Adult-onset Still's disease in focus: Clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology, characterized by a clinical triad of high spiking fever, arthralgia (± arthritis), and evanescent skin rash. Management of AOSD poses several challenges, including difficulty in diagnosis and limited therapeutic options. In this review, we examined whether AOSD and systemic juvenile idiopathic arthritis (SJIA) represent a continuum of the same disease. We also explored the latest available evidence related to prevalence, clinical and laboratory manifestations, complications, diagnostic challenges, novel biomarkers, and treatment options in the era of biologics and identified the unmet needs of patients with AOSD. METHODS: A comprehensive systematic literature search was performed in the Embase and MEDLINE (via PubMed) literature databases. The search was limited to human studies published in English from inception up to March 2020. Additionally, abstracts presented at various conferences were screened and hand searches were performed. Publications were processed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 123 publications were identified through the literature search, majority of which were case series and retrospective observational studies. AOSD and SJIA are widely considered part of the same disease spectrum owing to similarities in their clinical and biological features. The clinical presentation of AOSD is highly variable, accompanied by a broad spectrum of disease manifestations. Recent evidence suggests that the AOSD disease course can be classified into two distinct categories: "systemic" and "articular." Furthermore, AOSD patients may experience various life-threatening complications, such as macrophage activation syndrome - reported in as high as 23% of AOSD patients and considered to be the most severe complication characterized by a high mortality rate. The ambiguity in presentation and lack of serologic markers make the diagnosis of AOSD difficult, often leading to a delay in diagnosis. Given these limitations, the Yamaguchi and Fautrel criteria are the most widely used diagnostic tools in clinical practice. It has been observed that a clinical diagnosis of AOSD is generally reached by exclusion while investigating a patient with fever of unknown origin. Recent advances have demonstrated a major role of proinflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-18, and IL-37, and other biomarkers in the pathogenesis and management of AOSD. Owing to the rarity of the disease, there are very limited clinical trials evaluating management strategies for AOSD. The current AOSD treatment paradigm includes non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids initially, conventional synthetic disease-modifying anti-rheumatic drugs in steroid-refractory patients, and biologics in those resistant to conventional treatment. Only a few country-specific guidelines for the management of AOSD have been published, and a treat-to-target approach, as previously recommended for SJIA, is still lacking. Canakinumab is the only FDA-approved biologic for the treatment of AOSD. CONCLUSION: Emerging evidence supports that AOSD and SJIA represent a continuum of the same disease entity. Despite advancements in the understanding of AOSD, it continues to pose a substantial burden on patients and the healthcare systems, and substantial unmet needs exist across key domains such as the pathway to diagnosis, use of biomarkers in clinical practice, and standardized treatment strategies. Further research and collaboration is crucial for optimizing the diagnosis and management of AOSD patients.

Clear or almost clear skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic review and meta-analysis.

Psoriasis Area and Severity Index (PASI) 75 response is currently considered the gold standard for assessing treatment efficacy in moderate-to-severe psoriatic patients. PASI 90 response denotes better clinical improvement compared to PASI 75. Very few studies have assessed if a greater PASI clinical response is associated with greater improvements in Dermatology Life Quality Index (DLQI). A systematic review and meta-analysis was performed to assess the association between PASI response and DLQI. The study was conducted to assess whether greater improvement in PASI scores from PASI 75-89 to PASI 90 is associated with greater Quality of life (QoL) improvements, specifically DLQI scores. Systematic searches were conducted in MEDLINE, EMBASE and Cochrane Library to identify studies evaluating biologic interventions in adult moderate-to-severe psoriasis patients reporting PASI response and their corresponding DLQI change from baseline score. The quality of evidence was assessed through Jadad score for randomized controlled trials and Downs and Black's checklist for observational studies. Meta-analysis estimated change from baseline in DLQI for PASI 75-89 responders to be 78% (95% credible intervals [CrI]: 75-82%) and for PASI 90 responders to be 90% (95% CrI: 88-93%). This implies 12% greater improvement in DLQI score for PASI 90 responders compared with PASI 75-89 responders. In addition, the meta-analysis also showed a statistically significant difference in DLQI score of 0/1 between PASI 75-89 and PASI 90 responders (45% [95% Crl]; 41.0-50.0% and 73% [95% Crl]; 70.0-76.0%), respectively, Bayesian P < 0.0001). In conclusion, substantial improvement in clinical efficacy is associated with improved QoL in patients with moderate-to-severe psoriasis suggesting that PASI 90 responders (clear or almost clear skin) could achieve a superior QoL compared to PASI 75-89 responders.

Tobacco use among medical students in Orissa.

BACKGROUND: Tobacco use is the most important cause of preventable morbidity, disability and premature mortality. There is a lack of adequate and reliable data on tobacco use among medical students and their perceived role as future doctors in tobacco control. We aimed to find out factors associated with tobacco use among medical students and their perceived role in tobacco control as future doctors. METHODS: A cross-sectional study was conducted among 1189 undergraduate medical students (68.5% men, median age: 21 years, age range: 17-27 years) in all 3 medical colleges of Orissa. Information on tobacco use, associated factors and their perceived role in tobacco control as future doctors was collected using a pre-tested anonymous questionnaire. Bivariate and multivariate analyses were done among the men respondents to find out associations between current tobacco use and predictor variables. RESULTS: The prevalence of current tobacco use was 8.7% (95% CI: 7.1-10.3); men: 12.4%, women: 0.8%. Among 286 ever users, 34% started using tobacco after joining medical college. Students with a higher personal monthly expenditure and with a family history of tobacco use were more likely to be current users. Third-year students were 3.2-times more likely to be currenttobacco users (OR: 3.21; CI: 1.43-7.19) compared to first-year students. Students who reported own tobacco use as not very harmful were 4.7-times more likely to be current users compared with those who reported otherwise (OR: 4.7; CI: 2.64-8.37). Compared to non-users, current tobacco users were less likely (p = 0.026) to assess tobacco use in their patients and were less likely (p = 0.012) to advise patients against tobacco use. CONCLUSION: Steps should be initiated early in medical colleges to prevent tobacco use, particularly among men students and those with a family history of tobacco use.

A mixed approach to artifacts minimization in a continuous-rotate X-ray based tomographic imaging system using linear detector array.

Adaptation of a general-purpose digital radiographic scintillator-based linear detector array (LDA) in a continuous-rotate third generation X-ray industrial tomographic imaging system and the resulting artifacts are discussed. Sources of error in the projection data are identified and a mixed approach, involving neighborhood averaging and row-wise application of a low-pass filter for the minimization of artifacts in the reconstructed images using weighted convolution back projection algorithm is illustrated. It is observed that the recently launched LDA can easily be adapted for industrial tomographic imaging of low-density specimen in a cost effective way by incorporating the suggested artifact removal technique in the given configuration.