Intensive Phase Research Articles

Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration

BackgroundAnti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD.MethodsTwo clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial.Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included.ResultsMean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity.ConclusionLong-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy.Trial registrationsVIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008.Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

Gut microbiome variation in pulmonary TB patients with diabetes or HIV comorbidities

BackgroundThe gut microbiota is known to play a critical role in shaping the host immunity, and metabolism and influences the onset and progression of both communicable and non-communicable diseases. This study assessed the gut microbiome of tuberculosis (TB) cases with diabetes mellitus (DM) or HIV comorbidities before anti-TB therapy and after the intensive phase anti-TB therapy.MethodsNinety cases comprising 60 TB-only, 23 TB-DM, 7 TB-HIV were recruited, among which 35 TB-only, 10 TB-DM, 5 TB-HIV were also sampled after 2 months of anti-TB treatment. Total gut microbiome was detected by 16S rRNA gene sequencing of DNA extracted from collected stool specimen. The taxonomic and functional diversity of the different groups were compared in addition to changes that could occur after 2 months antibiotics use.ResultsCompared to the healthy controls, the gut microbiome of all the TB cohorts was characterized by a significant decreased alpha diversity and significant compositional changes. All the three TB cohorts were enriched with inflammatory related microorganisms of the genera Escherichia-shigella, Streptococcus, Enterococcus and Erysipelatoclostridium with depletion in beneficial taxa of the genera Faecalibacterium, Bifidobacterium and Clostridium. In pairwise comparison with the healthy controls, the TB-only cohort were enriched with Streptococcus and Erysipelatoclostridium, the TB-DM enriched with Bacteroides, and TB-HIV enriched with Escherichia-shigella, Dialister and Erysipelatoclostridium. After the intensive phase anti-TB therapy, there was general enrichment of the genera Erysipelotrichaceae_UCG 003, Veillonella and Fusobacterium.ConclusionOur findings show a dysbiotic gut microbiome and associated upregulation of inflammation related microorganism in gut microbiome of TB individuals with or without comorbidity.

Prevalence and associated factors of delayed sputum smear conversion in patients treated for smear positive pulmonary tuberculosis: A retrospective follow up study in Sabah, Malaysia.

Tuberculosis remains a major health problem globally and in Malaysia, particularly in the state of Sabah. Delayed sputum conversion is associated with treatment failure, drug-resistant tuberculosis and mortality. We aimed to determine the prevalence of delayed sputum conversion among smear positive pulmonary tuberculosis (PTB) patients and its associated factors in Sabah, Malaysia. A retrospective follow up study on all patients newly diagnosed with smear positive pulmonary tuberculosis from 2017 to 2019 was conducted at three government health clinics in Sabah, utilizing data from a national electronic tuberculosis database and medical records. Descriptive statistics and binary logistic regression were applied for data analysis. The outcome of the study was the sputum conversion status at the end of the two-month intensive treatment phase with either successful conversion to smear negative or non-conversion. 374 patients were included in the analysis. Our patients were generally younger than 60 years old with no medical illness and varying proportions of tuberculosis severity as judged by radiographic appearance and sputum bacillary load upon diagnosis. Foreigners constituted 27.8% of our sample. 8.8% (confidence interval: 6.2-12.2) did not convert to smear negative at the end of the intensive phase. Binary logistic regression showed that older patients ≥60 years old (adjusted odds ratio, AOR = 4.303), foreigners (AOR = 3.184) and patients with higher sputum bacillary load at diagnosis [2+ (AOR = 5.061) and 3+ (AOR = 4.992)] were more likely to have delayed sputum smear conversion. The prevalence of delayed sputum conversion in our study was considerably low at 8.8% with age ≥60 years old, foreigners and higher pre-treatment sputum bacillary load associated with delayed conversion. Healthcare providers should take note of these factors and ensure the patients receive proper follow up treatment.

Clinical impact of plasma concentrations of first-line antituberculosis drugs.

