Intensive Phase Of Treatment Research Articles

Longitudinal trends in glycated hemoglobin during and after tuberculosis treatment

AimsTo investigate the impact of pulmonary TB on glycemic status during and after TB treatment, and associations of glycemic trends with antidiabetic therapy and TB outcomes. MethodsData from two prospective cohort studies of adults in Chennai, India, with pulmonary TB were combined for this analysis. Participants were classified by baseline hemoglobin A1c (A1C) as having normoglycemia (NG; n = 74), prediabetes (pre-DM; n = 110), or diabetes (DM; n = 244). Repeat A1C measurements were performed at TB treatment months 3 and 6, and then 6 and 12 months after TB treatment completion. ResultsMedian A1C at baseline declined after TB treatment initiation in all groups. No baseline NG or pre-DM participants progressed to DM by end of study, while 16.7% of baseline DM participants shifted to pre-DM or NG levels of A1C. In the baseline DM group, rising A1C after the intensive phase of TB treatment was significantly associated with adverse TB outcomes. ConclusionsIncident TB promotes transient glucose elevation but was not conclusively shown to promote chronic dysglycemia. Rising A1C during and after TB treatment may predict unfavorable treatment response in persons presenting with A1C ≥ 6.5 % at the time of TB diagnosis.

Treatment outcomes of extended versus nonextended intensive phase in pulmonary tuberculosis smear positive patients with delayed sputum smear conversion: A retrospective cohort study at primary care clinics in Kota Kinabalu.

Delayed sputum smear conversion in patients with smear-positive pulmonary tuberculosis is a crucial problem at primary care clinics in Sabah resulting in poor treatment outcomes. This study aimed to compare the treatment outcomes between extended and nonextended intensive phase treatments among patients with delayed sputum smear conversion and to identify the factors associated with unsuccessful treatment outcomes. This retrospective cohort study was conducted using data from a Malaysian tuberculosis registry, medical records and clinic referral emails from five primary care clinics in Kota Kinabalu from January 2014 to December 2018. A total of 163 patients with delayed sputum smear conversion were selected and divided into cohort groups: 90 patients received 3 months of intensive phase treatment (extended intensive phase), and 73 patients received 2 months of intensive phase treatment (non-extended intensive phase). Of the 163 patients, 33.7% had unsuccessful treatment outcomes (25.2% had treatment failure; 0.6% died; 3.7% defaulted; and 4.3% transferred out), and 3.7% had relapse. There were no significant differences in the prevalence of unsuccessful treatment outcomes (37.6% vs 28.6%, OR=1.51, CI=0.77-2.94, P=0.226) and relapse (2.2% vs 5.7%, 0R=0.36, CI=0.65-2.04, P=0.404) between the extended and non-extended intensive phase groups. High sputum acid-fast bacilli grade (AFB) at 2 months, drug resistance and lack of directly observed treatment, short-course supervision (DOTS) were associated with unsuccessful treatment outcomes. Extended intensive phase treatment in patients with delayed sputum smear conversion does not prevent unsuccessful treatment outcomes and relapse.

Parents Knowledge and Experiences of Child TB Patients about Medicine Administration in the Intensive Phase

BACKGROUND: Children with pulmonary tuberculosis (TB) who are undergoing intensive phase of treatment often experience negative things, resulting in disobedience in taking medication. Exploration of the experiences of pediatric TB patients in the treatment process needs to be known as information for management from the aspect of drug adherence. The role of parents in overcoming these problems is very important, so it is necessary to know the extent of their knowledge about pulmonary TB disease. METHODS: A qualitative study to explore the experiences of pediatric TB patients was conducted by interviewing 15 patients aged 8–12 years. In addition, a questionnaire was filled out to assess the knowledge about TB of the patient’s parents. The results of the recorded interviews were written and analyzed using the thematic method, while the results of the questionnaire from parents were analyzed descriptively. RESULTS: The results of the questionnaire showed that as many as ten respondents (66.6%) had a sufficient level of knowledge with 9 (60%). Analysis of the data using the Spearman rank test obtained a significance value (p) of 0.11 where p < 0.05, which means there is no relationship between adherence to medication for pulmonary tuberculosis in children and the knowledge of parents in the intensive phase. CONCLUSION: Parental knowledge is sufficient or good does not guarantee that it can change the behavior of individuals or children in complying with the treatment in the intensive phase, although knowledge plays an important role in increasing adherence to taking medication in the intensive phase, there may be other factors that influence so that there is no relationship.

