Optimising Palliative Care for Children with Metastatic Neuroblastoma and the Paediatrician's Role in a Shared Care Model - Proposal from a Regional Cancer Centre in India.

Objectives: The burden of advanced and metastatic cancer is high among children in developing countries, and palliative care (PC) services for children are sparsely available and poorly accessed. To estimate the burden of PC requirements in children with metastatic neuroblastoma (NB), and to evaluate the PC services offered. Materials and Methods: Retrospective analysis of case records of children 1-14 years diagnosed with metastatic NB from 1 January 2008 to 31 December 2017. Results: One hundred and nineteen patients with metastatic NB were included, of which 87 patients received PC consultation. Early PC referral occurred only in 13 patients (14.9%), and pain was the most prominent symptom. Shifting of care from oncology to PC occurred at disease relapse in 58 patients (66.6%) and at end-of-life in 16 patients (18.3%). Nausea/vomiting, constipation and abdominal distension were the most common symptoms during end-of-life. Seventy-one patients (85%) died of disease, median time to death being 9 months from diagnosis and 4 months from relapse. The mean time from initiation of PC to death was 4.2 months. Conclusion: Timely integration of PC and shared care incorporating the oncology team, PC team and local paediatricians can ease out transition in care, ensure a continuum of care and improve the quality of treatment delivered to children with metastatic cancer.

Clinical profile and outcome of children with anaplastic large cell lymphoma treated with short-course chemotherapy - ten years experience from a tertiary care center in a LMIC.

Anaplastic large-cell lymphoma (ALCL) constitutes 10-15% of non-Hodgkin lymphoma in children. With short-course chemotherapy, outcome has improved up-to 90% in developed-countries. There is limited-data on outcome of pediatric ALCL treated with ALCL99 protocol from low-middle income countries. Children ≤14 years, diagnosed with ALCL between 1st January 2007 and 31st December 2016 were analyzed. Details regarding clinical-presentation and treatment were recorded and outcome was analyzed. Fourteen-children were diagnosed. Median-age was 114 months (range 24 - 162 months). Male:female ratio was 3.6:1. Stage-I, II and III disease was seen in three (21.4%), three (21.4%), and eight (57.1%) children, respectively. Low, standard and high-risk disease was seen in two (14.2%), six (42.9%) and six (42.9%), respectively. All children were treated using ALCL99 protocol. Three (21.4%) children had disease-progression/relapse and five (35.7%) died (three from treatment-related mortality, and two from disease). At median follow-up of 54-months, four-year EFS and OS were 64.3% and 64.3%, respectively. Log-rank test demonstrated female gender (p = 0.005), stage-III disease (p < 0.001), visceral-organ involvement (p = 0.035), high-risk disease (p = 0.016) and, serum albumin ≤3.5 g/dL (p = 0.031) associated with significantly worse 4-year EFS. Cox-regression analysis demonstrated female gender associated with poor EFS (p = 0.02) and female gender and visceral-organ involvement associated with poor OS (p = 0.02, p = 0.011, respectively). Good survival could be achieved for children with ALCL using uniform treatment protocol in a resource-limited setting, especially among low and standard-risk children. Female-sex, high-risk disease, stage-III disease, visceral organ involvement and low albumin levels were associated with poor outcome, however these findings need to be corroborated in larger studies.

Blockchain applications in health care for COVID-19 and beyond: a systematic review.

