Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard Treatment of Pulmonary Tuberculosis.

The effects on ventricular repolarization-recorded on the electrocardiogram (ECG) as lengthening of the QT interval-of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady state (month 1) in a subset of patients. We compared treatment effects on the QTc and modeled the effect of individual drugs' maximum concentrations of drug in serum (Cmax) on the Fridericia-corrected QT interval. A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline (mean age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5°C. Pretreatment, the nonlinear model estimated the best correction factor at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of -0.9% (95% confidence interval [CI], -2.0% to 2.3%; P = 0.12) and 0.1% (95% CI, -0.6% to 0.9%; P = 0.75), respectively, between the test and control arms. One hundred six (6.6%) patients had a peak measurement change from baseline of >60 ms (adjusted between-arm difference, 0.8%; 95% CI, -1.4% to 3.1%; P = 0.47). No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis. This is to date the largest data set studying the effects of antituberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT00216385.).

A four-month gatifloxacin-containing regimen for treating tuberculosis.

BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen. CONCLUSIONS: Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.).

Assessing the economic burden of illness for tuberculosis patients in Benin: determinants and consequences of catastrophic health expenditures and inequities.

OBJECTIVES: To inform policy-making, we measured the risk, causes and consequences of catastrophic expenditures for tuberculosis and investigated potential inequities. METHODS: Between August 2008 and February 2009, a cross-sectional study was conducted among all (245) smear-positive pulmonary tuberculosis patients of six health districts from southern Benin. A standardised survey questionnaire covered the period of time elapsing from onset of tuberculosis symptoms to completion of treatment. Total direct cost exceeding the conventional 10% threshold of annual income was defined as catastrophic and used as principal outcome in a multivariable logistic regression. A sensitivity analysis was performed while varying the thresholds. RESULTS: A pure gradient of direct costs of tuberculosis in relation to income was observed. Incidence (78.1%) and intensity (14.8%) of catastrophic expenditure were high; varying thresholds was insensitive to the intensity. Incurring catastrophic expenditure was independently associated with lower- and middle-income quintiles (adjusted odd ratio (aOR) = 36.2, 95% CI [12.3-106.3] and aOR = 6.4 [2.8-14.6]), adverse pre-diagnosis stage (aOR = 5.4 [2.2-13.3]) and less education (aOR = 4.1[1.9-8.7]). Households incurred important days lost due to TB, indebtedness (37.1%), dissaving (51.0%) and other coping strategies (52.7%). CONCLUSIONS: Catastrophic direct costs and substantial indirect and coping costs may persist under the 'free' tuberculosis diagnosis and treatment strategy, as well as inequities in financial hardship.

A care pathway analysis of tuberculosis patients in benin: Highlights on direct costs and critical stages for an evidence-based decision-making.

BACKGROUND: Free tuberculosis control fail to protect patients from substantial medical and non-medical expenditure, thus a greater degree of disaggregation of patient cost is needed to fully capture their context and inform policymaking. METHODS: A retrospective cross-sectional study was conducted on a convenience sample of six health districts of Southern Benin. From August 2008 to February 2009, we recruited all smear-positive pulmonary tuberculosis patients treated under the national strategy in the selected districts. Direct out-of-pocket costs associated with tuberculosis, time delays, and care-seeking pattern were collected from symptom onset to end of treatment. RESULTS: Population description and outcome data were reported for 245 patients of whom 153 completed their care pathway. For them, the median overall direct cost was USD 183 per patient. Payments to traditional healers, self-medication drugs, travel, and food expenditures contributed largely to this cost burden. Patient, provider, and treatment delays were also reported. Pre-diagnosis and intensive treatment stages were the most critical stages, with median expenditure of USD 43 per patient and accounting for 38% and 29% of the overall direct cost, respectively. However, financial barriers differed depending on whether the patient lived in urban or rural areas. CONCLUSIONS: This study delivers new evidence about bottlenecks encountered during the TB care pathway. Financial barriers to accessing the free-of-charge tuberculosis control strategy in Benin remain substantial for low-income households. Irregular time delays and hidden costs, often generated by multiple visits to various care providers, impair appropriate patient pathways. Particular attention should be paid to pre-diagnosis and intensive treatment. Cost assessment and combined targeted interventions embodied by a patient-centered approach on the specific critical stages would likely deliver better program outcomes.

Facteurs associes a l'asthme severe chez les patients asthmatiques suivis au Centre National Hospitalier de Pneumo-phtisiologie de Cotonou (Benin) en 2014

Introduction: la presente etude vise a determiner la frequence de l'asthme severe chez les patients asthmatiques suivis au Centre National Hospitalier de Pneumo-Phtisiologie (CNHPP) de Cotonou et identifier les facteurs de risque qui lui sont associes. Methodes: l'etude transversale; descriptive et analytique a porte sur 213 patients asthmatiques de la file active 2013 du CNHPP. Les donnees ont ete collectees par l'exploitation des dossiers et l'entretien individuel avec les patients. Elles ont ete traitees et analysees a l'aide des logiciels EPIINFO7 et STATA11. Le test Chi2 de Pearson; la regression logistique uni variee et multi variee ont ete utilises au seuil de signification de 0;05. Resultats: au total; 154 patients asthmatiques soit 72;7% ont repondu au questionnaire. Parmi eux 20;8% (IC95% :(14;67 ; 28;05)) souffraient d'asthme severe. L'age des patients s'etendait de 10 a 76 ans avec une mediane de 41 ans; 51;3% etaient de sexe feminin; 79;9% avaient des antecedents d'allergie; 61;7% ont commence leur asthme apres l'age de 12 ans et seuls 11% ont consomme ou consommaient du tabac. Les facteurs associes a la survenue de l'asthme severe etaient : l'age de 46 a 55 ans (p = 0;04) ; les troisieme et quatrieme quintiles du bien-etre economique (p = 0;01) et le debut de l'asthme apres l'age de 12 ans (p 0;001). Conclusion: l'etude a montre une frequence elevee de l'asthme severe au Benin et permettra d'ameliorer sa prise en charge au CNHPP