Prescription-based cost analysis of medicines for cardiovascular risk factors at Indian Council of Medical Research-Rational Use of Medicine Centre Hospitals of India.

OBJECTIVES: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs. MATERIALS AND METHODS: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers. The prices of medicines prescribed were compared based on presence or absence in NLEM India-2015 and prescribing by generic versus brand name. The price was standardized and presented as average price per medicine per year for a given medicine. The results are presented in Indian rupee (INR) and as median (range). RESULTS: Of the 4,736 prescriptions collected, 843 contained oral antidiabetic, antihypertensive, and/or hypolipidemic medicines. The price per medicine per year for NLEM oral antidiabetics was INR 2849 (2593-3104) and for non-NLEM was INR 5343 (2964-14364). It was INR 806 (243-2132) for generic and INR 3809 (1968-14364) for branded antidiabetics. Antihypertensives and hypolipidemics followed the trend. The price of branded non-NLEM medicines was 5-22 times higher compared to generic NLEM which, for a population of 1.37 billion, would translate to a potential saving of 346.8 billion INR for statins. The variability was significant for sulfonylureas, angiotensin receptor blockers, beta-blockers, diuretics, and statins (P < 0.0001). CONCLUSION: The study highlights an urgent need for intervention to actualize the maximum benefit of government policies and minimize the out-of-pocket expenditure on medicines.

Short-Term Outcomes and Quality-of-Life Assessment Following Rives-Stoppa and Transversus Abdominis Release Procedures of Open Ventral Hernia Repair.

INTRODUCTION: Ventral hernia is one of the common surgical conditions that can significantly impact a patient's quality of life (QoL). Open ventral hernia repair using the Rives-Stoppa (RS) and Transversus Abdominis Release (TAR) procedures has gained recognition for its effectiveness in achieving hernia repair and reducing the risk of further recurrence. However, limited research has been performed to explore the short-term outcomes and QoL assessment following these two surgical techniques. The aim of this study was to know the result after RS and TAR methods of hernia repair in terms of short-term recurrences, pain, postoperative complications, and QoL. METHODS: This was a prospective, interventional study, which included 30 patients fulfilling the inclusion criteria. The study group was subjected to posterior component separation (PCS)-TAR and RS repair as per surgical indication (RS if defect size 4-10cm; PCS-TAR if defect size >10cm and

Incremental value of endoscopic brush cytology in response assessment after chemo-irradiation for Esophageal cancer.

BACKGROUND: Response assessment after chemo-radiotherapy (CTRT) in locally advanced esophageal cancer is usually performed using a PET-CT scan, an upper GI endoscopy (UGIE) and histological correlation with biopsy or cytology. We aim to study the incremental value of brush cytology in addition to PET-CT for response assessment. MATERIALS AND METHODS: In this retrospective analysis, 40 patients with Stage II- IV carcinoma esophagus treated with radical intent between June 2015 and August 2019 were included. Patients were treated with either upfront concurrent CTRT or neo-adjuvant chemotherapy followed by CTRT. All patients underwent PET-CT and UGIE for initial staging and response assessment on follow-up. Patients with esophageal stricture (disease related or treatment induced) had brush cytology done during UGIE. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of brush cytology were calculated considering serial clinical follow-up as gold standard. RESULTS: Twenty-three male (57.5%) and 17 (42.5%) female patients with median age of 57 years (range: 27 - 79 years) were analyzed. Concurrent CTRT was delivered in 52.5%; 75% patients were treated with intensity-modulated radiotherapy (IMRT); median RT dose was 63 Gy (range- 41.4 to 64 Gy). At a median follow-up of 16 months (range 6- 54 months), 20 patients (55.5%) were clinically controlled, 9 (25%) had local recurrence, 5 (13.8%) had loco-regional recurrence and 2 had distant metastasis. Considering clinical follow-up as the gold standard, sensitivity, PPV and NPV of PET-CT combined with brush cytology improved compared to PET-CT alone and was found to be 75%, 90%, 85.7% and 81.8% respectively. CONCLUSION: We found that brush cytology on endoscopy is a simple tool with high specificity which adds value to the findings of response assessment PET-CT scan and thereby can increase the confidence of the treating oncologist in making clinical decisions.

Comparative Assessment of Digital Pathology Systems for Primary Diagnosis.

