Unfavorable Treatment Research Articles

Outpatient prescription drug interactions at a city-affiliated healthcare center in Vietnam

Context: Adverse drug interactions increase the risk of hospitalization, treatment costs, unfavorable treatment outcomes, and prolonged hospital stays. However, there are a limited number of studies conducted in city-affiliated healthcare settings in Vietnam. Aims: To identify drug interactions in outpatient treatment prescriptions at a city-based healthcare center in the southern region of Vietnam. Methods: A cross-sectional descriptive study was conducted on outpatient treatment prescriptions stored in the outpatient department of a city-affiliated healthcare center from January to June, 2023. The study used two databases for drug interaction checking: the Drug Interactions Checker and Medscape Interactions Checker. Univariate and multivariate regression analyses were used to identify predictors of clinically significant drug interactions. Results: Among 1203 surveyed prescriptions, 36.7% contained at least one clinically-significant drug interaction, with 3% of prescriptions having severe interactions. The highest frequency of drug interactions involved amlodipine and metformin (9.9%). Patients with five or more prescribed medications (OR = 3.305; 95% CI: 2.320-4.708), hypertension (OR = 7.142; 95% CI: 4.658-10.950), dyslipidemia (OR = 2.242; 95% CI: 1.665-3.020), and non-insulin-dependent diabetes (OR = 2.447; 95% CI: 1.817-3.295) had a higher likelihood of experiencing clinically significant drug interactions. Conclusions: This study revealed that over one-third of outpatient prescriptions were associated with clinically-significant drug interactions. This study highlights the importance of clinical pharmacists screening prescriptions to detect and reduce interactions, as well as the application of computerized alert systems with intelligent screening software to minimize drug interactions.

Exploring Genomic Patterns to Identify Drug-Resistant TB: A Comprehensive Study of Age, Gender, Lineage, and Outcome

Background: Tuberculosis (TB) is a prevalent bacterial infection caused by Mycobacterium tuberculosis (Mtb), primarily affecting the lungs, with rising incidence rates. Drug-resistant TB strains, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) types, pose challenges with poor treatment success rates and increased mortality. Demographic factors and genomic patterns contribute to drug resistance, emphasizing the need for new drugs targeting specific genomic patterns.Methods: This study analyzes the impact of demographics, treatment outcomes, and genomic mutations on drug-resistant TB using pattern identification techniques and whole-genome sequencing to discover therapeutic targets. This study primarily focused on the identification and analysis of MDR and XDR strains, considering various demographic characteristics and treatment outcomes. A dataset comprising 2,602 observations was utilized, and pattern recognition techniques were employed to identify significant features. Additionally, the study employs the whole-genome sequencing (WGS) pipeline to identify single nucleotide polymorphisms (SNPs) that result in new mutations in drug-resistant Mtb strains.Results: The findings of the study revealed that XDR and MDR non-XDR TB were the most prevalent types of drug resistance, and they were associated with unfavorable treatment outcomes, including death or treatment failure. Males exhibited a higher susceptibility to both XDR and MDR non-XDR TB compared to females. The age of onset for both types of resistance was approximately 40 years. Among the observed variants in 31 commonly occurring genes,Conclusion: These findings introduce a novel set of therapeutic targets specific to MDR and XDR Mtb types, which warrant further investigation for potential therapeutic interventions.Keywords: Tuberculosis; Drug Resistance; Multidrug resistance; Demographics; Dataset; Gene; Mutations

Linkage of cell division cycle 42 with clinical features, treatment response and survival in adult Philadelphia chromosome negative acute lymphoblastic leukemia

