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(searched for: Vitamin D Levels in Chronic Diseases in Primary Care)
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Luca Spiezia, Sciprofile linkAnnalisa Boscolo, Christelle Correale, Nicolò Sella, Elisa Pesenti, Luca Beghetto, Elena Campello, Francesco Poletto, Lorenzo Cerruti, Marco Cola, et al.
Thrombosis and Haemostasis; doi:10.1055/s-0040-1714350

The publisher has not yet granted permission to display this abstract.
Hannah Elizabeth Forde, Jane Noble, David Gibbons, John Holian, Connaghan Daniel Gerard, Rachel K Crowley
Journal of the Endocrine Society, Volume 4; doi:10.1210/jendso/bvaa046.1742

Abstract:
Introduction: Primary adrenal lymphoma (PAL) is a rare cause of adrenal enlargement with approximately 200 cases reported in the literature to date. It tends to affect elderly men and has a high incidence of bilateral involvement at diagnosis. We report the case of a 66 year old man, whose PAL manifested with symptomatic hypercalcaemia. A 66 year old male, originally from the Philippines, was referred to the emergency department with nausea, vomiting, weight loss and right flank pain. His past medical history was significant for hypertension, gout and stage 3b chronic kidney disease. His medications were amlodipine, losartan and febuxostat. His family history was significant for hypertension. On examination he was hypertensive (blood pressure, 160/100 mmHg) and hyperpigmented. His laboratory investigations revealed; corrected calcium of 3.79 mmol/l, undetectable PTH, vitamin D 49 nmol/l. He was treated with intravenous (IV) 0.9% saline and IV zoledronic acid and his calcium levels improved. To investigate causes of non-PTH mediated hypercalcaemia, computerised tomography of the thorax, abdomen and pelvis (CT TAP) as well as a positron emission tomography (PET) scan were performed. These demonstrated bilateral, large, metabolically active adrenal masses with no evidence of extra-adrenal disease. Differential diagnosis at this point included bilateral adrenal hyperplasia, metastases, lymphoma or adrenal TB. There were no radiological features of adrenocortical carcinoma (ACC) or phaeochromocytoma and subsequent biochemical investigations confirmed no evidence of cortisol, androgen or catecholamine excess. Adrenocorticotrophic hormone (ACTH) levels were elevated however, and a synacthen test revealed inadequate adrenal reserve (peak cortisol 214 nmol/l). The patient was commenced on maintenance steroids and with stress dose steroid cover, proceeded to adrenal biopsy. Histology confirmed diffuse large B cell non-Hodgkin’s lymphoma. Haematology became involved in his care and he commenced polychemotherapy in the form of R-CHOP, 1 week post confirmation of the diagnosis. His treatment is ongoing and he has tolerated it well with minimal side effects, except a flare of gout. Learning points: PAL should be considered in the differential diagnosis in patients with bilateral adrenal masses. Image guided adrenal biopsy is the gold standard for diagnosis, though caution must be exercised and an ACC or phaeochromocytoma should be excluded prior to biopsy. The prognosis of PAL is poor and therefore early diagnosis and prompt initiation of treatment are required to improve outcomes.
A. Sabic, Dz. Sabic, A. Zejcirovic, F. Mumic, S. Bosankic, S. Hasanovic
Archives of Clinical and Biomedical Research, Volume 4, pp 83-88; doi:10.26502/acbr.50170091

Abstract:
The aim of this paper is to highlight the role and level of vitamin D in chronic diseases at the primary level of their treatment. Methods and patients: At Zivinice Health Care Center 81 patients were analyzed between March and September 2019, with 39 men (48.1%) and 42 (51.9%) women. The mean age of the patients was 62 ± 10 years. The youngest patient was 24 years old and the oldest 80 years old. Patients with long-term hypertension (71 patients, 36 women and 35 men), coronary heart disease (16 patients, 8 women and 8 men), type 2 diabetes (T2DM, 45 patients, 22 women and 23 men) were observed, hyperlipoproteinemia (32 patients, 17 women and 15 men), depressive disorder (8 patients, 3 women and 5 men), and anxiety (13 patients, 8 women and 5 men). Vitamin D levels were determined at the University Clinical Center Tuzla, Department of Biochemistry, and 36.8-171.0 mmol / L were taken as reference values. The statistics were analyzed in the SSPS. Results: The mean vitamin D level in patients with chronic diseases was 53.3 mmol / L. Standard deviation (SD) ± 20.9. The reference values for vitamin D levels were 62 patients or 76.5% and 19 or 23.5% had decreased vitamin D. In patients with hypertension, 17 had a reduced vitamin D level (p 0.063). Of the 45 diabetic patients, 13 had reduced levels of vitamin D (p 0.202). Patients with ischemic heart disease 4 of them had lowered vitamin D (p 0.873). In patients with hyperlipoproteinemia, 9 of them have lowered vitamin D (p 0,429). There are 4 patients with reduced levels of vitamin D with depressive disorder and 4 with patients with anxiety disorders with reduced levels of vitamin D (p 0,113). One patient had a body mass index (BMI) of less than 18.5, 6 patients had a neat BMI, 30 patients were overweight. 26 patients had grade I thickness, 16 patients had grade II thickness and two BMI patients over 40 m2 / kg.In the ITM group 30-34.9 there were 10 patients with reduced vitamin D values (p 0.002), which is a statistically significant difference compared to other patient groups according to the BMI. Conclusion: Vitamin D was 53.3 mol / L (36.8-171.0 mmol / L) in the majority of patients. No statistically significant difference in vitamin D levels was found between the groups of patients with chronic diseases. A statistically significant difference was found in the decreased vitamin D in the group of patients with BMI 30-34.9 compared to other groups of patients according to the BMI.
George Bertsias
Plenary I: Lupus Manifestations and Comorbidities: How Have Our Strategies Improved?, Volume 6; doi:10.1136/lupus-2019-la.6

