Tuberculosis knowledge and awareness in tribal-dominant districts of Jharkhand, India: implications for ACSM.

SETTING: Forty hard-to-reach villages in the East and West Singhbhum Districts of Jharkhand State, India. OBJECTIVES: To document knowledge and awareness of tuberculosis (TB) among the general population, understand gender differences and inform intervention activities for the improvement of TB control programmes in tribal-dominant hard-to-reach areas in India. DESIGN: A cross-sectional community-based survey was carried out among 825 respondents using population proportionate sampling. RESULTS: Most of the respondents were in the 18-35 years age group, tribal and married; 44% were illiterate. The study shows poor knowledge about TB symptoms, causes, modes of transmission and moderate awareness about government TB services. Correct knowledge about the cause of TB was negligible: half of the respondents reported local liquor as the cause, 61% considered TB as transmissible and one third considered sharing of food as the mode of transmission. Awareness about the availability of free treatment services at government health facilities was high, but awareness about DOTS was low. Significant gender differences were observed in knowledge and awareness levels. CONCLUSION: Study findings point to the importance of urgent intensification of culturally congruent and gender-sensitive advocacy, communication and social mobilisation activities.

Contexte : Quarante villages difficiles d'accès de l'Est et de l'Ouest des districts de l'état de Singhbhum, Jharkhand, Inde.Objectifs : Documenter les niveaux de connaissances et de sensibilisation en matière de la tuberculose (TB) parmi les membres de la communauté, de comprendre les différences entre les sexes et de contribuer à l'élaboration d'activités d'intervention afin d'améliorer le programme de lutte contre la TB dans des zones à dominante tribale difficiles d'accès en Inde.Schéma : Une enquête transversale à base communautaire a été réalisée auprès de 825 répondants grâce à une méthode d'échantillonnage proportionnel de la population.Résultats : La majorité des répondants appartenait à la tranche d'âge 18­35 ans, à une minorité ethnique et étaient mariés ; 44% étaient illettrés. L'étude a montré une faible connaissance des symptômes, causes et modes de transmission de la TB et une connaissance modérée des services gouvernementaux de TB. Les connaissances relatives à la cause exacte de la TB était négligeables­la moitié des répondants a attribué la TB à la consommation d'alcool local ; 61% savaient que la TB était transmissible et un tiers affirmait que le partage de nourriture était une voie de transmission. La connaissance de la disponibilité de services gratuits de prise en charge dans des structures de santé étatiques était élevée, mais la stratégie DOTS était très mal connue. Des différences significatives entre les sexes ont été observées en matière de niveau de connaissance et de sensibilisation.Conclusion : Les résultats de l'étude soulignaient l'importance d'une intensification urgente des activités de plaidoyer, de communication et de mobilisation sociale culturellement adaptées et spécifiques au genre.

Marco de referencia: Cuarenta poblaciones de difícil acceso de los distritos de Singhbhum oriental y occidental en el estado de Jharkhand de la India.Objetivos: Documentar los conocimientos y la sensibilización en materia de tuberculosis (TB) de los miembros de la comunidad general, comprender las diferencias asociadas con el sexo y aportar recomendaciones a la formulación de intervenciones destinadas a mejorar el programa contra la TB en las zonas de difícil acceso con predominio de población tribal, en la India.Método: Se llevó a cabo una encuesta transversal comunitaria a 825 personas escogidas mediante un muestreo proporcional a la población.Resultados: La mayoría de las personas que respondieron a la encuesta se encontraba en el grupo etario de 18 años a 35 años, pertenecía a un grupo tribal y su estado civil era casado; el 44% era analfabeto. El estudio puso en evidencia un conocimiento precario de la TB con relación a los síntomas, las causas y los modos de transmisión y una sensibilización moderada a la existencia de servicios gubernamentales de atención de la TB. El grado de conocimientos sobre causa real de la TB era exiguo, pues en la mitad de las respuestas se atribuía la TB al consumo de un licor local. El 61% de quienes respondieron consideraba que la enfermedad era contagiosa y un tercio atribuía el modo transmisión al hecho de compartir los alimentos. Se observó un alto grado de conocimiento de la existencia de servicios de tratamiento sin costo en las instituciones públicas de salud, pero pocos conocían la estrategia DOTS. Se observaron diferencias notables entre los sexos en materia de conocimientos y sensibilización.Conclusión: Los resultados del estudio destacan la urgencia de intensificar las actividades de promoción, comunicación y movilización social que sean culturalmente adaptadas y tomen en consideración las diferencias entre los sexos.