The COVID-19 pandemic has had a substantial and global impact on health care, and has greatly accelerated the adoption of digital technology. One of these emerging digital technologies, blockchain, has unique characteristics (eg, immutability, decentralisation, and transparency) that can be useful in multiple domains (eg, management of electronic medical records and access rights, and mobile health). We conducted a systematic review of COVID-19-related and non-COVID-19-related applications of blockchain in health care. We identified relevant reports published in MEDLINE, SpringerLink, Institute of Electrical and Electronics Engineers Xplore, ScienceDirect, arXiv, and Google Scholar up to July 29, 2021. Articles that included both clinical and technical designs, with or without prototype development, were included. A total of 85 375 articles were evaluated, with 415 full length reports (37 related to COVID-19 and 378 not related to COVID-19) eventually included in the final analysis. The main COVID-19-related applications reported were pandemic control and surveillance, immunity or vaccine passport monitoring, and contact tracing. The top three non-COVID-19-related applications were management of electronic medical records, internet of things (eg, remote monitoring or mobile health), and supply chain monitoring. Most reports detailed technical performance of the blockchain prototype platforms (277 [66·7%] of 415), whereas nine (2·2%) studies showed real-world clinical application and adoption. The remaining studies (129 [31·1%] of 415) were themselves of a technical design only. The most common platforms used were Ethereum and Hyperledger. Blockchain technology has numerous potential COVID-19-related and non-COVID-19-related applications in health care. However, much of the current research remains at the technical stage, with few providing actual clinical applications, highlighting the need to translate foundational blockchain technology into clinical use.

Outcomes of pediatric mixed phenotype acute leukemia treated with lymphoid directed therapy: Analysis of an institutional series from India.

There is limited data regarding pediatric mixed phenotype acute leukemia (MPAL) and there is no global consensus on its management yet. In this retrospective study, we analyzed the outcomes of children diagnosed with MPAL at our institute. This study included children ≤ 14 years with MPAL who presented to a tertiary cancer center in India from January 1st 2009 to December 31st 2015. Over a seven-year period, 1390 patients with leukemia presented to our institute of which 22 patients (1.5%) had MPAL. Sixteen patients (72.7%) had B/myeloid leukemia, while 4 (18.1%) and 2 (9%) patients had T/myeloid and B/T leukemia respectively. Twenty-one patients were treated with a modified BFM ALL 95 protocol. 76.1% (n = 16) of patients had a good prednisolone response (GPR) on day 8 and end-of-induction (EOI) marrow was in remission in 90.5% (n = 19). A poor prednisolone response (PPR) on day 8 correlated with an inferior relapse-free survival (25% vs 79.5%, P=.025). The 4-year event-free survival (EFS) and overall survival (OS) for the entire group was 60.8% and 64.9% respectively while the EFS for patients who had a GPR and remission at the EOI (n = 15) was 80% as compared to 16.7% in patients with PPR or induction failure. Lymphoid directed chemotherapy is seen to have good survival outcomes in pediatric MPAL. However, a PPR on day 8 or a positive EOI marrow may be an indication for more aggressive treatment.

Isolated parapharyngeal cold abscess in a 9-year-old boy.

Tuberculous adenitis presenting as an isolated cold abscess in the parapharyngeal space is very uncommon and has not been reported in the paediatric age group; presentation as a retropharyngeal abscess, however, is well known. Nine-year-old boy with a progressively increasing swelling on the right side of the neck for 2 months was referred with a clinical diagnosis of neuroblastoma. Surgical exploration of the parapharyngeal space by needle aspiration yielded a cheesy material and Mycobacterium tuberculosis was detected by DNA TB PCR. Tuberculosis should always be considered in the differential diagnosis of a cervical swelling in a child.

Trait and Marker Associations in Oryza nivara and O. rufipogon Derived Rice Lines under Two Different Heat Stress Conditions.

Wild species and derived introgression lines (ILs) are a good source of genes for improving complex traits such as heat tolerance. The effect of heat stress on 18 yield traits was studied in four treatments in two seasons, under field conditions by subjecting 37 ILs and recurrent parents Swarna and KMR3, N22 mutants, and wild type and 2 improved rice cultivars to heat stress using polycover house method in wet season and late sowing method in dry season. Normal grown unstressed plants were controls. Both correlation and path coefficient analysis showed that the major contributing traits for high yield per plant (YPP) under heat stress conditions were tiller number, secondary branches in panicle, filled grain number, and percent spikelet fertility. Three ILs, K-377-24, K-16-3, and S-148 which gave the highest YPP of 12.30-32.52 g under heat stress in both the seasons were considered the most heat tolerant. In contrast, K-363-12, S-75, and Vandana which gave the least YPP of 5.36-10.84 g were considered heat susceptible. These lines are a good genetic resource for basic and applied studies on heat tolerance in rice. Genotyping using 49 SSR markers and single marker analysis (SMA) revealed 613 significant marker- trait associations in all four treatments. Significantly, nine markers (RM243, RM517, RM225, RM518, RM525, RM195, RM282, RM489, and RM570) on chromosomes 1, 2, 3, 4, 6, and 8 showed association with six traits (flag leaf spad, flag leaf thickness, vegetative leaf temperature, plant height, panicle number, and tiller number) under heat stress conditions in both wet and dry seasons. Genes such as heat shock protein binding DnaJ, Hsp70, and temperature-induced lipocalin-2 OsTIL-2 close to these markers are candidates for expression studies and evaluation for use in marker assisted selection for heat tolerance.

