Intensive Phase Research Articles

Co-infection with Mycobacterium and 20% acid-fast Nocardia in an immunocompetent patient – A case report

Nocardiosis is an opportunistic infectious disease in immunocompromised individuals, which may be fatal and in people with healthy immune systems, which is reported as a case. Mixed infections with Nocardia and Mycobacterium tuberculosis complex (MTBC) are rare. We are reporting a case of co-infection with Nocardia spp. and MTBC in an immunocompetent patient presenting with neck swelling. Interestingly, in this case, the primary identification of Nocardia was done using 20% H2SO4 as decolorizer for Ziehl–Neelsen staining. The patient was given first-line anti-tubercular treatment for the first 2 months as an intensive phase, followed by isoniazid and rifampicin for an additional 4 months, with a total of 6 months treatment, along with linezolid (600 mg twice daily for 15 days). The patient subsequently improved.

Thyroid Function in Newly Diagnosed Pulmonary Tuberculosis Patients Pre- and -Post Intensive Phase: A Study in a Tertiary Medical College in Eastern Uttar Pradesh

Thyroid Function in Newly Diagnosed Pulmonary Tuberculosis Patients Pre- and -Post Intensive Phase: A Study in a Tertiary Medical College in Eastern Uttar Pradesh

Use of Dispersible Fixed-Dose Combinations in Chemotherapy of Drug Susceptible Tuberculosis: Results of the Observational Study

The objective: to assess effectiveness, safety and pharmacoeconomic feasibility of using a dispersible fixed-dose combination (isoniazid 150 mg, rifampicin 150 mg, pyrazinamide 375 mg) in patients with respiratory tuberculosis and preserved susceptibility of Mycobacterium tuberculosis (MTB) to anti-tuberculosis drugs.Subjects and Methods. A post-registration observational study was conducted to assess treatment effectiveness of pulmonary tuberculosis in 60 adult patients with drug susceptible tuberculosis. In Main Group, patients received the fixed-dose combination (isoniazid 150 mg, rifampicin 150 mg, pyrazinamide 375 mg), while in Control Group, patients were treated with the regimen consisting of single anti-tuberculosis drugs.Results. Sputum conversion rate made 76.7% by the end of the intensive phase (60 doses) when replacing isoniazid, rifampicin and pyrazinamide with the dispersible fixed-dose combination, while with the standard choice of drugs, it was 66.7%. The incidence of adverse reactions was 7-fold lower when using the investigational drug which contributed to a high level of adherence and high effectiveness of therapy. Pharmacoeconomic analysis convincingly demonstrated advantages and economic benefits of the dispersible fixed-dose combination (isoniazid 150 mg, rifampicin 150 mg, pyrazinamide 375 mg), which was more costly than the combination of single drugs.

Continuous digital cough monitoring during 6-month pulmonary tuberculosis treatment

IntroductionThe recent advances in digital and wearable technologies with artificial intelligence (AI) enable the use of continuous cough monitoring (CCM) to objectively monitor symptoms as surrogate markers of treatment efficacy in pulmonary tuberculosis (PTB). The objectives of this study are to describe the evolution of cough during PTB treatment in adult and to assess the feasibility of community-based CCM.MethodsWe prospectively enrolled PTB adult participants upon treatment initiation. Participants’ coughs were continuously monitored during 6 months with a smartphone loaded with an app able to detect cough by using an AI algorithm.ResultsTwenty-two participants were included. The median age was 28.5 (IQR: 22–42) and 62% were male. The median cough per hour (medCPH) was 11.0 (IQR: 7.0–27.0) at week 1. By the end of the intensive phase of PTB treatment at week 8, the medCPH was 3.5 (IQR: 1.5–7.0), which was significantly lower than the medCPH at week 1 (p=0.002). At week 26 (end of treatment), the medCPH was 1.0 (IQR: 1.0–2.5). The adherence to CCM was high during the first 13 weeks of PTB treatment and then waned over time. The adherence was similar during daytime and nighttime.ConclusionCough counts rapidly drop during the intensive phase of PTB treatment and then slowly decrease to a low baseline level by the end of the treatment. Community-based CCM using digital technology is feasible in low resource settings but requires evaluation of alternative approaches to overcome adherence issues and technical limitations (mobile internet and electricity availability).

