Beyond Pathology- Exploring Salutogenesis as a Novel Approach to Eye Inflammatory Disease Prevention and Management: A Perspective.

The aim of this perspective is to promote the theory of salutogenesis as a novel approach to addressing ophthalmologic inflammatory conditions, illustrating several concepts in which it is based upon and how they can be applied to medical practice. This theory can better contextualize why patients with similar demographics and exposures are not uniform in their clinical presentations. Stressors in daily life can contribute to a state of ill-health and there are various factors that help alleviate their negative impact. These alleviating factors are significantly impaired in people with poor vision, one of the most common presentations of ophthalmologic conditions. Salutogenic principles can guide the treatment of eye conditions to be more respectful of patient autonomy amidst shifting expectations of the doctor-patient relationship. Being able to take ownership of their health and feeling that their cultural beliefs were considered improves compliance and subsequently gives more optimal outcomes. Population-level policy interventions could also utilize salutogenic principles to identify previously overlooked domains that can be addressed. We identified several papers about salutogenesis in an ophthalmological context and acknowledged the relatively few studies on this topic at present and offer directions in which we can explore further in subsequent studies.

Artificial intelligence-based preventive, personalized and precision medicine for cardiovascular disease/stroke risk assessment in rheumatoid arthritis patients: a narrative review.

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP3) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™-aiP3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized.

Performance assessment and multiobjective optimization of a biomass waste-fired gasification combined cycle for emission reduction.

The use of renewable fuels leads to reduction in the use of fossil fuels and environmental pollutants. In this study, the design and analysis of a CCPP based on the use of syngas produced from biomass is discussed. The studied system includes a gasifier system to produce syngas, an external combustion gas turbine and a steam cycle to recover waste heat from combustion gases. Design variables include syngas temperature, syngas moisture content, CPR, TIT, HRSG operating pressure, and PPTD. The effect of design variables on performance components such as power generation, exergy efficiency and total cost rate of the system is investigated. Also, through multi-objective optimization, the optimal design of the system is done. Finally, it is observed that at the final decisioned optimal point, the produced power is 13.4 MW, the exergy efficiency is 17.2%, and the TCR is 118.8 $/h.

Economics of Artificial Intelligence in Healthcare: Diagnosis vs. Treatment.

Motivation: The price of medical treatment continues to rise due to (i) an increasing population; (ii) an aging human growth; (iii) disease prevalence; (iv) a rise in the frequency of patients that utilize health care services; and (v) increase in the price. Objective: Artificial Intelligence (AI) is already well-known for its superiority in various healthcare applications, including the segmentation of lesions in images, speech recognition, smartphone personal assistants, navigation, ride-sharing apps, and many more. Our study is based on two hypotheses: (i) AI offers more economic solutions compared to conventional methods; (ii) AI treatment offers stronger economics compared to AI diagnosis. This novel study aims to evaluate AI technology in the context of healthcare costs, namely in the areas of diagnosis and treatment, and then compare it to the traditional or non-AI-based approaches. Methodology: PRISMA was used to select the best 200 studies for AI in healthcare with a primary focus on cost reduction, especially towards diagnosis and treatment. We defined the diagnosis and treatment architectures, investigated their characteristics, and categorized the roles that AI plays in the diagnostic and therapeutic paradigms. We experimented with various combinations of different assumptions by integrating AI and then comparing it against conventional costs. Lastly, we dwell on three powerful future concepts of AI, namely, pruning, bias, explainability, and regulatory approvals of AI systems. Conclusions: The model shows tremendous cost savings using AI tools in diagnosis and treatment. The economics of AI can be improved by incorporating pruning, reduction in AI bias, explainability, and regulatory approvals.

Outcome Measures and Biomarkers for Disease Assessment in Takayasu Arteritis.

