Drug Treatment Outcomes Research Articles

The 340B Program and Health Disparities Among Medicare Beneficiaries With Chronic Asthma.

The study objective was to determine whether the discounts provided under the 340B program help address disparities in drug treatment and adverse outcomes among Medicare Fee-For-Service (FFS) beneficiaries initially Medicare-diagnosed with moderate to severe chronic asthma. Using Medicare FFS claims data from 2017 to 2019, we conducted a cross-sectional study that compared risk-adjusted differences in 5 treatment measures and 5 adverse outcomes among beneficiaries treated within 340B and non-340B hospital systems that met the disproportionate share (DSH) criteria and the ownership classification requirement to qualify as a 340B DSH hospital. Our analysis focused on potential disparities that are historically associated with challenges to accessing quality health care. We did not observe fewer disparities in drug treatments or adverse outcomes for beneficiaries with moderate to severe asthma treated at 340B hospital systems compared to non-340B hospital systems. These results raise questions as to whether 340B hospital systems are effectively using discounts to focus on improved access and outcomes for vulnerable beneficiaries.

Drug resistance patterns and treatment outcomes in DR-TB patients at a tertiary care centre in Mumbai

BackgroundDrug-resistant tuberculosis (DR-TB) is a major health problem and threatens Tuberculosis (TB) control and outcomes globally. India holds one-fourth of global DR-TB burden.1 Aims1- To study drug resistance patterns and outcomes in DR-TB patients under National Tuberculosis Elimination Programme (NTEP) at a tertiary care-centre. 2- To correlate outcome of DR-TB with drug resistance patterns. MethodsIt is a retrospective study of 302 Drug Resistant Tuberculosis patients from Jan 2020 to May 2022. Common mutations of drug resistance, pyrazinamide resistance in DR-TB patients, correlation of High dose Moxifloxacin sensitivity by Line Probe Assay (LPA) and drug sensitivity test (DST), outcome of DR-TB patients with drug resistance patterns and correlation of outcome of DR-TB patients with their initial body-weight were studied. ResultsKat G was the most common mutation in Isoniazid (96%) resistance for MDR TB as well as Isoniazid Mono-resistance TB (p = 0.001). 91% cases with MDR-TB were resistant to pyrazinamide. 51.2% cases had low dose Fluroquinolone resistance. 18.8% cases had low and high dose Fluroquinolone resistance. 8.5% cases had resistance to injectables. 21.7% of cases who were resistant to High dose Moxifloxacin on second line LPA were found to be sensitive on DST. Outcomes were not dependent on the LPA resistance patterns. Body-weight greater than 45 Kg at the time of initiation of treatment was associated with better outcomes (p = 0.007). ConclusionDR-TB patients are resistant to pyrazinamide in nearly all cases; hence pyrazinamide is not suitable for initial replacement sequence. Second line resistance doesn't impact outcome in DR-TB patients.

Study protocol of the HD-MED study aiming to personalize drug treatment in Huntington's disease: a longitudinal, observational study to assess medication use and efficacy in relation to pharmacogenetics.

Huntington's disease (HD) is a hereditary, neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Currently, HD can only be managed symptomatically, including a large variety of prescribed drugs. Many HD patients experience negative medication effects (e.g. side effects or non-response). Pharmacogenetic (PGx) studies show how genetic variation affects both medication efficacy and toxicity and holds the potential to improve these outcomes of drug treatment. To classify the effect of the PGx profile of CYP2C19 and CYP2D6 in HD gene expansion carriers on negative medication effects of HD-related medication. Multicenter, observational study with 1-year follow-up. Adult HD gene expansion carriers who use one or more HD-related medications are eligible to participate. A detailed overview of medication use, medication efficacy, and side effects is retrospectively and prospectively collected via medication diaries, questionnaires, phone calls, and pharmacy medication verification schemes. PGx analysis on whole blood-extracted DNA is performed with Agena Bioscience VeriDose® Core Panel and long-range polymerase chain reaction copy number variation analysis. Per the study protocol-defined negative medication effects in HD gene expansion carriers with a genotype predicted poor or ultrarapid metabolizer phenotype will be compared with HD gene expansion carriers with a predicted intermediate and normal metabolizer phenotype. Frequencies will be analyzed via χ2 and logistic multivariate regression analysis. In addition, we summarize in this manuscript HD-relevant PGx prescription recommendations to improve drug therapy. The original study protocol was approved by the medical research ethics committee Leiden Den Haag Delft on 26 November 2019. HD-MED is a low-risk study that will generate personalized PGx results that can immediately be implemented in clinical practice, thus potentially improving pharmacovigilance and patients' quality of life. This study is registered in the International Clinical Trial Registry Platform under registration number NL8251, URL https://trialsearch.who.int/Trial2.aspx?TrialID=NL8251.