The clinical significance of low antituberculosis (anti-TB) drug concentrations has not been fully elucidated. To investigate the clinical consequences of first-line drug concentrations in adult patients with drug-susceptible pulmonary TBin South Africa (SA). We conducted a pharmacokinetic study nested within the control arm of the Improving Treatment Success (IMPRESS) trial(NCT02114684) in Durban, SA. During the first 2 months of treatment, participants received weight-based dosing of first-line anti-TBdrugs (rifampicin, isoniazid, pyrazinamide and ethambutol), and had plasma drug concentrations measured at 2 and 6 hours after drugadministration during the 8th week of treatment. Intermediate (8 weeks), end-of-treatment (6 months) and follow-up TB outcomes wereassessed using World Health Organization criteria. We measured plasma drug concentrations on available samples in 43 participants. Peak drug concentrations were below thetherapeutic range in 39/43 (90.7%) for rifampicin, 32/43 (74.4%) for isoniazid, 27/42 (64.3%) for pyrazinamide and 5/41 (12.2%) forethambutol. At the end of the intensive phase of treatment (week 8), 20.9% (n=9/43) of participants remained culture positive. We did notfind a relationship between the concentrations of first-line drugs and treatment outcomes at week 8. All participants were cured at the endof treatment, and there were no relapses during the 12-month follow-up period. Treatment outcomes were favourable despite low drug concentrations as defined by current reference thresholds.

A cross-sectional study of extent and causes of interruption of treatment of tuberculosis in a tuberculosis unit of Purba Bardhaman district of West Bengal, India

Background: Tuberculosis (TB) is a communicable disease which requires prolonged treatment and having both medical and social dimensions. Adherence to treatment is very important issue in successful treatment of TB. Directly observed therapy was a key strategy in The Revised National TB Control Program. However, treatment interruption is very common. Aims and Objectives: The objective of this study is to assess the nature, extent, and reasons for interruption of treatment in Bhatar TB Unit (TU) of Purba Bardhaman district of West Bengal. Materials and Methods: The study was a descriptive and cross-sectional study with two components. The study was conducted in the area covered under Bhatar TU of Burdwan district of West Bengal. Complete enumeration technique was followed in the study. In the first component of the study, 231 study subjects were found by complete enumeration, out of which 26 were discarded due to incomplete records. In the other component, 90 study subjects were interviewed at the beginning of treatment and after treatment interruption, if any. Data were analyzed using RStudio. Results: Out of the group with only record review, 205 subjects were included in the study, out of which 160 (78.05%) were male and 45 (21.95%) were female. In the other group with both record review and interview, out of 90 subjects, 64 (71.1%) were male and 26 (28.9%) were female. Out of 295 cases, 270 (91.5%) were new and 25 (8.5%) were previously treated. Out of 295 subjects, 36 (12.2%) had interrupted treatment. Seven persons out of 36 had interrupted more than once. Thirty-four persons had interrupted in intensive phase of treatment. Thirty-two persons had taken 10–20 days before interruption of treatment. The most common reason for interruption of treatment was “Not willing to take tablets.” Among the other reasons were “Side effects,” “Hospitalization,” “Away from home,” etc. Conclusion: Non-compliance to anti-tubercular drugs remains an important issue in the elimination of TB.

Effects of the healthy lifestyle community program (cohort 1) on stress-eating and weight change after 8 weeks: a controlled study

Stress-eating (eating more or more unhealthily in order to accommodate to stress), contributes to the development and maintenance of obesity. The effect of comprehensive weight loss interventions on changes in stress-eating as well as the contributing role of stress-eating on weight reduction has not been examined. The impact of the 8-week intensive phase of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on emotional, external and restrained eating, as expressions of stress-eating was evaluated in a non-randomized controlled trial. Intervention: 14 seminars (twice per week, including practical units), complemented by stress-regulation and cooking workshops and coaching sessions empowering participants to change their behaviour towards a healthy plant-based diet (ad libitum), stress regulation, regular exercise and to focus on social support. Participants were recruited from the general population. In the intervention group, 91 participants (IG; age: 56 ± 10, 77% female) and in the control group, 52 (CG; age: 62 ± 14, 57% female) were enrolled. At baseline, participants of the IG reported higher levels of stress (9.7 ± 5.4 points [P] vs. 7.6 ± 6.2; p < 0.011), and of emotional eating (27.9 ± 9.4 vs. 20.0 ± 7.1; p < 0.001) and external eating (29.1 ± 4.9 vs. 25.5 ± 5.6; p < 0.001) than participants of the CG. Within 8 weeks, in the IG, scores of emotional eating (− 3.5 ± 5.4 P) and external eating significantly decreased (= − 2.0 ± 3.8 P), while restrained eating increased (2.7 ± 5.0 P; p for all < 0.001). Weight change was negatively correlated with change of external eating (R2 = 0.045; CC = − 0.285; p = 0.014), indicating that a greater weight change was associated with a smaller change of external eating. This is the first study to prospectively investigate the role of stress-eating on the weight reduction effect of comprehensive lifestyle interventions. Our data confirm that overweight is associated with EE and external eating and suggest that the HLCP is capable to reduce both, weight and stress-eating.Trial registration: German Clinical Trials Register (DRKS; reference: DRKS00018821; September 18th 2019; retrospectively registered).

