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PURPOSEThe effectiveness of a dexamethasone (DEX)-free regimen for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) is not known.METHODSThis was a double-blind, phase III trial designed to show the noninferiority of a DEX-free regimen (olanzapine, palonosetron, and fosaprepitant [OPF]) compared with the DEX-containing regimen (olanzapine, palonosetron, and DEX [OPD]). Chemotherapy-naïve patients age 18-80 years receiving single-day HEC were randomly assigned 1:1 to receive either the OPD regimen or the OPF regimen. The primary objective was to compare complete response (CR) rates for vomiting during the overall period (start of chemotherapy to 120 hours). Secondary objectives included CR for vomiting during the acute period (0-24 hours) and delayed period (24-120 hours), CR for nausea, and comparison of toxicities and patient-reported outcomes.RESULTSThree hundred forty-six patients received the study interventions, 174 in the OPD arm and 172 in the OPF arm. The DEX-free OPF arm had significantly higher CR rates for vomiting compared with the DEX-containing OPD arm in acute (94.7% v 85.6%; P < .004), delayed (81.9% v 50.5%; P < .001), and overall (79.6% v 48.8%; P < .001) periods. For nausea, CR rates in the OPF arm were higher in delayed (53.4% v 39.6%; P = .009) and overall (50.5% v 39.1%; P = .031) periods but not in the acute period (77.9% v 81.6%; P = .39). Fatigue (P = .009) and drowsiness (P = .002) were more in the OPF arm in the acute period and insomnia (P < .001) in the OPD arm in the overall period.CONCLUSIONThis study shows that a DEX-free OPF regimen is efficacious and should be considered a standard option for acute and delayed CINV prophylaxis for HEC.

Abstract Benchtop tissue cultures have become increasingly complex in recent years, as more on-a-chip biological technologies, such as microphysiological systems (MPS), are developed to incorporate cellular constructs that more accurately represent their respective biological systems. Such MPS have begun facilitating major breakthroughs in biological research and are poised to shape the field in the coming decades. These biological systems require integrated sensing modalities to procure complex, multiplexed datasets with unprecedented combinatorial biological detail. In this work, we expanded upon our polymer-metal biosensor approach by demonstrating a facile technology for compound biosensing that was characterized through custom modeling approaches. As reported herein, we developed a compound chip with 3D microelectrodes, 3D microfluidics, interdigitated electrodes (IDEs) and a microheater. The chip was subsequently tested using the electrical/electrochemical characterization of 3D microelectrodes with 1 kHz impedance and phase recordings and IDE-based high-frequency (~1 MHz frequencies) impedimetric analysis of differential localized temperature recordings, both of which were modeled through equivalent electrical circuits for process parameter extraction. Additionally, a simplified antibody-conjugation strategy was employed for a similar IDE-based analysis of the implications of a key analyte (l-glutamine) binding to the equivalent electrical circuit. Finally, acute microfluidic perfusion modeling was performed to demonstrate the ease of microfluidics integration into such a polymer-metal biosensor platform for potential complimentary localized chemical stimulation. Overall, our work demonstrates the design, development, and characterization of an accessibly designed polymer-metal compound biosensor for electrogenic cellular constructs to facilitate comprehensive MPS data collection.

With the increasing incidence of diverse global bacterial outbreaks, it is important to build an immutable decentralized database that can capture regional changes in bacterial resistance with time. Herein, we investigate the use of a rapid 3D printed µbiochamber with a laser-ablated interdigitated electrode developed for biofilm analysis of Pseudomonas aeruginosa, Acinetobacter baumannii and Bacillus subtilis using electrochemical biological impedance spectroscopy (EBIS) across a 48 h spectrum, along with novel ladder-based minimum inhibitory concentration (MIC) stencil tests against oxytetracycline, kanamycin, penicillin G and streptomycin. Furthermore, in this investigation, a search query database has been built demonstrating the deterministic nature of the bacterial strains with real and imaginary impedance, phase, and capacitance, showing increased bacterial specification selectivity in the 9772.37 Hz range.