Genomic characterization of Plasmodium falciparum genes associated with anti-folate drug resistance and treatment outcomes in eastern India: A molecular surveillance study from 2008 to 2017.

After being used vigorously for the previous two decades to treat P. falciparum, chloroquine and sulfadoxine-pyrimethamine were replaced in 2009 with an artemisinin-based combination therapy (artesunate-sulfadoxine-pyrimethamine) in an effort to combat multidrug-resistant parasites. We set out to assess the genetic variants of sulfadoxine-pyrimethamine resistance and the effectiveness of its treatment in eastern India prior to, during, and 6 to 8 years following the introduction of the new pharmacological regime. In 2008-2009, 318 P. falciparum-positive patients got the recommended doses of sulfadoxine-pyrimethamine. We used 379 additional isolates from 2015 to 2017 in addition to the 106 isolates from 2010. All 803 isolates from two study sites underwent in vitro sulfadoxine-pyrimethamine sensitivity testing and genomic characterisation of sulfadoxine-pyrimethamine resistance (pfdhfr and pfdhps). In Kolkata and Purulia, we observed early treatment failure in 30.7 and 14.4% of patients, respectively, whereas recrudescence was found in 8.1 and 13.4% of patients, respectively, in 2008-2009. In 2017, the proportion of in vitro pyrimethamine and sulfadoxine resistance steadily grew in Kolkata and Purulia despite a single use of sulfadoxine-pyrimethamine. Treatment failures with sulfadoxine-pyrimethamine were linked to quintuple or quadruple pfdhfr- pfdhps mutations (AICII-AGKAT, AICII-AGKAA, AICII-SGKGT, AICII-AGKAA, AICNI-AGKAA) in 2008-2009 (p < 0.001). The subsequent spread of mutant-haplotypes with higher in vitro sulfadoxine-pyrimethamine resistance (p < 0.001), such as the sextuple (dhfr-AIRNI+dhps-AGEAA, dhfr-ANRNL+dhps-AGEAA) and septuple (dhfr-AIRNI+dhps-AGEAT), mutations were observed in 2015-2017. This successive spread of mutations with high in vitro sulfadoxine-pyrimethamine resistance confirmed the progressive increase in antifolate resistance even after an 8-year withdrawal of sulfadoxine-pyrimethamine.

Clinical Pharmacist role and their Importance in the Systematic Analysis of Diabetes Management Studies

Pharmacy practice has moved from medication delivery to a patient-focused approach during the last four decades. The pharmacist role has shifted from a compounding pharmacist and distributor of pharmaceuticals to one of the services and finally to a care provider. Progressively, the pharmacist's job is to ensure that the patient's medication is adequate and the best possible and readily available. Pharmacists can depend on the personal needs of their patients, thus making an essential contribution to drug therapy outcomes and quality of life. The number of people affected by diabetes and the costs associated with its management is relatively high worldwide, especially in developing countries like India. Aside from contributing to the financial strain, the problems arising from delays in detection and management are numerous. Clinical pharmacists have been inducted as important healthcare team members in many developing countries medical centers. This article discusses the role of the clinical pharmacist in the treatment of diabetes mellitus, including drug therapy, diabetes care, and education. The main aim of treatment in diabetes treatment has been to optimize drug therapy to achieve improved clinical results without causing drug-related issues. Clinical pharmacists who are well-trained and readily available are key healthcare practitioners who can help patients achieve improved drug treatment outcomes.

