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BACKGROUND: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). RESEARCH DESIGN AND METHODS: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure. RESULTS: Candida infections had an IR of 1.9 per 100 PY in patients with PsO (N = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA (N = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (N = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit. CONCLUSIONS: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. TRIAL REGISTRATION: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.
Ixekizumab (IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis. IXE belongs to the class of molecules that blocks a protein called interleukin-17A. Since interleukin-17A is involved in the defense against fungi, the clinical use of this class of drug has the potential to increase the risk of developing fungal infections, such as Candida infections.Therefore, researchers collected safety data from 25 clinical studies comprising 9225 adult patients treated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932 with axial spondyloarthritis. Researchers looked at the rate of new cases of Candida infections, the so-called incidence rate, and found that 1.9 per 100 patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0 per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100 patient-years in the axial spondyloarthritis group.Across indications, the majority of Candida infections (i) were experienced only once by patients, (ii) were mild or moderate in severity, (iii) involved infections caused by superficial skin fungus in the mouth or genitals, (iv) were considered recovered/resolved during the studies, (v) did not lead to IXE discontinuation, (vi) were managed with topical anti-fungal medications or no medications, and (vii) were typically resolved before next visit.In conclusion, this safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications.
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Background: Hematologic malignancies (HMs) are well-known underlying comorbidities of pyoderma gangrenosum (PG). However, studies quantifying the likelihood of PG after HMs are yet to be performed. Objective: To investigate the bidirectional association between PG and several HMs, namely acute leukemia, chronic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma. Methods: A population-based retrospective cohort study was conducted to study the risk of HMs in patients with PG (n = 302) as compared to age-, sex-and ethnicity-matched control subjects (n = 1,799). A case-control design was used to estimate the likelihood of PG in individuals with a preexisting history of HMs. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively. Results: The prevalence of preexisting HM was higher in patients with PG than in controls (6.7% vs. 0.9%, respectively). The likelihood of having PG was significantly greater among patients with a history of HM (adjusted OR, 7.88; 95% CI, 3.85-16.15; p < 0.001), particularly during the first year following the diagnosis. This association was significant for acute leukemia, chronic leukemia, non-Hodgkin lymphoma, and multiple myeloma but not for Hodgkin lymphoma. The incidence rate of HM was 3.3 (95% CI, 1.2-7.4) and 1.6 (95% CI, 0.9-2.6)/1,000 person-years among patients with PG and controls, respectively. Relative to controls, patients with PG were not more likely to develop subsequent HM (adjusted HR, 2.22; 95%CI, 0.77-6.45; p = 0.142). Compared to other patients with PG, those with HM-associated PG experienced an increased all-cause mortality rate (adjusted HR, 2.19; 95%CI, 1.09-4.40; p = 0.028). Conclusion: HM, particularly acute leukemia and multiple myeloma, are associated with an elevated likelihood of provoking PG.
