Marking the Micro Details in Potentially Malignant Disorders of Oral Cavity

Background- The malignancy of the oral cavity constitutes the most important group of malignancies in South and Southeast Asia.The risk increases with the use of tobacco products. Materials & Methods- Micronuclei frequency scoring was used as a biomarker to identify different potentially malignant disorders. Results- Mean micronuclei index was found higher using Hematoxylin and Eosin stain than Papanicolaou's stainand May Grunwald's stain. Conclusion- We concluded that the micronuclei frequencies in oral exfoliated epithelial cells using three different stains- Hematoxylin and Eosin stain, Papanicolaou's stain, May Grunwald's stain may be useful in predicting the malignant potential of premalignant lesions.

Smokeless tobacco cessation interventions: A systematic review

Background & objectives: Smokeless tobacco (SLT) consumption is a global health issue with about 350 million users and numerous adverse health consequences like oral cancer and myocardial disorders. Hence, cessation of SLT use is as essential as smoking cessation. An update on the available literature on SLT cessation intervention studies is provided here. Methods: Through an extensive literature search on SLT cessation intervention studies, using keywords such as smokeless tobacco, cessation, interventions, quitlines, brief advice, nicotine replacement therapy, nicotine gum, nicotine lozenge, nicotine patch, bupropion, varenicline, mHealth, etc., 59 eligible studies were selected. Furthermore, efficacy of the interventions was assessed from the reported risk ratios (RRs) [confidence intervals (CIs)] and quit rates. Results: Studies were conducted in Scandinavia, India, United Kingdom, Pakistan and the United States of America, with variable follow up periods of one month to 10 years. Behavioural interventions alone showed high efficacy in SLT cessation; most studies were conducted among adults and showed positive effects, i.e. RR [CI] 0.87 [0.7, 1.09] to 3.84 [2.33, 6.33], quit rate between 9-51.5 per cent, at six months. Regular telephone support/quitlines also proved beneficial. Among pharmacological modalities, nicotine lozenges and varenicline proved efficacious in SLT cessation. Interpretation & conclusions: Globally, there is limited information available on SLT cessation intervention trials, research on which must be encouraged, especially in the low-resource, high SLT burden countries; behavioural interventions are most suitable for such settings. Appropriate training/sensitization of healthcare professionals, and school-based SLT use prevention and cessation programmes need to be encouraged.

Relationship between type of smokeless tobacco & risk of cancer: A systematic review

Background & objectives: Causative linkages of smokeless tobacco (SLT) use with oral potentially malignant disorders and cancers of oral cavity, oesophagus and pancreas have been reported. Published meta-analyses have provided pooled risk estimates for major cancers caused by SLT, both on global and regional levels. This systematic review was aimed at summarizing the available studies on occurrence and mortality risk of common cancers due to various SLT products. Methods: PubMed and Google Scholar databases were systematically searched from 1985 till January 2018 for observational studies on SLT and cancer. The included studies were evaluated and data were extracted and reviewed. Results: The review included 80 studies providing 121 risk estimates for various cancers. Majority of the studies from South-East Asian Region (SEAR) and Eastern Mediterranean Region (EMR) showed a significant positive association of SLT use with oral [odds ratio (OR) ranging from 1.48 to 27.4] and oesophageal cancers (OR between 2.06 and 12.8), while studies from European Region (EUR) reported a positive association with pancreatic cancer (OR between 1.6 and 2.1). Cancer-related mortality was evaluated in a few reports with higher risk of mortality for lung (OR between 2.0 and 9.1), cervical (OR 2.0) and prostate (OR 2.1) cancers. A wide variation was noted in the association of various cancers and specific SLT products based on their nature, methods of use and inherent toxicity. The majority of chewing tobacco products displayed higher risk for oral and oesophageal cancers while the same was not observed for snus. Interpretation & conclusions: This review emphasizes on the significantly positive association of SLT use with oral and oesophageal cancers in SEAR and EMR and pancreatic cancer in EUR. Mortality estimates for SLT-associated cancers need further analysis. Risk analysis for cancers of other sites in SLT users also requires multicentric well-designed studies.