Study the Occurrence of Mycobacterium Bovis in Tuberculosis of Peripheral Lymph Nodes and its Effect on the Course of the Disease.

The incidence of tuberculosis caused by Mycobacterium bovis, not only the pulmonary form, but also the form developing in the extrapulmonary organs, is also increasing from year to year. Despite the large number of EPTB, TBPLN occupies a leading place among diseases of this type and the study of its pathogenic strains is an urgent task in ensuring the effectiveness of treatment. In this regard, the main purpose of the presented manuscript is to determine the frequency of M. bovis in TBPLN, its effect on the development and course of the disease, as well as the effectiveness of treatment. For this purpose, for the first time, the features of education that occur in patients in peripheral lymph nodes using instrumental methods of ultrasound, computed tomography, and magnetic resonance imaging have been identified. In subsequent studies, 110 patients with peripheral lymph node pathology were diagnosed with TBPLN by detecting mycobacteria in pathological material using general hematological, microbiological and gene-molecular (Gene Xpert) methods. In order to ensure the high effectiveness of drugs used for medicinal purposes, strains of the pathogen were detected using histological, cytological studies, BCG test and specific analyzes such as Diaskintest, Quantiferon test, immunological tests. The study showed that about 80% of patients had M bovis in the overall assessment, 76.4% of patients were sensitive to rifampicin, 9.1% of patients had rifampicin-resistant bacteria, and 14.5% of patients did not have mycobacteria. Therapeutic measures were carried out in 2 different modes, such as standard and individual or with replacement, when all patients were divided into 2 groups. During the period from the 56-day intensive phase of standard treatment to the 84-day intensive phase, a total of 40 patients had a sharp decrease in lymph nodes, elimination of purulent inflammation, and after a while 22 patients in this group had a relapse. In the individual treatment regimen, Levofloxacin and linezolid were used instead of pyrazinamide. While the effectiveness of treatment was achieved in 48 patients of group II after 56 and 84 days of the intensive phase, relapses after a certain time were observed in only 6 patients. When choosing an individual treatment regimen in patients diagnosed with M. bovis, a decrease in relapses to 11.5% is achieved. When M. bovis is detected, an individual scheme of antibacterial treatment of tuberculosis is selected, in which, instead of pyrazinamide, it is recommended to choose one of the reserve lines, depending on the sensitivity of the pathogen to drugs.

EVALUASI PENGGUNAAN OBAT ANTITUBERKULOSIS PARU DIPUSKESMAS: NARRATIVE LITERATURE REVIEW

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. While it primarily affects the lungs, it can also impact other organs. In Indonesia, pulmonary TB remains a significant health issue. This study aims to evaluate the use of anti-tuberculosis medications at various community health centers (puskesmas) in Indonesia through a literature review. The research method employed involves a literature review with searches conducted on Google Scholar and PubMed databases. Out of 360 articles found on Google Scholar and 13,026 articles on PubMed, 8 relevant articles were identified for this study. The results indicate that the most commonly used treatment regimen is Category 1, which includes a 2-month intensive phase with a combination of Isoniazid 75 mg, Rifampicin 150 mg, Pyrazinamide 400 mg, and Ethambutol 275 mg, followed by a 4-month continuation phase with Rifampicin 150 mg and Isoniazid 150 mg. This medication regimen aligns with the Tuberculosis Control Guidelines issued by the Indonesian Ministry of Health in 2016. The evaluation shows that Indonesian puskesmas generally adhere to the established treatment guidelines but still require further monitoring to ensure adherence and effectiveness of the treatment.