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BACKGROUND: The risk of life-threatening major cardiovascular outcomes among patients with bullous pemphigoid (BP) is inconsistent in the current literature. OBJECTIVE: To evaluate the risk and prognostic outcomes of myocardial infarction (MI), cerebrovascular accident (CVA), peripheral vascular disease (PVD) and pulmonary embolism (PE) in patients with BP. We additionally aimed to explore the influence of different therapeutic approaches on the risk of these outcomes. METHODS: A population-based retrospective cohort study was conducted to compare BP patients (n = 3924) with age-, gender- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of MI, CVA, PVD and PE. Adjusted hazard ratio (HR) and 95% confidence intervals (CI) were estimated by multivariate Cox regression analysis. Data were retrieved from Clalit Health Services' computerized database. RESULTS: Relative to their matched controls, patients with BP were at an elevated risk of MI (fully-adjusted HR: 1.44; 95% CI: 1.14-1.81; p = 0.002), CVA (fully-adjusted HR: 1.24; 95% CI: 1.06-1.45; p = 0.007), PVD (fully-adjusted HR: 1.60; 95% CI: 1.27-2.03; p = 0.003) and PE (fully-adjusted HR: 1.72; 95% CI: 1.28-2.32; p < 0.008). Patients with BP experienced heightened risk of all-cause mortality in the presence of comorbid MI (fully-adjusted HR: 1.61; 95% CI: 1.44-1.81; p < 0.001), CVA (fully-adjusted HR: 1.70; 95% CI: 1.52-1.89; p < 0.001), PVD (fully-adjusted HR: 1.38; 95% CI: 1.20-1.58; p < 0.001) and PE (fully-adjusted HR: 1.44; 95% CI: 1.10-1.88; p = 0.007). The therapeutic approach utilized to manage BP did not significantly influence the risk of cardiovascular outcomes. CONCLUSIONS: BP is associated with an elevated risk of MI, CVA, PVD, PE and cardiovascular mortality. Primary, secondary and tertiary cardiovascular prevention measures should be implemented among patients with BP.
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BACKGROUND AND AIMS: Emerging evidence suggests an arrhythmogenic effect of Anti-Ro/SSA (anti-Ro) and anti-La/SSB (anti-La) antibodies in adults, potentially involving a subclinical intracardiac inflammatory process. Despite the established association between inflammation and ischemic heart disease (IHD), it is noteworthy that as of now no study has delved into the potential link between these antibodies and IHD. This population-based study aimed to examine the association between anti-Ro/La seropositivity and IHD in the general adult population. METHODS: We conducted a retrospective study using electronic medical records from the largest health maintenance organization in Israel. Patients with positive serology for either or both anti-Ro and anti-La antibodies were included, along with matched controls. Multivariate logistic regression models were utilized to assess the odds of IHD in seropositive patients compared to controls. RESULTS: Among 17,231 seropositive patients and 84,368 controls, the rate of IHD was significantly higher in the seropositive group (9.7 % vs. 8.1 %,OR = 1.23; 95%CI 1.14-1.31; p<0.001). The association was more pronounced in younger patients [<40 years old (OR = 3.36; 95%CI 1.66-6.82; p<0.001), 40-49 years old (OR = 1.85; 95%CI 1.26-2.73; p<0.01), 50-59 years old (OR = 1.87; 95%CI 1.55-2.26; p<0.001), 60-69 years old (OR = 1.26; 95%CI 1.11-1.42; p<0.001), ≥70 years old (OR = 1.11; 95%CI 1.03-1.20; p<0.01)], as well as in patients with fewer traditional cardiovascular risk-factors (none:OR = 1.29; 95 % CI 1.09 to 1.77; p<0.01, 1-2:OR = 1.30; 95 % CI 1.19 to 1.41; p<0.001, ≥3:OR = 1.09; 95 % CI 0.99 to 1.21; p=0.076). CONCLUSIONS: Our study demonstrates for the first time a positive association between anti-Ro/La seropositivity and IHD in the general adult population, especially among younger individuals with fewer traditional cardiovascular risk factors.
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Anticuerpos Antinucleares , Isquemia Miocárdica , Humanos , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/sangre , Isquemia Miocárdica/inmunología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Israel/epidemiología , Anciano , Factores de Riesgo , Anticuerpos Antinucleares/sangre , Modelos Logísticos , Oportunidad Relativa , Análisis Multivariante , Biomarcadores/sangre , Factores de EdadRESUMEN
BACKGROUND: While the contribution of environmental factors including smoking, overweight and stress has been validated, data mining for the association between socioeconomic status (SES) and psoriasis prevalence has yielded contradicting observations. OBJECTIVE: To evaluate the association between psoriasis prevalence and SES. METHODS: This was a nationwide population-based cross-sectional retrospective study that included all patients insured by the "Clalit" Health Services (N=4,604,994). Univariable and multivariable logistic regression analyses were conducted to explore the association between psoriasis and SES while controlling for potential sociodemographic and clinical confounders. RESULTS: The study population included 129,855 patients with psoriasis and 4,475,139 individuals without psoriasis. Higher SES was associated with an increased prevalence of psoriasis; in a fully adjusted model, Clalit members within the highest SES were 1.43-fold more likely to have psoriasis (95% CI, 1.39-1.48; P< 0.001), and those at medium SES were 1.2-fold more likely to have psoriasis, compared to those at the lowest SES group (95% CI, 1.18-1.26; P< 0.001; P for linear trend <0.001). CONCLUSIONS: Positive correlation was found between SES and psoriasis prevalence. Further investigation is warranted to elucidate the factors accounting for this observation.