Takayasu arteritis (TAK) is a less common large vessel vasculitis where histopathology of involved arteries is difficult to access except during open surgical procedures. Assessment of disease activity in TAK, therefore, relies on surrogate measures. Clinical disease activity measures such as the National Institutes of Health (NIH) score, the Disease Extent Index in TAK (DEI.TAK) and the Indian TAK Clinical Activity Score (ITAS2010) inconsistently associate with acute phase reactants (APRs). Computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), or color Doppler Ultrasound (CDUS) enables anatomical characterization of stenosis, dilatation, and vessel wall characteristics. Vascular wall uptake of 18-fluorodeoxyglucose or other ligands using positron emission tomography computerized tomography (PET-CT) helps assess metabolic activity, which reflects disease activity well in a subset of TAK with normal APRs. Angiographic scoring systems to quantitate the extent of vascular involvement in TAK have been developed recently. Erythrocyte sedimentation rate and C-reactive protein have a moderate performance in distinguishing active TAK. Numerous novel biomarkers are under evaluation in TAK. Limited literature suggests a better assessment of active disease by combining APRs, PET-CT, and circulating biomarkers. Validated damage indices and patient-reported outcome measures specific to TAK are lacking. Few biomarkers have been evaluated to reflect vascular damage in TAK and constitute important research agenda.

Cost-effectiveness analysis of 'test and treat' policy for antiretroviral therapy among heterosexual HIV population in India.

Background & objectives: The World Health Organisation recommended immediate initiation of antiretroviral therapy (ART) in all adult human immunodeficiency virus (HIV) patients regardless of their CD4 cell count. This study was undertaken to ascertain the cost-effectiveness of implementation of these guidelines in India. Methods: A Markov model was developed to assess the lifetime costs and health outcomes of three scenarios for initiation of ART treatment at varying CD4 cell count <350/mm[3], <500/mm[3] and test and treat using health system perspective using life-time horizon. A few input parameters for this model namely, transition probabilities from one stage to another stage of HIV and incidence rates of TB were calculated from the data of Centre of Excellence for HIV treatment and care, Chandigarh; whereas, other parameters were obtained from the published literature. Total HIV-related deaths averted, HIV infections averted and incremental cost-effectiveness ratio per quality adjusted life years (QALYs) gained were calculated. Result: Test and treat intervention slowed down the progression of disease and averted 18,386 HIV-related deaths, over lifetime horizon. It also averted 16,105 new HIV infections and saved 343,172 QALYs as compared to the strategy of starting ART at CD4 cell count of 500/mm[3]. Incremental cost per QALY gained for the immediate initiation of ART as compared to ART at CD4 cell count of 500/mm[3] and 350/mm[3] was ₹ 46,599 and 80,050, respectively at reported rates of adherence to the therapy. Interpretation & conclusions: Immediate ART (test and treat) is highly cost-effective strategy over the past criteria of delayed therapy in India. Cost-effectiveness of this policy is largely because of reduction in the transmission of HIV.

Medicaid Payer Status Is Associated With Increased 90-Day Resource Utilization, Reoperation, and Infection Following Aseptic Revision Total Hip Arthroplasty.

Background: Prior literature has demonstrated increased resource utilization and perioperative complications in patients with a Medicaid payor status undergoing primary total hip and knee arthroplasty. This relationship has yet to be explored in patients undergoing revision total hip arthroplasty (rTHA). Methods: The National Readmissions Database was queried from 2010 to 2015 for all patients undergoing aseptic rTHA. 90-day complication data were collected, and patients were separated into two cohorts based on insurance payor type: Medicaid and non-Medicaid. Patients were propensity score matched 2:1 on a number of comorbid and operative characteristics. The relationship between Medicaid payor status and postoperative outcomes was then assessed using binomial logistic regression analysis. Results: 3,110 Medicaid patients were identified and matched to 6,175 non-Medicaid patients. Medicaid patients had increased odds of an early prosthetic joint infection (Odds Ratio [OR] 1.29, p=0.019), superficial surgical site infection (OR: 1.48, p=0.003), and early reoperation (OR: 1.18, p=0.045). Medicaid patients also experienced higher odds of readmissions, extended length of stay, non-home discharge status, and medical complications. Finally, the Medicaid cohort had a $3,332 (95% CI: 2,412-4,253, p<0.001) increased adjusted total cost of care when compared to the non-Medicaid cohort. Conclusion: This study identifies the Medicaid payor status as an independent risk factor for increased resource utilization, reoperation, and infection in the early postoperative period for patients undergoing rTHA. This relationship is likely due to an interplay of multiple variables, including socioeconomic status and access to care. Level of Evidence: IV.

Physician Global Assessment as a Disease Activity Measure for Relapsing Polychondritis.