Optimized anti-tuberculosis duration for drug-susceptible pulmonary tuberculosis-diabetes mellitus comorbidities: study protocol for a multicenter randomized controlled trial

BackgroundThe coexistence of tuberculosis (TB) and type 2 diabetes mellitus (DM) presents unique challenges in treatment optimization and management, given the mutual exacerbation of disease processes.ObjectiveThis multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of two different treatment durations (6-month versus 9-month regimens) regimen for patients with drug-susceptible pulmonary tuberculosis (DS-PTB) and concurrent type 2 diabetes (DM).MethodsPatients with DS-PTB and type-2 DM from 22 hospitals in China are enrolled. They are randomized in a 1:1 ratio into either the 6-month regimen arm(2HRZE/4HR) or the 9-month regimen arm(2HRZE/7HR). At the end of the intensive phase (the 8th week), patients in both arms who with sputum positive smear will extent one more month of intensive treatment. The primary outcome is the proportion of unfavorable outcomes at 24 months after randomization. Secondary outcomes include treatment success rate at the end of treatment, proportion of recurrence at 24 months after randomization, time to recurrence after treatment completion, proportion of intensive phrase extension, occurrence of adverse events grade 3 or above during treatment.DiscussionThe study focuses on assessing the optimal treatment duration to maximize treatment success while minimizing recurrence and adverse events. The trial is expected to provide vital insights into the appropriate treatment duration for patients with TB-DM, aiming to reduce recurrence rates and improve overall treatment outcomes in this vulnerable population.Trail registrationChictr.org.cn, ChiCTR2100044663. Registered on March 25, 2021.

Clinical and radiological characteristics of mediastinal melioidosis: A four-year retrospective cohort from Sabah, Malaysia

BackgroundMelioidosis is a potentially fatal tropical infection. Little is known about mediastinal involvement in melioidosis. This study aimed to (a) describe the prevalence and demographics of various morphologies of mediastinal melioidosis, (b) propose a classification for radiological morphologies of mediastinal melioidosis. MethodsA retrospective cohort study was performed. Case records of consecutive patients with culture-positive melioidosis who underwent computed tomography (CT) thorax from January 1, 2018–February 28, 2022, were reviewed. Results486 culture-positive melioidosis patients were identified, of which 70 underwent CT thorax. 41 patients demonstrating mediastinal involvement were included in the final analysis, of which four were mediastinal collections, while the rest were classified into those with necrotic or matted appearances, and subcentimeter and larger than 1 cm. Culture-positivity was proven from blood in 83 % of patients (n = 34), with the remaining from chest wall pus, neck abscess pus, sputum, liver abscess, seminal vesicle, pleural, pericardial and peritoneal fluid. The most commonly associated pulmonary manifestations were consolidation and pleural effusion. Half had diabetes; a quarter had chronic kidney disease, while one had syphilis. Exposure to soil was present in six patients: quarry (n = 1), construction (n = 2), farmer (n = 1), living environment (n = 2). Seven patients succumbed before the end of 6-week intensive phase antibiotic treatment. ConclusionMediastinal melioidosis is a spectrum with multiple overlapping features consisting of necrosis, matted lymph nodes, multiseptated and non-septated collections. Further studies will elucidate the prognostic implications of mediastinal melioidosis.

Adverse Drug Reactions During Intensive Phase of Treatment Among Multi- Drug Resistant Tuberculosis Cases Registered at a DR-TB Centre of Southern India

Adverse Drug Reactions During Intensive Phase of Treatment Among Multi- Drug Resistant Tuberculosis Cases Registered at a DR-TB Centre of Southern India

Conducting two evidence syntheses in six weeks – experiences with and evaluation of a pilot project

