Unfavorable Treatment Research Articles

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

CXC chemokine ligand 13 and galectin-9 plasma levels collaboratively provide prediction of disease activity and progression-free survival in chronic lymphocytic leukemia

The clinical outcome of lymphocytic leukemia (CLL) is quite heterogeneous. The purpose of this observational study was to investigate the clinical merit of measuring plasma galectin-9 and CXCL-13 concentrations as predictors of CLL activity, prognosis, and early indicators of therapeutic response. These biomarkers were compared with other prognostic indicators, progression-free survival (PFS), time to first treatment (TTT), and overall survival (OS) over a follow-up period (4 years). First, plasma galectin-9 and CXCL-13 concentrations were analyzed in CLL patients at the time of diagnosis as well as healthy controls. Compared to controls, CLL patients had significantly higher serum levels of CXCL-13 and galectin-9. Second, we observed that CLL patients with high soluble CXCL-13 and galectin-9 levels had advanced clinical stages, poor prognosis, 17p del, short PFS, short TTT, and therapy resistance. The levels of CXCL-13, β2-microglobulin, LDH, CD38%, and high grade of Rai-stage were all strongly correlated with the galectin-9 levels. Soluble CXCL-13 and galectin-9 had very good specificity and sensitivity in detecting CLL disease progression and high-risk patients with the superiority of galectin-9 over CXCL-13. Although the two biomarkers were equal in prediction of TTT and treatment response, the soluble CXCL13 was superior in prediction of OS. High CXCL-13 and galectin-9 plasma levels upon CLL diagnosis are associated with disease activity, progression, advanced clinical stages, short periods of PFS, short TTT, and unfavorable treatment response.

Domestic work and health on trial:

In Brazil, domestic workers had an unfavorable legal treatment in relation to other workers for a long time. This legal inequality was mitigated with Constitutional Amendment (EC) 72/2013 – which extended rights related to workers’ health for the group – and Complementary Law (LC) 150/2015 – focused on, above all, on rights related to working hours. This research investigated the recognition of domestic workers’ health rights in the Brazilian labor Judiciary, by using judicial decisions related to domestic work and health, considering the period of COVID-19 pandemic. The investigation used a qualitative approach and an inductive reasoning, with a bibliographic and documental study, based on the analysis of judicial decisions.

Data-Independent Acquisition Mass Spectrometry Analysis of FFPE Rectal Cancer Samples Offers In-Depth Proteomics Characterization of the Response to Neoadjuvant Chemoradiotherapy.

Locally advanced rectal cancer (LARC) presents a challenge in identifying molecular markers linked to the response to neoadjuvant chemoradiotherapy (nCRT). This study aimed to utilize a sensitive proteomic method, data-independent mass spectrometry (DIA-MS), to extensively analyze the LARC proteome, seeking individuals with favorable initial responses suitable for a watch-and-wait approach. This research addresses the unmet need to understand the response to treatment, potentially guiding personalized strategies for LARC patients. Post-treatment assessment included MRI scans and proctoscopy. This research involved 97 LARC patients treated with intense chemoradiotherapy, comprising radiation and chemotherapy. Out of 97 LARC included in this study, we selected 20 samples with the most different responses to nCRT for proteome profiling (responders vs. non-responders). This proteomic approach shows extensive proteome coverage in LARC samples. The analysis identified a significant number of proteins compared to a prior study. A total of 915 proteins exhibited differential expression between the two groups, with certain signaling pathways associated with response mechanisms, while top candidates had good predictive potential. Proteins encoded by genes SMPDL3A, PCTP, LGMN, SYNJ2, NHLRC3, GLB1, and RAB43 showed high predictive potential of unfavorable treatment outcome, while RPA2, SARNP, PCBP2, SF3B2, HNRNPF, RBBP4, MAGOHB, DUT, ERG28, and BUB3 were good predictive biomarkers of favorable treatment outcome. The identified proteins and related biological processes provide promising insights that could enhance the management and care of LARC patients.

