Retreatment Of Patients Research Articles

Analysis of the epidemic characteristics and treatment outcomes of rifampicin-resistant pulmonary tuberculosis in Yangzhou City from 2012 to 2020

Information on patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) in Yangzhou City from 2012 to 2020 was obtained from the Information System of the Chinese Center for Disease Control and Prevention. The epidemic characteristics of RR-PTB patients were analyzed by using χ2 test. The average annual registered incidence rate of RR-PTB patients in Yangzhou City from 2012 to 2020 was 0.57/100 000, and the difference between the registered incidence rates in each year was statistically significant (χ2=29.326, P<0.001). The proportion of re-treated patients (64.8%) was higher than that of newly treated patients (35.2%, χ2=50.593, P<0.001). The registered incidence rate in males (0.91/100 000) was higher than that in females (0.24/100 000, χ2=80.566, P<0.001). The age distribution showed that the highest incidence rate was in the age group≥60 years (0.96/100 000) and the lowest was in the age group 0-<45 years (0.31/100 000, χ2=55.853, P<0.001). From 2012 to 2020, Baoying County had the largest number of registered RR-PTB patients (44 cases), and its registered incidence rate (0.64/100 000) was only lower than that of Guangling District (0.98/100 000). The registered incidence rate of RR-PTB patients in Baoying County during 2016-2020 also increased significantly compared to 2012-2015 (P=0.001). Logistic regression was used to analyze the factors related to the treatment outcome of RR-PTB patients. The results showed that patients aged≥60 years and those classified as the re-treatment were risk factors for successful treatment of RR-PTB patients (P<0.05). In summary, males, people aged≥60 years, patients classified as the re-treatment, and residents of Baoying County should be the key populations for RR-PTB epidemic prevention and control in Yangzhou City.

Identifying Predictors of Unfavorable Treatment Outcomes in Tuberculosis Patients

Objectives: In South Korea, there has been a continuous decrease in the incidence of tuberculosis (TB) attributable to a national TB elimination program; however, TB still poses a significant socioeconomic burden. This study aimed to analyze factors associated with successful TB treatment and to identify refractory patient groups with unfavorable outcomes. Methods: We analyzed anonymized data on 89,150 patients with TB provided by the Korea Disease Control and Prevention Agency. Specifically, we collected independent variables, which were categorized as individual, regional, and medical facility factors. Individual factors included age, sex, nationality, TB type, drug-resistant status, category of TB, housing type, underlying disease status, number of referrals, and smoking status. Regional factors referred to the region where the TB case was reported. Medical facility factors included the first visit to a medical facility, categorized by hospital type and the distinction between private–public mix (PPM) and non-PPM depending on the presence or absence of dedicated TB nurses. These factors were analyzed in relation to treatment success to identify refractory patient groups with unfavorable outcomes. Results: Multivariable logistic regression analysis revealed the following significant factors associated with successful TB treatment: sex, nationality, status of drug-resistant TB, category of TB, number of referrals, region of TB registry, underlying diseases, and smoking status. Specifically, compared with their relevant counterparts, male patients had a lower rate of successful treatment (adjusted odds ratio [aOR]: 0.66, reference [Ref.]: women); Korean nationals had a higher rate of treatment success (aOR: 7.20, Ref. foreign residents in Korea); resistant TB was associated with a lower rate of treatment success (aOR: 0.35, Ref.: non-resistant TB status); newly treated patients had a higher rate of treatment success (aOR: 1.75, Ref.: retreatment patient); switching hospitals once (aOR: 1.78), never (aOR: 1.41), or twice (aOR: 1.37) was associated with increased treatment success (Ref.: three or more times); having zero (aOR: 1.45), one (aOR: 1.31), or two (aOR: 1.24) underlying diseases was associated with a higher rate of treatment success (Ref. three or more underlying diseases); and past smokers (aOR: 1.40) and non-smokers (aOR: 1.35) had a higher rate of treatment success (Ref.: current smokers). Conclusions: Our study identified several factors contributing to unfavorable treatment outcomes in tuberculosis patients, including male patients, foreign residents in Korea, drug-resistant TB, retreatment patients, frequent hospital switching, multiple underlying diseases, and current smoking status. These research findings could inform the development of efficient management strategies and policies for improving the treatment success rate among patients with TB.

Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children's cancer group ALL-2015 protocol: a single center results.

This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS. As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse. Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University.

Construction and Validation of a Predictive Model for Culture Results of Mycobacterium Tuberculosis in Superficial Lymph Nodes.

