Strategies for smoking cessation (pharmacologic intervention versus enhanced motivation vs. standard motivation) in TB patients under treatment in the RNTCP, India - A cluster - Randomized trial.

BACKGROUND: Tuberculosis burden is still high and smoking prevalence among males has increased in India. It is found that increased morbidity, mortality and relapse among TB smokers. METHOD: Setting: Patients from two Revised National Tuberculosis Control Program Centres of Tamilnadu form the study population. OBJECTIVE: To compare the effectiveness of Bupropion therapy along with standard counselling versus enhanced counseling versus standard counseling for smoking cessation among TB patients. STUDY DESIGN: Cluster randomized effectiveness trial. PROCEDURE: Patients from each of the thirty-six Designated Microscopic Centres were randomly allocated to receive one of the three interventions using cluster randomization. Smoking cessation was assessed by self-reporting and confirmed by Carbon monoxide(CO) monitors, done at three-time points and TB treatment outcome at the end of ATT. RESULTS: Out of 517 male patients enrolled to the study, the smoking status is available only to 381 subjects. The proportion of patients who have quit smoking in drug, enhanced and standard arms at the end of treatment was 67%, 83% and 52% (P= < 0.001). There was no statistical significance in response to TB treatment between those who quit and those who did not (Favourable response 99.2% vs 97.6%). CONCLUSION: Both enhanced counselling arm and drug arm are effective strategies for smoking cessation among TB patients and their implementation in the TB programs are recommended.

A call for neurologists to take up stroke intervention.

Recent data have provided overwhelming evidence in favor of benefits of emergent endovascular intervention in large vessel acute ischemic stroke (AIS). India with its large population has a huge burden of AIS. Hence, neurologists need to gear up to the new challenge of providing interventional care to huge populations of AIS in the country. The best way to cover this unprecedented unmet need is to encourage neurologists to take up interventional subspecialty interests through new but sound training pathways.

Influence of socioeconomic status on in-hospital mortality and morbidity after stroke in India: retrospective hospital-based cohort study.

OBJECTIVES: To determine an association between socioeconomic status and in-hospital outcome in Indian patients with stroke. MATERIALS AND METHODS: Retrospective hospital-based cohort study. The hospital stroke register was used for this study. The independent variables were demographic job status, education, cardiovascular risk factors, comorbidities and the score on the Glasgow Coma Scale (GCS). The outcome variables were mortality and Barthel's index (BI) score at discharge. RESULTS: Data of 599 consecutive patients comprising 370 men (54.3%) and 229 women (33.6%) was available for analysis. Their mean age was 55.63±15.36 years. Age, diagnosis (ischemic or hemorrhagic), midline shift, smoking and GCS were significantly associated with mortality and BI score (P<0.05). There was a statistically significant association between employment status and BI at discharge (P=0.03) in univariate analysis. In multivariate analysis, joblessness was associated with lower BI at discharge (P=0.02) after adjustment for GCS motor score and stroke subtype. CONCLUSION: Our study shows that in patients with stroke, lower employment status is associated with poor outcome at discharge from the hospital. The association is independent of other prognostic factors.

Plasma efavirenz in HIV infected children treated with generic antiretroviral drugs in India.

We measured plasma concentration of efavirenz (EFV) in 16 HIV-infected Indian children receiving antiretroviral treatment at Government ART centres. The mean 12 hour concentration was 2.39 ug/mL (range: 0.72- 7.82 ug/mL). The majority of children treated with generic EFV at currently recommended doses had blood levels within the therapeutic range.

Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation.

CONTEXT: Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging. OBJECTIVE: To review diagnostic features and localisation accuracy for insulinomas. DESIGN: Cross-sectional, retrospective analysis. SETTING: A single tertiary referral centre. PATIENTS: Patients with insulinoma in the years 1990-2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes. INTERVENTIONS: Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated. MAIN OUTCOME MEASURE(S): Insulinoma localisation was compared to histologically confirmed location following surgical excision. RESULTS: Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results. CONCLUSIONS: Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.

Surgery for medically intractable epilepsy due to postinfectious etiologies.

Medically intractable epilepsy (MIE) resulting from postinfectious etiologies requiring surgery have been uncommonly reported. A series of 28 cases are presented (hospital prevalence 5.7%). The mean duration of epilepsy prior to surgery was 8.2 +/- 2.1 years. The mean time of onset of epilepsy after central nervous system infection was 1.4 +/- 0.9 years (range 0-19 years). The pathologies included postpyogenic meningitic/encephalitic sequel (8), neurocysticercosis (6), tuberculomas/posttuberculous etiology (4), postpyogenic abscess of otogenic etiology (4), posttraumatic abscess-related gliosis (2), and gliosis of unknown infectious etiology (4) cases. Surgery included mesial temporal (11), lateral temporal (4), frontal (9), parietal (2) resections and hemispherotomy (1). Hippocampal sclerosis was seen in nine cases (4 neurocysticercosis) and this occurred in younger persons as compared to neocortical epilepsies. Good outcome (Engel class I and II) was seen in 23 of 28 cases (Engel class I in 17).