Female sex and burden of depressive symptoms predict insufficient response to telemedical treatment in adult attention-deficit/hyperactivity disorder: results from a naturalistic patient cohort during the COVID-19 pandemic.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neuropsychiatric disorder, that typically manifests itself during childhood and persists in a majority of the affected individuals into adulthood, negatively affecting physical and mental health. Previous studies have shown detrimental effects of the COVID-19 pandemic on mental health in individuals with ADHD. Thus, telemedicine could be a useful tool for optimizing treatment-outcomes in adult ADHD by improving treatment adherence and persistence. However, data on telemedical treatment outcomes in adult patients with ADHD is scarce. We report here the sub-cohort analysis of a naturalistic cohort of adult patients (N = 254) recruited between April 2020-April 2021, comparing the effects of telemedical treatment on participants either clinically diagnosed with depression (N = 54) or ADHD (N = 67). Participants were asked to fill out the WHO-5 repetitively during >12 weeks of telemedical treatment. Furthermore scores of WHO-5, SCL-90R and BDI-II, psychopathology, psychosocial functioning, sociodemographic data, medical records and a feedback survey were analyzed for both groups and compared. Participants with ADHD were further stratified according to the development of well-being during the study period in order to identify factors associated with a satisfactory treatment outcome. Participants with depression reported a significant improvement of well-being during the course of the study, while no such effect could be seen in participants with ADHD on a group level. Despite the good outcome, participants with depression were more severely affected at baseline, with significantly worse psychopathology and a more precarious labor and financial situation. A detailed analysis of ADHD participants without clinical improvement revealed significantly higher BDI-II scores than for ADHD participants with a satisfactory outcome (p = 0.03, Mann-Whitney-U-Test), suggesting successful treatment was hampered by the combination of ADHD and depressive symptoms. Furthermore, female sex among ADHD patients was correlated with an unfavorable treatment outcome during the course of the study (p = 0.001, Spearman correlation) as well as living with children (p = 0.02, Spearman correlation). Besides screening for depressive symptoms before telemedical treatment, future research should address the specific needs of female ADHD patients as these patients may be at a particularly high risk of being overburdened with family work.

COVID-19 pandemic and other factors associated with unfavorable tuberculosis treatment outcomes-Almaty, Kazakhstan, 2018-2021.

The COVID-19 pandemic negatively influenced the availability of tuberculosis (TB) services, such as detection, diagnosis and treatment, around the world, including Kazakhstan. We set out to estimate the COVID-19 pandemic influence on TB treatment outcomes by comparing outcomes among people starting treatment before the pandemic (2018-2019) and during the pandemic (2020-2021) and to determine risk factors associated with unfavorable outcomes. We conducted a retrospective cohort study among all people newly diagnosed with drug-sensitive pulmonary or extrapulmonary TB at least 18 years old who initiated treatment from 2018 to 2021 in Almaty. We abstracted data from the national electronic TB register. Unfavorable treatment outcomes were ineffective treatment, death, loss to follow-up, results not evaluated, and transferred. We used multivariable Poisson regression to calculate adjusted relative risk (aRR) and 95% confidence intervals (95%CI). Among 1548 people newly diagnosed with TB during the study period, average age was 43 years (range 18-93) and 52% were male. The number of people initiating treatment was higher before than the pandemic (935 vs. 613, respectively). There was significantly different proportions before compared to during the pandemic for people diagnosed through routine screening (39% vs. 31%, p < 0.001), 60 years and older (16% vs. 22%, p = 0.005), and with diabetes (5% vs. 8%, p = 0.017). There was no difference in the proportion of HIV (8% in both periods). Unfavorable outcomes increased from 11 to 20% during the pandemic (aRR = 1.83; 95% CI: 1.44-2.31). Case fatality rose from 6 to 9% (p = 0.038). Risk factors for unfavorable TB treatment outcomes among all participants were being male (aRR = 1.44, 95%CI = 1.12-1.85), having HIV (aRR = 2.72, 95%CI = 1.99-3.72), having alcohol use disorder (aRR = 2.58, 95%CI = 1.83-3.62) and experiencing homelessness (aRR = 2.94, 95%CI = 1.80-4.80). Protective factors were being 18-39 years old (aRR = 0.33, 95%CI = 0.24-0.44) and 40-59 years old (aRR = 0.56, 95%CI = 0.41-0.75) compared to 60 years old and up. COVID-19 pandemic was associated with unfavorable treatment outcomes for people newly diagnosed with drug-sensitive TB in Almaty, Kazakhstan. People with fewer comorbidities were at increased risk. Results point to the need to maintain continuity of care for persons on TB treatment, especially those at higher risk for poor outcomes during periods of healthcare service disruption.