The efficacy and tolerability of a sunitinib 3-week administration schedule in metastatic renal cell carcinoma patients: report of three cases.

Sunitinib, an orally multitargeted tyrosine kinase inhibitor and standard first-line treatment for metastatic renal cell carcinoma, is usually administered on a 6-week schedule. Toxicities reported with this drug are usually of moderate grade, which results in good treatment tolerability and patients' compliance. However, in some cases high-grade or prolonged toxicities require temporary treatment interruption or dose adjustment, possibly resulting in reduced treatment efficacy. We describe three cases of metastatic renal cell carcinoma patients (a 53-year-old male, a 70-year-old woman, and a 65-year-old woman) who received a shortened 3-week sunitinib administration schedule, 2 weeks daily administration followed by 1 week of rest (2/1) due to toxicities developed on the classic 6-week schedule, which would have required a temporary treatment interruption or a dose reduction. Treatment was generally well tolerated with manageable toxicities. A 3-week administration schedule of sunitinib may represent a valid alternative for managing toxicity while maintaining the planned dose intensity over a 6-weeks period of time. Sunitinib may thus be administered using a flexible dosing schedule to meet individual patient needs, achieving better tolerability and maintaining significant response to treatment.

Response and safety of sunitinib in a heavily pre-treated metastatic non-small cell lung carcinoma patient.

BACKGROUND: The activity of sunitinib, a multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activities, has been explored in several solid malignancies such as breast, lung, prostate and pancreatic cancer. Currently it is approved for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Non-small cell lung cancer usually presents at an advanced or metastatic stage at diagnosis. Treatment options are limited for this disease, therefore symptom palliation and patient's quality of life are primary objectives of therapy. CASE REPORT: We describe the case of a patient (male, 67 years old) with heavily pre-treated metastatic non-small cell lung carcinoma who received sunitinib according to the following 3-week schedule: 50 mg daily for 2 weeks followed by a 1-week rest. The patient completed six months of therapy achieving a major disease response without high-grade toxicities. CONCLUSION: In this case, sunitinib shows promising single-agent activity in pretreated non-small cell lung cancer, with a good toxicity profile and flexible administration schedule.

Gemcitabine plus irinotecan as first-line weekly therapy in locally advanced and/or metastatic pancreatic cancer.

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.

Weekly administration of docetaxel and epirubicin as first-line treatment for hormone-refractory prostate carcinoma.

Androgen-independent prostate carcinoma (AICP) is one of the tumors that continue to respond poorly to chemotherapy. Recently, protocols based on the use of docetaxel have significantly improved survival for patients in this disease. In other types of neoplastic disease, combined therapy with taxanes and anthracycline derivatives has been shown to produce additive effects in terms of growth inhibition, and superior tolerability when associated with weekly administration schedules. These findings prompted us to examine the tolerability and efficacy of weekly treatment of AICP with docetaxel (DOX) plus epirubicin (EPI). We enrolled 35 chemotherapy-naive men with AICP (mean age 72 years, range 68-77) and normal hepatic, renal, and cardiac function. The chemotherapy protocol provided for the IV administration of DOX (30 mg/m2) and EPI (30 mg/m2) on days 1, 8, and 15 every 28 days. Treatment was continued for 6 months or until disease progression and/or unacceptable toxicity was observed. Serum levels of prostate-specific antigen (PSA) were monitored in all patients, and reductions from baseline values of >50% were considered indicative of positive responses to treatment. Thirty-four patients were included in the analysis of toxicity, and objective responses to treatment were assessed in the 28 patients with measurable lesions. Nineteen patients (56%) experienced PSA reductions of >50% that persisted for more than 4 weeks. The response to therapy was classified as complete in 1 of the 28 patients (4%) with measurable disease (at the lymph node level). Thirteen others (13/28, 46%) had partial responses, in nine (32%) the disease remained unchanged, and progression was observed in the remaining five (18%); overall response rate was 50% (CR + PR). Of the 27 patients with pain at the time of enrollment, 16 (59%) experienced pain reduction during treatment. The median time to disease progression was 11.7 months (95% CI: 7.7-15.7) while the median survival time was 18.7 months (95% CI: 12.3-25.1). During the study, four patients developed grade 3 anemia and leukopenia, which was reversible in all cases. Lower grades of asthenia, nausea, vomiting, diarrhea, and peripheral edema were also observed. There were no cases of cardiotoxic effects. Alopecia was frequent but reversible in all cases. The results of this preliminary study indicate that the combined administration of DOX and EPI for treatment of AIPC is effective and well tolerated. The weekly administration of the drug combination appears to be a promising approach to the treatment of these tumors.

