Continuation Phase Of Treatment Research Articles

The long-term course and prognosis of postpartum depression: a retrospective longitudinal cohort study.

The purpose is to investigate the natural course and long-term prognosis of postpartum depression (PPD). In this retrospective longitudinal cohort study, mothers diagnosed as either suffering from PPD or without PPD were reassessed 5-8 years thereafter by a semi-structured interview and their charts were reviewed for past psychiatric illness prior to the index (initial) episode and for new-onset episodes in the following years. Present psychiatric state was also evaluated by interview and questionnaires. Sixty-five mothers with and 35 without past PPD underwent the full assessment. A total of 66.2% of mothers with past PPD had any axis I psychopathology before their index PPD episode, compared with only 8.6% in the non-PPD group (p < 0.001, φ = .55). Furthermore, 37.2% of the females who had a history of PPD and experienced subsequent childbirths during the follow-up years, developed at least one new episode of PPD. Throughout the 5 years subsequent to the index PPD episode, 42.5% of the PPD group compared with only 3.7% for the non-PPD group developed a new episode of depression (p < 0.001). Lastly, reported psychopathology was higher and functional level was significantly worse in the PPD group at the time of reassessment. Females who develop an episode of PPD show a high degree of subsequent psychopathology and unfavorable prognosis. Clinicians treating females for PPD should consider a longer treatment continuation phase in an effort to prevent further psychopathology and a closer follow-up program.

A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis

BackgroundLinezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure–response and exposure–toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.MethodsSeventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response.Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course.DiscussionDECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages.Trial registrationDECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832).

Survey to measure the quality of life of patients with tuberculosis in Alexandria, Egypt: a cross-sectional study

BackgroundAssessment of quality of life (QoL) in patients with tuberculosis (TB) may improve healthcare providers’ understanding of the disease burden. This study aimed to investigate the QoL of patients with TB in Alexandria, Egypt.MethodsThis cross-sectional study was conducted in chest clinics and main chest hospitals in Alexandria, Egypt. A structured interview questionnaire was used to collect data from participants through face-to-face interviews from November 20, 2021, until the June 30, 2022. We included all adult patients aged 18 years or above during the intensive or continuation phase of treatment. The World Health Organization (WHO) WHOQOL-BREF instrument was used to measure QoL, which includes the physical, psychological, social relationships, and environmental health domains. Using propensity score matching, a group of TB free population was recruited from the same setting and completed the questionnaire.ResultsA total of 180 patients participated in the study: 74.4% were males, 54.4% were married, 60.0% were 18–40 years old, 83.3% lived in urban areas, 31.7% were illiterate, 69.5% reported insufficient income, and 10.0% had multidrug-resistant TB. The TB-free population group had higher QoL scores than the TB patients’ group: (65.0 ± 17.5 vs. 42.4 ± 17.8) for the physical domain, (59.2 ± 13.6 vs. 41.9 ± 15.1) for the psychological domain, (61.8 ± 19.9 vs. 50.3 ± 20.6) for the social domain, (56.3 ± 19.3 vs. 44.5 ± 12.8) for the environment domain, (4.0(3.0–4.0) vs. 3.0(2.0–4.0)) for general health, and (4.0(3.0–4.0) vs. 2.0(2.0–3.0)) for the general QoL, P < 0.0001. Patients with TB aged 18–30 years had the highest environmental score compared with the other age groups (P = 0.021).ConclusionsTB had a significant negative impact on QoL, with the physical and psychological domains being the most affected. This finding necessitates strategies to improve QoL of patients with to enhance their compliance to treatment.

Use of a Sustainable Livelihood Framework-Based Measure to Estimate Socioeconomic Impact of Tuberculosis on Households.

Tuberculosis (TB) disproportionally affects impoverished members of society. The adverse socioeconomic impact of TB on households is mostly measured using money-centric approaches, which have been criticized as one-dimensional and risk either overestimating or underestimating the true socioeconomic impacts of TB. We propose the use of the sustainable livelihood framework, which includes 5 household capital assets (human, financial, physical, natural, and social) and conceptualizes that households employ accumulative strategies in times of plenty and coping (survival) strategies in response to shocks such as TB. The proposed measure ascertains to what extent the 5 capital assets are available to households affected by TB as well as the coping costs (reversible and nonreversible) that are incurred by households at different time points (intensive, continuation, and post-TB treatment phase). We assert that our approach is holistic and multidimensional and draws attention to multisectoral responses to mitigate the socioeconomic impact of TB on households.

Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis.

To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB). In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods. Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment. Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.

Age-specific associations between serum cholesterol levels and suicidal behaviors in patients with depressive disorders: A naturalistic prospective observational cohort study.

