Impact of integrated psycho-socio-economic support on treatment outcome in drug resistant tuberculosis - A retrospective cohort study.

OBJECTIVE: To assess the impact of providing integrated psycho-socio-economic support to drug resistant tuberculosis (DRTB) patients on the treatment outcome under programmatic conditions. STUDY DESIGN: Retrospective cohort study. SETTING: An urban district TB centre in India under the Revised National Tuberculosis Control Programme. PARTICIPANTS: A cohort of 123 patients who started DRTB treatment between June 2010 and May 2013. METHODS: Patients started on treatment for DRTB between June 2010 and May 2013 who were provided with the integrated support package for at least 3 months formed the supported group while the other patients of the cohort formed the non-supported group. The treatment outcomes and sputum culture conversion rates were compared between the two groups. RESULTS: The supported group consisted of 60 patients and the non-supported group of 63 patients. The treatment success rate was found to be significantly higher in the supported group (65% vs 46.03%; p=0.0349). Support duration was significantly associated with lower incidence of death [HR 0.876, 95% CI 0.811-0.947; p=0.0009] and loss to follow up [OR: 0.752, 95% CI 0.597-0.873; p=0.0023]. The treatment failure rate was higher in the supported group (16.66% vs 4.76%) with 60% of the failures in the supported group occurring after 24 months of compliant treatment. There was no significant association found between support duration and treatment failure or sputum culture conversion. CONCLUSION: Integrated support seems to significantly increase the treatment success rate and improve survival and treatment adherence of DRTB patients. However, early diagnosis and effective pharmacotherapy are crucial for reducing treatment failures.

Efficacy of alternate day Directly Observed Treatment Short-course (DOTS) in skeletal tuberculosis - A retrospective study.

OBJECTIVE: To assess the efficacy of alternate day (thrice a week) Directly Observed Treatment Short-course (DOTS) regimen spanning six to nine months in providing sustained cure for skeletal tuberculosis (TB) under programmatic conditions. DESIGN: Retrospective cohort study. SETTING: An urban district tuberculosis centre in India under the Revised National Tuberculosis Programme. PARTICIPANTS: A cohort of 218 patients treated with alternate day DOTS regimen for skeletal TB between 2007 and 2012. METHODS: All patients with the diagnosis of skeletal TB registered between 2007 and 2012 who successfully completed treatment were followed up for evidence of disease recurrence or relapse using structured interviews conducted between August 2013 and October 2015 after ensuring a minimum follow up of two years. RESULTS: Of the 200 patients eligible for follow up in this study, 117 (58.5%) had a minimum follow up of two years. The remaining 83 cases could not be traced. 105 (89.7%) of these 117 patients were symptom free for two years or more after the completion of treatment. There were four cases who had a relapse of the disease within two years of completion of treatment. Eight cases were administered further ATT soon after the completion of treatment under DOTS. CONCLUSIONS: This study confirms the efficacy of the alternate day DOTS regimen in successfully treating all forms of skeletal TB, including spinal TB, with a success rate of 89.7%.

Induction of apoptosis using inhibitors of lysophosphatidic acid acyltransferase-beta and anti-CD20 monoclonal antibodies for treatment of human non-Hodgkin's lymphomas.

PURPOSE: Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is a transmembrane enzyme critical for the biosynthesis of phosphoglycerides whose product, phosphatidic acid, plays a key role in raf and AKT/mTor-mediated signal transduction. EXPERIMENTAL DESIGN: LPAAT-beta may be a novel target for anticancer therapy, and, thus, we examined the effects of a series of inhibitors of LPAAT-beta on multiple human non-Hodgkin's lymphoma cell lines in vitro and in vivo. RESULTS: We showed that five LPAAT-beta inhibitors at doses of 500 nmol/L routinely inhibited growth in a panel of human lymphoma cell lines in vitro by >90%, as measured by [3H]thymidine incorporation. Apoptotic effects of the LPAAT-beta inhibitors were evaluated either alone or in combination with the anti-CD20 antibody, Rituximab. The LPAAT-beta inhibitors induced caspase-mediated apoptosis at 50 to 100 nmol/L in up to 90% of non-Hodgkin's lymphoma cells. The combination of Rituximab and an LPAAT-beta inhibitor resulted in a 2-fold increase in apoptosis compared with either agent alone. To assess the combination of Rituximab and a LPAAT-beta inhibitor in vivo, groups of athymic mice bearing s.c. human Ramos lymphoma xenografts were treated with the LPAAT-beta inhibitor CT-32228 i.p. (75 mg/kg) daily for 5 d/wk x 4 weeks (total 20 doses), Rituximab i.p. (10 mg/kg) weekly x 4 weeks (4 doses total), or CT-32228 plus Rituximab combined. Treatment with either CT-32228 or Rituximab alone showed an approximate 50% xenograft growth delay; however, complete responses were only observed when the two agents were delivered together. CONCLUSIONS: These data suggest that Rituximab, combined with a LPAAT-beta inhibitor, may provide enhanced therapeutic effects through apoptotic mechanisms.

Epidemiological features of skeletal tuberculosis at an urban district tuberculosis centre.

Skeletal tuberculosis is an important component of extra-pulmonary tuberculosis. It can lead to substantial morbidity and poses serious occupational and economic problem. We conducted a study in an urban District Tuberculosis Centre (DTC) to assess the burden and distribution of skeletal tuberculosis in the community. Our centre was catering to a population of 6-7 lakhs between 2007 and 2012. During this period, we treated 11,274 cases of tuberculosis. Out of these, 3086 (27.3%) were cases of extrapulmonary tuberculosis and 219 (1.94%) were cases of skeletal tuberculosis. Skeletal TB predominantly affects the young Indian population with incidence peaking in the second and third decades of life. 172 patients (78.5%) in our study were new cases. There were no drugs resistant (DRTB) skeletal TB cases till we concluded our study. Tuberculosis commonly involves joints more than long bones. The spinal column was the most commonly involved skeletal site affecting 62.6% of all cases. The rate of spinal TB in our study is much higher than that reported in literature. The high number of patients calls for close co-ordination between managing orthopaedic surgeons, treating physicians and DOT providers to ensure adequate patient care.

Synthesis and in vivo antitumor activity of poly(l-glutamic acid) conjugates of 20S-camptothecin.

Poly-alpha-(l-glutamic acid) (PG) conjugates of 20(S)-camptothecin (1, CPT) displayed improved aqueous solubility compared to CPT, were stable in aqueous solution at neutral pH, and were potent antitumor agents in vivo. Evaluation of PG molecular weight, CPT loading, aqueous solubility, and CPT equivalent dosing with respect to in vivo antitumor potencies of various linked conjugates led to identification of a preferred conjugate composition.

Synthesis, SAR, and antitumor properties of diamino-C,N-diarylpyrimidine positional isomers: inhibitors of lysophosphatidic acid acyltransferase-beta.

2,4-Diamino-N(4),6-diarylpyrimidines were identified as potent, isoform specific inhibitors of lysophosphatidic acid acyltransferase-beta (LPAAT-beta). Active inhibitors also blocked proliferation of tumor cell lines in vitro. The effect of 2j in an in vivo tumor model was investigated.