Validation of Hindi version of the Pittsburg Sleep Quality Index.

BACKGROUND: Sleep quality is poorly understood in the Indian population. Lack of a suitable tool to assess sleep quality in Hindi language is the main reason behind this. Pittsburg sleep quality index (PSQI) is widely used in different population groups to assess subjective sleep quality over last one month. OBJECTIVES: To assess the reliability and validity of the Hindi translated version of Pittsburgh Sleep Quality Index (PSQI-H). gt;Methods: The PSQI-H was developed from PSQI according to following steps: (a) translation, (b) back-translation, (c) comparison between translation and back-translation performed by a group of experts, and (d) pre-pilot test in intended population. The PSQI-H was applied to 105 bilingual individuals knowing Hindi and English. The internal consistency of PSQI-H was assessed by Cronbach's alpha. For test-retest reliability assessment intraclass correlation coefficient (ICC) was measured between PSQI-H at baseline and PSQI after 4 weeks. The Pearson's coefficient was used to assess the correlation between the score of the questions and the PSQI-H scores. RESULTS: The seven components of PSQI-H shows acceptable level of internal consistency with Cronbach's alpha of 0.776. There is good test-retest reliability between PSQI-H and PSQI as measured by ICC of 0.979. The score of individual items and global scores of PSQI-H were highly correlated with each other (p< 0.001). The mean of the seven individual components score and global scores of PSQI-H at baseline and original PSQI after 4 weeks did not differ significantly. CONCLUSION: This study results demonstrate that the PSQI-H is a valid and reliable instrument for the assessment of sleep quality. PSQI-H can be used for the assessment of sleep quality in the predominantly Hindi speaking population.

Screening for Hydroxychloroquine Retinal Toxicity in Indian Patients.

OBJECTIVE: Several studies have reported hydroxychloroquine (HCQ) retinal toxicity in East Asian patients. However, at present, there are limited data from Indian patients. The aim of this study was to investigate the prevalence and pattern of HCQ retinal toxicity in Indian population and to see if screening protocol for retinal toxicity in Indian patients should be any different to others. METHODS: This was a cross-sectional study involving adult patients with autoimmune rheumatic diseases who had received HCQ for at least 5 years or a cumulative dose of at least 500 g. Retinal toxicity was evaluated using fundus examination, visual fields 10-2 and 30-2 protocol, and spectral domain optical coherence tomography. RESULTS: Of 110 patients screened, retinal toxicity was found in 7 patients (6.36%). A parafoveal pattern was found in 4 patients, whereas a mixed parafoveal and perifoveal pattern was found in 3 patients. None of the patients had isolated perifoveal pattern. Except for the one patient, all the patients with retinal toxicity had more than 10 years (mean, 13 ± 4.89 years; range, 5-20 years) of HCQ usage with a mean cumulative dose of 1573.7 ± 771.5 g. The mean daily dose was 5 ± 1.6 mg/kg per day. CONCLUSIONS: Hydroxychloroquine retinal toxicity is more common than previously recognized in patients who have used the drug for more than 5 years. The toxicity manifests as a parafoveal or a mixed parafoveal and perifoveal pattern in Indian patients.

Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial.

OBJECTIVE: To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID). METHODS: Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5. RESULTS: Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study. CONCLUSION: In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment. TRIAL REGISTRATION: Clinical Drug Trial Registry-India, www.ctri.nic.in, CTRI/2008/091/000063.

Fibromyalgia and mental health in rheumatoid arthritis: a cross-sectional prevalence study from the COVID-19 pandemic.

OBJECTIVES: This study evaluated the prevalence of fibromyalgia (FM), anxiety and depression in patients with rheumatoid arthritis (RA) and their effects on the clinical parameters of RA during the COVID-19 pandemic. DESIGN: Cross-sectional, outpatient clinic, observational, non-interventional. SETTING: Single-centre, tertiary care, multispecialty, service and research hospital, north-central India. PARTICIPANTS: Adult patients with RA, controls. RESULTS: This cross-sectional study included 200 patients with RA diagnosed with the American College of Rheumatology/European League Against Rheumatism 2010 (ACR) criteria and 200 controls. FM was diagnosed using the revised 2016 ACR FM Criteria. Disease activity, quality of life and functional disability in patients with RA were assessed using multiple Disease Activity Scores. The presence of depression and anxiety was determined using the Hospital Anxiety and Depression Scale. FM was present in 31% of patients with RA compared with 4% of controls in our study. Patients with RA with FM were older, predominantly females with longer disease duration, and more likely to be on steroids. Patients with RA with FM had a higher disease activity, and none of our RA with FM patients were in remission. The multivariable analysis found FM to be an independent predictor of the Simplified Disease Activity Index for RA. Patients with RA with FM had worse functional ability and poorer quality of life. The prevalence of anxiety and depression was 12.5% and 30%, significantly higher in RA with FM patients. CONCLUSION: During the COVID-19 pandemic, around one-third of our study patients had FM and depression, significantly higher than pre-COVID-19 times. Thus, mental health assessment should be incorporated into the routine management of patients with RA.

