Study of treatment outcomes of multidrug-resistant tuberculosis under programmatic conditions and factors influencing the outcomes in Hyderabad District

BackgroundTreatment outcomes for Multidrug-Resistant Tuberculosis (MDR TB) is generally poor. The study aims to know about the treatment outcomes of MDR-TB under programmatic conditions in Hyderabad District and to analyze the factors influencing the treatment outcomes.MethodsThis is a retrospective study in which 377 patients of Hyderabad district, Telangana state who were diagnosed with MDR TB and registered at Drug Resistance TB Treatment site of Government General & Chest Hospital, Hyderabad from 4th quarter 2008 to 4th quarter 2013 were included in the study. Impact of Demographic factors (age, sex; Nutritional status (BMI); Co-morbid condition (Diabetes, HIV, Hypothyroidism); Programmatic factors (time delay in the initiation of treatment); Initial Resistance pattern on the outcomes were studied and analyzed.ResultsThe treatment outcomes of Multidrug-Resistant Tuberculosis under Programmatic Conditions were: 57% cured, 21.8% died, 19.6% defaulted, 1.1% failed and 0.5% switched to XDR. Age, Sex, BMI had a statistically significant impact on treatment outcomes. Hypothyroidism and Delay in the initiation of treatment >1 a month had an impact on the outcomes though not statistically significant. NO impact on treatment outcomes was found when Rifampicin resistance & INH sensitive patients were compared with those resistant to both INH and Rifampicin.ConclusionTo reduce MDR-TB transmission in the community, improvement of treatment outcomes, via ensuring adherence, paying special attention to elderly patients is required. The Programmatic Management of Drug Resistance Tuberculosis (PMDT) should seriously think of providing Nutritional support to patients with low BMI to improve outcomes. In the programmatic conditions if we could address the problems like delay in initiation of treatment and proper management of comorbidities like HIV, Diabetes, Hypothyroidism would definitely improve the treatment outcomes.     

Adsorption and sensing of CO and NH3 on chemically modified graphene surfaces

We have studied the electronic structure and adsorption characteristics of environmentally potent gaseous molecules like carbon monoxide (CO) and ammonia (NH₃) on chemically modified surfaces of graphene, employing ab initio density functional methods. An insight into the changes made in the electronic band structure due to intrinsic and extrinsic doping and through a combined effect of both is discussed. With this regard, the adsorption of these gaseous moieties is investigated on substitutionally p- and n- doped graphene surfaces, doped with various mole fractions and having different configurational patterns on the surface. Even though the electronic properties are modified with various mole fractions of doping they do not show a methodical increase with the increase in the dopant concentration. This is attributed to the sub-lattice induced symmetry breaking for the dopant configurations where equivalent lattice sites are occupied on the surface. An appreciable band gap opening of around 0.63 eV is observed on doping, due to sub-lattice symmetry breaking. This is further improved on molecular doping, with CO and NH₃, where an increase up to 0.83 eV is noted with adsorption of ammonia. While both the molecules are physisorbed on nitrogen doped surfaces, carbon monoxide is strongly physisorbed and ammonia molecules are chemisorbed on a few boron doped surfaces resulting in notable changes in the adsorption energy. Therefore, it is clear that changes in the transport properties can be brought about by adsorption of these molecules on such surfaces and this study clearly indicates the invaluable prospects of such doped surfaces as potential sensors for these molecules.

We have studied the electronic structure and adsorption characteristics of environmentally potent gaseous molecules like carbon monoxide (CO) and ammonia (NH₃) on chemically modified surfaces of graphene, employing ab initio density functional methods.     

Kinetics and Characterization of Non-enzymatic Fragmentation of Monoclonal Antibody Therapeutics

Purpose

To understand non-enzymatic hydrolytic fragmentation of a monoclonal antibody therapeutic under temperature stressed conditions and investigating possible mechanism for the same.

Methods

The mAb therapeutic was incubated at 50°C in phosphate buffer at pH 6.5 and fragmentation was monitored at different ionic strengths under stressed conditions. The incubated mAb was sampled at regular time intervals by analytical Size Exclusion Chromatography (SEC).

Results

It was observed that 57% of the mAb product fragmented over 4 days into two fragment species – Fc-Fab and Fab with molecular weights of 97 KDa and 47 KDa, respectively, as measured by mass spectrometry (MS) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The fragmentation rate was slow initially and then accelerated with time. No change in % aggregate level was observed in this duration, implying that degradation was primarily via fragmentation at high temperature. Kinetics of hydrolytic fragmentation was hypothesized and SEC data was fitted to estimate the kinetic rate constants. While degradation of the monomer into fragment species was non-Arrhenius with a negative activation energy, further degradation of Fab-Fc fragments into Fab or Fc fragments followed Arrhenius Law with an activation energy of 2.1 and 15.38 kcal/mol, respectively.

Conclusion

High temperature (50°C) causes mAb to cleave at the hinge region to form Fab-Fc and Fab/Fc, as confirmed by dynamic light scattering, SDS-PAGE, SEC, and MS. A kinetic model for hydrolytic fragmentation has been proposed. The results are expected to assist end users in formulation development as well as in monitoring stability of biotherapeutic products.

     

Intravesical botulinum toxin A injections in the treatment of painful bladder syndrome/interstitial cystitis: a systematic review

Introduction and hypothesis  

Intravesical botulinum toxin A (BTX-A) is emerging as a potential new treatment for refractory interstitial cystitis (IC). However, there has been conflicting evidence on this treatment's effectiveness. The aim of our systematic review was to assess the effectiveness and adverse effects of intravesical BTX-A in IC.     