КОРОТКИЕ КУРСЫ ХИМИОТЕРАПИИ ТУБЕРКУЛЕЗА ОРГАНОВ ДЫХАНИЯ НА ОСНОВЕ ФТОРХИНОЛОНОВ У ДЕТЕЙ ИЗ ОЧАГОВ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ ВОЗБУДИТЕЛЯ У ИСТОЧНИКА ИНФЕКЦИИ: ВОЗМОЖНОСТИ ИСПОЛЬЗОВАНИЯ

Objective: to justify the potentials for use of fluoroquinolone-based short-course chemotherapy for the treatment of pulmonary TB in children from nidi of multi-drug resistant TB. Materials and methods. We carried out a cohort prospective study of 18 patients aged 2–5 years with newly diagnosed pulmonary TB with history of exposure to multidrug resistant TB in 2018–2020. The criteria for inclusion were as follows: local or small TB processes without bacterioexcretion, potential to form the initial combination containing at least four TB drugs including fluoroquinolones, use of TB drugs consideringpreserved drug susceptibility in the infection source. The criteria for exclusion: presence of diseases requiring long-term immunosuppressive therapy, administration of bedaquiline at any point of treatment. We used individualized chemotherapy regimens: 4 drugs in the intensive phase and 3 drugs in the continuation phase. The treatment course was 9–12 months. Results. All the patients completed treatment with effective outcomes, no relapse was detected one year later. Intoxication symptoms were removed after 3 months, positive X-ray dynamics was observed after 3 and 6 months in 66.7% of patients. Conclusion. We proved the effectiveness of fluoroquinolone-based short-course chemotherapy regimens in children with local or small forms of TB and history of exposure to multidrug resistant TB. The criteria for the total treatment duration (9 or 12 months) were the duration of the intensive phase and the duration of fluoroquinolone administration. If the intensive phase of treatment was less than 3 months or the administration of fluoroquinolones was less than 6 months, the total treatment duration was prolonged to 12 months.

К ВОПРОСУ О СОКРАЩЕНИИ ДЛИТЕЛЬНОСТИ ЛЕЧЕНИЯ ТУБЕРКУЛЕЗА ОРГАНОВ ДЫХАНИЯ У ПОДРОСТКОВ ПРИ ПОЛУЧЕНИИ ТЕСТА ЛЕКАРСТВЕННОЙ ЧУВСТВИТЕЛЬНОСТИ НА ЭТАПЕ ХИМИОТЕРАПИИ

We carried out a cohort retrospective study to justify the possibilities to continue the main TB treatment course in adolescents with determined drug susceptibility during treatment (without return to treatment commencement) in order to reduce the total duration of treatment. Out of 123 patients who completed treatment in 2019–2022 we selected 31 patients with drug susceptibility test (DST) results obtained by only cultural studies using BACTEC MGIT 960 after 1.5-2 months of treatment. We established that DST results obtained using BACTEC MGIT 960 during treatment would determine further treatment tactics. We compared two groups of patients. Group 1 included 17 patients susceptible to at least 3 TB drugs and positive clinical and X-ray dynamics; their treatment regimens were corrected without return to the intensive phase. Group 2 included 14 patients susceptible to 1-2 TB drugs of the administered regimen without positive clinical and X-ray dynamics; after treatment correction they received the intensive phase of treatment again. The comparison of the main chemotherapy course duration showed that the patients of group 2 received treatment for a significantly longer period of time as compared to the patients of group 1 (the Mann–Whitney U test – 30.5, the critical value 67; р < 0.05).

Outcome of tuberculous meningitis in children aged 9 months to 12 years at the end of intensive phase of treatment

