Home nursing in clinical trials: Result from semi-structured qualitative interviews.

There is a need to transition from conventional (on-site) clinical trials (CTs) to trials conducted within the comfort of a patient's home or community (decentralized CT) through e-consent, remote data monitoring, and telemedicine consults. This shift in trial procedures will positively impact recruitment rates, compliance and participant retention, protocol deviations, and delays or missed visits. Home nursing in CTs (HNCTs) will be an important component of this decentralization effort. A few limitations may impact the implementation of HNCT in India. In this regard, the workstream conducted semi-structured qualitative interviews with experts from diverse domains of CT conduct (researchers from academia and industry, clinicians, investigators, nursing staff, patient research advocates, institutional ethics committee, or institutional review board members, legal experts, and trial participants) to collect their understanding, perspectives, and the ground realities about HNCTs in India. The current review puts forth the key areas that would facilitate the establishment of HNCTs in India and provides recommendations for the same.

Daridorexant, a Recently Approved Dual Orexin Receptor Antagonists (DORA) in Treatment of Insomnia.

Insomnia is one of the major challenges in medical science nowadays as it leads to great socio-economic burden by impairing daytime function as well as the development of exhaustion, depression, and memory disturbance in affected individuals. Several important classes of drugs have been tried, including the BZDs and non-BZD hypnotics. Available drugs to combat this disease have the limitations of abuse potential, tolerance, and cognitive impairment. In some instances, withdrawal symptoms have been observed upon the abrupt cessation of those drugs. The Orexin system has been very recently targeted as a therapeutic option to overcome those limitations. Treatment of insomnia with Daridorexant as a Dual Orexin Receptor Antagonist (DORA) has been evaluated in several preclinical and clinical studies. Available information obtained from those studies has shown a promising future for this drug in the management of insomnia. Beyond its effectiveness in insomnia, it has been successfully used in patients suffering from obstructive sleep apnoea, chronic obstructed airway disease (COAD), Alzheimer's disease (AD), hypertension, and cardiovascular disorders. Larger studies need to address the safety issues as well as obtain robust pharmacovigilance information to safeguard the risk-benefit aspect of this drug in insomniac adults.

Daridorexant, a Recently Approved Dual Orexin Receptor Antagonists (DORA) in the Treatment of Insomnia.

Insomnia is one of the major challenges in medical science nowadays as it leads to the great socio-economic burden by impairing daytime function as well as the development of exhaustion, depression and memory disturbance in affected individuals. Several important classes of drugs have been tried including the BZDs and Non-BZD hypnotics. Available drugs to combat this disease have the limitations of abuse potential, tolerance and cognitive impairments. In some instances, withdrawal symptoms have been observed on abrupt cessation of those drugs. The Orexin system has been very recently targeted as a therapeutic option to overcome those limitations. Daridorexant as a Dual Orexin Receptor Antagonists (DORA) in the treatment of insomnia has been evaluated in several preclinical and clinical studies. Available information obtained from those studies has shown promising future for this drug in the management of insomnia. Beyond its effectiveness in insomnia, it has been successfully used in patients suffering from Obstructive sleep apnoea, Chronic Obstructive Airway Disease (COAD), Alzheimer's Disease (AD), hypertension and cardiovascular disorders. Larger studies need to address the safety issues as well as obtain robust pharmacovigilance information to safeguard the risk-benefit aspect of this drug in insomniac adults.

Cefiderocol: A new Antimicrobial for Complicated Urinary Tract Infection (CUTI) Caused by Carbapenem-resistant Enterobacteriaceae (CRE).

The incidence of carbapenem-resistant gram-negative (CRGNB) bacterial infections has increased globally. The wide diversity of strains, multiplicity of infections, and rapid development and spread of resistance are a matter of great concern both in community and hospital settings. Cefiderocol is a novel injectable siderophore containing cephalosporin with potent microbicidal activity against most carbapenem-resistant Enterobacteriaceae (CRE). It has recently been approved by USFDA for the treatment of complicated urinary tract infections (cUTI) caused by susceptible gram-negative microorganisms. This review focuses on the salient pharmacological profile of the drug and the clinical studies that were undertaken. Cefiderocol is first in class injectable siderophore cephalosporin showing potency against carbapenem- resistant Enterobacteriaceae. It has recently been approved by US FDA for the treatment of adult patients with complicated urinary tract infections (cUTI) caused by susceptible Gram-negative microorganisms, where there are limited or no alternative treatment options.

