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V K Arora

Publications and source records attributed to V K Arora.

At least 19 recordsLinked to original sources

Cost and cost-effectiveness of PPM-DOTS for tuberculosis control: evidence from India.

OBJECTIVE: To assess the cost and cost-effectiveness of the Public-Private Mix DOTS (PPM-DOTS) strategy for tuberculosis (TB) control in India. METHODS: We collected data on the costs and effects of pilot PPM-DOTS projects in Delhi and Hyderabad using documentary data and interviews. The cost of PPM-DOTS was compared with public sector DOTS (i.e. DOTS delivered through public sector facilities only) and non-DOTS treatment in the private sector. Costs for 2002 in US$ were assessed for the public sector, private practitioners, and patients/attendants. Effectiveness was measured as the number of cases successfully treated. FINDINGS: The average cost per patient treated was US$ 111-123 for PPM-DOTS and public sector DOTS, and US$ 111-172 for non-DOTS treatment in the private sector. From the public sector's perspective, the cost per patient treated was lower in PPM-DOTS projects than in public sector DOTS programmes (US$ 24-33 versus US$ 63). DOTS implementation in either the public or private sectors improved treatment outcomes and substantially lowered costs incurred by patients and their attendants, compared to non-DOTS treatment in the private sector (US$ 50-60 for DOTS compared to over US$ 100 for non-DOTS). The average cost-effectiveness of PPM-DOTS and public sector DOTS was similar, at US$ 120-140 per patient successfully treated, compared to US$ 218-338 for non-DOTS private sector treatment. Incremental cost-effectiveness analysis showed that PPM-DOTS can improve effectiveness while also lowering costs. CONCLUSION: PPM-DOTS can be an affordable and cost-effective approach to improving TB control in India, and can substantially lower the economic burden of TB for patients.

Cost-Benefit Analysis↗

Comparative cytomorphology of skin, lymph node, liver and bone marrow in patients with lepromatous leprosy.

OBJECTIVE: The aim of this study was to compare the cytological changes in skin, lymph nodes, liver and bone marrow in patients with lepromatous leprosy. METHODS: Skin lesion, lymph node, liver and bone marrow aspirates were analysed. May-Grunwald-Giemsa (MGG) and Ziehl-Neelsen (Z-N) stains were employed. Comparative cytomorphology was studied. RESULTS: Twenty patients with lepromatous leprosy were studied. Lepra cells (LC) predominated in the skin aspirates of 12 patients with lepromatous leprosy (LL), lymphocytes accompanied LC in eight patients with borderline-lepromatous (BL) leprosy. Three patients of LL leprosy and two of BL leprosy in type 2 reaction additionally had numerous neutrophils. Two patterns of lymph node aspirates were seen: partial replacement with few LC in a reactive lymphoid background (10), complete replacement with either only LC or LC in a background of degenerating neutrophils (10), the latter a feature of type 2 reaction. Liver aspiration was performed in seven patients and of bone marrow in eight patients. Occasional LC were present in five liver-aspirated patients, steatosis and Kupffer cell hyperplasia in four patients, and myelopoiesis in two patients. Bone marrow smears invariably had occasional LC and a relative increase in mature plasma cells; sea-blue histiocytes were seen in six patients. CONCLUSION: Lepra cells predominated in skin and lymph node aspirates with complete replacement. In comparison, liver, bone marrow and lymph node aspirates with partial replacement were dominated by a preponderance of cells native to these organs with only few or occasional LC.

Adolescent↗

Performance evaluation of APACHE II score for an Indian patient with respiratory problems.