BACKGROUND: Despite increasing interest in whole-slide imaging (WSI) over optical microscopy (OM), limited information on comparative assessment of various digital pathology systems (DPSs) is available. MATERIALS AND METHODS: A comprehensive evaluation was undertaken to investigate the technical performance-assessment and diagnostic accuracy of four DPSs with an objective to establish the noninferiority of WSI over OM and find out the best possible DPS for clinical workflow. RESULTS: A total of 2376 digital images, 15,775 image reads (OM - 3171 + WSI - 12,404), and 6100 diagnostic reads (OM - 1245, WSI - 4855) were generated across four DPSs (coded as DPS: 1, 2, 3, and 4) using a total 240 cases (604 slides). Onsite technical evaluation revealed successful scan rate: DPS3 < DPS2 < DPS4 < DPS1; mean scanning time: DPS4 < DPS1 < DPS2 < DPS3; and average storage space: DPS3 < DPS2 < DPS1 < DPS4. Overall diagnostic accuracy, when compared with the reference standard for OM and WSI, was 95.44% (including 2.48% minor and 2.08% major discordances) and 93.32% (including 4.28% minor and 2.4% major discordances), respectively. The difference between the clinically significant discordances by WSI versus OM was 0.32%. Major discordances were observed mostly using DPS4 and least in DPS1; however, the difference was statistically insignificant. Almost perfect (κ ≥ 0.8)/substantial (κ = 0.6-0.8) inter/intra-observer agreement between WSI and OM was observed for all specimen types, except cytology. Overall image quality was best for DPS1 followed by DPS4. Mean digital artifact rate was 6.8% (163/2376 digital images) and maximum artifacts were noted in DPS2 (n = 77) followed by DPS3 (n = 36). Most pathologists preferred viewing software of DPS1 and DPS2. CONCLUSION: WSI was noninferior to OM for all specimen types, except for cytology. Each DPS has its own pros and cons; however, DPS1 closely emulated the real-world clinical environment. This evaluation is intended to provide a roadmap to pathologists for the selection of the appropriate DPSs while adopting WSI.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.

Unveiling Taenia solium kinome profile and its potential for new therapeutic targets.

Background: Helminth infections cause widespread morbidity and are a significant global disease burden. One among them is Neurocysticercosis, a central nervous system infection caused by the larvae Taenia solium, leading to epilepsy. Helminths are strong immune modulators and can survive for a long time in adverse host environments. Kinases are molecular switches and are essential to initiate/propagate signaling cascades and are detrimental to the regulation of homeostasis. They have been implicated in the progression of many diseases and are potentially lucrative drug targets.Objective: To identify kinases in T. solium proteome and prioritize them as drug targets.Methodology: A Hidden Markov Model (HMM) was used to curate and classify kinases into families based on sequence homology to model organisms followed by phylogenetic analysis of each family. To predict potential drug targets, kinases were identified based on a homologically lethal relationship to C. elegans but non-lethal to humans. Kinases thus selected were searched for matching ligands in SARFkinase and DrugBank databases.Result and conclusion: T. solium kinases make up 1.8% of its proteome, CMGC is the largest kinase family and RGC is the smallest and catalytically inactive family. We predict 23-potential kinases to be drug targets for T. solium.[Figure: see text].

Traffic noise mapping of Indian roads through smartphone user community participation.

Road traffic noise pollution is a global hazard, and rapid urbanization has aggravated the problem. This paper explores a novel approach which involves a smartphone user community to monitor the prevalent noise. The system involves a client application on smartphones that records noise, processes the information and communicates to a server and shares the information as visual noise levels on Google® Maps. A fuzzy logic-based classification of noise is proposed. Results from residential, commercial, and industrial areas of the northern region of India are demonstrated. The noise levels are generally found to be higher than the prescribed standards. The experiment demonstrates the huge potential of user community participation in monitoring noise pollution.

Calciphylaxis: A Disease of Pannicular Thrombosis.

