Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline.

IMPORTANCE: Adults with Down syndrome (DS) are at high-risk of revealing Alzheimer's disease (AD) pathology, in part due to the triplication of chromosome 21 encoding the amyloid precursor protein. Adults with DS are uniformly affected by AD pathology by their 30's and have a 70% to 80% chance of clinical dementia by their 60's. Our previous studies have assessed longitudinal changes in amyloid beta (Aß) accumulation in DS. OBJECTIVE: The goal of the present study was to assess the presence of brain tau using [18F]AV-1451 positron emission tomography (PET) in DS and to assess the relationship of brain tau pathology to Aß using Pittsburgh Compound B (PiB)-PET. DESIGN: Cohort study. SETTING: Multi-center study. PARTICIPANTS: Participants consisted of a sample of individuals with DS and sibling controls recruited from the community; exclusion criteria included contraindications for magnetic resonance imaging (MRI) and/or a medical or psychiatric condition that impaired cognitive functioning. EXPOSURES: PET brain scans to assess Aß ([11C]PiB) and tau ([18F]AV-1451) burden. MAIN OUTCOMES AND MEASURES: Multiple linear regression models (adjusted for chronological age, sex and performance site) were used to examine associations between regional [18F]AV-1451 standard uptake value ratio (SUVR) (based on regions associated with Braak stages 1-6) and global [11C]PiB SUVR (as both a continuous and dichotomous variable). RESULTS: A cohort of 156 participants (mean age = 39.05, SD(8.4)) were examined. These results revealed a significant relationship between in vivo Aß and tau pathology in DS. As a dichotomous variable, [18F]AV-1451 retention was higher in each Braak region in PiB(+) participants. We also found, based on our statistical models, starting with the Braak 3 region of interest (ROI), an acceleration of [18F]AV-1451 SUVR deposition with [11C]PiB SUVR increases.

Big data highlights the association between psoriasis and fibromyalgia: a population-based study.

Data on the association between fibromyalgia syndrome (FMS) and psoriasis are scarce. We aimed to examine the association between FMS and psoriasis using a large-scale observational population-based study. This cross-sectional study analyzed data from a big computerized database to evaluate potential differences in the prevalence of psoriasis between patients with FMS and matched control subjects. The study included 18,598 patients with FMS and 36,985 controls. The prevalence of psoriasis was increased in patients with FMS as compared with control subjects (6.7% vs. 4.8%, respectively; OR, 1.4; 95% CI, 1.3-1.5; P < 0.001). This association was robust to multivariate analysis adjustment for sex, age, ancestry, socioeconomic status, and healthcare utilization (OR, 1.3; 95% CI, 1.2-1.4; P < 0.001). When compared with patients with only FMS, patients with a dual diagnosis of FMS and psoriasis presented with FMS at a significantly older age, had a higher mean BMI, and a higher frequency of smoking. To conclude, we found a significant association between FMS and psoriasis. More extensive cooperation between dermatologists and rheumatologists is suggested to enable early identification of their co-occurrence.

Amyloidosis in hidradenitis suppurativa: a cross-sectional study and review of the literature.

BACKGROUND: Coexistence of hidradenitis suppurativa (HS) and amyloidosis has been anecdotally described, but the association between these conditions is yet to be firmly established. AIM: To study the association between HS and amyloidosis using a large-scale computerized database, and to perform a literature review to characterize all reported patients with coexistent HS and amyloidosis. METHODS: A cross-sectional study was conducted comparing the prevalence of amyloidosis among patients with HS and age-, sex- and ethnicity-matched healthy controls (HCs). Additionally, a review of literature was performed to summarize all reported cases with a dual diagnosis of both conditions. RESULTS: In total, 4417 patients with HS and 22 085 controls were included in the study. The prevalence of amyloidosis was increased in patients with HS compared with the HC group [n = 7 (0.2%) vs. n = 2 (0.0%), respectively; OR = 17.5; 95% CI 3.6-84.4; P < 0.001]. In a multivariate analysis, HS was still associated with amyloidosis (OR = 11.2; 95% CI 1.3-94.5; P = 0.03). The literature review identified nine patients who developed amyloidosis during the course of HS, with 44.4% eventually having renal failure. ‬Favourable outcomes were reported in patients managed by tumour necrosis factor (TNF)-α inhibitors. CONCLUSION: This study establishes the association between HS and amyloidosis. Screening for amyloidosis may be considered in patients with HS with a relevant clinical picture, mainly proteinuria. TNF-α inhibitors may be preferred in patients with a dual diagnosis of these conditions.