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BACKGROUND: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with a heavy burden of morbidity and cost. OBJECTIVES: To provide standardized estimates of trends in HS incidence and prevalence among patients in Israel between 2016 and 2019. METHODS: We conducted a population-based analysis of routinely collected electronic health records data from Clalit Health Services, the largest nationwide public health service provider in Israel. Age- and sex-adjusted rates were reported by using the standard European population as a reference. RESULTS: The study included 3488 HS incident cases. The mean ± SD age of onset was 30.3 years and was similar in males and females. HS was more common among Jews with low and medium socioeconomic status. The annual HS incidence rate increased throughout the study period. HS prevalence increased from 0.12% in 2016 to 0.17% in 2019. CONCLUSIONS: HS prevalence and incidence rates steadily rose among the Israeli population between 2016 and 2019. Awareness of these findings can help provide an optimal allocation of healthcare resources by policymakers and health service providers and prevent delays in diagnosis.
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Hidradenitis Supurativa , Humanos , Israel/epidemiología , Hidradenitis Supurativa/epidemiología , Hidradenitis Supurativa/diagnóstico , Masculino , Incidencia , Femenino , Prevalencia , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Judíos/estadística & datos numéricos , Niño , AncianoRESUMEN
OBJECTIVE: COVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. METHODS: A population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. RESULTS: A total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). CONCLUSION: Based on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.
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Vacunas contra la COVID-19 , COVID-19 , Tiroiditis Subaguda , Humanos , Tiroiditis Subaguda/epidemiología , Tiroiditis Subaguda/etiología , Femenino , Masculino , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/complicaciones , Persona de Mediana Edad , Adulto , Vacunas contra la COVID-19/efectos adversos , Anciano , Vacunación/estadística & datos numéricos , Estudios de Casos y Controles , SARS-CoV-2RESUMEN
Diabetes Mellitus (DM) is more common among individuals with severe mental illness (SMI). We aimed to assess quality-of-care-indicators in individuals with SMI following the 2015 Israel's Mental-Health-reform. We analyzed yearly changes in 2015-2019 of quality-of-care-measures and intermediate-DM-outcomes, with adjustment for gender, age-group, and socioeconomic status (SES) and compared individuals with SMI to the general adult population. Adults with SMI had higher prevalences of DM (odds ratio (OR) = 1.64; 95% confidence intervals (CI): 1.61-1.67) and obesity (OR = 2.11; 95% CI: 2.08-2.13), compared to the general population. DM prevalence, DM control, and obesity rates increased over the years in this population. In 2019, HbA1c testing was marginally lower (OR = 0.88; 95% CI: 0.83-0.94) and uncontrolled DM (HbA1c > 9%) slightly more common among patients with SMI (OR = 1.22; 95% CI: 1.14-1.30), control worsened by decreasing SES. After adjustment, uncontrolled DM (adj. OR = 1.02; 95% CI: 0.96-1.09) was not associated with SMI. Cardio-metabolic morbidity among patients with SMI may be related to high prevalences of obesity and DM rather than poor DM control. Effective screening for metabolic diseases in this population and social reforms are required.