Glycated Hemoglobin Trajectories and Their Association With Treatment Outcomes Among Patients With Pulmonary TB in India: A Prospective Cohort Study

Transient hyperglycemia is seen commonly during TB treatment, yet its association with unfavorable treatment outcomes is unclear. Does an association exist between glycated hemoglobin (HbA1c) trajectories and TB treatment outcomes? Adults with pulmonary TB were evaluated prospectively for 18months after the second HbA1c measurement. HbA1c trajectories during the initial 3months of treatment were defined as follows: persistent euglycemia, HbA1c< 6.5%at baseline and 3-month follow-up; persistent hyperglycemia, HbA1c≥ 6.5%at baseline and 3-month follow-up; transient hyperglycemia, HbA1c≥ 6.5%at baseline and< 6.5%at 3-month follow-up; incident hyperglycemia, HbA1c< 6.5%at baseline and≥ 6.5%at 3-month follow-up. Multivariable Poisson regression was used to measure the association between HbA1c trajectories and unfavorable treatment outcomes of failure, recurrence, and all-cause mortality. Of the 587 participants, 443 participants (76%) had persistent euglycemia, 118 participants (20%) had persistent hyperglycemia, and 26 participants (4%) had transient hyperglycemia. One participant had incident hyperglycemia and was excluded. Compared with participants with persistent euglycemia, those with transient hyperglycemia showed a twofold higher risk of experiencing an unfavorable treatment outcome (adjusted incidence rate ratio [aIRR], 2.07; 95%CI, 1.04-4.15) after adjusting for confounders including diabetes treatment, and BMI; we did not find a significant association with persistent hyperglycemia (aIRR, 1.64; 95%CI, 0.71-3.79). Diabetes treatment was associated with a significantly lower risk of unfavorable treatment outcomes (aIRR, 0.38; 95%CI, 0.15-0.95). Transient hyperglycemia and lack of diabetes treatment was associated with a higher risk of unfavorable treatment outcomes in adults with pulmonary TB.

Clinic presentation delay and tuberculosis treatment outcomes in the Lake Victoria region of East Africa: A multi-site prospective cohort study.

In the Lake Victoria region of East Africa, little is known about delays between tuberculosis (TB) symptom onset and presentation at a clinic. Associations between clinic presentation delay and TB treatment outcomes are also poorly understood. In 2019, we abstracted data from routine TB treatment records for all adults (n = 776) initiating TB treatment in a 6-month period across 12 health facilities near Lake Victoria. We interviewed 301 cohort members and assessed whether they experienced a clinic presentation delay longer than 6 weeks. We investigated potential clinical and demographic correlates of clinic presentation delay and examined the association between clinic presentation delay and an unfavorable TB treatment outcome (death, loss to follow-up, or treatment failure). Clinic presentation delay was common, occurring among an estimated 54.7% (95% CI: 48.9%, 61.2%) of cohort members, though no specific correlates were identified. Clinic presentation delay was slightly associated with unfavorable TB treatment outcomes. The 180-day risk of an unfavorable outcome was 14.2% (95% CI: 8.0%, 20.4%) among those with clinic presentation delay, compared to 12.7% (95% CI: 5.1%, 20.3%) among those presenting earlier. Multi-level community-based interventions may be necessary to reduce clinic presentation delays in communities near Lake Victoria.