An improved algorithm of white matter hyperintensity detection in elderly adults.

Automated segmentation of the aging brain raises significant challenges because of the prevalence, extent, and heterogeneity of white matter hyperintensities. White matter hyperintensities can be frequently identified in magnetic resonance imaging (MRI) scans of older individuals and among those who have Alzheimer's disease. We propose OASIS-AD, a method for automatic segmentation of white matter hyperintensities in older adults using structural brain MRIs. OASIS-AD is an approach evolved from OASIS, which was developed for automatic lesion segmentation in multiple sclerosis. OASIS-AD is a major refinement of OASIS that takes into account the specific challenges raised by white matter hyperintensities in Alzheimer's disease. In particular, OASIS-AD combines three processing steps: 1) using an eroding procedure on the skull stripped mask; 2) adding a nearest neighbor feature construction approach; and 3) applying a Gaussian filter to refine segmentation results, creating a novel process for WMH detection in aging population. We show that OASIS-AD performs better than existing automatic white matter hyperintensity segmentation approaches.

Drug survival in patients with psoriasis is associated with the availability of biologic medications.

BACKGROUND: Drug survival rates in patients with psoriasis had been described extensively. Different survival rates of TNF-α inhibitors (TNFIs), ustekinumab and secukinumab were reported. OBJECTIVES: To investigate drug survival rates of TNFIs, ustekinumab and secukinumab, with particular emphasis on the difference between ustekinumab and secukinumab. METHODS: Survival analysis was performed in patients with moderate-to-severe psoriasis who received adalimumab, infliximab, etanercept, ustekinumab and secukinumab treatment in 2002-2018, using the Clalit Health Services database. Stratified analysis was performed according to biologic treatment lines. Multivariate analysis was performed adjusting for demographic variables, calendar year, metabolic syndrome, psoriatic arthritis, biologic treatment line, biologic naivety, co-administration of oral treatments and previous oral systemic treatment exposure. RESULTS: Among 1459 patients treated with 3070 biologic medication courses, ustekinumab had a significantly higher crude survival as compared with TNFIs and secukinumab. The mean drug survival of ustekinumab, adalimumab, etanercept, infliximab and secukinumab was 43.5 (CI: 39.7-47.2), 38.2 (CI: 34.8-41), 33.9 (CI: 30.8-37.1), 28.2 (CI: 22.5-33.8) and 17.1 (CI: 15.6-18.6) months, respectively, with significant statistical differences for all comparisons (P < 0.001). The differences between ustekinumab and secukinumab were not significant following adjustment to factors that included treatment line (hazard rate 1.16, CI: 0.93-1.43). CONCLUSION: Different drug survival rates between ustekinumab and secukinumab are determined by the treatment line and calendar year, reflecting the availability of biologic medications, and not only by the biologic attributes of each medication.

Treatment and clinical outcomes in anti-p200 pemphigoid: a systematic review.

BACKGROUND: Current treatment paradigms in anti-p200 pemphigoid rely on low levels of evidence, primarily originating from case reports and case series. OBJECTIVE: To systematically review the utilized treatment modalities for anti-p200 pemphigoid and to synthesize the available clinical outcomes of treated patients. METHODS: We conducted a systematic review of the literature using Ovid-Medline (1946-2018), Embase (1947-2018) and Web of Science (1900-2018) databases with a broad and inclusive search strategy along with a subsequent search of retrieved articles. All case reports and case series of patients with anti-p200 pemphigoid were included. RESULTS: Sixty-eight eligible studies comprising 113 anti-p200 pemphigoid patients with a mean age of 65.5 years were included in the qualitative synthesis. The clinical outcome of patients following treatment was reported for 91 (80.5%) patients, of whom 83 (91.2%) had achieved complete remission at least once. Complete remission on-therapy was observed in 51 (56.0%) and complete remission off-therapy in 12 (13.2%) patients. Thirty-six (39.6%) patients had experienced at least one flare during the duration of follow-up. A combination of systemic corticosteroids and adjuvant immunomodulatory agents was the leading therapeutic approach (63.0%) required for disease control. Systemic and topical corticosteroids as monotherapy were sufficient to control the disease in 19.6% and 13.0% of cases, respectively. Dapsone was the most commonly used (41.3%) adjuvant agent. The highest rates of complete remission were achieved in patients managed by systemic corticosteroids as monotherapy (100%) and in those managed by systemic corticosteroids with adjuvant agents (90.7%). Conversely, 45.5% of patients treated only by topical corticosteroids experienced at least one relapse during follow-up. CONCLUSION: The vast majority of patients had reached a complete remission during the course of the disease, whereas a considerable proportion of patients experienced at least one relapse. A combination of systemic corticosteroids and adjuvant immunomodulatory agents was the most frequently utilized therapeutic approach.