BackgroundEvidence synthesis organisations are trying to meet commissioners’ needs for rapid responses to their evidence synthesis commissions. In this project we piloted an intensive process, working to complete evidence syntheses within six-weeks, rather than the standard lead time of 4–6 months. Our objective was to explore how researchers experience working intensively, identify barriers and facilitators, and determine how a more intensive approach to evidence synthesis could be more systematically introduced in the future.MethodsIn a pre-planning phase, an intensive work group was established, and two commissions were selected for this pilot project. The evidence synthesis process was divided into two phases: planning and intensive. The planning phase, involved scheduling the intensive phase, exploring new digital tools, and identifying peer reviewers. The intensive phase encompassed the entire evidence synthesis process. Two review teams were formed, each with a team lead supported by a process lead and leadership contact point. Throughout the project, teams engaged in reflective meetings to evaluate and adjust processes as needed.ResultsDuring the planning phase, teams identified significant uncertainties regarding scopes, research questions, and inclusion criteria. To address this, they engaged with commissioners earlier than originally planned, clarified these aspects, and prepared protocols. Despite some minor deviations from the original plan, both reviews were completed on schedule, with one team expanding their scope due to the absence of eligible studies. Teams operated flexibly, held regular meetings, and found the process seamless due to fewer interruptions. Machine learning tools facilitated rapid study selection. The process lead role, created to guide and evaluate the project, proved beneficial, providing structure and support, although clearer role delineation with the leadership contact point could have improved efficiency.ConclusionsOverall, the intensive process fostered focus and productivity, allowing teams to manage short-term deliverables effectively. The researchers preferred working intensively with one evidence synthesis over being involved with many projects at the same time. They felt that time use was more effective, and they were able to complete the tasks in a focused way. However, there are several implications that should be considered before implementing an intensive approach in future evidence syntheses.

Association of polymorphism of the glutathione-s-transferase M1 gene and tumor necrosis factor alpha with the formation and size of decay cavities in patients with pulmonary tuberculosis

The aim. To study the association of polymorphic variants of the GSTM1 (E/D) and TNF-s (308G>A (rs1800629) genes with the formation of decay cavity sizes in patients with pulmonary tuberculosis.Material and methods. The study group is represented by 335 patients suffering from pulmonary tuberculosis (212 people were diagnosed with pulmonary tuberculosis for the first time; 123 people with chronic pulmonary tuberculosis) aged 18 to 65 years; receiving an intensive phase of chemotherapy. To conduct molecular genetic studies; 335 people had whole blood taken from a vein into a test tube with EDTA. Genomic DNA was isolated using Arrow Blood DNA 500 reagent kits from whole blood (at the NorDiag Arrow station). After; the polymerase chain reaction was staged in real time using sets of reagents for genotyping SNPs: GSTM1 (E/D) and TNF-s (–308G>A (rs1800629).Results and discussion. In patients with pulmonary tuberculosis; the genotype DD of the gene GSTM1 (E/D) and the genotype GG of the gene TNF-s –308G>A (rs1800629) is most often associated with the formation of the size of decay cavities.Conclusion. It is advisable to introduce genotyping of the GSTM1 and TNF-s genes into the practice of a phthisiologist in order to predict the probability of the formation of the size of decay cavities in patients with pulmonary tuberculosis.

Analysis of Hematological Examination Results in Pulmonary Tuberculosis (TB) Patients Undergoing Intensive Phase Anti-Tuberculosis Drug Therapy

Analysis of Hematological Examination Results in Pulmonary Tuberculosis (TB) Patients Undergoing Intensive Phase Anti-Tuberculosis Drug Therapy

Infections in Children with Acute Lymphoblastic Leukemia.

