Correlations of response rate and progression-free survival with overall survival in immunotherapy trials for metastatic non-small-cell lung cancer: an FDA pooled analysis.

BACKGROUND: Radiographic changes might not fully capture the treatment effects of immune checkpoint inhibitors (ICIs). We aimed to assess correlations of overall response rate and progression-free survival with overall survival in trials of ICIs for metastatic non-small-cell lung cancer (NSCLC). METHODS: To assess trial-level and patient-level correlations of overall response rate and progression-free survival with overall survival, we conducted a pooled analysis of first-line randomised trials (including patients aged ≥18 years with metastatic squamous and non-squamous NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1) submitted to the US Food and Drug Administration from June 24, 2016, to March 16, 2021. Eligible trials evaluated at least one ICI in the experimental group versus chemotherapy in the control group. At the trial level, we used weighted linear regression to derive coefficients of determination (R2). At the patient level, we used Cox proportional hazards models to compare overall survival between responders versus non-responders per Response Evaluation Criteria in Solid Tumours (version 1.1). FINDINGS: A total of 13 trials including 9285 patients evaluated ICIs alone or in combination with chemotherapy versus chemotherapy alone. At the trial level, the R2 was 0·61 (95% CI 0·32-0·84) for correlation of overall response rate with overall survival and 0·70 (0·40-0·89) for correlation of progression-free survival with overall survival. Correlations ranged from weak to moderate when evaluating subgroups by PD-L1 expression and were consistent across trials evaluating ICIs alone or in combination with chemotherapy. At the patient level, responders had longer overall survival than non-responders (hazard ratio [HR] 0·28 [95% CI 0·26-0·30]). Among responders, overall survival was longer in patients enrolled in experimental groups than in control groups (HR 0·54 [95% CI 0·48-0·61]). INTERPRETATION: Correlations of overall response rate and progression-free survival with overall survival were generally moderate in this pooled analysis. The findings support routine analysis of mature overall survival data, where feasible, in first-line randomised trials of ICIs for metastatic NSCLC. FUNDING: US Food and Drug Administration.

Biophysical characterization of chloride intracellular channel 6 (CLIC6).

Chloride intracellular channels (CLICs) are a family of proteins that exist in soluble and transmembrane forms. The newest discovered member of the family CLIC6 is implicated in breast, ovarian, lung gastric, and pancreatic cancers and is also known to interact with dopamine-(D(2)-like) receptors. The soluble structure of the channel has been resolved, but the exact physiological role of CLIC6, biophysical characterization, and the membrane structure remain unknown. Here, we aimed to characterize the biophysical properties of this channel using a patch-clamp approach. To determine the biophysical properties of CLIC6, we expressed CLIC6 in HEK-293 cells. On ectopic expression, CLIC6 localizes to the plasma membrane of HEK-293 cells. We established the biophysical properties of CLIC6 by using electrophysiological approaches. Using various anions and potassium (K+) solutions, we determined that CLIC6 is more permeable to chloride-(Cl-) as compared to bromide-(Br-), fluoride-(F-), and K+ ions. In the whole-cell configuration, the CLIC6 currents were inhibited after the addition of 10 µM of IAA-94 (CLIC-specific blocker). CLIC6 was also found to be regulated by pH and redox potential. We demonstrate that the histidine residue at 648 (H648) in the C terminus and cysteine residue in the N terminus (C487) are directly involved in the pH-induced conformational change and redox regulation of CLIC6, respectively. Using qRT-PCR, we identified that CLIC6 is most abundant in the lung and brain, and we recorded the CLIC6 current in mouse lung epithelial cells. Overall, we have determined the biophysical properties of CLIC6 and established it as a Cl- channel.

The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Impact of Increasing PD-L1 Levels on Outcomes to PD-1/PD-L1 Inhibition in Patients With NSCLC: A Pooled Analysis of 11 Prospective Clinical Trials.