India's Revised National Tuberculosis Control Programme: looking beyond detection and cure.

SETTING: Pune District, Maharashtra State, India. OBJECTIVES: To examine delays experienced by patients in accessing directly observed treatment. DESIGN: Data were collected from 117 new sputum-positive patients using a semi-structured interview schedule. RESULTS: Patient delays as well as diagnostic and treatment delays, which reflect the performance of a National TB Programme, were minimal. Provider delays, however, contributed significantly to delayed entry into India's Revised National TB Control Programme (RNTCP). Patients had to resort to multiple contacts with providers due to limitations of these providers in diagnosing or directing patients to the RNTCP. Patients who consulted a private provider participating in the public-private mix (PPM) were more likely to be suspected (OR 2.63, 90% CI 1.04-6.64) and referred (OR 6.8, 95%CI 2.08-22.21) to the RNTCP. Once the patients entered the RNTCP, the response of the system was rapid, with diagnosis offered and treatment initiated within on average 7 days. CONCLUSION: Interventions aimed at providers to encourage early suspicion and referral to the RNTCP, such as the PPM, are more important in improving patient access to TB care than those focusing on reducing patient delays.

Once weekly thyroxine treatment as a strategy to treat non-compliance.

Hypothyroidism is a common disorder, which is mainly treated in primary rather than secondary care. Once daily thyroxine replacement restores euthyroidism in most patients; some patients, however, remain hypothyroid despite adequate thyroxine replacement. Non-compliance is the most common cause of lack of response to thyroxine treatment. We describe two cases of primary hypothyroidism in which daily thyroxine treatment did not restore biochemical euthyroidism but once weekly thyroxine treatment was successful. In addition we review the evidence and discuss the differential diagnosis of lack of response to thyroxine treatment. Once weekly thyroxine treatment can be a safe, well-tolerated, and effective therapy for patients with non-compliance.

Grave's Eye disease developing following radioiodine treatment for toxic nodular goitre.

The development of Grave's ophthalmopathy (GO) following radioiodine (RI) treatment for Grave's thyrotoxicosis, though controversial, is well described. The development of ophthalmopathy following RI treatment for toxic nodular goitre is much less recognised. We report a 49 year-old female patient who developed thyrotoxicosis and GO after receiving RI treatment for toxic nodular goitre and we also review the relevant literature.

Tuberculosis control in rural India: lessons from public-private collaboration.

SETTING: A rural tuberculosis (TB) Unit (population 350 794) in Pune district, Maharashtra State, India. OBJECTIVE: To develop a 'model' partnership between rural private medical practitioners (PMPs) and the Revised National Tuberculosis Control Programme (RNTCP). DESIGN: A partnership was developed between 100 PMPs in the study area and the district health and tuberculosis staff through facilitation by a non-governmental organisation (NGO). Participatory research methods were used to plan and implement the partnership. The process of creation and implementation of the partnership was analysed using quantitative and qualitative research methods. RESULTS: The partnership contributed to 30% of the cases detected in the TB Unit over a 5-month period. Six months after withdrawal of the NGO, referrals from the private sector to the RNTCP were continuing to a lesser extent, but there was a breakdown of the communication and documentation systems. CONCLUSION: The project highlights the importance of organisational and individual commitment to these partnerships, the key roles of the District Health Officer and the District Tuberculosis Officer in guiding and supporting these initiatives from the public sector, the potential role of process and outcome 'indicators' in monitoring partnerships and the important role of NGOs as intermediaries and facilitators.

The Mumbai experience in building field level partnerships for DOTS implementation.

In February 1999, the Revised National Tuberculosis (TB) Control Programme (RNTCP) was implemented in the city of Mumbai after a pilot phase of 5 years. The city has a population of more than 12 million people and an estimated annual TB incidence of 21,000 cases, 8000 of these being infectious. This paper describes a partnership between the TB programme and a Non Governmental Organization (NGO), which began with a methodological analysis of the problems faced by the programme to help identify other key organizations, who might usefully be involved. The work focussed on "networking" to ensure the optimum use of existing resources. The problems encountered affected all levels of TB control from access to drug supply and treatment. The major issues related to an inadequate public health infrastructure resulting in poor technical and administrative support to field staff. There was confusion over roles of the health personnel in the TB programme and the public health facility, as well as poor technical performance. Partnerships were found to be useful in addressing the following areas: (1) the implementation of an external quality assurance scheme for sputum microscopy through involvement of microbiologists from large hospitals and research organizations; (2) training and capacity strengthening of programme and public health facility staff through innovative training and team building exercises organized by the programme, NGOs and the private sector; (3) development of Information, Education and Communication (IEC) material through partnerships with NGOs, and (4) the involvement of local NGOs and private doctors to increase case finding and to improve access to direct observation of treatment (DOT). The paper discusses the lessons learnt in this process and identifies some of the key issues in urban TB control, for consideration by policy makers.

