Drug misuse in India: Where do we stand & where to go from here? Ajit Avasthi, Abhishek Ghosh Indian Journal of Medical Research 2019 149(6):689-692

Progress in multiple myeloma Reinhold Munker, Gregory Monohan Indian Journal of Medical Research 2019 149(6):693-694

Overnutrition: Current scenario & combat strategies Prashant Mathur, Rakesh Pillai Indian Journal of Medical Research 2019 149(6):695-705 Large population-based surveys by the Government of India and several other regional studies have reconfirmed the coexisting burden of over- and undernutrition. While time trends from the 2nd, 3rd and 4th rounds of the National Family Health Survey show declining trends in the prevalence of the underweight, it also highlights increasing rates in the overweight/obesity. Dose-response relationships with different micro- and macronutrient consumption with overweight/obesity prevalence have been established. In this context, it was attempted to identify the specific diet pattern and socio-behavioural determinants of overnutrition along with its combat strategies. This review highlights that while the proportion of chronic energy deficiency is decreasing in India, the intake of micronutrients and food groups continues to be below the recommended dietary allowance set by the Indian Council of Medical Research. Distal factors that determine the nutritional imbalance among Indians are presented under (i) household contextual factors, (ii) peer and socio-cultural influencers, and (iii) business and neighbourhood environment. Accumulation of such factors increases the density of obesogenic environment around individuals. Further, the review offers action points at individual, society and policy levels, presented in a 'logframe matrix' for bringing convergence actions across sectors in consultation with programme managers from different ministries/departments.

Anti-Wolbachia therapy for onchocerciasis & lymphatic filariasis: Current perspectives Wan Aliaa Wan Sulaiman, Joseph Kamtchum-Tatuene, Mohd Hazmi Mohamed, Vasudevan Ramachandran, Siew Mooi Ching, Sazlyna Mohd Sazlly Lim, Hasnur Zaman Hashim, Liyana Najwa Inche Mat, Fan Kee Hoo, Hamidon Basri Indian Journal of Medical Research 2019 149(6):706-714 Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.

A systematic review of standard treatment guidelines in India Paresh Girdharlal Koli, Nilima A Kshirsagar, Yashashri C Shetty, Dhvani Mehta, Yashaswini Mittal, Urwashi Parmar Indian Journal of Medical Research 2019 149(6):715-729 Background & objectives: Standard treatment guidelines (STGs) are the cornerstone to therapeutics. Multiple agencies in India develop STGs. This systematic review was conducted to find out STGs available in India, evaluate if these were as per World Health Organization (WHO) recommendations for STGs and compare these with National Institute for Health and Care Excellence (NICE) guidelines. Information on legal authority and responsibility for formulating STGs was also sought. Methods: PRISMA guidelines were followed. Publications from PubMed and Google Scholar were searched for STGs using terms 'Standard Treatment Guidelines AND India'. Data from STGs were compiled in excel as per the WHO and authors' criteria for STGs and compared with NICE guidelines. Results: PubMed and Google Scholar search provided 56 publications (out of 1695 search results) mentioning 27 STGs. Google search and replies from authors led us 36 STGs, totalling to 63 STGs. No STG mentioned any specific period of revision, eight STGs were not evidence-based, 55 had some Indian references, 48 STGs were for single disease and the remaining multi-disease, three STGs did not include diagnostic criteria, 16 STGs did not give prescribing information of recommended treatment and 16 STGs provide no referral criteria for patients. Fifty five STGs did not mention level of health care. While NICE is a single legal authority in England and guidelines are as per WHO recommendations for STGs, in India although Acts and rules do not vest authority, National Health Systems Resource Center is generally designated responsible for STGs. Interpretation & conclusions: In India, although there are multiple STGs developed by various authorities and professionals for the same conditions, these fulfil WHO recommendations only partially. Authority with statutory duty collaborating with professional organizations, a standard methodology for adopting international guidelines, Indian data for evidence base, attention to local needs will help in developing better STGs and their acceptance.

