Assessment of vitamin D deficiency in recurrent BPPV patients: A cross-sectional study.

PURPOSE: This study aimed to investigate the vitamin D deficiency of patients with BPPV recurrence and to evaluate the differences of 25-hydroxy vitamin D (25(OH)D) and serum calcium levels among gender and age categories. METHODS: This cross-sectional study enrolled patients with BPPV. The diagnosis of BPPV was based on positional nystagmus and vertigo induced by certain head positions (The Dix-Hallpike maneuver and head roll tests). All patients' age, serum 25(OH)D, calcium measurements and recurrence data were collected and analyzed. RESULTS: The median of 25(OH)D was 15.32 (IQR 10.61, 20.90) ng/ml. The recurrent group showed lower 25(OH)D levels than that of non-recurrent group [13.28 (IQR 9.47, 17.57) ng/ml vs 16.21 (IQR 11.49, 21.13) ng/ml]. There were significant differences of 25(OH)D levels among age categories. The proportion of vitamin D deficiency in patients ≥60 years old was lower than that in the other two groups. CONCLUSION: Our study suggested that BPPV patients had a decreased 25(OH)D level and a high incidence of vitamin D deficiency. The 25(OH)D level of recurrent BPPV patients was lower than that in non-recurrent ones. Among them, the elderly group (≥60 years) took the preponderance, which had the lowest incidence of vitamin D deficiency and the highest incidence of vitamin D sufficiency.

The First Convergent Synthesis of 23,23-Difluoro-25-hydroxyvitamin D3 and Its 24-Hydroxy Derivatives: Preliminary Assessment of Biological Activities.

In this paper, we report an efficient synthetic route for the 23,23-difluoro-25-hydroxyvitamin D3 (5) and its 24-hydroxylated analogues (7,8), which are candidates for the CYP24A1 main metabolites of 5. The key fragments, 23,23-difluoro-CD-ring precursors (9-11), were synthesized starting from Inhoffen-Lythgoe diol (12), and introduction of the C23 difluoro unit to α-ketoester (19) was achieved using N,N-diethylaminosulfur trifluoride (DAST). Preliminary biological evaluation revealed that 23,23-F2-25(OH)D3 (5) showed approximately eight times higher resistance to CYP24A1 metabolism and 12 times lower VDR-binding affinity than its nonfluorinated counterpart 25(OH)D3 (1).

Eficacia y seguridad del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica / Efficacy and safety of calcipotriol and betamethasone dipropionate in adult patients with moderate or severe plaque psoriasis vulgaris, unresponsive to conventional topical and systemic therapy, and not amenable to biological therapy