Clinical and socio-demographic profile, drug sensitivity pattern and treatment outcome of drug resistant DR TB patients registered for treatment at a tertiary care centre in South India

Drug resistant tuberculosis is a major threat to TB elimination activities. In our study, we address the clinical, socio-demographic profile, drug sensitivity pattern and treatment outcome of drug resistant TB patients.A record based cross sectional study was conducted in 77 Drug Resistant TB cases registered for standardized treatment at a tertiary care centre in South India from January 2012 to December 2019. The clinical, socio-demographic, radiological characteristics, drug sensitivity pattern and treatment outcome of these patients were recorded. 51 were males and 26 were females. 31 (40.3%) were diabetic, 30 (39%) were tobacco users, 12 (15.6%) were health care workers, 40 (52%) had low BMI and 4 (5.2%) were HIV-TB. 66 (85.7%) showed resistance to isoniazid, 62 (80.5%) to rifampicin, 8 (10.4%) to ethambutol, 9 (11.7%) to Fluoroquinolones, 2 (2.6%) to Second Line Injectables and 6 (7.8%) to Streptomycin. Treatment outcomes were as follows: cured 41 (61%), treatment completed 2 (2.6%), failure 2 (2.6%), lost to follow up 9 (11.7%), regimen changed 3 (3.9%), died 11 (14.3%), not evaluated 2 (2.6%) and treatment stopped due to adverse drug reactions 1 (1.3%). Unfavourable treatment outcomes were associated with low BMI, previous ATT and fluoroquinolone resistance.More than half of the patients had favourable treatment outcomes. Low BMI, previous ATT and fluoroquinolone resistance were factors associated with poor outcomes.

Machine learning and statistic analysis to predict drug treatment outcome in pediatric epilepsy patients with tuberous sclerosis complex

ObjectivesWe aimed to investigate the association between multi-modality features and epilepsy drug treatment outcomes and propose a machine learning model to predict epilepsy drug treatment outcomes with multi-modality features. MethodsThis retrospective study consecutively enrolled 103 epilepsy children with rare TSC. Multi-modality data were used to characterize risk factors for epilepsy drug treatment outcome of TSC, including clinical data, TSC1, and TSC2 genes test results, magnetic resonance imaging (MRI), computerized tomography (CT), and electroencephalogram (EEG). Three common feature selection methods and six common machine learning models were used to find the best combination of feature selection and machine learning model for epilepsy drug treatment outcomes prediction with multi-modality features for TSC clinical application. ResultsThe analysis of variance based on selected 35 features combined with multilayer perceptron (MLP) model achieved the best area-under-curve score (AUC) of 0.812 (±0.005). Infantile spasms, EEG discharge type, epileptiform discharge in the right frontal area of EEG, drug-resistant epilepsy, gene mutation type, and type II lesions were positively correlated with drug treatment outcome. Age of onset and age of visiting doctors were negatively correlated with drug treatment outcome (p < 0.05). Our machine learning results found that among MRI features, lesion type is the most important in the outcome prediction, followed by location and quantity. ConclusionWe developed and validated an effective prediction model for epilepsy drug treatment outcomes of TSC. Our results suggested that multi-modality features analysis and MLP-based machine learning can predict epilepsy drug treatment outcomes of TSC.

Pharmacometabolomics-Based Translational Biomarkers: How to Navigate the Data Ocean.