Is Tobacco Use Associated With Risk of Recurrence and Mortality Among People With TB?: A Systematic Review and Meta-Analysis

Associations between tobacco use and poor TB treatment outcomes are well documented. However, for important outcomes such as TB recurrence or relapse and mortality during treatment, as well as for associations with smokeless tobacco (ST), the evidence is not summarized systematically. Is tobacco use associated with risk of poor treatment outcomes among people with TB? The MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health Literature databases were searched on November 22, 2021. Epidemiologic studies reporting associations between tobacco use and at least one TB treatment outcome were eligible. Independent double-screening, extractions, and quality assessments were undertaken. Random effects meta-analyses were conducted for the two primary review outcomes (TB recurrence or relapse and mortality during treatment), and heterogeneity was explored using subgroups. Other outcomes were synthesized narratively. Our searches identified 1,249 records, of which 28 were included in the meta-analyses. Based on 15 studies, higher risk of TB recurrence or relapse was found with ever using tobacco vsnever using tobacco (risk ratio [RR], 1.78; 95%CI, 1.31-2.43; I2= 85%), current tobacco use vsno tobacco use (RR, 1.95; 95%CI, 1.59-2.40; I2= 72%), and former tobacco use vsnever using tobacco (RR, 1.84; 95%CI, 1.21-2.80; I2= 4%); heterogeneity arose from differences in study quality, design, and participant characteristics. Thirty-eight studies were identified for mortality, of which 13 reported mortality during treatment. Ever tobacco use (RR, 1.55; 95%CI, 1.32-1.81; I2= 0%) and current tobacco use (RR, 1.51; 95%CI, 1.09-2.10; I2= 87%) significantly increased the likelihood of mortality during treatment among people with TB compared with never using tobacco and not currently using tobacco, respectively; heterogeneity was explained largely by differences in study design. Almost all studies in the meta-analyses scored high or moderate on quality assessments. Narrative synthesis showed that tobacco use was a risk factor for other unfavorable TB treatment outcomes, as previously documented. Evidence on ST was limited, but identified studies suggested an increased risk for poor outcomes with its use compared with not using it. Tobacco use significantly increases the risk of TB recurrence or relapse and mortality during treatment among people with TB, highlighting the need to address tobacco use to improve TB outcomes. PROSPERO; No.: CRD42017060821; URL: https://www.crd.york.ac.uk/prospero/.

Vulnerability and tuberculosis treatment outcomes in urban settings in England: A mixed-methods study.

Evidence on factors contributing to poor treatment outcome and healthcare priorities in vulnerable populations affected by tuberculosis (TB) in urban areas of England other than London is needed to inform setting-specific prevention and care policies. We addressed this knowledge gap in a cohort of TB patients and healthcare providers in Birmingham and Leicester, UK. A mixed-methods study was performed. Logistic regression was used to identify TB patients more likely to have poor treatment outcomes according to clinical and demographic characteristics and social risk factors (SRFs) in a 2013-18 cohort. 25 semi-structured interviews were undertaken in purposely selected individuals (9 patients and 16 healthcare professionals) to glean insights on their healthcare priorities and the factors that contribute to poor treatment outcome. The quantitative cohort comprised 2252 patients. Those who were ≥ 55 years of age, foreign-born from Central Europe, East Asia and Sub Saharan Africa and with MDR-TB were more likely to have poor treatment outcomes. According to patients and healthcare professionals, the factors that contribute to vulnerability to develop TB and poor treatment outcomes include poor working and living conditions, inadequate or absent welfare protection, poor primary healthcare responsiveness, treatment duration and side effects. These factors could be addressed by increased networking, partnership and integration between healthcare and social services and better integration between primary and secondary healthcare. In both cities, being ≥ 55 years of age, having MDR-TB and being of foreign-birth are predictors of unfavourable treatment outcome. Risk of poor treatment outcome and vulnerability seem to be multidimensional. A better understanding of specific vulnerabilities and how they affect patient care pathway is needed to design adequate support programmes.

