Balancing Routine and Pandemic: The Synergy of India's Universal Immunization Program and COVID-19 Vaccination Program.

The COVID-19 pandemic posed substantial challenges to healthcare systems globally and severely disrupted essential health services, including routine immunization programs. In India, these disruptions were exacerbated due to the sudden emergence of the pandemic and lockdown measures, leading to mass migrations and a shortage of healthcare workers. Caregivers' concerns about routine immunization sessions further compounded the problem, resulting in a sharp increase in zero-dose children. This review paper examines India's strategies for conducting one of the world's largest COVID-19 vaccination programs while effectively restoring and perpetuating its Universal Immunization Program (UIP). The UIP played a pivotal role in sustaining immunization services during the pandemic, ultimately improving immunization coverage compared to pre-pandemic levels. India's accomplishments in this regard are highlighted through key performance indicators, the reach of immunization services, a reduction in zero-dose children, and antigen-wise coverage. The paper also discusses the successful integration of COVID-19 vaccination within the UIP framework, underscoring the significance of existing infrastructure, technology, and capacity building. India's dedication to concurrently managing routine immunization and COVID-19 vaccination showcases the adaptability and resilience of its healthcare system. India's journey serves as a global example of efficient mass immunization during challenging times, emphasizing the importance of political will, healthcare infrastructure investment, skilled healthcare workforces, and comprehensive vaccination programs. In a world grappling with the dual challenge of COVID-19 and routine immunization, India's experience provides a roadmap for strengthening healthcare systems and promoting public health as the critical agenda in challenging times.

Scaling a group intervention to promote caregiver mental health in Uttarakhand, India: A mixed-methods implementation study.

Caregivers are integral to health and social care systems in South Asian countries yet are themselves at higher risk of mental illness. Interventions to support caregiver mental health developed in high-income contexts may be contextually inappropriate in the Global South. In this mixed-methods study, we evaluated the implementation and scaling of a locally developed mental health group intervention for caregivers and others in Uttarakhand, India. We describe factors influencing implementation using the updated Consolidated Framework for Implementation Research, and selected implementation outcomes. Key influencing factors we found in common with other programs included: an intervention that was relevant and adaptable; family support and stigma operating in the outer setting; training and support for lay health worker providers, shared goals, and relationships with the community and the process of engaging with organisational leaders and service users within the inner setting. We identified further factors including the group delivery format, competing responsibilities for caregivers and opportunities associated with the partnership delivery model as influencing outcomes. Implementation successfully reached target communities however attrition of 20% of participants highlights the potential for improving outcomes by harnessing enablers and addressing barriers. Findings will inform others implementing group mental health and caregiver interventions in South Asia.

Mission Indradhanush and Intensified Mission Indradhanush-Success Story of India's Universal Immunization Program and the Role of Mann Ki Baat in Bridging the Immunization Gap.

Child immunization is crucial for reducing the morbidity and mortality associated with vaccine-preventable diseases (VPDs). The program grew over the years, however, progress towards full immunization coverage (FIC) remained slow, with only 44% of children fully immunized in 1992-1993, and 62% in 2015-2016, as reported in the National Family Health Survey. To address this challenge, Government of India launched Routine Immunization intensification drive- Mission Indradhanush (MI) in 2014, with the aim of achieving 90% FIC. The success of MI led to the launch of Intensified Mission Indradhanush (IMI) in 2017, with more intensive planning, monitoring, review, and inter-sectoral partnerships.

Deciphering the enigmatic crosstalk between prostate cancer and Alzheimer's disease: A current update on molecular mechanisms and combination therapy.

Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.

Point of care ultrasound as initial diagnostic tool in acute dyspnea patients in the emergency department of a tertiary care center: diagnostic accuracy study.

BACKGROUND: Dyspnea is one of the common symptoms patients present to the emergency department (ED). The broad spectrum of differentials often requires laboratory and radiological testing in addition to clinical evaluation, causing unnecessary delay. Point of care ultrasound (PoCUS) has shown promising results in accurately diagnosing patients with dyspnea, thus, becoming a popular tool in ED while saving time and maintaining safety standards. Our study aimed to determine the utilization of point of care ultrasound in patients with acute dyspnea as an initial diagnostic tool in our settings. METHODOLOGY: The study was conducted at the emergency department of a tertiary healthcare center in Northern India. Adult patients presenting with acute dyspnea were prospectively enrolled. They were clinically evaluated and necessarily investigated, and a provisional diagnosis was made. Another EP, trained in PoCUS, performed the scan, blinded to the laboratory investigations (not the clinical parameters), and made a PoCUS diagnosis. Our gold standard was the final composite diagnosis made by two Emergency Medicine consultants (who had access to all investigations). Accuracy and concordance of the ultrasound diagnosis to the final composite diagnosis were calculated. The time to formulate a PoCUS diagnosis and final composite diagnosis was compared. RESULTS: Two hundred thirty-seven patients were enrolled. The PoCUS and final composite diagnosis showed good concordance (κ = 0.668). PoCUS showed a high sensitivity for acute pulmonary edema, pleural effusion, pneumothorax, pneumonia, pericardial effusion, and low sensitivity for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). High overall specificity was seen. A high positive predictive value for all except left ventricular dysfunction, pericardial effusion, non-cardiopulmonary causes of dyspnea, and a low negative predictive value was seen for pneumonia. The median time to make a PoCUS diagnosis was 16 (5-264) min compared to the 170 (8-1346) min taken for the final composite diagnosis. Thus, time was significantly lower for PoCUS diagnosis (p value <0.001). CONCLUSION: By combining the overall accuracy of PoCUS, the concordance with the final composite diagnosis, and the statistically significant reduction in time taken to formulate the diagnosis, PoCUS shows immense promise as an initial diagnostic tool that may expedite the decision-making in ED for patients' prompt management and disposition with reliable accuracy.

