Economic evaluation of integrating nutritional support intervention in India's National Tuberculosis Elimination Programme: implications for low-income and middle-income countries.

Objectives: This study aimed to evaluate the cost-effectiveness of integrating nutritional support into India's National Tuberculosis Elimination Programme (NTEP) using the MUKTI initiative.

Design: Economic evaluation.

Setting: Primary data on the cost of delivering healthcare services, out-of-pocket expenditure and health-related quality of life among patients with tuberculosis (TB) were collected from Dhar district of Madhya Pradesh, India.

Validation of a Compact and Self-Contained Pyrosequencing Platform for Clinical Screening of Mutations in Thyroid Cancers.

Accurate screening of clinically significant tumor mutations is critical for precision medicine in oncology. This requires genotyping platforms with high accuracy and compatibility with varying DNA yields from challenging sample types. Here, we have validated a new, improved, compact, and self-contained pyrosequencing platform (Pyromark Q48 Autoprep; Q48) for screening -, - and mutations in thyroid cancers.

Utilisation of rural primary health centers for outpatient services - a study based on Rajasthan, India.

Introduction: Outpatient services are crucial for strengthening primary healthcare and reducing out-of-pocket spending, which has been one of the major causes of impoverishment. So it is also critical to comprehend the people's preferences in accessing primary healthcare facilities, as government primary healthcare facilities in India are underutilized. The current paper explores the factors that construct the individual's decision to seek outpatient care in primary healthcare facilities in India's largest state Rajasthan.

Role of Prescription Practice in Ensuring Patient Safety in the Primary Health-Care Settings in India.

"Completeness (a measure of adequacy)" and the "appropriateness (a measure of the quality of care)" are two dimensions of good prescription practice. The study assessed the prescription practices at the primary health centers (PHCs); to demonstrate the effect of individual and system-level factors, on adequacy and appropriateness of prescription practices, with special reference to e-prescription over manual prescription given the rising acceptance of teleconsultation in health care. A total of 600 manual and 1000 e-prescriptions were randomized using a probability-proportional-to-size sampling method to distribute/allocate samples across manual and e-prescriptions.

Target Enrichment Approaches for Next-Generation Sequencing Applications in Oncology.

Screening for genomic sequence variants in genes of predictive and prognostic significance is an integral part of precision medicine. Next-generation sequencing (NGS) technologies are progressively becoming platforms of choice to facilitate this, owing to their massively parallel sequencing capability, which can be used to simultaneously screen multiple markers in multiple samples for a variety of variants (single nucleotide and multi nucleotide variants, insertions and deletions, gene copy number variations, and fusions). A crucial step in the workflow of targeted NGS is the enrichment of the genomic regions of interest to be sequenced, against the whole genomic background.

Reliable energy and responsive built environment: the missing links in COVID-19 response in resource-limited settings.

Irrespective of how the COVID-19 pandemic evolves over time across the globe, our past experiences with comparable zoonotic diseases demonstrate the significance of having resilient primary healthcare systems to successfully respond to public health emergencies. However, literature corroborates that in low- and middle-income countries, the primary healthcare systems are plagued with significant energy insecurity and inadequate built environment. These gaps in reliable energy and responsive built environment in primary healthcare systems are exacerbated during disruptive public health emergencies such as COVID-19.

Next-Generation Sequencing in High-Sensitive Detection of Mutations in Tumors: Challenges, Advances, and Applications.

Next-generation sequencing (NGS) technologies have come of age as preferred technologies for screening of genomic variants of pathologic and therapeutic potential. Because of their capability for high-throughput and massively parallel sequencing, they can screen for a variety of genomic changes in multiple samples simultaneously. This has made them platforms of choice for clinical testing of solid tumors and hematological malignancies.

Hybrid oncocytic/chromophobe renal tumors are molecularly distinct from oncocytoma and chromophobe renal cell carcinoma.

Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney represents a poorly understood clinicopathologic entity with pathologic features that overlap between benign renal oncocytoma (RO) and malignant chromophobe renal cell carcinoma (ChRCC). Consequently, characterization of HOCT and its separation from the foregoing entities are clinically important. The aim of this study was to describe the pathologic and molecular features of HOCT and to compare them with those of RO and ChRCC.