Field level evaluation of rice introgression lines for heat tolerance and validation of markers linked to spikelet fertility.

Rice lines derived from wild species and mutants can serve as a good resource for favorable alleles for heat tolerance. In all, 48 stable lines including 17 KMR3/O. rufipogon introgression lines (KMR3 ILs), 15 Swarna/O. nivara ILs (Swarna ILs) along with their parents, Nagina 22 (N22) and its 4 EMS induced mutants and 7 varieties were evaluated for heat tolerance under irrigated conditions under field in two seasons, wet season 2012 using poly cover house method and dry season 2013 using late sown method. Spikelet fertility (SF), yield per plant (YP) and heat susceptibility index (HSI) for these two traits were considered as criteria to assess heat tolerance compared to control. Four KMR3 ILs and eight Swarna ILs were identified as heat tolerant based on SF and YP and their HSIs in both wet and dry seasons. S-65 and S-70 showed low SF and high YP consistently in response to heat in both seasons. We provide evidence that SF alone may not be the best criterion to assess heat tolerance and including YP is important as lines with low SF but high YP and vice versa were identified under heat stress. Out of 49 SSR markers linked to spikelet fertility, 18 were validated for five traits. RM229 in wet season and RM430 and RM210 in dry season were significantly associated with both SF and its HSI under heat stress. RM430 was also significantly associated with both YP and its HSI in dry season. Thirty two candidate genes were identified close to nine markers associated with traits under heat stress.

A study of community-associated methicillin-resistant Staphylococcus aureus in patients with pyoderma.

BACKGROUND: Health care-associated methicillin-resistant Staphylococcus aureus(HA-MRSA) are resistant to multiple antibiotics, therefore infections caused by them are difficult to treat resulting in high morbidity and mortality. While most of the research activities and public health initiatives are focused on HA-MRSA, the newly emerging pathogen, community-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) is gaining in significance in respect to patient morbidity. There is a significant paucity of data regarding CA-MRSA in the developing parts of the world. AIM: To study the proportions of HA-MRSA and CA-MRSA infections among patients with culture-proven S. aureus infection and to find out how many of these patients showed presence of MRSA in nasal cultures of healthy contacts. MATERIALS AND METHODS: Clinical details of 227 patients were recorded in the study, such as the duration and recurrence of the infection, history of antibiotic intake, and the presence of other medical illnesses. A pus swab was taken from each lesion and sent for culture and sensitivity. If the culture grew S. aureus, they were screened for methicillin resistance. A swab from the anterior nares of the healthy contact of each patient, whenever available, was collected and it was screened for MRSA. RESULTS: Furunculosis was most common among the primary pyodermas (53/134; 39. 5%). Out of 239 pus culture samples obtained from 227 patients, 192 (84.58%) grew S. aureus; of these 150 (78.12%) were methicillin-sensitive S. aureus (MSSA), whereas 42 (21.98%) were MRSA. Out of the 42 MRSA isolated, 33 turned out to be CA-MRSA (78%) and 9 (22%) were HA-MRSA. Nasal swabs of healthy contacts of 34 MRSA patients were cultured. Out of them, two grew MRSA in the culture. CONCLUSION: The isolation rate of S. aureus was high in our study. Furthermore, our study, although hospital based, clearly indicated the substantial magnitude of the CA-MRSA problem in the local population.

