Association of Target Volume Margins With Locoregional Control and Acute Toxicities for Non-small cell lung cancer Treated With Concurrent Chemoradiation Therapy

Purpose

This study aimed to investigate the association between target volume margins and clinical outcomes for patients with inoperable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy.

Acceptability of human papillomavirus vaccination among medical students in Mangalore,India

Background

The highly prevalent cervical cancer can be prevented through a vaccine. However, the uptake of the Human Papillomavirus vaccine in the general population continues to be low. Medical students, as healthcare providers in the future, would be influential in affecting the community's views and thereby the uptake of the Human Papillomavirus vaccine. Hence, there is a need to promote the right attitude for prompt implementation of this vaccine among medical students. None of the studies in India have so far documented the proportion of vaccinated population among medical students or an intervention strategy to eliminate the barriers to Human Papillomavirus vaccine.

Subacute sclerosing panencephalitis resembling Rasmussen’s encephalitis on magnetic resonance imaging

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressing but invariably fatal disease that is related to a prior measles virus infection and most commonly affects paediatric patients. Magnetic resonance (MR) imaging is the modality of choice for determining such changes in white matter. SSPE typically demonstrates bilateral but asymmetric periventricular and subcortical white matter involvement. We herein report a rare case of unilateral white matter involvement in a 13-year-old boy with SSPE that closely simulated Rasmussen’s encephalitis. To the best of our knowledge, this is the first report of an atypical presentation on MR imaging in which SSPE was a rare cause of unilateral brain parenchymal involvement in a patient with intractable seizures.     

Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Narratives of Food Insecurity in Tippecanoe County,Indiana: Economic Constraints in Local Meanings of Hunger

Food insecurity and its most extreme form, hunger, have increased exponentially in the United States since 2006. This essay seeks to contribute to our understanding of hunger by attending to the context of the financial crisis as an organizing frame for understanding local meanings of hunger. Within a broader framework of the culture-centered approach (CCA) that works to identify and develop locally rooted solutions to food insecurity, we describe through locally grounded stories of food insecurity the financial climate where large percentages of U.S. households have been cast into poverty because of the crash of an unregulated economy. These local understandings of hunger in the context of the economy offer entry points for organizing a food-insecure coalition that seeks to address the stigma around food insecurity.     

Digitally Enabled,Patient‐Centric Clinical Trials: Shifting the Drug Development Paradigm

The rapidly advancing field of digital health technologies provides a great opportunity to radically transform the way clinical trials are conducted and to shift the clinical trial paradigm from a site‐centric to a patient‐centric model. Merck’s (Kenilworth, NJ) digitally enabled clinical trial initiative is focused on introduction of digital technologies into the clinical trial paradigm to reduce patient burden, improve drug adherence, provide a means of more closely engaging with the patient, and enable higher quality, faster, and more frequent data collection. This paper will describe the following four key areas of focus from Merck’s digitally enabled clinical trials initiative, along with corresponding enabling technologies: (i) use of technologies that can monitor and improve drug adherence (smart dosing), (ii) collection of pharmacokinetic (PK), pharmacodynamic (PD), and biomarker samples in an outpatient setting (patient‐centric sampling), (iii) use of digital devices to collect and measure physiological and behavioral data (digital biomarkers), and (iv) use of data platforms that integrate digital data streams, visualize data in real‐time, and provide a means of greater patient engagement during the trial (digital platform). Furthermore, this paper will discuss the synergistic power in implementation of these approaches jointly within a trial to enable better understanding of adherence, safety, efficacy, PK, PD, and corresponding exposure‐response relationships of investigational therapies as well as reduced patient burden for clinical trial participation. Obstacle and challenges to adoption and full realization of the vision of patient‐centric, digitally enabled trials will also be discussed.