Metabolome is the end point of the genome-environment interplay, and enables an important holistic overview of individual adaptability and host responses to environmental, ecological, as well as endogenous changes such as disease. Pharmacometabolomics is the application of metabolome knowledge to decipher the mechanisms of interindividual and intraindividual variations in drug efficacy and safety. Pharmacometabolomics also contributes to prediction of drug treatment outcomes on the basis of baseline (predose) and postdose metabotypes through mathematical modeling. Thus, pharmacometabolomics is a strong asset for a diverse community of stakeholders interested in theory and practice of evidence-based and precision/personalized medicine: academic researchers, public health scholars, health professionals, pharmaceutical, diagnostics, and biotechnology industries, among others. In this expert review, we discuss pharmacometabolomics in four contexts: (1) an interdisciplinary omics tool and field to map the mechanisms and scale of interindividual variability in drug effects, (2) discovery and development of translational biomarkers, (3) advance digital biomarkers, and (4) empower drug repurposing, a field that is increasingly proving useful in the current era of Covid-19. As the applications of pharmacometabolomics are growing rapidly in the current postgenome era, next-generation proteomics and metabolomics follow the example of next-generation sequencing analyses. Pharmacometabolomics can also empower data reliability and reproducibility through multiomics integration strategies, which use each data layer to correct, connect with, and inform each other. Finally, we underscore here that contextual data remain crucial for precision medicine and drug development that stand the test of time and clinical relevance.

Ineffectiveness of Antiresorptive Agent Drug Holidays in Osteoporosis Patients for Treatment of Medication-Related Osteonecrosis of the Jaw: Consideration from Immunohistological Observation of Osteoclast Suppression and Treatment Outcomes.

In patients with osteoporosis receiving antiresorptive agents (ARs), it has been widely practiced to withdraw ARs for several months before tooth extraction and during treatment if medication-related osteonecrosis of the jaw (MRONJ) develops. This study examined the effects of drug holidays on recovery from osteoclast suppression and the treatment outcomes. The relationship between the period of the drug holidays and treatment outcomes was examined retrospectively in 166 osteoporosis patients with MRONJ who received ARs. Histological examinations using hematoxylin and eosin staining and cathepsin K stains were performed to observe the recovery from osteoclast suppression in 43 patients in whom living bone was observed in the resection margins of the surgical specimens. Three-month AR drug holidays were not significantly correlated with the treatment outcomes of the 139 patients who underwent surgical treatment and the 27 who underwent conservative treatment. Of the 43 patients who underwent histological investigations, 16 had drug holidays from 7 to 678 days. Osteoclast suppression was observed in almost all patients, except in one without a drug holiday and one with a 261-day drug holiday. These findings suggest that AR drug holidays for approximately 3 months neither recover osteoclast suppression nor affect treatment outcomes.

Clinical Study of Different Treatment Methods for Tuberculous Pleuritis Complicated with Pleural Tuberculoma.

Objective To compare the clinical efficacy and adverse drug reactions of four different schemes in the treatment of pleural tuberculoma. Methods A total of 120 patients with pleural tuberculoma admitted to the Tuberculosis Department of our hospital from January 2018 to January 2021 were selected as the research subjects. According to different treatment methods, the patients were divided into four groups, with 30 cases in each group. They were as follows: group A received classical HRZE regimen, group B received HRZE+pleural injection, group C received HZE+rifabutin, and group D received HZE+rifabutin+pleural injection. All patients were treated intensively for 3 months and then consolidated treatment for 6 months according to the patient's condition. The absorption of lesions in the four groups at different time was compared, and the occurrences of adverse drug reactions and treatment outcomes during treatment were recorded. Results After 3 months of treatment, compared with groups A, B, and C, the number of significantly absorbed cases and effective cases in group D increased, while the number of invalid cases decreased. However, there was no statistical significance in the absorption of lesions between the four groups (χ2 = 8.272, P = 0.507). In addition, pairwise comparison showed no significant difference in the absorption of lesions (P > 0.05). After 9 months of treatment, there was no significant difference in the absorption of lesions among the four groups (χ2 = 8.795, P = 0.185), but the absorption of lesions in group D was significantly better than that in group A (P < 0.05). During treatment, the incidence of adverse reactions in the four groups was significantly different (χ2 = 8.779, P = 0.032). Pairwise comparison showed that the incidence of adverse reactions in groups C and D was significantly lower than that in group A (P < 0.05). The total treatment course of group A was 9-16 months, and 10 cases (33.33%) still had residual lesions or pleural thickening at the end of treatment. The total course of treatment in group B was 9-12 months, and 7 cases (23.33%) still had residual lesions or pleural thickening at the end of the course of treatment. The total treatment course of group C was 9-16 months, and 8 cases (26.67%) still had residual lesions or pleural thickening at the end of treatment. The total course of treatment in group D was 9-12months, and there were still 2 cases of residual lesions (6.67%) at the end of the course. Conclusions HZE+rifabutin+pleural injection against tuberculosis therapy has a significant clinical efficacy in the treatment of pleural tuberculoma, which can more effectively improve the clinical symptoms of patients, improve the efficacy, and reduce complications, with a good prognosis, worthy of clinical promotion.