Attention to gender issues in tuberculosis control.

Although a seventy per cent excess of male over female TB cases are reported globally each year, the reasons for this difference are unclear. Generally, women in poor countries confront more barriers than men in accessing health care services. Yet, research is lacking to explain the impact of gender inequalities in access to care on reported sex ratios for TB. A review of the limited available literature and field visits to TB programmes offered insights and suggested a framework to study gender differentials in TB. This paper considers the role of gender at various steps in effective TB care. A research strategy to study and account for gender differences in TB control is proposed.

Comparison of three assays for cytomegalovirus detection in AIDS patients at risk for retinitis.

The purpose of this study was to determine the sensitivity and specificity of three different methods of cytomegalovirus (CMV) detection for AIDS patients at risk for CMV retinitis. Patients with CD4(+) counts of <100/microl and negative baseline screening eye examinations were tested for CMV infection by (i) pp65 antigenemia expression in leukocytes, (ii) the Digene Hybrid Capture CMV DNA System, and (iii) the Roche Amplicor Qualitative PCR Test. The incidence of CMV retinitis in our study of 296 patients at the Medical Center of Louisiana-New Orleans HIV Outpatient Clinic was 7. 2 per 100 person-years (a total of 20 episodes in 18 patients from April 1997 to February 1999). Receiver operating characteristic curves were calculated for each assay to determine optimal cutoff points which maximized the sensitivity and specificity of each assay. The sensitivities of the assays compared to the eye examinations were 80% for the pp65 antigenemia assay (cutoff, >0 cell per 1.5 x 10(5) leukocytes), 85% for the Digene assay (cutoff, 1,400 genome copies/ml of whole blood), and 60% for the Amplicor assay. The specificities of the assays were 84, 84, and 87%, respectively. The Digene assay with a cutoff of >/=1,400 genome copies/ml gave optimal sensitivity and specificity and was found to have predictive values equal to those of the more technically cumbersome antigenemia assay.

Shifting the paradigm in tuberculosis control: illustrations from India.

Drawing on literature from India and key contributions from social science, this paper asks and attempts to answer the question 'who is to blame for treatment failures in TB'? Some key lessons emerge: effective tuberculosis control cannot be achieved so long as the disease is considered in isolation from the social processes that maintain it, create the conditions facilitating its spread and act as barriers to care. Insights into the economic and social burdens incurred with a diagnosis of TB are essential to understand why many patients, especially the most disadvantaged, are unable to comply with treatment regimens. TB and health care interventions need to be appropriate to the health service contexts in which they are applied, and sensitive to the competing demands, needs and priorities of people's lives. The paper argues for the need to reorient TB control programmes towards enabling patients to obtain care. The problem of access emerges as central to people's ability to obtain and maintain appropriate therapy. Examples and characteristics of successful non-governmental projects, from which policy makers, programmers and practitioners could learn, are outlined and contrasted with more rigid directly observed treatment approaches. We conclude that treatment failures are not patient failures, and that TB control programmes need to address the social dimensions of TB, and adhere to the principles of good TB care, with the same commitment that is devoted to ensuring patients follow treatment guidelines. We suggest a paradigm shift away from a focus on diseased patients towards enabling health in the community.

Delayed deterioration of hearing following bacterial meningitis.

Bacterial meningitis is an important cause of acquired sensorineural deafness in childhood. Deafness following meningitis may be progressive. Previous reports have shown deterioration in hearing up to 12 years after the illness. We present two cases of sensorineural deafness following meningitis. Severe to profound sensorineural hearing losses were detected immediately after meningitis in these patients. The hearing subsequently deteriorated in both cases. Deterioration in hearing thresholds occurred 17 years after the illness in one case. In the other patient the hearing got progressively worse three years after meningitis. She subsequently required a cochlear implant.

Tuberculosis patients and practitioners in private clinics in India.

