Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis.

OBJECTIVES: The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis. METHODS: Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models. RESULTS: Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001). CONCLUSIONS: The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.

The Utility of Laboratory Investigations for the Assessment and Management of Rheumatic Immune Related Adverse Events.

Immune checkpoint inhibitors (ICIs) have greatly improved survival of several cancers with historically very poor prognosis. ICIs act by stimulating the patient's own immune system to fight cancer. Simultaneously, this immune activation can lead to immune-related adverse events (irAEs), including rheumatic manifestations (Rh-irAEs). Rh-irAEs mimic primary rheumatic diseases including arthritis, polymyalgia rheumatica, myositis, vasculitis, sarcoidosis, and sicca. This article summarizes the latest evidence regarding the utility of laboratory investigations in Rh-irAEs.

Incidence and disease burden of autoimmune inflammatory rheumatic diseases after non-pharmaceutical interventions in the COVID-19 era: A nationwide observational study in Korea.

BACKGROUND: Infections are considered risk factors for autoimmune inflammatory rheumatic diseases (AIRDs), the incidence of which is considered to have been impacted by the COVID-19 pandemic. The impact of non-pharmaceutical interventions (NPIs) on the incidence of AIRDs and their associated health care services and medical expenses in Korea was investigated. METHODS: We included all AIRD cases reported between January 2016 and February 2021 based on the National Health Insurance Service data. We evaluated changes in incidence trends for each AIRD before and after NPI implementation (Feb 2020 to Feb 2021) using segmented regression analysis. Changes in health care utilization and medical costs for each AIRD before and after NPI implementation were also investigated. RESULTS: After NPI implementation, monthly incidence rates declined significantly by 0.205 per 1 000 000 (95% confidence interval [CI], -0.308 to -0.101, p < .001) in patients with systemic lupus erythematosus (SLE). No significant changes in the incidence of all AIRDs other than SLE were observed before and after implementation. Further, annual outpatient department visits per patient were lower during implementation for all diseases, except juvenile idiopathic arthritis (JIA). The prescription days per outpatient visit increased significantly during implementation for all diseases, except JIA and ankylosing spondylitis. During implementation, the total annual medical costs per patient tended to decrease for all diseases, except JIA and mixed connective tissue disease. CONCLUSION: Implementation of NPIs to contain the pandemic led to a reduction in the incidence of SLE and changed patterns of medical care utilization and treatment cost for most AIRDs.

[Quality of life, disease burden and healthcare need of patients with vitiligo]. / Lebensqualität, Krankheitslast und Versorgungsbedarf von Patienten mit Vitiligo.

BACKGROUND: With a prevalence of 0.5-2%, vitiligo is one of the most common skin disorders worldwide with loss of pigment. The skin disease has a disfiguring, often stigmatising character and is often associated with psychosocial distress. OBJECTIVE: To provide an overview of the psychosocial impairment, disease burden and resulting health care needs of patients with vitiligo. MATERIALS AND METHODS: Narrative review based on a literature search in PubMed for the years 1996-2022 on disease burden, quality of life and stigmatization is provided. RESULTS: The search yielded 175 relevant original papers including clinical studies, meta-analyses and systematic reviews (n = 65) for the search period. A large number of studies document that vitiligo is associated with considerable psychosocial stress and relevant losses in quality of life. Problem areas particularly concern stigmatisation, sexual dysfunction, anxiety, reduced self-esteem and problems at work. The observed increased levels of anxiety and depression correlate with the severity and activity of vitiligo. Often, comorbidity also contributes to reduced self-esteem and social isolation. These factors determine a high need for care in a relevant proportion of those affected. CONCLUSION: Vitiligo is not primarily a cosmetic problem, but a disease requiring treatment according to the World Health Organisation's definition of health as physical, mental and social well-being. The benefits of treatment options are to be measured by their effects on patient-reported outcomes.

Estimated prevalence, incidence and healthcare costs of Sjögren's syndrome in France: a national claims-based study.