Abstract The benefit of three-drug induction chemotherapy over a two-drug induction has not been evaluated in pediatric acute myeloid leukemia (AML). We, therefore, conducted a randomized controlled trial to ascertain the benefit of a three-drug induction regimen. Patients aged 1–18 years with newly diagnosed AML were randomized to two cycles of induction chemotherapy with daunorubicin and ara-C (DA) or two cycles of ara-C, daunorubicin, and etoposide (ADE). After induction, patients in both arms received consolidation with two cycles of high-dose ara-C. The study’s primary objective was to compare the event-free survival (EFS) between the two arms. The secondary objectives included comparing the composite complete remission (cCR) rates, overall survival (OS), and toxicities. The study randomized 149 patients, 77 in the DA and 72 in the ADE arm. The median age was 8.7 years, and 92 (62%) patients were males. The median follow-up was 50.9 months. The cCR rate in the DA and ADE arm were 82% and 79% (p = 0.68) after the second induction. There were 13 (17%) induction deaths in the DA arm and 12 (17%) in the ADE arm (p = 0.97). The 5-year EFS in the DA and ADE arm was 34.4% and 34.5%, respectively (p = 0.66). The 5-year OS in the DA and ADE arms was 41.4% and 42.09%, respectively (p = 0.74). There were no significant differences in toxicities between the regimens. There was no statistically significant difference in EFS, OS, CR, or toxicity between ADE and DA regimens in pediatric AML. The trial was registered with the Clinical Trial Registry of India (Reference number: CTRI/2014/11/005202).

Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two varied antigenic sources and a good manufacturing practice (GMP)-compliant, manual method for generating clinical-grade DCs at a limited-resource academic setting. After obtaining ethical committee-approved informed consent, the recruited patients underwent leukapheresis, and single-batch DC production was carried out. Using responder-independent flow cytometric assays as quality control (QC) criteria, we propose a differentiation and maturation index (DI and MI, respectively), calculated with the QC cut-off and actual scores of each batch for comparison. Changes during cryopreservation and personnel variation were assessed periodically for up to two to three years. Using our harmonized batch production protocol, the average DI was 1.39 and MI was 1.25. Allogenic responder proliferation was observed in all patients, while IFN-gamma secretion, evaluated using flow cytometry, was detected in 10/36 patients and significantly correlated with CD8+ T cell proliferation (p value-0.0002). Tracking the viability and phenotype of cryopreserved MDCs showed a >90% viability for up to three years, while a mature DC phenotype was retained for up to one year. Our results confirm that the manual/semi-automated protocol was simple, consistent, and cost-effective, without the requirement for expensive equipment and without compromising on the quality of the final product.

Objectives In resource-constrained settings, cancer epidemiology research typically relies on self-reported diagnoses. To test a more systematic alternative approach, we assessed the feasibility of linking a cohort with a cancer registry.Setting Data linkage was performed between a population-based cohort in Chennai, India, with a local population-based cancer registry.Participants Data set of Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) cohort participants (N=11 772) from Chennai was linked with the cancer registry data set for the period 1982–2015 (N=140 986).Methods and outcome measures Match*Pro, a probabilistic record linkage software, was used for computerised linkages followed by manual review of high scoring records. The variables used for linkage included participant name, gender, age, address, Postal Index Number and father’s and spouse’s name. Registry records between 2010 and 2015 and between 1982 and 2015, respectively, represented incident and all (both incident and prevalent) cases. The extent of agreement between self-reports and registry-based ascertainment was expressed as the proportion of cases found in both data sets among cases identified independently in each source.Results There were 52 self-reported cancer cases among 11 772 cohort participants, but 5 cases were misreported. Of the remaining 47 eligible self-reported cases (incident and prevalent), 37 (79%) were confirmed by registry linkage. Among 29 self-reported incident cancers, 25 (86%) were found in the registry. Registry linkage also identified 24 previously not reported cancers; 12 of those were incident cases. The likelihood of linkage was higher in more recent years (2014–2015).Conclusions Although linkage variables in this study had limited discriminatory power in the absence of a unique identifier, an appreciable proportion of self-reported cases were confirmed in the registry via linkages. More importantly, the linkages also identified many previously unreported cases. These findings offer new insights that can inform future cancer surveillance and research in low-income and middle-income countries.