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen que expone la evaluación de la eficacia y seguridad del calcipotriol y dipropionato de betametasona (DB) en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. Así, la médico dermatóloga, Dra. Lorraine Lía Málaga Medina del Servicio de Dermatología del Hospital Nacional Carlos Seguin Escobedo, siguiendo la Directiva N.° 003-IETSI-ESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso por fuera del petitorio farmacológico de EsSalud el producto farmacéutico calcipotriol en combinación con el (DB), para el tratamiento de los pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. ASPECTOS GENERALES: La psoriasis vulgar en placas es una enfermedad crónica de la piel que se presenta como placas eritematosas y escamosas que aparecen, mayoritariamente, en el cuero cabelludo, el tronco, los glúteos, y los miembros inferiores y superiores (de Rie et al., 2004). Esta enfermedad es considerada como un problema de salud pública por su alta prevalencia, alto riesgo de morbilidad y porque deteriora la calidad de vida y salud mental en los pacientes que la padecen (Boehncke & Schón, 2015). La psoriasis afecta del 1 % al 3 % de la población mundial; y la psoriasis vulgar en placas representa hasta el 90 % de todas las manifestaciones de la psoriasis (Augustin et al., 2010). Además, la presencia de esta enfermedad se asocia a mayor riesgo de sufrir artritis psoriásica, enfermedades cardiovasculares, diabetes mellitus, obesidad, enfermedad del hígado graso no alcohólico y enfermedades inflamatorias del intestino (Gisondi et al., 2020). Asimismo, el 75 % de estos pacientes percibe un deterioro en su calidad de vida y cerca del 10 % ha tenido ideación suicida (Bhosle et al., 2006). METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad del CAL-DB, en comparación con mejor terapia de soporte, en pacientes adultos con psoriasis vulgar en placas moderada o severa no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica. La búsqueda se realizó en las bases de datos bibliográfica de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish I ntercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Institute for Quality and Efficiency in Health Care (IQWIG), el Scottish Medicines Consortium (SMC), la Comissáo Nacional de I ncorpornáo de Tecnologías no Sistema Único de Saúde (CONITEC), el Instituto de Evaluación Tecnológica en Salud (IETS) y el Instituto de Efectividad Clínica y Sanitaria (IECS). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o aún no publicados. RESULTADOS: Tras ampliar los criterios de selección de documentos, se incluyó una GPC publicada por el NICE (2012) que realiza recomendaciones sobre la evaluación y el tratamiento de pacientes con psoriasis vulgar de severidad moderada o severa. Además, se incluyeron dos ETS publicadas por la CONITEC (2012), y la HAS (2019) que tuvieron como objetivo evaluar la evidencia disponible acerca de la eficacia y seguridad del uso del Cal-DB en pacientes adultos con psoriasis vulgar en placas e incluyeron, en su cuerpo de evidencia, ECA donde participaron pacientes con psoriasis vulgar de severidad moderada a severa. También, se incluyó el estudio pivotal citado en la ficha técnica del Daivobet ® aprobada por DIGEMID (2018), el cual es un ECA de fase II que comparó la eficacia y seguridad del uso del CAL-DB versus el calcipotriol en monoterapia, el DB en monoterapia y placebo, en pacientes con psoriasis vulgar de cualquier severidad de enfermedad (Fleming et al., 2010). Por último, se incluyó un estudio observacional que comparó el uso de la fototerapia y el CAL-DB en pacientes con severidad de enfermedad de moderada a severa (Polanska et al., 2019). ONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación no aprueba el uso combinado del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar moderada o severa, no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud.

Assessment of the relationship between 25-hydroxyvitamin D and albuminuria in type 2 diabetes mellitus.

BACKGROUND: Diabetic nephropathy occurs in about one-third of diabetic patients. This health problem is characterized by increased urinary albumin excretion, leading to decreased glomerular filtration rate and renal failure. In this regard, previous investigations have revealed the possibility of a relationship between vitamin D deficiency and diabetic nephropathy. The present study assessed the relationship between vitamin D deficiency and albuminuria in patients with type 2 diabetes. METHODS: This study was conducted with 200 participants with type 2 diabetes mellitus from December 2019 to January 2021. The patients' 25-hydroxyvitamin D (25OHD) serum level and urinary albumin-to-creatinine ratio (UACR) were measured concurrently. Afterward, the subjects were divided into three groups based on their albuminuria level. Finally, 25OHD serum level and other clinical characteristics were compared among these albuminuria groups, and the relation between albuminuria level and 25OHD was analyzed. RESULTS: The prevalence of vitamin D deficiency in macroalbuminuric patients (UACR≥300 mg/g) was 61.8%, and in microalbuminuric (30 ≤ UACR< 300 mg/g) and normoalbuminuric groups (UACR< 30 mg/g) was 33.3% and 24%, respectively. Further analysis revealed a significant negative relationship between 25OHD and albuminuria(r = - 0.257, p-value< 0.001). According to ROC curve analysis, a 25OHD level ≤ 21 ng/ml was considered an optimal cut-off point value for having macroalbuminuria in diabetic patients. CONCLUSIONS: The current study evaluates the relation between vitamin D deficiency and the prevalence of albuminuria in the setting of diabetes. Overall, the prevalence of macroalbuminuria increased when the 25OHD serum level was less than 20 ng/ml.

