas em 24 semanas. Os seguintes resultados foram observados: burosumabe (43,1%) versus placebo (7,7%); Odds ratio OR 16,8 (IC95% não reportado); p<0,0001. Os estudos em adultos foram comparados com placebo, logo os resultados favoráveis ao burosumabe foram esperados. Em relação à segurança, tanto na população pediátrica quanto adulta, o burosumabe não acarretou nenhum evento adverso grave nos estudos realizados. AVALIAÇÃO ECONÔMICA: O demandante realizou uma análise de custo-efetividade. O modelo foi construído em uma planilha MS Excel com base em uma estrutura de Markov com horizonte temporal de toda a vida. Dois modelos de custo-efetividade foram apresentados, um considerando a população pediátrica (idades de 1 a 17 anos) e outro a população adulta (idade ≥18 anos). A razão de custo-efetividade incremental (RCEI) do burosumabe em relação ao uso de fosfato e vitamina D em pediatria foi de R$ 2.401.312,64/QALY e para a população adulta de R$ 2.534.873,52 /QALY. Nas análises de sensibilidade univariada para ambas as populações o modelo se mostrou sensível ao custo do burosumabe e idade de início do tratamento. O modelo possui limitações, entre elas a ausência de dados de incidência da HLX na população brasileira e os dados disponíveis no DATASUS relacionados a procedimentos e tratamentos provavelmente estão subestimados em relação a doença. Por tratar-se de doença rara, a falta de registro de dados e suas implicações podem impactar no modelo e suas análises de sensibilidade. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A análise de impacto orçamentário (AIO) realizada pelo demandante previu população de pacientes elegíveis para o tratamento com burosumabe baseada em referências internacionais pela ausência de dados registrados no Brasil. Foi adotado um horizonte de 5 anos. O demandante apresentou um cenário base com incorporação de burosumabe para 100% dos pacientes. No cenário ­base os impactos orçamentários em cinco anos foram: R$ 197.249.738,34 para a população pediátrica e R$ 224.968.284,47 para a população adulta. Um outro cenário considerando que 50% seriam diagnosticados e tratados com burosumabe ou fosfato e vitamina D em 5 anos foi apresentado: R$ 98.624.869,17 para a população pediátrica e R$ 67.490.485,34 para a população adulta. O cenário 3 considerou a introdução gradual do burosumabe em 20%, 40%, 50% e 75%, chegando a 100% no quinto ano, assim o impacto em 5 anos foi de: R$ 65.209.976,69 para a população pediátrica R$ 48.026.685,80 para a população adulta. Apesar desse cenário ser o mais próximo do real, a disseminação pode ser maior já que há ausência de tratamento eficaz para a doença. Além disso, a AIO têm provavelmente subestimativas da população por usar uma média internacional e não considerar a incidência da doença ao longo do horizonte temporal. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: De acordo com os critérios adotados nessa análise, não foram localizados medicamentos em desenvolvimento clínico para a doença. DISCUSSÃO: A análise da evidência clínica apresentada sugere que a tecnologia proposta apresenta efetividade superior à única alternativa disponível atualmente para tratamento da HLX no SUS, com confiabilidade moderada, corroborando atuais recomendações para seu uso em diretrizes internacionais. Por ser uma doença rara, com limitações de dados brasileiros disponibilizados, as análises econômicas submetidas pelo demandante indicam limitações metodológicas, reduzindo a confiabilidade das conclusões a respeito de custo-efetividade e impacto orçamentário no cenário brasileiro podendo ter os valores subestimados. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do plenário não consideraram como robustas as evidências científicas de eficácia e segurança do borusomabe. Além disso, foi considerado elevado o valor de custo-efetividade incremental, assim como o impacto orçamentário. Sendo assim, no dia 7 de outubro de 2020, em sua 91ª reunião de plenário, os membros da Conitec foram desfavoráveis à recomendação de incorporação no SUS do "Burosumabe para o tratamento de hipofosfatemia ligada ao cromossomo X em adultos e crianças". CONSULTA PÚBLICA: a Consulta Pública nº 56 foi realizada entre os dias 04/11/2020 e 30/11/2020. Foram recebidas 619 contribuições, sendo 103 pelo formulário para contribuições técnico-científicas e 516 pelo formulário para contribuições sobre experiência ou opinião. Após apreciação das contribuições recebidas, o Plenário da Conitec entendeu que houve argumentação suficiente para mudança de entendimento acerca de sua recomendação preliminar. A maioria das contribuições foram contra recomendação e se concentraram nos seguintes benefícios do medicamento: eficácia do tratamento; melhora dos sintomas; melhora dos níveis de fosfato e qualidade de vida. Desse modo, a Comissão mudou a recomendação inicial. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da Conitec presentes na 94ª reunião ordinária, no dia 04 de fevereiro de 2021, consideraram que os benefícios clínicos do tratamento foram mais acentuados na população pediátrica apresentando desfechos consistentes. Diante do exposto, os membros presentes deliberaram, por unanimidade, a recomendação do burosumabe para o tratamento de hipofosfatemia ligada ao cromossomo X em crianças conforme protocolo Clínico e Diretrizes Terapêuticas (PCDT) e recomendar a não incorporação do burosumabe para o tratamento de hipofosfatemia ligada ao cromossomo X em adultos. Assim, foi assinado o Registro de Deliberação nº 589/2021. DECISÃO: incorporar o burosumabe para o tratamento da hipofosfatemia ligada ao cromossomo X em crianças conforme Protocolo Clínico e Diretrizes Terapêuticas (PCDT) e não incorporar o burosumabe para o tratamento da hipofosfatemia ligada ao cromossomo X em adultos, do Sistema Único de Saúde - SUS, conforme Portaria nº 01, publicada no Diário Oficial da União nº 34, seção 1, página 93, em 22 de fevereiro de 2021.

