Private practitioners' contributions to the Revised National Tuberculosis Control Programme in a South Indian district.

SETTING: Tumkur District, South India. OBJECTIVE: To assess the participation of for-profit, formal private practitioners (PPs) under the Revised National Tuberculosis Control Programme's (RNTCP's) public-private mix (PPM) schemes and document their contribution to RNTCP pulmonary tuberculosis (TB) case finding. DESIGN: RNTCP reports at district TB centre were reviewed. PPs were mapped and their referrals of presumptive TB cases to the RNTCP during 2011 were assessed using laboratory registers at designated microscopy centres (DMCs). RESULTS: None of the 424 PPs had signed up for any PPM scheme. However, 22% made at least one referral to a DMC in 2011. PP referrals constituted 15% of the presumptive TB cases examined at the DMCs, and PPs contributed to 23% of the sputum smear-positive TB cases detected. Among PP referrals, the proportion of confirmed smear-positive cases was high (24%). CONCLUSION: Fifteen years after the start of PPM, formal engagement of PPs with RNTCP was non-existent. However, PPs do refer cases to the RNTCP and contribute to a fraction of TB case detection. The high proportion of confirmed sputum smear-positive cases suggests that PPs tend to make selective referrals. More efforts are needed to promote the engagement of PPs in the RNTCP.

Manual liquid culture on simple Middlebrook 7H9 or MGIT for the diagnosis of smear-negative pulmonary tuberculosis.

OBJECTIVES: To compare the performance of liquid culture on simple Middlebrook 7H9 to the one of manual mycobacterial growth indicator tube (MGIT) and solid culture on Ogawa for the diagnosis of smear-negative tuberculosis (SN-TB) in a high-burden, resource-constrained setting. METHODS: Sputum samples from patients with clinical suspicion of SN-PTB admitted to two-third-level hospitals in Lima between September 2005 and May 2008 were cultured in parallel on simple Middlebrook 7H9, manual MGIT and Ogawa. A case of SN-TB was defined as one with a positive culture in any medium. RESULTS: Among samples from 542 patients, 151 (28%) cases of SN-TB were identified. The sensitivity of Middlebrook 7H9 (0.76, 95% CI 0.69-0.83) was not substantially different from that of MGIT (0.85, 95% CI 0.79-0.91). Ogawa had the lowest sensitivity (0.63, 95% CI 0.55-0.71). The median turnaround time was similar for both liquid media (18 days), and it was shorter than that of Ogawa (30 days). CONCLUSIONS: Culture on simple Middlebrook 7H9 performs almost as well as MGIT, at a probably more affordable cost. Further studies on the cost-effectiveness of this overlooked technique should be performed.

Comparative performance of Thin Layer Agar and Löwenstein-Jensen culture for diagnosis of tuberculosis.

Sputum smear microscopy for the diagnosis of tuberculosis (TB) is cheap and simple but its sensitivity is low. Culture on Löwenstein-Jensen (LJ) is more sensitive but it takes a long time to yield results. Thin-Layer Agar (TLA) culture was suggested as an equally sensitive and faster alternative. We evaluated the performance of TLA for diagnosing TB in Jogjakarta, Indonesia. People with suspected TB presenting from July 2010 to July 2011 to two chest clinics of the National TB Control Programme network of Jogjakarta were eligible for inclusion. A sputum sample was sent to the Gadjah Mada University microbiology laboratory for concentration, smearing, Ziehl-Neelsen staining and culture on LJ and TLA. Sensitivity of cultures was evaluated against a composite reference standard (any positive culture). Time to detection of Mycobacteria was recorded. Out of 1414 samples, 164 (12%) were smear positive, 99 (7%) were scanty and 1151 (81%) were negative. On TLA and LJ respectively, 168 (12%) and 149 (11%) samples were positive, 72 (5%) and 32 (2%) were contaminated (κ = 0.64; 95% CI 0.59-0.69, p <0.01). Using the reference standard, 196 (14%) TB cases were identified. The sensitivity of TLA was 0.86 (95% CI 0.80-0.90), significantly higher (p 0.03) than for LJ (0.76; 95% CI 0.69-0.81). The median time to detection in days was significantly shorter (p <0.01) for TLA (12; 95% CI 11-13) than for LJ (44; 95% CI 43-45). TLA is a rapid and sensitive method for the diagnosis of TB. Implementation studies to evaluate the cost-effectiveness and impact of its introduction into programmatic settings are urgently needed.