Objectives: To identify risk factors associated with Coronavirus disease 2019 (COVID-19) in a Tertiary care cancer hospital-based cluster and recommend control measures. Methods: We conducted tracing and confirmation among hospital and community contacts. We telephonically interviewed and abstracted information from hospital records and registers. We described the cluster by time, place and person. We conducted unmatched case-control study to compare risk factors and computed Odds Ratio (OR) and 95% confidence interval. Results: We confirmed COVID-19 in 21 of 1478 tested (1.4%). Secondary attack (%) of COVID-19 among 824 contacts was higher among in-patients of block A (18), household contacts (3.4), housekeeping staff (3.3) and nurses (1.7). The cluster started on April 22 with two successive peaks five days apart and lasted until May 8. Being male, patients aged >33 years [OR = 30·7; 95% CI = 3·6 to 264], having hypertension [OR = 4·3; 95% CI = 1·1 to 16·7] or diabetes [OR = 3·8; 95% CI = 1·0 to 14·1] were associated with COVID-19. Mask compliance was poor (20%) among hospital workers. Discussion: We recommended screening of all patients for diabetes and hypertension and isolation/testing of anyone with influenza-like illness for preventing COVID-19 clusters in hospital settings.

Plotter cutters in stencil mask prototyping are underutilized but have several advantages over traditional MEMS techniques. In this paper we investigate the use of a conventional plotter cutter as a highly effective benchtop tool for the rapid prototyping of stencil masks in the sub-250 μm range and characterize patterned layers of organic/inorganic materials. Furthermore, we show a new diagnostic monitoring application for use in healthcare, and a potential replacement of the Standard Kirby-Bauer Diffusion Antibiotic Resistance tests was developed and tested on both Escherichia coli and Xanthomonas alfalfae as pathogens with Oxytetracycline, Streptomycin and Kanamycin. We show that the reduction in area required for the minimum inhibitory concentration tests; allow for three times the number of tests to be performed within the same nutrient agar Petri dish, demonstrated both theoretically and experimentally resulting in correlations of R ≈ 0.96 and 0.985, respectively for both pathogens.

Objectives To determine current tobacco use in 2018/2019, quit attempts made and to explore the enablers and barriers in quitting tobacco among tobacco users identified in the Tamil Nadu Tobacco Survey (TNTS) in 2015/2016.Setting TNTS was conducted in 2015/2016 throughout the state of Tamil Nadu (TN) in India covering 111 363 individuals. Tobacco prevalence was found to be 5.2% (n=5208).Participants All tobacco users in 11 districts of TN identified by TNTS (n=2909) were tracked after 3 years by telephone. In-depth interviews (n=26) were conducted in a subsample to understand the enablers and barriers in quitting.Primary and secondary outcomes Current tobacco use status, any quit attempt and successful quit rate were the primary outcomes, while barriers and enablers in quitting were considered as secondary outcomes.Results Among the 2909 tobacco users identified in TNTS 2015/2016, only 724 (24.9%) could be contacted by telephone, of which 555 (76.7%) consented. Of those who consented, 210 (37.8%) were currently not using tobacco (ie, successfully quit) and 337 (60.7%) continued to use any form of tobacco. Of current tobacco users, 115 (34.1%) have never made any attempt to quit and 193 (57.3.8%) have made an attempt to quit. Those using smoking form of tobacco products (adjusted relative risk (aRR)=1.2, 95% CI: 1.1 to 1.4) and exposure to smoke at home (aRR=1.2, 95% CI: 1.1 to 1.3) were found to be positively associated with continued tobacco use (failed or no quit attempt). Support from family and perceived health benefits are key enablers, while peer influence, high dependence and lack of professional help are some of the barriers to quitting.Conclusion Two-thirds of the tobacco users continue to use tobacco in the last 3 years. While tobacco users are well aware of the ill-effects of tobacco, various intrinsic and extrinsic factors play a major role as a facilitator and lack of the same act as a barrier to quit.