To establish and validate a nomogram for predicting the culture results of Mycobacterium tuberculosis in superficial lymph nodes. The clinical data of patients with superficial lymph node tuberculosis admitted to Xi'an City Chest Hospital from November 23, 2018, to May 30, 2024, were selected and divided into a training set and a validation set according to a ratio of 7:3. Influencing factors were identified through multivariate logistic regression analyses. Using R version 4.3.2, we developed a predictive model and generated a nomogram based on this model. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curve analysis (CCA), and decision curve analysis (DCA). The positive rate of superficial lymph node tuberculosis culture was 23.0% (103/446). Multivariate Logistic regression analysis showed that anti-tuberculosis treatment duration (OR=0.98, 95% CI: 0.97 ~ 0.99), initial treatment or retreatment (OR=0.12, 95% CI: 0.05 ~ 0.28), and adenosine deaminase (OR=1.12, 95% CI: 1.03 ~ 1.22) were independent factors affecting the culture results of Mycobacterium tuberculosis in superficial lymph nodes. The areas under the ROC curves were 0.86 (95% CI: 0.82-0.91) for the training set and 0.89 (95% CI: 0.84-0.95) for the validation set. The P values of calibration curves were 1.000 and 0.961, respectively, and the predicted values were in good agreement with the actual values. The threshold probabilities of clinical decision curves were 3%~64% and 1%~68%, respectively. The positive rate of Mycobacterium tuberculosis culture in superficial lymph nodes is low. The increase in retreatment patients and anti-tuberculosis treatment time are obstacle factors for Mycobacterium tuberculosis culture positivity, while an increase in adenosine deaminase is a promoting factor for Mycobacterium tuberculosis culture positivity. The nomogram model established based on these factors can be used to predict the results of Mycobacterium tuberculosis culture in superficial lymph nodes.

Spatiotemporal distribution and risk factors for patient and diagnostic delays among groups with tuberculous pleurisy: an analysis of 5-year surveillance data in eastern China.

To understand and analyze the factors relating to patient and diagnostic delays among groups with tuberculous pleurisy (TP), and its spatiotemporal distribution in Zhejiang Province. Data of all tuberculous pleurisy patients were collected from the existing Tuberculosis Information Management System. A time interval of > 2 weeks between first symptom onset and visit to the designated hospital was considered a patient delay, and a time interval of > 2 weeks between the first visit and a confirmed TP diagnosis was considered a diagnostic delay. Univariate and multivariate logistic regression analyses were used to explore factors influencing patient and diagnostic delays in patients with TP. Spatial autocorrelation and spatiotemporal scan analyses were used to identify hot spots and risk clusters, respectively. In total, 10,044 patients with TP were included. The median time and interquartile range for patients seeking medical care and diagnosis were 15 (7-30) and 1 (0-8) days, respectively. The results showed that people aged > 65 years, retirees, and residents of Jinhua, Lishui, and Quzhou were positively correlated with patient delay, whereas retreatment patients, houseworkers, unemployed people, and residents of Zhoushan or Ningbo were positively correlated with diagnostic delay. Additionally, high-risk clusters of patient delays were observed in the midwestern Zhejiang Province. The most likely clusters of TP diagnostic delays were found in southeast Zhejiang Province. In summary, patient delay of TP in Zhejiang province was shorter than for pulmonary tuberculosis in China, while the diagnostic delay had no difference. Age, city, occupation, and treatment history were related to both patient and diagnostic delays in TP. Interventions in central and western regions of Zhejiang Province should be initiated to improve the early detection of TP. Additionally, the allocation of health resources and accessibility of health services should be improved in the central and eastern regions of Zhejiang Province.

An Epidemiological Profile of Previously Treated Patients Registered in Tuberculosis Units in Urban Visakhapatnam

Background: Tuberculosis (TB) remains a major global public health problem. Retreatment patients havehigher risk of drug resistance compared with new cases. The objective of the study is to describe the typesof retreatment (previously treated) patients and assess the Socio demographic characteristics, co morbidand behavioural conditions of retreatment patients and to identify the factors associated with relapseunder Revised National Tuberculosis Control Program ( RNTCP) in the tuberculosis units located in UrbanVisakhapatnam. The main aim of the study is to study epidemiological profile of previously treated patientsto identify the factors which make tuberculosis patients prone for retreatment so that necessary action canbe taken.Methods: This is an Observational Analytical Cross-sectional study done in Tuberculosis units in GVMC. All thesubjects(193) who were registered as Previously treated patients in TUs during the second and third quarter ofthe year 2016 i.e April to September 2016. A pretested semi structured schedule was administered. Categoricaldata was analysed by Chi square test. Quantitative variables were represented as means and standard deviation.Unpaired t test was used for testing statistical significance in quantitative data.Results : Among 193 study subjects 168 (87%) were having pulmonary TB and remaining 25 (13%) were havingextra pulmonary TB. Majority of the study participants, 141 (73%) were males whereas only 52 (27%) were females.Relapse patients were 125(64.9%) Defaulters were 12 (6.2%), Treatment failure was 9 (4.6%) and Others previouslytreated were 47 (24.3%). Chi square test was used for testing statistical significance of association betweencategorical variables.Conclusion: Socio demographic factors, behavioural and co morbid factors have an effect on Relapse andmodifying these risk factors may bring about favourable outcomes. There is further need for exploring the reasonsfor high rates of relapse.