Significance of neutrophil to lymphocyte ratio as a predictor of outcome in head and neck cancer treated with definitive chemoradiation.

The role of host immune system in carcinogenesis and response to treatment is increasingly studied, including predictive potential of circulating neutrophils and lymphocytes. The objective of the study was to evaluate the prognostic value of pre- and post-treatment neutrophil-to-lymphocyte (NLR) for treatment outcome in patients diagnosed with squamous cell carcinoma of head and neck (HNSCC) treated with definitive chemoradiation. Electronic medical records of patients were evaluated and NLR was calculated. Cox regression was used to assess the impact of selected variables on overall survival (OS), disease specific survival (DSS), progression free survival (PFS) and distant failure free survival (DFFS). Logistic regression was used to estimate odds ratios of complete response with NLR. 317 patients' records were included in the study. Increases in both pre-and post-NLR were associated with decreased OS in univariable analysis [hazard ratio (HR): 2.26 (1.25-4.07), p = 0.0068 and HR: 1.57 (1.03-2.37), p = 0.035 respectively). Post-NLR remained significant for OS in multivariable analysis [HR: 1.93 (1.22-3.1), p = 0.005] as well as for unfavorable DSS [HR: 2.31 (1.22-4.4), p = 0.01]. Pre-treatment NLR and nodal status correlated with shorter DFFS in multivariable analysis [HR 4.1 (1.14-14), p = 0.03 and HR 5.3: (1.62-18), p = 0.0062, respectively]. Strong correlation of increased both pre- and post-NLR with probability of clinical tumor response (CR) was found [odds ratio (OR): 0.23 (0.08-0.6), p = 0.003, and OR: 0.39 (0.2-0.8), p = 0.01 respectively]. NLR evaluated before and post treatment was a strong predictor of unfavorable treatment outcome and can be used for risk evaluation and clinical decision about treatment and post-treatment surveillance.

The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. Registration: PROSPERO (CRD42022309818).

Determining threshold values for success after surgical treatment of lumbar spondylodiscitis using quality of life scores.

This study aimed to determine threshold values of validated quality of life (QoL) scores, including Oswestry Disability Index (ODI) and Core Outcome Measures Index (COMI), for predicting a successful outcome following surgical treatment of lumbar spondylodiscitis (LS). Patients with lumbar spondylodiscitis (LS) undergoing surgery in a tertiary referral hospital were included prospectively from 2008-2019. Data were collected both before surgery (T0) and one year after surgery (T1). QoL was measured using ODI and COMI. The successful clinical outcome was defined by the combination of the following four criteria: no recurrence of spondylodiscitis, back pain ≤4 on visual analogue scale or relief of ≥3 points, absence of LS-related neurological deficit, and radiological fusion of the affected segment. For subgroup analysis, group 1 consisted of patients with a favorable treatment outcome (meeting all four criteria), while group 2 included patients with unfavorable treatment outcome (meeting ≤3 criteria). Ninety-two LS patients (median age = 66 years; age range = 57-74) were analyzed. QoL scores improved significantly. Threshold values for the ODI and COMI were calculated at 35 and 4.2 points, respectively. The area under curve for the ODI was 0.856 (95%-CI 0.767- 0.945; P<0.001) and 0.839 (95% CI-0.749-0.928; P<0.001) for the COMI score. Eighty percent of patients achieved a favorable outcome. Objective measurement and evaluation of successful surgical treatment of spondylodiscitis require defined thresholds of quality of life scores. We were able to define such thresholds for Oswestry Disability Index and Core Outcome Measures Index. These can be useful to assess clinically relevant changes and therefore allow a more precise estimation of the post-surgical outcome. Level II, Prognostic study.