Clinical molecular testing for ASXL1 c.1934dupG p.Gly646fs mutation in hematologic neoplasms in the NGS era.

ASXL1 (additional sex combs like 1) is a gene that is mutated in a number of hematological neoplasms. The most common genetic alteration is c.1934dupG p.

Challenges in next generation sequencing analysis of somatic mutations in transplant patients.

Analysis of somatic mutations in solid tumors and hematologic malignancies using targeted next generation sequencing (NGS)-based assays has become part of routine oncology practice as well as clinical trials. The use of paired tumor-normal DNA samples increases confidence of somatic calls. NGS assays that utilize unique patient identifiers (SNP IDs) allow further comparison of samples within a run or paired tumor/normal samples.

amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer.

To investigate the prognostic impact of copy number (-CN) in patients with non-small cell lung cancer (NSCLC), we retrospectively reviewed clinical and pathologic data of NSCLC patients whose tumors were assessed for -CN using fluorescence hybridization (FISH). We correlated -CN status with patient overall survival (OS) and optimized -FISH reporting criteria. The study group included 384 patients with NSCLC of which 88% were adenocarcinoma and 55.

Detection of somatic mutations in cell-free DNA in plasma and correlation with overall survival in patients with solid tumors.

A suitable clinical-grade platform is required for detection of somatic mutations with high sensitivity in cell-free DNA (cfDNA) of patients with solid tumors. In this study, we evaluated in parallel ultra-deep NGS with MassARRAY and allele-specific droplet digital PCR (ddPCR) for cfDNA genotyping and correlated cfDNA yield and mutation status with overall survival (OS) of patients. We assessed plasma samples from 46 patients with various advanced metastatic solid tumors and known mutations by deep sequencing using an Ampliseq cancer hotspot panel V2 on Ion Proton.

Versatile ion S5XL sequencer for targeted next generation sequencing of solid tumors in a clinical laboratory.

Background: Next generation sequencing based tumor tissue genotyping involves complex workflow and a relatively longer turnaround time. Semiconductor based next generation platforms varied from low throughput Ion PGM to high throughput Ion Proton and Ion S5XL sequencer. In this study, we compared Ion PGM and Ion Proton, with a new Ion S5XL NGS system for workflow scalability, analytical sensitivity and specificity, turnaround time and sequencing performance in a clinical laboratory.

Study of Preanalytic and Analytic Variables for Clinical Next-Generation Sequencing of Circulating Cell-Free Nucleic Acid.

Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next-generation sequencing (NGS) has opened up new possibilities for monitoring treatment response and disease progression in patients with solid tumors. However, implementation of cfDNA genotyping in diagnostic laboratories requires systematic assessment of preanalytical parameters and analytical performance of NGS platforms. We assessed the effects of peripheral blood collection tube and plasma separation time on cfDNA yield and integrity and performance of the Ion PGM, Proton, and MiSeq NGS platforms.

Validation of quantitative PCR-based assays for detection of gene copy number aberrations in formalin-fixed, paraffin embedded solid tumor samples.

Gene copy number changes are important somatic alterations in cancers. A number of high throughput methods, such as next generation sequencing, are capable of detecting copy number aberrations, but their use can be challenging and cost prohibitive for screening a small number of markers. Furthermore, detection of CNAs by high throughput platforms needs confirmation by an orthogonal technique, especially in cases with low level CNAs.

Analytical Validation of the Next-Generation Sequencing Assay for a Nationwide Signal-Finding Clinical Trial: Molecular Analysis for Therapy Choice Clinical Trial.

The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial is a national signal-finding precision medicine study that relies on genomic assays to screen and enroll patients with relapsed or refractory cancer after standard treatments. We report the analytical validation processes for the next-generation sequencing (NGS) assay that was tailored for regulatory compliant use in the trial. The Oncomine Cancer Panel assay and the Personal Genome Machine were used in four networked laboratories accredited for the Clinical Laboratory Improvement Amendments.