Drug-resistant pulmonary tuberculosis at Maradi Regional Hospital Center, Niger (2014-2018)

To describe the clinical, therapeutic and evolutionary profile of patients followed for rifampicin-resistant pulmonary tuberculosis (RR-TB) at the Regional Hospital Centre (RHC) of Maradi (Niger) from 2014 to 2018. We conducted a retrospective and descriptive study based on the records of patients followed for Multidrug-resistant tuberculosis (MDR-TB) between January 1, 2014 and June 30, 2018 at the resistant tuberculosis management unit in Maradi (Niger). This unit is located within the RHC of Maradi and has a capacity of 20 beds in 4 wards. It receives patients with tuberculosis resistant to first-line anti-tuberculosis drugs. In this study, patients diagnosed with RR-TB by genotypic (GeneXpert MTB/RIF) or phenotypic (culture) testing were included. We excluded from this study: patients previously treated for more than 1 month with second-line anti-TB drugs; patients with resistance to second-line injectables (SLI) and/or fluoroquinolones (FQ); patients with an electrocardiogram QTc greater than 500 ms (the corrected QT (QTc) estimates the QT interval at a rate of 60 beats per second); cases of atypical mycobacteriosis detected by phenotypic testing.Patients were previously on 2RHZE/4RH prior to the discovery of resistance. The treatment protocol for resistant TB was as follows: 4KmMfxPtoCfzHZE/5MfxCfzZE (The second-line injectable was replaced by Lzd in case of initial or treatment-emergent deafness). HIV co-infected patients received, in addition to anti-tuberculosis drugs, antiretrovirals and cotrimoxazole in preventive doses. A total of 80 patients were included in the present study (70 males and 10 females, mean age 34.4 years with extremes ranging from 18 to 71 years). Patients aged 18-35 years accounted for more than half. Patients with primary treatment failure were the most frequent type (36%) followed by patients with retreatment failure (24%) and patients with retreatment relapse (17%). It should be noted that 77 patients (96%) were previously treated for TB and only 3 patients (4%) were new cases. The majority of patients (70%) had a Body mass index of less than 18 kg/m2. 7.5% of patients were HIV positive, one was diabetic, 52% of the patients had grade 2 radiological lesions. Grade 1 deafness was noted at the beginning of treatment in 3%. A third of patients (36%) were primary treatment failures. The treatment protocol was as follows: 4KmMfxPtoCfzHZE/5MfxCfzZE. Only 1 patient had a positive culture at the end of the 4th month of treatment. Most of the patients had experienced adverse events, mainly digestive, with vomiting being the most common. The therapeutic success rate was 88%. We noted 10% of deaths, 1% of therapeutic failure and 1% of lost to follow-up.Six months after treatment, 48 patients (60%) were smear negative and 43 (54%) were culture negative. In 32 patients (40%), the smear was not performed and culture was not performed in 37. The short treatment regime gives satisfactory results in the absence of resistance to fluoroquinolones, with rare adverse effects. In Niger, further efforts should be made to minimize the delay in diagnosis which is responsible for most deaths during treatment. A centre could usefully be designated to organize "TB consiliums" allowing any practitioner to submit difficult cases of MDR-TB.

Sustained high fatality during TB therapy amid rapid decline in TB mortality at population level: A retrospective cohort and ecological analysis from Shiselweni, Eswatini.

Despite declining TB notifications in Southern Africa, TB-related deaths remain high. We describe patient- and population-level trends in TB-related deaths in Eswatini over a period of 11 years. Patient-level (retrospective cohort, from 2009 to 2019) and population-level (ecological analysis, 2009-2017) predictors and rates of TB-related deaths were analysed in HIV-negative and HIV-coinfected first-line TB treatment cases and the population of the Shiselweni region. Patient-level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient-level and population-level predictors of deaths. Of 11,883 TB treatment cases, 1302 (11.0%) patients died during treatment: 210/2798 (7.5%) HIV-negative patients, 984/8443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV-status. The treatment case fatality ratio remained above 10% in most years. At patient-level, fatality risk was higher in PLHIV (aRR 1.74, 1.51-2.02), and for older age and extra-pulmonary TB irrespective of HIV-status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18-1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47-1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB-LAM testing (aRR 0.65, 0.35-0.90). At population-level, mortality rates decreased 6.4-fold (-147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (-826/100,000 vs. HIV-negative: -23/100,000), the relative population-level mortality risk remained higher in PLHIV (aRR 4.68, 3.25-6.72) compared to the HIV-negative population. TB-related mortality rapidly decreased at population-level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.