Regulation of toxic contents of smokeless tobacco products

Effective regulation of contents of tobacco products is one of the primary milestones to reduce negative health effects associated with the use of smokeless tobacco (SLT) products. As per the available sources, testing of some SLT products has been done on ad hoc basis, but there is a lack of comprehensive and periodic analysis of these products. In addition, the available results indicate huge variations among the levels of pH, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosonornicotine, benzo[a]pyrene, heavy metals and nicotine within different products as well as within different brands of the same product. This review was aimed to throw light on the variations and gaps in testing of SLT products and emphasize the need for strong policy regulation for monitoring the chemical constituents of these products.

Role of World Health Organization Framework Convention on Tobacco Control Global Knowledge Hub on Smokeless Tobacco

Smokeless tobacco (SLT) is a recognized public health challenge, having over 350 million users globally, concentrated particularly in South-East Asia. A need for research on curbing major challenges in regulating SLT use has been long felt and subsequently highlighted in several sessions of the Conference of Parties (COP) of the Framework Convention on Tobacco Control (FCTC). The sixth session of COP established a knowledge hub on SLT at the Indian Council of Medical Research- National Institute of Cancer Prevention and Research India, with a mandate to (i) generate and share expertise, information and knowledge; (ii) promote and facilitate communication among Parties, organizations and stakeholders; and (iii) support the Convention Secretariat in contributing to technical aspects of SLT control. The hub disseminates scientific evidence through an interactive website and publications and supports national and international partners in SLT research. The hub is a contributor to many events/conferences and has conducted several workshops on SLT control, including an inter-country meeting on SLT policy implementation status, which brought together representatives from across the globe, and framed recommendations for policy reform. The hub is dedicated to interaction and collaboration with relevant tobacco control organizations to generate evidence, support and policy orientation in line with its mandates and recommendations under the World Health Organization FCTC.

Dohra- a mixture of potent carcinogens

Background & objectives: Dohra is a areca nut preparation used with or without tobacco in a few of the areas of Uttar Pradesh (UP), India. There is evidence that it causes potentially malignant disorders and oral cancer. This study was undertaken to provide information on dohra by searching through literature and also through a survey in three areas of Uttar Pradesh (UP), India. Methods: The information on dohra was collected through literature search, study tour to different areas of UP, where group discussions with dohra vendors and with community members of different age group were done to obtain information. Results: Dohra was prepared by the users for their personal use or prepared by small-scale industry for sale. It was available mostly in betel shops or any other store/kiosks and was also available in special dohra shops. Dohra was available in both dry and wet form. Its common constituents were areca nut, catechu (Acacia catechu), edible lime, peppermint (Mentha piperita), cardamom (Elettaria cardamomum) and some flavoring agents. Dohra was consumed as such or with tobacco. Interpretation & conclusions: Different varieties of Dohra were available such as sukha dohra, sukha mulethi dohra and geela dohra. Different processing methods for producing dohra existed. As dohra increases the risk of cancer, it needs to be banned or it should be sold in packets with the details of its constituents and also statutory warning about its adverse health effects.

Implementation of Article 20 of the World Health Organization Framework Convention on Tobacco Control

Background & objectives: Article 20 of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) deals with surveillance and research on all tobacco products including smokeless tobacco (SLT). Here we describe the availability of indicators related to SLT among 180 Parties to the convention (countries ratifying the WHO FCTC are referred as Parties to the Convention). Methods: Data on SLT use among adults and adolescents and SLT-related economic and health indicators among Parties were obtained through rigorous literature search. Data analysis for high-burden parties was done using SPSS. Results: Nearly 92 per cent (166) of the Parties reported SLT use prevalence among adults or adolescents at national or subnational level, of these nearly one-fifth of the Parties (20.5%) were high-burden Parties. Comparable SLT tax incidence rate was available for 19.4 per cent (n=35) Parties, and SLT attributable morbidity and mortality risks of major diseases were available for only five per cent (n=10) of Parties. Interpretation & conclusions: SLT use is a global epidemic widespread among Parties to the Convention. There are a data gap and dearth of research on SLT-related issues. Parties need to monitor SLT use and related health and economic indicators regularly at periodic intervals.