Management of Connective Tissue Disease-related Interstitial Lung Disease.

Purpose of Review: This review aims to collate current evidence on the screening, diagnosis, and treatment of various connective tissue disease (CTD)-associated interstitial lung diseases (CTD-ILD) and present a contemporary framework for the management of such patients. It also seeks to summarize treatment outcomes including efficacy and safety of immunosuppressants, anti-fibrotics, and stem cell transplantation in CTD-ILD. Recent Findings: Screening for ILD has been augmented by the use of artificial intelligence, ultra-low dose computerized tomography (CT) of the chest, and the use of chest ultrasound. Serum biomarkers have not found their way into clinical practice as yet. Identifying patients who need treatment and choosing the appropriate therapy is important to minimize the risk of therapy-related toxicity. The first-line drugs for systemic sclerosis (SSc) ILD include mycophenolate and cyclophosphamide. Nintedanib, an anti-fibrotic tyrosine kinase inhibitor, is approved for use in SSc-ILD. The US Food and Drug Administration (FDA) has recently approved tocilizumab subcutaneous injection for slowing the rate of decline in pulmonary function in adult patients with SSc-ILD. Autologous stem cell transplantation may have a role in select cases of SSc-ILD. Summary: CTD-ILD is a challenging area with diverse entities and variable outcomes. High-resolution CT is the investigative modality of choice. Treatment decisions need to be individualized and are based on patient symptoms, lung function, radiologic abnormalities, and the risk of disease progression. Precision medicine may play an important role in determining the optimal therapy for an individual patient in the future.

A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project.

The multidisciplinary "New Millennium Indian Technology Leadership Initiative" Arthritis Project was undertaken to validate Ayurvedic medicines. Herbal formulations in popular use were selected by expert consensus and standardized using modern tools. Our clinical strategy evolved from simple exploratory evaluations to better powered statistically designed drug trials. The results of the first drug trial are presented here. Five oral formulations (coded A, B, C, D and E), with a common base of Zingiber officinale and Tinospora cordifolia with a maximum of four plant extracts, were evaluated; with placebo and glucosamine as controls. 245 patients suffering from symptomatic OA knees were randomized into seven arms (35 patients per arm) of a double blind, parallel efficacy, multicentric trial of sixteen weeks duration. The groups matched well at baseline. There were no differences for patient withdrawals (17.5%) or adverse events (AE) of mild nature. Intention-to-treat efficacy analysis, demonstrated no significant differences (P < .05) for pain (weight bearing) and WOMAC questionnaire (knee function); placebo response was high. Based on better pain relief, significant (P < .05) least analgesic consumption and improved knee status, "C" formulation was selected for further development. Controlled exploratory drug trials with multiple treatment arms may be used to economically evaluate several candidate standardized formulations.

Updated APLAR consensus statements on care for patients with rheumatic diseases during the COVID-19 pandemic.

AIM: To update previous guidance of the Asia Pacific League of Associations for Rheumatology (APLAR) on the management of patients with rheumatic and musculoskeletal diseases (RMD) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Research questions were formulated focusing on diagnosis and treatment of adult patients with RMD within the context of the pandemic, including the management of RMD in patients who developed COVID-19. MEDLINE was searched for eligible studies to address the questions, and the APLAR COVID-19 task force convened 2 meetings through video conferencing to discuss its findings and integrate best available evidence with expert opinion. Consensus statements were finalized using the modified Delphi process. RESULTS: Agreement was obtained around key aspects of screening for or diagnosis of COVID-19; management of patients with RMD without confirmed COVID-19; and management of patients with RMD with confirmed COVID-19. The task force achieved consensus on 25 statements covering the potential risk of acquiring COVID-19 in RMD patients, advice on RMD medication adjustment and continuation, the roles of telemedicine and vaccination, and the impact of the pandemic on quality of life and on treatment adherence. CONCLUSIONS: Available evidence primarily from descriptive research supported new recommendations for aspects of RMD care not covered in the previous document, particularly with regard to risk factors for complicated COVID-19 in RMD patients, modifications to RMD treatment regimens in the context of the pandemic, and COVID-19 vaccination in patients with RMD.

Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India.

OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. METHODS: A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. RESULTS: In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one-half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. CONCLUSION: This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

Increased expression of cell adhesion molecules in inflammatory myopathies: diagnostic utility and pathogenetic insights.

