Using machine learning to study the effect of medication adherence in Opioid Use Disorder

Background: Opioid Use Disorder (OUD) and opioid overdose (OD) impose huge social and economic burdens on society and health care systems. Research suggests that Medication for Opioid Use Disorder (MOUD) is effective in the treatment of OUD. We use machine learning to investigate the association between patient’s adherence to prescribed MOUD along with other risk factors in patients diagnosed with OUD and potential OD following the treatment. Methods: We used longitudinal Medicaid claims for two selected US states to subset a total of 26,685 patients with OUD diagnosis and appropriate Medicaid coverage between 2015 and 2018. We considered patient age, sex, region level socio-economic data, past comorbidities, MOUD prescription type and other selected prescribed medications along with the Proportion of Days Covered (PDC) as a proxy for adherence to MOUD as predictive variables for our model, and overdose events as the dependent variable. We applied four different machine learning classifiers and compared their performance, focusing on the importance and effect of PDC as a variable. We also calculated results based on risk stratification, where our models separate high risk individuals from low risk, to assess usefulness in clinical decision-making. Results: Among the selected classifiers, the XGBoost classifier has the highest AUC (0.77) closely followed by the Logistic Regression (LR). The LR has the best stratification result: patients in the top 10% of risk scores account for 35.37% of overdose events over the next 12 month observation period. PDC score calculated over the treatment window is one of the most important features, with better PDC lowering risk of OD, as expected. In terms of risk stratification results, of the 35.37% of overdose events that the predictive model could detect within the top 10% of risk scores, 72.3% of these cases were non-adherent in terms of their medication (PDC <0.8). Targeting the top 10% outcome of the predictive model could decrease the total number of OD events by 10.4%. Conclusions: The best performing models allow identification of, and focus on, those at high risk of opioid overdose. With MOUD being included for the first time as a factor of interest, and being identified as a significant factor, outreach activities related to MOUD can be targeted at those at highest risk

Prescription practices and availability of artemisinin monotherapy in India: where do we stand?

<p>Abstract</p> <p>Background</p> <p>The World Health Organization has urged all member states to deploy artemisinin-based combination therapy and progressively withdraw oral artemisinin monotherapies from the market due to their high recrudescence rates and to reduce the risk of drug resistance. Prescription practices by physicians and the availability of oral artemisinin monotherapies with pharmacists directly affect the pattern of their use. Thus, treatment practices for malaria, with special reference to artemisinin monotherapy prescription, in selected states of India were evaluated.</p> <p>Methods</p> <p>Structured, tested questionnaires were used to conduct convenience surveys of physicians and pharmacists in eleven purposively selected districts across six states in 2008. In addition, exit interviews of patients with a diagnosis of uncomplicated malaria or a prescription for an anti-malarial drug were also performed. Logistic regression was used to determine patient clinical care, and institutional factors associated with artemisinin monotherapy prescription.</p> <p>Results</p> <p>Five hundred and eleven physicians from 196 health facilities, 530 pharmacists, and 1, 832 patients were interviewed. Artemisinin monotherapy was available in 72.6% of pharmacies and was prescribed by physicians for uncomplicated malaria in all study states. Exit interviews among patients confirmed the high rate of use of artemisinin monotherapy with 14.8% receiving such a prescription. Case management, i.e. method of diagnosis and overall treatment, varied by state and public or private sector. Treatment in the private sector (OR 8.0, 95%CI: 3.8, 17) was the strongest predictor of artemisinin monotherapy prescription when accounting for other factors. Use of the combination therapy recommended by the national drug policy, artesunate + sulphadoxine-pyrimethamine, was minimal (4.9%), with the exception of one state.</p> <p>Conclusions</p> <p>Artemisinin monotherapy use was widespread across India in 2008. The accessible sale of oral artemisinin monotherapy in retail market and an inadequate supply of recommended drugs in the public sector health facilities promoted its prescription. This study resulted in notifications to all state drug controllers in India to withdraw the oral artemisinin formulations from the market. In 2010, artesunate + sulphadoxine-pyrimethamine became the universal first-line treatment for confirmed <it>Plasmodium falciparum </it>malaria and was deployed at full scale.</p

Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation

Aim To evaluate the impact of ultra-rapid FLASH mouse whole brain irradiation on hippocampal dendritic spines and neuroinflammation, factors associated with cognitive impairment after brain irradiation. Methods We administered 30 Gy whole brain irradiation to C57BL6/J mice in sub-second (FLASH) vs. 240 s conventional delivery time keeping all other parameters constant, using a custom configured clinical linac. Ten weeks post-irradiation, we evaluated spatial and non-spatial object recognition using novel object location and object recognition testing. We measured dendritic spine density by tracing Golgi-stained hippocampal neurons and evaluated neuroinflammation by CD68 immunostaining, a marker of activated microglia, and expression of 10 pro-inflammatory cytokines using a multiplex immunoassay. Results At ten weeks post-irradiation, compared to unirradiated controls, conventional delivery time irradiation significantly impaired novel object location and recognition tasks whereas the same dose given in FLASH delivery did not. Conventional delivery time, but not FLASH, was associated with significant loss of dendritic spine density in hippocampal apical dendrites, with a similar non-significant trend in basal dendrites. Conventional delivery time was associated with significantly increased CD68-positive microglia compared to controls whereas FLASH was not. Conventional delivery time was associated with significant increases in 5 of 10 pro-inflammatory cytokines in the hippocampus (and non-significant increases in another 3), whereas FLASH was associated with smaller increases in only 3. Conclusion Reduced cognitive impairment and associated neurodegeneration were observed with FLASH compared to conventional delivery time irradiation, potentially through decreased induction of neuroinflammation, suggesting a promising approach to increasing therapeutic index in radiation therapy of brain tumors

Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL), a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h) was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required.</p> <p>Methods</p> <p>One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa) were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers <it>msp</it>-<it>1 </it>and <it>msp</it>-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in <it>pfmdr</it>1 was also carried out in the samples obtained from patients before and after the treatment.</p> <p>Results</p> <p>The PCR corrected cure rates were high at both the sites viz. 100% (n = 53) in Assam and 98.6% (n = 71) in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91) and 184 (91.3%, n = 91) of <it>pfmdr1 </it>gene.</p> <p>Conclusion</p> <p>AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria in India. The polymorphism in <it>pfmdr</it>1 gene is not co-related with clinical outcome. However, treatment failure can also occur due to incomplete absorption of the drug as is suspected in one case of failure at D7 in the study. AL can be a viable alternative of artesunate plus sulphadoxine/pyrimethamine (AS + SP), however, the drug should be used rationally and efficacy needs to be monitored periodically.</p

Dynamics of Hot QCD Matter -- Current Status and Developments

The discovery and characterization of hot and dense QCD matter, known as Quark Gluon Plasma (QGP), remains the most international collaborative effort and synergy between theorists and experimentalists in modern nuclear physics to date. The experimentalists around the world not only collect an unprecedented amount of data in heavy-ion collisions, at Relativistic Heavy Ion Collider (RHIC), at Brookhaven National Laboratory (BNL) in New York, USA, and the Large Hadron Collider (LHC), at CERN in Geneva, Switzerland but also analyze these data to unravel the mystery of this new phase of matter that filled a few microseconds old universe, just after the Big Bang. In the meantime, advancements in theoretical works and computing capability extend our wisdom about the hot-dense QCD matter and its dynamics through mathematical equations. The exchange of ideas between experimentalists and theoreticians is crucial for the progress of our knowledge. The motivation of this first conference named "HOT QCD Matter 2022" is to bring the community together to have a discourse on this topic. In this article, there are 36 sections discussing various topics in the field of relativistic heavy-ion collisions and related phenomena that cover a snapshot of the current experimental observations and theoretical progress. This article begins with the theoretical overview of relativistic spin-hydrodynamics in the presence of the external magnetic field, followed by the Lattice QCD results on heavy quarks in QGP, and finally, it ends with an overview of experiment results.Comment: Compilation of the contributions (148 pages) as presented in the `Hot QCD Matter 2022 conference', held from May 12 to 14, 2022, jointly organized by IIT Goa & Goa University, Goa, Indi