Digital clinical trial: A new norm in clinical research.

The advent of digital technologies has been well blended with every aspect of human lives. Despite not being a new concept, the adoption of digital health technologies in clinical research, i.e., digital clinical trial has not been utilized extensively. However, with the prevailing COVID-19 pandemics, such transformation in clinical trial seems imminent. Few components of a trial such as consent, remote site monitoring, recruitment process which can be modified through digital technologies, are further specified by the regulatory authorities such as FDA and EMA. However, such novel method cannot be implemented without facing any limitations. All stakeholders pertinent to virtual clinical trial including the provider of digital technologies should align themselves with the patient-centric approach to propagate this concept. It is expected that such a transition is well accomplished and adopted by the sponsors without any compromise in scientific as well as ethical standard.

Hypertension Clinical Practice Guidelines (ISH, 2020): What Is New?

OBJECTIVE: In May 2020, the International Society of Hypertension (ISH) published "Practice Guidelines for the Management of Hypertension." The ISH 2020 guidelines were developed based on evidence criteria (i) to be used globally, (ii) to be fit for application in low-middle-income and high-income settings, and (iii) to be concise, simple, and easy to use by clinicians, nurses, and community health workers, as appropriate. The defined purpose was to adhere to the current evidence and develop a balanced proposal for global use in line with the ISH mission. METHODOLOGY: Multiple novel approaches have been included keeping in mind about lifestyle modification and flexibility in treatment options. RESULTS AND CONCLUSIONS: The ISH 2020 guidelines are practical and physician friendly. It also proves immensely helpful for low-resource countries without national guidelines on the management of hypertension.

Impact of oral anticholinergic on insulin response to oral glucose load in patients with impaired glucose tolerance.

BACKGROUND: Preliminary data indicates there is a cholinergic basis to insulin secretion. AIMS & OBJECTIVE: To investigate the impact of oral anticholinergics on insulin secretion in subjects with impaired glucose tolerance (IGT), in comparison with volunteers having normal glucose tolerance (NGT). Material & Methods: This prospective observational study recruited 10 IGT and 10 NGT subjects. An oral glucose tolerance test (OGTT) was conducted twice in the absence and presence of hyoscine butyl-bromide (HBB). The plasma glucose (PG) and insulin levels were serially estimated at 30-min increments for 2 h after the OGTT. Early (ΔI30/ΔPG30) & late (insulin/PGAUC 60-120) phase insulin activity were assessed subsequently. RESULTS: The study constituted of 10 IGT (4M/6F, BMI: 28.80 ± 2.30) and 10 NGT (5M/5F, BMI: 23.00 ± 0.80) subjects. In the NGT group, the pre-HBB mean glucose levels (0-120 min) were comparable with those recorded after HBB intake. However, after HBBB, the mean insulin levels decreased significantly at t = 90 and 120min, confirmed by attenuated late phase insulin activity in IGT (P = 0.023) & NGT (P = 0.006) group. On the other hand, in the IGT group, however, HBB did not impact on the mean PG and insulin levels (0-120 min). CONCLUSIONS: Our study findings indicate that insulin secretion is influenced by cholinergic system and that oral anticholinergics may attenuate the late phase insulin activity in varying degrees of glycemic status.

Immunohistochemical analysis of beta-catenin expression: a probable prognostic marker and potential therapeutic target in renal cell carcinoma.