Abstract:
Patients with systemic lupus erythematosus (SLE) manifest increased frequency of several comorbidities, particularly cardiovascular diseases, infections, osteoporosis and fragility fractures, and also, malignant disorders such as lymphoma.1 Comorbid diseases may develop both early and later during the course of the disease due to complex interaction between lupus inflammation and administered treatments, especially glucocorticoids. Their prevention, early diagnosis and management is of great importance to ensure favourable long-term patient outcomes, as highlighted in the 2019 Update of the EULAR recommendations for the management of SLE.2 Despite extensive research, there is paucity of controlled studies to guide the treatment of comorbidities in SLE patients, and it remains elusive whether therapeutic goals (e.g. target levels of serum LDL-cholesterol) in SLE should be different than those in the general population. The increased cardiovascular disease (CVD) burden seen in SLE patients emphasizes the need for primary prevention strategies cardiovascular disease. This includes the use of validated CVD risk prediction tools (e.g. Framingham Risk Score, Systematic COronary Risk Evaluation (SCORE), QRISK2), which however tend to underestimate the actual risk in patients with SLE.3 The role and indications in clinical practice for non-invasive modalities for assessing subclinical atherosclerosis (e.g. coronary artery assessment, carotid intima media thickness) is less clear.4 General non-pharmacological interventions include smoking cessation, avoidance of sedentary lifestyle and maintenance of ideal body mass index. High blood pressure should be adequately controlled preferentially with renin-angiotensin-aldosterone axis blockade, and dyslipidemia be treated with statins. Aspirin may be considered in SLE patients with high-risk antiphospholipid antibodies profile and/or high estimated CVD risk after careful evaluation of the bleeding risk.5 At the chronic maintenance stage, the dose of glucocorticoids should be minimized to less than 7.5 mg/day of prednisone equivalent. Importantly, hydroxychloroquine should be considered – unless contraindicated – in all cases due to its putative atheroprotective role.6 Infections and sepsis represent another important comorbidity associated with increased risk for hospitalization and death in patients with SLE.7 Application of general preventative strategies such as hygiene measures and immunizations cannot be overemphasized.8 Modification of SLE-related risk factors such as reduction of exposure to glucocorticoids and avoidance of treatment-related leukopenia/neutropenia are important.9 High-intensity immunosuppressive (high-dose azathioprine, mycophenolate, cyclophosphamide) or biologic (rituximab) therapies have also been associated with increased risk for infections, especially when used in combination with moderate or high doses of glucocorticoids10 11. Pre-emptive use of antibiotics is not recommended, nevertheless a low index of suspicion to diagnose an infection – including possible Pneumocystis pneumonia12 – and commence antibiotics promptly is warranted in high-risk groups including elderly or neutropenic patients, those with comorbidities (e.g. diabetes) or who are receiving glucocorticoids. Osteoporosis and fragility fractures are potentially avoidable and readily treated comorbidities in patients with SLE.13 14 Factors impacting adversely on bone mass density, particularly chronic use of glucocorticoids, should be corrected.15 Osteoprotective and/or anti-osteoporotic interventions should be similar to those in the general population or patients with other chronic inflammatory disorders, yet caution is recommended in cases of kidney disease and reduced glomerular filtration rate. To this end, SLE patients should also be screened for vitamin D insufficiency, which should be corrected considering its presumed multifaceted effects on the disease.16 Learning objectives Describe primary prevention strategies for SLE comorbidities including cardiovascular disease, infection and osteoporosis Explain screening and treatment options for key comorbid diseases in patients with SLE References Gonzalez LA, Alarcon GS. The evolving concept of SLE comorbidities. Expert review of clinical immunology 2017;13(8):753–68. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Annals of the rheumatic diseases2019;78(6):736–45. Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ2017;357:j 2099. Wu GC, Liu HR, Leng RX, et al. Subclinical atherosclerosis in patients with systemic lupus erythematosus: A systemic review and meta-analysis. Autoimmunity reviews 2016;15(1):22–37. Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis. JAMA 2019;321(3):277–87. Fasano S, Pierro L, Pantano I, et al. Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus. The Journal of rheumatology 2017;44(7):1032–38. Tektonidou MG, Wang Z, Dasgupta A, et al. Burden of Serious Infections in Adults With Systemic Lupus Erythematosus: A National Population-Based Study, 1996–2011. Arthritis care & research 2015;67(8):1078–85. van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Annals of the rheumatic diseases 2011;70(3):414–22. Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus...
Kuo-Kai Chin, Jason Hom, Marilyn Tan, Christopher Sharp, Suwei Wang, Yi-Ren Chen, Sciprofile linkDoris Chen
Journal of General Internal Medicine, Volume 34, pp 1697-1699; doi:10.1007/s11606-019-05057-9