Effect of permeation enhancers in the mucoadhesive buccal patches of salbutamol sulphate for unidirectional buccal drug delivery.

The purpose of this work was to study the effect of various permeation enhancers on the permeation of salbutamol sulphate (SS) buccal patches through buccal mucosa in order to improve the bioavailability by avoiding the first pass metabolism in the liver and possibly in the gut wall and also achieve a better therapeutic effect. The influence of various permeation enhancers, such as dimethyl sulfoxide (DMSO), linoleic acid (LA), isopropyl myristate (IPM) and oleic acid (OA) on the buccal absorption of SS from buccal patches containing different polymeric combinations such as hydroxypropyl methyl cellulose (HPMC), carbopol, polyvinyl alcohol (PVA), polyvinyl pyrollidone (PVP), sodium carboxymethyl cellulose (NaCMC), acid and water soluble chitosan (CHAS and CHWS) and Eudragit-L100 (EU-L100) was investigated. OA was the most efficient permeation enhancer increasing the flux greater than 8-fold compared with patches without permeation enhancer in HPMC based buccal patches when PEG-400 was used as the plasticizer. LA also exhibited a better permeation enhancing effect of over 4-fold in PVA and HPMC based buccal patches. In PVA based patches, both OA and LA were almost equally effective in improving the SS permeation irrespective of the plasticizer used. DMSO was more effective as a permeation enhancer in HPMC based patches when PG was the plasticizer. IPM showed maximum permeation enhancement of greater than 2-fold when PG was the plasticizer in HPMC based buccal patches.

Titanium dioxide as an osteoconductive material: an animal study.

The purpose of the present study was to evaluate the biocompatibility and osteoconductive potential of pure and pigment forms of titanium dioxide. Pure and pigment forms of titanium dioxide were incorporated into prepared bur holes in the femur bone of rabbits. Implantation was done on six Albino rabbits which were sacrificed at the end of 3rd, 4th and 5th months after implantation. Radiographic, histologic and scanning electron microscopic evaluations of the implanted sites were performed. Heamatologic and soft tissue response to these materials were also evaluated. The results showed that both pure and pigment forms of titanium dioxide are biocompatible and have good osteoconductive properties. It was concluded that titanium dioxide can be effectively used in the augmentation of osseous defects and inadequate ridge forms.

Interaction of herbs and glibenclamide: a review.

Herbs and herbal products are considered to be safer and people mix it often with the oral hypoglycemic agent in diabetes therapy. But numerous reports say that every combination of herbs and drugs is not safe. Some combinations may be beneficial and some may be harmful also. So before taking any herbal remedies with oral hypoglycemic agent, patient should consult physician. In this paper we are summarizing the reports available on the interaction of herbal remedies to one of the oral hypoglycemic agents (glibenclamide) and categorizing the effect of the combination is beneficial and harmful.

Efficacy and Safety of COX-2 Inhibitors in the Clinical Management of Arthritis: Mini Review.

In the clinical management of arthritis, the choice of nonsteroidal anti inflammatory drug (NSAID) remains confusing and controversial. A common practice on the choice of NSAID in clinical management of arthritis is the risk benefit ratio. The main objective of this review is to addresses the main arguments for the pharmacological and clinical use of COX-2 inhibitors in relation to nonselective NSAIDs for the clinical management of arthritis. This review concluded that, both NSAIDs and COX-2 inhibitors are equally effective and are associated with increased risk of GI, renal, and CV, adverse effects. Complete understanding of the patient's comorbid conditions and concomitant medications, coupled with precise monitoring during the treatment, may help to decrease the threat of adverse effects induced by nonselective NSAIDs and selective COX-2 inhibitors.

Microsatellite based analysis of genetic diversity of popular black pepper genotypes in South India.