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe

Evaluating readiness to change health behaviours in individuals with chronic pain

Readiness to change health behaviours is an important element in clinical evaluations for individuals with chronic conditions, as it influences individuals’ engagement in self-management programs. By evaluating an individual’s readiness, clinicians are in a better position to assess whether individuals can benefit from the program and tailor interventions according to individual needs. A comprehensive readiness evaluation also requires assessment of predictors of readiness such as knowledge, attitudes, and current health behaviours. However, existing readiness measures do not address these predictors, or the range of behaviours that will be targeted by many programs, nor do they align closely with disease management program goals. They often do little to assist patients and clinicians in having a collaborative discussion; creating action plans; and tailoring interventions according to their health needs. Currently, our research team is implementing an integrated primary-care low back pain (LBP) program that aims to use an interdisciplinary approach for delivering health-care services. Services include prevention, early intervention, and optimal management of chronic pain through pharmacological and non-pharmacological interventions. We used the LBP program as an exemplar to develop a comprehensive readiness evaluation tool that can be incorporated into a chronic disease management program. Prior to creating the tool, we reviewed existing measures to determine the content coverage of available tools, and to inform the development of a new tool.The research objectives for each Manuscript in this thesis were:Manuscript 1:(I) To identify the content coverage of measures currently used to assess readiness to change health behaviours among individuals with chronic diseases;(II) To identify the optimal items needed for a tool to evaluate readiness to change health behaviours among individuals with chronic pain;Manuscript 2:(III) To develop the content for a comprehensive behaviour evaluation tool kit to be used to guide the development of an individualized education and intervention program for individuals with LBP;(IV) To obtain preliminary data regarding the content validity among individuals with chronic LBP.The results of the study showed that while existing tools address a range of health behaviours and attitudes, the way in which they operationalized the evaluation of domains was not specific enough to the common components of most interdisciplinary chronic disease management programs. The final tool kit evaluated four predictors of readiness that were considered important for evaluating the needs of individuals in the LBP program. It consisted of five domains- knowledge about back care, beliefs about pain medications, physical activity, use of pain coping strategies and effective communication.The tool kit will allow clinicians to use information derived from the evaluation to assess which behaviours should be targeted to individualize behaviour change action plans with clients attending the program. Future work will further validate the tool kit and aim to increase its applicability across disease management programs by highlighting sections where content can be tailored to address the specific elements of any program.La volonté de changer les comportements de santé est un élément important dans les évaluations cliniques pour les personnes atteintes de maladies chroniques, car il influe sur l'engagement des individus dans des programmes d'auto-gestion. En évaluant la volonté d'un individu, les cliniciens sont en meilleure position pour évaluer si les particuliers peuvent bénéficier des interventions du programme et sur mesure selon les besoins individuels. Une évaluation complète de l'état de préparation exige également une évaluation des prédicteurs de préparation tels que les connaissances, les attitudes et les comportements de santé actuels. Toutefois, les mesures de préparation existants ne abordent pas ces prédicteurs, ou la gamme de comportements qui seront ciblés par de nombreux programmes, ni se alignent-ils étroitement avec les objectifs du programme de gestion de la maladie. Ils font souvent peu pour aider les patients et les cliniciens à avoir une discussion collaborative; la création de plans d'action; et d'adapter les interventions en fonction de leurs besoins de santé.Actuellement, notre équipe de recherche met en oeuvre un programme de faible douleur intégrée de soins primaires dos qui vise à utiliser une approche interdisciplinaire pour la prestation de services de soins de santé. Les services comprennent la prévention, l'intervention précoce et la gestion optimale de la douleur chronique par des interventions pharmacologiques et non pharmacologiques. Nous avons utilisé le programme lombalgie (LBP) comme un exemple de développer un outil d'évaluation de l'état de préparation complète qui peut être incorporé dans un programme de gestion des maladies chroniques. Avant de créer l'outil, nous avons examiné des mesures pour déterminer l'étendue et la portée des outils disponibles, et d'informer le développement d'un nouvel outil existant. Les objectifs de recherche pour chaque manuscrit dans cette thèse sont les suivants:Manuscrit 1:(I) pour évaluer la portée et l'ampleur des mesures actuellement utilisées pour évaluer la volonté de changer les comportements de santé chez les personnes atteintes de maladies chroniques;(II) identifier les éléments optimales nécessaires pour un outil pour évaluer la volonté de changer les comportements de santé chez les personnes souffrant de douleur chronique;Manuscrit 2:(III) Pour développer le contenu pour un kit individualisé comportement de l'outil d'évaluation globale pour un programme de LBP existante;(IV) Pour obtenir des données préliminaires concernant la validité de contenu entre les individus souffrant de lombalgie chronique.Les résultats de l'étude ont montré que si les outils existants portent sur un éventail de comportements et d'attitudes santé, la manière dont ils ont opérationnalisé l'évaluation des domaines ne était pas suffisamment spécifique pour les composants communs des programmes de gestion des maladies chroniques les plus interdisciplinaires. L'outil-kit final évalué quatre prédicteurs de préparation qui ont été considérées comme importantes pour évaluer les besoins des individus dans le programme de LBP. Elle se composait de cinq connaissances sur les soins domains- arrière, les croyances sur les médicaments de la douleur, l'activité physique, l'utilisation de stratégies d'adaptation à la douleur et une communication efficace. La trousse à outils permettra aux cliniciens d'utiliser les informations provenant de l'évaluation d'évaluer les comportements qui devraient être ciblés pour individualiser les plans d'action de changement de comportement avec les clients participant au programme. Les travaux futurs seront encore valider le kit d'outils et viser à accroître son applicabilité dans tous les programmes de gestion des maladies en mettant en évidence les sections où le contenu peut être adapté pour répondre aux éléments spécifiques de ne importe quel programme