Cell division cycle 42 (CDC42) regulates the progression of leukemia via mediating proliferation and immune evasion of malignant cells. The study aimed to investigate the correlation of CDC42 with clinical features, treatment response, event-free survival (EFS) and overall survival (OS) in adult Philadelphia chromosome negative acute lymphoblastic leukemia (Ph− ALL) patients. CDC42 expression in bone marrow mononuclear cells was detected in 78 adult Ph− ALL patients and 10 donors using real-time reverse transcriptase-polymerase chain reaction. CDC42 was increased in adult Ph− ALL patients compared with donors (p < .001). Besides, elevated CDC42 was linked with pro-B ALL or early-T ALL (p = .038) and white blood cell (WBC) elevation at diagnosis (p = .025). Fifty (64.1%) and 23 (29.5%) patients had complete remission (CR) at 1 month and minimal residual disease (MRD) after CR, respectively. CDC42 was inversely associated with CR at 1 month (p = .034), but not MRD after CR (p = .066). Concerning survival, patients with CDC42 ≥ 3.310 (cut by median value in patients) showed a shortened EFS (p = .006) and OS (p = .036) compared to those with CDC42 < 3.310. In detail, patients with CDC42 ≥ 3.310 and CDC42 < 3.310 had 5-year EFS rate of 29.9% and 45.4%, and 5-year OS rate of 39.4% and 63.6%, correspondingly. Further multivariate Cox’s regression analyses revealed that CDC42 ≥ 3.310 was independently related to shorter EFS (hazard ratio = 2.933, p = .005). Elevated CDC42 is related with pro-B ALL or early-T ALL, WBC elevation at diagnosis, unfavorable treatment response and worse survival in adult Ph− ALL patients.

Incidence, Outcomes, and Risk Factors for Isoniazid-Resistant Tuberculosis from 2012 to 2022 in Eastern China.

Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. Between January 2012 and December 2022, all Hr-TB patients' information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients' clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment.

TRIM47-CDO1 axis dictates hepatocellular carcinoma progression by modulating ferroptotic cell death through the ubiquitin‒proteasome system

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer, characterized by high morbidity and mortality rates, as well as unfavorable treatment outcomes. Tripartite motif-containing protein 47 (TRIM47) has been implicated in various diseases including tumor progression with the activity of E3 ubiquitin ligase. However, the precise regulatory mechanisms underlying the involvement of TRIM47 in HCC remain largely unexplored. Here, we provide evidence that TRIM47 exhibits heightened expression in tumor tissues, and its expression is in intimate association with clinical staging and patient prognosis. TRIM47 promotes HCC proliferation, migration, and invasion as an oncogene by in vitro gain- and loss-of-function experiments. TRIM47 knockdown results in HCC ferroptosis induction, primarily through CDO1 involvement to regulate GSH synthesis. Subsequent experiments confirm the interaction between TRIM47 and CDO1 dependent on B30.2 domain, wherein TRIM47 facilitates K48-linked ubiquitination, leading to a decrease in CDO1 protein abundance in HCC. Furthermore, CDO1 is able to counteract the promotional effect of TRIM47 on HCC biological functions. Overall, our research provides novel insight into the mechanism of TRIM47 in CDO1-mediated ferroptosis in HCC cells, highlighting its value as a potential target candidate for HCC therapeutic approaches.

Assessing the outcome of drug therapy in adult patients with epilepsy who have experienced seizure recurrence after remission