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Diabetes Mellitus , Trastornos Mentales , Adulto , Humanos , Salud Mental , Hemoglobina Glucada , Reforma de la Atención de Salud , Israel/epidemiología , Indicadores de Calidad de la Atención de Salud , Diabetes Mellitus/epidemiología , Trastornos Mentales/complicaciones , Trastornos Mentales/epidemiología , Trastornos Mentales/diagnóstico , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
OBJECTIVES: Israel is regarded as a country with a developed economy and a moderate income inequality index. In this population-based study, we aimed to measure the inequalities in colorectal cancer screening within Clalit Health, an organization with universal insurance, before and during the coronavirus disease 2019 pandemic. SETTING: Retrospective analysis within Clalit Health Services, Israel. METHODS: We evaluated the rate of being up to date with screening (having a colonoscopy within 10 years or a fecal occult blood test within 1 year) and the colonoscopy completion rate (having a colonoscopy within 6 months of a positive fecal occult blood test) among subjects aged 50-75 in 2019-2021. RESULTS: In 2019, out of 918,135 subjects, 61.3% were up to date with screening; high socioeconomic status: 65.9% (referent), medium-socioeconomic status: 60.1% (odds ratio 0.81, 95% confidence interval 0.80-0.82), low-socioeconomic status: 59.0% (odds ratio 0.75, 95% confidence interval 0.74-0.75); Jews: 61.9% (referent), Arabs: 59.7% (odds ratio 0.91, 95% confidence interval 0.90-0.92), Ultraorthodox-Jews: 51.7% (odds ratio 0.77, 95% confidence interval 0.75-0.78). Out of 21,308 with a positive fecal occult blood test, the colonoscopy completion rate was 51.8%; high-socioeconomic status: 59.8% (referent), medium-socioeconomic status: 54.1% (odds ratio 0.79, 95% confidence interval 0.73-0.86), low-socioeconomic status: 45.5% (odds ratio 0.60, 95% confidence interval 0.56-0.65); Jews: 54.7% (referent), Ultraorthodox-Jews: 51.4% (odds ratio 0.91, 95% confidence interval 0.90-0.92), Arabs: 44.7% (odds ratio 0.77, 95% confidence interval 0.75-0.78). In 2020-2021, there was a slight drop in the rate of being up to date with screening, while most of the discrepancies were kept or slightly increased with time. CONCLUSIONS: We report significant inequalities in colorectal cancer screening before and during the coronavirus disease 2019 pandemic in Israel, despite a declared policy of equality and universal insurance.
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Reports from many settings suggest that pediatric overweight and obesity increased in 2020 and 2021, presumably due to lifestyle changes associated with the COVID-19 pandemic. Many of these previous reports have relied on convenience samples or subsets of the population. Here, we present results of a longitudinal study of the entire population of Israel, a nation of approximately 9 million people, with the proportion with underweight, normal weight, overweight, and obesity at age 7 and at age 14-15, across the years 2017-2021. Our results show that the prevalence of overweight and obesity, which had been steady or improving through 2019, increased relatively quickly in 2020 and 2021. For example, among 7-year-olds, the percentage of children with obesity in 2019 was 6.8% (99% CI: 6.69-7.05), and by 2021, it had increased to 7.7% (99% CI: 7.53-7.93). There were important disparities in overweight and obesity based on SES; for example, the rate ratio for obesity comparing the poorest with the wealthiest 14-15-year-olds in 2019 was 1.63 (99% CI: 1.55-1.72). However, these disparities did not change meaningfully in 2020 and 2021, implying that while obesity did become more prevalent, this increase in prevalence was not differential across socioeconomic status. Like many other nations, Israel too experienced considerable increases in pediatric overweight and obesity in 2020-2021, erasing the improvements of the previous years among younger children.