BackgroundTuberculous meningitis (TBM) is associated with high morbidity and mortality. Most of the literature focuses on outcomes at the end of therapy when it may be too late for intervention to improve the outcomes. So, the present study addresses outcomes by the end of intensive course of therapy. MethodsIt was a prospective cohort observational study that enrolled 80 patients with TBM between 9 months and 12 years of age. Participants were classified into Definite, Probable and Possible TBM using Marais criteria. Survival/Mortality was evaluated at the end of hospital stay. Demographic, clinical, cerebrospinal fluid and radiological parameters were evaluated for predictors of morbidity and mortality. Standardized tools were used to assess possible impairments in different domains at the end of intensive phase of treatment, namely Gross Motor Functional Classification System for motor functional ability, Pediatric-Mini Mental score examination (MMSE), Blantyre Coma Scale (BCS) score and Vineland Social Maturity Scale (VSMS) for cognitive outcome, Auditory Brainstem Evoked Responses for hearing outcome and using Teller's/Snellen's visual acuity charts to assess visual impairment. ResultsA high Mortality rate of 42.5% was seen in the enrolled patients. Out of the total 80 patients, 20% recovered completely while 36.25% survived with disability (morbidity). Motor, Hearing, Cognitive and Vision impairment was present in 33.3%, 4%, 33.3% and 48.9% of the survivors respectively. On multivariate regression, raised intracranial tension and stage III disease were significantly associated with mortality. Morbidity was significantly associated with Stage III disease on multivariate analysis. ConclusionsDespite advances in treatment, Tuberculous meningitis is associated with high burden of deaths and devastating neurological sequelae. Timely diagnosis and intervention of neurological impairments is needed to improve the outcome of TBM in survivors.

ПРОБЛЕМЫ ФОРМИРОВАНИЯ ИНТЕНСИВНОЙ ФАЗЫ РЕЖИМА ХИМИОТЕРАПИИ У ВПЕРВЫЕ ВЫЯВЛЕННЫХ ПАЦИЕНТОВ С ТУБЕРКУЛЕЗОМ ЛЕГКИХ

Presently the development of TB treatment regimens is aimed at systematization, standardization, and development of a unified approach to treatment throughout the country. TB treatment is difficult due to the proliferation of drug resistant mycobacteria. Drug resistance rates vary and depend on laboratory capacities in the region. The choice of a chemotherapy regimen is associated with the implementation of molecular genetic diagnostic methods, which allow drug resistance determination before treatment. According to the new clinical recommendations, some changes in chemotherapy regimens have been introduced. Treatment for pulmonary TB with multiple, pre-extensive, or extensive drug resistance (MDR, pre-XDR, or XDR) is significantly complicated. The article outlines issues of treatment tactics during the intensive phase of treatment of new pulmonary TB patients on the example of a TB dispensary with a well-equipped laboratory service.

Role of Biomarkers (Interleukins (IL)- 2,5,6,16,17,1ß) in Saliva and Serum for Diagnosis of Pulmonary Tuberculosis and for Monitoring Response to Intensive Phase Treatment

Introduction: Majority of the currently used diagnostic tests for Pulmonary Tuberculosis (PTB) have variability in sensitivity and specificity in diagnosing PTB. Therefore, evaluating new biomarkers in easily obtainable samples like serum and saliva can contribute to the diagnosis of PTB. Aim: To evaluate the role of Interleukins(IL)- 2,5,6,16,17,1β in the diagnosis of PTB by comparing their levels in Other Respiratory Diseases (ORD) group and monitoring the response to treatment in PTB group. Materials and Methods: This prospective observational study was conducted between January 2021 to May 2022 in a tertiary care hospital in New Delhi, India. A total of 80 cases were taken of which 40 cases of PTB and 40 cases having diagnosis of ORD were studied. IL-2,5,6,16,17,1β levels were measured in saliva and serum using Enzyme Linked Immune Sorbent Assay (ELISA) kits. These IL were also measured in diagnosed PTB patients in serum and saliva after two months of treatment. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 16.0. Kruskal Wallis H Test, Wilcoxon signed-rank sum test, Chi-square test and Fisher’s exact test were applied at appropriate areas and a p-value <0.05 was taken as significant. Results: On comparing the levels of IL between serum and saliva in PTB group at baseline, IL-2, IL-17 levels were higher in serum while IL-5, IL-1β levels were higher in saliva with these results being statistically significant (p-value <0.001). However, after two months of treatment, the levels of IL-2, IL16 decreased significantly in both serum and saliva whereas IL-17 level decreased significantly only in serum after treatment. None of the IL showed significant difference in levels between serum and saliva in PTB and ORD groups. Conclusion: The diagnostic role of IL in PTB could not be established whereas IL-2, IL-16 and IL-17 can be used for monitoring response to treatment as the levels decreased significantly with treatment.