Setting research priorities in smokeless tobacco control: A retrospective review

Background & objectives: Smokeless tobacco (SLT) has become a global menace; India being one of the high-burden countries contributes about 67 per cent of its users. Although research is ongoing on various aspects of SLT use and its effects, there is a need to identify the still under-researched areas in this field. This study was aimed at delineating the quantum of research on various topics of SLT, with intent to delineate research gaps for guiding future research priorities. Methods: Data about research in SLT were collected from PubMed database using ‘smokeless tobacco’ as a keyword and applying Medical Subject Headings (MeSH) terms filter. Data were extracted in XML (Extensible Markup Language) format and parsed into database to extract necessary fields such as PubMed IDs, authors' names, affiliations and MeSH terms. Quantum of research in various aspects of SLT was identified for individual MeSH terms and compared for global and Indian data. Results: Data analysis of 2857 records revealed that maximum number of articles was devoted to adverse effects (35.6%) followed by epidemiology (32.4%). In comparison, India contributed only 11.7 per cent of records with maximum number of articles on the topics of epidemiology (26%) and adverse effects (45.8%). Higher proportion of research was published on epidemiology, aetiology and prevention and control at global level, while adverse effects of SLT were researched more in Indian studies as compared to global data. Interpretation & conclusions: The present analysis highlighted the paucity of research studies on important topics such as economics and alternative strategies of SLT control, both on the global and regional levels.

A review of trade practices of smokeless tobacco products in terms of prohibition on sale, manufacturing & importation in Framework Convention on Tobacco Control ratified Parties

Background & objectives: Over the past decade, the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) has served as a powerful tool to initiate and advance global tobacco control efforts. However, the control strategies have mainly targeted demand-side measures. The goal of a tobacco-free world by 2040 cannot be achieved if the supply-side measures are not addressed. This analysis was undertaken to examine the tobacco control legislations of various Parties ratifying WHO FCTC with an objective to ascertain the status of prohibition of importation, sale and manufacturing of smokeless tobacco products. Methods: All 180 Parties to WHO FCTC were included for the study. A comprehensive database of all the parties to FCTC was created and tobacco control legislations and regulations of all parties were studied in detail. Results: Overall, the sale of smokeless tobacco (SLT) products was prohibited in 45 Parties. Eleven Parties prohibited manufacturing of SLT products and six Parties imposed a ban on importation of SLT products. Australia, Bhutan, Singapore and Sri Lanka banned all three. Interpretation & conclusions: Comprehensive tobacco control strategy with effective tobacco cessation programme should complement strong legal actions such as prohibition on trade in SLT products to meet the public health objective of such laws and regulations. In addition, multisectoral efforts are needed for effective implementation of such restrictions imposed by the governments.

A systematic review on association between smokeless tobacco & cardiovascular diseases

Background & objectives: The association of smokeless tobacco (SLT) with cardiovascular diseases has remained controversial due to conflicting reports from various countries. Earlier meta-analyses have shown significantly higher risk of fatal myocardial infarction and stroke in SLT users. However, the risk of hypertension (HTN) with SLT products has not been reviewed earlier. This systematic review was undertaken to summarize the evidence available from global literature on the association of SLT with cardiovascular outcomes – heart disease, stroke and HTN. Methods: A systematic literature search was performed in PubMed and Google Scholar since their inception till October 2017 using pre-decided search terms and inclusion/exclusion criteria. Data were extracted from studies included independently by two authors and reviewed. Results: The review included 50 studies - 23 on heart disease, 14 on stroke and 14 on HTN. Majority of the studies evaluating heart disease or stroke were conducted in the European Region and most of these did not find a significant association between SLT use and either of these outcomes. On the other hand, 70 per cent of the studies on HTN were reported from South-East Asian Region and about half of the studies found a higher risk of HTN in SLT users. Interpretation & conclusions: Current available evidence is insufficient to conclusively support the association of cardiovascular diseases with SLT use due to variability in results and methodological constraints in most of the studies. Region and product-specific well-designed studies are required to provide this evidence to the policymakers. However, advice on cessation of SLT products should be offered to patients presenting with cardiovascular diseases.

Tobacco control legislation in India: Past and present.

Beginning with the Cigarettes Act, 1975, a number of legislative strategies and programs to curb tobacco use have been implemented in India, with limited success. Currently, the Cigarettes and Other Tobacco Products Act, 2003, is designed to curb the use of tobacco in order to protect and promote public health. This review presents a critical appraisal of the current situation in its historical context.