High-dose chemotherapy followed by autologous stem cell transplant for multiple myeloma: Predictors of long-term outcome Lalit Kumar, Dev Ramavath, Babita Kataria, Akash Tiwari, Abhishek Raj, Santosh Kumar Chellapuram, Anjali Mookerjee, Ranjit Kumar Sahoo, Prabhat S Malik, Atul Sharma, Ritu Gupta, Om dutt Sharma, Ahitagni Biswas, Rakesh Kumar, Sanjay Thulkar, for AIIMS Myeloma Group  Indian Journal of Medical Research 2019 149(6):730-739 Background & objectives: Survival of patients with multiple myeloma (MM) has improved in the past two decades following use of novel agents and autologous stem cell transplantation. To determine predictors of long-term outcome, data of MM patients who underwent autologous stem cell transplantation (ASCT) at a tertiary care centre in north India were retrospectively analyzed. Methods: Between 1995 and 2016, 349 MM patients underwent ASCT. Patients' median age was 52 yr, ranging from 29 to 68 yr, 68.2 per cent were males. Thirty three per cent patients had international staging system (ISS) Stage III and 68.5 per cent had received novel agents-based induction. High-dose melphalan (200 mg/m2) was used for conditioning; patients with renal insufficiency (estimated glomerular filtration rate <40 ml/min) received melphalan 140-150 mg/m2. Results: Post-transplant, 317 of 349 (90.8%) patients responded; complete [complete response (CR)] −213 (61%)], very good partial response (VGPR) −62 (17.8%) and PR in 42 (12%)]. Induction with novel agents, pre-transplant chemosensitive disease, transplant in first remission and serum albumin (≥3.5 g/dl) were predictors of significant response. At a median follow up of 73 months, median overall survival (OS) was 90 months [95% confidence interval (CI) 70.8-109.2], and progression-free survival (PFS) was 41 months (95% CI 33.0-49.0). On multivariate analysis, achievement of CR post-transplant, transplant in first remission, ISS Stages I and II (vs. III), absence of extramedullary disease and serum albumin ≥3.5 g/dl were predictors of prolonged OS. For PFS, achievement of post-transplant CR and transplant in first remission were predictors of superior outcome. Interpretation & conclusions: Treatment with novel agents, achievement of complete remission post-transplant, ISS Stages I and II, absence of extramedullary disease and transplant in first remission were predictors of long-term survival for patients with MM.

Completeness of death registration in the Civil Registration System, India (2005 to 2015) G. Anil Kumar, Lalit Dandona, Rakhi Dandona Indian Journal of Medical Research 2019 149(6):740-747 Background & objectives: In many developing countries including India, the civil registration data are incomplete, inadequate and not timely, therefore, compromising the usefulness of these data. The completeness of registration of death (CoRD) in the Indian Civil Registration System (CRS) was assessed from 2005 to 2015 at State level to understand its current status and trends over time and also to identify gaps in data to improve CRS data quality. Methods: CoRD for each year for each State was calculated from the CRS reports for 2005-2015. Data were analyzed nationally by geographic region and individual State. The availability of CoRD by age group and sex was also reported. Results: About 40 per cent increase in CoRD was documented for India between 2005 and 2015, with CoRD of 76.6 per cent in 2015. CoRD was >90 per cent in the western and southern regions and the eastern, central and northeastern regions had CoRD lower than the Indian average in 2015. Among the 29 States, 16 (55.2%) State had CoRD >80 per cent and five (17.2%) <50 per cent and 10 States recorded 100 per cent CoRD. Despite the highest per cent increase during 2005-2015 (108.5%), CoRD in Uttar Pradesh was 44.2 per cent in 2015. Varying levels of progress in 2015 were seen between the State with similar CoRD estimates in 2015. Nagaland (−63.3%), Manipur (−33.1%) and Tripura (−30.3%) were the only States that documented a decrease in CoRD during 2005-2015. The age non-availability for India ranged from 37.0 per cent in 2009 to 37.9 per cent in 2015, an average of 41.5 per cent over the seven years and was an average of 35.6 and 36.6 per cent for males and females, respectively. Age was available for all registered deaths only in five (17.2%) of the 29 States in 2009 and four (13.8%) in 2015. Sex non-availability for the recorded deaths was much lower as compared with that for age. Interpretation & conclusions: Despite the significant progress made in CoRD in India, critical differences between the States within the CRS remain, with poor availability of reporting by age and sex. Concentrated efforts to assess the strengths and weaknesses at the State level of the CRS processes, quality of data and plausibility of information generated are needed in India.