OBJECTIVE: Relapsing polychondritis (RP) is a systemic inflammatory disorder of cartilage that lacks validated disease activity measures. Our objective was to test physician global assessment (PhGA), a measure of disease activity commonly used in rheumatic diseases, in a cohort of patients with RP, which has not been done before. METHODS: Adult patients in an observational cohort of RP underwent standardized, comprehensive evaluation at approximately 6-month intervals. PhGA was scored by 3 physicians from the evaluating institution on a scale of 0-10 for each visit. A random subset of 20 visits was scored by 3 independent physicians not affiliated with the evaluating institution. Treatment change between consecutive visits was categorized as increased, decreased, or unchanged. RESULTS: In total, 78 patients were evaluated over 164 visits. The intraclass correlation coefficient (ICC2,1 ) for the 3 raters from the evaluating institution was excellent (0.79 [95% confidence interval (95% CI) 0.73, 0.84]) but was poor in the subset of cases scored by the additional raters (ICC2,1 0.27 [95% CI -0.01, 0.53]). Median PhGA was 3 (range 0-7). PhGA weakly correlated with C-reactive protein level (rs = 0.30, P < 0.01). In response to increased treatment, median PhGA decreased from 3 (interquartile range [IQR] 2, 4) to 2 (IQR 2, 3) (P < 0.01) but rarely went to 0. CONCLUSION: Within a single center, PhGA can be used to quantify disease activity and monitor disease response in RP. Persistent disease activity despite treatment, rather than a relapsing-remitting pattern, is observed for most patients with RP. Reliability of PhGA may not generalize across different institutions. A validated disease-specific activity index is needed in RP.

Multi-targeted loop mediated amplification PCR for diagnosis of extrapulmonary tuberculosis.

AIMS: The present study was conceived to evaluate multi-targeted loop mediated amplification (MLAMP) for the rapid diagnosis of extrapulmonary tuberculosis (EPTB). METHODS AND RESULTS: A total of 700 patients were included who were classified into 2 groups: Group 1 (n = 400) included a 100 culture confirmed EPTB patients and 300 culture negative, suspected EPTB patients. Group 2 (n = 300) included negative controls from non-tubercular patients. All samples were subjected to Ziehl-Neelsen microscopy, solid culture on Lowenstein Jensen media, Polymerase chain reaction (PCR) targeting IS6110 gene and LAMP targeting both IS6110 and MPB64 individually and as MLAMP. The overall sensitivity of microscopy, culture, IS6110 PCR, IS6110 LAMP, MPB64 LAMP and the MLAMP assay were 12%, 25%, 72.5%, 80% and 86.6% respectively and the specificity of all the tests was 100%. CONCLUSION: MLAMP is a rapid robust tool for the diagnosis of EPTB and utilizing two targets for M. tuberculosis can improve the overall sensitivity and increase the yield of detection from extrapulmonary samples. The rapidity, ease of performance and low cost make MLAMP an excellent alternative in low-income, resource limited settings.

Magnetic bead flocculation test: Improving the diagnosis of tuberculous meningitis (TBM) in low-resource settings.

BACKGROUND: Despite several recent advances in detection techniques, there is still an unmet need for simple tests for the diagnosis of tuberculous meningitis (TBM). Therefore, in an effort towards developing a simple and rapid diagnostic test for resource-poor settings, we designed an assay in which magnetic bead flocculation test (MBF) was used to detect the amplified DNA. Multi-targeted (using two multicopy gene targets IS6110 and IS1081) loop-mediated isothermal amplification (MLAMP) was used for amplification. METHODS: MLAMP-MBF assay was performed on CSF samples of 600 patients, out of which 120 were definite TBM (culture confirmed), 280 were probable TBM and 200 were non-TB controls, based on Marais's criteria. The performance of assay was evaluated by comparing the result of definite TBM with culture and that of probable TBM with composite reference standard consisting of clinical, microbiological(smear/culture) and radiological parameters. RESULTS: The overall sensitivity of MLAMP-MBF (using any of the two gene targets) was 89.5% and specificity was 100%. The sensitivity was 96.6% (116/120) in diagnosing definite TBM and 86.4% (242/280) in diagnosing probable TBM. The sensitivity of IS1081 was 88% and that of IS6110 was 83% in diagnosing TBM. Specificity of both the gene targets was 100%. There were 20 cases positive only by IS1081 LAMP and 6 cases positive only by IS6110; thus 26 of 400 (6.5%) TBM cases could be additionally detected following multi-targeted approach. CONCLUSION: MLAMP-MBF is a sensitive, robust, cost-effective and promising technique for diagnosis of TBM in low-resource high-endemic settings.