Genome-wide microRNA profiles identify miR-107 as a top miRNA associating with expression of the CYP3As and other drug metabolizing cytochrome P450 enzymes in the liver.

Cytochrome P450 (CYP) drug metabolizing enzymes are responsible for the metabolism of over 70% of currently used medications with the CYP3A family being the most important CYP enzymes in the liver. Large inter-person variability in expression/activity of the CYP3As greatly affects drug exposure and treatment outcomes, yet the cause of such variability remains elusive. Micro-RNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression and are involved in diverse cellular processes including metabolism of xenobiotics and therapeutic outcomes. Target prediction and in vitro functional assays have linked several miRNAs to the control of CYP3A4 expression. Yet, their co-expression with CYP3As in the liver remain unclear. In this study, we used genome-wide miRNA profiling in liver samples to identify miRNAs associated with the expression of the CYP3As. We identified and validated both miR-107 and miR-1260 as strongly associated with the expression of CYP3A4, CYP3A5, and CYP3A43. Moreover, we found associations between miR-107 and nine transcription factors (TFs) that regulate CYP3A expression, with estrogen receptor alpha (ESR1) having the largest effect size. Including ESR1 and the other TFs in the regression model either diminished or abolished the associations between miR-107 and the CYP3As, indicating that the role of miR-107 in CYP3A expression may be indirect and occur through these key TFs. Indeed, testing the other nine CYPs previously shown to be regulated by ESR1 identified similar miR-107 associations that were dependent on the exclusion of ESR1 and other key TFs in the regression model. In addition, we found significant differences in miRNA expression profiles in liver samples between race and sex. Together, our results identify miR-107 as a potential epigenetic regulator that is strongly associated with the expression of many CYPs, likely via impacting the CYP regulatory network controlled by ESR1 and other key TFs. Therefore, both genetic and epigenetic factors that alter the expression of miR-107 may have a broad influence on drug metabolism.

Latent profile analysis of data from the brief inventory of neurocognitive impairment (BINI) to develop neuro-cognitive profiles among opioid-dependent patients in drug treatment

Background Neurocognitive dysfunction is common among individuals with opioid use disorders (OUD) and can impede a range of treatment outcomes. We developed the 57-item Brief Inventory of Neuro-cognitive Impairment (BINI) to help detect and monitor neurocognitive dysfunction in the context of drug treatment settings. To date, no study has examined the possible presence of BINI subgroups among OUD patients, which could enhance our ability to tailor intervention strategies to meet individual treatment needs. The purpose of this study was to conduct a latent profile analysis to identify BINI subgroups that differ in terms of their reported and objective neurocognitive dysfunction. We hypothesized that subgroups would emerge, suggesting the potential benefit of implementing tailored strategies for optimal treatment outcomes. Methods Latent profile analyses included data from opioid-dependent patients (N = 177) enrolled in a methadone maintenance treatment program between July 2018 and October 2019. Results We found three profiles of self-reported neurocognitive symptoms, including those with 1) minimal concerns 2) moderate concerns, and 3) many concerns across multiple domains. Conclusions If these results are confirmed, the BINI may be used to rapidly identify persons who require specific accommodation strategies to improve their drug treatment outcomes.