Elevated pretreatment squamous cell Carcinoma Antigen indicates unfavorable treatment outcomes in cervical cancer patients receiving definitive radiotherapy

AbstractObjectiveTo investigate the prognostic value of pretreatment squamous cell carcinoma antigen (SCC Ag) levels for treatment failure prediction in patients with cervical cancer.MethodsA quantity of 985 patients satisfying the eligibility criteria were included, with a median follow‐up duration of 63.7 months. The optimal cutoff value for pretreatment SCC Ag levels was verified by the receiver operating characteristic (ROC) curve. Five‐year disease‐free survival (DFS), overall survival (OS), and local control (LC) rates were evaluated utilizing the Kaplan‐Meier method. Log‐rank test and Cox proportional hazards model was implemented to recognize independent prognostic predictors.ResultsThe optimal pretreatment SCC Ag cutoff value was 8.85 ng/mL. Patients with pretreatment SCC Ag levels ≥ 8.85 ng/mL presented significantly inferior 5‐year DFS (63.8% vs. 81.8%), OS (71.7% vs. 88.7%), and LC (80.5% vs. 91.0%) compared to those with levels &lt; 8.85 ng/mL (all p &lt; 0.001). The results of the multivariate analysis indicated that the pretreatment SCC Ag level was an independent predictor of treatment failure (HR,1.772; 95% CI, 1.366 to 2.299; p &lt; 0.001).ConclusionPretreatment SCC Ag is an effective prognostic factor in patients with cervical cancer undergoing definitive radiotherapy, with a ROC‐identified cutoff value of 8.85 ng/mL and elevated SCC Ag indicates unfavorable outcomes.

Correlation of N-acetyltransferase 2 genotype and acetylation status with plasma isoniazid concentration and its metabolic ratio in ethiopian tuberculosis patients

Unfavorable treatment outcomes for tuberculosis (TB) treatment might result from altered plasma exposure to antitubercular drugs in TB patients. The present study investigated the distribution of the N-Acetyltransferase 2 (NAT2) genotype, isoniazid acetylation status, genotype–phenotype concordance of NAT2, and isoniazid plasma exposure among Ethiopian tuberculosis patients. Blood samples were collected from newly diagnosed TB patients receiving a fixed dose combination of first-line antitubercular drugs daily. Genotyping of NAT2 was done using TaqMan drug metabolism assay. Isoniazid and its metabolite concentration were determined using validated liquid chromatography-tandem mass spectrometry (LC–MS/MS). A total of 120 patients (63 male and 57 female) were enrolled in this study. The mean daily dose of isoniazid was 4.71 mg/kg. The frequency of slow, intermediate, and fast NAT2 acetylators genotypes were 74.2%, 22.4%, and 3.3% respectively. The overall median isoniazid maximum plasma concentration (Cmax) was 4.77 µg/mL and the AUC0–7 h was 11.21 µg.h/mL. The median Cmax in slow, intermediate, and fast acetylators were 5.65, 3.44, and 2.47 μg/mL, respectively. The median AUC0–7 h hour in slow, intermediate, and fast acetylators were 13.1, 6.086, and 3.73 mg•h/L, respectively. The majority (87.5%) of the study participants achieved isoniazid Cmax of above 3 µg/mL, which is considered a lower limit for a favorable treatment outcome. There is 85% concordance between the NAT2 genotype and acetylation phenotypes. NAT2 genotype, female sex, and dose were independent predictors of Cmax and AUC0–7 h (p < 0.001). Our finding revealed that there is a high frequency of slow NAT2 genotypes. The plasma Cmax of isoniazid was higher in the female and slow acetylators genotype group. The overall target plasma isoniazid concentrations in Ethiopian tuberculosis patients were achieved in the majority of the patients. Therefore, it is important to monitor adverse drug reactions and the use of a higher dose of isoniazid should be closely monitored.