Background. Remission in general sense means disappearance of signs and symptoms of the disease. The risk of recurrence of seizures is usually evaluated only in terms of the risk of a second unprovoked seizure after the first one or the risk of recurrence of seizures after discontinuation of therapy. There are no studies that assess the probability of achieving a second remission in patients with recurrent seizures.Aim. To develop a tool for assessing the probability of favorable and unfavorable treatment outcomes after recurrent seizures in adult patients with different forms of epilepsy.Materials and methods. We analyzed data from 215 patients with recurrent seizures after achieving remission, followed up for 12 or more months, and analyzed disease outcomes.Results and conclusion. At the end of the study, repeat remission was observed in 67 patients, improvement in 48, and no effect in 100. Patients with remission and improvement were combined into a “favorable outcome” group (n = 115), while patients with no effect from therapy formed an “unfavorable outcome” group (n = 100).Patients with an unfavorable outcome were statistically significantly more likely to have factors such as longer disease duration, coexisting serious somatic diseases, structural etiology of epilepsy, bilateral tonic-clonic seizures with focal onset, focal forms of epilepsy, daily seizures, epileptogenic changes on neuroimaging, and regional epileptiform activity on EEG (p &lt;0.05). In turn, patients with a favorable outcome were statistically significantly more likely to have factors such as genetic etiology of epilepsy, generalized tonic-clonic seizures, absences, myoclonic seizures, generalized forms of epilepsy, no pathology on neuroimaging, diffuse epileptiform activity on electroencephalogram, and no pathology on electroencephalogram (p &lt;0.05).Based on the obtained data using the results of constructing contingency tables, a scale for assessing the probability of achieving repeat remission in patients with recurrent epileptic seizures was developed, consisting of 9 sections. To assess the effectiveness of the model, ROC analysis was performed, confirming statistically significant sensitivity and specificity of the obtained scale.Further research is needed to develop more accurate predictors of epilepsy outcomes to understand the peculiarities of the disease pathogenesis.

Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Prevalence and risk factors of anxiety and depression in patients with multi-drug/rifampicin-resistant tuberculosis.

Mental health disorders in patients with multi-drug or rifampicin-resistant tuberculosis (MDR/RR-TB) receive consistent attention. Anxiety and depression can manifest and may impact disease progression in patients with MDR/RR-TB. Given the heightened stressors resulting from the COVID-19 pandemic, this scenario is even more concerning. To evaluate the prevalence of and risk factors associated with anxiety and depression among patients with MDR/RR-TB in southern China. A facility-based cross-sectional study was undertaken at Guangzhou Chest Hospital in southern China, encompassing a cohort of 219 patients undergoing outpatient and inpatient treatment for MDR/RR-TB. Anxiety and depressive symptoms were assessed using the 7-Item Generalized Anxiety Disorder (GAD-7) scale and Patient Health Questionnaire-9 (PHQ-9). The ramifications of anxiety and depression were examined using univariate and multivariate logistic regression analyses, with odds ratios (ORs) and age- and sex-adjusted ORs (AORs) employed to quantify their influence. All data underwent statistical analysis using SPSS 25.0, with statistical significance established at P < 0.05. Two hundred and nineteen individuals with MDR/RR-TB were included in the study. The prevalence of anxiety and depression was 57.53% (n = 126) and 65.75% (n = 144), respectively, with 33.3% (n = 73) of the participants experiencing both conditions simultaneously. Multivariate logistic regression analysis revealed that an age of 20-40 years [anxiety AOR = 3.021, 95% confidence interval (CI): 1.240-7.360; depression AOR = 3.538, 95% CI: 1.219-10.268], disease stigma (anxiety AOR = 10.613, 95% CI: 2.966-37.975; depression AOR = 4.514, 95% CI: 2.051-10.108) and poor physical health (anxiety AOR = 7.636, 95% CI: 2.938-19.844; depression AOR = 6.190, 95% CI: 2.468-15.529) were significant risk factors for moderate levels of anxiety and depression. We found that individuals with MDR/RR-TB had an elevated risk of anxiety and depression. To decrease the likelihood of unfavorable treatment outcomes, it is imperative to carefully monitor the psychological wellbeing of patients with MDR/RR-TB and promptly address any detrimental psychiatric conditions.