Treatment-related deaths and non-fatal severe toxicities during the intensive treatment phases of the icicle-all-14 risk-stratified treatment protocol for newly-diagnosed acute lymphoblastic leukaemia

Treatment-related deaths and non-fatal severe toxicities during the intensive treatment phases of the icicle-all-14 risk-stratified treatment protocol for newly-diagnosed acute lymphoblastic leukaemia

Tuberculosis yield among contacts of non-pulmonary bacteriologically confirmed index TB patients in the urban setting of central Uganda.

The World Health Organization (WHO) recommends systematic and active investigation of TB contacts. However, lower priority is given to contact investigation among other non-pulmonary bacteriologically confirmed (PBC) cases; it thus contributes to the scarce information on the yield of TB among contacts of index TB patients without microbiological confirmation (non-PBC patients). This study therefore aimed at establishing the yield of TB among contacts of PBC and non-PBC index TB patients in the urban setting of central Uganda. We abstracted data from the Uganda national TB contact investigation registers present at 48 health facilities for the period January 2018 to August 2020. The screening yield for both PBC and non-PBC, timing of TB diagnosis among contacts were determined. Logistic regression was used to examine predictors for diagnosing contacts as non PBC TB patients. From January 2018 to August 2020, 234 persons were diagnosed with TB from a total of 14,275 contacts traced for both PBC and non-PBC TB index patients at 48 facilities. Of these, 100(42.7%) were contacts of non-PBC index patients. TB screening yield was higher among contacts of non PBC 100(2.0%) compared to 134(1.4%) among contacts of PBC index patients. For both groups, over 80% of their contacts were diagnosed with TB within 3 months from the day of TB treatment start of the index case. On multivariate logistic regression the only predictor for diagnosing contacts as non PBC TB patients was age under15 years (adjusted odds ratio [aOR] 7.53, 95% CI [3.27-17.3] p = <0.05). The yield of TB among contacts of non-PBC index case is nearly the same for contacts of PBC index cases and most contacts were diagnosed with TB disease during the intensive TB treatment phase of the index case. There was no association between the type of TB (PBC, non-PBC) disease diagnosed in the contacts, and that of index TB patients. To improve TB case-finding, emphasis should be placed on contact investigation for household and close contacts of all other index cases with pulmonary tuberculosis regardless of whether PBC or non-PBC during the intensive phase of treatment.

A CASE OF DISSEMINATED MULTI-DRUG RESISTANT TUBERCULOSIS WITH BONY INVOLVEMENT

Drug resistant tuberculosis continues to be a public health problem, Early diagnosis and initiation of treatment play important role in management of MDR-TB. Here, we report a patient who is 27 year old female diagnose initially as a case of TB pleural effusion and was initiated on 1st line antiTB drugs, after initial response to therapy and completing intensive phase of treatment, in forth month of continuation phase patient presented with symptoms of fever, anorexia and weight loss. Further evaluation with CT scan thorax revealed bony involvement with osteolytic lesions involving multiple ribs and vertebral column leading to multiple paraspinal collections and cold abscess formation involving anterior chest wall, pus CBNAAT showed mycobacterium tuberculosis resistant to rifampicin which was conrm on culture. Patient was diagnosed as case of disseminated MDR-tuberculosis.

Applying Psychological and Educational Health Models to Determine the Effect of a Pharmacist-led Cognitive and Behavioral Intervention on Tuberculosis Treatment Outcomes in Plateau State, Nigeria.

Background: The prolonged multi-drug treatment regimen for tuberculosis (TB) can lead to non-adherence and unsuccessful treatment outcomes. Educational and psychological health models can be used to design cognitive and behavioral interventions to improve adherence and treatment outcomes. Objective: To determine the effect of cognitive and behavioral interventions on TB treatment outcomes. Methods: The quasi-experimental study conducted in six TB treatment centers involved reinforced medication education and adherence counseling (MEAC), designed from a structured validated psychometric scale. Data were collected three different times during the intensive and continuation phases of treatment from 463 TB patients (232 in the control and 231 in the intervention group). Baseline demographic and clinical characteristics were compared between the groups. The generalized estimating equation model was used to analyze the repeated measures by determining if treatment success was associated with the cognitive and behavioral interventions and medication adherence. Results: The males made up 290(62.6 %) of the population. The mean age was 36.75±13.9. Most of the TB patients were newly diagnosed 413(89.2%) and HIV negative 315(68%), with secondary level of education 216(46.6%). There was no significant difference in baseline characteristics between the groups. The intervention group was four times more likely to have treatment success (p<0.01; CI=1.5-8.4), compared to the control group. Medication-adherent TB patients were 24 times more likely to have treatment success than patients who did not adhere (p<0.001; 10.8-52.1). TB patients' emotions, attitudes, and perceptions of their medicines were predictors of treatment success (p<0.05; 1.0 - 1.1). Conclusion: The cognitive and behavioral interventions administered to TB patients improved successful treatment outcomes.