Low framingham risk score despite high prevalence of metabolic syndrome in asymptomatic north-Indian population.

Background : Conflicting data exists regarding relationship between the Framingham risk score (FRS) and presence of metabolic syndrome (MS). Strong influence of age on FRS may further modify this relationship as prevalence of MS at younger age increases in South-Asian countries including India. However, only limited information is available about the prevalence of MS and its relationship with FRS in such populations at present. Methods : Clinical examination and biochemical investigations were performed in 1905 asymptomatic office executives who underwent routine health check-up at a tertiary care centre in India during the year 2005. Diagnosis of MS and FRS were based on the modified National Cholesterol Education Program- Adult Treatment Panel III guidelines. Results : Mean age of the subjects was 45.2 ± 10.3 years and 71.8% were males. MS was present in 47.5% (905 of 1905) subjects. Overall, 76.8% patients with MS had 10-year cardiovascular (CV) risk <10%, 20.6% had 10-20% risk and only 2.7% had >20% risk according to FRS. In the lowest age-quartile, 95.9% patients had 10-year risk <10%, 4.1% patients had 10-20% risk and none had >20% risk. In contrast, in the highest age-quartile, less than half of the patients had 10-year risk <10% and nearly half had 10-20% risk of CV events. Conclusions : Although the prevalence of MS is markedly high in young asymptomatic Indians, majority have low 10-year risk of CV events as estimated by FRS. These findings necessitate continued emphasis on detection of MS in these populations as reliance on FRS alone may result in underestimation of CV risk in them. ©

Efficacy of teriparatide in increasing bone mineral density in postmenopausal women with osteoporosis--an Indian experience.

BACKGROUND AND OBJECTIVE: Osteoporosis is emerging as a leading cause of substantial morbidity in India, particularly in postmenopausal women. Teriparatide (recombinant human parathyroid hormone [1-34]) increases bone formation and improves bone microarchitecture, thereby reducing the risk of fractures. This study was conducted to evaluate the efficacy of teriparatide in increasing bone mineral density (BMD) in postmenopausal women with osteoporosis. MATERIAL AND METHODS: A randomised, prospective, multicentre, open-label, controlled study was conducted on 82 postmenopausal women with established osteoporosis. Patients were randomly divided into control and teriparatide groups, each group consisting of 41 patients. All the patients were supplemented with 1000 mg of elemental calcium and 500 IU of vitamin D throughout the study period of 180 days. Besides, teriparatide group patients were administered teriparatide 20 microg daily subcutaneously. Lumbar spine, femoral neck and total hip BMD, bone mineral content (BMC) and bone area were measured by dual energy x-ray absorptiometry (DXA) at baseline and at the end of 6 months of treatment. Bone biomarkers, such as serum bone specific alkaline phosphatase (BSAP) and serum osteocalcin (OC), representing bone formation, and urinary deoxypyridinoline (DPD), representing bone resorption were assessed at baseline, and at 3 and 6 months of treatment. RESULTS: During the study period, 9 patients (11%) were lost to follow-up--6 in control group (7.3%) and 3 in teriparatide group (3.7%). There was an excellent compliance to both oral and injectable medication. The investigational product teriparatide was well tolerated and there were no serious adverse events. In addition, there were no significant differences between the groups in the incidence of adverse events. The percentage of increase in lumbar spine BMD, which is the primary endpoint, was significantly (P < 0.001) higher in teriparatide group compared to that in control group (6.58% vs. 1.06%). Further, teriparatide significantly increased percentage of change in lumbar spine T-score (P < 0.001), BMC (P < 0.001) and bone area (P < 0.028) compared to control group at 6 months. Administration of teriparatide resulted in a significant percentage of increase in all the bone biomarkers in teriparatide group compared to control group patients at 3 and 6 months over baseline, thereby showing that there was a significant increase in bone turnover in teriparatide group of patients. CONCLUSION: These results show that teriparatide is an effective and safe drug in increasing the BMD and therefore, teriparatide provides yet another new therapeutic option for reducing the risk management of osteoporosis in postmenopausal women (clinicaltrials.gov number, NCT00500409).

Oral squamous cell carcinoma: etiology, pathogenesis and prognostic value of genomic alterations.