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COVID-19 , Sobrepeso , Niño , Humanos , Israel , Estudios Longitudinales , Pandemias , ObesidadRESUMEN
BACKGROUND: Previous studies demonstrated unclear and vast variability in the association between Ankylosing Spondylitis (AS) and the risk of cancer. OBJECTIVES: To assess the risk of overall and site-specific malignancies for AS patients in Israel, while examining the role of comorbidities and immunomodulatory therapy. METHODS: We conducted a retrospective electronic data-based study including all AS patients diagnosed between 2002 and 2018, with no history of cancer prior to enrollment, with 5:1 ratio matched-control by age, gender, and place of residence. The odds Ratios (OR) for site-specific malignancies, comparing AS patients and controls, were calculated using logistic regression. Risk factors for malignancies within the AS cohort were evaluated in the same manner. RESULTS: This study comprised 5825 AS patients and 28,356 matched controls. There was a higher overall risk of cancer in AS patients compared to controls (OR = 1.4, 95% CI 1.24-1.6), specifically for solid malignancies (OR = 1.5, 95% CI 1.3-1.7), CNS (OR = 3.72, 95% CI 1.29-10.7), kidney (OR = 2.06, 95% CI 1.12-3.8), and malignancy of unknown primary (OR = 3.06, 95% CI 2.35-3.98). Regarding predictors for malignancy within AS patients, older age at diagnosis (OR = 1.31, 95%,CI 1.25-2.36), diabetes (OR = 1.52, 95% CI 1.18-1.97), IBD (OR = 2.61, 95% CI 1.75-3.89), and treatment with DMARDs (OR = 2.17, 95% CI 1.65-2.83) were associated with a higher risk of solid malignancies, while NSAIDs treatment alone had a protective effect for solid malignancies (OR = 0.78, 95% CI 0.61-0.99). No significant association was found between anti-TNF therapy and the risk of solid or hematologic malignancies within the AS group. CONCLUSION: AS is associated with an increased risk of overall and site-specific malignancies, with independently higher risk for older age, comorbidity of DM, IBD, and treatment with DMARDs.
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BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the sacroiliac joint and axial skeleton with associated extra-articular involvement including cardiovascular system disease including aortic valve disease with variable reported prevalence. The aim of this study is to determine the prevalence of heart valve disorders in AS patients. METHODS: This was a retrospective, population-based, cross-sectional study that retrieved data from the Clalit Health Services registry. Cases were defined as having AS, whereas controls were frequency matched by age and sex in a ratio of 5:1. The prevalence of valvular heart diseases was compared between the two groups; a multivariate logistic regression model was applied to estimate the association after controlling for potential confounders. RESULTS: We included 4082 AS patients and 20 397 controls frequency matched by age and sex. AS patients had a significantly higher prevalence of cardiovascular risk factors (P < .001) and a higher prevalence of valvular heart disease. In the multivariate logistic regression model, adjusting for multiple confounding factors, AS was independently associated with aortic stenosis [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.57-3.23, P < 0.001], aortic insufficiency (OR: 2.44, 95% CI: 1.50-3.94, P < 0.001), and mitral insufficiency (OR: 1.75, 95% CI: 1.17-2.61, P < 0.001) but not mitral stenosis (OR: 1.31, 95% CI: 0.60-2.70, P = 0.47). CONCLUSIONS: Our study reports the increased risk of valvular heart diseases in patients with AS, possibly due to the inflammatory milieu associated with the disease process and the result of biomechanical stress affecting the enthesis-like valvular structures.
