Good Pharmacy Practice in India: Its past, Present and Future with Need and Status in COVID 19

The pandemic of COVID-19 has highlighted the importance of emergency preparedness and response (EP and R) in India’s education, training, capacity building, and infrastructure growth. Healthcare professionals, especially pharmacy professionals (PPs) in India, continued to provide drugs, supplies, and services during the pandemic. The public-private healthcare system in India is complicated and of varying quality. Patients face problems as a result of gaps in pharmacy practice education and training, as well as a lack of clarity about pharmacists’ positions. Job requirements and effective placement of healthcare professionals in patient care, as well as on (EP and R) task forces or policy representation, are complicated by this lack of distinction. We have also seen malpractice and spurious distribution in the healthcare and pharmaceutical domain in terms of personal protective kits, medications, injectable, life-saving oxygen, and other items during this unprecedented pandemic situation. A few of the incidents are as follows. The central division police in Bangalore (the Global BPO & IT Hub of India) booked a case of bed-blocking at a private hospital and arrested three people, one of whom is an Arogya Mitra (primary contact for the beneficiaries at every empaneled hospital care provider), for allegedly extorting ₹1.20 lakh from the son of a COVID-19 patient who later passed away. At least 178 COVID-19 patients in India have died because of oxygen shortage in recent weeks. Another 70 deaths have been attributed to an oxygen shortage by patients\' families, but this has been denied by the authorities. The Allahabad High court made a remark “Death of COVID patients due to non-supply of oxygen not less than genocide” on reports circulating on social media regarding the death of COVID-19 patients due to lack of oxygen in Lucknow and Meerut. A day ago, the Delhi police busted an industrial manufacturing unit in Uttarakhand’s Kotdwar where fake Remdesivir injections were being manufactured and arrested five people. These depict the ground reality and ethical standards of good pharmacy practice in this country. There is an utmost necessity to relook and re-establish the standards of pharmacy practice in healthcare setups available in each and every corner of the country in line with guidelines provided by the World Health Organization (WHO) and the International Pharmaceutical Federation (FIP). For that, the dependency and responsibilities are very high on healthcare professionals, particularly in this pandemic situation. The pharmacy zone is adaptable, evolving, and increasingly diverse, offering a wide range of work and management opportunities to execute. PPs are human service professionals whose responsibilities include safeguarding individuals by dispensing medications based on prescriptions. Representing the world\'s third-largest medicinal services with active gathering, and in India, there are over 1,000,000 (1 million) enrolled PPs employed in various capacities and readily contributing to the country\'s well-being. Pharmacy practice, which includes clinical, community, and hospital pharmacy, is referred to as total healthcare in its true sense. Through adaptation and implementation of GPP in healthcare setup, PPs form an essential link between physicians, nurses, and patients in the social community group, with an ultimate emphasis on patient well-being and protection. To instill quality and raise the standard in this chaotic situation there are strict measures required in the country. The International Pharmaceutical Federation and World Health Organization define good pharmacy practice (GPP) as practices that meet the personal needs of patients or those using pharmacy services by offering appropriate evidence-based care. In developed countries, pharmaceutical assistance is defined as a pharmaceutical practice model that involves attitudes, ethical values, behaviors, skills, appointments, and co-responsibility to prevent diseases, promote and recovery health in an integrated manner as part of the healthcare process, highlighting, among other, the requirement that the institution fully adopts the GPP. There is a need for a GPP Program designed by the Indian Govt. or its stakeholders in the context of the Indian healthcare system and adopting “new normal” due to the unprecedented event of COVID 19 and also raising the standard and importance of GPP for the healthcare professionals in the current scenario.

INSIGHTS FROM THE AUTHOR: LISA J. HARDY

Why India Needs Oxygen More Urgently Than Vaccines was first published on Vox.com and is reprinted here with permission from the authors, Vox.com, and Vox Media, LLC. The original article (with additional links) can be accessed at URL:<https://www.vox.com/22428619/india-covid-oxygen-shortage-supply-tankers-vaccines>.

Improving oxygen capacity at ITBP Referral Hospital during the second wave of COVID-19 infections in Greater Noida, India An operative targeted intervention

Due to factors that still remain under debate, both social and virological, the COVID-19 pandemic has continued to flare up in India, particularly in northern and western areas. This has led to an incidence of approximately 350,000 cases per day and a daily death toll of around 4,000 in the weeks between the 1st and 14th May 2021. The current pandemic is testing the adaptability of the oxygen distribution and consumption. Following India’s request for support, the EU Civil Protection Mechanism coordinated the response agreed by EU Member States providing shipments of oxygen and equipment. In this scenario, our Emergency Medical Team (EMT)-2, based in Italy, organized a cargo and a twelve member team of technicians and medical professionals with the main objective of installing a novel source of oxygen. The installation of a PSA oxygen plant provided the ITBP hospital in Greater Noida, India, with a sustainable solution to combat oxygen shortage in less than 48 hours. The supply of oxygen could not be deemed a successful intervention without a proper plan to guarantee the rational use of the source so additional training was carried out. Our EMT were among the first responders in mitigating this public health crisis.