Background and Objectives: Infections are the most common and potentially life-threatening complications of the treatment of children with acute lymphoblastic leukemia (ALL). The aim of this study was to determine epidemiological, clinical, and microbiological characteristics of infections in pediatric patients with ALL. Materials and Methods: Twenty-three children (16 males and 7 females, with a mean age of 5.9 years (range of 1.3 to 12.2 years)) with ALL, treated at the Division of Hematology, Oncology, and Clinical Genetics, Department of Pediatrics, Clinical Hospital Center Rijeka, Croatia, from 1 January 2015 to 31 December 2020, were included in the study. Results: One hundred and four infectious episodes (IEs) were reported (an average of 4.5 IE per patient). IEs were more frequent in the intensive phases of antileukemic treatment. Neutropenia was present in 48 IEs (46.2%) with a duration greater than 7 days in 28 IEs (58.3%). The respiratory tract was the most common infection site (48.1%). We documented 49 bacterial (47.1%), 4 viral (3.9%), 4 fungal (3.9%), and 10 mixed isolates (9.6%), while in 37 IEs (35.6%), a pathogen was not isolated. The most common causes of bacteremia were coagulase-positive staphylococci. The most frequent empirical therapy was third- and fourth-generation cephalosporins, followed by piperacillin/tazobactam. The modification of first-line antimicrobial therapy was performed in 56.9% of IEs. Granulocyte-colony stimulating factor was administered in 53.8% of IEs, and intravenous immunoglobulins were administered in 62.5% of IEs. One patient required admission to the intensive care unit. No infection-related mortality was reported. Conclusions: ALL patients have frequent IEs. Close monitoring, the identification of risk factors, the rapid empirical use of antibiotics in febrile neutropenia, and the timely modification of antimicrobial therapy play key roles in reducing infection-related morbidity and mortality in children with ALL.

Exploring mean platelet volume and neutrophil-to-albumin ratio as surrogate markers for monitoring tuberculosis treatment: a prospective longitudinal study

BackgroundTuberculosis (TB) remains a global health challenge, with India bearing a significant burden. Despite advancements in TB diagnosis and treatment, monitoring TB treatment is challenging, particularly in resource-limited settings. This study aimed to explore the mean platelet volume (MPV) as a potential surrogate marker for monitoring TB treatment and assessing if the neutrophil-to-albumin ratio (NAR) enhances treatment monitoring.MethodsPatients diagnosed with TB following NTEP guidelines were recruited. Participants underwent routine blood tests during the six-month Anti-Tubercular therapy course at the start, end of the intensive phase, and end of the continuous phase. Statistical analyses included Spearman correlation, Friedman test, linear mixed effects (LME) models, and multiple linear regression.Results150 individuals were included for analysis. Deviations from normality were noted. Significant associations were found between CRP and sputum grade. MPV mediated between CRP and sputum grade. Significant differences were observed across the three-time points. LME models showed changes in MPV and CRP levels over time. Including NAR enhanced predictive capability.ConclusionsMPV may serve as a promising surrogate marker for monitoring ATT. Personalized approaches are crucial in TB treatment monitoring. LME models revealed MPV and CRP level trends. Future research should explore MPV’s treatment response mechanisms and cost-effectiveness.

Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice

Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44–0.84) and 0.67, 95 % CI (0.53–0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23–0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35–0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.

Evaluation of therapeutic effectiveness of antituberculosis injection based on conversion time in drug-resistant tuberculosis

Drug-resistant tuberculosis is a condition in which Mycobacterium tuberculosis is resistant to first-line anti-tuberculosis drugs, namely isoniazid and rifampicin, which are the two most effective anti-tuberculosis agents. Conversion time is a parameter to assess whether the therapeutic effect of injection has been achieved by carrying out two acid-resistant bacilli (ARB) sputum examinations within a maximum period of 2 consecutive months. Kanamycin and capreomycin are injectable drugs that are used in the intensive phase. This cross-sectional study aimed to evaluate the therapeutic effect of injection using ARB sputum conversion time and to analyze other factors related to ARB sputum conversion time. The study used retrospective data from patients’ medical records, collected with purposive sampling technique. The results of the study showed that from 101 patients who met the inclusion criteria 57.4% used kanamycin and 42.6% received capreomycin. The therapeutic effect was achieved in 87.1%. There was no significant correlation between the type of injection therapy and therapeutic effectiveness (p-value = 0.983). In conclusion, therapy using injections for drug-resistant tuberculosis is effective but still requires close monitoring due to the high adverse drug reaction (ADR).