Associação fixa de hidrato de calcipotriol e dipropionato de betametasona para psoríase vulgar após falha de corticoide tópico isolado / Fixed association of calcipotriol hydrate and betamethasone dipropionate for psoriasis vulgaris after failure of topical corticosteroid alone

INTRODUÇÃO: A psoríase vulgar, também conhecida como psoríase em placas, é uma doença inflamatória crônica que impacta significativamente na qualidade de vida dos indivíduos acometidos. Trata-se do tipo de psoríase mais prevalente na população (75-90%), caracterizada por lesões cutâneas localizadas principalmente nos joelhos, cotovelos, couro cabeludo e região lombossacra. O tratamento de primeira linha consiste na administração de medicamentos pela via tópica, incluindo ceratolíticos, emolientes e corticoides, isolados ou em associação. Contudo, após a falha terapêutica com corticoide tópico, recomenda-se a associação de análogos de vitamina D (ex: calcipotriol) ao esquema terapêutico, considerando que estudos prévios apontaram a superioridade, em termos de eficácia, desta combinação em relação à monoterapia com qualquer um eles. Porém, considerando que a adesão ao tratamento contribui significativamente para o sucesso do tratamento, a associação fixa de calcipotriol e corticoide, com uma única aplicação diária, pode representar uma estratégia terapêutica mais viável. TECNOLOGIA: Hidrato de Calcipotriol + Dipropionato de Betametasona pomada (Daivobet®). PERGUNTA: A associação de hidrato de calcipotriol + dipropionato de betametasona pomada é eficaz, segura e viável e

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

Paricalcitol para o tratamento de pacientes com hiperparatireoidismo secundário à doença renal crônica estágio 5D / Paricalcitol for the treatment of patients with hyperparathyroidism secondary to kidney disease chronic stage 5d