Purpose: Cancer-related stigma influences the way people perceive cancer, which renders cancer control—beginning with prevention and proceeding to palliation—a challenging task. This study aimed to assess the current levels of awareness and perceptions about cancer among people with various socioeconomic status and diverse backgrounds in the city of Chennai, India. Patients and Methods: The sample population (N = 2,981; 18 to 88 years of age) was stratified into four groups: patients (n = 510), caregivers (n = 494) consulting at the Cancer Institute (Women Indian Association), college students (n = 978), and general public (n = 999). Fourteen statements related to cancer stigma or myths were identified and categorized by awareness (10 items) or perception (4 items). Responses to those statements were recorded by using a Likert scale (yes, no, and don’t know). The data were described by frequency analysis and χ2 test using SPSS Version 13 (SPSS, Chicago, IL). Results: More than 70% of the study participants were aware that cancer is curable, that cancer is not contagious, and that cancer is not a curse or a death sentence. However, only approximately half believed that surgery or biopsy do not cause cancer to spread to other organs or that radiation therapy does not consist of receiving an electric shock. Higher education, younger age, male sex, personal experience with cancer (either as a patient or caregiver), and high socioeconomic status were the categories of people with increased awareness about cancer. Conclusion: These factors need to be taken into consideration in tailoring information, education, and communication campaigns. Resource allocation for these campaigns is an investment in cancer control.

The widespread adaptation of 3D printing in the microfluidic, bioelectronic, and Bio-MEMS communities has been stifled by the lack of investigation into the biocompatibility of commercially available printer resins. By introducing an in-depth post-printing treatment of these resins, their biocompatibility can be dramatically improved up to that of a standard cell culture vessel (99.99%). Additionally, encapsulating resins that are less biocompatible with materials that are common constituents in biosensors further enhances the biocompatibility of the material. This investigation provides a clear pathway toward developing fully functional and biocompatible 3D printed biosensor devices, especially for interfacing with electrogenic cells, utilizing benchtop-based microfabrication, and post-processing techniques.

Laser micromachining is a direct write microfabrication technology that has several advantages over traditional micro/nanofabrication techniques. In this paper, we present a comprehensive characterization of a QuikLaze 50ST2 multimodal laser micromachining tool by determining the ablation characteristics of six (6) different materials and demonstrating two applications. Both the thermodynamic theoretical and experimental ablation characteristics of stainless steel (SS) and aluminum are examined at 1064 nm, silicon and polydimethylsiloxane (PDMS) at 532 nm, and Kapton® and polyethylene terephthalate at 355 nm. We found that the experimental data aligned well with the theoretical analysis. Additionally, two applications of this multimodal laser micromachining technology are demonstrated: shadow masking down to approximately 1.5 µm feature sizes and interdigitated electrode (IDE) fabrication down to 7 µm electrode gap width.

Adverse cardiac events are a major cause of late-stage drug development withdrawals. Improved in vitro systems for predicting cardiotoxicity are of great interest to prevent these events and to reduce the expenses involved in the introduction of cardiac drugs into the marketplace. Interdigitated electrodes (IDEs) affixed with a culture well provide a simple, suitable solution for in vitro analysis of cells because of their high sensitivity, ease of fabrication, and label-free, nondestructive analysis. Culturing human pluripotent stem cell differentiated cardiomyocytes onto these IDEs allows for the use of the IDE–cell combination in predictive toxicity assays. IDEs with smaller interdigitated distances allow for greater sensitivity, but typically require cleanroom fabrication. In this communication, we report the definition of a simple IDE geometry on a printed nanostructured substrate, demonstrate a Cellular Index (CI) increase from 0 to 7.7 for human cardiomyocytes, and a decrease in CI from 2.3 to 1 with increased concentration of the model drug, norepinephrine. The nanostructuring results in an increased sensitivity of our 1 mm pitch IDEs when compared to traditionally fabricated IDEs with a pitch of 10 μm (100 times larger electrode gap). The entire nanostructured IDE (nIDE) is fabricated and assembled in a rapid nanofabrication environment, thus allowing for iterative design changes and robust fabrication of devices.