Characteristics and contributing factors of adverse drug reactions: an analytical study of patients with tuberculosis receiving treatment under the National TB Program of India

Background Tuberculosis (TB) continues to pose a serious threat to the public health system in India. Although the National Tuberculosis Elimination Program (NTEP) is providing a wide range of interventions from early diagnosis to complete treatment to reduce morbidity and mortality from TB, adverse drug reactions (ADR) remain a challenge in treatment adherence and completion. Methods An observational cross-sectional study was conducted in selected districts of Gujarat state. A total of 593 reported TB patients were recruited with an adjusted unified distribution based on the type of cases, site of diseases, and service facility through a simple random sampling method. A semi-structured questionnaire tool was used to collect socio-demographic, clinical, and ADR-related data from the TB patients. Data was analyzed for the frequency, percentage, chi-squared, and adjusted odds ratio to find the association between the variables. Results The majority of the study participants were male (87.2%), aged 15 to 60 (57.8%), daily laborers (22.4%), and married (64.2%). Over 75% of individuals had pulmonary TB, with 87% having experienced their first episode, 83% being new cases, and 44.7% having a history of addiction. ADR with mild symptoms was reported by more than a quarter (29%) of TB patients during the intensive phase (77%). The association between ADR experience and drug susceptibility was significant (p&lt;0.005) and drug-resistant TB patients experience two times more ADRs than drug-sensitive TB patients (OR 2.04). Binomial logistic regression was carried out to describe the association between various variables and occurrence of ADRs. Conclusion The study highlighted a need to enhance health care providers’ capacity and program structure for managing ADRs among TB patients. In order to completely eliminate TB across the country, it also emphasized the attention for a holistic and all-encompassing strategy for managing TB patients at the field level.

Evaluating the Efficacy of Transcranial Magnetic Stimulation in Symptom Relief and Cognitive Function in Obsessive–Compulsive Disorder, Substance Use Disorder, and Depression: An Insight from a Naturalistic Observational Study

The utilization of non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), is increasingly prevalent in psychiatry due to their efficacy and safety. Although the precise therapeutic mechanisms remain partially unclear, repetitive TMS, particularly high-frequency stimulation, may enhance cognitive functions, contributing to therapeutic benefits. This within-subjects study examined the impact of TMS on cognitive and symptomatic outcomes in patients with obsessive–compulsive disorder (OCD), substance use disorder (SUD), and major depressive disorder (MDD). A total of 44 patients underwent cognitive tests and symptom assessments before and after an intensive four-week TMS treatment phase, followed by a four-week maintenance phase. Cognitive assessments included Raven’s matrices, verbal fluency, and digit span tests, while symptom severity was measured using the Italian version of the SCL-90-R. Decision-making performance was also evaluated by administering a delay discounting (DD) test. Principal component analysis was used to generate a dimensional characterization of subjects along cognitive and symptom-related axes before and after treatment. The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical analysis based on linear mixed-effects models confirmed these findings, showing a significant fixed effect of TMS treatment on symptoms but not on cognitive performance. DD metrics remained unchanged. These findings suggest that while TMS effectively alleviates clinical symptoms, it does not produce consistent or appreciable enhancement of cognitive functions in these protocols. This study highlights the need for more personalized and combined therapeutic approaches to maximize the benefits of TMS, potentially incorporating cognitive enhancement strategies. Future studies will be useful to explore whether the results we obtained are valid for other pathologies, cognitive tests, and stimulation protocols.

P-297 Intensive luteal phase support regimens for endometriosis and adenomyosis patients in hormone replacement therapy frozen embryo transfer cycles – subcutaneous or intramuscular progesterone treatment?