A case of anterior abdominal wall tuberculosis

A rare case of a middle-aged woman who presented to our emergency department with a huge swelling over lower part of abdomen for 3 years that was associated with continuous purulent foul-smelling discharge from multiple sites over swelling for past 2 years and all her past history was irrelevant except for her significant loss of weight for 6 months and unable to ambulate due to huge swelling for 6 months. She is known diabetes mellitus type 2 for 6 years on oral hypoglycemic drugs. On examination she had stable vital signs, mild pallor, a large globular swelling of about grossly 30×30×20 cm extending from 2 cm below umbilicus superiorly till pubic symphysis inferiorly, bilaterally extending till anterior superior iliac spine, flanks not full, multiple dilated veins over skin. Multiple foul smelling pus discharging sinuses, prominence on leg raise test and absent cough impulse, rest of the abdomen is soft and non-tender with no organomegaly and present bowel sounds. Bilateral inguinal group of lymph nodes were palpable and matted. Swelling was exclusive extra peritoneal on computed tomography (CT) scan. Excision of swelling was done up to anterior rectus raw area open wound with bilateral inguinal lymph node excision was under general anesthesia was done. Histopathology showed granuloma with caseating necrosis from lymph nodes. Anti-tuberculosis therapy intensive phase was started post operative wound was healthy, and after 6 weeks of initiation of anti-tubercular treatment wound was closed with secondary suturing.

Journey of the tuberculosis patients in India from onset of symptom till one-year post-treatment.

Historically, economic studies on tuberculosis estimated out-of-pocket expenses related to tuberculosis treatment and catastrophic cost, however, no study has yet been conducted to understand the post-treatment economic conditions of the tuberculosis patients in India. In this paper, we add to this body of knowledge by examining the experiences of the tuberculosis patients from the onset of symptoms till one-year post-treatment. 829 adult drug-susceptible tuberculosis patients from general population and from two high risk groups: urban slum dwellers and tea garden families were interviewed during February 2019 to February 2021 at their intensive and continuation phases of treatment and about one-year post-treatment using adapted World Health Organization tuberculosis patient cost survey instrument. Interviews covered socio-economic conditions, employment status, income, out-of-pocket expenses and time spent for outpatient visits, hospitalization, drug-pick up, medical follow-ups, additional food, coping strategies, treatment outcome, identification of post-treatment symptoms and treatment for post-treatment sequalae/recurrent cases. All costs were calculated in 2020 Indian rupee (INR) and converted into US dollar (US$) (1 US$ = INR 74.132). Total cost of tuberculosis treatment since the onset of symptom till one-year post-treatment ranged from US$359 (Standard Deviation (SD) 744) to US$413 (SD 500) of which 32%-44% of costs incurred in pre-treatment phase and 7% in post-treatment phase. 29%-43% study participants reported having outstanding loan with average amount ranged from US $103 to US$261 during the post-treatment period. 20%-28% participants borrowed during post-treatment period and 7%-16% sold/mortgaged personal belongings. Therefore, economic impact of tuberculosis persists way beyond treatment completion. Major reasons of continued hardship were costs associated with initial tuberculosis treatment, unemployment, and reduced income. Therefore, policy priorities to reduce treatment cost and to protect patients from the economic consequences of the disease by ensuring job security, additional food support, better management of direct benefit transfer and improving coverage through medical insurances need consideration.

Catastrophic Costs among Tuberculosis-Affected Households in Egypt: Magnitude, Cost Drivers, and Coping Strategies.