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Enfermedades de las Válvulas Cardíacas , Espondilitis Anquilosante , Humanos , Estudios Transversales , Estudios Retrospectivos , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/complicaciones , Prevalencia , Enfermedades de las Válvulas Cardíacas/epidemiologíaRESUMEN
OBJECTIVES: Several studies have shown a higher prevalence of irritable bowel syndrome (IBS) among patients with fibromyalgia yet, data regarding association between fibromyalgia and other gastrointestinal disorders have been relatively overlooked. Our aim was to investigate the association between fibromyalgia and gastrointestinal disorders including both benign and malignant conditions. METHODS: We conducted a retrospective cross-sectional study based on the comprehensive electronic database of the largest health maintenance organisation in Israel. All subjects with a diagnosis of fibromyalgia in their medical records and age- and sex-matched controls were included in the study. We investigated the association of fibromyalgia with benign gastrointestinal disorders including IBS, gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), celiac disease, Crohn's disease, ulcerative colitis, and with gastrointestinal malignancies including colorectal, pancreatic, stomach, liver, and bile duct cancers. RESULTS: The study enrolled 18,598 patients with fibromyalgia and 36,985 controls. The mean age was 56.5 years (standard deviation=14) with a female predominance (91%). Fibromyalgia was significantly associated with IBS (OR 4.61, 95% CI 4.09-5.2, p<0.001), GERD (OR 2.62, 95% CI 2.5-2.75, p<0.001), PUD (OR 2.13, 95% CI 1.98-2.3, p<0.001), celiac disease (OR 2.08, 95% CI 1.63-2.65, p<0.001), Crohn's disease (OR 1.85, 95% CI 1.408-2.32, p<0.001) and ulcerative colitis (OR 1.81, 95%CI 1.4-2.33, p<0.001). Nonetheless, no significant differences were found regarding the prevalence of gastrointestinal malignancies between the fibromyalgia patients and controls. CONCLUSIONS: Our findings suggest that FM is positively associated with various benign but not malignant GI disorders.
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Enfermedad Celíaca , Colitis Ulcerosa , Enfermedad de Crohn , Fibromialgia , Reflujo Gastroesofágico , Síndrome del Colon Irritable , Neoplasias , Humanos , Femenino , Persona de Mediana Edad , Masculino , Fibromialgia/diagnóstico , Fibromialgia/epidemiología , Fibromialgia/complicaciones , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/complicaciones , Estudios Transversales , Síndrome del Colon Irritable/epidemiología , Síndrome del Colon Irritable/complicaciones , Enfermedad Celíaca/complicaciones , Estudios Retrospectivos , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/complicaciones , Neoplasias/epidemiología , Neoplasias/complicaciones , PrevalenciaRESUMEN
INTRODUCTION: Active metabolite of vitamin D has neuro-immunomodulatory and neuroprotective properties. However, there is still a debate about the potential association between low serum levels of hydroxy-vitamin D and increased risk for dementia. OBJECTIVES: To determine an association between hypovitaminosis D and dementia for different 25-hydroxyvitamin-D (25(OH)D) serum level cutoffs. METHODS: Patients were identified utilizing the database of Clalit Health Services (CHS), the largest healthcare provider in Israel. For each subject, all available values of 25(OH)D during the study period, which lasted from 2002 to 2019, were obtained. Rates of dementia were compared across different cutoffs of 25(OH)D levels. RESULTS: Cohort included 4278 patients, of whom 2454 (57%) were women. The mean age at the beginning of follow-up was 53 (±17). During the 17-year study period, a total of 133 patients (3%) were diagnosed with dementia. In a fully adjusted multivariate analysis, the risk for dementia was almost 2-fold higher in patients with an average of vitamin D insufficiency (<75 nmol/l) measurements (OR = 1.8, 95% C.I. = 1.0-3.2) compared to reference values (≥75 nmol/l). Patients with vitamin D deficiency (<50 nmol/l) demonstrated higher rates of dementia (OR = 2.6, 95% C.I. = 1.4-4.8). In our cohort, patients were diagnosed with dementia at a younger age in the deficiency (77 vs. 81 P-value = 0.05) and the insufficiency groups (77 vs. 81 P-value = 0.05) compared to the reference values (≥75 nmol/l). CONCLUSION: Insufficient levels of vitamin D are associated with dementia. Dementia is diagnosed at a younger age in patients with insufficient and deficient vitamin D levels.