The publisher has not yet granted permission to display this abstract.
Sciprofile linkC. Droitcourt, Groupe De Recherche Sur L’Eczéma Atopique De La Société Française De Dermatologie (Great), Sébastien Barbarot, Annabel Maruani, Laure Darrieux, Laurent Misery, Emilie Brenaut, Henri Adamski, Cécile Chabbert, Annie Vermersch, et al.
Trials, Volume 20; doi:10.1186/s13063-019-3276-9

Abstract:
Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates. This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter. This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health. ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.
Sciprofile linkMarc G. Vervloet, J-DAVID Investigators, Shoji T, Inaba M, Fukagawa M, Ando R, Emoto M, Fujii H, Fujimori A, Fukui M, et al.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Volume 320; doi:10.3410/f.734608792.793557918

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Sciprofile linkJosep Anton De La Fuente, Cristina López Mompó, Ignacio López Pavón, Cristina Vedia Urgell, M. Luisa Granada Ybern, Dolores Reina Rodriguez
Published: 1 March 2019
Atención Primaria Práctica, Volume 1, pp 30-35; doi:10.1016/j.appr.2018.11.001

Abstract:
Evaluar la adecuación de las peticiones de vitamina D (VD). Analizar la relación entre niveles séricos y presencia de factores de riesgo de déficit de VD. Servicio de atención primaria que atiende a 441.198 personas mayores de 14 años. Personas mayores de 14 años con una determinación de VD en 2016. Estudio observacional descriptivo retrospectivo. Edad, género, fecha de petición. Factores de riesgo: institucionalización, paciente en atención domiciliaria (ATDOM), obesidad, enfermedad renal crónica (ERC), hepatopatía crónica, malabsorción (MA), tratamiento con antiepilépticos o corticoides. Otras variables: osteoporosis, tratamiento con antiosteoporóticos, niveles de VD. Se consideraron adecuadas las peticiones en pacientes con algún factor de riesgo. Déficit VD < 20 ng/ml e insuficiencia entre 20-30 ng/ml. Se analiza la diferencia de niveles de VD entre población con y sin criterios de riesgo. Se realiza un análisis de regresión logística. Un total de 7.287 peticiones de VD. El 83,9% eran mujeres. Media de edad: 64,57 años (DE: 15). 2,5% institucionalizados, 5,7% ATDOM. 13,3% ERC, 23,3% obesidad, 0,5% hepatopatía, 1,4% MA, 8,3% tomaban antiepilépticos y 1,3% corticoides. En el 57,5% de los casos la petición se consideró adecuada. Presentaban déficit el 45,75%. El déficit era significativamente más frecuente en los pacientes institucionalizados, obesos y con ERC. El 60% de los sujetos con déficit no recibían VD. El 57,5% de las peticiones eran adecuadas. El déficit se asoció con institucionalización, ATDOM, obesidad y ERC. La mayoría de pacientes con déficit no recibían VD. El aumento de peticiones no está basado en la evidencia, confirmando la «moda» de la VD; esto hace necesaria la elaboración de protocolos que ayuden a la toma de decisiones, para evitar el elevado gasto de las solicitudes no justificadas y los tratamientos sin beneficio. Evaluate the adequacy of the vitamin D (VD) requests. To analyze the relationship of serum levels with the presence of risk factors for VD deficit. Primary Care Service that serves 441,198 people over 14. Persons over 14 years of age with a VD determination in 2016. Retrospective descriptive observational study. Age, gender, analytical month. Risk factors: institutionalization, patient in home care, obesity, chronic kidney disease (CKD), chronic liver disease or malabsorption (MN), treatment with antiepileptics or corticosteroids. Other variables: osteoporosis, treatment with antiosteoporotic, VD, calcium. The requests were considered adequate in patients with some risk factor. We consider deficit VD concentrations < 20 ng/mL and insufficiency between 20-30 ng/mL. The difference in VD levels between risk groups and population without risk criteria is analyzed. A logistic regression analysis is performed. A total of 7,287 requests of VD. 83.9% women. Mean age: 64.57 years (SD: 15). 2.5% admitted to residences and 5.7% patients in home care; 13.3% CKD, 23.3%...
J-DAVID Investigators, Sciprofile linkTetsuo Shoji, Masaaki Inaba, Masafumi Fukagawa, Ryoichi Ando, Masanori Emoto, Hisako Fujii, Akira Fujimori, Mitsuru Fukui, Hiroki Hase, et al.
Published: 11 December 2018
JAMA, Volume 320, pp 2325-2334; doi:10.1001/jama.2018.17749

Abstract:
Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Treatment with 0.5 μg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. UMIN-CTR...
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