EVALUATION OF DEPRESSION AND ANXIETY AMONG TUBERCULOSIS PATIENTS

To evaluate prevalence of depression and anxiety among Tuberculosis patients. A Prospective Study was carried out at Department of Bakhtawar Amin Hospital Multan from July 2021 to July 2022. The study was conducted on 400 patients. HADS, a 14-item questionnaire, was used to assess depression and anxiety. The 14 items were subdivided into 7 items for depression (HAD-D) and anxiety (HAD-A). Data was analyzed using SPSS v23. Independent association of variables was identified by calculating adjusted odds ratio with 95% CI. Prevalence of depression and anxiety were 224 (56%) and 220 (55%) respectively. Depression was more common in females, 127 (67%), as compared to males, 99 (47%). Anxiety was also common among females 131, (69%). Low body mass index, lack of formal education and perceived TB stigma was significantly associated with depression. More than half of the sample had depression and anxiety. Intensive treatment phase, high perceived stress and perceived stigma were associated with anxiety and depression.

Depression Among Patients With Tuberculosis at a Directly Observed Treatment Short-Course (DOTS) Center in Rural Delhi.

Background Psychiatric disorders, particularly depression is prevalent among patients with tuberculosis (TB) and affect their treatment compliance. Patients with tuberculosis can develop depression due to multiple factors like longer treatment duration, social stigma, lack of family support, etc.In this study, depression and its associated factors were examined among patients with tuberculosis enrolled in a directly observed treatment short-course (DOTS) center in North Delhi. Methods In this DOTS center-based, cross-sectional study, 320 patients with pulmonary and extra-pulmonary TB above 18 years old were included. Basic socio-demographic information was gathered using a Hindi questionnaire, and depression was identified using the patient health questionnaire-9. People who received a score of 10 or higher were deemed to have depression. The Statistical Package for Social Sciences (SPSS) version 21 (IBM Corp., Armonk, NY, USA) was used for data analysis. Analysis between depression and no-depression groups was done by the chi-square test and a p-value< 0.05 was considered statistically significant. Results The study involved 320 patients in all, 193 (60.3%) of whom were men. The median age was 38 years, and the interquartile range (IQR) was 24 to 52 years. Depression was found to be present in half of the patients. Patients with a higher proportion of depression were male, belonged to the middle or below socio-economic status, were currently unemployed and literate, had monthly family income less than 8000 rupees, weight below 45 kg, used alcohol and tobacco, and were undergoing intensive phase (IP) of TB treatment (p-value< 0.05). Depression was not found to be associated with age, site of TB, previous history of anti-tubercular treatment (ATT) intake, marital status, and family size. Conclusion Depression among patients with TB is common and affects half of the patients afflicted with it. When evaluating patients with TB, physicians and DOTS providers should have a high index of suspicion for depression.

Family accommodation as a predictor of treatment outcome in outpatient intensive cognitive behavioral therapy of adult obsessive compulsive disorder

Family accommodation in obsessive compulsive disorder (OCD) consists of participation in symptoms and modification of family routines in order to reduce patients' anxiety and impairment, manage relatives’ own distress, and maintain family functioning. Higher levels of accommodation are associated with increased symptom severity and worse treatment outcome. However, this has not been investigated for adults with OCD receiving intensive cognitive behavioral therapy (iCBT). The aim of this study was to examine if change in family accommodation during the intensive phase of iCBT predicted treatment outcome. Within an observational study design, 52 adult patients received iCBT with pre-, between- and post-treatment measurements. Results showed that family accommodation was reported by 94% of relatives of OCD patients and was associated with self-reported OCD symptoms but not global functioning. Family accommodation was significantly reduced from pre-to post-treatment. Greater reductions in family accommodation were associated with lower levels of OCD symptom severity and better global functioning at post-treatment, and greater likelihood of achieving remission status. However, changes on the outcome measures from pre-to post-treatment were not dependent on the magnitude of change in family accommodation during the intensive phase of treatment. Therefore, findings are inconclusive in supporting that targeting family accommodation might directly affect treatment outcome for adults with OCD receiving iCBT.