OBJECTIVES: To estimate prevalence, incidence and mortality rates, and annual healthcare costs of primary Sjögren's syndrome (pSS) and SS associated with other autoimmune disorders (SS+AID) in France. METHODS: French national healthcare claims-based study within the prospective Système National des Données de Santé database that includes the majority of the French population. An algorithm was developed to identify patients with SS and SS-related healthcare claims were analysed between 2011 and 2018. RESULTS: Overall, 23 848 patients with pSS and 14 809 with SS+AID were identified. From 2011 to 2018, the prevalence rate increased slightly for pSS (23-32 per 100000) and SS+AID (16-20 per 100 000), with females comprising 90%-91% and 92%-93% of cases, respectively. The incidence rate of SS per 100 000 persons decreased from 2012 (pSS: 4.3; SS+AID: 2.0) to 2017 (pSS: 0.7; SS+AID: 0.3). Mortality rates per 100 000 persons increased from 2012 to 2018 in patients with pSS (0.2-0.8) or SS+AID (0.1-0.5); mean age of death also increased. Artificial tears and hydroxychloroquine were the most common drug reimbursements. Less than half of patients received annual specialist care from a dentist or ophthalmologist. Healthcare costs associated with SS increased from 2011 to 2018 and exceeded the national estimate of expected costs for chronic diseases. CONCLUSION: In this large French population database study, the low prevalence of pSS confirms that it is an orphan disease. SS is clinically and economically burdensome; these findings may help clinicians better understand routine healthcare received by patients.

Assessment of COVID-19 Morbidity and Mortality Among Patients With Autoimmune Diseases at King Abdulaziz University Hospital.

Background The coronavirus disease 2019 (COVID-19) pandemic has raised significant concerns about the effects of the virus on patients with autoimmune diseases. Therefore, understanding the COVID-19 outcomes in this population is crucial for effective prevention and management. Objective This study aimed to investigate the association between autoimmune diseases and the severity of COVID-19 in terms of mortality and morbidity. Despite substantial advancements in pandemic-related research concerning COVID-19 and autoimmune diseases, there remain noteworthy gaps in our comprehension of this association, particularly due to limited investigations conducted in Saudi Arabia. Methods This was a retrospective record review of a tertiary center from January 2020 to January 2022. We included 120 patients, among whom 40 were diagnosed with autoimmune diseases, and 80 were age- and sex-matched controls. Afterward, we assessed their demographics, year of admission, intensive care unit (ICU) admission, health status, length of hospitalization, comorbidities, diagnosis of autoimmune diseases, and type of immunosuppressant therapy. Results Most of the included patients (mean age: 45.4 years) were females (65.8%). The ratio of non-autoimmune diseases to autoimmune diseases was 2:1, the mean length of hospitalization was 8.83 ± 8.16 days, and the median was seven days (interquartile range (IQR) = 3 to 11 days). Among them, 17.5% were admitted to the ICU and 10% died. The prevalence of autoimmune diseases was higher in women than in men (77.5%). The most common diseases were systemic lupus erythematosus (40%), rheumatoid arthritis (20%), and ankylosing spondylitis (10%). Regarding COVID-19 outcomes, ICU admissions were higher among patients with autoimmune diseases than those with non-autoimmune diseases (35% vs. 8.8%) (p<0.05). This trend was also observed in mortality, with a higher percentage of deaths among patients with autoimmune diseases (27.5% vs. 1.7%) (p<0.05). In addition, there were no significant differences between genders in terms of ICU admission, health status outcomes, or length of hospitalization among patients with autoimmune diseases (p>0.05). Notably, 25 patients were administered immunosuppressants. Of these, 18 (72%) used steroids only, while seven (28%) used both biological and steroid therapy. However, no significant associations were observed between the type of treatment used and outcomes such as ICU admission, health status at discharge, and length of hospitalization (p>0.05).  Conclusion This study suggests that individuals with autoimmune diseases have more severe COVID-19 outcomes, as shown by ICU admission and mortality rates, than patients with non-autoimmune diseases. Furthermore, we observed that the use of immunosuppressant medications among patients with autoimmune diseases showed no noticeable effect on these outcomes.

Time trends in the burden of autoimmune diseases across the BRICS: an age-period-cohort analysis for the GBD 2019.