This study investigated the effects of total cholesterol levels on prevalent, and incident suicidal behaviors according to age group (<60 vs. ≥60 years) in depressed patients. Consecutive outpatients with depressive disorders who visited the Chonnam National University Hospital between March 2012 and April 2017 were recruited. Among 1,262 patients assessed at baseline, 1,094 agreed to blood sampling for measurement of serum total cholesterol levels. Among the patients, 884 completed the 12-week acute treatment phase and were followed up at least once during the 12-month continuation treatment phase. Suicidal behaviors assessed at baseline included baseline suicidal severity; behaviors assessed at the 1-year follow-up included increased suicidal severity and fatal/non-fatal suicide attempts. Associations of baseline total cholesterol levels with the above-mentioned suicidal behaviors were analyzed using logistic regression models after adjustment for relevant covariates. Of 1,094 depressed patients, 753 (68.8%) were women. The mean (SD) age of patients was 57.0 (14.9) years. Lower total cholesterol levels (87-161 mg/dl) were associated with increased suicidal severity (Linear Wald = 4.478, p < 0.05) and fatal/non-fatal suicide attempt (Linear Wald = 7.490, p < 0.01) in patients <60 years of age. U-shaped associations between total cholesterol levels and 1-year follow-up suicidal outcomes (increased suicidal severity, Quadratic Wald = 6.299, p < 0.05; fatal/non-fatal suicide attempt, Quadratic Wald = 5.697, p < 0.05) were observed in patients ≥60 years of age. These findings suggest that differential consideration of serum total cholesterol levels according to age group may have clinical utility for predicting suicidality in patients with depressive disorders. However, because our research participants came from a single-hospital, the generalizability of our findings may be limited.

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.

Interactive Effects of Serum Leptin Levels and Physical Comorbidity on the Pharmacotherapeutic Response of Depressive Disorders.

To investigate individual and interactive associations of baseline serum leptin levels and physical comorbidity with short- and long-term treatment outcomes in outpatients with depressive disorders who received stepwise antidepressant treatment in a naturalistic prospective study design. Baseline serum leptin levels were measured, and the number of concurrent physical disorders ascertained from 1,094 patients. These patients received initial antidepressant monotherapy; then, for patients with an insufficient response or who experienced uncomfortable side effects, treatment was administered using alternative strategies every 3 weeks in the acute treatment phase (at 3, 6, 9, and 12 weeks) and every 3 months in the continuation treatment phase (at 6, 9, and 12 months). Then, 12-week and 12-month remission, defined as a Hamilton Depression Rating Scale score of ≤7, was estimated. In multivariable logistic regression analyses, individual effects were found only between higher baseline serum leptin levels and 12-week non-remission. Significant interactive effects between higher leptin levels and fewer physical disorders (< 2 physical disorders) on 12-week non-remission were observed. However, neither individual nor interactive effects between leptin levels and physical comorbidity were associated with 12-month remission. The combination of serum leptin level and number of physical disorders may be a useful predictor of short-term treatment responses in patients with depressive disorders receiving pharmacotherapy.

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.

Safety and Effectiveness of Desvenlafaxine in Korean Patients with Major Depressive Disorder: A 6-month Postmarketing Surveillance Study.

ObjectiveAlthough the safety and efficacy of desvenlafaxine have been demonstrated, long-term evidence in Asians is lacking. We examined the safety and effectiveness of desvenlafaxine for up to 6 months in routine clinical practice in Korea.MethodsThis multicenter, open-label, prospective observational study was conducted from February 2014 to February 2020 as a postmarketing surveillance study of desvenlafaxine (ClinicalTrials.gov identifier NCT02548949). Adult patients with major depressive disorder (MDD) were observed from the initiation of treatment for 8 weeks (acute treatment phase) and then up to 6 months (continuation treatment phase) in a subsample. Safety was evaluated by incidence of adverse events (AE) and adverse drug reactions. Treatment response was assessed using the Clinical Global Impression- Improvement (CGI-I) scale.ResultsWe included 700 and 236 study subjects in the analysis of acute and continuation treatment phase, respectively. In acute treatment phase, AE incidence was 9.86%, with nausea being most common (2.00%). In continuation treatment phase, AE incidence was 2.97%, with tremor occurring most frequently. After acute treatment (n = 464), the treatment response rate according to the CGI-I score at week 8 was 28.9%. In long-term users (n = 213), the response rate at month 6 was 45.5%. During the study period, no clinically relevant changes in BP were found regardless of concomitant use of antihypertensive drugs.ConclusionThis study provides evidence on the safety and effectiveness of desvenlafaxine in adults with MDD, with a low incidence of AE, consistent AE profile with previous studies, and improved response after long-term treatment.