Abstract Study question Does subcutaneous (SC) progesterone treatment provide progesterone levels comparable to intramuscular (IM) progesterone when using a cut-off level of 118nmol/l(37.1ng/ml) during intensive luteal phase support? Summary answer As part of an intensive luteal phase support regimen SC progesterone provides higher P4 levels compared to the use of IM progesterone. What is known already Low serum progesterone (P4) levels in HRT-FET cycles negatively impact reproductive outcomes. This effect is particularly pronounced in patients with endometriosis and adenomyosis, due to reduced progesterone actions and progesterone resistance at the receptor level. Therefore, higher serum P4 levels are required to maintain an optimal reproductive outcome during HRT-FET. A P4 cut-off of 118nmol/l (37.1ng/ml) or above has been suggested, a level four times higher than that of the non-endometriosis patient. To achieve high P4 levels, intensive luteal phase support (LPS) regimen has been suggested. This includes vaginal progesterone administration and additional treatment via IM, SC or rectal administration. Study design, size, duration This cohort study includes 380 HRT-FET cycles in endometriosis/adenomyosis patients. Patients were treated from January 2016 until August 2019 with one type of intensive LPS regimen (n = 262) and from January 2000 to January 2023 with two different LPS regimens depending on whether serum P4 levels were lower or higher than 118nmol/l on the day of blastocyst transfer (BT) (n = 118). P4 was measured in a standardised manner. Participants/materials, setting, methods Patients received treatment in a public university affiliated fertility clinic. Endometrial priming involved the use of estradiol followed by vaginal progesterone. From the fourth day of progesterone, one of the following intensive LPS regimens were added: A) 50mg IM progesterone, B) 25mg SC progesterone BD, or C) 25mg SC progesterone BD plus 400mg rectal rescue progesterone BD if P4&amp;lt;118nmol/l. Blastocyst transfer (BT) and P4 measurement were performed on the sixth day of progesterone administration. Main results and the role of chance The overall pregnancy rate, live birth rate (LBR) and total pregnancy loss rates for the whole cohort were 63%, 41% and 36%, respectively. For the three groups A, B and C the mean serum P4 levels on the day of BT were 103.1 ±44.4nmol/l, 170.5 ±62.9nmol/l and 90.1 ±21.5nmol/l. In Group A (IM) 67% of patients (176/262) had P4 levels &amp;lt;118 nmol/l whereas only 36% (43/118; p &amp;lt; 0.001) had P4 &amp;lt;118 nmol/l in the groups of patients treated with SC progesterone (Group B and C). The unadjusted LBR was not significantly different between groups, 39%, 39%, 51%, (p = 0.32). However, a sub-group analysis showed that comparing patients with serum P4 levels &amp;lt;118nmol/l on the BT day in Group A with patients with P4 levels &amp;lt;118nmol/l in Group C a significantly higher LBR was found if intensive LPS included both SC and rectally administered progesterone compared to IM progesterone, only: 51% (44/86) vs 34% (59/176), p = 0.03. The adjusted odds ratio for live birth was 2.04 (95% CI [1.00, 4.16], p = 0.05) after adjusting for age, vitrification day 5 or 6, blastocyst quality and numbers of blastocysts transferred, if intensive LPS included SC and rectal rescue compared to IM, only in patients with P4 levels &amp;lt;118nmol/l. Limitations, reasons for caution This cohort study was conducted over two different time periods. Single embryo transfer was performed only during the later period. The bio-pharmacological profiles of SC and IM progesterone differ, which can influence serum P4 levels. However, in the present study, all blood samples were collected in a standardised manner. Wider implications of the findings This study is the first to report reproductive outcomes following different intensive LPS regimens in a cohort of endometriosis/adenomyosis patients. To increase reproductive outcomes, individualisation of the HRT-FET cycle may be beneficial and, importantly, rectal progesterone administration can be used as a rescue regimen in addition to SC progesterone. Trial registration number Due to the retrospective study design no ethical approval was needed.