Hidradenitis suppurativa and schizophrenia: a nationwide cohort study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, debilitating, dermatological disease that causes substantial psychosocial impediments with increased suicidal risk. Yet data on psychiatric comorbidity in HS have not been sufficiently elucidated in population-based studies. The current study sought to investigate the association between HS and schizophrenia, a major psychiatric disease, in a nationwide population-based study in Israel. METHODS: Data mining was performed on the database of Clalit Health Services (CHS), the largest managed healthcare company in Israel. Patients diagnosed with HS (n = 4191) were examined and compared to age- and sex-matched controls (n = 20 941). The association between HS and schizophrenia was assessed via multivariate binary logistic regression, adjusting for demographic factors and smoking status. RESULTS: The analysis revealed a tenfold increase in the prevalence of schizophrenia in HS patients compared to controls (1.4% and 0.4%, respectively, P < 0.001). In multivariate analysis, HS was found to be associated with schizophrenia (OR 1.44, 95% CI 1.01-2.07, P < 0.05). CONCLUSIONS: Hidradenitis suppurativa is associated with schizophrenia. Screening for severe mental illness during the assessment of patients with HS is of great importance, as comorbid psychiatric disorders may affect treatment outcomes.

Incidence and prevalence of psoriasis in Israel between 2011 and 2017.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease associated with a heavy burden of morbidity, disability and cost. The occurrence of the disease in Israel has not been previously investigated. OBJECTIVES: To provide standardized estimates of trends in psoriasis incidence, prevalence and mortality among patients in Israel between 2011 and 2017. METHODS: Using electronic health records from Clalit Health Services, the largest nationwide public health provider in Israel, we conducted a population-based study investigating trends in the annual incidence and prevalence of psoriasis between the years 2011 and 2017. We report age- and sex-adjusted rates, using the standard European population as a reference. RESULTS: We identified 71 094 incident psoriasis cases. The mean (SD) age of onset was 42.4 (21.0) years with a bimodal distribution, peaking in the early '30s and early '60s. Late-onset psoriasis, occurring after 40 years of age, accounted for 51.1% of incident cases. The annual psoriasis incidence rate was constant throughout the study period (280/100 000 person-years). Psoriasis prevalence rose from 2.5% in 2011 to 3.8% in 2017. CONCLUSIONS: Psoriasis prevalence is increasing in Israel, although its incidence is stable. Clinicians and policymakers should plan to address the growing demands in the clinical, economic and societal burden of psoriasis.

Atopic dermatitis and the metabolic syndrome: a cross-sectional study of 116 816 patients.

BACKGROUND: Data regarding the association between atopic dermatitis (AD) and the metabolic syndrome are controversial. OBJECTIVE: To evaluate the prevalence of the metabolic syndrome and its components in a large group of patients with AD compared to a matched reference group. METHODS: A cross-sectional study of AD patients diagnosed by a dermatologist between 1998 and 2016, and a matched comparison group was performed. We analysed the association between AD and metabolic syndrome, its components and possible complications for the entire study population, adults (age > 18) and adults with moderate-to-severe AD. RESULTS: The study included 116 816 patients with AD and 116 812 comparison enrollees. AD in the entire group of patients and in the adult patients was associated with a higher prevalence of dyslipidaemia and a lower prevalence of diabetes and metabolic syndrome. Moderate and severe AD were associated, respectively, with higher prevalence rates of the metabolic syndrome (17.0% vs. 9.4%), its components (obesity: 22.2% vs. 18.6%; diabetes: 15.9% vs. 9.2%; hypertension 27.9% vs. 15.3%; dyslipidaemia 47.1% vs. 28.5%, all P values < 0.001) and cardiovascular morbidity (all P values < 0.001). Multivariate analysis demonstrated a significant overrepresentation of the metabolic syndrome in moderate-to-severe AD (P = 0.04). CONCLUSIONS: Severely affected patients with AD may have one or more undiagnosed components of metabolic syndrome.