BACKGROUND AND AIMS: Renal cell carcinoma (RCC) seems to be the most aggressive type of genitourinary neoplasm. Down regulation of normal beta-catenin expression contributes to development of RCC, reflecting the role of beta-catenin/Wnt signaling pathway in pathogenesis. This study aims to evaluate the significance of beta-catenin expression and its correlation with the prognostic parameters. METHODS: A cross-sectional observational study was carried out in a tertiary care center on 58 RCC cases using variables like histological grade and type, tumor stage, necrosis. Formalin fixed, paraffin-embedded blocks were evaluated for beta-catenin expression by immunohistochemistry using scoring system. Data were analyzed by mean ± SD, χ2 test, Pearson's correlation test. RESULTS: Membranous score (MS) had a strong negative correlation with tumor stage (r=-0.407, p=0.044) and grade (r=-0.787, p=<0.001). Mean membranous score difference between low (Stage 1 and 2) vs. high stage (Stage 3 and 4) and low (Grade 1 and 2) vs. high grade (Grade 3 and 4) was statistically significant (p<0.001). Cytoplasmic score (CS) had positive correlation with tumor stage (r=0.586; p=0.002). No significant correlation was evident between cytoplasmic scores and tumor grade, however the mean cytoplasmic score difference between low grade vs. high grade was statistically significant (p < 0.001). CONCLUSION: Beta-catenin may play a crucial role in the pathogenesis of RCC and has a positive correlation with the biological behavior of this tumor. The important role of beta-catenin as a prognostic parameter and probably a critical evaluator of targeted chemotherapy cannot be overemphasized.

Accelerated drug approvals in oncology: Pros and cons.

The inevitable surge of the accelerated approval process, especially for oncology drugs, has been a success story. However, the use of surrogate end-points and its validation has been debatable over the years. Over the years, US Food and Drug Administration has been rigorously working for the validation of these end-points to capture the real clinical benefit and appropriateness of clinical study designs. However, the high cost imposed by the manufacturer attributed to the faster drug access can be prohibitive and well undermine the whole process. We discuss issues that must be addressed and solved accordingly for managed care in oncology.

Past, Present, and Future of Remdesivir: An Overview of the Antiviral in Recent Times.

In the current COVID-19 pandemic, evidence to justify the use of any specific antiviral drug with proven efficacy is not yet available. Antiviral drug development always remains a challenge to the scientists. Remdesivir has emerged as a promising molecule, based on results of clinical trials and observational studies and has receieved marketing approval for COVID-19 treatment under "emergency use authorization" in countries such as United States. Remdesivir is a newer antiviral drug that acts as an RNA-dependent RNA polymerase (RdRp) inhibitor targeting the viral genome replication process. Therapeutic efficacy was first demonstrated by suppressing viral replication in Ebola-infected rhesus monkeys. It is available for parenteral use with reasonable safety and tolerability profile. Multiple clinical trials are going on in many countries to evaluate its safety, efficacy and tolerability. Positive outcome will make the drug capable of meeting the demand generated by both the current pandemic and future outbreak. HOW TO CITE THIS ARTICLE: Choudhury S, Chakraborty DS, Lahiry S, Chatterjee S. Past, Present, and Future of Remdesivir: An Overview of the Antiviral in Recent Times. Indian J Crit Care Med 2020;24(7):570-574.

Career Planning for Physicians Within the Pharmaceutical Industry.

Transitioning into 'pharma' is a challenging career decision since it is very different from working in individual patient care. However, for many, the opportunity to develop innovative medicines, communicate their benefits, and, thus, influence the care of thousands of patients at a time is a rewarding alternative. The current paper explores the "Why-What-How" of successful physician careers within the pharmaceutical industry, realizing both professional and philosophical perspectives.

Real-world perspective on career of pharmaceutical physicians in India: A working report (2018).