Despite national programs covering the cost of treatment for tuberculosis (TB) in many countries, TB patients still face substantial costs. The end TB strategy, set by the World Health Organization (WHO), calls for "zero" TB households to be affected by catastrophic payments by 2025. This study aimed to measure the catastrophic healthcare payments among TB patients in Egypt, to determine its cost drivers and determinants and to describe the coping strategies. The study utilized an Arabic-validated version of the TB cost tool developed by the WHO for estimating catastrophic healthcare expenditure using the cluster-based sample survey with stratification in seven administrative regions in Alexandria. TB payments were considered catastrophic if the total cost exceeded 20% of the household's annual income. A total of 276 patients were interviewed: 76.4% were males, 50.0% were in the age group 18-35, and 8.3% had multidrug-resistant TB. Using the human capital approach, 17.0% of households encountered catastrophic costs compared to 59.1% when using the output approach. The cost calculation was carried out using the Egyptian pound converted to the United States dollars based on 2021 currency values. Total TB cost was United States dollars (USD) 280.28 ± 29.9 with a total direct cost of USD 103 ± 10.9 and a total indirect cost of USD 194.15 ± 25.5. The direct medical cost was the main cost driver in the pre-diagnosis period (USD 150.23 ± 26.89 pre diagnosis compared to USD 77.25 ± 9.91 post diagnosis, p = 0.013). The indirect costs (costs due to lost productivity) were the main cost driver in the post-diagnosis period (USD 4.68 ± 1.18 pre diagnosis compared to USD 192.84 ± 25.32 post diagnosis, p < 0.001). The households drew on multiple financial strategies to cope with TB costs where 66.7% borrowed and 25.4% sold household property. About two-thirds lost their jobs and another two-thirds lowered their food intake. Being female, delay in diagnosis and being in the intensive phase were significant predictors of catastrophic payment. Catastrophic costs were high among TB households in Alexandria and showed wide variation according to the method used for indirect cost estimation. The main cost driver before diagnosis was the direct medical costs, while it was the indirect costs, post diagnosis.

Association of serum cathelicidin and Vitamin D levels with infectiousness in patients with pulmonary tuberculosis: A prospective cohort study.

The immunomodulatory effects of Vitamin D expand to induce the synthesis of an antimicrobial peptide, cathelicidin. There is evidence showing altered levels of cathelicidin in tuberculosis (TB). It has been suggested that Vitamin D-mediated antimicrobial activity depends on its ability to induce cathelicidin. The present study was designed to assess the alterations in serum anti-microbial peptide cathelicidin and 25-hydroxy Vitamin D levels in patients with newly diagnosed pulmonary TB at different treatment times and to study the association between serum Vitamin D levels and cathelicidin. Serum 25-hydroxyvitamin D and cathelicidin levels were estimated in 147 patients with newly diagnosed pulmonary TB at different times: at the start of anti-tubercular treatment, end of the intensive phase of treatment, and at the end of treatment. There was a statistically significant difference between the levels of serum 25-hydroxyvitamin D and serum cathelicidin at different treatment periods. However, no significant correlation was found between serum Vitamin D and cathelicidin levels or between serum Vitamin D and cathelicidin levels with infectiousness in patients with pulmonary TB. Serum Vitamin D levels and serum cathelicidin levels were significantly reduced at diagnosis, and there was an incremental increase following treatment. However, there was no correlation between the levels of serum cathelicidin and serum Vitamin D or with the infectiousness of the illness.

Diagnostic Problem in a Patient with Tuberculosis Arthritis

Extra-pulmonary tuberculosis (TB) remains a big public health problem worldwide. Although TB most commonly affects the lungs, any organ or tissue can be involved. TB arthritis is a rare form of extra-pulmonary TB. TB arthritis usually manifests as mild and non-specific arthritis. A 35-year-old male was admitted to the emergency room of Dr. Soetomo General Academic Hospital Surabaya due to pain of left knee since two days prior to admission. His symptom began on previous six months with the swelling of the left knee that gradually worsened so that he had an antalgic gait. Radiological examination of left knee joint showed inflammatory arthritis, accompanied by joint effusion and soft tissue swelling. USG examination of the left knee showed the presence of non-specific left knee arthritis. Patient underwent debridement. Anatomical pathology examination of the tissue obtained at the time of debridement, showed the TB granulomatous inflammation. The Ziehl-Nielson stain of left knee tissue also showed the TB granulomatous inflammation. Patient was then treated with analgesics and anti-TB drugs. The intensive phase of anti-TB therapy was planned to be 2 month, then evaluated and followed by continuation phase for about 7 months. The knee joint is the third most common site of osteoarticular TB after spine and hip. Insidious onset of pain which, in some patients may be present for years, is the usual presentation. The joint is usually warm, and wasting of the thigh muscles is usually marked. Synovial hypertrophy and effusion are present in most patients. The gold standard for diagnosis of TB arthritis is synovial biopsy, with positive results in 80% of cases. It shows caseating granulomas, lymphocytes, and giant cells with caseation, which are characteristics of TB arthritis. Synovial biopsy is generally recommended in any arthritis where clinical evaluation and routine investigations do not give a clear diagnosis.