Fluorodeoxyglucose positron emission tomography/computed tomography in the diagnosis, assessment of disease activity and therapeutic response in relapsing polychondritis.

OBJECTIVE: To evaluate 18F-fluorodeoxyglucose (FDG) PET/CT in the assessment of disease activity, extent of the disease and response to therapy in relapsing polychondritis. METHODS: Twenty-five patients (9 men, 16 women) with a mean age of 38.2 years (s.d. 13.7; range 18-62), diagnosed to have relapsing polychondritis according to Damiani and Levine's modification of McAdam's criteria, who underwent PET/CT examination were included. Ten patients underwent a second PET/CT examination after therapy or during follow-up. Clinical symptoms and auxiliary examination findings were recorded. PET/CT findings were reviewed and correlated with the clinical symptoms. RESULTS: The major symptoms were aural pain (n = 21), nasal pain (n = 10), stridor (n = 5), cough (n = 9), fever (n = 8) and laryngeal tenderness (n = 8). The initial PET/CT was positive in 23/25 patients. PET/CT revealed involvement of auricular (n = 14), nasal (n = 8), laryngeal (n = 7), tracheobronchial (n = 6) and Eustachian (n = 3) cartilages with a mean maximum standardized uptake value (SUVmax) of 4.1 (s.d. 2.5; range 1.7-12.7). Fair correlation of aural/nasal pain/stridor with FDG avidity of cartilage involvement on PET/CT was noted. The key finding was detection of asymptomatic large airway involvement in seven patients (28%). Re-examination PET in 10 patients revealed complete therapeutic response (n = 5), partial response (n = 1), stable disease (n = 1), progressive disease (n = 1) and disease recurrence (n = 2). CONCLUSION: FDG PET/CT is a useful tool for the assessment of the disease activity and extent. It identified activity in clinically inaccessible sites that are of clinical significance. It is also useful in assessing treatment response and finding relapse.

Comparative evaluation of Xpert MTB/RIF assay with multiplex polymerase chain reaction for the diagnosis of tuberculous meningitis.

BACKGROUND: Rapid and specific diagnosis of tuberculous meningitis (TBM) is of paramount importance to decrease morbidity and mortality. Therefore, the present study was undertaken to compare the efficacy of Xpert MTB/RIF assay (GXpert) and multiplex PCR (MPCR) using three targets (IS6110, MPB64 and protein B) for diagnosing tuberculous meningitis. METHODS: GXpert and MPCR were performed on cerebrospinal fluid samples of 225 patients out of which 80 were culture-positive confirmed cases of TBM, 100 were 'suspected' cases of TBM and 45 were non-TBM controls. rpoB gene sequencing was done for diagnosing rifampicin (Rif) resistance in all positive cases. RESULTS: GXpert and MPCR were positive in 91/180 (50.5%) and 157/180 (87.2%) confirmed or suspected TBM patients respectively. Both the tests were negative in all 45 controls. Rif resistance was detected in 14 cases by GXpert and in 13 cases by MPCR. Rif resistance was confirmed in 13 cases with rpoB gene sequencing. There was one case of false Rif resistance detected by GXpert which was Rif susceptible on rpoB gene sequencing. Cost of doing MPCR was less than USD1 whereas GXpert required USD10 per isolate. CONCLUSION: MPCR has a higher sensitivity than GXpert for diagnosing TBM. MPCR is a robust and cost effective method for diagnosis of TBM in low-resource and high-endemic countries.

Rheumatology science and practice in India.

The practice of rheumatology in a country like India presents its own unique challenges, including the need to manage patients in a cost-constrained setting, where the lack of uniform government funding for healthcare merits the need to optimize the use of cheaper medicines, as well as devise innovative strategies to minimize the use of costlier drugs such as biologic disease-modifying agents. Use of immunosuppressive agents is also associated with increased risks of infectious complications, such as the reactivation of tuberculosis. In this narrative review, we provide a flavor of such challenges unique to Rheumatology practice in India, and review the published literature on the management of common rheumatic diseases from India. In addition, we critically review existing guidelines for the management of rheumatic diseases from this part of the world. We also discuss infectious etiologies of rheumatic complaints, such as leprosy, tuberculosis, and Chikungunya arthritis, which are often encountered here, and pose a diagnostic as well as therapeutic challenge for clinicians. There remains a need to identify and test more cost-effective strategies for Indian patients with rheumatic diseases, as well as the requirement for more government participation to enhance scant facilities for the treatment of such diseases as well as foster the development of healthcare services such as specialist nurses, occupational therapists and physiotherapists to enable better management of these conditions.