The epidemiology of drug-resistant tuberculosis in Bulawayo and Matabeleland South provinces, Zimbabwe 2017

ObjectiveTo investigate determinants of drug resistance and treatment outcomes among patients with drug-resistant tuberculosis (DR-TB). DesignThis was a cross-sectional study on patients diagnosed with DR-TB in Bulawayo and Matabeleland South provinces, 2015. ResultsA total of 129 participants were identified. DR-TB patients were 3.4 times more likely to have been treated previously for sensitive TB (95% confidence interval 1.3–9.2). Approximately 88.5% of DR-TB patients were diagnosed before completing the sensitive TB course and another 82.1% developed DR-TB within 6 months of completing sensitive TB treatment. The likelihood diminished with increasing time interval, becoming less likely at >12 months post-treatment. Most DR-TB patients (87.5%) were likely to have resided outside Zimbabwe and to have fallen ill there (85.2%). Overall, hearing loss was the most prevalent (70%) medication side effect experienced. Unfavourable interim treatment outcomes were high for patients <6 months on treatment (prevalence odds ratio 2.7, 95% CI 1.2–6.1), becoming 44% less likely after 18 months (95% CI 1.2–11.4). ConclusionsThe majority of DR-TB patients were diagnosed during sensitive TB treatment, suggesting missed DR-TB diagnosis or inadequate treatment. Delays in starting effective TB regimens negatively affect treatment outcomes. Drug sensitivity testing at diagnosis, patient monitoring, and enhanced adherence counselling are recommended.

Mycobacterium tuberculosis mixed infections and drug resistance in sub-Saharan Africa: a systematic review.

Sub-Saharan Africa, is a region that records high rates of TB infection. Mycobacterium tuberculosis mixed strain infection, especially when the strains involved are of different susceptibilities, is an area of great interest because it is linked with an increased risk of treatment failure and transmission of resistant strains within the population. This paper reviewed original studies that reported MTB mixed infection and heteroresistance in the region between 2010 and 2020 to understand the extent of mixed strain infection and heteroresistance in the region. This information is very critical in the control of TB and ending the TB epidemic by 2035 as per the World Health Organization's vision. pubmed, Scopus, JSTOR, AJOL, and Google Scholar databases were searched through both key terms and subject headings. The literature was screened, assessed for the quality and evidence synthesized. Eighteen original articles were included in this review after having met the inclusion criteria. The frequency of mixed strain infection reported in these studies varied between 2.8% and 21.1% while drug resistance range between 0.06% to 19% depending on the study design and the drug susceptibility screening technique utilized. The majority of the studies (50%) utilized Spoligotyping in conjunction with MIRU-VNTR typing in the detection of mixed infections. Despite the scarcity of data on mixed infections and heteroresistance in sub-Saharan Africa, various studies have revealed that these conditions are frequent in the region than previously thought. Given the evidence of the effect of mixed infections on drug resistance and treatment outcome, we conclude that mixed infection is an unavoidable topic for future studies.

Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review

BackgroundExtensively drug resistant tuberculosis (XDR-TB) is considered as a major threat to global health. This study aimed to analyse the treatment outcomes and identify the factors significantly associated with unfavourable treatment outcomes among XDR-TB patients. MethodsWe conducted a retrospective observational study at 10 Programmatic Management Units of the National Tuberculosis Control Program of Pakistan. The Electronic Nominal Recording Reporting System records were used to collect data of all eligible XDR-TB patients registered at the study sites between March 2012 and August 2018. Treatment outcomes were analysed as per the standard criteria. Factors associated with unfavourable treatment outcomes were analysed by using multivariate binary logistic regression analysis. ResultsOut of the total 184 patients, 59 (32.1%) completed their treatment successfully. Whereby, 83 patients (45.1%) died, 24 (13%) had treatment failure, and 11 (6%) were lost to follow-up. Treatment outcomes were not evaluated in 7 (3.8%) patients. Factors significantly associated with unfavourable treatment outcomes included; conventional therapy with bedaquiline, unfavourable interim treatment outcomes and occurrence of adverse drug events (negative association). ConclusionTreatment success rate in the study cohort was sub-optimal (i.e., <75%). The poor success rate and high mortality are concerning, and requires immediate attention of the program managers and clinicians.