Prescription pattern & adverse drug reactions of prokinetics Mansij Biswas, Kritarth Naman Mithileshwar Singh, Yashashri C Shetty, Paresh G Koli, Sushrut Ingawale, Shobna J Bhatia Indian Journal of Medical Research 2019 149(6):748-754 Background & objectives: Prokinetics are extensively prescribed leading to several adverse events (AEs). The aim of this study was to assess the prescription pattern in patients receiving prokinetics, and characteristics of adverse drug reactions (ADRs) in an outpatient department set up in a tertiary care hospital in western India. Methods: Patients attending outpatient departments of a tertiary care hospital and who had received prokinetic agent for at least seven days over the last one month were enrolled. Causality assessment of AEs was done and assessed for severity, preventability, seriousness and predictability. Results: A total of 304 patients [161 males (52.96%); 143 females (47.04%)] were enrolled. Most prescriptions (299/304, 98%) included domperidone, most commonly prescribed as fixed-dose combination (FDC) with pantoprazole (274/304, 90%). Prokinetic dose was not mentioned in 251/304 (83%) prescriptions, and 18/304 (6%) did not mention frequency. Of the 378 AEs reported from 179 patients (47.35%), 306 (81%) were mild, all non-serious; 272 (72%) not preventable and 291 (77%) predictable in nature. Decreased appetite (n=31, 8.2%) and fatigue (n=27,7.14%) were most commonly reported. Causality assessment by the World Health Organization-Uppsala Monitoring Centre scale showed that 180 AEs were related to suspected drug (17 probable and 163 possible ADRs). Significant correlation was observed for AEs with increasing number of drugs per prescription (Spearman's R=+0.8, P =0.05) and with increasing therapy duration (Spearman's R=+1.00, P <0.001). Interpretation & conclusions: Our findings showed that prokinetics were often prescribed as FDCs, with incomplete prescriptions. Domperidone was found to be associated with multiple AEs. It is suggested that regular prescription monitoring should be done in hospitals to encourage rational use of drugs.

Evaluation of new non-invasive & conventional invasive methods of haemoglobin estimation in blood donors Diptiranjan Rout, Suchet Sachdev, Neelam Marwaha Indian Journal of Medical Research 2019 149(6):755-762 Background & objectives: The non-invasive method of haemoglobin (Hb) estimation has unique advantages of exemption of finger prick and associated pain, over invasive methods. This study was done to compare invasive and non-invasive methods of Hb estimation in blood donors keeping haematology analyzer (HA) as a reference method. Methods: The blood donors selected or deferred on the basis of CuSO4method (Hb ≥12.5 g/dl), were included in the study. Hb values of the donors were estimated by HemoCue and then by OrSense methods. An immediate post-donation venous sample was drawn for analysis on HA. Results: The mean Hb value was 13.98±1.27 g/dl on HA, 14.87±1.03 g/dl on OrSense and 15.03±1.31 g/dl on HemoCue. CuSO4, HemoCue and OrSense demonstrated sensitivities of 18.7, 18.7 and 13.1 per cent, positive predictive values (PPV) of 64.5, 83.3 and 60.9 per cent and specificities of 98.9, 99.6 and 99.1 per cent, respectively. The intra-class correlation coefficient for OrSense was 0.726 while that for HemoCue was 0.851. Bland-Altman plots demonstrated 2SD difference of >2.0 g/dl in Hb estimations between HA and HemoCue/OrSense. Interpretation & conclusions: The non-invasive modality may provide the near-ideal pre-donation Hb screening platform if an improvement can be done in the sensitivity and PPV of the non-invasive method keeping in view its unique advantages.

Association of endotoxaemia & gut permeability with complications of acute pancreatitis: Secondary analysis of data Namrata Singh, Ujjwal Sonika, Praneeth Moka, Brij Sharma, Vikas Sachdev, Sushil Kumar Mishra, Ashish Datt Upadhyay, Anoop Saraya Indian Journal of Medical Research 2019 149(6):763-770 Background & objectives: In acute pancreatitis (AP) gut barrier dysfunction is considered as an important predisposing factor leading to increased intestinal permeability (IP). In this study a pooled analysis of data published in our previous four studies on various aspects of gut permeability and endotoxaemia in patients with AP was attempted to find an association between increased IP and severity of disease and associated complications. Methods: This study was a pooled analysis of data of four previously published prospective studies on AP. Gut permeability, assessed by lactulose/mannitol excretion in urine and endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM) were measured on days zero and seven (D0 and D7) of admission. All patients received standard treatment of AP. We studied whether IgG and IgM anti-endotoxin titres and lactulose-mannitol ratio (LMR) at admission and D7 were associated with organ failure, infection and mortality. Results: The titres of anti-endotoxin IgG and IgM were lower in all patients of AP (n=204), both in mild AP (n=24) and severe AP (n=180) in the first week, compared to controls (n=15). There was no significant difference in serum IgG and IgM anti-endotoxin levels and LMR at baseline and at D7 among patients with organ failure, infection and mortality. Interpretation & conclusions: Our findings showed that serum IgG and IgM anti-endotoxin titres and LMR at admission and at day 7 were not associated with organ failure, infection, and death of patients with AP.