Forgiveness Is the Attribute of the Strong: Nonadherence and Regimen Shortening in Drug-sensitive Tuberculosis.

Rationale: "Forgiveness" charts the ability of a drug or regimen to withstand nonadherence without negative clinical consequences. Objectives: We aimed to determine the influence of regimen length, regimen drugs, and dosing, and when during treatment nonadherence occurs on the forgiveness of antituberculosis regimens. Methods: Using data from three randomized controlled trials comparing experimental 4-month regimens for drug-sensitive tuberculosis with the standard 6-month regimen, we used generalized linear models to examine how the risk of a negative composite outcome changed as dose-taking decreased. The percentage of doses taken and the absolute number of doses missed were calculated during the intensive and continuation phases of treatment, and overall. A mediation analysis was undertaken to determine how much the association between intensive phase dose-taking and the negative composite outcome was mediated through continuation phase dose-taking. Measurements and Main Results: Forgiveness of the 4- and 6-month regimens did not differ for any treatment period. Importantly, 4-month regimens were no less forgiving of small numbers of absolute missed doses than the 6-month regimen (e.g., for 3-7 missed doses vs. no missed doses [baseline], 6-month regimen adjusted risk ratio 1.65 [95% confidence interval, 0.80-3.41] and 4-month regimens 1.80 [1.33-2.45]). No 4-month regimen was conclusively more forgiving than another. We found evidence of mediation by continuation phase dose-taking on the intensive phase dose-taking and negative composite outcome relationship. Conclusions: With the current appetite for, and progress toward, shorter drug-sensitive tuberculosis regimens worldwide, we offer reassurance that shorter regimens are not necessarily less forgiving of nonadherence. Given the importance of continuation phase adherence, patient support during this period should not be neglected.

Associations of Serum Serotonin Levels with 12-week and 12-month Remission in Patients with Depressive Disorders.

ObjectiveTo investigate associations between baseline serum serotonin levels and short- and long-term treatment outcomes in outpatients with depressive disorders in a naturalistic one-year prospective study design.MethodsPatients were recruited at a University hospital in South Korea from March 2012 to April 2017. At baseline, blood samples were obtained from 1,094 patients who received initial antidepressant monotherapy (Step 1). After the Step 1 treatment, further treatment steps (at least Steps 2−4) could be administered every 3 weeks during the acute treatment phase (3, 6, 9, and 12 weeks; n = 1,086), and every 3 months during the continuation treatment phase (6, 9, and 12 months; n = 884). In cases showing an insufficient response or intolerable side effects, patients were asked to choose whether to remain at the current step or enter the next treatment step, with alternative strategies including switching, augmentation, combination, and a mixture of these approaches. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7.ResultsThe remission group had significantly higher baseline serum serotonin levels among patients who received Step 1 monotherapy in both acute and continuation treatment phases. These associations remained significant after adjustment for relevant covariates. No associations were found with any other treatment steps.ConclusionBaseline serum serotonin levels may be used as a biomarker for predicting short- and long-term treatment outcomes in antidepressant monotherapy-treated patients with depressive disorders in a real-world clinical setting.

Prospective associations of multimodal serum biomarkers with 12-week and 12-month remission in patients with depressive disorders receiving stepwise psychopharmacotherapy

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. They received initial antidepressant monotherapy followed, as required by a protocol of successive alternative pharmacological strategies administered in 3-week steps during the acute (3–12 week) phase (N = 1086), and in 3-month steps during the continuation (6–12 month) phase (N = 884). Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Remission was achieved in 490 (45.1%) over the 12-week, and in 625 (70.7%) over the 12-month, treatment periods. Combination scores of four serum biomarkers (high-sensitivity C-reactive protein, interleukin-1 beta, interleukin-6, and leptin) were prospectively associated with 12-week remission; and four (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, and brain-derived neurotrophic factor) were prospectively associated with 12-month remission in a clear gradient manner (P-values < 0.001) and after adjustment for relevant covariates. These associations were evident after the Step 1 treatment monotherapy but weakened with increasing treatment steps, falling below statistical significance after 4 + treatment steps. Application of combined multiple serum biomarkers, particularly on inflammatory markers, could improve predictability of remission at acute and continuation treatment phases for depressive disorders. Patients with unfavourable biomarkers might require alternative treatment regimes for better outcomes.