BACKGROUND: This study aims to evaluate the long-term trend of prevalence and DALY (disability-adjusted life-year) rate on the age, period and cohort (APC) of the BRICS (Brazil, Russia, India, China and South Africa) country for autoimmune diseases (rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis). METHODS: The data are sourced from the Global Burden of Disease Study 2019, and it uses the Joinpoint regression model to estimate the time trends of autoimmune diseases from 1990 to 2019. Additionally, it employs the Age-Period-Cohort (APC) model to estimate the age, period, and cohort effects from 1990 to 2019. RESULTS: For 1990 to 2019, the ASPR (age-standardised prevalence rate) of IBD increased significantly for China and South Africa, and decreased significantly for Brazil, India, Russian. The Russian ASPR of MS demonstrated a significantly decreasing trend (average annual percent change=-0.5%, 95% CI -0.6 to -0.5), with the most increased occurring in Brazil at 2009-2014. The cohort effect on DALY rates for Psoriasis displayed an ongoing decreasing trend from the 1929-1933 birth cohort to the 1999-2003 birth cohort. Specifically, the five countries relative risk values (RRs) of DALYs due to RA increased significantly by 7.98, 16.07, 5.98, 3.19, 9.13 times, from 20 to 24 age group to 65 to 69 age group. CONCLUSIONS: The population of the BRICS countries accounts for more than 40% of the global population. And we found that the age effect of various autoimmune diseases is heavily influenced by population ageing.

A global assessment of incidence trends of autoimmune diseases from 1990 to 2019 and predicted changes to 2040.

AIM: To analyze the global incidence trends for four autoimmune diseases (ADs) including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis from 1990 to 2019, and further predict their changes to 2040 at global, regional, and national levels. METHODS: The estimates and 95% uncertainty intervals (UIs) for case number and agestandardized incidence rate (ASIR) of RA, IBD, MS and psoriasis were derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Estimated annual percentage change (EAPC) was utilized to quantify the global incidence trends for RA, IBD, MS and psoriasis from 1990 to 2019. Furthermore, a log-linear age-period-cohort model was adopted to predict the new case number and incidence rates for these four ADs through 2040. RESULTS: From 1990 to 2019, the global ASIR rose significantly for RA (EAPC = 0.30%, 95% CI: 0.26 to 0.34) whereas declined significantly for IBD (EAPC = -0.60%, 95% CI: -0.72 to - 0.48), MS (EAPC = -0.19%, 95% CI: -0.24 to -0.13) and psoriasis (EAPC = -0.77%, 95% CI: -0.78 to -0.76). From 2020 to 2040, the global ASIR of RA, IBD, and psoriasis was predicted to decrease whereas the global ASIR of MS was predicted to increase, with continuous increasing case number of all these diseases. Furthermore, the predicted incidence trends of these four ADs varied significantly across 195 countries and territories, with a prominent higher burden in high-income North America and Western Europe. CONCLUSIONS: There are strong heterogeneities in the global incidence trends (1990-2019) and predicted changes (2020-2040) of ADs across the world, highlighting prominent challenges in the control of ADs, including both growing case number and distributive disparities of these diseases worldwide, which may be instructive for better public health policy establishment and healthcare resource allocation.

Virgin Coconut Oil in Paste Form as Treatment for Dyspareunia and Vaginal Dryness in Patients With and Without Rheumatic Autoimmune Diseases: An Efficacy and Safety Assessment Pilot Study.