Disseminated Tuberculosis in Breastfeeding Mother: A Case Report

Background: Disseminated tuberculosis is defined as the involvement of two or more extrapulmonary organs due to Mycobacterium tuberculosis infection, which spreads hematogenously. Disseminated tuberculosis is a life-threatening condition, especially if diagnosis and treatment are delayed. This study aimed to describe disseminated tuberculosis in a breastfeeding mother.&#x0D; Case presentation: A 21-year-old woman was admitted to Dr. M. Djamil General Hospital with chief complaints of shortness of breath. The symptoms were accompanied by chronic cough, fever, night sweats, and weight loss. From the physical examination, there was a decrease in left lung breath sounds as high as right intercostal V. On the gene expert results, the PCR was positive for Mycobacterium tuberculosis. Chest X-ray shows a miliary pattern and left pleural effusion. Pleural fluid analysis reveals the presence of exudate. Patients were treated with anti-tuberculosis drugs, namely Isoniazid, rifampicin, pyrazinamide, and ethambutol, with pyridoxine. Anti-tuberculosis drug therapy in the intensive phase is given for 2 months and is continued for 6-9 months for the continuation phase, depending on the patient's clinical condition. Breastfeeding was still continued in this case. The patient's baby is advised to be evaluated for active tuberculosis. &#x0D; Conclusion: There are no contraindications for giving anti-TB drugs to breastfeeding mothers unless the mother has mammary TB or drug-resistant TB. In children under 5 years who have close contact with active tuberculosis patients and, after being evaluated, do not have active tuberculosis, the child is treated as suspected latent TB infection with Isoniazid for at least 6 months and accompanied by pyridoxine administration.

Magnitude of undernutrition and associated factors among adult tuberculosis patients attending public health facilities in Haramaya District, Eastern Ethiopia

BackgroundTuberculosis is one of the top ten causes of illness, death, and disability throughout the world. Undernutrition reduces immunity, which makes latent tuberculosis more likely to become active tuberculosis. Tuberculosis makes these conditions worse. The body of a person suffering from TB has an increased demand for energy, which often causes a TB patient to lose a significant amount of weight and this can worsen acute undernutrition. The aim of this study was to assess the magnitude of undernutrition and its associated factors among adult TB patients in public health facilities in Haramaya district, eastern Ethiopia.MethodsInstitution-based cross-sectional study was conducted among 330 adult tuberculosis patients on follow-up in public health facility of Haramaya District, eastern Ethiopia from January 10, 2021 to February 20, 2021. An anthropometric assessment was done after a face-to-face interview using a pretested structured questionnaire. SPSS 24 was used to analyze the data. Bivariable and multivariable logistic regression model was used to identify factors associated with undernutrition.ResultsThe overall prevalence of undernutrition was 43.6% (95% CI 38.2–49.1%). Proportion of severe, moderate and mild undernutrition was 11.8%, 12.4%, and 19.4%, respectively. Age group of 18–24 years (AOR = 4.12; 95% CI 1.36–12.51), not have formal education (AOR = 1.76; 95% CI 1.01–3.08), having large family size (AOR = 2.62; 95% CI 1.43–4.82), low dietary diversity (AOR = 2.96; 95% CI 1.75–4.99), lack of latrine (AOR = 2.14; 95% CI 1.26–3.65), history of TB treatment (AOR = 2.56; 95% CI 1.19–5.54) and taking intensive phase of anti-TB drugs (AOR = 3.18; 95% CI 1.62–6.25) were factors found significantly associated with under nutrition.ConclusionThe prevalence of undernutrition was high. Age, educational status, family size, dietary diversity, toilet facility, history of tuberculosis medication and intensive phase of anti-TB drugs were found significantly associated with undernutrition. The nutritional derangement could call for fast nutritional intervention in the management of pulmonary tuberculosis patients.

The Role of Omega-3/Omega-6 Ratio on Appetite in Pulmonary Multidrug-Resistant Tuberculosis Patients