Temporal trends of pharmacologic treatments for tuberculosis and multidrug resistant tuberculosis following dissemination of treatment guidelines in South Korea.

The World Health Organization (WHO) released treatment guidelines for multidrug resistant tuberculosis (MDR-TB) in 2008, with subsequent revisions in 2011; Korea disseminated corresponding guidelines in 2011 and 2014, respectively. Thus, we aimed to investigate the temporal trends of and the updated guideline's impact on the prescription patterns of anti-TB drugs. We conducted a time-series study using Korea's nationwide healthcare database (2007-2015), where patients with TB or MDR-TB were included. Only anti-TB drugs prescribed during the intensive phase of treatment for TB (two months) or MDR-TB (eight months) were assessed. We estimated the annual utilization of TB treatment regimens and the relative difference (RD) in the proportion of MDR-TB treatment medications between the following periods: before the first Korean guideline (June 2008 to March 2011); between the first and revised guidelines (April 2011 to July 2014); after the revised guideline (August 2014 to December 2015). Of 3523TB (mean age 54.1 years; male 56.8%) patients, treatment regimens for TB complied with guideline recommendations as >80% of patients received either quadruple (mean 66.8%) or triple (14.5%) therapy of first-line anti-TB drugs. Following the WHO's guideline update, prescription patterns changed accordingly among 111 MDR-TB (mean age 46.0 years; male 67.6%) patients, as use of pyrazinamide (RD +20.3%) and prothionamide (+11.5%) increased (recommended to be compulsory), and streptomycin (-43.1%) decreased (ototoxicity risks). Anti-TB drug prescription patterns for both TB and MDR-TB well reflected WHO's treatment guideline as well as corresponding domestic guidelines of South Korea.

Effectiveness of a digital medication event reminder and monitor device for patients with tuberculosis (SELFTB): a multicenter randomized controlled trial

BackgroundTuberculosis remains the leading cause of death from a single infectious disease worldwide. Trials evaluating digital adherence technologies for tuberculosis in low- and middle-income countries are urgently needed. We aimed to assess whether a digital medication event reminder and monitor (MERM) device-observed self-administered therapy improves adherence and treatment outcomes in patients with tuberculosis compared with the standard in-person directly observed therapy (DOT).MethodsWe did a two-arm, attention-controlled, effectiveness-implementation type 2 hybrid, randomized controlled trial in ten healthcare facilities in Addis Ababa, Ethiopia. We included adults with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary tuberculosis who were eligible to start anti-tuberculosis therapy. Participants were randomly assigned (1:1) to receive a 15-day tuberculosis medication supply in the evriMED500® MERM device to self-administer and return every 15 days (intervention arm) or visit the healthcare facilities each day to swallow their daily dose with DOT by healthcare providers (control arm). Both arms were followed throughout the standard two-month intensive treatment phase (2RHZE). For control participants, some provider-approved take-home doses might be allowed for extenuating circumstances in real-world practice. Data were collected on patient information (demographic, socioeconomic, behavioral, social, and clinical information), medication adherence measures (MERM vs. DOT records, IsoScreenTM urine colorimetric isoniazid test, and adherence self-report), and clinical measures (pre-post treatment sputum Xpert MTB/RIF assay or microscopy, and adverse treatment outcomes). The intention-to-treat (ITT) primary endpoints were (1) individual-level percentage adherence over the two-month intensive phase measured by adherence records compiled from MERM device vs. DOT records that also considered all take-home doses as having been ingested and (2) sputum smear conversion following the standard two-month intensive phase treatment. Secondary endpoints were (1) individual-level percentage adherence over the two-month intensive phase measured by adherence records compiled from the MERM device vs. DOT records that considered all take-home doses as not ingested, (2) negative IsoScreen urine isoniazid test, (3) adverse treatment outcome (having at least one of the three events: treatment not completed; death; or loss to follow-up), and (4) self-reported adherence. The MERM device has an electronic module and a medication container that records adherence, stores medication, emits audible and visual on-board alarms to remind patients to take their medications on time and refill, and enables providers to download the data and monitor adherence.ResultsParticipants were enrolled into the study between 02 June 2020 and 15 June 2021, with the last participant completing follow-up on 15 August 2021. A total of 337 patients were screened for eligibility, of whom 114 were randomly assigned and included in the final analysis [57 control and 57 intervention participants]. Participants were 64.9% male, 15% with HIV, 10.5% retreatment, and 5.3% homeless. Adherence to TB medication was comparable between the intervention arm [geometric mean percentage (GM%) 99.01%, geometric standard deviation (GSD) 1.02] and the control arm [GM% 98.97%, GSD 1.04] and was within the prespecified margin for non-inferiority [mean ratio (MR) 1.00 (95% CI 0.99–1.01); p = 0.954]. The intervention arm was significantly superior to the control arm in the secondary analysis that considered all take-home doses in the control were not ingested [control GM% 77.71 (GSD 1.57), MR 1.27 (95% CI 1.33–1.43)]. Urine isoniazid testing was done on 443 (97%) samples from 114 participants; 13 participants had at least one negative result; a negative test was significantly more common among the control group compared with the intervention group [11/57 (19.3%) vs 2/57 (3.5%); p = 0.008]. There was no significant difference between the control and intervention arms for smear conversion [55 (98.2%) vs 52 (100%); p>0.999], adverse treatment outcomes [0 vs 1 (1.9%); p = 0.48], and self-report non-adherence [5 (8.9%) vs 1 (1.9%); p = 0.21].ConclusionsIn this randomized trial of patients with drug-sensitive pulmonary tuberculosis, medication adherence among participants assigned to MERM-observed self-administered therapy was non-inferior and superior by some measures when compared with the standard in-person DOT. Further research is needed to understand whether adherence in the intervention is primarily driven by allowing self-administered therapy which reduced challenges of repeated clinic visits or by the adherence support provided by the MERM system. To avoid contributing to patient barriers with DOT, tuberculosis medical programs should consider alternatives such as medication event monitors.Trial registrationClinicalTrials.gov, NCT04216420.