We present a novel benchtop-based microfabrication technology: 3D printing, ink casting, micromachined lamination (3D PICLμM) for rapid prototyping of lab-on-a-chip (LOC) and biological devices. The technology uses cost-effective, makerspace-type microfabrication processes, all of which are ideally suited for low resource settings, and utilizing a combination of these processes, we have demonstrated the following devices: (i) 2D microelectrode array (MEA) targeted at in vitro neural and cardiac electrophysiology, (ii) microneedle array targeted at drug delivery through a transdermal route and (iii) multi-layer microfluidic chip targeted at multiplexed assays for in vitro applications. The 3D printing process has been optimized for printing angle, temperature of the curing process and solvent polishing to address various biofunctional considerations of the three demonstrated devices. We have depicted that the 3D PICLμM process has the capability to fabricate 30 μm sized MEAs (average 1 kHz impedance of 140 kΩ with a double layer capacitance of 3 μF), robust and reliable microneedles having 30 μm radius of curvature and ~40 N mechanical fracture strength and microfluidic devices having 150 μm wide channels and 400 μm fluidic vias capable of fluid mixing and transmitted light microparticle visualization. We believe our 3D PICLμM is ideally suited for applications in areas such as electrophysiology, drug delivery, disease in a dish, organ on a chip, environmental monitoring, agricultural therapeutic delivery and genomic testing.

We report on microfabrication and assembly process development on transparent, biocompatible polymers for patterning electrodes and growing electrically active cells for in vitro cell-based biosensor applications. Such biosensors are typically fabricated on silicon or glass wafers with traditional microelectronic processes that can be cost-prohibitive without imparting necessary biological traits on the devices, such as transparency and compatibility for the measurement of electrical activity of electrogenic cells and other biological functions. We have developed and optimized several methods that utilize traditional micromachining and non-traditional approaches such as printed circuit board (PCB) processing for fabrication of electrodes and growing cells on the transparent polymers polyethylene naphthalate (PEN) and polyethylene terephthalate (PET). PEN-based biosensors are fabricated utilizing lithography, metal lift-off, electroplating, wire bonding, inkjet printing, conformal polymer deposition and laser micromachining, while PET-based biosensors are fabricated utilizing post-processing technologies on modified PCBs. The PEN-based biosensors demonstrate 85–100% yield of microelectrodes, and 1-kHz impedance of 59.6 kOhms in a manner comparable to other traditional approaches, with excellent biofunctionality established with an ATP assay. Additional process characterization of the microelectrodes depicts expected metal integrity and trace widths and thicknesses. PET-based biosensors are optimized for a membrane bow of 6.9 to 15.75 µm and 92% electrode yield on a large area. Additional qualitative optical assay for biomaterial recognition with transmitted light microscopy and growth of rat cortical cells for 7 days in vitro (DIV) targeted at biological functionalities such as electrophysiology measurements are demonstrated in this paper.

Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53). Conclusion The stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers.

Background: Cancer burden in India is rapidly growing, with oral, breast, and uterine cervix being the three most commonly affected sites. It has a catastrophic epidemiological and financial impact on rural communities, the vast majority of whom are socio‐economically disadvantaged. Strengthening the health system is necessary to address challenges in the access and provision of cancer services, thus improving outcomes among vulnerable populations. Objective: To develop, test, and validate a health system capacity assessment (HSCA) tool that evaluates the capacity and readiness for cancer services provision in rural India. Methods: A multi‐method process was pursued to develop a cancer‐specific HSCA tool. Firstly, item generation entailed both a nominal group technique (to identify the health system dimensions to capture) and a rapid review of published and gray literature (to generate items within each of the selected dimensions). Secondly, tool development included the pre‐testing of questionnaires through healthcare facility visits, and item reduction through a series of in‐depth interviews (IDIs) with key local stakeholders. Thirdly, tool validation was performed through expert consensus. Results: A three‐step HSCA multi‐method tool was developed comprising: (a) desk review template, investigating policies and protocols at the state level, (b) facility assessment protocol and checklist, catering to the Indian public healthcare system, and (c) IDI topic guide, targeting policymakers, healthcare workforce, and other relevant stakeholders. Conclusions: The resulting HSCA tool assesses health system capacity, thus contributing to the planning and implementation of context‐appropriate, sustainable, equity‐focused, and integrated early detection interventions for cancer control, especially toward vulnerable populations in rural India and other low‐resource settings. [ABSTRACT FROM AUTHOR]