Introduction: Tumour necrosis factor-alpha (TNF-α) levels, pro-inflammatory cytokines that suppress appetite, were discovered to be much higher in multidrug-resistant tuberculosis (MDR-TB) than in drug-sensitive TB. Research on the omega-3/omega-6 (ꞷ-3/ꞷ-6) polyunsaturated fatty acids (PUFAs) intake, which can support appetite in patients with MDR-TB, has never been performed. This study aimed to examine the relationship between ꞷ-3/ꞷ-6 PUFAs intake ratio and appetite mediated by TNF-α in pulmonary MDR-TB patients. Methods: This was a cross-sectional study conducted on 46 male and female adults with MDR-TB undergoing intensive phase therapy. Data were collected through questionnaires, 1x24 hours food recall, anthropometric measurements, 100 mm visual analogue appetite scale, and venous blood collection. Results: Correlation analysis used the Pearson and Spearman tests. The findings revealed the ratio of ꞷ-3/ꞷ-6 PUFAs intake of 0.11 ± 0.05, the median value of TNF-α 7.49(1.66-447.62) pg/mL, and an average appetite of 58.72 ± 26.7. There was no relationship between ꞷ-3/ꞷ-6 PUFAs intake ratio and TNF-α (r = 0.016; p = 0.91), likewise between ꞷ-3/ꞷ-6 PUFAs intake ratio with appetite (r = -0.1; p = 0.54), but there was a relationship between TNF-α and appetite (r = 0.031; p = 0.04). Conclusion: There was no relationship between ꞷ-3/ꞷ-6 PUFAs intake ratio and TNF-α and appetite in pulmonary MDR-TB patients. However, there was a relationship between TNF-α and appetite. This study is the first to determine the correlation between ꞷ-3/ꞷ-6 PUFAs intake ratio and appetite in pulmonary MDR-TB patients.

Management of Polydrug-Resistant Tuberculosis

Background and Objectives: There is a lack of information regarding the effective duration of treatment necessary to prevent the development of acquired resistance when fluoroquinolones (FQ), and/or pyrazinamide (Z) resistance has occurred in patients with polydrug-resistant tuberculosis and isoniazid resistance. The management of these kinds of patients should be carried out in experienced centers according to drug susceptibility test results, clinical status of the patient and the extensity of the disease. Materials and Methods: We evaluated treatment regimens, treatment outcomes, and drug adverse effects in seven patients with polydrug-resistant tuberculosis, including those with Z and/or FQ resistance in a retrospective analysis Results: Regarding the patients with polydrug-resistant tuberculosis in addition to isoniazid (H) resistance, three had Z, two had FQ, and the remaining two had both Z and FQ resistance. In the intensive phase of the treatment, the patients were given at least four drugs according to drug susceptibility tests, and at least three drugs in the continuation phase. The duration of treatment was 9-12 months. Two of the patients were foreign nationals, and could not be followed up with due to returning to their home countries. Regarding the remaining five patients, three of them were terminated as they completed treatment, and two as cured. No recurrence was observed in the first year of the treatment. The most common, and serious drug side effect was seen for amikacin. Conclusions: In patients with polydrug-resistant TB, if Z and/or FQ resistance is detected in addition to H resistance, the treatment of these patients should be conducted on a case-by-case basis, taking into account the patient's resistance pattern, clinical condition, and disease prognosis. Close monitoring of the side effects will increase the success rate of the treatment.

Hepatotoxicity and tuberculosis treatment outcomes in chronic liver disease.

The treatment of tuberculosis (TB) is known to cause liver injury, however, there is limited data to guide optimal treatment for patients with chronic liver disease. We undertook a retrospective case series of patients with chronic liver disease and TB disease. The primary objective was to determine if there was a difference in the incidence of drug-induced liver injury (DILI) in patients with cirrhosis versus those with chronic hepatitis. Additionally, we sought to compare TB treatment outcomes, type and duration of therapy, and incidence of adverse events. We included 56 patients (chronic hepatitis 40; cirrhosis 16). There were 33 patients (58.9%) who experienced DILI requiring treatment modification, with no significant difference between groups (65% versus 43.8%, p = 0.23). Patients with chronic hepatitis were more likely to receive treatment with standard first-line intensive phase therapy that included a combination of rifampin (RIF), isoniazid, and pyrazinamide (80.8% versus 19.2%, p = 0.03) and any regimen than included isoniazid (92.5% versus 68.8%, p = 0.04). The risk of DILI was higher when more hepatotoxic TB medications were used. Overall treatment success in this cohort was low (55.4%), with no significant difference between groups (62.5% versus 37.5%, p = 0.14). Most patients with treatment success (97%) were able to tolerate a rifamycin. The risk of DILI is high, especially with the use of isoniazid, in patients with TB and chronic liver disease. This risk can be effectively mitigated with no difference in treatment outcomes in the presence of cirrhosis.