BACKGROUND & OBJECTIVES: Realising the utility of scoring systems in mortality prediction of critically ill patients admitted to intensive care units (ICUs), studies worldwide have expressed a need to validate the Acute Physiology and Chronic Health Evaluation (APACHE) II score for databases of respective countries. Literature available in this area in the Indian context is scanty. The present study was undertaken to evaluate the performance of APACHE II score in prediction of mortality risk, as well as in determination of model validity in critically ill Indian patients with respiratory problems. METHODS: The study was prospectively carried out over 18 months at respiratory ICU of a tertiary Institute in New Delhi, which admitted consecutive medical (with lung ailments) and surgical (who had undergone any elective thoracic surgical procedure under general anaesthesia) patients. Based on chief indication of ICU admission, the medical patients were further divided into sub-groups I (respiratory) and II (non-respiratory). APACHE II points were assigned to all patients for calculating their individual predicted risks of mortality. Standard mortality ratio (SMR) was computed with 95 per cent confidence intervals (CI). Calibration of model was analysed by calculating Lemeshow and Hosmer goodness of fit X(2) statistic and by plotting calibration curve, whereas discrimination was evaluated by calculating area under a receiver operating characteristic (ROC) curve. RESULTS: Of the 393 consecutive patients admitted to respiratory ICU during the study period, 63 were left out on account of exclusion criteria. Mean APACHE II score of the remaining 330 patients was 12.87+/-8.25 and range from 1 to 47. There were 287 (87%) survivors and 43 (13%) non-survivors, whose mean APACHE II scores, being respectively 11.34+/-6.75 (range 1-37) and 23.09+/-10.01 (range 5-47), were significantly different (P<0.01). The study had a predicted mortality of 7.9 per cent and an SMR value of 1.65 (95% CI from 0.4 to 3.0). Mean APACHE II score of those having medical ailments was significantly higher (P<0.01) than surgical patients. The non-respiratory sub-group had a significantly higher (P<0.01) mean APACHE II score than respiratory sub-group. 59 per cent of patients did not get APACHE II points owing to being <45 yr of age. In addition, against 10 immunocompromised patients, 77 others did not get APACHE II points despite having apparently compromised immunity due to co-existence of tuberculosis (TB), diabetes mellitus, dual pathologies or past history of anti-TB treatment. Observed and predicted mortality rose with 5-point APACHE II score, but did not correlate for patients of any comparable group. Average ICU stay of 16 days for those with medical disease was significantly longer (P<0.01) than 9.5 days for surgical patients. APACHE II scoring system showed a poor calibration and discrimination ability for Indian respiratory patients. INTERPRETATION & CONCLUSION: Despite the rise in observed and predicted mortality with 5-point APACHE II score, predicted mortality did not correlate with observed mortality for critically ill patients admitted to an Indian respiratory ICU. The scoring system also showed a poor calibration as well as discrimination. The model may be more useful for Indian patients by lowering down the cut-off value in allotment of age points and by awarding the weightage to factor like co-existing immunocompromised state.

APACHE↗

Directly observed treatment for tuberculosis.

Directly Observed Treatment-Short Course (DOTS) has been a successful strategy in the global control of tuberculosis (TB) in adults. However, reports of implementation are scantily available in pediatric context. Present article reviews diagnostic uncertainties of TB in children commonly faced by physicians on account of the vague clinical presentations, unreliable tuberculin tests or TB score charts, non-specific hematological, biochemical or radiological evidence, difficulty in sputum expectoration and non-availability or ill-affordability of specialised tests. It also describes therapeutic problems arising due to the physician's inexpertise, child's incomprehensibility and parental anxiety. DOTS was found to be highly effective in 930 Indian children having TB over the 6-year study period, during which, a rise in number of cases with adult pattern of disease was also noted. The trend change in pediatric TB scenario is thought to have taken place due to malnutrition so widely prevalent in this country. Irrespective of the changing trend, DOTS strategy was found to be effective for all types of pediatric TB. A need, therefore, exists for quick resolution of the programme issues related to pediatric drug dispensing, physicians' reservations about acceptance of strategy in this age-group, service-utilisation of DOTS providers for the selected cases unable to visit DOTS centres and giving executional priority to children during ongoing expansion of Revised National TB Control Programme (RNTCP) in country.

Adolescent↗

Adherence to tuberculosis treatment: lessons from the urban setting of Delhi, India.

The Revised National Tuberculosis Control Programme (RNTCP), which incorporated the WHO DOTS strategy was introduced in India in the mid-1990s. An operational research project was conducted between 1996 and 1998 to assess the needs and perspectives of patients and providers in two chest clinics in Delhi, Moti Nagar and Nehru Nagar, during the introduction of the new strategy. This paper reports on the findings of the project, concentrating on information collected from 40 in-depth interviews with patient defaulters and from non-participant observations in clinics and directly observed treatment centres. In Moti Nagar chest clinic, 117 of 1786 (6.5%) patients and 195 of 1890 (10%) patients in Nehru Nagar left care before their treatment was complete. It was argued that the reasons for default stem from a poor correlation between patient and programme needs and priorities, and from particular characteristics of the disease and its treatment. Patient needs that were not met by the health system included convenient clinic timings, arrangements for the provision for treatment in the event of a family emergency and provision for complicated cases like alcoholics. The problems facing the provider were poor interpersonal communication with the health staff, lack of attention and support at the clinic, difficulty for patients to re-enter the system if they missed treatment and, in certain areas, long distances to the clinic. Problems related to diseases were inability of the staff to deal with drug side-effects, and patients' conception of equating well-being with cure. Simple, practical measures could improve the provision of tuberculosis (TB) treatment: more flexible hours, allowances for poor patients to reach the clinics and training health care staff for respectful communication and monitoring drug side-effects. The findings indicate a need to rethink the label of 'defaulter' often given to the patients. The important areas for future operational research is also highlighted.