SETTING: Rural and urban areas of Maharashtra, a large state in Western India. OBJECTIVE: To understand tuberculosis (TB) management practices among private medical practitioners (PPs) and the treatment behaviour of the patients they manage. DESIGN: Prospective study of help-seeking patterns and treatment behaviour among 173 pulmonary TB patients diagnosed in private clinics, and the TB management practices of 122 PPs treating these patients. RESULTS: The first source of help for 86% of patients was a PP. The diagnostic and treatment practices of PPs were inadequate; 15% did not consider sputum examination to be necessary, and 79 different treatment regimens were prescribed by 105 reporting PPs. Sixty-seven percent of the patients diagnosed in private clinics remained with the private sector, and the rest shifted to public health services within six months of treatment. The treatment adherence rate among the patients in private clinics was 59%. There were discrepancies between the reported management practices of the PPs and what their patients actually followed. CONCLUSION: The study identifies and highlights the need to educate PPs and their TB patients, and indicates ways in which PPs could be meaningfully involved in efforts to revitalize the national TB control programme.

Private doctors and tuberculosis control in India.

Over three quarters of the 8 million registered doctors in India are engaged in private medical practice. In urban and rural areas alike people prefer private doctors to public health services for their health care needs. A majority of patients and those with suspected tuberculosis also report first to private doctors. Nevertheless private doctors seem to be alienated from national efforts towards control of tuberculosis, there being no well-defined role for them in the National Tuberculosis Programme. This study of private doctors practising in the low income areas of a metropolis of India reports on the knowledge of private doctors about diagnosis and treatment of tuberculosis and their awareness and perceptions about the public health services available for tuberculosis control. The study reveals gaps and weaknesses in the private doctors' reported practice of managing lung tuberculosis, the most important and persistent problem of public health concern in India. The need for organized efforts towards involving private doctors in disease control programmes wherein their curative functions could contribute significantly is stressed.

Community health awareness among recent medical graduates of Bombay.

BACKGROUND: Since Independence in 1947, the need for reorientation of our western-style, hospital-based, urban-oriented medical education has been well recognized and much discussed but little action has been taken to make it more community-based. Against a background of 40 years of debate, we conducted a study of 342 medical graduates commencing their internship training in one government and two municipal medical colleges to assess the effects of medical education on them. METHODS: A questionnaire was administered to examine recent interns' awareness of some aspects of community health, their perceptions of the concept of Primary Health Care and their knowledge of rational prescriptions for minor ailments and for major illnesses of public health importance. RESULTS: We found a lack of basic health information among recent medical graduates, an apathy towards matters of public health importance, and gaps in their knowledge of curative care and rational prescribing. CONCLUSION: We suggest that there is a need not only to effect changes in the curriculum but also to assess whether these changes might lead to the making of doctors more suited to work in our villages.

Enhanced frequency of spontaneous B cell lines from Epstein-Barr virus (EBV) seropositive donors 80 years and older.

Based on the well-recognized decline in immunocompetence which develops with advancing age, we have evaluated the effect of age on the frequency of development of spontaneous Epstein-Barr virus (EBV)-infected B cell lines. Blood mononuclear cells were isolated from 38 clinically healthy seropositive donors. The cells were maintained in vitro according to routine culture conditions for lymphocytes. Eight spontaneously EBV-infected B lymphoblastoid cell lines (LCL) were isolated. The LCL developed in 12.5, 14.3, or 6.3% of the samples derived from donors in the three age groups 20-39, 40-59, 60-79, respectively. In contrast, samples from five of seven (71%) donors 80 years and older yielded LCL. Although the reason(s) for the increased frequency of occurrence of spontaneous LCL from the older adults is yet to be explored, the possible role of the virus-specific T lymphocytes as a contributing factor is discussed.

Comparison of methods for HIV isolation from monocytes and lymphocytes of seropositive asymptomatic hemophiliacs and homosexuals.

1. Since monocyte-macrophages have been recognized as HIV targets in addition to CD4+ T-lymphocytes, we have evaluated HIV infection of purified peripheral blood mononuclear cell fractions obtained from 10 seropositive asymptomatic hemophiliacs and compared it with that of 10 asymptomatic homosexual patients. 2. HIV was isolated more frequently from the lymphocytes than the monocytes of both groups of patients. 3. HIV preferentially replicated in phytohemagglutinin-stimulated lymphocytes compared with growth factor-treated monocytes. Monocytes did not preferentially harbour HIV in either group.