BACKGROUND: Programmed death ligand 1 (PD-L1) expression is recognized as a key biomarker in the treatment of non-small cell lung cancer (NSCLC) with anti-PD(L)1 inhibitors. Previous work has highlighted that outcomes in patients with NSCLC treated with anti-PD(L)1 inhibitors generally improve with increasing PD-L1 expression. The objectives of these analyses are to quantitate the effect of PD-L1 expression on outcomes, to characterize the potentially nonlinear relationship between PD-L1 expression and outcomes, and to assess potential differences in these relationships across subgroups. PATIENTS AND METHODS: We performed a retrospective, pooled analysis of 11 clinical trials submitted to the US FDA between 2015 and 2022 that included patients with advanced NSCLC treated with anti-programmed death 1 or anti-PD-L1 immune checkpoint inhibitor (ICI) monotherapy in the first-line (1L) or second-line (2L) treatment setting. The clinical outcomes explored were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: The primary analysis population included 3806 patients with advanced NSCLC, of which 2040 were treated in 1L and 1766 in 2L. For patients with a PD-L1 score of 100% in the 1L setting, the hazard ratio versus a patient with 1% PD-L1 was 0.55 (95% CI, 0.43 to 0.70) for OS and 0.50 (95% CI, 0.41 to 0.61) for PFS. For patients with a PD-L1 score of 100% in the 2L setting, the hazard ratio versus a patient with 0% PD-L1 was 0.55 (95% CI, 0.43 to 0.71) for OS and 0.51 (95% CI, 0.41 to 0.63) for PFS. Subgroup analyses suggested that this relationship may vary by subgroup, particularly by region. CONCLUSIONS: These analyses suggest PD-L1 expression has an appreciable impact on clinical outcomes for patients with NSCLC treated with ICI. As the impact of PD-L1 expression on outcomes may vary across regions, it is critical that future trials are multiregional and enroll a diverse patient population.

FDA approval summary: fam-trastuzumab deruxtecan-nxki for unresectable or metastatic non-small cell lung cancer with activating HER2 mutations.

On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2-mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥ 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence's Project Optimus. This is the first approval of a targeted therapy for HER2-mutated NSCLC.

Characterizing the Conformational Dynamics of Human SUMO2: Insights into its Interaction with Metal Ions and SIMs.

SUMO (Small Ubiquitin-like Modifiers) proteins are involved in a crucial post-translational modification commonly termed as SUMOylation. In this work, we have investigated the native-state conformational flexibility of human SUMO2 and its interaction with Cu2+ and Zn2+ ions using 15N-1H based 2D NMR spectroscopy. After SUMO1, SUMO2 is the most studied SUMO isoform in humans which shares 45 % and ~80 % similarity with SUMO1 in terms of sequence and structure, respectively. In this manuscript, we demonstrate that compared to SUMO1, several amino acids around the α1-helix region of SUMO2 access energetically similar near-native conformations. These conformations could play a crucial role in SUMO2's non-covalent interactions with SUMO interaction motifs (SIMs) on other proteins. The C-terminal of SUMO2 was found to bind strongly with Cu2+ ions resulting in a trimeric structure as observed by gel electrophoresis. This interaction seems to interfere in its non-covalent interaction with a V/I-x-V/I-V/I based SIM in Daxx protein.

Incidentally detected diaphragmatic eventration as para-cardiac thoracic activity on myocardial perfusion imaging.

Diaphragmatic eventration is the elevation of hemi-diaphragm without any disruption to diaphragmatic continuity which can be congenital or acquired. The most common acquired cause is phrenic nerve paralysis due to traumatic causes and is usually incidentally diagnosed on chest radiograph or computed tomography. We hereby report a case of a patient who had road traffic accident with fracture of the left proximal femur. Stress Myocardial Perfusion Imaging (MPI) done for pre-operative clearance showed an incidental tracer avidity adjoining to left myocardium in the thorax. It was confirmed on anatomical imaging to be gastric cavity uptake due to diaphragm eventration.

Potential application of 68Ga-FAPI PET/CT for diagnosing cardiac sarcoidosis.

