Oral Fluid, Electrolytes, and Energy Management in Various Adult and Geriatric Illnesses beyond Diarrhea: An Indian Expert Panel Delphi Consensus Recommendation.

BACKGROUND: Dehydration is a highly prevalent clinical challenge in adults which can go undetected. Although dehydration is commonly associated with an increased risk of hospitalization and mortality, only a few international guidelines provide recommendations regarding oral fluids, electrolytes, and energy (FEE) management in adults/geriatrics with dehydration due to nondiarrheal causes. Currently, there is a lack of comprehensive recommendations on the role of oral FEE in nondiarrheal dehydration in adult and geriatric Indian patients. MATERIALS AND METHODS: A modified Delphi approach was designed using an online questionnaire-based survey followed by a virtual meeting, and another round of online surveys was used to develop this consensus recommendation. In round one, 130 statements, including 21 open-ended questions, were circulated among ten national experts who were asked to either strongly agree, agree, disagree, or strongly disagree with statements and provide responses to open-ended questions. The consensus was predefined at 75% agreement (pooling "strongly agree" and "agree" responses). Presentation of relevant literature was done during a virtual discussion, and some statements (the ones that did not achieve predefined agreement) were actively discussed and deliberately debated to arrive at conclusive statements. Those statements that did not reach consensus were revised and recirculated during round two. RESULTS: Consensus was achieved for 130/130 statements covering various domains such as assessment of dehydration, dehydration in geriatrics, energy requirement, impact of oral FEE on patient outcome, and fluid recommendations in acute and chronic nondiarrheal illness. However, one statement was not added as a recommendation in the final consensus (129/130) as further literature review did not find any supporting data. Oral FEE should be recommended as part of core treatment from day 1 of acute nondiarrheal illness and started at the earliest feasibility in chronic illnesses for improved patient outcomes. Appropriately formulated fluids with known electrolyte and energy content, quality standards, and improved palatability may further impact patient compliance and could be a good option. CONCLUSION: These consensus recommendations provide guidance for oral FEE recommendations in Indian adult/geriatric patients with various nondiarrheal illnesses.

Epidemiology of Non-Hodgkin's Lymphoma in India.

Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy. The age-adjusted incidence rates for NHL in men and women in India are 2.9/100,000 and 1.5/100,000, respectively. These are about one fourth of the incidence rates reported from Western Europe or North America. Within India, the incidence is several-fold higher in urban cancer registries compared to rural areas; the incidence being higher in metropolitan cities and Indian immigrants suggesting that urban lifestyles and economic progress may increase the cancer incidence. Compared to developed nations, the key differences in the presentation in India include: median age of 54 years (almost a decade less), higher male to female ratio, higher proportion of patients with B-symptoms (40-60 vs. 20-30%), poor ECOG performance status (≥2) at diagnosis (50 vs. 20-30%), higher frequency of diffuse large B-cell lymphomas (60-70 vs. <40%), lower frequency of follicular NHL (<20 vs. 30-40%) and T-cell type in 10-20 vs. <10%. The estimated mortality rate due to NHL is higher in India than in North America and Western Europe. Diagnostic and treatment delays, incorrect diagnosis and inappropriate or suboptimal treatment may be possible reasons for the poor outcome. Any improvement in the outcomes for NHL in India will require a nationwide approach, e.g. creation of several regional and district-level centers with expertise in lymphoma management. Collection of data on patient- and disease-related characteristics, treatment outcome, development of infrastructure, centralized review of histopathology subtype, novel treatment protocols, rigorous follow-up, training of staff, and financial support towards treatment could be possible strategies to improve the outcome.

The growing burden of cancer in India: epidemiology and social context.

Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600,000-700,000 deaths in India were caused by cancer in 2012. In age-standardised terms this figure is close to the mortality burden seen in high-income countries. Such figures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of India's cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affluent. In this first of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India.

History of the Growing Burden of Cancer in India: From Antiquity to the 21st Century.

This review traces the growing burden of cancer in India from antiquity. We searched PubMed, Internet Archive, the British Library, and several other sources for information on cancer in Indian history. Paleopathology studies from Indus Valley Civilization sites do not reveal any malignancy. Cancer-like diseases and remedies are mentioned in the ancient Ayurveda and Siddha manuscripts from India. Cancer was rarely mentioned in the medieval literature from India. Cancer case reports from India began in the 17th century. Between 1860 and 1910, several audits and cancer case series were published by Indian Medical Service doctors across India. The landmark study by Nath and Grewal used autopsy, pathology, and clinical data between 1917 and 1932 from various medical college hospitals across India to confirm that cancer was a common cause of death in middle-aged and elderly Indians. India's cancer burden was apparently low as a result of the short life expectancy of the natives in those times. In 1946, a national committee on health reforms recommended the creation of sufficient facilities to diagnose and manage the increasing cancer burden in all Indian states. Trends from the Mumbai population-based cancer registry revealed a four-fold increase in patients with cancer from 1964 to 2012. Depending on the epidemiologic transition level, wide interstate variation in cancer burden is found in India. We conclude that cancer has been recognized in India since antiquity. India's current burden of a million incident cancers is the result of an epidemiologic transition, improved cancer diagnostics, and improved cancer data capture. The increase in cancer in India with wide interstate variations offers useful insights and important lessons for developing countries in managing their increasing cancer burdens.

Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.

Prevalence estimation of microsatellite instability in colorectal cancers using tissue microarray based methods - A tertiary care center experience.