CONTEXTO: O hiperparatireoidismo secundário (HPTS) à doença crônica renal é caracterizado por elevados níveis séricos de paratormônio (PTH), hiperplasia das glândulas paratireoides, doença óssea de alto remanejamento e doença cardiovascular. O nível de PTH considerado adequado para pacientes com DRC estágio 5D está situado entre 150 e 300 pg/ml ou duas a nove vezes o valor limite do método de dosagem. Segundo o censo da Sociedade Brasileira de Nefrologia (SBN), em 2020, estima-se que 144.779 pacientes estão em tratamento dialítico no Brasil. Destes, aproximadamente 18% apresentavam níveis de PTH acima de 600 pg/mL em 2019, enquanto em 2014 eram em torno de 26%, sugerindo que houve certo impacto na redução dos níveis de PTH com a incorporação do paricalcitol e implementação do PCDT em 2017. Para a redução dos níveis do PTH, estão disponíveis no mercado brasileiro três classes de medicamentos: ativadores não seletivos do receptor da vitamina D (calcitriol e alfacalcidol), ativadores seletivos de VDR (paricalcitol) e calcimiméticos (cinacalcete). Dentre os medicamentos supracitados, o SUS disponibiliza calcitriol oral, tendo sido descontinuados a apresentação intravenosa, em 2020, e o alfacalcidol oral, em 2017. Em relação ao paricalcitol, sua disponibilização no SUS está voltada aos pacientes com PTH igual ou superior a 500 pg/ml e, para o cinacalcete, aos pacientes com níveis de PTH acima de 800 pg/ml. Neste sentido o objetivo deste documento é analisar novas evidências científicas existentes sobre o paricalcitol, visando sua ampliação de uso para o tratamento do HPTS associado à DRC estágio 5D em pacientes com resposta inadequada ao calcitriol para manutenção dos níveis de PTH < 300 pg/ml, ou como primeira linha nos pacientes com HPTS moderado (PTH > 300 pg/ml) na ausência de hiperfosfatemia e hipercalcemia ou ainda nos pacientes em uso de cinacalcete que apresentem hipocalcemia e/ou necessitem da associação de paricalcitol para atingir os níveis alvo de PTH. TECNOLOGIA: Paricalcitol. PERGUNTA: O uso do paricalcitol é eficaz, seguro e custo-efetivo em pacientes com Hiperparatireoidismo secundário à DRC estágio 5D quando comparado ao calcitriol? EVIDÊNCIAS CIENTÍFICAS: A partir da busca das evidências conduzida nas bases de dados The Cochrane Library, MedLine (via PubMed), Embase (Elsevier), PubMed Central, Epistemonikos, NICE e Biblioteca Virtual de Saúde, uma revisão sistemática foi incluída para a síntese de evidências, por ser considerada a de melhor qualidade metodológica e a mais completa por atender à PICO definida. Quanto aos desfechos clínicos, a mortalidade por todas as causas, com RR 0,84; IC 95% 0,79- 0,90; <0,00001 demonstrau maior eficácia do tratamento com paricalcitol do que com outros análogos não seletivos de vitamina D. Não foram observadas diferenças significativas na incidência de eventos adversos como hipercalcemia e hiperfosfatemia e no controle dos níveis de PTH. A qualidade metodológica geral da revisão sistemática selecionada para atualização foi classificada como moderada. Segundo o GRADE, a qualidade da evidência para o desfecho de mortalidade por todas as causas foi moderada; muito baixa para níveis séricos de fósforo e baixa para os demais desfechos avaliados. AVALIAÇÃO ECONÔMICA: Com base nos dados da literatura, foi construído um modelo de árvore de decisão para a análise de custo-efetividade, que considerou o desfecho de morte evitada e um horizonte temporal de 1 ano. Como resultado da comparação entre paricalcitol e calcitriol oral na perspectiva do SUS, a análise mostrou que a relação de custo efetividade (C/E) foi de R$ 1.213,68 ao ano e uma efetividade incremental de 0,032, referente a morte evitada em um ano. A RCEI foi de R$ 37.927,50 por morte evitada para o paricalcitol. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: CONSIDERADOS três cenários, sendo dois de demanda aferida, com dados do Departamento de Assistência Farmacêutica e Insumos Estratégicos do Ministério da Saúde (DAF) e da Sala Aberta de Inteligência em Saúde (SABEIS); e um cenário de abordagem epidemiológica, baseado nos dados da SBN. Como resultados, estimou-se um impacto orçamentário incremental com a ampliação do uso do paricalcitol no SUS entre R$ 1.600.202,28 e R$ 4.128.565,65 no primeiro e, ao final de 5 anos de ampliação de uso, entre R$ 48.596.855,50 e R$ 62.90.555,73 considerando os cenários principal, baseado nos dados do DAF e nos dados da SABEIS e o epidemiológico com base nos dados da SBN. Já ao final de 5 anos de ampliação de uso, estimou-se um impacto incremental que variou de R$ 59.717.279,99 a R$ 101.637.532,13 a depender do cenário considerado. Monitoramento do Horizonte Tecnológico: Identificou-se apenas um medicamento, denominado etelcalcetide, o qual não possui registro sanitário na Anvisa. Entretanto, obteve registro na Europa (EMA) em 2016 e nos EUA (FDA) em 2017. CONSIDERAÇÕES FINAIS: O paricalcitol foi incorporado pelo SUS em 2015, sendo contemplado como segunda linha de tratamento para pacientes com HPTS à DRC, em diálise. Entretanto, com base em diretrizes nacionais e internacionais sobre o tema, avaliou-se a sua ampliação para pacientes com PTH acima de 300 pg/ml na ausência de hiperfosfatemia e hipercalcemia ou ainda nos pacientes em uso de cinacalcete que apresentem hipocalcemia e/ou necessitem da associação de paricalcitol para atingir os níveis alvo de PTH. As evidências clínicas selecionadas demonstraram que paricalcitol é mais eficaz que outros análogos não seletivos de vitamina D, como calcitriol, nos desfechos de mortalidade por todas as causas, enquanto que não foram observadas diferenças significativas na incidência de eventos adversos como hipercalcemia e hiperfosfatemia e nos níveis de PTH. A maioria dos desfechos apresentou qualidade da evidência baixa, com exceção da mortalidade que foi moderada. Na avaliação econômica, a análise mostrou que o uso de paricalcitol resulta em um custo incremental de R$ 1.213,68 ao ano e uma efetividade incremental de 0,032, referente a morte evitada em um ano. A RCEI foi de R$ 37.927,50 por morte evitada para o paricalcitol. Estimou-se que o impacto orçamentário incremental com a ampliação do uso do paricalcitol no SUS estará entre R$ 1.600.202,28 e R$ 4.128.565,65 no primeiro e, ao final de 5 anos de ampliação de uso, entre R$ 48.596.855,50 e R$ 62.90.555,73 a depender do cenário considerado. PERSPECTIVA DO PACIENTE: A chamada pública de número 54/2021 para participar da Perspectiva do Paciente sobre o tema foi aberta de 14/09/2021 a 20/09/2021 e três pessoas se inscreveram. A indicação dos representantes titular e suplente para fazer o relato da experiência foi feita a partir de definição consensual por parte do grupo de inscritos. No relato, o participante descreveu sua experiência de tratamento com o cinacalcete ­ que era suspenso e retomado quando as alterações nos níveis de PTH assim exigiam. O paciente não mais utiliza o medicamento desde a realização do segundo transplante renal, visto que desde então os níveis de PTH se mantêm estáveis. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O Plenário da Conitec, em sua 104ª Reunião Ordinária, no dia 09 de dezembro de 2021, deliberou que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar favorável à ampliação de uso do paricalcitol para o tratamento de pacientes com hiperparatireoidismo secundário à doença renal crônica, submetidos à diálise, com níveis de PTH acima de 300 pg/ml e ausência de hiperfosfatemia e hipercalcemia. Os membros da Conitec consideraram que o paricalcitol possui eficácia superior e segurança semelhante ao comparador calcitriol, diminuindo a mortalidade geral dos pacientes em diálise. CONSULTA PÚBLICA: Foram recebidas sete contribuições, sendo duas pelo formulário técnico-científico e cinco pelo formulário sobre experiência ou opinião. Das duas contribuições de cunho técnico-científico recebidas, uma foi favorável e outra contra à recomendação inicial da Conitec. Não houve apresentação de dados sobre evidências clínicas, análise de impacto orçamentário ou avaliação econômica. As cinco contribuições recebidas sobre experiência com a tecnologia ou opinião sobre o tema concordaram com a recomendação inicial da Conitec. RECOMENDAÇÃO FINAL DA CONITEC: O Plenário da Conitec, em sua 105ª Reunião Ordinária, no dia 09 de fevereiro de 2022, deliberou por unanimidade recomendar a ampliação de uso do paricalcitol para o tratamento de pacientes com hiperparatireoidismo secundário à doença renal crônica, submetidos à diálise, com níveis de PTH acima de 300 pg/ml e com normo ou hipocalcemia. Por fim, foi assinado o Registro de Deliberação nº 699/2022. DECISÃO: Ampliar o uso do paricalcitol para o tratamento de pacientes com hiperparatireoidismo secundário à doença renal crônica, submetidos à diálise, com níveis de PTH acima de 300 pg/ml e com normo ou hipocalcemia, e conforme protocolo estabelecido pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde ­ SUS, conforme a Portaria nº 36, publicada no Diário Oficial da União nº 72, seção 1, página 447, em 14 de abril de 2022.