Introduction The use of virgin coconut oil (VCO) as an over-the-counter (OTC) treatment for vaginal dryness and dyspareunia (VDD) in the general population has increased worldwide despite the absence of evidence-based studies supporting its efficacy. The principal objective of our pilot study was to scientifically validate the significant benefits and safety of using intra- and peri-vaginal application of VCO in paste form (VCOPF) for the treatment of VDD in patients with and without rheumatic autoimmune diseases (RAD). Additionally, multiple psychosocial, sexuality, and disease activity variables were also assessed.  Methods A survey study of patients with chronic VDD, with and without RAD, treated with a single proprietary brand of VCOPF via the 'CocoRelief' protocol continuously for at least six months in an outpatient rheumatology practice setting. We evaluated the comparison of group characteristics, treatment outcomes, and satisfaction questions by Fisher's exact test or chi-square test for independence for categorical variables and two-sample t-tests for continuous variables. Results Of the 53 respondents, 31 (58%) had an RAD and 22 (42%) did not. Rheumatoid arthritis and primary Sjogren's syndrome comprised 75% of the RAD group. The non-RAD cohort had both a higher baseline mean of intercourse pain (on a scale of 0-5) before VCOPF use (4.4 (SD 1.1) vs 3.9 (SD 1.0) (p = 0.094)) and a higher mean intercourse pain after VCOPF (2.0 (SD 1.3) vs 1.3 (SD 1.1) (p = 0.039)). VDD decreased by 55% in the non-RAD and 66% in the RAD population. Although not statistically significant (p = 0.195), VCOPF was at worst comparable to estrogen-containing therapies (ECT). No adverse events (AE) were documented. Conclusion A high percentage of women with VDD, with and without RAD, needlessly continue to experience quality-of-life-altering physical and psychosocial morbidity due to the underutilization and lack of awareness of VCO-containing therapy. The small sample size, non-blinded, non-randomized, pilot platform, and the use of a non-validated assessment tool represent the principal limiting factors. This study revealed that VCOPF, when used in paste form via the CocoRelief protocol, provided statistically significant long-term VDD-related efficacy not inferior to ECT without AE in patients with and without RAD. VCOPF is, therefore, likely to be a useful, cost-effective alternative in a substantial percentage of patients with and without RAD, particularly in women hesitant to utilize ECT due to cost and/or fear of adverse effects.

Assessment of Real-World Patient-Reported Outcomes in Patients Initiating Biologic Agents for the Treatment of Autoimmune Diseases: An Observational Study in Four Patient-Powered Research Networks.

Background: The most reliable and meaningful approach for inclusion of patient-reported outcomes (PROs) in the evaluation of real-world clinical effectiveness of biologics in the treatment of autoimmune diseases is u ncertain. This study aimed to assess and compare the proportions of patients who had abnormalities in PROs measuring important general health domains at the initiation of treatment with biologics, as well as the effects of baseline abnormalities on subsequent improvement. Methods: PROs were collected for patient participants with inflammatory arthritis, inflammatory bowel disease, and vasculitis using Patient-Reported Outcomes Measurement Information System instruments. Scores were reported as T-scores normalized to the general population in the United States. Baseline PROs scores were collected near the time of biologic initiation, and follow-up scores were collected 3 to 8 months later. In addition to summary statistics, the proportion of patients with PROs abnormalities (scores ≥5 units worse than the population norm) was determined. Baseline and follow-up scores were compared, and an improvement of ≥5 units was considered significant. Results: There was wide variation across autoimmune diseases in baseline PROs scores for all domains. For example, the proportion of participants with abnormal baseline pain interference scores ranged from 52% to 93%. When restricted to participants with baseline PROs abnormalities, the proportion of participants experiencing an improvement of ≥5 units was substantially higher. Conclusion: As expected, many patients experienced improvement in PROs following initiation of treatment with biologics for autoimmune diseases. Nevertheless, a substantial proportion of participants did not exhibit abnormalities in all PROs domains at baseline, and these participants appear less likely to experience improvement. For PROs to be reliably and meaningfully included in the evaluation of real-world medication effectiveness, more knowledge and careful consideration are needed to select the most appropriate patient populations and subgroups for inclusion and evaluation in studies measuring change in PROs.

Assessment of type I interferon response in routine practice in France in 2022.

An European Alliance of Associations for Rheumatology task force recently recommended specific points to consider for exploring type I interferon pathway in patients, highlighting the lack of analytical assays validated for clinical routine. We report here the French experience on a type I interferon pathway assay that has been set up and used routinely since 2018 in Lyon, France.

Temporal trends in the prevalence of autoimmune diseases from 1990 to 2019.