The association between the socioeconomic status and anxiety-depression comorbidity in patients with psoriasis: a nationwide population-based study.

BACKGROUND: Numerous studies have indicated that comorbid anxiety and depression are associated with a more severe course of illness. Yet generally, the study of the effect of psoriasis on patients' mental health has considered anxiety and depression to be separate states. OBJECTIVE: To measure the association between psoriasis and anxiety, depression and anxiety-depression co-occurrence among patients according to their socioeconomic statuses (SES). METHODS: A nationwide population-based study of psoriasis patients and age and gender frequency-matched controls (n = 255 862) was designed. Diagnostic data were obtained from Clalit Health Services, the largest managed care organization in Israel. This database was established using continuous real-time input from healthcare providers, pharmacies, medical care facilities and administrative computerized operating systems. RESULTS: After controlling for demographic and clinical variables, psoriasis was associated with anxiety (OR 1.11, 95% CI 1.01-1.23, P < 0.05), depression (OR 1.17, 95% CI 1.08-1.26, P < 0.001), and anxiety and depression co-occurrence (OR 1.32, 95% CI 1.21-1.45, P < 0.001) among patients with low SES, yet was associated only with anxiety (OR 1.15 95% CI 1.04-1.27, P < 0.001) but not depression or comorbid anxiety-depression among patients with high SES. Survival analyses indicated that between the ages of 40 and 60, the cumulative probability of psoriasis patients with low SES to suffer from anxiety, depression and their co-occurrence inclined more sharply with age as compared to psoriasis patients with high SES. CONCLUSIONS: As psoriasis patients with low SES are prone to suffer from more severe courses of anxiety and depression, the choice of treatment of psoriasis should address the SES as well as the underlying psychiatric disease.

Association between schizophrenia and an autoimmune bullous skin disease-pemphigus: a population-based large-scale study.

AIMS: Immunological hypotheses have become increasingly prominent suggesting that autoimmunity may be involved in the pathogenesis of schizophrenia. Schizophrenia was found to be associated with a wide range of autoimmune diseases. However, the association between pemphigus and schizophrenia has not been established yet. We aimed to estimate the association between pemphigus and schizophrenia using a large-scale real-life computerised database. METHODS: This study was conducted as a cross-sectional study utilising the database of Clalit Health Services. The proportion of schizophrenia was compared between patients diagnosed with pemphigus and age-, gender- and ethnicity-matched control subjects. Univariate analysis was performed using χ2 and Student's t-test and a multivariate analysis was performed using a logistic regression model. RESULTS: A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of schizophrenia was greater in patients with pemphigus as compared to the control group (2.0% v. 1.3%, respectively; p = 0.019). In a multivariate analysis, pemphigus was significantly associated with schizophrenia (OR, 1.5; 95% CI, 1.1-2.2). The association was more prominent among females, patients older than 60 years, and Jews. CONCLUSIONS: Pemphigus is significantly associated with schizophrenia. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid schizophrenia and be treated appropriately.

Chronic urticaria and osteoporosis: a longitudinal, community-based cohort study of 11 944 patients.

BACKGROUND: Chronic urticaria (CU) carries many risk factors for osteoporosis, but data on the relationships between CU and osteoporosis are lacking. OBJECTIVES: To evaluate the association between CU and osteoporosis in a large community-based study. METHODS: A nationwide observational longitudinal cohort study was conducted. CU was defined as four pairs of urticaria diagnoses; each pair was recorded within a period of 6 weeks and was registered by physicians in a primary-care setting. Patients with CU and their age- and sex- matched controls were followed for the incidence of osteoporosis and other laboratory data between 2002 and 2017. Data regarding systemic steroid exposure and other relevant risk factors for osteoporosis were obtained. Analyses of risk for osteoporosis were performed in Cox regression models adjusted for age, sex, exposure to systemic corticosteroids, obesity, smoking and hyper- and hypothyroid disease. RESULTS: The study included 11 944 patients with CU and 59 829 controls. During the study's observation period, 1035 (8·7%) patients with CU were diagnosed with osteoporosis, compared with 4046 (6·8%) controls. The adjusted multivariate analysis demonstrated that CU was significantly associated with a higher risk for osteoporosis (hazard ratio 1·23, 95% confidence interval 1·10-1·37, P < 0·001). CONCLUSIONS: CU may impose a risk for osteoporosis. Appropriate targeted screening should be considered.