Tumours of the head and neck comprise an important group of neoplasia, the incidence of which is increasing in many parts of the world. This increase remains high, despite all the advances in modern medicine. This malignancy is more prevalent in the developing world and unfortunately, has not received satisfactory attention as the more prevalent cancers of the developed world, like lung, breast, or colon cancer. Recent advances in diagnosis and therapeutic techniques of these lesions have yielded novel molecular targets, uncovered signal pathway dominance and advanced early cancer detection. This review covers recent advances in our understanding of the etiology, molecular changes and the possible role that genomic and proteomic research might play in the diagnosis and effective cure of this modern-day scourge.

Management of chronic hepatitis B with New Livfit in end stage renal disease.

New Livfit (NLF) is a standardized, poly-herbal formulation that has been found useful in the management of hepatitis. The aim of this placebo-controlled study was to evaluate its usefulness against hepatitis B virus in the patients of end stage renal disease (ESRD). Patients were regularly evaluated at 6, 12, 24 and 36 weeks of therapy. With 36 weeks of treatment of NLF, there was rapid clearing of HBV-DNA in a significant number of patients. Significant seroconversion of the other markers of hepatitis B and restoration of the raised levels of ALT and AST was observed. The study suggests the potential usefulness of NLF in the control of HBV infection in the patients of ESRD prior to renal transplant.

Dissociation of clinical and laboratory diagnosis in hypothyroidism.

AIMS OF THE STUDY: To assess the significance of clinical versus biochemical diagnosis of hypothyroidism using a clinical scoring index and optimize the therapeutic dose of levothyroxine in Indian patients. METHODOLOGY: Three hundred and eighty eight cases of primary hypothyroidism (male:female ratio 1:5.8) were clinically classified as hypothyroid, euthyroid or inconclusive by Billewicz score. TSH estimation was repeated at 6-8 week intervals and appropriate adjustments in levothyroxine dosage made till the TSH was within the normal range. RESULTS: Of 388 biochemically confirmed hypothyroid subjects less than one fourth (21.6%) could be classified as hypothyroid, almost one half were euthyroid (48.4%) and the remaining (29.9%) fell in the inconclusive category according to Billewiz score. Of 227 patients who returned for complete follow up there was a positive correlation of replacement dose with age and initial weight in females, but not in males. Baseline TSH values were not found to have a significant correlation with the initial dose. The mean replacement dose of levothyroxine (T4) in our subjects was 109.4 +/- 24.05 microg/d (range 1.25-3.84 microg/kg). CONCLUSION: Clinical parameters alone fare poorly in establishing an unequivocal diagnosis of hypothyroidism. A biochemical confirmation is mandatory. The replacement done of T4 was found to be independent of the basal TSH level.

Age specific incidence rate and pathological spectrum of oral cancer in Allahabad.

BACKGROUND: Cancer of the oral cavity is one of the commonest cancers in India. Use of smokeless tobacco (Pan masala, Zarda etc ) is on the increase in North India and specially in Uttar Pradesh. AIMS: To assess the patients characteristics and histopathological subtypes of the oral cancer in our region. SETTINGS AND DESIGN: A single institutional retrospective study of 11 years from 1990 to 2000 was designed. Data was collected year wise using the tumour registry data. MATERIAL AND METHODS: A total of 40,559 biopsies were examined in the department during 1990-2000, out of which the oral cavity constituted 759 biopsies. The data was analysed with emphasis on age, sex, risk factors, site and histology. STATISTICAL ANALYSIS: The data was analysed utilizing the Kolomogroo-Smirnov two sample test. RESULTS: A comparison of the age specific incidence rates of oral cancer during 1990-2000 in Allahabad showed that the incidence was maximum in the 50-59 years age group and squamous cell carcinoma grade I was the most prevalent type. Of the total of 759 biopsies from oral cavity, 303 malignant cases. 232 (76.57%) were males and 71 (23.43% were females with a male to female ratio of 3.27:1. The tongue was the most frequently involved site--found in 42.57% cases. On an average, 63 new cases of oral cavity per annum were detected during this period. CONCLUSIONS: Properly structured site specific data like this can augment National Cancer Registry Programme (NCRP) and is an essential indicator for the magnitude and the pattern of the cancer problem in India Urgent public health measures like public education and oral cancer awareness are required to curb this avoidable epidemic.