Differential Regulation of Degradation and Immune Pathways Underlies Adaptation of the Ectosymbiotic Nematode Laxus Oneistus to Oxic-Anoxic Interfaces

Eukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia is underexplored. One such animal is the marine nematode Laxus oneistus. It thrives, invariably coated by its sulfur-oxidizing symbiont Candidatus Thiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not, L. oneistus mostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also highly expressed when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, when L. oneistus was subjected to anoxic sulfidic conditions, lectin and mucin genes were also upregulated, potentially to promote the attachment of its thiotrophic symbiont. Furthermore, the nematode appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm’s Toll-like innate immunity pathway and several immune effectors (e.g., Bacterial Permeability Increasing proteins, fungicides). In conclusion, we hypothesize that, in anoxic sulfidic sand, L. oneistus upregulates degradation processes, rewires oxidative phosphorylation and by reinforces its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development.

Differential regulation of degradation and immune pathways underlies adaptation of the symbiotic nematode Laxus oneistus to oxic-anoxic interfaces

Eukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia underexplored. One such animal is the symbiotic marine nematode Laxus oneistus. It thrives, invariably coated by its sulfur-oxidizing bacterium Candidatus Thiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not, L. oneistus mostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also highly expressed when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification, chaperone-encoding genes, and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, when L. oneistus was subjected to anoxic sulfidic conditions, lectin genes were also upregulated, potentially to promote the attachment of its thiotrophic anaerobic symbiont. Furthermore, L. oneistus appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm's Toll-like innate immunity pathway and several immune effectors (e.g., Bacterial Permeability Increasing proteins, fungicides). In conclusion, we hypothesize that, in anoxic sulfidic sand, L. oneistus survives by overexpressing degradation processes, rewiring oxidative phosphorylation and by reinforcing its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development.

Investigating gene methylation signatures for fetal intolerance prediction

Pregnancy is a complicated and long procedure during one or more offspring development inside a woman. A short period of oxygen shortage after birth is quite normal for most babies and does not threaten their health. However, if babies have to suffer from a long period of oxygen shortage, then this condition is an indication of pathological fetal intolerance, which probably causes their death. The identification of the pathological fetal intolerance from the physical oxygen shortage is one of the important clinical problems in obstetrics for a long time. The clinical syndromes typically manifest five symptoms that indicate that the baby may suffer from fetal intolerance. At present, liquid biopsy combined with high-throughput sequencing or mass spectrum techniques provides a quick approach to detect real-time alteration in the peripheral blood at multiple levels with the rapid development of molecule sequencing technologies. Gene methylation is functionally correlated with gene expression; thus, the combination of gene methylation and expression information would help in screening out the key regulators for the pathogenesis of fetal intolerance. We combined gene methylation and expression features together and screened out the optimal features, including gene expression or methylation signatures, for fetal intolerance prediction for the first time. In addition, we applied various computational methods to construct a comprehensive computational pipeline to identify the potential biomarkers for fetal intolerance dependent on the liquid biopsy samples. We set up qualitative and quantitative computational models for the prediction for fetal intolerance during pregnancy. Moreover, we provided a new prospective for the detailed pathological mechanism of fetal intolerance. This work can provide a solid foundation for further experimental research and contribute to the application of liquid biopsy in antenatal care.

Arabidopsis phenotyping reveals the importance of alcohol dehydrogenase and pyruvate decarboxylase for aerobic plant growth

Alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC) are key to the establishment of the fermentative metabolism in plants during oxygen shortage. Most of the evidence that both ADH and PDC are required for plant tolerance to hypoxia comes from experiments performed by limiting oxygen in the environment, such as by exposing plants to gaseous hypoxia or to waterlogging or submergence. However, recent experiments have shown that hypoxic niches might exist in plants grown in aerobic conditions. Here, we investigated the importance of ADH and PDC for plant growth and development under aerobic conditions, long-term waterlogging and short-term submergence. Data were collected after optimizing the software associated with a commercially-available phenotyping instrument, to circumvent problems in separation of plants and background pixels based on colour features, which is not applicable for low-oxygen stressed plants due to the low colour contrast of leaves with the brownish soil. The results showed that the growth penalty associated with the lack of functional ADH1 or both PDC1 and PDC2 is greater under aerobic conditions than in hypoxia, highlighting the importance of fermentative metabolism in plants grown under normal, aerobic conditions.

Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy

It is generally accepted that metabolism is able to shape the immune response. Only recently we are gaining awareness that the metabolic crosstalk between different tumor compartments strongly contributes to the harsh tumor microenvironment (TME) and ultimately impairs immune cell fitness and effector functions. The major aims of this review are to provide an overview on the immune system in cancer; to position oxygen shortage and metabolic competition as the ground of a restrictive TME and as important players in the anti-tumor immune response; to define how immunotherapies affect hypoxia/oxygen delivery and the metabolic landscape of the tumor; and vice versa, how oxygen and metabolites within the TME impinge on the success of immunotherapies. By analyzing preclinical and clinical endeavors, we will discuss how a metabolic characterization of the TME can identify novel targets and signatures that could be exploited in combination with standard immunotherapies and can help to predict the benefit of new and traditional immunotherapeutic drugs.