OBJECTIVE: To identify coagulation risk factors in patients with calciphylaxis and the relationship between anticoagulation use and overall survival. PATIENTS AND METHODS: Study subjects were 101 patients with calciphylaxis seen at Mayo Clinic from 1999 to September 2014. Data including thrombophilia profiles were extracted from the medical records of each patient. Survival status was determined using patient registration data and the Social Security Death Index. Survival was estimated using the Kaplan-Meier method, and associations were evaluated using Cox proportional hazards models. RESULTS: Sixty-four of the 101 patients underwent thrombophilia testing. Of these, a complete test panel was performed in 55 and a partial panel in 9. Severe thrombophilias observed in 60% (33 of 55) of the patients included antiphospholipid antibody syndrome protein C, protein S, or antithrombin deficiencies or combined thrombophilias. Of the 55 patients, severe thrombophilia (85%, 23 of 27) was noted in patients who were not on warfarin at the time of testing (27). Nonsevere thrombophilias included heterozygous factor V Leiden (n=2) and plasminogen deficiency (n=1). For the comparison of survival, patients were divided into 3 treatment categories: Warfarin (n=63), other anticoagulants (n=20), and no anticoagulants (n=18). There was no statistically significant survival difference between treatment groups. CONCLUSION: Laboratory testing reveals a strikingly high prevalence of severe thrombophilias in patients with calciphylaxis, underscoring the importance of congenital and acquired thrombotic propensity potentially contributing to the pathogenesis of this disease. These findings may have therapeutic implications; however, to date, survival differences did not vary by therapeutic choice.

Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization.

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation.

Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo-generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.

Benefits of adding small financial incentives or optional group meetings to a web-based statewide obesity initiative.

OBJECTIVE: To examine whether adding either small, variable financial incentives or optional group sessions improves weight losses in a community-based, Internet behavioral program. METHODS: Participants (N = 268) from Shape Up Rhode Island 2012, a 3-month Web-based community wellness initiative, were randomized to: Shape Up+Internet behavioral program (SI), Shape Up+Internet program+incentives (SII), or Shape Up+Internet program+group sessions (SIG). RESULTS: At the end of the 3-month program, SII achieved significantly greater weight losses than SI (SII: 6.4% [5.1-7.7]; SI: 4.2% [3.0-5.6]; P = 0.03); weight losses in SIG were not significantly different from the other two conditions (SIG: 5.8% [4.5-7.1], P's ≥ 0.10). However, at the 12-month no-treatment follow-up visit, both SII and SIG had greater weight losses than SI (SII: 3.1% [1.8-4.4]; SIG: 4.5% [3.2-5.8]; SI: 1.2% [-0.1-2.6]; P's ≤ 0.05). SII was the most cost-effective approach at both 3 (SII: $34/kg; SI: $34/kg; SIG: $87/kg) and 12 months (SII: $64/kg; SI: $140/kg; SIG: $113/kg). CONCLUSIONS: Modest financial incentives enhance weight losses during a community campaign, and both incentives and optional group meetings improved overall weight loss outcomes during the follow-up period. However, the use of the financial incentives is the most cost-effective approach.

Adding evidence-based behavioral weight loss strategies to a statewide wellness campaign: a randomized clinical trial.

OBJECTIVES: We determined the efficacy and cost-effectiveness of adding an evidence-based Internet behavioral weight loss intervention alone or combined with optional group sessions to ShapeUp Rhode Island 2011 (SURI), a 3-month statewide wellness campaign. METHODS: We randomized participants (n = 230; body mass index = 34.3 ±6.8 kg/m(2); 84% female) to the standard SURI program (S) or to 1 of 2 enhanced programs: SURI plus Internet behavioral program (SI) or SI plus optional group sessions (SIG). The primary outcome was weight loss at the end of the 3-month program. RESULTS: Weight losses differed among all 3 conditions (S: 1.1% ±0.9%; SI: 4.2% ±0.6%; SIG: 6.1% ±0.6%; Ps ≤ .04). Both SI and SIG increased the percentage of individuals who achieved a 5% weight loss (SI: 42%; SIG: 54%; S: 7%; Ps < .001). Cost per kilogram of weight loss was similar for S ($39) and SI ($35); both were lower than SIG ($114). CONCLUSIONS: Although weight losses were greatest at the end of SURI with optional group sessions, the addition of an Internet behavioral program was the most cost-effective method to enhance weight losses.

Improving weight loss outcomes of community interventions by incorporating behavioral strategies.

OBJECTIVES: We examined whether adding behavioral weight loss strategies could improve the outcomes of a community weight loss campaign. METHODS: Shape Up RI is a 12-week, online, team-based program for health improvement in Rhode Island. In study 1, we randomly assigned participants to the standard Shape Up RI program or to the program plus video lessons on weight loss. In study 2, we randomly assigned participants to the standard program or to the program plus video lessons; daily self-monitoring of weight, eating, and exercise; and computer-generated feedback. RESULTS: Adding video lessons alone (study 1) did not result in significantly improved weight loss (2.0 ±2.8 kg vs 1.4 ±2.9 kg; P = .15). However, when the video lessons were supplemented with self-monitoring and feedback (study 2), the average weight loss more than doubled (3.5 ±3.8 kg vs 1.4 ±2.7 kg; P < .01), and the proportion of individuals achieving a weight loss of 5% or more tripled (40.5% vs 13.2%; P < .01). Participants in study 2 submitted self-monitoring records on 78% of days, and adherence was significantly related to outcome. CONCLUSIONS: Adding behavioral strategies to community campaigns may improve weight loss outcomes with minimal additional cost.