Adolescent↗

Feasibility and effectiveness of a public-private mix project for improved TB control in Delhi, India.

SETTING: New Delhi, India. OBJECTIVE: To assess the feasibility of a public-private mix (PPM) project for improved tuberculosis (TB) control and determine its impact on case detection, case-management quality, treatment outcome and patient convenience. DESIGN: 1) Monitoring of case detection through the review of record data; 2) cohort analysis of patients treated by private providers (PPs); 3) questionnaire-based surveys of patients and private providers. RESULTS: A total of 612 cases were detected, of whom 168 (27%) were new sputum-positive cases. Incremental case notification due to PPs was 47% for new cases and 29% for new sputum-positive cases. Sputum examination for diagnosis and evaluation was performed in 100% and 84%, respectively, of notified patients. The treatment success rate for new sputum-positive cases treated by PPs was 81%, which was not significantly different from the 86% in the public sector. Directly observed treatment (DOT) was confirmed by 95% of patients. CONCLUSIONS: This PPM project, carried out with government funding in accordance with the RNTCP recommendations and with the support from several government and private organisations, achieved improved case detection as well as acceptable treatment outcome for patients receiving DOT from PPs.

Adolescent↗

TB control, poverty, and vulnerability in Delhi, India.

The Revised National Tuberculosis Control Programme (RNTCP), based on the World Health Organization's DOTS strategy,* was introduced in India in the mid-1990s. This paper reports the findings from operational research studies in two pilot sites in New Delhi from 1996 to 1998. A variety of operational research methods were used, including semi-structured interviews, focus group discussions, non-participant observations and collection of data from the tuberculosis registers. The cure rates for the clinics were 71 and 75% with a default rate of 6 and 11%, respectively. An important finding was that health workers screened patients to determine their ability to conform to the direct observation of treatment element of the RNTCP. If the health worker was confident that the patient would comply and/or be easy to trace in the community in the event of 'default', they were provided with short-course treatment under the RNTCP. Other patients, largely those who were in absolute poverty, socially marginalized, itinerant labourers, poorly integrated in the city, were put on standard tuberculosis (TB) treatment as for the previous National TB Programme. The programme was evidently excluding the most vulnerable from the best available care. These findings demonstrate the potential dangers of target-driven programmes where there is an absence of support to both frontline health workers and patients. The paper also highlights the importance of operations research in helping to identify problems within TB programmes.

Antitubercular Agents↗

Genetic and functional diversity of human immunodeficiency virus type 1 subtype B Nef primary isolates.

We have characterized the functional integrity of seven primary Nef isolates: five from a long-term nonprogressing human immunodeficiency virus (HIV)-infected individual and one each from two patients with AIDS. One of the seven Nefs was defective for CD4 downregulation, two others were defective for PAK-2 activation, and one Nef was defective for PAK-2 activation and major histocompatibility complex (MHC) class I downregulation. Five of the Nefs were tested and found to be functional for the enhancement of virus particle infectivity. The structural basis for each of the functional defects has been analyzed by constructing a consensus nef, followed by mutational analysis of the variant amino acid residues. Mutations A29V and F193I were deleterious to CD4 downregulation and PAK-2 activation, respectively, while S189R rendered Nef defective for both MHC class I downregulation and PAK-2 activation. A search of the literature identified HIVs from five patients with Nefs predominantly mutated at F193 and from one patient with Nefs predominantly mutated at A29. A29 is highly conserved in all HIV subtypes except for subtype E. F193 is conserved in subtype B (and possibly in the closely related subtype D), but none of the other HIV group M subtypes. Our results suggest that functional distinctions may exist between HIV subtypes.

Acquired Immunodeficiency Syndrome↗

Efficacy and safety of sparfloxacin in combination with kanamycin and ethionamide in multidrug-resistant pulmonary tuberculosis patients: preliminary results.