Relapse after First-Line Fixed Duration Ibrutinib + Venetoclax: High Response Rates to Ibrutinib Retreatment and Absence of BTK Mutations in Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) with up to 5 Years of Follow-up in the Phase 2 Captivate Study

Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of ibrutinib + venetoclax as first-line treatment for CLL/SLL in 2 cohorts: minimal residual disease (MRD)-guided randomized-discontinuation (MRD cohort) and Fixed Duration (FD cohort). Results from the FD cohort with 4 years of follow-up (Barr, ASCO 2023) showed 4-year progression-free survival (PFS) and overall survival (OS) rates of 79% and 98%, respectively. After completing fixed-duration treatment, ibrutinib-based retreatment was allowed per protocol in patients with an indication for treatment after experiencing progressive disease (PD). Here, we report retreatment outcomes in patients from the FD cohort or the MRD cohort placebo arm, as well as updated results with an additional year of follow-up (up to 5 years) from the FD cohort. Methods: Patients aged ≤70 years with previously untreated CLL/SLL received 3 cycles of ibrutinib, then 12 cycles of combined ibrutinib + venetoclax (ibrutinib, 420 mg/day orally; venetoclax, standard 5-week ramp up to 400 mg/day orally). Response was assessed by investigators per International Workshop on CLL (iwCLL) 2008 criteria. Duration of response (DOR), PFS, and OS were estimated using Kaplan-Meier methodology. Per protocol, on-study retreatment included single-agent ibrutinib; patients with PD &amp;gt;2 years after treatment completion could be retreated with the FD regimen (3 cycles of ibrutinib + 12 cycles of ibrutinib + venetoclax). Results: Of 202 patients treated with fixed-duration ibrutinib + venetoclax in the FD cohort (n=159) or the MRD cohort placebo arm (n=43), 53 have had PD to date (Table 1), with PD occurring &amp;gt;2 years after completion of treatment in the majority of patients (33/53 [62%]). Of the 40 patients with available samples at PD, one had an acquired resistance-associated mutation in BCL2 (A113G); no other patient had clinically relevant mutations in BTK, BCL2, or PLCG2. A total of 22 patients have initiated retreatment on study with single-agent ibrutinib. With a median time on retreatment of 17 months (range, 0-45), overall response rate (ORR) in 21 evaluable patients was 86% (with best responses of complete response [CR], n=1 [5%]; partial response [PR], n=17 [81%]; PR with lymphocytosis, n=1 [5%]; stable disease, n=1 [5%]; PD [Richter transformation], n=1 [5%]). The most frequent adverse events (AEs; occurrence ≥10%) during single-agent ibrutinib retreatment were COVID-19 (n=6, all grade 1/2), diarrhea (n=5), hypertension (n=4), and pyrexia (n=3). No dose reductions or discontinuations due to AEs occurred among retreated patients. Eighteen patients have not received subsequent treatment, 7 patients have initiated other subsequent therapies, and 6 patients have started retreatment with ibrutinib + venetoclax (time on retreatment, 5-15 months). Best responses in patients retreated with ibrutinib + venetoclax are CR, n=2; PR, n=3; and SD, n=1. Response data for the patient with BCL2 (A113G) is pending. To date, with a median time on study of 56 months (range, 1-61) for patients in the FD cohort, the 54-month PFS and OS rates were 70% (95% CI, 62-77) and 97% (95% CI, 93-99), respectively. Best response rates remained unchanged from the 4-year follow-up analysis (CR, including CR with incomplete bone marrow recovery [CRi], 58%; ORR, 96%). In patients who achieved CR/CRi (n=92), median duration of CR/CRi was not reached; 90/92 patients (98%) achieved durable CR/CRi (lasting ≥12 cycles). PFS in patients with high-risk features was promising (Table 2), but it was numerically lower in the subset with del(17p)/mutated TP53 (54-month rate, 45% [95% CI, 25-64]). Serious AEs considered related to study treatment and second malignancies continued to be collected after completion of fixed-duration treatment. One AE of basal cell carcinoma occurred during this additional year of follow-up. In total, second malignancies have occurred in 8% of patients since completion of ibrutinib + venetoclax treatment. Conclusion: Ibrutinib-based retreatment results in the CAPTIVATE study show promising responses in patients needing subsequent therapy after receiving this all-oral, once-daily fixed-duration regimen for first-line treatment of CLL/SLL. With up to 5 years of follow-up, fixed-duration ibrutinib + venetoclax continues to provide deep remissions with clinically meaningful PFS, including in patients with high-risk genomic features.

An Insight Into Tuberculosis Patients in the Chest Clinic of North India: Epidemiological Profile and Treatment Outcomes in the Wake of COVID-19.

Objectives Our study aims to re-evaluate the epidemiological profile and treatment outcomes of TB patients enrolled at the chest clinic of a tertiary care center after the third wave of COVID-19 in New Delhi. Patients and methods We have conducted an observational analytical study after taking the IEC approval from October 2022 to February 2022 on the TB patients enrolled from March 2022 to August 2022. The total data of 1114 TB patients was analyzed. The association between various factors and treatment outcomes was assessed using the chi-square test. To identify the independent effects of these factors on treatment outcomes, we did a multiple logistic regression analysis. Results We found that the treatment outcomes were mostly successful (83.9%, n=935), while a few patients lost to follow-up (11.7%, n=130) and died (4.4%, n=49). Deaths were significantly higher among geriatrics (19%, n=15), PTB (4.9%, n=30), and MDR TB (15%, n=3). The treatment success was highest among the new category of patients (85.1%, n=807), followed by retreatment patients (80.1%, n=117) and MDR TB patients (55%, n=11). Adults and geriatrics had a significantly higher risk of death (4.45 times and 27.93 times, respectively) compared to pediatrics. In addition, death risks were higher among males (1.6 times for females), MDR TB patients (17 times for new patients), and HIV-reactive patients (3.05 times for HIV non-reactive patients). Conclusion We found that males, HIV-TB co-infection, the geriatric population, pulmonary TB patients, and MDR TB were at a higher risk of death. By identifying high-risk groups, policymakers can prioritize targeted interventions and allocate resources effectively to address the specific needs of these vulnerable populations.