The rapidly advancing field of digital health technologies provides an opportunity to transform the pharmaceutical industry and the way clinical trials are conducted. Although the conduct of clinical trials has evolved over the last century to improve the unbiased evaluation of new therapies, there remain several limitations in the current clinical trial paradigm. Pharmaceutical clinical trials are often site‐centric, requiring patients to come to the clinical site for sample and data collection. The need to travel to the clinical site often restricts the trial population to those that live in geographic proximity to the clinical site, and, thus, restricts who participates and limits patient diversity, leaving many patients excluded and underserved. ¹ , ² , ³ , ⁴ , ⁵ The current trial paradigm provides only static snapshots of data (corresponding to the time of the clinical visit), resulting in lost opportunity to monitor end points of disease progression, pharmacokinetics (PK), pharmacodynamics (PD), and safety and tolerability end points in between clinical visits. Additionally, clinical trial outcome measures may not be particularly meaningful to patients or their health care providers, and end points may be limited by categorical, episodic, subjective assessments that progress slowly, thus requiring large, long, expensive clinical trials to enable detection of meaningful change in the end point. Furthermore, patient medication adherence and persistence to therapy in clinical trials is often low, ⁶ , ⁷ limiting the researcher’s ability to adequately assess the drug’s safety, efficacy, and exposure‐response relationships. Lastly, patients often find the clinical trial language confusing and the trial’s expectation of what they are supposed to do intrusive into their daily lives, limiting the number of patients that participate in clinical trials and threatening the retention of those patients that do consent to participate. ¹ , ² , ³ , ⁴ , ⁵ The potential benefits of digital health and outpatient sampling technologies in clinical trials are tremendous. They can enable increased access to the appropriate patient population, reduced patient burden to participate, augmented, more informed, objective data sets (both in collecting and measuring existing end points at home and in access to new end points that would have been impossible to collect in the past), increased engagement with the patient, and better understanding of the patient experience throughout the trial. All these benefits will ultimately improve the patient experience during the trial and enable improved drug development decisions and understanding of drug and disease effects. ⁸ Despite all these potential improvements, the relative “explosion” in both the number of digital health technologies as well as their capabilities, and an increased adoption of consumer‐grade health‐tracking devices in the marketplace, adoption of use of such technologies in pharmaceutical trials has been lagging by comparison. ⁹ , ¹⁰ , ¹¹ Some of the challenges to pharmaceutical trial adoption include questions around patient privacy, lack of sufficient validation for digital end points, lack of transparency for calculation of end points (“black box” algorithms), challenges related to patient adherence and burden of wearing and using devices, operational and data transfer challenges, and regulatory unknowns. However, use of digital end points in drug development trials, including as primary and secondary end points and to support label claims, is becoming a reality, and “pilot” trials evaluating technologies of interest, often evaluating digital end points in comparison to a traditionally accepted clinical standard end point, are being increasingly conducted. ¹² , ¹³ , ¹⁴ The digitally enabled clinical trials initiative at Merck (Kenilworth, NJ) is aimed at using innovative, digital technologies in clinical trials both at the clinical site and in at‐home settings to reduce patient burden, collect higher quality, enrich clinical trial data sets, and ultimately enable more rapid and informed clinical decisions. We ultimately aim to shift the clinical trial paradigm from one that is site‐centric to patient‐centric. Key areas of focus include (i) collection of at‐home PK, PD, and biomarker samples (outpatient sampling), (ii) use of technologies to monitor and improve patient adherence (smart dosing), (iii) use of digital devices to collect and measure physiological and behavioral data (digital biomarkers), and (iv) development and use of data platforms that can acquire the data from digital devices, provide real‐time analytic capabilities, and maintain patient engagement throughout the trial (digital platform; Figure  1 ). Application of these components in clinical trials will lead to access to higher quality and previously unattainable data for more informed clinical decision making.Open in a separate windowFigure 1Areas of focus for digitally enabled clinical trials.This paper describes the four key areas of focus of our digitally enabled clinical trials initiative and reviews corresponding enabling technologies. Furthermore, this paper discusses the synergistic power in implementation of these approaches jointly within a trial to enable a more accurate understanding of adherence, safety, PK, and corresponding exposure‐response relationships of investigational new drugs (INDs) as well as reduced patient burden for clinical trial participation. Obstacles and challenges to adoption and fully realizing the vision of patient‐centric, digitally enabled trials are also discussed.