PHF19 before and post induction treatment possess favorable potency of reflecting treatment response to protease inhibitors, event-free survival, and overall survival in multiple myeloma patients

ABSTRACT Objective Plant homeodomain finger protein 19 (PHF19) regulates hematopoietic stem cell differentiation and promotes multiple myeloma (MM) progression. This study intended to explore the potency of PHF19 at baseline and post induction treatment in estimating treatment response to protease inhibitors and survival in MM patients. Methods This retrospective study screened 69 MM patients who received protease inhibitors with bone marrow (BM) samples available at both baseline and post induction treatment. Twenty healthy BM donors were included as healthy controls (HCs). PHF19 in plasma cells from BM was quantified by reverse transcription-quantitative polymerase chain reaction. Results PHF19 at baseline and post induction treatment in MM patients were increased than in HCs. In MM patients, PHF19 was declined post induction treatment. Elevated PHF19 at baseline and post induction treatment were correlated with renal impairment, beta-2-microglobulin ≥5.5 mg/L, t (4; 14), higher international staging system (ISS) stage, and higher revised ISS (R-ISS) stage. Concerning treatment response, PHF19 at baseline and post induction treatment were negatively associated with complete response and overall response rate. Notably, abnormal PHF19 (above 95% quantile value of PHF19 in HCs) at baseline and post induction treatment were linked with shortened event-free survival (EFS) and overall survival (OS). After adjustment, abnormal PHF19 post induction treatment was independently related to shortened EFS (hazard ratio = 2.474) and OS (hazard ratio = 3.124). Conclusion PHF19 is aberrantly high and declines post induction therapy, which simultaneously reflects unfavorable treatment response to protease inhibitors as well as shorter EFS and OS in MM patients.

Assessment of treatment outcome among HIV positive tuberculosis patients in Visakhapatnam

In March 2016, RNTCP revised its technical and operational guidelines. One of the major additions was introduction of Daily Regimen in the treatment of Drug sensitive TB, started initially among TB-HIV co-infected patients in 2017. The present study was taken up to assess the treatment outcomes of Tuberculosis among TB-HIV co-infected patients and certain factors related to the poorer outcome of the treatment.An Observational Longitudinal study conducted at an ART centre, attached to King George Hospital in Visakhapatnam District, Andhra Pradesh, among all TB-HIV co-infected patients newly diagnosed with Drug Susceptible Tuberculosis, aged above 18years, at the selected ART centre, from the month of June 2018 to December 2018. The sample size calculated was 88 with an absolute precision of 10. Ethical clearance from Institutional Ethics Committee, Andhra Medical College; Written informed consent from all the study participants were taken prior to start of study. Confidentiality of the study participants was maintained Qualitative variables were presented as proportions. Analytical statistics include chi-square test and regression analysis. 74% of the patients had a favourable treatment outcome, 15% of the patients died and 11% of the patients were lost to follow up. Occupational status of the study participant, Socio- economic class, tobacco using habit and their CD4 counts had a statistically significant impact on their TB treatment outcome.CD4 count below 200cells/mm, Tobacco use, Diabetes Mellitus- factors responsible for unfavourable treatment outcome of Tuberculosis treatment Case-specific approaches among LFUs may be carried out to bring improvements in the strategies which are already existing or framing new strategies.

Clinical usefulness of a host signature based on TRAIL, IP10, and CRP (MeMed BV) as infection biomarkers in intensive care units’ patients. A retrospective observational study

IntroductionInfection complications are common in intensive care unit patients, and early detection remains a diagnostic challenge. Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers. A novel diagnostic approach focuses on the host immune response. One of the approaches, the MMBV index, is based on measuring in a blood sample three parameters: (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), (ii) interferon-γ-induced protein-10 (IP10), and (iii) CRP. This study aimed to evaluate the usefulness of MMBV as an infection biomarker in an ICU cohort. Patients and MethodsForty-six patients treated in the University Clinical Center in Gdansk ICU were enrolled in the study, and their clinical data were retrospectively analyzed. In total, 91 MMBV results were analyzed. ResultsMost of the patients had high MMBV values, suggesting bacterial etiology. A weak correlation between PCT and MMBV was observed, and no correlation between parameter changes was noted. There was a correlation between CRP/MMBV and between changes in CRP / changes in MMBV. ConclusionIt seems that MMBV is not valuable for ICU patients neither in diagnosing nor monitoring infection. Higher MMBV values may predict unfavorable treatment outcomes.