Interactive Effects of Maternal Vitamin D Status and Socio-Economic Status on the Risk of Spontaneous Abortion: Evidence from Henan Province, China.

BACKGROUND: Maternal vitamin D deficiency might generate adverse reproductive outcomes, and socio-economic inequalities in micronutrient-related diseases have often been found. This study aimed to explore the interactive effects of maternal vitamin D status and socio-economic status (SES) on risk of spontaneous abortion. METHODS: A population-based case-control study was conducted including 293 women with spontaneous abortion and 498 control women in December 2009 and January, 2010 in Henan Province, China. Information on pregnancy outcomes, maternal demographic, lifestyle and exposure factors and blood samples were collected at the same time. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. SES index was constructed with principal component analysis by aggregating women's and their husbands' education level and occupation, and household income and expenditure. Interactive effects were assessed on a multiplicative scale with ratio of the odds ratio (ROR). RESULTS: Compared to those with high SES and vitamin D sufficiency, women with vitamin D deficiency and low SES index had an increased risk of spontaneous abortion (aOR: 1.99; 95% CI: 1.23-3.23). The ROR was 2.06 (95% CI: 1.04-4.10), indicating a significant positive multiplicative interaction. CONCLUSIONS: Maternal low SES may strengthen the effect of vitamin D deficiency exposure on spontaneous abortion risk in this Chinese population.

Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.

Assessment of Vitamin D Metabolism in Patients with Cushing's Disease in Response to 150,000 IU Cholecalciferol Treatment.

In this study we aimed to assess vitamin D metabolism in patients with Cushing's disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

Potential of Vitamin D Food Fortification in Prevention of Cancer Deaths-A Modeling Study.