Algorithm for the diagnosis and pharmacotherapy of arterial hypertension, chronic heart failure in patients with newly diagnosed tuberculosis and chronic obstructive pulmonary disease in the the intensive phase of tuberculosis chemotherapy

Chronic heart failure (CHF), arterial hypertension (AH), chronic obstructive pulmonary disease (COPD) worsen the prognosis for the cure of newly diagnosed pulmonary tuberculosis (TB), including due to an increase in negative symptoms and a deterioration in the quality of life of patients in the intensive phase of TB treatment. This requires the algorithmic diagnostic actions of a doctor for the subsequent appointment of rational pharmacotherapy with a proven best outcome in the treatment of TB.Objective. To develop an algorithm for the diagnosis and pharmacotherapy of patients with hypertension, CHF and COPD in the intensive phase of chemotherapy for newly diagnosed TB in terms of the best outcome of TB cure.Design and methods. An open, prospective, randomized comparative study included 135 patients who were admitted to a tuberculosis dispensary for the treatment of newly diagnosed TB. Depending on concomitant cardiac pathology, patients were divided into 2 groups: 76 patients with TB, COPD and AH; 59 patients with TB, COPD and CHF. In patients on the background of intensive chemotherapy for newly diagnosed TB, symptoms such as shortness of breath, tachycardia, and increased blood pressure (BP) were first detected or intensified. The selection of treatment regimens was carried out with an assessment of the best tolerability and effectiveness. Duration of follow-up was 6 months with an assessment of the outcomes of TB treatment in comparison with retrospective control (a similar group according to the inclusion and exclusion criteria treated in 2018).Results. During intensive chemotherapy of newly diagnosed TB, increasing symptoms were assessed and analyzed, indicating the appearance or exacerbation of comorbid pathology: AH, CHF and COPD. Based on the results of the study, an algorithm of doctor’s actions was developed for the differential diagnosis of cardiovascular (AH and CHF) and bronchopulmonary (COPD) pathologies with recommendations for prescribing a rational combination of drugs. In patients with TB, hypertension and COPD, the best effect was obtained in reducing the average daily systolic and diastolic BP during therapy with an angiotensin II receptor antagonist and a dihydropyridine calcium antagonist with satisfactory tolerability. For patients with TB, COPD and CHF, an angiotensin-converting enzyme inhibitor (if intolerant, an angiotensin II receptor antagonist) in combination with a mineralocorticoid receptor antagonist and titration of a beta-blocker with the addition of a myocardial cytoprotector to the above therapy showed an optimal effect on the severity of CHF symptoms. These treatment regimens for 3 months led to the achievement of target indicators for BP, heart rate, exercise tolerance in the test with a 6-minute walk, and improvement in echocardiography. Continuation of treatment up to 6 months showed a significant improvement in the outcomes of TB chemotherapy, expressed in an increase in the number of people who achieved cessation of bacterial excretion and closure of decay cavities, without increasing antibiotic therapy.Conclusions. Algorithm of doctor’s diagnostic actions and prescription of rational pharmacotherapy of AH, CHF and COPD in patients with newly diagnosed pulmonary TB leads not only to improved tolerability of TB therapy, but also to the outcomes of curing newly diagnosed TB without intensifying antibiotic therapy.