LncRNA MCM3AP-AS1 promotes chemoresistance in triple-negative breast cancer through the miR-524-5p/RBM39 axis.

Triple-negative breast cancer (TNBC) is the most lethal subtype of BC, with unfavorable treatment outcomes. Evidence suggests the engagement of lncRNA MCM3AP-AS1 in BC development. This study investigated the action of MCM3AP-AS1 in chemoresistance of TNBC cells. Drug-resistant TNBC cell lines SUM159PTR and MDA-MB-231R were constructed by exposure to increasing concentrations of doxorubicin/docetaxel (DOX/DXL). MCM3AP-AS1 and miR-524-5p expression levels were determined by RT-qPCR. RNA binding motif 39 (RBM39) level was measured using Western blot. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The targeted binding of miR-524-5p with MCM3AP-AS1 or RBM39 was predicted by ECORI database and validated by dual-luciferase assays. The gain-and-loss of function assays were conducted in cells to investigate the interactions among MCM3AP-AS1, miR-524-5p, and RBM39. TNBC xenograft mouse models were established through subcutaneous injection of MCM3AP-AS1-silencing MDA-MB-231R cells and intraperitoneally administrated with DOX/DXL to verify the role of MCM3AP-AS1 in vivo. MCM3AP-AS1 was upregulated in drug-resistant TNBC cells, and MCM3AP-AS1 silencing could sensitize drug-resistant TNBC cells to chemotherapeutic drugs by promoting apoptosis. MCM3AP-AS1 targeted miR-524-5p. After DOX/DXL treatment, miR-524-5p inhibition partially reversed the effect of MCM3AP-AS1 silencing on inhibiting chemoresistance and promoting apoptosis of drug-resistant TNBC cells. miR-524-5p targeted RBM39. Silencing MCM3AP-AS1 promoted apoptosis via the miR-524-5p/RBM39 axis, thereby enhancing chemosensitivity of drug-resistant TNBC cells. MCM3AP-AS1 knockdown upregulated miR-524-5p, downregulated RBM39, and restrained tumor development in vivo. MCM3AP-AS1 silencing potentiates apoptosis of drug-resistant TNBC cells by upregulating miR-524-5p and downregulating RBM39, thereby suppressing chemoresistance in TNBC.

Estimands for clinical endpoints in tuberculosis treatment randomized controlled trials: a retrospective application in a completed trial

BackgroundRandomized trials for the treatment of tuberculosis (TB) rely on a composite primary outcome to capture unfavorable treatment responses. However, variability between trials in the outcome definition and estimation methods complicates across-trial comparisons and hinders the advancement of treatment guidelines. The International Council for Harmonization (ICH) provides international regulatory standards for clinical trials. The estimand framework outlined in the recent ICH E9(R1) addendum offers a timely opportunity for randomized trials of TB treatment to adopt broadly standardized outcome definitions and analytic approaches. We previously proposed and defined four estimands for use in this context. Our objective was to evaluate how the use of these estimands and choice of estimation method impacts results and interpretation of a large phase III TB trial.MethodsWe reanalyzed participant-level data from the REMoxTB trial. We applied four estimands and various methods of estimation to assess non-inferiority of both novel 4-month treatment regimens against standard of care.ResultsWith each of the four estimands, we reached the same conclusion as the original trial analysis that the novel regimens were not non-inferior to standard of care. Each estimand and method of estimation gave similar estimates of the treatment effect with fluctuations in variance and differences driven by the methods applied for handling intercurrent events.ConclusionsOur application of estimands defined by the ICH E9 (R1) addendum offers a formalized framework for addressing the primary TB treatment trial objective and can promote uniformity in future trials by limiting heterogeneity in trial outcome definitions. We demonstrated the utility of our proposal using data from the REMoxTB randomized trial. We outlined methods for estimating each estimand and found consistent conclusions across estimands. We recommend future late-phase TB treatment trials to implement some or all of our estimands to promote rigorous outcome definitions and reduce variability between trials.Trial registrationClinicalTrials.gov NCT00864383. Registered on March 2009

Improving treatment adherence among tuberculosis patients through evening DOTS in Chennai, India.