The genotypes of black pepper are morphologically and genotypically highly diverse and carry all the cumulative variations inherited and maintained through generations. The present study describes the Simple Sequence Repeat (SSR) or microsatellite based assessment of genetic diversity among forty popular genotypes and four different species of black pepper in Southern region of India. For isolation of SSR primers, our earlier attempts with enrichment strategies like 'Triplex affinity capture' did not extract a single SSR primer due to close proximity of restriction sites to the SSR motif. Hence we developed a 'Sequential Reverse Genome Walking (SRGW)' strategy with better enrichment efficiency of 72% that generated seven new SSR primers. Genotyping precisely discriminated majority of genotypes which indicated that the SSR primers are very informative. A total of 62 alleles with an average of 15.5 alleles over 4 loci were identified. All the SSR primers showed an average Polymorphism Information Content (PIC) value of 0.85. The estimated average Shared Allele Frequency ranged between 1.57 and 20.12%. The PCA plot revealed four closely related individual groups and identified Karimunda, Wild pepper and a local landrace 'local b' as the most divergent genotypes. Cluster analysis exposed the genetic relatedness between hybrids and selections with other known cultivars. The introduction of black pepper from South India to Malaysia was emphasized from the observation of genetic similarity of Malaysian cultivar 'Kuching' with other indigenous popular cultivars. The study was first to portray the precise genetic relatedness among the major indigenous genotypes of black pepper.

Mucoadhesive patches of Salbutamol sulphate for unidirectional buccal drug delivery: development and evaluation.

Mucoadhesive buccal patches of Salbutamol Sulphate were prepared using five different polymers (polyvinylpyrrolidone [PVP]), polyvinyl alcohol [PVA], water soluble chitosan [CH(WS)], acid soluble chitosan [CH(AS)], hydroxypropyl methyl cellulose [HPMC])in various proportions and combinations (CH(WS)/PVP/HPMC, CH(WS)/PVA/HPMC, CH(AS)/PVP/HPMC, and CH(AS)/PVA/HPMC). A 3(2) full factorial design was used to design the experiments. A total of 72 patches were prepared. Thickness of the patches ranged between 0.3±0.003 and 0.6±0.009 mm. Mass of the patches were in the range of 68.12±4.6 to 95.02±7.2 mg. Patches showed increased mass whenever PEG -400 was used as plasticizer. The surface pH of patches were acidic to neutral (pH 4-pH 7). Patches showed satisfactory drug loading efficiency (85%to 97%). Eight formulations(C9, C18, C27, C36, D9, D18, D27, and D36)-which showed high folding endurance- were selected for further characterization. Patches with PEG -400 showed higher swelling index when compared to PG. The residence time of the patches ranged between 115 min and 120 min. Formulation C18 showed the maximum in vitro drug release of 101.4 % over a period of 120 min. Formulations D36 and C36 were best fitted to Higuchi model. The remaining formulations were best fitted to the Korsmeyer-Peppas model. Drug permeation was fast and showed the similar profile as that of the in vitro drug release. Patches were stable, during and at the end of the accelerated stability study.

Formulation and in vitro-in vivo evaluation of ketoprofen-loaded albumin microspheres for intramuscular administration.

The objective of this work was to prepare and evaluate ketoprofen-loaded albumin microspheres for intramuscular administration. Microspheres were prepared by emulsion cross-linking method using a 2(3) factorial design and the effect of different factors on entrapment efficiency was determined. Microspheres were evaluated for entrapment efficiency, percentage yield, particle size and release behaviour. Selected formulations were then tested by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Further they were analysed for residual solvents, syringeability and stability. Microspheres were then sterilized and bioavailability studies were carried out in New Zealand white rabbits. The physical characteristics of microspheres showed that they were suitable for IM administration. The sterilization technique adopted was adequate to maintain sterility. In vivo studies showed increase in C(max), AUC, t(1/2) and MRT (p < 0.05) administered in the form of microspheres. MRT of ketoprofen was almost 3.2-times in the form of microspheres. From these results it was concluded that the developed albumin microspheres of ketoprofen is a potential delivery system for once-a-day intramuscular administration.

Clinical evaluation of 5-fluorouracil from transdermal patches on EAC and DLA cell-induced tumors in mice.