Assessment of X-ray readers in TB prevalence surveys.

A prevalence study was carried out a rural community in Tiruvallur district in Tami Nadu to standardize the method of assessing an X-ray reader in tuberculosis (TB) prevalence surveys by means of different measures of agreement between the reader and a Standard Reader (SR). The exercise on assessing the X-ray readers was carried out on two occasions; one involving three trainee readers (R1, R2, and R3), and the other involving one trainee reader (R4). The extent of agreement was estimated using Kappa statistics (K), over-diagnosis, under-diagnosis, crude agreement and prevalence adjusted bias adjusted kappa (PABAK). The overall performance of readers R1, R2, and R3 was not satisfactory in terms of K (21, 34 and 14%) in the first assessment. The K, over-diagnosis and under-diagnosis were estimated to be 61, 28 and 4% for R1, 63, 18 and 4% for R2 and 58, 31 and 5% for R3 in the final assessment. This suggested that R2 performed well compared to the other two readers. The K was 68% for R4 in the first assessment. As the over-diagnosis was to the extent of 40%, the trainee reader underwent one more assessment. The K was 64% which was as good as before, but there was no improvement in the over-diagnosis (43.5%) in the second assessment. Based on the performance, only one reader (R2) was certified as qualified for X-ray reading in the first occasion while the reader (R4) assessed in the second occasion was not qualified. These findings were subject to the inherent variation in the SR's readings against which the readers were assessed.

Weight gain in patients with tuberculosis treated under directly observed treatment short-course (DOTS).

UNLABELLED: SET UP: One Tuberculosis Unit (TU) in Tiruvallur district, Tamil Nadu, India where Tuberculosis (TB) patients treated under Directly Observed Treatment Short Course (DOTS) programme. OBJECTIVE: To identify the effects of weight gain among TB patients at the end of treatment on different factors such as socio-economic and demographic characteristics, smoking and drinking habits, treatment under supervision, the type of DOTS centres and problems in taking drugs. METHODS: TB patients registered between May 1999 and December 2004 formed the study population. Multiple regression method was used for the analysis. RESULTS: Among 1557 smear-positive TB patients registered under DOTS programme, the changes in weight ranged from a loss of 4 kgs to a gain of 20 kgs at the end of TB treatment; the average change in weight was 3.22 kgs. The gain in weight at the end of treatment was associated with age (<45 years), DOT at government centres, no problems in taking drugs as reported by patients and cure rate. CONCLUSION: The findings showed that there is an association between gain in weight with DOT at government centres and cure of patients.

'Primary cutaneous mucormycosis during induction chemotherapy in a child with acute lymphoblastic leukemia'.

We report a child with acute lymphoblastic leukemia who developed primary cutaneous mucormycosis at the site of lumbar puncture during induction chemotherapy. Though high mortality rates are reported with invasive mucormycosis, prompt biopsy, early identification and antifungal therapy using a combination regime of amphotericin-B and rifampicin along with extensive surgical debridement led to complete cure of the lesions in the index case.

Perceptions of tuberculosis patients about private providers before and after implementation of Revised National Tuberculosis Control Programme.

BACKGROUND: Most of the persons with chest symptoms in India approach private providers (PPs) for health care. It has been observed that patients who start treatment with PPs for tuberculosis (TB) frequently switch over subsequently to the public sector. The reasons for this discontinuation and their perceptions of the TB care provided by the PPs are unknown. OBJECTIVE: To document the perceptions about PPs India's Revised National TB Control Programme (RNTCP) and the reasons for discontinuation of treatment with PPs and subsequent attendance at a public provider. METHODS: This was a cross sectional study on patients registered under TB programme during 1997 and 2005 in rural and urban areas. During this period patients who were initially diagnosed and treated for TB in a private clinic and subsequently shifted to public health facility were considered for the study. A semi-structured interview schedule was used to collect the factors related to patient's perceptions on PPs, the factors responsible for initiating treatment with PPs, reasons for discontinuing treatment with PPs, and their willingness to continue treatment from government health facilities were collected. This data was compared with data collected in 1997 before implementation of the RNTCP. RESULTS: A total of 1000 and 1311 TB patients were registered during 1997 and 2005 respectively. Among them, 203 (20%) and 104 (8%) patients were identified as having been initially diagnosed and started on TB treatment by PPs and subsequently shifted to government health facilities. There were significant changes in reasons for selecting PPs between the two periods: being convenient (47% vs 10%; p < 0.001), quality care (41% vs 19%; p < 0.001), motivated by others (49% vs 19%; p < 0.001), confidentiality (19% vs 9%; p < 0.05) and known doctor (6% vs 28%; p < 0.001) respectively. Financial problems were the most common reason for discontinuation of treatment in both periods. The use of sputum test for diagnosing TB by PPs was significantly increased after RNTCP implementation. CONCLUSION: This study suggests that slowly perceptions of patients have changed towards PPs, and RNTCP has begun to gain acceptance amongst patients in terms of convenience, confidentiality and personal care.