Guidelines for management of rheumatic diseases in developing countries from basics to real-world situation: relevance, need, and processes for development.

Guidelines or recommendations help to provide uniform standards in medical practice. The development of guidelines requires adherence to pre-defined norms prescribed by different international organizations such as the European League against Rheumatism (EULAR). We searched Pubmed and LILACS to identify published papers in five major rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathies, osteoarthritis, and scleroderma) from different countries based on their economic prosperity and could find a lack of published literature from most economically weaker regions. Similarly, published guidelines in these rheumatic diseases were sparse from Asia and Africa, which are economically developed to a lesser extent than other regions of the world. Considering differing economic realities driving patient care in different regions of the world, unique challenges in certain geographic areas such as musculoskeletal manifestations of infectious diseases like leprosy and tuberculosis, as well as distinct risk of malignancies and other comorbid conditions, National Rheumatology societies should work towards developing more guidelines for rheumatic diseases from regions such as Asia and Africa, while following strictly the prescribed norms for the same. With a paucity of guidelines for such regions currently, an alternative (although less preferable) suggestion would be that major international societies, whose guidelines are widely read and followed the world over, should consider inputs from experts from diverse regions of the world while developing these guidelines.

Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis.

No previous study has compared mycophenolate mofetil (MMF) with low-dose cyclophosphamide (CYC) in the treatment of lupus nephritis (LN). To do so, we recruited patients with LN (class III, IV, or V) and randomized them to receive either low-dose CYC or oral MMF. Those with crescentic LN, a serum creatinine over 265 µmol/l, and neurological or pulmonary lupus were excluded. MMF was prescribed at daily doses of 1.5-3 g for 24 weeks, while CYC was administered as six fortnightly infusions of 500 mg each. All patients received three methylprednisolone injections, followed by oral corticosteroids. Maintenance therapy with azathioprine and low-dose corticosteroid was started at end of induction therapy. The primary end point was treatment response at 24 weeks, while secondary end points were complete remission, Systemic Lupus Erythematosus Disease Activity Index and adverse events. Of the 173 patients recruited, 100 were equally randomized to receive either CYC or MMF. Baseline characteristics were similar, except for higher 24 h proteinuria in the CYC group. At 24 weeks, 37 patients in each group achieved the primary end point. The complete remission rate was 50% in CYC and 54% in MMF group. Gastrointestinal symptoms were significantly more frequent in patients receiving MMF (52 vs. 4%). However, other adverse events were similar. Thus, low-dose intravenous CYC is comparable in safety and efficacy to oral MMF in the induction treatment of less severe LN.

Cost analysis and benefits of opt-out HIV testing at a tertiary care centre in northern India.

Currently, in India, the National AIDS Control Organization does not recommend HIV screening for all patients attending health care facilities. The objective of study was to evaluate cost and benefits of opt-out HIV testing at a tertiary care hospital from India. This is a retrospective cohort study of patients who had undergone HIV testing. The cost for HIV testing and cost per HIV-infected patient were determined. A total of 6512 patients (66.4% men and 905 patients younger than 14 years) with mean (SD) age of 30.3 (20.7) years were tested for HIV infection during the study period. Overall, 137 (2.1%) patients tested positive for HIV infection. Total cost for performing HIV tests during study period was Indian Rupees (INR) 649,319 (US dollar [USD] 11805.8). The estimated cost per person tested was INR 99.71 (USD1.8) and cost per HIV-infected patient identified and referred to the antiretroviral therapy centre was INR 4739.55 (USD86.2). We determined a 2.1% period prevalence estimate for HIV infection. Based on cost per HIV-infected patient identified and referred to the antiretroviral therapy centre and the burden of HIV infection, it may be cost effective to perform routine opt-out screening for HIV infection in all patients attending health care facilities in developing countries like India.