Detecting cardiac sarcoidosis; a potentially life-threatening condition is challenging and requires a multimodality imaging approach using echocardiography, PET/CT and CMR. Although 18F-FDG is the recommended PET tracer for evaluating cardiac sarcoidosis, it is limited by physiological cardiac FDG uptake and requires stringent patient preparation/ dietary modifications before imaging. We hereby present a case of cardiac sarcoidosis demonstrating myocardial FAPI uptake on cardiac PET, highlighting the potential role of 68Ga-FAPI PET in the evaluation of cardiac sarcoidosis.

Charge-symmetric and -asymmetric fragmentation dynamics of argon dimers in slow Ar8+-Ar2 collisions.

We present an experimental study of multiple-electron capture-induced fragmentation dynamics of Ar2m+ (4 ≤m≤ 7) dimer ions in 4 keV/u Ar8+-Ar2 collisions. The fragment recoil ion pairs and the charge-changing projectiles are coincidentally measured using a double coincidence technique. The branching ratios between the different charge-sharing fragmentation channels show an inherent enhancement of the asymmetric channels. The kinetic energy release (KER) distributions for the associated electron capture process show a shift in the mean KER values toward the higher side with increasing capture stabilization. The interplay between the different projectile autoionization processes sheds light on the energy depositions to the system during collisions. The Coulomb potential energy curves give a physical insight into the role of the projectile final states in the dimer fragmentation dynamics. The dimer-axis orientation-dependent cross sections for the asymmetric fragmentation channels reveal a forward-backward asymmetry that arises from the geometry of the collision system. Our findings thus give insight into the impact parameter-controlled fragmentation dynamics of multiply charged Ar2m+ dimer ions in highly charged ion-dimer slow collisions.

Complex Three-Dimensional Microscale Structures for Quantum Sensing Applications.

We present a novel method for fabricating highly customizable three-dimensional structures hosting quantum sensors based on nitrogen vacancy (NV) centers using two-photon polymerization. This approach overcomes challenges associated with structuring traditional single-crystal quantum sensing platforms and enables the creation of complex, fully three-dimensional, sensor assemblies with submicroscale resolutions (down to 400 nm) and large fields of view (>1 mm). By embedding NV center-containing nanoparticles in exemplary structures, we demonstrate high sensitivity optical sensing of temperature and magnetic fields at the microscale. Our work showcases the potential for integrating quantum sensors with advanced manufacturing techniques, facilitating the incorporation of sensors into existing microfluidic and electronic platforms, and opening new avenues for widespread utilization of quantum sensors in various applications.

Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty.

In healthy older adults, the immune system generally preserves its response and contributes to a long, healthy lifespan. However, rapid deterioration in immune regulation can lead to chronic inflammation, termed inflammaging, which accelerates pathological aging and diminishes the quality of life in older adults with frailty. A significant limitation in current aging research is the predominant focus on comparisons between young and older populations, often overlooking the differences between healthy older adults and those experiencing pathological aging. Our study elucidates the intricate immunological dynamics of the CD4/Treg axis in frail older adults compared to comparable age-matched healthy older adults. By utilizing publicly available RNA sequencing and single-cell RNA sequencing (scRNAseq) data from peripheral blood mononuclear cells (PBMCs), we identified a specific Treg cell subset and transcriptional landscape contributing to the dysregulation of CD4+ T-cell responses. We explored the molecular mechanisms underpinning Treg dysfunction, revealing that Tregs from frail older adults exhibit reduced mitochondrial protein levels, impairing mitochondrial oxidative phosphorylation. This impairment is driven by the TNF/NF-kappa B pathway, leading to cumulative inflammation. Further, we gained a deeper understanding of the CD4/Treg axis by predicting the effects of gene perturbations on cellular signaling networks. Collectively, these findings highlight the age-related relationship between mitochondrial dysfunction in the CD4/Treg axis and its role in accelerating aging and frailty in older adults. Targeting Treg dysfunction offers a critical basis for developing tailored therapeutic strategies aimed at improving the quality of life in older adults.

Evaluation of the Efficacy and Safety of Intravenous Immunoglobulin (IVIG) in Moderate-to-Severe Hospitalized COVID-19 Patients: A Randomized, Open-Label Parallel-Group Study.