BACKGROUND: Pharmaceutical physicians support drug development in various capacities and contribute tremendously to the healthcare system. However, there is lack of substantial information on career progression of pharmaceutical physicians in India. MATERIALS AND METHODS: This cross-sectional survey involved distribution of a questionnaire via internet, to be self-administered and returned electronically from March 1, 2018, to May 31, 2018 (3 months). Respondents were pharmaceutical physicians from India. RESULTS: Of the 410 surveyed across 32 specialties, 197 completed responses (48%) were analyzed. Top physician specialty noted was Pharmacology. Medical Advisors constituted bulk responders. Oncology and Medical Affairs were the preferred therapeutic segment and portfolio, respectively. Medical affairs also recorded the highest physician recruitment and retention figures. Majority cited a need for Pharmaceutical Medicine as a specialty curriculum in India. 'MBA' was perceived to be nonenabling for entry-level hires; sensitization through 'industry apprenticeship' was highly recommended in this regard. Better work-life balance and aversion to clinical work were top reasons for physician influx in the industry. Important challenges at workplace included diversified work and difficult colleagues. Work-related issues were a common basis for most job attritions. Annual compensation figures ranged from INR 10-20 Lakhs (at entry-level) to INR 30-40 Lakhs (at senior-manager level); however, salary dissatisfaction was prevalent (58%). Lack of information and aversion to corporate work culture were top reasons for physician hesitancy when considering career options in the pharmaceutical industry. CONCLUSION: A career in pharmaceutical medicine has tremendous scope for young medical graduates. One should thoroughly explore such career option and inculcate a learner-centric approach.

Suboptimal compliance to aerosol therapy in pediatric asthma: A prospective cohort study from Eastern India.

BACKGROUND: Suboptimal compliance to aerosol medication is common in pediatric asthma. Accordingly, the objective of this study is to assess noncompliance to aerosol therapy in childhood asthma and determine contributory factors. MATERIALS AND METHODS: A prospective cohort study was conducted among pediatric patients attending asthma clinic. Patients (n = 215) having "mild" and "moderate" asthma severity rating were included. The total study duration was 12 months (June 2016-June 2017), with an active recruitment phase of 6 months. The minimum period for follow-up was 90 days. Caregivers were instructed to maintain an "asthma diary" for daily dosages of inhalers. At follow-up, the diary entries were corroborated with the amount of inhaler medication unused. Subsequently, medication compliance ratio (CR) was calculated according to the following formula: CR = number of medication doses taken/number of medication doses prescribed. CR% >80 was considered as "good compliance". RESULTS: A total of 169 patients (78.6%) returned for follow-up. The mean compliance to asthma medication was suboptimal (75.3%). The children were primarily prescribed inhaled corticosteroids and short-acting beta-agonist (SABA)-based regimens on index visit. Leukotriene receptor antagonist was added in select cases (67.9%). Nearly 45.6% of the patients had "good compliance." CR correlated with the sociodemographic profile and disease severity. Higher socioeconomic status and proper inhaler technique reflected better symptom control. Fear of side effects, behavioral difficulties, and economic restrictions were the identified causes of medication default. CONCLUSION: In the Eastern part of India, compliance to aerosol therapy in pediatric asthma is suboptimal. Sociodemographics, disease severity, and inhaler technique are important determinants.

Advances in Vasodilatory Shock: A Concise Review.

Vasodilatory shock is a critical manifestation of cardiovascular failure. There is uncontrolled vasodilation and vascular hyporesponsiveness to endogenous vasoconstrictors, causing the failure of physiologic vasoregulatory mechanisms. Unfortunately, only few randomized studies exist to guide clinical management and hemodynamic stabilization in patients who do not respond to the standard approach of managing vasodilatory shock. The present review offers the latest updates in management of this important clinical entity and a guidance framework for future research. HOW TO CITE THIS ARTICLE: Lahiry S, Thakur S, Chakraborty DS. Advances in Vasodilatory Shock: A Concise Review. Indian J Crit Care Med 2019;23(10):475-480.

The National Guidelines for Stem Cell Research (2017): What academicians need to know?

India recently updated its guidelines on stem cell research (SCR), the National Guidelines for Stem Cell Research 2017. It was drafted under a collaborative effort from the Indian Council of Medical Research and Department of Biotechnology. The new guidelines are a part of a continuous endeavor to tackle scientific, technical, as well as perceived challenges in the field of SCR. It seeks to facilitate safe, ethical, and regulated translational and clinical SCR by engaging all stakeholders proactively.