Survival and Recurrence Patterns in Patients With Stomach Adenocarcinoma Receiving Chemotherapy or Chemoradiotherapy After D2 Gastrectomy in a Tertiary Care Cancer Institute: A Retrospective Real-World Evidence Cohort Study.

Purpose: Clinical trials comparing the efficacy of adjuvant chemotherapy (CT) and chemo radiation therapy (CTRT) for stomach adenocarcinoma have reported equivocal results. Hence, the current retrospective cohort study assessed the long-term survival and recurrence outcomes of these therapies, to generate evidence in a real-world scenario. Methods and Materials: Pathologically confirmed patients with stomach adenocarcinoma aged ≥18 years who underwent gastrectomy and D2 lymph nodal dissection at a tertiary cancer hospital from January 2010 to October 2017 were enrolled. Hospital-based follow-up was performed until December 2021. Data were gathered from electronic medical records, supplemented by telephonic interviews for patients who could not come for physical follow-up. CT-alone and CTRT cohorts were compared in terms of survival and recurrence outcomes. Results: The analysis included 158 patients (mean age, 56.42 years; 63.9% male; CT-alone cohort, 69; CTRT cohort, 89). Patients in the CTRT cohort had significantly worse tumor characteristics at baseline (29.2% had the diffuse type of tumor, 94.4% had stage II or III, 68.5% had lympho-vascular space invasion, and 85.4% had lymph node involvement). Recurrence was observed in 13 (19.7%) of the 76 followed-up patients. Although locoregional recurrence was higher in the CT-alone cohort (7 vs 2), distant metastasis was higher in the CTRT cohort (3 vs 1). The overall 5-year survival was 67.0% (SE, 5.0%) and 5-year recurrence-free survival (RFS) was 75.0% (SE, 5.0%). On multivariate Cox regression, no variable was significantly associated with the overall survival, whereas age, positive lymph nodes without extracapsular extension, and lymph node-negative were significantly associated with RFS. The CTRT cohort had significantly (84.0%) higher RFS (hazard ratio, 0.161; 95% CI, 0.056-0.464; P < .001). Conclusions: Patients who received adjuvant CTRT after D2 dissection showed similar overall survival but significantly higher RFS than the CT-alone cohort, despite having worse baseline tumor characteristics.

Use of Structured Template and Reporting Tool for Real-World Evidence for Critical Appraisal of the Quality of Reporting of Real-World Evidence Studies: A Systematic Review.

OBJECTIVES: Real-world evidence (RWE) studies are increasingly being used to support healthcare decisions. Various frameworks, tools, and checklists exist for ensuring quality of real-world data, designing robust studies, and assessing potential for bias. In January 2021, Structured Template and Reporting Tool for RWE (STaRT-RWE) was released to further reduce ambiguity, assumptions, and misinterpretation while planning, implementing, and reporting RWE studies of the safety and effectiveness of treatments. The objective of this study was to identify gaps in the reporting quality of published RWE studies by using this template for critical appraisal. METHODS: Two reviewers conducted a keyword search on PubMed for free-full-text research articles using real-world data, RWE design, and safety with or without effectiveness outcomes of a medicinal product or intervention in humans of any age or gender, published in English between January 13, 2021, and January 13, 2022. Assessment of risk of bias was done using Assessment of Real-World Observational Studies critical appraisal tool. Deficiencies in methods and findings as per STaRT-RWE template were reported as frequencies. RESULTS: A total of 54 of 2374 retrieved studies were included in the review. Based on the STaRT-RWE template, the studies inadequately reported empirically defined covariates, power and sample size calculation, attrition, sensitivity analyses, index date (day 0) defining criterion, predefined covariates, outcome, metadata about data source and software, objective, inclusion and exclusion criteria, analysis specifications, and follow-up. CONCLUSIONS: The use of STaRT-RWE template along with its tables, design diagram, and library of published studies has a potential of improving robustness of RWE studies.

Community-based follow-up of participants of a mother-friendly clinical trial: A patient-centric methodology for pregnant women.

Repeated visits to clinical trial sites inflict hardships on study participants, especially pregnant women. A newer trend is community-based follow-up for measurements, dosage, or monitoring, through technology or physical visits. We conducted a methodological experiment of performing "community-based physical follow-up" of participants of a trial, receiving facility-based diagnosis and pathogen-specific antibiotics for asymptomatic bacteriuria, guided by an optical-sensor-based rapid point-of-care test. We were able to retain 95.8% participants in the study. Here we describe challenges faced and socio-economic and gender issues encountered in this approach in a low-resource Indian scenario, to guide researchers world-wide for designing mother-friendly clinical trials.

Effectiveness of antenatal screening of asymptomatic bacteriuria in reduction of prematurity and low birth weight: Evaluating a point-of-care rapid test in a pragmatic randomized controlled study.