Psychological distress and well-being assessment among Indian people during COVID-19 pandemic.

Background: A rapid spread of the COVID-19 pandemic restricted millions of people in their homes and affected them with anxiety, stress, and psychological distress. This online study was conducted to assess the psychological distress among the Indian population. Method: This is a cross-sectional study, data collected via an online self-reported questionnaire using a snowball sampling technique. COVID-19 psychological stress was measured through the COVID-19 peritraumatic distress index (CPDI). This questionnaire was open-access and adapted from the Shanghai Mental Health Centre. Data were extracted to Microsoft Excel and analyzed in SPSS 23 version. Ordinal logistic regression was used to calculate the odds ratio for predicting variables. Results: A total of 625 responses were received. The mean age of the respondents was 26.41 years (standard deviation [SD] = 9.35; range = 17-79 years) with 320 (51.2%) males and the majority (68.8%) of the respondents were students. Youth with age group between 21 and 25 years were observed to be having peritraumatic distress 2.42 times more than the other groups (P = 0.001). Females were found to be more nervous and anxious (χ2 = 5.12; P = 0.02), more sluggish reaction due to anxiety (χ2 = 9.46; P = 0.002) as compared to males. Unmarried respondents were observed to be more sluggish due to anxiety (χ2 = 7.2; P = 0.007), felt more tired and exhausted (χ2 = 6.12; P = 0.013) in comparison to married. Conclusion: COVID-19 pandemic crisis significantly affected a major segment of society. The psychological distress level was observed to be high among youth, females, and a group of people in quarantine or isolation.

Early Initiation of Low-Dose Hydrocortisone Therapy for Septic Shock in Geriatric Patients: A Randomized Control Trial.

BACKGROUND: The management of septic shock has undergone significant modifications in the past decade. Various studies have concluded that while corticosteroids reduce the duration of shock, they do not have any proven mortality benefit. Moreover, the time of initiation of corticosteroids has been debatable. Since, little literature is available on geriatric patients, we have designed a randomized trial to assess the importance of early initiation of low dose hydrocortisone comparing with the standard therapy. OBJECTIVES: To determine the efficacy of early initiation of low dose hydrocortisone in reducing mortality in septic shock in geriatric patients. METHODS: We conducted a single blinded, randomized controlled trial at a tertiary care hospital in India. Geriatric patients (age>60 years) fulfilling the criteria for septic shock were included in the study. All the participants were randomly assigned to two arms- intervention and standard therapy group. The outcomes were studied in terms of 28-day mortality, duration of ICU stay, duration of vasopressor requirement and need for mechanical ventilation. RESULTS: Total 120 patients were randomized to either Intervention arm (N=61) or the Standard therapy arm (N=59). The number of patients with reversal of shock was higher in the intervention arm (53.4%) but no statistically significant association (p= 0.575) was found. There was no significant difference between the two groups in terms of 28- day mortality, length of ICU stay, need for mechanical ventilation and duration of vasopressor support. CONCLUSION: This single centre trial demonstrated that there was no survival benefit associated with the early initiation of low dose hydrocortisone treatment in patients with vasopressor-dependent septic shock. It raised the concern that whether steroids are safe in elderly patients with septic shock.

Nutritional and Functional Status as a Predictor of Short-Term Mortality in Hospitalized Elderly Patients in a Tertiary Care Hospital.