Meta-analyses of randomized controlled trials (RCTs) have estimated a 13% reduction of cancer mortality by vitamin D supplementation among older adults. We evaluated if and to what extent similar effects might be expected from vitamin D fortification of foods. We reviewed the literature on RCTs assessing the impact of vitamin D supplementation on cancer mortality, on increases of vitamin D levels by either supplementation or food fortification, and on costs of supplementation or fortification. Then, we derived expected effects on total cancer mortality and related costs and savings from potential implementation of vitamin D food fortification in Germany and compared the results to those for supplementation. In RCTs with vitamin D supplementation in average doses of 820-2000 IU per day, serum concentrations of 25-hydroxy-vitamin D increased by 15-30 nmol/L, respectively. Studies on food fortification found increases by 10-42 nmol/L, thus largely in the range of increases previously demonstrated by supplementation. Fortification is estimated to be considerably less expensive than supplementation. It might be similarly effective as supplementation in reducing cancer mortality and might even achieve such reduction at substantially larger net savings. Although vitamin D overdoses are unlikely in food fortification programs, implementation should be accompanied by a study monitoring the frequency of potentially occurring adverse effects by overdoses, such as hypercalcemia. Future studies on effectiveness of vitamin D supplementation and fortification are warranted.

Assessment of Low Bone Mineral Density in Untreated Patients with Takayasu's Arteritis.

Chronic inflammation affects bone metabolism and accelerates bone loss. This study is aimed at analyzing the prevalence of low bone mineral density (LBMD) in patients with untreated Takayasu's arteritis (TA) and risk factors. Forty untreated TA patients were enrolled, including 38 premenopausal women and 2 men before 50 years old. The control group included 60 age- and gender-matched healthy persons. Bone mineral density (BMD) of lumbar vertebrae and hip in patients with TA and the control group was measured by the dual-energy X-ray method. Serum 25OHD and ß-CTX were also measured. The lumbar BMD of TA patients (0.89 ± 0.11 g/cm2) was significantly lower than that of the healthy control (0.97 ± 0.11 g/cm2). The prevalence of LBMD at the lumbar spine (17.50%) was significantly higher than that of the control group (3.33%). However, there was no significant difference at the hip. The 25OHD of TA patients was lower than that of healthy controls, while the level of ß-CTX was higher. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with LBMD were higher than those in patients with normal BMD. According to univariate correlation analysis, there was a significant negative correlation between LDL-C and lumbar BMD. Binary logistic regression analysis showed that LDL-C was an important factor affecting the occurrence of LBMD in patients with TA (OR = 25.269, P = 0.02). Our result reveals bone loss in TA patients, which hints the relationship among inflammation, lipid metabolism, and bone metabolism.

Assessment of serum total 25-hydroxyvitamin D assay commutability of Standard Reference Materials and College of American Pathologists Accuracy-Based Vitamin D (ABVD) Scheme and Vitamin D External Quality Assessment Scheme (DEQAS) materials: Vitamin D Standardization Program (VDSP) Commutability Study 2.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

Vitamin D Standardization Program (VDSP) intralaboratory study for the assessment of 25-hydroxyvitamin D assay variability and bias.

An intralaboratory study assessing assay variability and bias for determination of serum total 25-hydroxyvitamin D [25(OH)D] was conducted by the Vitamin D Standardization Program (VDSP). Thirteen assays for serum total 25(OH)D were evaluated in a single laboratory including 11 unique immunoassays and one liquid chromatography - tandem mass spectrometry (LC-MS/MS) assay. Fifty single-donor serum samples, including eight samples with high concentrations of 25(OH)D2 (> 30 nmol/L), were assigned target values for 25(OH)D2 and 25(OH)D3 using reference measurement procedures (RMP). Using four replicate measurements for each sample, the mean total percent coefficient of variation (%CV) and mean % bias from the target values were determined for each assay using the 50 single-donor samples and a 42-sample subset, which excluded 8 high 25(OH)D2 concentration samples, and compared with VDSP performance criteria of ≤ 10 % CV and ≤ ±5 % mean bias. All 12 assays achieved the performance criterion for % CV, and 9 of the 12 assays were within ≤ ±5 % mean bias. The Fujirebio Inc. assay exhibited the lowest %CV and highest percentage of individual measurements within ≤ ±5 % mean bias. Ten immunoassays exhibited changes in response due to the high 25(OH)D2 samples with Abbott, Biomérieux, DiaSorin, DIAsource, and IDS-iSYS assays having the largest deviations. The Fujirebio Inc. and Beckman Coulter assays were only minimally affected by the presence of the high 25(OH)D2 samples. Samples with high concentrations of 25(OH)D2 provided a critical performance test for immunoassays indicating that some assays may not have equal response or recovery for 25(OH)D2 and 25(OH)D3.