Discontinuation of Nucleos(t)ide Analog treatment in HBeAg-Negative Non-Cirrhotic Chronic Hepatitis B Patients: Real-Life Data of 20 Years.

Discontinuation of nucleos(t)ide analog is controversial in HBeAg-negative chronic hepatitis B patients not achieved HBsAg loss. We aimed to evaluate re-treatment rates and risk factors in non-cirrhotic HbeAg-negative chronic hepatitis B patients for whom nucleosi(t)ides analogs were discontinued. Demographic, clinical, and laboratory data before and at the end after discontinuation of nucleos(t)ide analogs were collected retrospectively. Seventy-two patients followed up between January 2000 and December 2019 were included; 43 were male, with a mean age of 46.3 (±10.8). Baseline median alanine aminotransferase (ALT) and hepatitis B virus DNA levels were 55.5 IU/L and 465 925 IU/mL, respectively. The median histologic activity index was 5.5 and the fibrosis score was 2. The median duration of treatment and consolidation therapy were 59 and 56 months, respectively. The median follow-up time after discontinuation of treatment was 55 months. Among 56 patients eligible for evaluation according to proposed re-treatment criteria, 29 (51.7%) patients were re-treated. The median time for relapse was 11 months. Re-treatment was significantly common in males (P = .034) and patients treated with tenofovir/entecavir (P = .04). Baseline hepatitis B virus DNA and levels of ALT, aspartate aminotransferase (AST) at the third and sixth months of treatment and at the end of treatment were statistically significantly higher in re-treated patients. A cutoff value of ≥405 000 IU/L for hepatitis B virus DNA discriminated patients for re-treatment. HBsAg was lost permanently in 2 non-re-treated patients. In resource-limited areas where follow-up of HBsAg or other markers is not possible, nucleos(t)ide analog discontinuation can be considered in patients in the early stage, with low baseline hepatitis B virus DNA and ALT levels, after a long consolidation therapy.

Endostatin in combination with PD-1 antibody plus chemotherapy as first-line regimen for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer: A real-world study.

e20564 Background: In recent years, treatment for advanced or metastatic NSCLC has been significantly improved with the emergence of a combination strategy of immunotherapy with antiangiogenic drugs plus chemotherapy. Although endostatin (an antiangiogenic agent) combined with chemotherapy has been approved by the China Food and Drug Administration in treatment-naïve and re-treatment NSCLC patients, the clinical evidence supporting its combination with programmed cell death-1 (PD-1) antibody for advanced or metastatic NSCLC is still insufficient. Therefore, we aimed to evaluate the effectiveness and safety of endostatin combined with PD-1 antibody plus chemotherapy as the first-line treatment for locally advanced or distant metastatic NSCLC with EGFR/ALK-negative. Methods: This was a retrospective, singer-center, real-world study conducted between June 2018 and December 2021. The primary endpoint was progression-free survival (PFS); the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Overall, 68 patients were included. The median PFS and OS were 22.0 months (95% confidence interval [CI]: 16.6-27.4 months) and 31.0 months (95% CI: 23.4 months-not reached [NR]), respectively, with a median follow-up of 21.4 months (range, 8.3-44.4 months). At the data cutoff, 33 patients (48.5%) remained progression-free and 24 patients (35.3%) had died. Short-term clinical efficacy was assessed after 2 consecutive treatment cycles, with an ORR of 72.06% (complete response [CR], n = 3; partial response [PR], n = 46) and a DCR of 95.59% (CR, n = 3; PR, n = 46; stable disease, n = 16). Further subgroup analysis determined that a significantly better ORR (89.2% vs. 51.6%), median PFS (23.4 vs. 13.2 months), and median OS (NR vs. 18.0 months) for patients with stage Ⅲ B/Ⅲ C vs. stage Ⅳ NSCLC (all p ≤ 0.001). Besides, the median PFS (8.0 months vs. 22.5 months, p = 0.004) and OS (13.0 vs. 31.0 months, p = 0.027) of patients with brain metastasis were significantly shorter than those without brain metastasis. The ORR in patients who had a PD-L1 tumor proportion score (TPS) of &lt; 1%, 1%-49%, ≥ 50%, and unknown were 50%, 50%, 75.0%, and 86.1%, respectively ( p = 0.025). All patients (100%) experienced treatment-related adverse events (AEs). The majority of AEs were grade 1 or 2 (57/68, 83.82%). Conclusions: In the real-world scenario, endostatin combination with PD-1 antibody plus chemotherapy obtained encouraging efficacy and favorable safety in advanced or metastatic NSCLC. The combination strategy in this study furnished beneficial evidence for the treatment of advanced or metastatic NSCLC and is essential for determining the best treatment option.