A mixed methods evaluation of a differentiated care model piloted for TB care in south India.

India's National TB Elimination Program emphasizes patient-centered care to improve TB treatment outcomes. We describe the lessons learned from the implementation of a differentiated care model for TB care among individuals diagnosed with active TB. Used mixed methods to pilot the Differentiated Care Model. Community health workers (CHWs) conducted a risk and needs assessment among individuals who were recently began TB treatment. Individuals identified with specific factors that are associated with poor treatment adherence were provided education, counseling, and linked to treatment and support services. Examined changes in TB treatment outcomes between the two cohorts of individuals on TB treatment before and after the intervention. We used qualitative research methods to explore the experiences of patients, family members, and front-line TB workers with the implementation of the DCM pilot. The CHWs were adept at the identification of individuals with risks to non-adherence. However, only a few provided differentiated care, as envisioned. There was no significant change in the TB treatment outcomes between the two cohorts of patients examined. CHWs' ability to provide differentiated care on a scale was limited by the short duration of implementation, their inadequate skills to manage co-morbidities, and the suboptimal support at the field level. It is feasible for a cadre of well-trained front-line workers, mentored and supported by counselors and doctors, to provide differentiated care to those at risk for unfavorable TB treatment outcomes. However, differentiated care must be implemented on a scale for a duration that allows a change from the conventional practice of front-line workers, in order to influence the outcomes of population-level TB treatment.

Second-Line Antiretroviral Treatment Outcomes and Predictors in Tigray Region, Ethiopia.

Ethiopia has one of the highest HIV burdens in sub-Saharan Africa. Despite the fact that second-line antiretroviral therapy (ART) has been available for more than ten years, studies on its effectiveness are scarce. To assess treatment outcomes and predictors of unfavorable outcomes in HIV patients receiving second-line ART at Ayder Comprehensive Specialized Hospital and Mekelle Hospital. An institution-based retrospective cohort study was conducted in two hospitals in Tigray Region, Ethiopia. We evaluated 192 patients aged ≥15 years who were switched to second-line from November 2009 to May 2020 after failure of first-line ART. The primary outcome was the time from the initiation of second-line ART to the occurrence of unfavorable treatment outcomes (treatment failure, death, and loss to follow-up). We performed Kaplan-Meier survival estimates to calculate the cumulative incidence rates of unfavorable outcomes. The mean age (SD) at the initiation of second-line ART was 39 (10.03) years, and the median CD4 cell count was 121 cells/microL. During a median follow-up of 4.6 years, 24 (12.5%) patients had died, 11 (5.7%) patients were lost to follow up, and 47 (24,4%) patients were experienced treatment failure. The incidence rates for unfavorable outcomes were 7.8 per 100 patients/years. Predictors for unfavorable outcomes were body mass index (BMI) <18.5 (adjusted hazard ratio [aHR] = 2.51, 95% confidence interval (CI): 1.27-4.95) and CD4 counts ≤100cells/microL (aHR = 1.74, 95% CI: 1.09-2.79). Despite the failure of second-line ART, none of the patients received third-line ART. The incidence rate of unfavorable treatment outcomes for second-line ART was found to be high. A low BMI and a low baseline CD4 count were significant predictors of unfavourable outcomes and should be given special consideration in HIV care. A third-line ART regimen should also be considered for people who have failed second-line ART.