Background Fixed days and timings of service are challenges in the care of patients with tuberculosis (TB). We assessed whether provision of evening DOTS (directly observed treatment, short course) improves treatment outcomes in a city with a working population. Methods We enrolled new adult patients with TB from seven tuberculous units (TUs) in this prospective cohort study. Participants were offered the option of DOTS during the day (8 a.m. to 3:30 p.m.) or evening (4 p.m. to 8 p.m.) and assigned accordingly. Results Of 127 patients enrolled between April and July 2017, 19 (15%) opted for evening DOTS. The number varied between the seven TUs (p=0.002). On an average, antitubercular therapy (ATT) was taken at 9:41 a.m. in the routine and 5:14 p.m. in the evening DOTS centres. Patients who were employed, left residence and returned back at 9:05 a.m. and 6:40 p.m., respectively. Around 96% (104/108) opted for day-time DOTS due to closeness of the centre to their residence. Around 74% (14/19) chose evening DOTS because of time convenience. Around 15% of patients on routine DOTS (16) had unfavourable treatment outcomes. All had favourable outcomes in the evening DOTS. Men were less likely and those withut alcohol disorders were more likely to have treatment success. Conclusion Provision of time convenient services might improve adherence and treatment outcome.

Phosphoglycerate Kinase 1: An Effective Therapeutic Target in Cancer.

Phosphoglycerate kinase 1 (PGK1) serves as a pivotal enzyme in the cellular glycolysis pathway, facilitating adenosine-triphosphate (ATP) production in tumor cells and driving the Warburg effect. PGK1 generates ATP through the reversible phosphorylation reaction of 1,3-bisphosphoglycerate (1,3-BPG) to Mg-adenosine-5'-diphosphate (Mg-ADP). In addition to its role in regulating cellular metabolism, PGK1 plays a pivotal role in autophagy induction, regulation of the tricarboxylic acid cycle (TCA), and various mechanisms including tumor cell drug resistance, and so on. Given its multifaceted functions within cells, the involvement of PGK1 in many types of cancer, including breast cancer, astrocytoma, metastatic colon cancer, and pancreatic ductal adenocarcinoma, is intricate. Notably, PGK1 can function as an intracellular protein kinase to coordinate tumor growth, migration, and invasion via posttranslational modifications (PTMs). Furthermore, elevated expression levels of PGK1 have been observed in cancer tissues, indicating its association with unfavorable treatment outcomes and prognosis. This review provides a comprehensive summary of PGK1's expression pattern, structural features, functional properties, involvement in PTMs, and interaction with tumors. Additionally highlighted are the prospects for developing and applying related inhibitors that confirm the indispensable value of PGK1 in tumor progression.

The magnitude of unfavorable tuberculosis treatment outcomes and their relation with baseline undernutrition and sustained undernutrition among children receiving tuberculosis treatment in central Ethiopia