Context Elderly people are at a high risk of malnutrition leading to poor outcomes and quality of life. Aims We aimed to find an association between the nutritional and functional status of hospitalized elderly patients and the three-month all-cause mortality among them. Settings and design A cross-sectional study was carried out at a tertiary care hospital in North India from July 2018 to December 2019. Methods and material A total of 177 patients were recruited for the study, and their demographic and clinical data were collected on a preformed questionnaire. Comorbidity, nutritional status, functional status, and depression were calculated using the Charlson Comorbidity Index (CCI), Mini Nutritional Assessment (MNA) form, Katz Index of Independence in Activities of Daily Living (Katz ADL), and Geriatric Depression Scale (GDS), respectively. Statistical analysis A Chi-square test was used to find the association between different qualitative variables. A regression model was used to find out the odds for mortality. Statistical significance was set at p<0.05. Results According to the MNA score, 49.7% (88) were at risk of malnutrition, and 22.6%(40) were malnourished. Malnutrition, Charlson Comorbidity Index, and the functional status of the patients were found to be associated with three-month mortality, with a p value of 0.005, 0.017, and 0.021, respectively. On regression analysis, malnutrition (odds ratio (OR): 3.796; 95% confidence interval (CI): 1.178-12.234; p=0.025) and the functional status (OR: 3.160; 95% CI: 1.256-7.952; p=0.015) of the study participants were found to have higher odds for three-month all-cause mortality. Conclusions Nutritional status and ADL assessed at the time of discharge are good prognostic markers of health outcomes in the elderly population. Key message ADL and nutritional assessment at admission and discharge should be routinely incorporated in the geriatric assessment of hospitalized patients to triage and prognosticate.

Efficacy of Pro-Kinetic Agents in Type 2 Diabetes Mellitus Patients With Gastroparesis Using Lactulose Hydrogen Breath Testing: A Randomized Trial.

Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.

Crosstalk between epigenetics and mTOR as a gateway to new insights in pathophysiology and treatment of Alzheimer's disease.

Epigenetics in the current times has become a gateway to acquire answers to questions that were left unanswered by classical and modern genetics, be it resolving the complex mystery behind neurodegenerative disorders or understanding the complexity behind life-threatening cancers. It has presented to the world an entirely new dimension and has added a dynamic angle to an otherwise static field of genetics. Alzheimer's disease is one of the most prevalent neurodegenerative disorders is largely found to be a result of alterations in epigenetic pathways. These changes majorly comprise an imbalance in DNA methylation levels and altered acetylation and methylation of histones. They are often seen to cross-link with metabolic regulatory pathways such as that of mTOR, contributing significantly to the pathophysiology of AD. This review focusses on the study of the interplay of the mTOR regulatory pathway with that of epigenetic machinery that may elevate the rate of early diagnosis and prove to be a gateway to the development of an efficient and novel therapeutic strategy for the treatment of Alzheimer's disease at an early stage.

Capacity building of primary care physician working at remote Uttarakhand, India: An integrated tertiary care approach during COVID 19 pandemic.

Strengthening primary care during this unprecedented pandemic of COVID-19 is an urgent demand for public health. It needs to relook into the healthcare machinery and reenergize the much overlooked primary and secondary tier in healthcare delivery to effectively combat COVID-19 and other similar epidemics. OBJECTIVES: Strengthening of primary care and enhance the skills and knowledge of primary care physician working at Community Health Center/Primary Health Center (CHC/PHC) in context of Family medicine and updating them in recent advancements in primary care management and COVID 19 guidelines for efficient delivery of primary care services. METHODOLOGY: Director general health services of Uttarakhand was intimated with the aim and objectives of this one-day hands-on workshop going to be conducted at All India institute of medical sciences. All Chief Medical Officers of the various districts had been communicated and sensitized for this noble cause. Total 30 primary care physicians attended the certificate program. This session commenced with a pre-test followed by the lectures, discussions and hands-on skills and ended with a post-test. RESULTS: Majority (60%) of the participants were male and 40% were female. A total of 30% had never attended any similar workshop in the past. 45% of them were never exposed to any hands-on training before. Only 10% of them were Postgraduates and the rest were only MBBS (undergraduate). As the scores were not normally distributed, Wilcoxon Signed-Ranks Test was applied for the dependent variable. There was a significant difference (p < 0.05) found between pre and post-test results. CONCLUSION: Imparting continuing medical knowledge to the physicians has proved to be an effective tool in good clinical practice. The success of this intervention can be used to further develop and implement workshops and other training sessions to enhance the skills and knowledge of Primary Care Physicians in similar settings that face a shortage of well-equipped physicians.

Association of the microbiome with colorectal cancer development (Review).