AIM: To describe current situation and analyze temporal trends of prevalence for four autoimmune diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis, at the global, continental, and national levels. METHODS: The estimates and 95% uncertainty interval (UI) for age-standardized prevalence rate (ASPR) of RA, IBD, MS and psoriasis were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. ASPR of RA, IBD, MS and psoriasis in 2019 was illustrated at the global, continental, and national levels. Joinpoint regression analysis was adopted to analyze the 1990-2019 temporal trends by calculating the annual percentage change (APC) and average APC (AAPC), as well as their 95% confidence interval (CI). RESULTS: In 2019, the global ASPR of RA, IBD, MS and psoriasis was 224.25 (95% UI: 204.94 to 245.99), 59.25 (95% UI: 52.78 to 66.47), 21.25 (95% UI: 18.52 to 23.91) and 503.62 (95% UI: 486.92 to 519.22), respectively, with ASPRs generally higher in Europe and America than in Africa and Asia. From 1990 to 2019, the global ASPR increased significantly for RA (AAPC = 0.27%, 95% CI: 0.24 to 0.30; P < 0.001) and decreased significantly for IBD (AAPC = -0.73%, 95% CI: -0.76 to -0.70; P < 0.001), MS (AAPC = -0.22%, 95% CI: -0.25 to -0.18; P < 0.001) and psoriasis (AAPC = -0.93%, 95% CI: -0.95 to -0.91; P < 0.001), with the most substantial changes occurring at different continents and periods. The trends of ASPR of these four autoimmune diseases varied significantly across 204 countries and territories. CONCLUSIONS: There is a strong heterogeneity in prevalence (2019), as well as their temporal trends (1990-2019) of autoimmune diseases across the world, highlighting the strong distributive inequities of autoimmune diseases worldwide, which may be instructive for better understanding the epidemiology of these diseases, appropriately allocating the medical resources, as well as making relevant health policies.

Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.

Survival in elderly patients with breast cancer with and without autoimmune disease.

BACKGROUND: Patients with certain autoimmune conditions are at a reduced risk of developing breast cancer compared to the general population. Despite this, little is known about outcomes in patients with breast cancer who have a concurrent autoimmune diagnosis. METHODS: This study compared differences in outcomes between women with breast cancer who had or did not have an autoimmune diagnosis. The SEER-Medicare databases (2007-2014) were used to identify patients with breast cancer and diagnosis codes were used to identify those with an autoimmune disorder. RESULTS: The studied autoimmune diseases had a prevalence of 27% among the 137,324 patients with breast cancer. Autoimmune disease was associated with significantly longer overall survival (OS) and significantly lower cancer-specific mortality (CSM) among stage IV breast cancer patients (p < 0.0001). After controlling for the effects of age, race, chronic kideny disease, chemotherapy, and radiation therapy autoimmune disease was still predictive of improved OS (HR: 1.45, 95% CI: 1.35-1.55, p < 0.0001) and CSM (HR: 1.40, 95% CI: 1.29-1.5, p < 0.0001). By contrast, in patients with stage I-III breast cancer, the presence of an autoimmune diagnosis was associated with a lower OS (p < 0.0001, p < 0.0001, and p = 0.026, respectively), compared to patients without autoimmune disease. CONCLUSIONS: We found a higher prevalence of rheumatoid arthritis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus in patients with breast cancer compared to age matched cohorts in the general population. The presence of an autoimmune diagnosis was associated with a lower OS in stages I-III breast cancer and improved OS and CSM in patients with stage IV disease. These results suggest that anti-tumor immunity plays an important role in late stage breast cancer and could potentially be exploited to improve the effectiveness of immunotherapy.

Global burden and cross-country inequalities in autoimmune diseases from 1990 to 2019.