Annual risk of tuberculosis infection in Chennai city.

AIM: To study the proportion of children infected with Mycobacterium Tuberculosis in Chennai city. METHODOLOGY: A cluster sampling methodology was adopted to select an estimated sample size of 7000 children from five corporation zones selected systematically from ten zones of the city. A total of 7098 children aged 1-9 years were subjected to Mantoux and test read; 1897 (27%) from slum area and 5201 (73%) from non-slum area. RESULTS: The prevalence of infection among children without BCG scar was estimated to be 10.5 % (ARTI of 2.0%) and was similar to that among children irrespective of scar status. The prevalence of infection was higher among children in slum areas (11.1%; ARTI 2.1%) compared to non-slum areas (8.9%; ARTI 1.7%); but the difference was not statistically different. CONCLUSION: The tuberculosis situation in Chennai as measured by risk of infection was higher in urban city area than rural areas and comparable to that found in other cities as reported from earlier studies. This information can be used as baseline information for monitoring the epidemiological trends in Chennai city in future.

Hemispherotomy for intractable epilepsy.

CONTEXT: Hemispherotomy is a surgical procedure for hemispheric disconnection. It is a technically demanding surgery. Our experience is presented here. AIMS: To validate and compare the two techniques for hemispherotomy performed in patients with intractable epilepsies. SETTINGS AND DESIGN: A retrospective study 2001-March 2007: Nineteen cases of hemispherotomies from a total of 462 cases operated for intractable epilepsy. MATERIALS AND METHODS: All the cases operated for intractable epilepsy underwent a complete epilepsy surgery workup. Age range 4-23 years (mean 5.2 years), 14 males. The seizure frequency ranged from 2-200 episodes per day; four were in status; three in epilepsia partialis continua. The pathologies included Rasmussen's, hemimegelencephaly (unilateral hemispheric enlargement with severe cortical and subcortical changes), hemispheric cortical dysplasia, post-stroke, post-traumatic encephalomalacia and encephalopathy of unknown etiology. The techniques of surgery included vertical parasaggital approach and peri-insular hemispherotomy. Neuronavigation was used in seven cases. RESULTS: Class I outcome [Engel's] was seen in 18 cases and Class II in one assessed at 32-198 weeks of follow-up. The four patients in status epilepticus had Class I outcome. Four patients had an initial worsening of weakness which improved to preoperative level in five to eight weeks. Power actually improved in three other patients at 32-36 weeks of follow-up, but hand grip weakness persisted. In all the other patients, power continued to be as in preoperative state. Cognitive profile improved in all patients and 11 cases returned back to school. CONCLUSIONS: Both techniques were equally effective, the procedure itself is very effective when indicated. Four of our cases were quite sick and were undertaken for this procedure on a semi-emergency basis.

Tuberculous infection in Saharia, a primitive tribal community of Central India.

A cross-sectional tuberculin survey was carried out to estimate the prevalence of tuberculous infection and the annual risk of tuberculosis infection (ARTI) among children of Saharia, a primitive ethnic group in Madhya Pradesh, Central India. A total of 1341 children aged 1-9 years were subjected to tuberculin testing with 1 TU of PPD RT 23 and the reaction sizes were read after 72 h. The proportion of BCG scar-positive children was 34.6%. The frequency distribution of children by reaction sizes indicated a clear-cut anti-mode at 11 mm and a mode at 18 mm at the right-hand side of the distribution. The prevalence of infection among children irrespective of BCG scar was estimated as 20.4% (95% CI 18.2-22.5%) and the ARTI was 3.9% (95% CI 3.5-4.3%). The corresponding figures were 21.1% (95% CI 18.3-23.8%) and 3.9% (95% CI 3.4-4.5%) among BCG scar-negative children and 19.0% (95% CI 15.4-22.5%) and 4.0% (95% CI 3.2-4.8%) among BCG scar-positive children. The findings of the present study show a high prevalence of tuberculous infection and high ARTI in this primitive ethnic group. There is an urgent need to further intensify tuberculosis control measures on a sustained and long-term basis in this area.

Survival of tuberculosis patients treated under DOTS in a rural Tuberculosis Unit (TU), south India.