Effect of teammates on changes in physical activity in a statewide campaign.

OBJECTIVE: Most Americans do not meet physical activity recommendations. Statewide campaigns can effectively increase activity levels. Reported herein are physical activity outcomes from Shape Up Rhode Island (SURI) 2007, a statewide campaign to increase steps through team-based competition. Given the importance of social networks in behavior change, this paper focused on the effects of team and team characteristics on activity outcomes. METHOD: For 16weeks, 5333 adults comprising 652 teams wore pedometers and reported their steps online. RESULTS: Participants' daily steps increased from 7029(3915) at baseline to 9393(5976) at SURI end (p<0.001). There was a significant intraclass correlation for step change among team members (ICC=0.09); thus, an individual's change in steps was influenced by what team they were on. Moreover, baseline team characteristics predicted individual step change; being on a more active team was associated with greater increases in activity for individual members (p<0.001), whereas being on a team with a broad range of steps was associated with smaller changes in activity for individual members (p=0.02). CONCLUSION: These findings are the first to suggest that team members influence individual activity outcomes in team-based statewide campaigns. Future research should explore ways to use social network factors to enhance team-based physical activity programs.

Lifetime exposure to arsenic in residential drinking water in Central Europe.

OBJECTIVE: Methods and results are presented for an arsenic exposure assessment integral to an epidemiological case-control study of arsenic and cancer-the European Commission funded ASHRAM (Arsenic Health Risk Assessment and Molecular Epidemiology) study carried out in some counties of Hungary, Romania and Slovakia. METHODS: The exposure history of each participant (N = 1,392) was constructed by taking into account how much water they consumed (as water, in drinks and in food), sources of drinking water in their various residences over their lifetime, and the concentrations of arsenic in their various water supplies measured by Hydride Generation-Atomic Absorption Spectrometry (HG-AAS). Concentrations of arsenic in previous water supplies were either derived from contemporary analyses of the same source, or from routine historical data from measurements performed by the authorities in each country. Using this approach, 80% of the recorded lifetime residential history was matched to an arsenic concentration. Seven indices of current, life time, and peak exposure were calculated. RESULTS: The exposure indices were all log-normally distributed and the mean and median lifetime average concentrations were in Hungary 14.7 and 13.3 microg l(-1), Romania 3.8 and 0.7 microg l(-1) and in Slovakia 1.9 and 0.8 microg l(-1), respectively. Overall 25% of the population had average concentrations over 10 microg l(-1) and 8% with exposure over 50 microg l(-1). CONCLUSIONS: Careful assessment of arsenic in drinking water supplies (both current and previous) enabled the majority of study participants' cumulative lifetime of potential exposure to arsenic in residential water to be characterised.

Determination of allele frequency in pooled DNA: comparison of three PCR-based methods.

Determination of allele frequency in pooled DNA samples is a powerful and efficient tool for large-scale association studies. In this study, we tested and compared three PCR-based methods for accuracy, reproducibility, cost, and convenience. The methods compared were: (i) real-time PCR with allele-specific primers, (ii) real-time PCR with allele-specific TaqMan probes, and (iii) quantitative sequencing. Allele frequencies of three single nucleotide polymorphisms in three different genes were estimated from pooled DNA. The pools were made of genomic DNA samples from 96 cases with basal cell carcinoma of the skin and 96 healthy controls with known genotypes. In this study, the allele frequency estimation made by real-time PCR with allele-specific primers had the smallest median deviation (MD) from the real allele frequency with 1.12% (absolute percentage points) and was also the cheapest method. However; this method required the most time for optimization and showed the highest variation between replicates (SD = 6.47%). Quantitative sequencing, the simplest method, was found to have intermediate accuracies (MD = 1.44%, SD = 4.2%). Real-time PCR with TaqMan probes, a convenient but very expensive method, had an MD of 1.47% and the lowest variation between replicates (SD = 3.18%).