Purpose: Since February 2020, the world has been overwhelmed by the SARS-CoV-2 outbreak, and several patients suffered interstitial pneumonia and respiratory failure requiring mechanical ventilation, threatening the capability of healthcare systems to handle this amount of critical cases. Intravenous immunoglobulins (IVIG) possess potential immunomodulatory properties beneficial for COVID-19 patients, yet evidence supporting IVIG as adjunctive therapy remains sparse. This study evaluated the outcomes of adjunctive IVIG with the standard of care (SoC) in moderate-to-severe COVID-19 patients. Methods: This randomized study included 59 moderate-to-severe COVID-19 patients with known comorbidities. One arm (n = 33) received high-dose IVIG (400 mg/kg/day) within 48 hours for five days alongside SoC, while the other arm (n = 26) received SoC, comprising steroids, enoxaparin, and remdesivir. The primary endpoint was clinical improvement, as measured by the National Early Warning Score 2 (NEWS2) and discharged/death proportions. Secondary outcomes included IVIG safety, hospitalization duration, changes in oxygen saturation, inflammatory markers, IgG titer, CTSS (CT severity score), and radiological findings. Results: There was an improvement in the NEWS2 at the end of treatment in the IVIG arm (5.67 vs. 5.96). A significant absolute effect improvement (Day 1 vs. Day 9) was seen in serum LDH, D-dimer, hs-CRP, IL-6, CTSS, procalcitonin, respiratory rate, and chest radiographic findings. SARS-CoV-2 IgG titer increased significantly in the IVIG arm. There was a statistically significant reduction in mortality in the IVIG group (5 vs. 10). Conclusion: IVIG was a safe and effective adjunctive therapy to SoC treatment in moderate-to-severe COVID-19 patients needing ventilatory support. Furthermore, studies are required to validate our findings. This trial is registered with CTRI/2021/05/033622.

Community-based study to describe the epidemiology of dengue infection in a large cantonment during one transmission season.

Background: Dengue is one of the most important vector-borne disease in India. It has been linked to monsoons when Aedes aegypti mosquitoes breed profusely in containers. No study exists in Armed Forces wherein a community-based sero-survey has described the epidemiology of dengue. The present study tries to fill this knowledge gap. Methods: A total of 422 participants were studied for one transmission season of July-December. Blood samples were collected for testing dengue IgG and IgM at the beginning and at end of the study period. The study participants were interviewed at least twice within this period of 6 months to assess clinical condition and follow-up. Point prevalence and incidence were measured. Distribution of presence or absence of symptoms was noted for positive as well as negative cases. Results: All participants were males. Average age was 31.75 years. Point prevalence at the beginning of transmission season was 11.6% (95% CI: 8.4%-14.6%) and 15.6% (95% CI: 12.1%-19.1%) towards the end. Incidence was found to be 147.4 per 1000 for 6 months. Forty percent of incident cases were asymptomatic. Conclusion: Healthcare planners and hospital commanders in stations across Armed Forces can use the prevalence and incidence figures obtained in this study as a general guide while planning for prevention and control of dengue. Also, this study points to the fact that dengue transmission in Delhi may have shifted earlier to months of April/May than the conventionally accepted season of July-December.

Genome screening, reporting, and genetic counseling for healthy populations.

Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.

FDA regulatory considerations for the review of drugs intended to treat pediatric cancers and rare tumors.

PURPOSE OF REVIEW: We describe select recent FDA approvals in pediatric cancers and rare tumors, and the unique regulatory considerations raised by each application. RECENT FINDINGS: The approvals of naxitamab, selumetinib, selpercatinib, and crizotinib for pediatric and adolescent patients between April 2020 and January 2021 all represented first FDA approvals in their respective pediatric or adolescent populations. In addition, all represent approvals of targeted therapies administered in select patient populations, and were based on overall response rate (ORR) and duration of response (DOR) data in single-arm trials. SUMMARY: Recent approvals for the pediatric oncology indications have often, but not always, relied in part upon investigator-sponsored clinical trials. Early engagement with regulatory agencies to discuss drug development in rare populations is critical to obtain early agreement on trial design and streamline development. Although reliance on ORR and DOR data may be feasible to support an approval, the ability to rely on response rate depends on many factors, including the disease context, reliability of radiographic assessment, and the results of the trial. In some cases, a time-to-event endpoint may be most appropriate to assess clinical benefit; early consideration should be given to the feasibility of conducting of a randomized trial.

Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer.

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas ß-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.

Bioactive phytocompounds against specific target proteins of Borrelia recurrentis responsible for louse-borne relapsing fever: Genomics and structural bioinformatics evidence.

Louse-borne relapsing fever (LBRF) with high untreated mortality caused by spirochete Borrelia recurrentis is predominantly endemic to Sub-Saharan Africa and has re-emerged in parts of Eastern Europe, Asia and Latin America due to population migrations. Despite subtractive evolution of lice-borne pathogenic Borrelia spp. from tick-borne species, there has been no comprehensive report on conservation of protein targets across tick and lice-borne pathogenic Borrelia nor exploration of phytocompounds that are toxic to tick against lice. From the 19 available whole genomes including B. recurrentis, B. burgdorferi, B. hermsii, B. parkeri and B. miyamotoi, conservation of seven drug targets (>80% domain identity) viz. 30 S ribosomal subunit proteins (RSP) S3, S7, S8, S14, S19, penicillin-binding protein-2 and 50 S RSP L16 were deciphered through multiple sequence alignments. Twelve phytocompounds (hydroxy-tyrosol, baicalein, cis-2-decanoic acid, morin, oenin, rosemarinic acid, kaempferol, piceatannol, rottlerin, luteolin, fisetin and monolaurin) previously explored against Lyme disease spirochete B. burgdorferi when targeted against LBRF-causing B. recurrentis protein targets revealed high multi-target affinity (2%-20% higher than conventional antibiotics) through molecular docking. However, based on high binding affinity against all target proteins, stable coarse-grained dynamics (fluctuations <1 Å) and safe pharmacological profile, luteolin was prioritized. The study encourages experimental evaluation of the potent phytocompounds and similar protocols for investigating other emerging vector-borne diseases.

Assessing the coverage of full antenatal care among adolescent mothers from scheduled tribe and scheduled caste communities in India.

BACKGROUND: The persistently high rates of maternal mortality and morbidity among historically marginalised social groups, such as adolescent Scheduled Castes (SCs) and Scheduled Tribes (STs) in India, can be attributed, in part, to the low utilisation of full antenatal healthcare services. Despite efforts by the Indian government, full antenatal care (ANC) usage remains low among this population. To address this issue, it is crucial to determine the factors that influence the utilisation of ANC services among adolescent SC/ST mothers. However, to date, no national-level comprehensive study in India has specifically examined this issue for this population. Our study aims to address this research gap and contribute to the understanding of how to improve the utilisation of ANC services among adolescent SC/ST mothers in India. DATA AND METHODS: Data from the fourth round of the National Family Health Survey 2015-16 (NFHS-4) was used. The outcome variable was full antenatal care (ANC). A pregnant mother was considered to have 'full ANC' only when she had at least four ANC visits, at least two tetanus toxoid (TT) injections, and consumed 100 or more iron-folic acid (IFA) tablets/syrup during her pregnancy. Bivariate analysis was used to examine the disparity in the coverage of full ANC. In addition, binary logistic regression was used to understand the net effect of predictor variables on the coverage of full ANC. RESULTS: The utilisation of full antenatal care (ANC) among adolescent SC/ST mothers was inadequate, with only 18% receiving full ANC. Although 83% of Indian adolescent SC/ST mothers received two or more TT injections, the utilisation of the other two vital components of full ANC was low, with only 46% making four or more ANC visits and 28% consuming the recommended number of IFA tablets or equivalent amount of IFA syrup. There were statistically significant differences in the utilisation of full ANC based on the background characteristics of the participants. The statistical analysis showed that there was a significant association between the receipt of full ANC and factors such as religion (OR = 0.143, CI = 0.044-0.459), household wealth (OR = 5.505, CI = 1.804-16.800), interaction with frontline health workers (OR = 1.821, CI = 1.241-2.670), and region of residence in the Southern region (OR = 3.575, CI = 1.917-6.664). CONCLUSION: In conclusion, the study highlights the low utilisation of full antenatal care services among Indian adolescent SC/ST mothers, with only a minority receiving the recommended number of ANC visits and consuming the required amount of IFA tablets/syrup. Addressing social determinants of health and recognising the role of frontline workers can be crucial in improving full ANC coverage among this vulnerable population. Furthermore, targeted interventions tailored to the unique needs of different subgroups of adolescent SC/ST mothers are necessary to achieve optimal maternal and child health outcomes.