Association of Interleukin-2 (IL-2) Levels With Acid-Fast Bacillus (AFB) Sputum Conversion In Drug-Resistant Pulmonary Tuberculosis Patient

Background: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb) which can be found on multiple organs, but mostly infect the lung. AFB smear is used to diagnose and evaluate therapy response, to show bacterial burden and the patient’s infectious status. Combination of antituberculosis drugs for a long period of time could cause poor compliance and increased risk of resistance. Mtb infection induce immune response and release cytokines, one of which is interleukin-2 (IL-2) that regulate T lymphocyte cell. Higher IL-2 levels is found on patient with high bacterial burdern. This study aims to see the assossciation between IL-2 levels before and 30 days after DR-TB treatment, to see pre and post-treatment IL-2 levels with conversion of AFB smear, and correlation between pre-treatment IL-2 levels and AFB smear. Method: This was a cohort prospective study at RSUD dr Saiful Anwar Malang. Thirty nine DR-TB patients underwent AFB smear before and 30 days after treatment, while IL-2 levels was also measured by Enzym-Linked Immunosorbent Assay (ELISA) technique. Results: The levels of IL-2 before treatment was significantly higher compared to 30 days after treatment (P&lt;0.001). There was no significant IL-2 levels difference between conversion and non-conversion group (P=0.23), and a weak, not-significant correlation between IL-2 levels and AFB smear (r=0.28; P=0.06). Conclusion: The levels of IL-2 was significantly higher before than after treatment and it cannot be used to determine the positivity of acid-resistant bacilli smears in the sputum of patients with DR-TB. The limited timeframe and biomarker in this study raise the possibility to observe IL-2 as well as other biomarkers after intensive phase of TB treatment for future studies.

Co-morbidity of Diabetes and Tuberculosis can Affect the Results of Treatment; A Case Control Study in Iran

Background and Purpose: Several evidences have shown some synergistic effect of diabetes co-morbidity on the tuberculosis (TB) treatment results, while some other studies have not found such associations. This study aimed to investigate the relationship between TB-diabetes co-morbidity and outcomes of TB treatment.&#x0D; Materials and Methods: The research population in this case control study were patients with smear positive tuberculosis. The cases were 158 patients with TB and diabetes selected by consensus method, while controls were 316 patients randomly selected from TB patients without diabetes.&#x0D; Results: Frequency of unfavorable outcome among cases was higher than among controls (7.6% vs 7.3% respectively, p-value =0.901). Multivariate logistic regression models showed that the odds ratios for adverse treatment outcome, death, treatment failure, positive smear after the intensive phase of treatment and high grade positivity (2+ &amp; 3+) were 0.97(0.45- 2.06), 0.97(0.42-2.24), 0.91(0.17-4.85), 1.39(0.79- 2.44) and 2.57(0.83- 7.92) respectively. Moreover, treatment adverse outcomes among patients with drug complications (22.2% vs. 6.5%, p-value =0.010) and rural residents (10% vs 4.9% respectively, p-value=0.037) were significantly higher than those among patients without complication and urban residents respectively.&#x0D; Conclusion: Although we did not observe any significant association between TB-diabetes co-morbidity and treatment results, there was a significant effect measure regarding the effect of smear positivity at the end of the intensive phase of treatment, especially high grade of smear positivity. Because of probable bias in the classification of the exposure, screening of TB patients regarding diabetes mellitus at the beginning of the treatment is recommended.