AIM: To describe burden, and to explore cross-country inequalities across sociodemographic development levels for four autoimmune diseases (ADs) including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis (PS). METHODS: The estimates and their 95% uncertainty interval (UI) for disability-adjusted life-years (DALYs) of RA, IBD, MS and PS were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age-standardized DALYs rate (ASDR) across 204 countries, as well as age and sex distribution of global DALYs rate of these four ADs were illustrated. Slope index of inequality and concentration index, which are two standard metrics of absolute and relative gradient inequality recommended by World Health Organization (WHO), were utilized to quantify the distributive inequalities in the burden of ADs. RESULTS: In 2019, the ASDR of RA, IBD, MS and PS varied remarkably across 204 countries, with different age and sex distribution of global DALYs rate. The slope index of inequality changed from 26.7 (95% CI: 20.7 to 32.8) in 1990 to 40.3 (95% CI: 31.9 to 48.7) in 2019 for RA, from 17.1 (95% CI: 12.4 to 21.7) in 1990 to 25.2 (95% CI: 20.1 to 30.2) in 2019 for IBD, from 19.3 (95% CI: 15.2 to 23.4) in 1990 to 28.9 (95% CI: 24.2 to 33.5) in 2019 for MS, from 42.3 (95% CI: 33.1 to 51.6) in 1990 to 40.2 (95% CI: 32.5 to 48.0) in 2019 for PS. Moreover, the concentration index showed 20.4 (95% CI: 18.9 to 22.0) in 1990 and 18.2 (95% CI: 16.7 to 19.6) in 2019 for RA, 25.0 (95% CI: 23.0 to 27.1) in 1990 and 33.5 (95% CI: 31.6 to 35.5) in 2019 for IBD, 46.7 (95% CI: 44.0 to 49.3) in 1990 and 41.8 (95% CI: 39.6 to 44.1) in 2019 for MS, 31.7 (95% CI: 29.0 to 34.4) in 1990 and 32.6 (95% CI: 29.9 to 35.2) in 2019 for PS. CONCLUSIONS: There is a strong heterogeneity in ASDR across all countries, as well as in age and sex distribution of global DALYs rate for four ADs including RA, IBD, MS and PS. Countries with higher sociodemographic development levels shouldered disproportionately higher burden of ADs, and the magnitude of this sociodemographic development level-related inequalities exacerbated over time.

A Pharmacoeconomic Outlook of the Biological Drugs Marketed in India: A Cost Variance Analysis.

Introduction Biologic drugs are used to treat various illnesses like autoimmune diseases, cancers, hormonal irregularities, anemia, etc., and to prevent various diseases as vaccines. Though various biologic drugs are already available, they are still not within reach of the common man due to financial constraints. Through many search engines, studies evaluating the cost variation of different brands of biologics were investigated; however, only a few studies that address this problem were found. Hence, this study was planned with the objective of addressing the cost variation of various brands of biologic medicines available in the Indian market. Methods The website for the Current Index of Medical Specialties (CIMS) for India's location was used to obtain the prices of the different brands of biologic medicines in Indian National Rupee (INR) currency, which different manufacturers market with identical forms in strength and dosage. The percentage cost variation and cost ratio were calculated with the help of the minimum and maximum prices of various brands of biologic drugs. Results The prices of biologics belonging to six different classes that are available in 23 formulations were analyzed. The highest cost variability was shown by pegfilgrastim 6 mg at 1,022.92%, and the minimum-cost variation was shown by darbepoetin alfa 200 mcg at 13.07%. Conclusion Our research found a vast variance in the costs of various brands of biologic medicines in India. The government should address this cost variation problem by developing various policies, such as breaking the monopoly of manufacturers, providing tax incentives to nonprofit generic medicine manufacturers, and incorporating more biologic drugs under the protection of the Drugs Prices Control Order (DPCO).

Ultrasound quantitative assessment of ventral finger microvasculopathy in systemic sclerosis with Raynaud's phenomena: a comparative study.

OBJECTIVE: To assess the finger vascularity of systemic sclerosis patients with Raynaud's phenomenon (RP-SSc) using various ultrasound techniques. METHODS: All fingers (except thumbs) of 18 RP-SSc patients and 18 controls were imaged at room temperature using four ultrasound vascular imaging techniques. The percent vascular area was quantified by counting blood flow pixels in a 25 mm2 square centred at the nail fold for the dorsal side and in 25 mm2 and 100 mm2 square from the fingertip for the ventral side. The mean vascular intensity was calculated from the corresponding areas for dorsal and ventral sides. RESULTS: The percent vascular areas and mean vascular intensities in RP-SSc were significantly lower than those in controls for both dorsal and ventral sides (p<0.01). The mean vascular intensities showed slightly higher area under the curve (AUC) than the percent vascular areas (0.53-0.91 vs 0.53-0.90) regardless of imaging technique and assessment side. For each imaging technique, the ventral side vascularity showed a higher AUC (0.74-0.91) compared with the dorsal side (0.53-0.81). Moreover, ventral side abnormalities were associated with a history of digital ulcers. CONCLUSIONS: Ultrasound demonstrated potential to quantify finger vascularity of RP-SSc. The ventral side of the fingers showed a higher accuracy in detecting RP-SSc than the dorsal side.