CONTEXT: Idiopathic inflammatory myopathies (IMs) have been postulated to be of autoimmune origin on the basis of expression of markers like MHC-1 and other mediators involved in autoimmunity such as cell adhesion molecules. AIMS: The present study aims to analyze the expression of cell adhesion molecules ICAM-1 and VCAM-1 and their respective ligands LFA-1 and VLA-4 in IMs, and to assess whether these markers, besides MHC-class 1 antigen and membrane attack complex (MAC), could be of any help in the diagnosis of these diseases. MATERIAL AND METHODS: Retrospective analysis of 119 muscle biopsies consisting of 55 IMs (21 dermatomyositis, 31 polymyositis and 3 inclusion body myositis) and 64 controls received in our department from January 2004 to December 2005 was carried out immunohistochemically using monoclonal antibodies. STATISTICAL ANALYSIS: Chi square test and test for validity were used for analysis of differences in expression. RESULTS: Expression of ICAM and VCAM was significantly upregulated on blood vessels and muscle fibres in IMs as compared to controls, in which expression was weak or absent. LFA and VLA-4 were expressed in inflammatory cells in all inflammatory diseases in almost equal numbers. CONCLUSIONS: IMs comprise 6% of all muscle diseases and IBM is not a common IM in India as reported in the Western literature. Our findings support the hypothesis of autoimmune origin of IMs. The difference between expression of these molecules in IMs and controls also has diagnostic implications and these markers should be included along with MHC-1 antigen and membrane attack complex (MAC) in the existing diagnostic armamentarium.

Bone mineral density in Indian women with rheumatoid arthritis.

Osteoporosis (OP) is being increasingly recognized in inflammatory rheumatic diseases like rheumatoid arthritis (RA). Ethnicity influences bone mineral density (BMD) and fracture risk. Due to paucity of data on this aspect of RA from Asian countries including India, we prospectively studied 84 premenopausal women with RA of at least 2 years duration and 247 healthy, age (within 5 years) and sex-matched controls. A significant difference in BMD between patients and controls was observed only at the femoral neck. As many as 22% patients with RA exhibited osteoporosis at least one site in contrast to 9% controls. Nearly 40% of patients exhibited osteopenia at all the three sites. Modified Sharp score, disease duration and DMARD naive period were found to correlate with low BMD. However, on multivariate analysis, only modified Sharp score was shown to be significantly associated with low BMD. Our study draws attention to the poor bone health in Asian Indian women with RA.

Tuberculous mycotic aneurysm of aortic root: an unusual cause of cardiac tamponade.

We describe a young male who presented to the emergency room with sudden onset dyspnea, and was found to have aortic root aneurysm with aortic regurgitation and cardiac tamponade. He underwent a Bentall procedure, and excised aortic root tissue showed epithelioid cell granulomas with panaortitis. He was started on anti-tubercular therapy, with which he improved. Although tubercular aortitis is fairly common, tuberculous mycotic aneurysm of the aorta is rare, with involvement of the aortic root being exceedingly uncommon. We report only the fifth case in English literature of tuberculous mycotic aneurysm of the aortic root.

Anti-drug antibodies and low serum trough infliximab levels correlate with disease activity measures in spondyloarthritis patients on an as-needed infliximab treatment.

AIM: In India, many centers use infliximab at lower doses of 3-5 mg/kg without the loading dose for spondyloarthritis (SpA) patients. It is then continued on an as-required basis, rather than a fixed schedule. Our study was undertaken to see if the trough drug levels and anti-drug antibodies in patients with SpA treated with as-needed infliximab dosing correlated with the disease activity measures. METHODS: Thirty-five adult SpA patients in the age group 18-70 years were recruited. They had received three or more infusions of infliximab at 3-5 mg/kg over the past 6 to 12 months. Patient's serum tumor necrosis factor-α, trough infliximab levels and anti-drug antibodies were measured by enzyme-linked immunosorbent assay technique. The disease activity was quantified by Ankylosing Spondylitis Disease Activity Score - erythrocyte sedimentation rate/ C-reactive protein (ASDAS-ESR/CRP) scores. Correlation between quantitative variables was analyzed by the Spearman's correlation assay. The difference in mean trough infliximab and ASDAS between the drug antibody positive and negative patients was assessed using the Mann-Whitney U test. RESULTS: There was a significant negative correlation between the trough infliximab levels and the ASDAS-ESR (rs = -0.57, P < 0.01) and ASDAS-CRP scores (rs = -0.53, P < 0.01). Anti-drug antibodies were positive in 68.7% of the patients and in comparison to the antibody negative patients, had significantly higher ASDAS-ESR and ASDAS-CRP scores. CONCLUSIONS: Spondyloarthritis patients on low-dose, as-needed infliximab therapy, have both the trough infliximab and anti-drug antibodies correlate significantly with the measures of disease activity. We hypothesize that trough infliximab levels and anti-drug antibodies may be used to predict a suboptimal response due to secondary resistance in SpA patients.

Osteoporosis in developing countries.

Osteoporosis poses a huge challenge in developing countries due to demographic transition and aging of the population coupled with limited availability of resources. The exact disease burden is difficult to quantify because of the paucity of data. Ethnicity affects bone density as well as fracture risk. Population-specific normative data for bone density are lacking in large parts of the world. Vitamin D deficiency is common even in sunny countries. The WHO has developed an algorithm for estimation of 10-year fracture risk which may be used even in the absence of bone mineral density.