BackgroundOne of the global key indicators for monitoring the implementation of the World Health Organization's End Tuberculosis (TB) Strategy is the treatment outcome rate. ObjectiveThis study aims to assess the magnitude of unfavorable treatment outcomes and estimate their relationship with baseline undernutrition and sustained undernutrition among children receiving TB treatment in central Ethiopia. MethodsThis retrospective cohort study included children treated for drug-susceptible TB between June 2014 and February 2022. The study comprised children aged 16 and younger who were treated in 32 randomly selected healthcare facilities. A log-binomial model was used to compute adjusted risk ratios (aRR) with 95% confidence intervals (CIs). ResultsOf 640 children, 42 (6.6%; 95% CI = 4.8–8.8%) had an unfavorable TB treatment outcomes, with 31 (73.8%; 95% CI = 58.0–86.1%) occurring during the continuation phase of TB treatment. We confirmed that baseline undernutrition (aRR = 2.68; 95% CI = 1.53–4.71), age less than 10 years (aRR = 2.69; 95% CI = 1.56–4.61), HIV infection (aRR = 2.62; 95% CI = 1.50–4.59), and relapsed TB (aRR = 3.19; 95% CI = 1.79–4.71) were independent predictors of unfavorable TB treatment outcomes. When we looked separately at children who had been on TB treatment for two months or more, we found that sustained undernutrition (aRR = 3.76; 95% CI = 1.90–7.43), age below ten years (aRR = 2.60; 95% CI = 1.31–5.15), and HIV infection (aRR = 2.26; 95% CI = 1.11–4.59) remained predictors of unfavorable outcomes, just as they had in the first two months. However, the effect of relapsed TB became insignificant (aRR = 2.81; 95% CI = 0.96–8.22) after the first two months TB treatment. ConclusionsThe magnitude of unfavorable TB treatment outcomes among children in central Ethiopia met the World Health Organization's 2025 milestone. Nearly three-quarters of unfavorable TB treatment outcomes occurred during the continuation phase of TB treatment. Baseline undernutrition, sustained undernutrition, younger age, HIV infection, and relapsed TB were found to be independent predictors of unfavorable TB treatment outcomes among children receiving TB treatment in central Ethiopia.

Self-driven solutions and resilience adapted by people with drug-resistant tuberculosis and their caregivers in Bengaluru and Hyderabad, India: a qualitative study

One-fifth of people with drug-resistance tuberculosis (DR-TB) who were initiated on newer shorter treatment regimen (with injection) had unfavourable treatment outcomes in India as on 2020. Evidence on self-driven solutions and resilience adapted by people with DR-TB (PwDR-TB) towards their multi-dimensional disease and treatment challenges are scarce globally, which we aimed to understand. In this qualitative study using positive deviance framework, we conducted semi-structured in-depth interviews among consenting adult PwDR-TB (7 women, 13 men) who completed shorter treatment regimen (including injections) with maximum treatment adherence. The study was conducted in the southern districts of Bengaluru and Hyderabad, India between June 2020 and December 2022. Caregivers (14 women, 6 men) and health providers (8 men, 2 women) of PwDR-TB were also interviewed. Interviews were conducted in local language (Kannada, Tamil, Telugu, Urdu and Hindi) and inquired about practices, behaviours, experiences, perceptions and attributes which enabled maximum adherence and resilience of PwDR-TB. Interviews were audio recorded, transcribed, and translated to English and coded for thematic analysis using inductive approach. Distinctive themes explanatory of the self-driven solutions and resilience exhibited by PwDR-TB and their caregivers were identified: (i) Self-adaptation towards the biological consequences of drugs, by personalised nutritional and adjuvant practices, which helped to improve drug ingestion and therapeutic effects. Also home remedies and self-plans for ameliorating injection pain. (ii) Perceptual adaptation towards drugs aversion and fatigue, by their mind diversion practices, routinisation and normalisation of drug intake process. and constant reinforcement and re-interpretation of bodily signs of disease recovery (iii) Family caregivers intense and participatory care for PwDR-TB, by aiding their essential life activities and ensuring survival, learning and fulfilling special nutritional needs and goal oriented actions to aid drug intake (iv) Health care providers care, marked by swift and timely risk mitigation of side-effects and crisis response (v) Acquired self-efficacy of PwDR-TB, by their decisive family concerns resulting in attitudinal change. Also being sensitised on the detrimental consequences of disease and being motivated through positive examples. Synthesised findings on self-driven solutions and resilience towards the multi-dimensional DR-TB challenges provides opportunity for developing and testing new interventions for its effectiveness in DR-TB care settings globally. Designing and testing personalised cognitive interventions for PwDR-TB: to inculcate attitudinal change and self-efficacy towards medication, developing cognitive reinforcements to address the perception burden of treatment, skill building and mainstreaming the role of family caregivers as therapeutic partners of PwDR-TB, curating self-adaptive behaviours and practices of PwDR-TB to normalise their drug consumptions experiences could be the way forward in building resilience towards DR-TB. United States Agency for International Development (USAID) through Karnataka Health Promotion Trust (KHPT), Bengaluru, India.