Generalizability of treatment outcome prediction in major depressive disorder using structural MRI: A NeuroPharm study

Brain morphology has been suggested to be predictive of drug treatment outcome in major depressive disorders (MDD). The current study aims at evaluating the performance of pretreatment structural brain magnetic resonance imaging (MRI) measures in predicting the outcome of a drug treatment of MDD in a large single-site cohort, and, importantly, to assess the generalizability of these findings in an independent cohort. The random forest, boosted trees, support vector machines and elastic net classifiers were evaluated in predicting treatment response and remission following an eight week drug treatment of MDD using structural brain measures derived with FastSurfer (FreeSurfer). Models were trained and tested within a nested cross-validation framework using the NeuroPharm dataset (n = 79, treatment: escitalopram); their generalizability was assessed using an independent clinical dataset, EMBARC (n = 64, treatment: sertraline). Prediction of antidepressant treatment response in the Neuropharm cohort was statistically significant for the random forest (p = 0.048), whereas none of the models could significantly predict remission. Furthermore, none of the models trained using the entire NeuroPharm dataset could significantly predict treatment outcome in the EMBARC dataset. Although our primary findings in the NeuroPharm cohort support some, but limited value in using pretreatment structural brain MRI to predict drug treatment outcome in MDD, the models did not generalize to an independent cohort suggesting limited clinical applicability. This study emphasizes the importance of assessing model generalizability for establishing clinical utility.

Effect of vitamin D deficiency on the metabolic profile of women with polycystic ovary syndrome.

Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 μg/ml vs. 5.5 μg/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 μg/ml vs. 10.9 μg/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 µg/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

Mobile Responsive App-A Useful Additional Tool for Data Collection in the German Pregnancy Register Rhekiss?

Background: The German pregnancy register Rhekiss is designed as a nationwide, web-based longitudinal observational cohort established in 2015. The register follows women with inflammatory rheumatic disease prospectively from child wish or early pregnancy until 2 years post-partum. Information on clinical and laboratory parameters, drug treatment, and (adverse) pregnancy outcomes are documented in pre-specified intervals. Physicians and patients report data for the same time periods via separated accounts and forms into a web-based application (app). As data entry on mobile devices might improve response rates of patients, a responsive app as a further convenient documentation option was developed.Methods: The Rhekiss-app is available for self-reported data retrieval since August 2017 from the App stores. For the current analysis, Rhekiss register data were used from the start of the register until 30 September 2020. The analyses were performed for forms containing information on devices. Outcome parameters were compared for mobile and desktop users for the quantity and quality of filled forms.Results: In total, 5,048 forms were received and submitted by 966 patients. About 57% of forms were sent from mobile devices with the highest numbers in patients with child wishes (63%). Users of mobile devices were slightly younger and often had less high-education level (62 vs. 79%) compared with desktop users. The proportion of forms submitted via mobile devices increased steadily from 48% in the fourth quarter of 2018 to 64% in the third quarter of 2020. The proportion of forms received before and after the Rhekiss-app implementation increased with the highest increase of 12% for forms filled at time point 12 months post-partum. Mobile users submitted significantly more forms than desktop users (2.9 vs. 2.1), data sent via desktops were more often complete (88 vs. 86%).Conclusion: The responsive app is a valuable additional tool for data collection and is well-accepted by patients as indicated by its increasing use in Rhekiss. Apart from desktop/browser developments, the technological adoptions within observational cohorts and registries should take smartphone requirements and developments into account, especially when patient-reported data in young, mobile patients are collected, bearing in mind that data quality could be compromised and concepts for improving data quality should be implemented.

Longitudinal evaluation of five nasopharyngeal carcinoma animal models on the microPET/MR platform.