Development and Evaluation of Patient Information Leaflets (PIL) Usefulness

A prospective study was conducted to develop, validate and assess the usefulness of the patient information leaflets for selected diseases among the patient population. Flesch readability ease score, Baker Able leaflet design criteria were applied to develop the patient information leaflets. The leaflets were validated for both content and translation. Eligible patients meeting the study criteria were enrolled in the study. Suitably designed knowledge, attitude and practice questionnaire was administered at base line followed by patient education complimented with an information leaflet. After a month, knowledge, attitude and practice questionnaire was administered once again to assess the influence of education and usefulness of patient information leaflets on knowledge, attitude and practice scores. The mean readability score of the information leaflets is 80 and Baker Able leaflet design criteria score is 22. Post education knowledge, attitude and practice scores were significantly (P<0.0001) improved in all the enrolled patients in all disease. The study concludes that patient education complemented with suitably designed information leaflet has greater impact on knowledge, attitude and practice of the patients towards their disease management.     

Discovery and Structure Optimization of a Series of Isatin Derivatives as Mycobacterium tuberculosis Chorismate Mutase Inhibitors

In this study, the crystal structure of the Mycobacterium tuberculosis (MTB) enzyme chorismate mutase (CM) bound to transition state analogue (PDB: 2FP2) was used as a framework for virtual screening of the BITS‐Pilani in‐house database (2500 compounds) to identify new scaffold. We identified isatin as novel small molecule MTB CM inhibitors; further twenty‐four isatin derivatives were synthesized and evaluated in vitro for their ability to inhibit MTB CM, and activity against M. tuberculosis as steps towards the derivation of structure–activity relationships (SAR) and lead optimization. Compound 3‐(4‐nitrobenzylidene)indolin‐2‐one, 24 emerged as the most promising lead with an IC₅₀ of 1.01 ± 0.22 μm for purified CM and MIC of 23.5 μm for M. tuberculosis, with little or no cytotoxicity.     

Development, validation and implementation of continuous professional development programmes for community pharmacists

In India, structured continuous professional development modules are not available to update the knowledge and skills of the practicing community pharmacists. A prospective study was designed to develop, validate and implement continuous professional development modules and to assess the impact of training programme on knowledge and skills of community pharmacists. Modules were developed by referring to standard texts and data bases and were validated for the content. The impact of training programme on pharmacists' knowledge and skills was assessed using suitably designed pre and post training knowledge attitude and practice questionnaires, pre and post training questionnaires for individual continuous professional development training sessions, pre and post training patient counseling skill assessment, blood pressure measurement skill assessment and capillary blood glucose check-up skill assessment check-lists. Data was analyzed by applying suitable statistical methods using InStat version 3.01 statistical software. Fourty eight community pharmacists were enrolled in to the study. A statistically significant (P<0.05) improvement was observed in post training knowledge attitude and practice scores and in post training scores of individual training sessions. A statistically significant (P<0.05) improvement was also observed in post training scores of professional skills such as Patient counseling, capillary blood glucose recording and blood pressure measurement skills. The study findings conclude that continuous training updates the knowledge and skills in practicing the pharmaceutical care in their pharmacies.     

Synthesis of a high-surface area V2O5/TiO2–SiO2 catalyst and its application in the visible light photocatalytic degradation of methylene blue

In the present study, we synthesized several high-surface area V₂O₅/TiO₂–SiO₂ catalysts (vanado titanium silicate, VTS). The synthesized materials were characterized by PXRD, FE-SEM/EDAX, TEM, FTIR, UV-Vis, XPS, fluorescence and photocatalytic activity studies. The small-angle powder X-ray diffraction pattern shows that the 110 and 200 planes are merged to become a single broad peak. Field-emission scanning electron microscopy shows that the titanosilicate is spherical in shape and V₂O₅ has a hexagonal rod-shaped morphology. The presence of various metal ions, such as V, Ti, Si and O, was observed by energy dispersive X-ray analysis and X-ray photoelectron spectroscopy. The transmission electron microscopy image shows clear hexagonal mesoporous fringes with V₂O₅ distribution. The BET surface area analysis shows that the VTS catalysts have higher surface areas than pure V₂O₅. Fourier transform infrared spectroscopic analysis shows the presence of Ti⁴⁺ ions connected to the silanol groups. The bandwidths of pure titanosilicate, V₂O₅ and their composites were calculated from their diffuse reflectance ultraviolet-visible spectra. The bandwidth was tuned by heterojunctions in the studied catalysts. The photoluminescence spectra of the VTS catalysts show a distinct behaviour as compared to those of the pure components. The photocatalytic activity of methylene blue degradation was determined with pure constituents and catalysts. VTS-1 (TS and VO weight ratio 2 : 1) shows higher conversion than other catalysts, pure titanosilicate and V₂O₅. This is probably due to the heterojunctions and higher surface area in VTS-1. Kinetic studies reveal that direct sunlight shows higher activity than pure visible light. A plausible physical and chemical mechanism for the photocatalytic activity is proposed.

In the present study, we synthesized several high-surface area V₂O₅/TiO₂–SiO₂ catalysts (vanado titanium silicate, VTS). The synthesized materials are characterized by PXRD, FE-SEM/EDAX, TEM, BET-surface area, FT-IR, UV-Vis, XPS, fluorescence and photocatalytic studies.