BACKGROUND: Premature babies suffer higher mortality and life-long disabilities. Asymptomatic bacteriuria (ASB) is postulated to induce preterm labor. Routine antenatal screening for ASB using urine culture is not feasible in most developing countries due to long turn-around time, user-unfriendliness, and lack of resources. The current parallel-group superiority pragmatic randomized controlled trial evaluated the effect of screening and evidence-based treatment of ASB using an optical-sensor-based point-of-care rapid-test on the incidence of preterm birth and low birthweight (LBW). METHODS: 240 consenting asymptomatic pregnant women visiting an Indian tertiary public hospital for first antenatal check-up, irrespective of trimester/gravida, who had not consumed antibiotics in the preceding week, were enrolled from February-May 2017. Computer-generated concealed simple randomization allocation sequence was used to assign participants to intervention (120) and control arm (120). Usual hospital-care was provided in the control arm. In the intervention arm, urine samples were additionally screened for ASB using the rapid-test and the positive women were prescribed susceptible antibiotics. Blinded outcome assessors followed up with women post-delivery. The study was registered with the Clinical Trials Registry-India (CTRI/2016/09/007240). FINDINGS: 213 participants were analyzed (intervention: 103, control: 110). 21 women were found positive for ASB and prescribed pathogen-specific antibiotics. The incidence of preterm birth/LBW in intervention arm (n = 27) was lower than control arm (n = 45) by 14·7% (95% CI: 2·2-27·2); RR: 0.64, (95% CI: 0·43-0·95); p = 0·023, X2=5·13. INTERPRETATION: Rapid-test-guided treatment for ASB reduced the incidence of preterm birth/LBW in a pragmatic setting without any adverse event. FUNDING: Department of Biotechnology, Government of India.

Demystifying Excess Immune Response in COVID-19 to Reposition an Orphan Drug for Down-Regulation of NF-κB: A Systematic Review.

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1ß, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.

Clinical Validation of Innovative Optical-Sensor-Based, Low-Cost, Rapid Diagnostic Test to Reduce Antimicrobial Resistance.

The antibiotic susceptibility test determines the most effective antibiotic treatment for bacterial infection. Antimicrobial stewardship is advocated for the rational use of antibiotics to preserve their efficacy in the long term and provide empirical therapy for disease management. Therefore, rapid diagnostic tests can play a pivotal role in efficient and timely treatment. Here, we developed a novel, rapid, affordable, and portable platform for detecting uropathogens and reporting antibiogram to clinicians in just 4 h. This technology replicates the basic tenets of clinical microbiology including bacterial growth in indigenously formulated medium, and measurement of inhibition of bacterial growth in presence of antibiotic/s. Detection is based on chromogenic endpoints using optical sensors and is analyzed by a lab-developed algorithm, which reports antibiotic sensitivity to the antibiotics panel tested. To assess its diagnostic accuracy, a prospective clinical validation study was conducted in two tertiary-care Indian hospitals. Urine samples from 1986 participants were processed by both novel/index test and conventional Kirby Bauer Disc Diffusion method. The sensitivity and specificity of this assay was 92.5% and 82%, respectively (p < 0.0005). This novel technology will promote evidence-based prescription of antibiotics and reduce the burden of increasing resistance by providing rapid and precise diagnosis in shortest possible time.

Unmet Need of Antenatal Screening for Asymptomatic Bacteriuria: A Risk Factor for Adverse Outcomes of Pregnancy.

Recommended urine culture is unsuitable for screening pregnant women for asymptomatic bacteriuria due to long turn-around time, unaffordability, and user-unfriendliness. The objective of this review was to evaluate the suitability of various tests for this purpose. A PubMed-based systematic review of published articles irrespective of year and language was done. Search terms included asymptomatic bacteriuria, screening test, urinary tract infection, and diagnostic test. Diagnostic accuracy studies conducted on human populations comparing tests with urine culture were included. One author extracted predefined data fields, including quality indicators, another validated it. Of 78 records, 25 studies describing 15 tests were included. All tests were rapid, seven were valid and two of them were affordable and easy-to-use. No test provided comprehensive identification with antibiotic susceptibility. Despite publication bias, no test was found suitable for screening asymptomatic bacteriuria antenatally and providing evidence-based prescription. Further research is needed to develop tests which suit this purpose.

Potential for Improving Intrauterine Device (IUD) Service Delivery Quality: Results from a Secondary Data Analysis.

Background: To accelerate progress toward Family Planning 2020 (FP2020) goals, the government of India focused on improving the quality of intrauterine device (IUD) services. EngenderHealth, an international sexual and reproductive health and rights organization, has been supporting the governments of Gujarat and Rajasthan since 2014 through the Expanding Access to IUD Services in India (EAISI) project by building the capacity of service providers, monitoring compliance with standard practices, and strengthening health systems. This study sought to assess whether EAISI-trained providers offer higher quality IUD services than non-EAISI-trained providers, as indicated by a reduction in confirmed IUD complications. Methods: The study team conducted an analytical cross-sectional study of secondary data collected from follow-up registers at 176 intervention facilities (38 in Gujarat and 138 in Rajasthan) during Phase I of the EAISI project. The analysis included follow-up clients who returned to the same facility between April 2018 and March 2019. We performed a multivariate logistic regression to determine factors associated with IUD complications. Results: During the period of assessment, 56,733 clients received IUD insertions, and 10,747 (18.9%) clients returned for follow-up services. Of the returning clients, 49.4% (N=5,305) had received IUDs from EAISI-trained providers, while 50.6% (N=5,442) had received IUDs from non-EAISI-trained providers. A total of 4.0% (N=432) of all returning clients experienced complications (expulsion: 1.3%, missing strings: 1.7%, infection: 1.1%). Clients who received IUDs from non-EAISI-trained providers were 55.5% more likely (95% CI [26.2%, 91.5%], p<0.0005) to have experienced complications than clients who received insertions from EAISI-trained providers. The type of IUD, the timing of the insertion, and the timing of the follow-up visit also affected complication prevalence. Conclusion: Our findings indicate that intensive, practical clinical skills training for IUD insertion can reduce the prevalence of complications.