The surfactant inhaled therapy in a complex lung tuberculosis treatment: clinical reviews

The article describes the clinical case reports of patients with respiratory tuberculosis who were hospitalized at the Regional Clinical Antituberculosis Center in Kursk. One of them was in the pediatric department for patients with tuberculosis of respiratory organs and the other in the 1st department for patients with multidrug-resistant tuberculosis. As pathogenetic therapy in the complex treatment of pulmonary tuberculosis, in the intensive phase of anti-tuberculosis chemotherapy, we added inhalation therapy with surfactant (medicinal product surfactant-BL lyophilisate for emulsion preparation, 75 mg, manufactured by Biosurf LLC, Russia) according to the instructions to the drug. Treatment of pulmonary tuberculosis is performed by multiple inhalations of surfactant-BL as part of complex therapy against the background of fully deployed antituberculosis drugs (ATD), i.e. when the patient empirically or based on data on drug sensitivity of the pathogen is selected 4-6 ATD that are well tolerated by the patient in the prescribed dose and combination. It should be noted that an adult patient during the intensive phase of anti-tuberculosis chemotherapy had COVID-19. Against the background of inhalation therapy with surfactant, it was possible to stabilize the clinical and radiological condition of the patients, and to improve their condition. Clinically it was expressed in reduction of coughing, increase of tolerance to physical exertion. For example, according to spirometry data on the admission of an adult patient and in dynamics, the vital capacity index (VCI) increased from an extremely sharp decrease (31.25%) to 75%, which corresponded to a very mild decrease. At the moment the patient from the children’s ward is completing a course of antituberculosis therapy with small residual changes in the lungs, and the adult patient was operated on at the Russian Ministry of Health at the Federal State Budgetary Institution “National Research Center of Pulmonary Medicine” for installation of a bronchial valve. Based on the above, we can conclude about the successful, pathogenetically sound use of surfactant-BL in patients with respiratory tuberculosis in both children and adults.

Patient-reported usability and satisfaction with electronic medication event reminder and monitor device for tuberculosis: a multicentre, randomised controlled trial

The success of a tuberculosis digital adherence technology relies on patients' satisfaction with and the usability of the technology. This study aimed to evaluate treatment satisfaction and usability of a digital medication event reminder and monitor (MERM) device for patients with tuberculosis to address the prespecified secondary endpoint of the SELFTB trial. In this multicenter, randomised controlled trial, adults (≥18 years) with new or previously treated, bacteriologically-confirmed, drug-sensitive pulmonary tuberculosis who were eligible to start anti-tuberculosis therapy were recruited from 10 healthcare facilities in Ethiopia. With a computer-generated random number sequence, participants were randomly assigned 1:1 to receive a 15-day tuberculosis medication supply dispensed with an evriMED500® MERM device to self-administer and return every 15 days or the standard in-person DOT. Both arms were followed throughout the standard two-month intensive treatment phase. Treatment was based on the WHO-recommended two-month fixed-dose-combination of first-line anti-tuberculosis drug delivered as a single daily dose (2RHZE). Treatment Satisfaction Questionnaire for Medication version 4 (TSQM 1.4©) was used to measure and compare treatment satisfaction between arms. Adapted System Usability Scale (SUS) was used to assess the usability of the device, with emphasis on ease of use, challenges, benefits, motivation, popularity, and recommendation. The findings were correlated with adherence and clinical endpoints including sputum smear conversion and IsoScreen urine isoniazid test results. This trial is registered with ClinicalTrials.gov, NCT04216420. Between June 2, 2020, and June 15, 2021, 337 patients were screened for eligibility, of whom 109 participants enrolled and completed the satisfaction [control (n=57) and intervention (n=52) arms] and usability [intervention arm (n=52)] questionnaires. TSQM 1.4© geometric mean scores were: Effectiveness 73.25 [geometric standard deviation (GSD) 1.28], Side Effects 100, Convenience 63.31 (GSD 1.45), and Global Satisfaction 77.29 (GSD 1.25). TSQM score was significantly higher in the intervention vs the control: Effectiveness [85.78 vs 63.43, 95% CI 1.35 (1.26-1.45), p<0.001], Convenience [85.41 vs 48.18, 95% CI 1.77 (1.63-1.93), p<0.001], and Global Satisfaction [90.19 vs 67.11, 95% CI 1.34 (1.26-1.43), p<0.001]. There were significant associations between Global Satisfaction and medication adherence (p=0.017). Average SUS score was 97.45%, which was close to the best imaginable SUS value of 100%. Likelihood to Recommend (LTR) value was ≥9, on a scale of 0-10, for 90.4% of MERM users, yielding higher net promoters. There was no significant association between usability and medication adherence (p=0.691). Our findings suggested that treatment satisfaction scores were superior in the intervention vs control arms and across the domains of Effectiveness, Convenience, and Global Satisfaction. There was excellent usability of the MERM device and a significantly higher number of users likely to promote the device. High tuberculosis burden countries may transform patient-centered care through ongoing evaluation and scale-up of digital health innovations. U.S. National Institute of Health (NIH) Fogarty International Center and National Institute of Allergy and Infectious Diseases (D43 TW009127) and the Emory Center for AIDS Research (P30 AI050409).