Whole-Genome Sequencing Exhibits Better Diagnostic Performance than Variable-Number Tandem Repeats for Identifying Mixed Infections of Mycobacterium tuberculosis.

Mixed infections of Mycobacterium tuberculosis, defined as the coexistence of multiple genetically distinct strains within a single host, have been associated with unfavorable treatment outcomes. Different methods have been used to detect mixed infections, but their performances have not been carefully evaluated. To compare the sensitivity of whole-genome sequencing (WGS) and variable-number tandem repeats (VNTR) typing to detect mixed infections, we prepared 10 artificial samples composed of DNA mixtures from two strains in different proportions and retrospectively collected 1,084 clinical isolates. The limit of detection (LOD) for the presence of a minor strain was 5% for both WGS and VNTR typing. The overall clinical detection rate of mixed infections was 3.7% (40/1,084) for the two methods combined, WGS identified 37/1,084 (3.4%), and VNTR typing identified 14/1,084 (1.3%), including 11 also identified by WGS. Multivariate analysis demonstrated that retreatment patients had a 2.7 times (95% confidence interval [CI], 1.2 to 6.0) higher risk of mixed infections than new cases. Collectively, WGS is a more reliable tool to identify mixed infections than VNTR typing, and mixed infections are more common in retreated patients. IMPORTANCE Mixed infections of M. tuberculosis have the potential to render treatment regimens ineffective and affect the transmission dynamics of the disease. VNTR typing, currently the most widely used method for the detection of mixed infections, detects mixed infections only by interrogating a small fraction of the M. tuberculosis genome, which necessarily limits sensitivity. With the introduction of WGS, it became possible to study the entire genome, but no quantitative comparison has yet been undertaken. Our systematic comparison of the ability of WGS and VNTR typing to detect mixed infections, using both artificial samples and clinical isolates, revealed the superior performance of WGS at a high sequencing depth (~100×) and found that mixed infections are more common in patients being retreated for tuberculosis (TB) in the populations studied. This provides valuable information for the application of WGS in the detection of mixed infections and the implications of mixed infections for tuberculosis control.

Comparison of Clear Aligner Treatment in First-Treatment and Re-Treatment Patients: A Retrospective Cohort Study

This retrospective real-world study aimed to evaluate the outcomes of clear aligner treatment (CAT) and patient demographics of patients seeking orthodontic re-treatment who had previously received orthodontic treatment in childhood or adolescence. The study was conducted using anonymized data from DrSmile (Berlin, Germany), a CAT provider in Europe. Data were collected from a total of 2080 patients in Germany (71.5% female, 28.5% male, ranging from 18–70 years, median 29.0 years), who completed their CAT between 1 June and 30 June 2022. Patients were divided into two groups: adult first-treatment patients (n = 1587) and adult re-treatment patients (n = 493). Results showed that re-treatment patients had a shorter treatment duration (p &lt; 0.05), required fewer interproximal reductions (IPR) (p &lt; 0.001), and had fewer clinical visits (mean 2.96 versus 4.14 visits) than first-treatment patients (p &lt; 0.001). Data collected from adult orthodontic re-treatment and first-treatment patients indicated that the demographic characteristics of these two groups were very similar. No significant differences were found between re-treatment patients and first-treatment patients in terms of motives for orthodontic treatment (p = 0.068), types of insurance (p = 0.615), and treatment satisfaction (p = 0.673). The study highlights the need for orthodontists and dentists to provide adequate information to patients about long-term retention and decision-making for orthodontic treatment, especially for re-treatment.

Drug Resistance of Mycobacterium tuberculosis Based on Whole-Genome Sequencing in the Yi Ethnic Group, Sichuan Province, China.

This study investigated drug-resistant tuberculosis (DR-TB) in the Yi ethnic group. The study was designed to identify risk factors for DR-TB and its relationship with HIV/AIDS. To establish the resistance to antituberculosis drugs, whole-genome sequencing (WGS) was performed using culture-positive Mycobacterium tuberculosis samples collected from people of the Yi ethnic group from March 2019 to March 2021. Baseline characteristics were obtained from China's tuberculosis surveillance system. A total of 116 M. tuberculosis strains were included in the final analysis. Lineage 2.2 (75.86%) was the dominant sublineage, followed by lineage 4.5 (18.97%) and lineage 4.4 (5.17%). The rates of rifampicin-resistant (RR-TB), multidrug-resistant (MDR-TB), and preextensively drug-resistant TB (pre-XDR-TB) were 18.97%, 10.34%, and 6.03%, respectively. Drug-resistant strains were not found in the elderly (age ≥ 65 years). The proportions of RR/MDR-TB and pre-XDR-TB cases among re-treatment patients were higher than those among new patients (χ 2 = 12.155, P = 0.003; χ 2 = 22.495, P = 0.001, respectively). The pre-XDR-TB case proportions were higher among female patients than among males and higher among referred patients (χ 2 = 5.456, P = 0.032; χ 2 = 15.134, P = 0.002, respectively). The rates of RR/MDR-TB and pre-XDR-TB did not differ appreciably among groups with different HIV infection statuses nor lineage populations. DR-TB poses a serious challenge to the Yi ethnic group. Re-treatment patients, women, and referred patients were at high risk of MDR/RR-TB or pre-XDR-TB while HIV and lineage 2 had negligible association with drug resistance. Whole-genome sequencing should be used to guide the design of treatment regimens and to tailor public interventions.