We longitudinally evaluated the tumour growth and metabolic activity of three nasopharyngeal carcinoma (NPC) cell line models (C666-1, C17 and NPC43) and two xenograft models (Xeno76 and Xeno23) using a micropositron emission tomography and magnetic resonance (microPET/MR). With a better understanding of the interplay between tumour growth and metabolic characteristics of these NPC models, we aim to provide insights for the selection of appropriate NPC cell line/xenograft models to assist novel drug discovery and evaluation. Mice were imaged by 18F-deoxyglucose ([18F]FDG) microPET/MR twice a week for consecutive 3-7weeks. [18F]FDG uptake was quantified by standardized uptake value (SUV) and presented as SUVmean tumour-to-liver ratio (SUVRmean). Longitudinal tumour growth patterns and metabolic patterns were recorded. SUVRmean and histological characteristics were compared across the five NPC models. Cisplatin was administrated to one selected optimal tumour model, C17, to evaluate our imaging platform. We found variable tumour growth and metabolic patterns across different NPC tumour types. C17 has an optimal growth rate and higher tumour metabolic activity compared with C666-1. C666-1 has a fast growth rate but is low in SUVRmean at endpoint due to necrosis as confirmed by H&E. NPC43 and Xeno76 have relatively slow growth rates and are low in SUVRmean, due to severe necrosis. Xeno23 has the slowest growth rate, and a relative high SUVRmean. Cisplatin showed the expected therapeutic effect in the C17 model in marked reduction of tumour size and metabolism. Our study establishes an imaging platform that characterizes the growth and metabolic patterns of different NPC models, and the platform is well able to demonstrate drug treatment outcome supporting its use in novel drug discovery and evaluation for NPC.

High rate of successful treatment outcomes among childhood rifampicin/multidrug-resistant tuberculosis in Pakistan: a multicentre retrospective observational analysis

BackgroundThere was a complete lack of information about the treatment outcomes of rifampicin/multidrug resistant (RR/MDR) childhood TB patients (age ≤ 14 years) from Pakistan, an MDR-TB 5th high burden country. Therefore, this study evaluated the socio-demographic characteristics, drug resistance pattern, treatment outcomes and factors associated with unsuccessful outcomes among childhood RR/MDR-TB patients in Pakistan.MethodsThis was a multicentre retrospective record review of all microbiologically confirmed childhood RR/MDR-TB patients (age ≤ 14 years) enrolled for treatment at seven units of programmatic management of drug-resistant TB (PMDT) in Pakistan. The baseline and follow-up information of enrolled participants from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. World Health Organization (WHO) defined criterion was used for deciding treatment outcomes. The outcomes of “cured” and “treatment completed” were collectively grouped as successful, whereas “death”, “treatment failure” and “lost to follow-up” were grouped together as unsuccessful outcomes. Multivariable binary logistic regression analysis was used to find factors associated with unsuccessful outcomes. A p-value < 0.05 reflected statistically significant findings.ResultsA total of 213 children RR/MDR-TB (84 RR and 129 MDR-TB) were included in the study. Majority of them were females (74%), belonged to the age group 10–14 years (82.2%) and suffered from pulmonary TB (85.9%). A notable proportion (37.1%) of patients had no history of previous TB treatment. Patients were resistant to a median of two drugs (interquartile range: 1–4) and 23% were resistant to any second line anti-TB drug. A total of 174 (81.7%) patients achieved successful treatment outcomes with 144 (67.6%) patients being cured and 30 (14.1%) declared treatment completed. Among the 39 (18.3%) patients with unsuccessful outcomes, 35 (16.4%) died and 4 (1.9%) experienced treatment failure. In multivariable analysis, the use of ethambutol had statistically significant negative association with unsuccessful outcomes (odds ratio = 0.36, p-value = 0.02).ConclusionsIn this study, the WHO target of successful treatment outcomes (≥ 75%) among childhood RR/MDR-TB patients was achieved. The notable proportion of patients with no history of previous TB treatment (37.1%) and the disproportionately high number of female patients (74%) respectively stress for infection control measures and provision of early and high quality care for female drug susceptible TB patients.