SETTING: Department of tuberculosis and chest diseases of a tertiary referral tuberculosis institute in New Delhi, India. OBJECTIVE: To study the efficacy and safety of sparfloxacin, in combination with kanamycin (for the initial 3-4 months) and ethionamide, in multidrug-resistant (MDR) pulmonary tuberculosis patients. DESIGN: Prospective, uncontrolled study of nine patients with pulmonary tuberculosis who had received adequate anti-tuberculosis treatment with first-line drugs, including supervised category II treatment regimen as per World Health Organization guidelines for 5 months, and were still sputum smear acid-fast bacilli positive. It was planned to give them kanamycin (initial 3-4 months), ethionamide and sparfloxacin for 2 years. RESULTS: All nine patients achieved sputum conversion within 6 months. Seven patients converted within 3.5 months, two of these within 1 month. All patients reported improvement in clinical symptoms, and chest X-ray improved in seven patients. Four patients developed mild to moderate phototoxicity. Eight patients have completed treatment for an average of 19 months (range 15-24 months), and are still under follow-up. One patient defaulted after 7 months of treatment. CONCLUSIONS: In MDR-TB patients, sparfloxacin, along with other anti-tuberculosis drugs, appears to be effective and safe. Mild to moderate phototoxicity is common. However, the long-term results, including relapses, are still awaited.

Adult↗

Quantitative determination of SC-68328 in dog plasma using flow injection and tandem mass spectrometry.

A flow injection/tandem mass spectrometric assay was developed to quantitate SC-68328 in dog plasma using its stable isotopic analog [13C4]SC-68328 as an internal standard (IS). Since SC-68328, a manganese-based superoxide dismutase mimetic, is very unstable, very polar and adheres to silica-based high-performance liquid chromatographic columns, the analyte and IS were derivatized to their bis-isothiocyanate forms followed by a liquid-liquid extraction with methylene chloride and analyzed using positive ion electrospray mass spectrometric detection. SC-68328 was quantitated using the peak-height ratio of SC-68328 to its IS using MS/MS in the multiple reaction monitoring mode. The lower limit of quantitation of the assay was 0.25 microg ml(-1) SC-68328 in dog plasma with an inter-day precision of 11.8% and an accuracy of 113% (n = 12). Acceptable precision and accuracy were also obtained for concentrations in the calibration curve range (0.25-10 microg ml(-1) SC-68328 in dog plasma).

Animals↗

Lentivirus Nef specifically activates Pak2.

Nef proteins from human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have been found to associate with an active cellular serine/threonine kinase designated Nef-associated kinase (Nak). The exact identity of Nak remains controversial, with two recent studies indicating that Nak may be either Pak1 or Pak2. In this study, we investigated the hypothesis that such discrepancies arise from the use of different Nef alleles or different cell types by individual investigators. We first confirm that Pak2 but not Pak1 is cleaved by caspase 3 in vitro and then demonstrate that Nak is caspase 3 sensitive, regardless of Nef allele or cell type used. We tested nef alleles from three lentiviruses (HIV-1 SF2, HIV-1 NL4-3, and SIVmac239) and used multiple cell lines of myeloid, lymphoid, and nonhematopoietic origin to evaluate the identity of Nak. We demonstrate that ectopically expressed Pak2 can substitute for Nak, while ectopically expressed Pak1 cannot. We then show that Nef specifically mediates the robust activation of ectopically expressed Pak2, directly demonstrating that Nef regulates Pak2 activity and does not merely associate with activated Pak2. We report that most of the active Pak2 is found bound to Nef, although a fraction is not. In contrast, only a small amount of Nef is found associated with Pak2. We conclude that Nak is Pak2 and that Nef specifically mediates Pak2 activation in a low-abundance complex. These results will facilitate both the elucidation of the role of Nef in pathogenesis and the development of specific inhibitors of this highly conserved function of Nef.

Alleles↗

Malakoplakia of the appendix. An unusual association with eggs of Taenia species.

Malakoplakia of the appendix is an unusual condition that has been reported to occur in association with tumors, infections, and immunocompromised states. We describe a case of appendicular malakoplakia associated with eggs of Taenia species. The diagnosis was made on histopathologic examination of surgically resected tissue from an appendicular mass. To the best of our knowledge, this is the first time that helminths have been documented to be associated with malakoplakia. We also discuss the implications of helminthic infestation in the pathogenesis of the lesion.

Animals↗