Short-Term Peg-IFN α-2b Re-Treatment Induced a High Functional Cure Rate in Patients with HBsAg Recurrence after Stopping Peg-IFN α-Based Regimens.

Little is known about the treatment of patients with hepatitis B surface antigen (HBsAg) recurrence after being clinically cured by peginterferon alpha(peg-IFN-α)-based regimens. This study aimed to investigate the efficacy and safety of peg-IFNα-2b in re-treating patients with HBsAg recurrence after stopping peg-IFN α-based regimens. In this two-center, prospective observational study, 33 patients with HBsAg recurrence after stopping peg-IFN α-based regimens were enrolled and re-treated with an individualized course of peg-IFN α-2b. The hepatitis B virus (HBV) vaccine could be injected immediately after HBsAg clearance, according to patients’ willingness. All patients were monitored and followed-up for 48 weeks after peg-IFN α-2b re-treatment stop. The primary endpoint was HBsAg clearance at the end of follow-up. At baseline, all patients had HBsAg levels of <10 IU/mL and undetectable HBV DNA, with the median HBsAg level of 1.66 (0.56−2.87) IU/mL. After a median of 24 (24−30) weeks of peg-IFN α-2b re-treatment, 87.9% (29/33) of the patients achieved HBsAg clearance again and 66.7% (22/33) of the patients achieved HBsAg seroconversion. At the end of follow-up, the HBsAg clearance and HBsAg seroconversion rates decreased to 78.8% (26/33) and 51.5% (17/33), respectively. Furthermore, 88.9% (16/18) of the patients with HBsAg clearance benefited from receiving the HBV vaccine therapy. Generally, both peg-IFN α-2b and HBV vaccine therapy were well tolerated. A high functional cure rate can be achieved by a short-course of peg-IFN α-2b re-treatment in patients with HBsAg recurrence after stopping peg-IFN α-based regimens. Furthermore, injecting HBV vaccine is beneficial after HBsAg clearance.

Trends of Rifampicin Resistance in Patients with Pulmonary Tuberculosis: A Longitudinal Analysis Based on Drug Resistance Screening in Eastern China Between 2015 and 2019.

To understand the trend of overall rifampicin resistance rates for tuberculosis in Zhejiang Province between 2015 and 2019. The basic demographic information of patients with tuberculosis who were screened for drug resistance in Zhejiang Province between January 1, 2015 and December 31, 2019 was collected through the national Tuberculosis Information Management System. The data were processed and analyzed using IBM SPSS 26.0 and GeoDa 1.14 software. The total rifampicin resistance rate was 5.9% in 53,893 validated cases of drug resistance screening conducted in patients with pulmonary tuberculosis in Zhejiang Province during the study period. There was a decreasing trend in the rifampicin resistance rate in both initial and re-treated patients (P<0.001), but the rifampicin resistance rate was higher in re-treated TB patients than in TB patients receiving their initial treatment (11.4% vs 4.2%). The rate of drug resistance steadily decreased in all prefectures, and there was a significant upward trend in the use of the Xpert MTB/RIF rapid assay. An increasing trend was also identified in the rate of rifampicin and ofloxacin co-resistance (P<0.001). The overall rate of rifampin resistance in patients with tuberculosis in Zhejiang Province in the past five years has shown a decreasing trend, but the rate of resistance to ofloxacin was high. Resistance testing to fluoroquinolones should be carried out as early as possible in patients whose diagnosis results indicate rifampin resistance, and more effective second-line treatment plans should be developed based on the results of this testing.

The Correlations of Minimal Inhibitory Concentration Values of Anti-TB Drugs with Treatment Outcomes and Clinical Profiles in Patients with Multidrug-Resistant Tuberculosis (MDR-TB) in China

ObjectiveIt is a challenge to obtain satisfactory treatment outcomes for patients with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB); the study aims to correlate the Minimum Inhibitory Concentration (MIC) value of drugs with the outcome of patients with MDR/RR-TB to obtain an understanding for better regimens and optimal outcomes.MethodsThe patients diagnosed with MDR/RR-TB were retrospectively enrolled from January 1, 2018 to December 31, 2019, recorded clinical characteristics, MIC DST (Drug Susceptibility Test) results, and followed the treatment outcome. The data were analyzed on the correlations of MIC DST values with outcomes and clinical characteristics.ResultsA total of 276 patients with MDR/RR-TB were included, containing 98 cases (35.5%) with newly treated patients and 178 cases (64.5%) with re-treated patients. A total of 220 cases recorded treatment success (79.7%) and 49 cases recorded treatment failure or died. MIC values of isoniazid (H), moxifloxacin (Mfx), and ethionamide (Eto) in newly treated patients were lower than those in retreated patients, and resistance levels of Mfx and H were closely associated with the treatment outcome (P < 0.05) while those of other drugs had no close association with treatment outcome.ConclusionsMIC values of some anti-TB drugs, such as fluoroquinolones (FQs) and H, can reflect the treatment outcome for patients with MDR/RR-TB, which can contribute to making regimens for better treatment outcomes.