Vitamin D status in pubertal children.

BACKGROUND: Optimal vitamin D status has a great importance in puberty, which is a period of peak bone mineral acquisition. In this study, we aimed to assess the effect of pubertal period on vitamin D status. METHODS: The study included totally 200 healthy children, aged between 4 and 14 years. Group 1 included 100 prepubertal, children, aged between 4 and 8 years. Group 2 included 100 pubertal children, aged between 9 and 14 years. They had no chronic illnesses. Ages, heights, weights, genders, Body Mass Indexes (BMIs), socioeconomic and educational status of families were established. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured by high performance liquid chromatography (HPLC). Serum parathyroid hormone (PTH) was evaluated using an immunoradiometric assay kit. Serum calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) levels were measured. RESULTS: We determined that 25(OH)D levels were lower with higher PTH levels in the group aged 9 to 14 years (pubertal children), compared to the group aged 4 to 8 (prepubertal children). Gender, weight, height or BMI, family socioeconomic and education status did not affect serum 25(OH)D levels of children in each group. CONCLUSIONS: We demonstrated that vitamin D deficiency was more commonly seen in the pubertal children, compared to pre pubertal period. Children should be supported with vitamin D supplements during the puberty, which has a great importance for rapid increase in bone mass.

The serum 25(OH)D level and hand grip strength for fall risk assessment among osteoporotic elderly Japanese women.

We investigated the relationship between serum 25(OH)D levels, grip strength, and fall score in elderly osteoporotic women for fall risk assessment. Both low serum 25(OH)D and low grip strength were independently associated with increased fall risk. The serum 25(OH)D cutoff specific to increased fall risk was 14 mg/dL (35 nmol/L). PURPOSE: This study aimed to establish a cutoff value of serum 25-hydroxyvitamin D (25(OH)D) for fall assessment and investigate the relationship between serum 25(OH)D, grip strength, and fall score adjusted for age in osteoporotic elderly Japanese women. METHODS: This is a cross-sectional study utilizing collected data of osteoporotic elderly (age ≥65 years) female patients. A questionnaire for fall risk assessment was used, in which a score ≥ 6 was determined as increased fall risk. Serum 25(OH)D levels and grip strength were measured, and the cutoff points were calculated by receiver operating curve (ROC) analysis. Logistic regression analysis with age adjustment was conducted for potential risk factors for fall. RESULTS: After applying eligibility criteria, finally, 349 patients were enrolled. The median patient age was 77.0 years, and the mean serum 25(OH)D level was 15.6 ng/mL (36 nmol/L). Based on the ROC analysis, we defined the cutoff values of serum 25(OH)D level and grip strength as 14 ng/mL (35 nmol/L) and 15 kg, respectively. A multivariate analysis adjusted for age was conducted. Low serum 25(OH)D level and grip strength were independent risk factors for ≥6 fall risk scores. CONCLUSION: Both low serum 25(OH)D level and low grip strength were independently associated with increased fall risk score in osteoporotic elderly women. The appropriate serum 25(OH)D cutoff specific to the increased fall risk group in this population was 14 mg/dL (35 nmol/L). These findings might be used for the identification of patients with high fall risks. These results should be confirmed in other patient groups.

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.

Assessment of the Role of Serum 25-Hydroxy Vitamin D Level on Coronary Heart Disease Risk With Stratification Among Patients With Type 2 Diabetes Mellitus.