Quality assessment of global health care system in the shadow of COVID-19: - a systematic review.

INTRODUCTION: The healthcare system is critical to the country's overall growth, which involves the healthy development of individuals, families, and society everywhere. This systematic review focuses on providing an overall assessment of the quality of healthcare delivery during COVID-19. METHODOLOGY: The literature search was conducted from March 2020 till April 2023 utilising the databases "PubMed," "Google Scholar," and "Embase." A total of nine articles were included. Descriptive statistics was performed using Microsoft Excel. PROSPERO registration ID- CRD42022356285. RESULTS: According to the geographic location of the studies included, four studies were conducted in Asia [Malaysia(n = 1); India (Madhya Pradesh) (n = 1); Saudi Arabia(n = 1); Indonesia (Surabaya) (n = 1)], three in Europe [U.K. (n = 1); Poland (n = 1); Albania (n = 1)] and two in Africa [Ethiopia(n = 1); Tunisia (n = 1)]. Overall patient satisfaction was found highest among studies conducted in Saudi Arabia (98.1%) followed by India (Madhya Pradesh) (90.6%) and the U.K. (90%). CONCLUSION: This review concluded five different aspects of patients satisfaction level i.e. reliability, responsiveness, assurance, empathy, and tangibility. It was found that the empathy aspect had the greatest value of the five factors, i.e., 3.52 followed by Assurance with a value of 3.51.

Trends in pulmonary tuberculosis mortality between 1985 and 2018: an observational analysis.

BACKGROUND: Pulmonary tuberculosis (TB) is a major source of global morbidity and mortality. Latent infection has enabled it to spread to a quarter of the world's population. The late 1980s and early 1990s saw an increase in the number of TB cases related to the HIV epidemic, and the spread of multidrug-resistant TB. Few studies have reported pulmonary TB mortality trends. Our study reports and compares trends in pulmonary TB mortality. METHODS: We utilized the World Health Organization (WHO) mortality database from 1985 through 2018 to analyze TB mortality using the International Classification of Diseases-10 codes. Based on the availability and quality of data, we investigated 33 countries including two countries from the Americas; 28 countries from Europe; and 3 countries from the Western Pacific region. Mortality rates were dichotomized by sex. We computed age-standardized death rates per 100,000 population using the world standard population. Time trends were investigated using joinpoint regression analysis. RESULTS: We observed a uniform decrease in mortality in all countries across the study period except the Republic of Moldova, which showed an increase in female mortality (+ 0.12 per 100,000 population). Among all countries, Lithuania had the greatest reduction in male mortality (-12) between 1993-2018, and Hungary had the greatest reduction in female mortality (-1.57) between 1985-2017. For males, Slovenia had the most rapid recent declining trend with an estimated annual percentage change (EAPC) of -47% (2003-2016), whereas Croatia showed the fastest increase (EAPC, + 25.0% [2015-2017]). For females, New Zealand had the most rapid declining trend (EAPC, -47.2% [1985-2015]), whereas Croatia showed a rapid increase (EAPC, + 24.9% [2014-2017]). CONCLUSIONS: Pulmonary TB mortality is disproportionately higher among Central and Eastern European countries. This communicable disease cannot be eliminated from any one region without a global approach. Priority action areas include ensuring early diagnosis and successful treatment to the most vulnerable groups such as people of foreign origin from countries with a high burden of TB and incarcerated population. Incomplete reporting of TB-related epidemiological data to WHO excluded high-burden countries and limited our study to 33 countries only. Improvement in reporting is crucial to accurately identify changes in epidemiology, the effect of new treatments, and management approaches.