Colorectal cancer (CRC) is the second most common malignancy causing cancer­related mortality globally. It is the third most common type of cancer detected worldwide. The recent concept of the human body supporting a diverse community of microbes has revealed the important role these microbes play synergistically in maintaining normal homeostasis. The balance between the microbiomes and epithelial cells of the human body is essential for normal physiology. Evidence from meta­genome analysis indicates that an imbalance in the microbiome is prominent in the guts of patients with CRC. Several studies have suggested that the gut microbiota can secrete metabolites [short­chain fatty acids (SCFAs), vitamins, polyphenols and polyamines] that modulate the susceptibility of the colon and rectum by altering inflammation and DNA damage. The state of microbiome imbalance (dysbiosis) has been reported in patients with CRC, with an increasing population of 'bad' microbes and a decrease in 'good' microbes. The 'good' microbes, also known as commensal microbes, produce butyrate; however, 'bad' microbes cause a pro­inflammatory state. The complex association between pathological microbial communities leading to cancer progression is not yet fully understood. An altered microbial metabolite profile plays a direct role in CRC metabolism. Furthermore, diet plays an essential role in the risk of gastrointestinal cancer development. High­fiber diets regulate the gut microbiome and reduce the risk of CRC development, and may be fruitful in the better management of therapeutics. In the present review, the current status of the microbiome in CRC development is discussed.12.

Bringing Health Care Closer to People - A Review of Various Telemedicine Models under the National Health Mission in India.

Telemedicine is an alliance between technology and medicine. It is a prevalent practice in developed countries; it has been widely used in developing countries to address the issues of access to medical care. India has been experimenting with telemedicine since long to address the issues of access and availability of specialist care and in recent years, with the rapid advancement of information technology, telemedicine has become a popular concept across the country. In this article, we have reviewed the various aspects of different government-funded telemedicine models functional in 12 states across India. We have also attempted to explore the levels of care delivery and services at facilities provided through telemedicine and challenges being faced in the implementation of the models. As a way forward, the health-care community needs to realize the full potential of telemedicine facility and utilize it to their benefit. Telemedicine will work best when it is one component of a well-functioning health system and not as an isolated gap-filling application.

Mechanistic basis of co-stimulatory CD40-CD40L ligation mediated regulation of immune responses in cancer and autoimmune disorders.

Generation of an accurate humoral and a cell mediated adaptive immune responsesare dictated by binding of an antigen to a T- and a B-cell receptor, respectively (first signal) followed by ligation of costimulatory molecules (second signal). CD40, a costimulatory receptor molecule, expressed mainly on antigen presenting cells, some non-immune cells and tumors, binds to CD40 ligand molecule expressed transiently on T-cells and non-immune cells under inflammatory conditions. In the past decade, the CD40-CD40L interaction has emerged as an immune-potentiating system that governs and regulates host immune response against various diseases and pathogens, failing of which results in detrimental patho-physiologies including cancer and autoimmune disorders. CD40-CD40L transduces immune signals intracellularly via TRAF-dependent and independent mechanisms and further downstream by different MAPK pathways and transcription factors such as NF-κB, p38 etc. While CD40 signaling pathway through its cognate interaction between B and T cells promotes activation and proliferation of B-cells, Ig class switching, and generation of B cell memory; however, CD40-CD40L interaction involving other APCs and non-immune cells relay distinct cell signaling resulting in production of a variety of cytokines/chemokines and cell adhesion molecules ultimately conferring host defense against pathogen. In cancer and autoimmune disorders, CD40-CD40L interaction is also responsible for aberrant expression of many disease specific markers, class I/II MHC molecules and other co-stimulatory molecules such as B7 and CD28 in cell- and disease-specific manner. In the present review, the current state of understanding about the CD40-CD40L mediated regulation of immune and non-immune cells is presented. The current paradigm is to target CD40 using agonist anti-CD40 mAbs alone or in synergistic combination with chemotherapy in order to harness or confer anti-tumor and anti-inflammatory immunity.

Are we Underestimating the Real Burden of Malnutrition? An Experience From Community-Based Study.

BACKGROUND: Since the inception of childhood nutritional programs in India, underweight has been taken to judge the nutritional status of children; but is it a true indicator of overall prevalence of malnutrition in a community? OBJECTIVE: To estimate the overall prevalence of malnutrition by using Composite Index of Anthropometric Failure (CIAF) and to assess its usefulness over various conventional anthropometric indicators among under 5 children residing in Agra city. MATERIALS AND METHODS: A cross-sectional, community-based study was conducted among under 5 years age children, from June 2012 to July 2013 in an urban slum of Agra. Nutritional status was assessed using anthropometry and clinical examination, and classified as per World Health Organization (WHO) 2006 Growth Standards and CIAF. RESULTS: Of the 458 children studied, 42.8% were underweight, 41.9% had stunting, while 22.7% had wasting. However, 60.04% of children were found to be malnourished as per the CIAF. Unlike three conventional anthropometric indicators of malnutrition, CIAF was observed to have a much consistent association with morbidity like diarrhea episodes in past 3 months (odds ratio (OR) = 2.09), acute respiratory tract infection (ARI) episode in past 3 months (OR = 1.58), and any illness requiring hospitalization (OR = 1.29). CONCLUSION: The CIAF should supplement the conventional indices of malnourishment, to provide a single, aggregated figure of actual number of undernourished children in a given population.