Adaptive/innate immunity balance in a complex social world

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. They received initial antidepressant monotherapy followed, as required by a protocol of successive alternative pharmacological strategies administered in 3-week steps during the acute (3–12 week) phase (N = 1086), and in 3-month steps during the continuation (6–12 month) phase (N = 884). Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Remission was achieved in 490 (45.1%) over the 12-week, and in 625 (70.7%) over the 12-month, treatment periods. Combination scores of four serum biomarkers (high-sensitivity C-reactive protein, interleukin-1 beta, interleukin-6, and leptin) were prospectively associated with 12-week remission; and four (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, and brain-derived neurotrophic factor) were prospectively associated with 12-month remission in a clear gradient manner (P-values < 0.001) and after adjustment for relevant covariates. These associations were evident after the Step 1 treatment monotherapy but weakened with increasing treatment steps, falling below statistical significance after 4 + treatment steps. Application of combined multiple serum biomarkers, particularly on inflammatory markers, could improve predictability of remission at acute and continuation treatment phases for depressive disorders. Patients with unfavourable biomarkers might require alternative treatment regimes for better outcomes.

Sex differences in the immune system: Implications for cocaine relapse

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. They received initial antidepressant monotherapy followed, as required by a protocol of successive alternative pharmacological strategies administered in 3-week steps during the acute (3–12 week) phase (N = 1086), and in 3-month steps during the continuation (6–12 month) phase (N = 884). Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Remission was achieved in 490 (45.1%) over the 12-week, and in 625 (70.7%) over the 12-month, treatment periods. Combination scores of four serum biomarkers (high-sensitivity C-reactive protein, interleukin-1 beta, interleukin-6, and leptin) were prospectively associated with 12-week remission; and four (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, and brain-derived neurotrophic factor) were prospectively associated with 12-month remission in a clear gradient manner (P-values < 0.001) and after adjustment for relevant covariates. These associations were evident after the Step 1 treatment monotherapy but weakened with increasing treatment steps, falling below statistical significance after 4 + treatment steps. Application of combined multiple serum biomarkers, particularly on inflammatory markers, could improve predictability of remission at acute and continuation treatment phases for depressive disorders. Patients with unfavourable biomarkers might require alternative treatment regimes for better outcomes.

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy

BackgroundSome tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described.MethodsWe conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan–Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation.Results2303 patients met inclusion criteria: 2003(87%) received TB treatment 5–7 days/week and 300(13%) 2–3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5–7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5–7 vs. 2–3 days/week (HR = 0.68; 95% CI = 0.51—0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5–7 days/week vs. 2–3 days/week (HR 0.75, 95%CI 0.55–1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83–2.45; P = 0.20).ConclusionsTB treatment 5–7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2–3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

Effectiveness of chemotherapy of multidrug-resistant tuberculosis using bedaquiline

The aim of the study was to evaluate the effectiveness of MDR/XDR TB treatment with bedaquiline. Methods. The author analyzed the treatment results of 56 patients in Staint Petersburg in 2017 with MDR/XDR TB whose treatment regimen included bedaquiline. All patients were smear/ culture-positive: 43 (67.8%) cases with XDR MBT; 7 (12.5%) with pre-XDR MBT and only 6 (10.7 %) cases with MDR TB. Results. 35 (62.5%) patients received full bedaquiline course, 16 received the treatment for a few days to 4 months and did not complete the course, 5 patients with XDR tuberculosis who underwent surgery were treated for more than 6 months. The average duration of bedaquiline course was 4.7 ± 0.3 months. Among the 27 (48.2%) patients who completed the treatment effectively, 22 had XDR TB, 3 – pre-XDR TB, and 2 – MDR TB. The median sputum conversion period was 4.00 ± 0.42 months (CI: 3.14 – 4.86). 13 (23.2%) patients interrupted the treatment, but 9 of them had negative cultures for MBT at this time. These patients received bedaquiline for 1 to 14 months. Treatment failure was recorded in 12 (21.4%) patients, and 4 (7.14%) patients died during the intensive treatment phase. In general, 27 patients with a successful outcome had negative cultures at the end of the intensive phase and 9 patients who effectively completed the intensive phase but interrupted the treatment continuation phase. In total, 36 patients (64.3%) had a successful treatment outcome. Conclusion. The analysis showed that routine administration of the drug without consideration for treatment compliance increases the effectiveness of the intensive phase (64.3%) and does not significantly affect general effectiveness of the treatment (48.2%). The high frequency of treatment interruption remains a serious obstacle to improving the treatment effectiveness.

Tuberculosis treatment within differentiated service delivery models in global HIV/TB programming.