OBJECTIVE: To estimate survival probabilities and identify risk factors for death of tuberculosis (TB) patients during treatment period. METHODS: TB patients registered during May 1999 to December 2004 from a rural TB unit (TU) with a population of 580,000 in Tiruvallur district, South India, formed study population. Life table and Cox's regression methods were used. RESULTS: Of the 3818 TB patients who were initiated on treatment, 96, 94 and 97% of category--I, II and III respectively, were surviving after completion of treatment. Higher death rates were independently associated with patient's age (45 years), previous history of treatment, alcoholism and initial body weight (<35 kgs). CONCLUSION: The survival probability was found to be similar in all patients irrespective of categorization. Necessary actions need to be initiated in the programme to improve body weight and abstain from alcoholism.

Function of the SIRT1 protein deacetylase in cancer.

The NAD(+)-dependent protein deacetylase SIRT1 is linked to cellular survival pathways by virtue of keeping the tumor suppressor gene p53 and members of the forkhead transcription factor family deacetylated. To validate SIRT1 as a therapeutic anti-cancer target, we performed immunohistochemistry experiments to study the in vivo expression of SIRT1 in cancer specimens. We show that human SIRT1 is highly expressed in cancer cell lines as well as in tissue samples from colon carcinoma patients. Interestingly, there is a strong cytosolic component in the SIRT1 expression pattern. We further characterized SIRT1 in p53-wild-type and -mutant cell lines and show that SIRT1 mRNA-knockdown leads to a p53-independent decrease of cell proliferation and induction of apoptosis. In addition, SIRT1 expression has been found to be inducible upon DNA damage. A previously discovered small molecule SIRT1 inhibitor with nanomolar in vitro activity has been tested in cancer relevant assays. The SIRT1 inhibitory compound showed no potent anti-proliferative activity despite hitting its molecular target within tumor cells. From these studies we conclude that it may not be sufficient to block the catalytic function of SIRT1, and that its survival effects may be mainly brought about by means other then the deacetylase function. The increased cytosolic expression of SIRT1 in cancer cells could be an indicator of such novel functions.

Comparison of tuberculin reaction sizes at 48 and 72 hours among children in Tiruvallur district, south India.

SETTING: A rural population in Tiruvallur district, south India. OBJECTIVE: To study the variability of skin test reaction sizes between 48 and 72 hours. METHODS: A tuberculin test survey was conducted among children aged less than 10 years. The reaction sizes were read by the same reader at 48 hours and 72 hours independently. The results of the tuberculin test were compared. RESULTS: Of 957 children aged below 10 years were included in the study; the male and female ratio was 1: 1.1. There were no significant differences between the readings of reaction size at 48 and 72 hours. CONCLUSION: The tuberculin test results can be read either at 48 hours or 72 hours without compromising the validity.

Risk factors for non-adherence to directly observed treatment (DOT) in a rural tuberculosis unit, South India.

OBJECTIVE: To identify risk factors for non-adherence of tuberculosis (TB) patients to DOT. METHODS: Retrospective study of TB patients by logistic regression analysis to identify risk factors for non-adherence. RESULTS: Of the 1666 patients interviewed, 1108 (67%) adhered and 558 (33%) did not adhere to DOT. Of 558 patients, the risk factors associated with non-adherence were illiteracy (39%), difficulty in accessing health facility (57%), and non-government DOT centre (43%). CONCLUSION: Patients should be educated about tuberculosis and importance of DOT. All DOT centres, including Non-government DOT centres, should be made more accessible and patient-friendly.

SIRT1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents.

The nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase SIRT1 has been linked to fatty acid metabolism via suppression of peroxysome proliferator-activated receptor gamma (PPAR-gamma) and to inflammatory processes by deacetylating the transcription factor NF-kappaB. First, modulation of SIRT1 activity affects lipid accumulation in adipocytes, which has an impact on the etiology of a variety of human metabolic diseases such as obesity and insulin-resistant diabetes. Second, activation of SIRT1 suppresses inflammation via regulation of cytokine expression. Using high-throughput screening, the authors identified compounds with SIRT1 activating and inhibiting potential. The biological activity of these SIRT1-modulating compounds was confirmed in cell-based assays using mouse adipocytes, as well as human THP-1 monocytes. SIRT1 activators were found to be potent lipolytic agents, reducing the overall lipid content of fully differentiated NIH L1 adipocytes. In addition, the same compounds have anti-inflammatory properties, as became evident by the reduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). In contrast, a SIRT1 inhibitory compound showed a stimulatory activity on the differentiation of adipocytes, a feature often linked to insulin sensitization.

Trimethoxypsoralen in vitiligo.

The treatment of vitiligo has been unsatisfactory. Introduction of systemic furocoumarins to treatment regimens has given very promising results. Trimethylpsoralen has been found to be more potent than 8-methoxypsoralen. In cases studied, ultraviolet irradiation of affected sites following topical application of trimethylpsoralen was found to hasten the process of repigmentation. Simultaneous treatment of underlying disease produced a quicker response followed by sustained relief.