AIM: Microsatellite instability (MSI) pathway is known to be implicated in carcinogenesis of 15% colorectal carcinomas (CRC), including 2%-3% of cases of Lynch syndrome, as per western literature. MSI status has important prognostic and therapeutic implications. The prevalence of MSI in Indian CRC patients is unknown. We aimed to determine the prevalence by studying 231 consecutive unselected cases of CRC. METHODS: Tissue microarrays using duplicate cores per case for 141 cases, and whole tissue sections for 90 cases, were used. Immunohistochemistry with four mismatch repair (MMR) markers - MLH1, MSH2, MSH6, and PMS2 was performed. Molecular analysis for MSI status was performed in 18 randomly selected cases. Correlation with various clinical and histopathological features was done using univariate and multivariate analysis. RESULTS: Loss of MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95% confidence interval 17.52%-28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2-MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed significant association with age (<60 years), right-sided tumor location, histologic type, high grade, the presence of severe intratumoral lymphocytic (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate analysis, independent variables were age < 60 years, right-sided location, and severe ITL. Molecular testing for MSI corroborated with the IHC results. CONCLUSION: The study results show a slightly higher prevalence of MSI-H phenotype, compared to Western literature, stressing the need for more widespread testing for better clinical management and identification of possible hereditary colon cancer syndrome.

Investigators' viewpoint of clinical trials in India: Past, present and future.

India's success in producing food and milk for its population (Green Revolution and White Revolution) happened because of scientific research and field trials. Likewise improving the health of Indians needs clinical research and clinical trials. A Large proportion of the sick Indians are poor, illiterate with no access to good health care. They are highly vulnerable to inducement and exploitation in clinical trials. The past two decades saw the rise and fall of clinical trials in India. The rise happened when our regulators created a favorable environment, and Indian investigators were invited to participate in global clinical trials. The gap between the demand and supply resulted in inadequate protection of the trial participants. Reports of abuses of the vulnerable trial participants followed by public interest litigations led to strengthening of regulations by the regulators. The stringent new regulations made the conduct of clinical trials more laborious and increased the cost of clinical trials in India. There was a loss of interest in sponsored clinical trials resulting in the fall in global clinical trials in India. Following repeated appeals by the investigators, the Indian regulators have recently relaxed some of the stringent regulations, while continuing to ensure the adequate patient protection. Clinical trials that are relevant to our population and conducted by well-trained investigators and monitored by trained and registered Ethics Committees will increase in the future. We must remain vigilant, avoid previous mistakes, and strive hard to protect the trial participants in the future trials.

Primary liver cancer deaths and related years of life lost attributable to hepatitis B and C viruses in India.

BACKGROUND AND AIMS: More than 25,000 people die of liver cancer annually in India. There is little information about the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to these deaths. We conducted a systematic review of published studies on HBV or HCV infection and liver cancer in India and estimated the population attributable fraction (PAF) of liver cancer deaths caused by these infections and the corresponding annual number of deaths and years of life lost (YLL) in the country. METHODS: We searched the PubMed and Scopus databases, as well as the reference list of relevant articles in the systematic review. For calculation of the number of liver cancer deaths attributable to HBV and HCV, we used two sources of outcome data and two relative risks for the association between HCV and liver cancer. RESULTS: The PAF was 67% for HBV, 17-19% for HCV, and 71-72% for HBV and/or HCV. The annual attributable number of liver cancer deaths was approximately 17,000 for HBV; 4500 for HCV; and 18,500 for HBV and/or HCV, corresponding to approximately 297,000, 75,000, and 315,000 YLL, respectively. There was little difference in these numbers using the two sources of outcome data or the two risk estimates for HCV. CONCLUSIONS: Our findings underscore the importance of primary prevention of HBV and HCV by appropriate measures, including vaccination (HBV only), prevention of transfusion-related infections, and increased awareness of the routes of transmission and long-term health outcomes.

Elevated CA125 Levels in a 72-Year-Old Ethnic Indian Patient: A Diagnostic Pointer Toward Tuberculosis?

Serum CA 125 is widely used as a tumor marker for epithelial ovarian cancer. Our laboratory receives few requests for evaluation of this marker in men. In males an elevation of this marker may occur due to malignant and benign lesions of organs derived from the coelomic epithelium. However, in the absence of evidence of a neoplasm (via clinical examination and other diagnostic modalities), it is useful to consider a diagnosis of tuberculosis, particularly in regions where the disease is endemic. Herein, we describe one such case that we investigated at our medical center in Kolkata, India.

Pharmacovigilance Symposium ISCR Annual Conference Jan 5, 2013: Safety aspects of hard endpoint or outcome trials.

The articles describes some highlights of the Pharmacovigilance Symposium held during Annual conference.

Modification and implementation of NCCN guidelines on colon cancer in the Middle East and North Africa region.

Colorectal cancer is less common in the Middle East and South Asia than in western countries, with the rectum the most common primary site, unlike in the United States. A project was planned to address various local issues regarding the management of common cancers, including colorectal cancer, and to adapt the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to the Middle East and North Africa (MENA) region. A survey of oncologists in this geographic area showed that the management practices and issues regarding colorectal cancer are similar to those presented in the NCCN Colorectal Cancer Guidelines. However, 2 major differences exist: most oncologists in the MENA region prefer chest radiograph over CT in pretreatment workup, and almost 50% of them prefer to use cetuximab in the first-line treatment of patients with the wild-type KRAS gene. The committee, comprising 9 oncologists from different countries, proposed 4 modifications to the 2009 version of the NCCN Colorectal Cancer Guidelines for use in the MENA region, relating to 1) short-course preoperative radiotherapy, 2) dose of capecitabine, 3) stereotactic radiotherapy for liver metastasis, and 4) qualification of surgeons performing colorectal surgery. The modification of NCCN Colorectal Cancer Guidelines for use in the MENA region represents a step toward creating a uniform practice in the region based on evidence and local experience.