We investigated the role of vitamin D on glycemic regulation and cardiac complications in patients with type 2 diabetes mellitus (T2DM). A total of 1139 patients (49.3% males vs 50.7% females) were included. Information on sociodemographic lifestyle, family history, blood pressure (BP), and coronary heart disease (CHD) complications was collected. Significant differences were found between males and females regarding age-groups (P = .002), body mass index (BMI; P = .008), physical activity (P = .010), sheesha smoking (P = .016), cigarette smoking (P = .002), hypertension (P = .050), metabolic syndrome (P = .026), and CHD (P = .020). There were significant differences between vitamin D deficiency, insufficiency, and sufficiency in relation to age-group (P = .002), income (P = .002), waist circumference (P = .002), hip circumference (P = .028), waist-hip ratio (P = .002), and BMI (P = .002). Further, mean values of hemoglobin, magnesium, creatinine, hemoglobin A1c (HbA1c), total cholesterol, uric acid, and diastolic BP were significantly higher among patients with vitamin D deficiency compared with those with insufficiency and sufficiency. Multiple logistic regression analysis revealed that 25-hydroxy vitamin D, 25(OH)D, HbA1c, waist circumference, uric acid, duration of T2DM, total cholesterol, systolic and diastolic BP, and BMI were strong predictor risk factors for CHD among patients with T2DM. The present study supports that 25(OH)D may have a direct effect on CHD and on its risk factors.

[Assessment of 25(OH)D concentration in people with metabolic syndrome working in agriculture]. / Ocena stezenia 25(OH)D u osób z zespolem metabolicznym pracujacych w rolnictwie.

BACKGROUND: Polish data on vitamin D deficiency in the population are incomplete. Vitamin D deficiency seems to be common, but there is a lack of studies concerning the concentration of 25(OH)D in people with high UV exposure. The aim of this study was to evaluate the plasma concentration of 25(OH)D in people with and without metabolic syndrome (MS), working in agriculture, the prevalence of its deficiency in these workers, and the correlation between the plasma concentration of 25(OH)D and traditional biomarkers of cardiovascular diseases. MATERIAL AND METHODS: The study included 332 people working in agriculture in the Lódz voivodeship, including 231 people with MS and 101 healthy ones. The plasma concentration of 25(OH)D was assessed using the chemiluminescent immunoassay technology. The vitamin D intake was assessed using a 24-h recall questionnaire using Diet 5.0 software. RESULTS: The mean plasma concentration of 25(OH)D was 13.64±8.01 ng/ml in MS workers, and it was significantly lower than in the healthy ones (26.61±10.12 ng/ml, p < 0.00001); the highest concentration of 25(OH)D was noted in summer months. Deficient plasma concentrations of 25(OH)D were found significantly more often in MS workers than in the controls (81.82% and 20.79%, respectively, p < 0.00001). No correlation was found between the plasma vitamin D concentration and its dietary intake. The plasma concentration of 25(OH)D correlated with age of the examined workers (r = -0.28, p = 0.023), high density lipoprotein concentration (r = 0.19, p = 0.036) and glucose concentration (Rho = -0.24, p = 0.02). A multivariate analysis of variance demonstrated that the body mass index affected significantly the mean value of the 25(OH)D concentration in MS workers. CONCLUSIONS: The concentration of vitamin D in the plasma of workers with MS was significantly lower than in the healthy controls despite the same high UV exposure; these workers also manifested significantly higher 25(OH)D deficiency than the control subjects. This study indicates the need for further research on the concentration of 25(OH)D in people with metabolic disorders regardless of UV exposure and vitamin D intake with a diet. Med Pr. 2021;72(1):9-18.

Differences in RAAS/vitamin D linked to genetics and socioeconomic factors could explain the higher mortality rate in African Americans with COVID-19.

COVID-19 is said to be a pandemic that does not distinguish between skin color or ethnic origin. However, data in many parts of the world, especially in the United States, begin to show that there is a sector of society suffering a more significant impact from this pandemic. The Black population is more vulnerable than the White population to infection and death by COVID-19, with hypertension and diabetes mellitus as probable predisposing factors. Over time, multiple disparities have been observed between the health of Black and White populations, associated mainly with socioeconomic inequalities. However, some mechanisms and pathophysiological susceptibilities begin to be elucidated that are related directly to the higher prevalence of multiple diseases in the Black population, including infection and death by COVID-19. Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system (RAAS) in Black people differ considerably from those of other races. The role of these factors in the development and progression of hypertension and multiple lung diseases, among them SARS-CoV-2 infection, is well established. In this sense, the present review attempts to elucidate the link between vitamin D and RAAS ethnic disparities and susceptibility to infection and death by COVID-19 in Black people, and suggests possible mechanisms for this susceptibility.