Effect of prediabetes on tuberculosis treatment outcomes: A study from South India

Background and aimsThe aim was to assess the effect of prediabetes on tuberculosis(TB) treatment outcomes. MethodsThis is a prospective observational cohort study of 569 eligible new smear positive cases screened for DM between 2014 and 2018 in TB units in North Chennai, South India. Based on study criteria, a total of 187 subjects were included and categorised into two groups: TB with normoglycaemia (groupI) (HbA1c<5.7%) and TB with prediabetes (group II) (HbA1c = 5.7–6.4%) and followed them at 3rd and 6th month and treatment outcomes were assessed at the end of the TB treatment. ResultsTotal cure rate was 72.7% with no significant difference between the groups. Higher proportion of deaths occurred in group II (6.3%) compared to group I (1.3%) (p = 0.09). At the end of intensive phase of directly observed therapy (DOTS) treatment, about 23.8% were observed to have positive sputum smear in group II compared to 8.6% in group I(p = 0.019). The estimated relative risk to remain as sputum smear positive among people with prediabetes at the end of intensive phase was 3.0(95% CI: 1.2–7.6). There was a significant association found with HbA1c at enrollment and unfavourable TB treatment outcomes (β = 1.38, [odds ratio (95% CI) 3.98(1.65–9.64); p = 0.007]. ConclusionDeath rate was high and there was a delay in sputum conversion among TB patients with prediabetes at the end of the intensive phase of TB treatment. HbA1c at the time of diagnosis of prediabetes was significantly associated with unfavourable TB treatment outcomes.

Is legislation to prevent genetic discrimination necessary in Japan? An overview of the current policies and public attitudes

Genetic discrimination (GD) has not been discussed in East Asia as extensively as in Europe and North America. Influenced by UNESCO’s universal declaration in 1997, the Japanese government took a stringent approach toward GD by releasing the Basic Principles on Human Genome Research in 2000. However, Japanese society has mostly been ignoring the prevention of GD for decades, and the principle of prohibiting GD was never adhered to in any of the Japanese laws. We conducted anonymous surveys among the general adult population in 2017 and 2022 to explore their experiences of GD and attitudes toward laws carrying penalties to prevent GD in Japan. In both years, approximately 3% of the respondents had experienced some unfavorable treatment regarding their genetic information. They showed higher recognition of the benefits of using genetic information and lower recognition of concerns about using genetic information and GD in 2022 than in 2017. However, the awareness regarding the need for legislation with penalties on GD had increased over the five-year period. In 2022, the framework of a bill to promote genomic medicine and prevent GD without any relevant penalties was released by the Bipartisan Diet Members Caucus. Considering that the absence of regulations may be a barrier to obtaining genomic medicine, as the initial step toward making the prohibition of GD more effective, legislation that no form of GD will be tolerated may stimulate education and awareness regarding respect for the human genome and its diversity.

Extensive traumatic detachment of soft tissue after accident: clinical experience of a multidisciplinary hospital

Relevance. Each case of traumatic skin detachment is specific due to localization and severity of lesions, as well as the decision-making algorithm of treatment remains a subject of discussion. Nowadays the Ministry of Health of the Russian Federation has not produced clinical recommendations or standards for the treatment of such trauma patients. The scope of examination, treatment methods, and efficiency criteria in such injuries are very controversial. Due to errors in the diagnosis of traumatic detachment, difficulties and complications arise during plastic closure of such wound defects.Objective. The study objective is to demonstrate clinical observations of our multidisciplinary hospital in the treatment of patients with traumatic skin detachment, to assess factors affecting surgery outcomes, to propose an algorithm for the treatment of patients with traumatic skin detachment.Materials and methods. 20 patients with traumatic skin detachment underwent wound defect closure upon admission according to Krasovitov surgery. Here the results of 3 clinical cases are presented. Types of traumatic skin detachment, timespan between the injury and start of surgical treatment were analyzed to identify the factors affecting graft healing.Results and discussion. The study reports 33 % of unfavorable treatment outcomes in multidisciplinary hospital. To improve the results, strategy for the management of traumatic skin detachments was proposed. Patients operated according to these recommendations reported satisfactory treatment results.Conclusion. Active introduction a dedicated algorithm for traumatic skin detachment diagnosis and treatment in clinical practice and high-tech methods allowed to achieve significant improvement in immediate and long-term treatment outcomes.