Genome-wide copy number aberrations and HER2 and FGFR1 alterations in primary breast cancer by molecular inversion probe microarray.

Breast cancer remains the second leading cause of cancer-related death in women despite stratification based on standard hormonal receptor (HR) and HER2 testing. Additional prognostic markers are needed to improve breast cancer treatment. Chromothripsis, a catastrophic genome rearrangement, has been described recently in various cancer genomes and affects cancer progression and prognosis.

Concurrent fine needle aspirations and core needle biopsies: a comparative study of substrates for next-generation sequencing in solid organ malignancies.

Minimally invasive procedures, such as fine needle aspiration and core needle biopsy, are commonly used for the diagnosis in solid organ malignancies. In the era of targeted therapy, it is crucial for molecular testing to be performed on these limited volume specimens. Although several recent studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to whether core needle biopsy specimens are more reliable than fine needle aspiration for molecular studies.

A Targeted High-Throughput Next-Generation Sequencing Panel for Clinical Screening of Mutations, Gene Amplifications, and Fusions in Solid Tumors.

Clinical next-generation sequencing (NGS) assay choice requires careful consideration of panel size, inclusion of appropriate markers, ability to detect multiple genomic aberration types, compatibility with low quality and quantity of nucleic acids, and work flow feasibility. Herein, in a high-volume clinical molecular diagnostic laboratory, we have validated a targeted high-multiplex PCR-based NGS panel (OncoMine Comprehensive Assay) coupled with high-throughput sequencing using Ion Proton sequencer for routine screening of solid tumors. The panel screens 143 genes using low amounts of formalin-fixed, paraffin-embedded DNA (20 ng) and RNA (10 ng).

Real-Time Genomic Characterization Utilizing Circulating Cell-Free DNA in Patients with Anaplastic Thyroid Carcinoma.

Background: Anaplastic thyroid carcinoma (ATC) is an aggressive disease that requires rapid diagnosis and multimodality treatment. Recent advances in targeted therapeutics have provided ATC patients with previously unavailable treatment options, which may improve clinical outcomes in the coming years. Continued development of high-throughput next-generation sequencing provides clinicians with an unparalleled ability to characterize the genomic background of tumors in order to guide treatment selection and clinical trial enrollment.

Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe-Based Single-Nucleotide Polymorphism Array.

Gene copy number aberrations (CNAs) represent a major class of cancer-related genomic alterations that drive solid tumors. Comprehensive and sensitive detection of CNAs is challenging because of often low quality and quantity of DNA isolated from the formalin-fixed, paraffin-embedded (FFPE) solid tumor samples. Here, in a clinical molecular diagnostic laboratory, we tested the utility and validated a molecular inversion probe-based (MIP) array to routinely screen for CNAs in solid tumors.

Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.

Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients.

Identification of Factors Affecting the Success of Next-Generation Sequencing Testing in Solid Tumors.

Objectives: Clinical laboratories are rapidly implementing next-generation sequencing (NGS) tests for mutation analysis, but there are few guidelines regarding sample quality for successful results.

Methods: We aimed to establish tissue quality parameters for successful NGS in solid tumors and to improve NGS performance.

Results: Analysis of 614 clinical cases tested in 2013 using a 50-gene hotspot mutation panel identified the major cause for unsuccessful NGS analysis was DNA less than 10 ng (91%, 67/74) associated with extremely small and low cellularity samples.

Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS.

Isolated isochromosome 17q, i(17q), accounts for less than 1% of myeloid neoplasms that are commonly classified as myelodysplastic/myeloproliferative neoplasms, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). We have shown previously that these cases have distinctive clinicopathologic features, a poor prognosis and absence of TP53 mutations. However, their molecular mutation profile has not been studied.

Single-Cell Quantitative PCR: Advances and Potential in Cancer Diagnostics.

Tissues are heterogeneous in their components. If cells of interest are a minor population of collected tissue, it would be difficult to obtain genetic or genomic information of the interested cell population with conventional genomic DNA extraction from the collected tissue. Single-cell DNA analysis is important in the analysis of genetics of cell clonality, genetic anticipation, and single-cell DNA polymorphisms.