The aim of the present study was formulate and clinically evaluate 5-fluorouracil (5-FU) transdermal patches. Cytotoxicity was measured by exposing cell suspensions to increasing concentrations of drug from 10-100 microg/ml and performing viable cell counts by the trypan blue exclusion method. Results confirmed 100 infinity g/ml and 50 microg/ ml of 5-FU to be cytotoxic to EAC and DLA cells. In mice, increase in the life span (ILS) by 87.1% with a maximum survival time of 30.5+/-1.87 days was found with EAC cell-induced tumors, with an ILS of 88.1% and a maximum survival time of 39.5+/-1.87 days for DLA cell-induced lesions with 5-FU transdermal patches. The results were statistically significant (p<0.01) compared to untreated controls. Pharmacokinetic studies in rabbits showed a t1/2 of 29+/-6 min, a Cmax (ng/ml) of 978.23, an AUC0-infinity (ng/ml/h) of 1213.73 +/-14 and a Tmax (h) of 0.5. 5-FU from transdermal patches exhibited a half-life of 95+/-0.5 min, a Cmax (ng/ml) of 863.25, an AUC0-infinity (ng/ml/h) of 1567+/-36 and a Tmax (h) of 1.5. Velcro protection jackets proved suitable in this study to stop mice licking, scratching and rubbing applied patches.

WebStruct and VisualStruct: Web interfaces and visualization for Structure software implemented in a cluster environment.

Structure, is a widely used software tool to investigate population genetic structure with multi-locus genotyping data. The software uses an iterative algorithm to group individuals into "K" clusters, representing possibly K genetically distinct subpopulations. The serial implementation of this programme is processor-intensive even with small datasets. We describe an implementation of the program within a parallel framework. Speedup was achieved by running different replicates and values of K on each node of the cluster. A web-based user-oriented GUI has been implemented in PHP, through which the user can specify input parameters for the programme. The number of processors to be used can be specified in the background command. A web-based visualization tool "Visualstruct", written in PHP (HTML and Java script embedded), allows for the graphical display of population clusters output from Structure, where each individual may be visualized as a line segment with K colors defining its possible genomic composition with respect to the K genetic sub-populations. The advantage over available programs is in the increased number of individuals that can be visualized. The analyses of real datasets indicate a speedup of up to four, when comparing the speed of execution on clusters of eight processors with the speed of execution on one desktop. The software package is freely available to interested users upon request.

Laboratory Information Management Software for genotyping workflows: applications in high throughput crop genotyping.

BACKGROUND: With the advances in DNA sequencer-based technologies, it has become possible to automate several steps of the genotyping process leading to increased throughput. To efficiently handle the large amounts of genotypic data generated and help with quality control, there is a strong need for a software system that can help with the tracking of samples and capture and management of data at different steps of the process. Such systems, while serving to manage the workflow precisely, also encourage good laboratory practice by standardizing protocols, recording and annotating data from every step of the workflow. RESULTS: A laboratory information management system (LIMS) has been designed and implemented at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) that meets the requirements of a moderately high throughput molecular genotyping facility. The application is designed as modules and is simple to learn and use. The application leads the user through each step of the process from starting an experiment to the storing of output data from the genotype detection step with auto-binning of alleles; thus ensuring that every DNA sample is handled in an identical manner and all the necessary data are captured. The application keeps track of DNA samples and generated data. Data entry into the system is through the use of forms for file uploads. The LIMS provides functions to trace back to the electrophoresis gel files or sample source for any genotypic data and for repeating experiments. The LIMS is being presently used for the capture of high throughput SSR (simple-sequence repeat) genotyping data from the legume (chickpea, groundnut and pigeonpea) and cereal (sorghum and millets) crops of importance in the semi-arid tropics. CONCLUSION: A laboratory information management system is available that has been found useful in the management of microsatellite genotype data in a moderately high throughput genotyping laboratory. The application with source code is freely available for academic users and can be downloaded from http://www.icrisat.org/gt-bt/lims/lims.asp.