Multidetector computed tomography (MDCT): Evaluation of anatomical variations of nose and paranasal sinuses in chronic rhinosinusitis

The aim of this study was to (1) detect the prevalence of anatomical variations of nose and paranasal sinuses in Chronic Rhinosinusitis (CRS) on ‘Nasal Endoscopy and Computed Tomography’, (2) study association of anatomical variations of nose and paranasal sinuses in Chronic Rhinosinusitis. This hospital based cross sectional study was performed during the period from January 2020 to October 2022 on patient between 20 to 60 yrs. of age referred to the department of Radiodiagnosis for evaluation of MDCT PNS from Dept. of ENT, S.C.B medical college and hospital Cuttack. Diagnostic Nasal Endoscopy and Computed Tomography of nose and Paranasal Sinuses of 80 patients of chronic rhinosinusitis were studied and results were. Maximum patients included in study population was 20-25 years with male predominance. Deviated Nasal Septum was the most common anatomical variation, which was detected in 70(87.5%) patients on Diagnostic Nasal Endoscopy and Agger nasii cells were observed in 60(75%) patients on Computed Tomography. The other anatomical variations like Concha bullosa 56(70%) were diagnosed both by Diagnostic Nasal Endoscopy. Anatomical variations like deviated nasal septum, agger nasi cells, medialised uncinated process, large concha bullosa were associated with chronic rhinosinusitis

Traditional skill of ethnic people of the Eastern Himalayas and North East India in preserving microbiota as dry amylolytic starters

184-190Preparation of ethnic fermented beverages using dry amylolytic starters is an integral part of socio-cultural practice of different ethnic groups of people residing in the Eastern Himalayan region of Nepal, Bhutan and India including North-East India. Alcoholic beverages are produced by traditional fermentation using specific amylolytic starters, which are prepared in different ways by diverse ethnic groups. This study is aimed at documenting the traditional skill of various ethnic groups of people of North East India and the Eastern Himalayas in preserving microbiota as dry amylolytic starters generally used for preparation of alcoholic beverages