Relationship between subjective report and objective assessment of neurocognitive functioning in persons with multiple sclerosis.

OBJECTIVE: Persons with multiple sclerosis (PwMS) are at increased risk for cognitive dysfunction. Considering the impact and potential ramifications of cognitive dysfunction, it is important that cognition is routinely assessed in PwMS. Thus, it is also important to identify a screener that is accurate and sensitive to MS-related cognitive difficulties, which can inform decisions for more resource-intensive neuropsychological testing. However, research focused on available self-report screeners has been mixed, such as with the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ). This study aims to clarify the relationship between subjective and objective assessment of cognitive functioning in MS by examining domain-specific performance and intraindividual variability (IIV). METHODS: 87 PwMS (F = 65, M = 22) completed a comprehensive neuropsychological battery which included self- and informant-report measures of neurocognitive functioning. Scores were examined in relation to mean performance on five domains of cognitive functioning and two measures of IIV. RESULTS: The MSNQ-Self was inversely associated with executive function, verbal memory, and visual memory; it was not associated with IIV. The MSNQ-Informant was inversely associated with executive function and verbal memory, and positively associated with one measure of IIV. The MSNQ-Self showed a correlation of moderate effect size with depression (r = .39) while the MSNQ-Informant did not. CONCLUSIONS: Results suggest that the MSNQ-Self and MSNQ-Informant show similar utility. Our findings also suggest that domains of executive function and memory may be most salient, thus more reflected in subjective reports of cognitive functioning. Future work should further examine the impact of mood disturbance with cognitive performance and IIV.

Expanded assessment of xenobiotic associations with antinuclear antibodies in the United States, 1988-2012.

BACKGROUND: The prevalence of autoimmunity in the U.S. has increased recently for undetermined reasons. Little is known about associations between autoimmunity and environmental causes. OBJECTIVES: In a large representative sample of the U.S. population, we expanded our prior exploratory study of how exposures to selected xenobiotics and dioxin-like (DL) mixtures relate to antinuclear antibodies (ANA), the most common biomarker of autoimmunity. METHODS: We analyzed cross-sectional data on 12,058 participants aged ≥ 12 years from three time periods of the National Health and Nutrition Examination Survey between 1988 and 2012, of whom 14% were ANA-positive. We used lognormal regression models and censored-data methods to estimate ANA associations with xenobiotic concentrations overall and in sex, age, and race/ethnicity subgroups. Our analyses adjusted for potential confounders and appropriately handled concentrations below detection limits. RESULTS: Observed ANA associations were positive for most DL compounds and nonDL polychlorinated biphenyls (PCBs), negative for most phthalates, and mixed for other xenobiotic classes. After correcting for multiple comparisons, some associations remained statistically significant. In subgroup analyses, the most significant finding was a positive ANA association with N-acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine (MHB2) in males, followed by positive associations with 2,2',3,5'-tetrachlorobiphenyl (PCB 44), 2,2',4,5'-tetrachlorobiphenyl (PCB 49), and 2,2',3,4',5',6-hexachlorobiphenyl (PCB 149) in 12-19 year-olds, and with 3,4,4',5-tetrachlorobiphenyl (PCB 81), 2,2',3,3',4,4',5,5',6-nonachlorobiphenyl (PCB 206), and N-acetyl-S-(phenyl)-L-cysteine (PMA) in Mexican Americans. Negative associations were found with mono-benzyl phthalate (MBzP) in 20-49 year-olds and mono-n-butyl phthalate (MnBP) in 12-19 year-olds. In overall analyses, combining stratum-specific results across race/ethnicity strata revealed a positive ANA association with PCB 81 and a negative ANA association with N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA). DISCUSSION: This study identified potential associations between ANA and various xenobiotics. Further investigation to confirm these observations and elucidate effects of certain xenobiotics on immune regulation could have important mechanistic, preventive, and treatment implications for a variety of immune-mediated disorders.