IntroductionProviding more convenient and patient‐centred options for service delivery is a priority within global HIV programmes. These efforts improve patient satisfaction and retention and free up time for providers to focus on new HIV diagnoses or severe illness. Recently, the coronavirus disease 2019 (COVID‐19) pandemic precipitated expanded eligibility criteria for these differentiated service delivery (DSD) models to decongest clinics and protect patients and healthcare workers. This has resulted in dramatic scale‐up of DSD for antiretroviral therapy, cotrimoxazole and tuberculosis (TB) preventive treatment. While TB treatment among people living with HIV (PLHIV) has traditionally involved frequent, facility‐based management, TB treatment can also be adapted within DSD models. Such adaptations could include electronic tools to ensure appropriate clinical management, treatment support, adherence counselling and adverse event (AE) monitoring. In this commentary, we outline considerations for DSD of TB treatment among PLHIV, building on best practices from global DSD model implementation for HIV service delivery.DiscussionIn operationalizing TB treatment in DSD models, we consider the following: what activity is being done, when or how often it takes place, where it takes place, by whom and for whom. We discuss considerations for various programme elements including TB screening and diagnosis; medication dispensing; patient education, counselling and support; clinical management and monitoring; and reporting and recording. General approaches include multi‐month dispensing for TB medications during intensive and continuation phases of treatment and standardized virtual adherence and AE monitoring. Lastly, we provide operational examples of TB treatment delivery through DSD models, including a conceptual model and an early implementation experience from Zambia.ConclusionsCOVID‐19 has catalysed the rapid expansion of differentiated patient‐centred service delivery for PLHIV. Expanding DSD models to include TB treatment can capitalize on existing platforms, while providing high‐quality, routine treatment, follow‐up and patient education and empowerment.

Predictors of Remission in Acute and Continuation Treatment of Depressive Disorders.

ObjectiveTo identify factors predicting remission of depression during acute (12 weeks) and continuation treatment (12 months) using a 1-year, naturalistic prospective study design.MethodsPatients with depressive disorders were recruited from Chonnam National University Hospital in South Korea from March 2012 to April 2017. At baseline, 1,262 patients received outpatient therapy, and sociodemographic and clinical data were obtained. Clinical visits took place every 3 weeks during the acute treatment phase (at 3, 6, 9, and 12 weeks; n = 1,246), and every 3 months during the continuation treatment phase (at 6, 9, and 12 months; n = 1,015). Remission was defined as a Hamilton Depression Rating Scale score ≤ 7.ResultsThe remission rate was 43.3% at 12 weeks and 70.4% at 12 months. In multivariate analyses, remission during the acute treatment phase was more likely in patients with a shorter-duration present episode, higher functioning, and good social support. Remission during the continuation treatment phase was more likely in patients with fewer previous depressive episodes and/or a lower baseline stress score.ConclusionFactors predicting depressive disorder remission may differ between the acute and continuation treatment phases.

Adverse Drug Reactions Monitoring in Patients on Antitubercular Treatment in Tertiary Care Hospital, Mandya

Background: Tuberculosis is one of the major public health concerns in India. Treatment of tuberculosis need multidrug combinations, which is associated with increased incidence of adverse drug reactions (ADRs). Hence there is a need of active monitoring for adverse effects in patients who are on antitubercular treatment (ATT). Objectives: To study the pattern of ADRs caused by antitubercular drugs and to assess causality, severity and predisposing factors. Methodology: A prospective observational study was conducted for 6 months in tertiary care hospital of Mandya. A total of 74 patients of tuberculosis who experienced ADRs were included in the study after obtaining informed consent. Their demographic, treatment and ADR data were collected and analysed. Causality was assessed using WHO scale and Naranjo’s algorithm, whereas severity was assessed by Modified Hartwig and Siegel scale. Results: Among 74 patients, 55(74.32%) were males and 19 (25.67%) were females. A total of 86 ADRs were recorded amongst 74 patients, as 11 patients experienced two ADRs. During intensive and continuation phase of treatment, 65 (87.63%) and 9 (12.16%)patients experienced ADRs respectively. Gastrointestinal side effects and hepatotoxicity were the most frequently observed ADRs with 23 (26.7%) each, followed by pruritus and rashes in 18 (20.93%) patients.63.51% of ADRs had an association with fixed dose combination (FDC) of isoniazid, rifampicin, pyrazinamide and ethambutol. As per WHO scale and Naranjo’s algorithm majority of ADRs were probable with 44 (59.45%) and 58 (78.37%) respectively. Most of the ADRs belonged to mild (67.56%) category as per Modified Hartwig and Siegel scale. Conclusion: ADRs induced by ATT are common. Hence counselling of patients regarding their life style along with early detection and management will minimize the occurrence of ADRs and improvethe adherence to treatment.