Factors contributing to the high prevalence of multidrug-resistance/Rifampicin-resistance in patients with tuberculosis: an epidemiological cross sectional and qualitative study from Khabarovsk krai region of Russia

BackgroundGrowing prevalence of multidrug-resistant/Rifampicin-resistant tuberculosis (MDR/RR-TB; resistance to Isoniazid and Rifampicin/Isolated resistance to Rifampicin) is putting in jeopardy the WHO End TB strategy. This study aimed to identify factors contributing to the high prevalence of MDR/RR-TB in Khabarovsk krai region of Russia.MethodsA cross-sectional retrospective study was conducted, analyzing clinical, demographic, and drug susceptibility testing data on 1440 patients. As a source of raw data, the national electronic TB surveillance system was used. Anonymous data was collected on every patient diagnosed with TB in all healthcare facilities of the region from January 2018 to December 2019. Only patients with proven excretion of m. tuberculosis were included in the study. Factors associated with MDR/RR-TB were identified through logistic regression analysis, in conjunction with in-depth interviews with eight patients, five healthcare managers and five doctors.Findings2661 patients were identified with TB, 1440 were incorporated in the study based on inclusion criteria. Of these, 618 (42.9%) were identified with MDR/RR-TB. Patients with a history of imprisonment were 16.53 times (95% CI 5.37 to 50.88,) more likely to have MDR/RR-TB, whereas re-treatment patients were 2.82 times (95% CI 2.16 to 3.66) more likely to have MDR/RR-TB. Other influencing factors included presence of disability (AOR is 2.32, 95% CI 1.38 to 3.89), cavitary disease (AOR is 1.76, 95% CI 1.37 to 2.25), and retirement status (AOR 0.65, 95% CI 0.43 to 0.98, p = 0.042). Poor patient knowledge and understanding of the disease, progressive weariness of prolonged TB treatment, and inability hospitalize infectious patients without their consent were perceived by the interviewees as major influencing factors.ConclusionsIncarceration and treatment history, regardless of outcome, were identified as major factors influencing MDR/RR-TB prevalence. It is essential for the TB care system to eliminate legal loopholes, which deprive doctors of means to enforce quarantine procedures and epidemiological surveillance on infected patients, former and current inmates. Increasing people’s awareness of TB, early detection and appropriate treatment of patients with TB are needed for successfully combating MDR/RR-TB.

Real-world treatment pattern and comprehensive comparative effectiveness of Endostar plus different chemotherapy in advanced patients with non-small cell lung cancer

Recombinant human endostatin (Endostar) plus vinorelbine/cisplatin (NP) had been approved for the treatment of non-small cell lung cancers (NSCLC). But the real-world treatment pattern and effectiveness of Endostar plus other combination chemotherapy, namely docetaxel/platinum (DP), gemcitabine/platinum (GP), pemetrexed/platinum (PP), and paclitaxel/platinum (TP) in both treatment-naïve and re-treatment patients with advanced NSCLC were still unclear. A retrospective observational study was conducted based on the electronic medical record (EMR) system and advanced patients with NSCLC were identified from 7 cancer hospitals in China from 2012 to 2019. These patients were divided into five groups, Endostar plus NP, Endostar plus DP, Endostar plus GP, Endostar plus PP, and Endostar plus TP groups. The disease control rate (DCR), overall response rate (ORR), and the progression-free survival (PFS) were evaluated. Of the eligible 512 advanced patients with NSCLC, 10.35% were in Endostar plus NP group, while the numbers were 15.43%, 32.42%, 26.56%, 15.23% in Endostar plus DP group, Endostar plus GP group, Endostar plus PP group, and Endostar plus TP group, respectively. The ORRs were 31%, 28%, 22%, 41% and 27%, and the DCRs were 71%, 72%, 57%, 72% and 76%, respectively. The median of PFSs for the above groups were 7.9, 6.8, 5.6, 13.7, and 5.4 months. Compared with Endostar plus NP group, the hazard ratios (HRs) and 95%CIs of Endostar plus other chemotherapy were 1.86 (0.75–4.61), 2.15 (0.83–5.60), 1.33 (0.51–3.44), and 2.42 (0.86–6.81). This real-world study found the effectiveness of Endostar plus DP, Endostar plus GP, Endostar plus PP, and Endostar plus TP were of no statistically significant differences compared with Endostar plus NP and reflected the good effectiveness of Endostar plus different chemotherapy in advanced patients with NSCLC.