The vitamin D for COVID-19 (VIVID) trial: A pragmatic cluster-randomized design.

OBJECTIVES: To determine the effect of vitamin D supplementation on disease progression and post-exposure prophylaxis for COVID-19 infection. We hypothesize that high-dose vitamin D3 supplementation will reduce risk of hospitalization/death among those with recently diagnosed COVID-19 infection and will reduce risk of COVID-19 infection among their close household contacts. METHODS: We report the rationale and design of a planned pragmatic, cluster randomized, double-blinded trial (N = 2700 in total nationwide), with 1500 newly diagnosed individuals with COVID-19 infection, together with up to one close household contact each (~1200 contacts), randomized to either vitamin D3 (loading dose, then 3200 IU/day) or placebo in a 1:1 ratio and a household cluster design. The study duration is 4 weeks. The primary outcome for newly diagnosed individuals is the occurrence of hospitalization and/or mortality. Key secondary outcomes include symptom severity scores among cases and changes in the infection (seroconversion) status for their close household contacts. Changes in vitamin D 25(OH)D levels will be assessed and their relation to study outcomes will be explored. CONCLUSIONS: The proposed pragmatic trial will allow parallel testing of vitamin D3 supplementation for early treatment and post-exposure prophylaxis of COVID-19. The household cluster design provides a cost-efficient approach to testing an intervention for reducing rates of hospitalization and/or mortality in newly diagnosed cases and preventing infection among their close household contacts.

Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United States.

BACKGROUND AND OBJECTIVES: With multiple medications indicated for mineral metabolism, dialysis providers can apply various strategies to achieve target phosphate and parathyroid hormone (PTH) levels. We describe common prescribing patterns and practice variation in mineral metabolism treatment strategies over the last decade. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of adults initiating hemodialysis at Dialysis Clinic, Inc. facilities, we assessed prescriptions of vitamin D sterols, phosphate binders, and cinacalcet longitudinally. To identify the influence of secular trends in clinical practice, we stratified the cohort by dialysis initiation year (2006-2008, 2009-2011, and 2012-2015). To measure practice variation, we estimated the median odds ratio for prescribing different mineral metabolism treatment strategies at 12 months post-dialysis initiation across facilities using mixed effects multinomial logistic regression. Sensitivity analyses evaluated strategies used after detection of first elevated PTH. RESULTS: Among 23,549 incident patients on hemodialysis, there was a decline in vitamin D sterol-based strategies and a corresponding increase in strategies without PTH-modifying agents (i.e., phosphate binders alone or no mineral metabolism medications) and cinacalcet-containing treatment strategies between 2006 and 2015. The proportion with active vitamin D sterol-based strategies at dialysis initiation decreased across cohorts: 15% (2006-2008) to 5% (2012-2015). The proportion with active vitamin D sterol-based strategies after 18 months of dialysis decreased across cohorts: 52% (2006-2008) to 34% (2012-2015). The odds of using individual strategies compared with reference (active vitamin D sterol with phosphate binder) varied from 1.5- to two-fold across facilities in 2006-2008 and 2009-2011 cohorts, and increased to two- to three-fold in the 2012-2015 cohort. Findings were similar in sensitivity analyses starting from first elevated PTH measurement. CONCLUSIONS: Over time, mineral metabolism management involved less use of vitamin D sterol-based strategies, greater use of both more conservative and cinacalcet-containing strategies, and increased practice variation, suggesting growing equipoise.

[Power station sun and hormone factory skin : A current assessment of the importance of vitamin D metabolism during human evolution and strategies for UV prevention]. / Kraftwerk Sonne und Hormonfabrik Haut : Aktuelle Standortbestimmung zur Bedeutung des Vitamin-D-Stoffwechsels während der menschlichen Evolution und Strategien zur UV-Prävention.

The sun is of great importance for human health. One important reason for this is the production of vitamin D, endorphins and many other hormones by the skin due to stimulation by sunlight. Insufficient access to sunlight increases the risk for vitamin D deficiency, a pandemic which would affect more than one billion people worldwide and under which ca. 60% of the population in Germany would suffer. The skin has a unique position in vitamin D metabolism as elementary steps for vitamin D production take place here and it is furthermore a target organ for actions of vitamin D. Due to the many positive effects of the sun, a healthy balance must be found between UV protection to shield against skin cancer but also ensuring sufficient vitamin D production. For regulation of this fragile balance between photoprotection and vitamin D production, which has accompanied mankind throughout evolution, sunscreens are an integral part of the modern lifestyle, although critical reports on possible risks for their use have recently become more frequent. This article discusses the current state of knowledge on the importance of vitamin D metabolism in human skin and the use of sun creams.