Effectiveness of Community-Based Multidrug-Resistant Tuberculosis Treatment in Nigeria: A Retrospective Cohort Study

Growing multidrug-resistant tuberculosis (MDR-TB) worldwide and new effective and affordable treatment modalities required exploring options such as the community model of MDR-TB treatment (CM), as introduced in Nigeria.To determine the most effective care model by comparing MDR-TB treatment outcomes at community-based sites with the hospital-based model of care in Nigeria.Treatment outcomes data were retrospectively accessed from the medical record of 423 MDR-TB patients to evaluate the effectiveness of HM and CM based on WHO criteria. Treatment success” is defined as the sum of cure and treatment completion. “Cure” is the “treatment completion” with at least three negative cultures taken at least 30 days apart after the intensive phase in the absence of “treatment failure. Predictors of treatment outcomes were also assessed on multivariate analysis. 423 patients (85% of the targeted sampling data) were available for analysis, of whom 272 (63.4%) had a conventional regimen, and 143 (33.8%) had a shorter treatment regimen. There is no significant difference in treatment outcomes between CM and HM; patients achieve similar treatment success in all models, 65.5% with HM compared to 68% at the CM (p = 0.608). Treatment failure was (4.1% versus 5.1%) in the HM versus CM, respectively; (p = 0.704). Death occurred in 20.9% of participants in the hospital model and 17.5% in the community model, and rates of Loss to follow-up were similar 9.5% HM vs 9.5% CM; (p = 0.704). On multivariate analysis, adjusting for age, HIV, sex, patient type, TB treatment history, resistance pattern, model of care and regimens, there was no change in treatment outcomes if patients were treated at the CM vs HM (adjusted odds ratio [aOR] 0.92; 95% CI 0.59 – 1.46, p = 0.735). MDR-TB patients with unknown HIV status (not on ART) were nine times more likely to have unsuccessful treatment outcomes compared with HIV-negative respondents (adjusted odds ratio [aOR] 8.83; 95% CI 1.79 – 43.60, p = 0.007). Similarly, HIV-positive respondents were 1.3 times more likely to have unsuccessful outcomes than HIV-negative (adjusted odds ratio [aOR] 1.26; 95% CI 0.71–2.26, p = 0.429, but the difference is not statistically significant. This retrospective study found that the community-based model is equally effective as care in a centralised hospital, based on similar treatment success rates, comparable default and death rates with hospital care and shorter time to treatment initiation at the community-based centres.

Recombinant human chorionic gonadotropin and gonadotropin-releasing hormone agonist differently affect the profile of extracellular vesicle microRNAs in human follicular fluid.

To compare the expression profile of extracellular vesicle microRNAs (EV-miRNAs) derived from follicular fluid after a trigger with recombinant human chorionic gonadotropin (r-hCG) or with a gonadotropin-releasing hormone GnRH agonist (GnRH-a) for final oocyte maturation. A retrospective analysis of a prospective cohort. Women undergoing in vitro fertilization at a tertiary university-affiliated hospital were recruited between 2014 and 2016. EV-miRNAs were extracted from the follicular fluid of a single follicle, and their expression was assessed using TaqMan Open Array®. Genes regulated by EV-miRNAs were analyzed using miRWalk2.0 Targetscan database, DAVID Bioinformatics Resources, Kyoto-Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO). Eighty-two women were included in the r-hCG trigger group and 9 in the GnRH-a group. Of 754 EV-miRNAs screened, 135 were detected in at least 50% of the samples and expressed in both groups and were further analyzed. After adjusting for multiple testing, 41 EV-miRNAs whose expression levels significantly differed between the two trigger groups were identified. Bioinformatics analysis of the genes regulated by these EV-miRNAs showed distinct pathways between the two triggers, including TGF-beta signaling, cell cycle, and Wnt signaling pathways. Most of these pathways regulate cascades associated with apoptosis, embryo development, implantation, decidualization, and placental development. Trigger with GnRH-a or r-hCG leads to distinct EV-miRNAs expression profiles and to downstream biological effects in ovarian follicles. These findings may provide an insight for the increased apoptosis and the lower implantation rates following GnRH-a trigger vs. r-hCG in cases lacking intensive luteal phase support.