Unsuccessful tuberculosis treatment outcomes across Brazil's geographical landscape before and during the COVID-19 pandemic: are we truly advancing toward the sustainable development/end TB goal?

BackgroundTuberculosis is one of the most significant infectious diseases for global public health. The reallocation of healthcare resources and the restrictions imposed by the COVID-19 pandemic have hindered access to TB diagnosis and treatment. Increases in unfavorable outcomes of the disease have been observed in Brazil. The objective of this study was to analyze the spatial distribution of unfavorable TB treatment outcomes in Brazil before and during the pandemic.MethodsAn ecological study with spatial analysis was conducted with all 5569 municipalities in Brazil. All reported cases of tuberculosis between January 2010 and December 2021, as well as reported cases of COVID-19 from February 2020 to December 2021, were included. The outcomes studied encompass loss to follow-up, drug-resistant tuberculosis, and death. The Getis Ord GI* technique was employed to assess spatial association, and the Kernel density estimator was used to identify areas with concentrated increases or decreases in outcomes. Bivariate Local Moran's I was used to examine the spatial association between outcomes and COVID-19 incidence. The study was approved by the Research Ethics Committee of Ribeirão Preto Nursing School, University of São Paulo.ResultsThere were 134,394 cases of loss to follow-up, 10,270 cases of drug resistance, and 37,863 deaths. Clusters of high and low values were identified for all three outcomes, indicating significant changes in the spatial distribution patterns. Increases in concentrations were observed for lost to follow-up cases in the Southeast, while reductions occurred in the Northeast, South, and Midwest. Drug-resistant tuberculosis experienced an increase in the Southern and Southeastern regions and a decrease in the Northeast and South. TB-related deaths showed notable concentrations in the Midwest, Northeast, South, and Southeast. There was an increase in high occurrence clusters for deaths after 2020 and 2021 in the Northeast.ConclusionsThe pandemic has brought additional challenges, emphasizing the importance of enhancing efforts and disease control strategies, prioritizing early identification, treatment adherence, and follow-up. This commitment is vital for achieving the goal of tuberculosis elimination.

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

Phytocompounds as potential inhibitors of mycobacterial multidrug efflux pump Rv1258c: an in silico approach

The number of infections and deaths caused by multidrug resistant (MDR) tuberculosis is increasing globally. One of the efflux pumps, that makes Mycobacterium tuberculosis resistant to a number of antibiotics and results in unfavourable treatment results is Tap or Rv1258c. In our study, we tried to utilize a rational drug design technique using in silico approach to look for an efficient and secure efflux pump inhibitor (EPI) against Rv1258c. The structure of Rv1258c was built using the homology modeling tool MODELLER 9.24. 210 phytocompounds were used for blind and site-specific ligand docking against the modelled structure of Rv1258c using AutoDock Vina software. The best docked plant compounds were further analysed for druglikeness and toxicity. In addition to having excellent docking scores, two plant compounds—ellagic acid and baicalein—also exhibited highly desirable drug-like qualities. These substances outperform more well-known EPIs like piperine and verapamil in terms of effectiveness. This data shows that these two compounds might be further investigated for their potential as Rv1258c inhibitors.