The risk of first venous thromboembolism during pregnancy and puerperium in double heterozygotes for factor V Leiden and prothrombin G20210A.

BACKGROUND: The risk of venous thromboembolism (VTE) during pregnancy in double heterozygous carriers of factor (F) V Leiden and prothrombin G20210A is not established. Hence, whether or not these women deserve antithrombotic prophylaxis when pregnant is unknown. PATIENTS AND METHODS: In the frame of a multicenter family study, 52 double heterozygous carriers of FV Leiden and prothrombin G20210A who had remained pregnant at least once before knowledge of thrombophilia, were retrospectively investigated with respect to the occurrence of first VTE during pregnancy and puerperium. They were compared with 104 heterozygous carriers of FV Leiden, 104 of prothrombin G20210A and 104 women without thrombophilia. RESULTS: Double heterozygotes were similar to single heterozygous carriers and non-carriers for the age at first pregnancy, age at testing and rate of full-term pregnancies. No VTE during pregnancy was observed in the four groups of women, whereas in the puerperium it occurred in two double carriers (1.8% of pregnancies, 95% CI: 0.5-6.3), three single FV Leiden carriers (1.5%, 0.5-4.3), two single prothrombin G20210A carriers (1%, 0.2-3.6) and one non-carrier (0.4%, 0-2.5). CONCLUSIONS: The risk of first VTE during pregnancy and puerperium in double heterozygous carriers of FV Leiden and prothrombin G20210A is low and similar to that of single carriers. As for single heterozygotes, antithrombotic prophylaxis in asymptomatic double heterozygous carriers appears to be justified only in puerperium.

Type and location of venous thromboembolism in patients with factor V Leiden or prothrombin G20210A and in those with no thrombophilia.

BACKGROUND: Patients with factor (F) V Leiden or the prothrombin G20210A polymorphism are at increased risk of developing deep vein thrombosis (DVT). On the other hand, the risk of developing pulmonary embolism (PE) appears to be low in carriers of FV Leiden, perhaps because of a lower tendency to develop iliofemoral DVT than non-carriers. For prothrombin G20210A, data are scanty and controversial. METHODS: The clinical manifestations (isolated DVT, DVT and PE, and isolated PE), the extension of DVT, and the presence of transient risk factors were retrospectively investigated in 115 patients with heterozygous FV Leiden, 87 with prothrombin G20210A and 200 with no thrombophilia marker. RESULTS: Isolated symptomatic PE was less prevalent in patients with FV Leiden (6%) than in those with prothrombin G20210A (21%) and no thrombophilia (23%) (P > 0.0001). The rate of distal DVT was higher in patients with no thrombophilia (16% vs. 7% for FV Leiden and 6% for prothrombin G20210A) (P = 0.02). No difference in the incidence of PE from distal and proximal DVT, the extension of proximal DVT and the type of transient risk factors for venous thromboembolism (VTE) was found in the three groups. Patients with prothrombin G20210A had a younger age at their first VTE (24 years, P < 0.0001) and a higher rate of DVT accompanying PE (P = 0.04) than those with FV Leiden or no thrombophilia. CONCLUSIONS: Carriers of prothrombin G20210A, unlike those of FV Leiden, have an increased risk of developing isolated PE. This difference was not explained by a different rate of distal DVT, extension of proximal DVT, or distribution of transient risk factors in the two groups. Patients with prothrombin G20210A have more severe clinical manifestations than those with FV Leiden or no thrombophilia.

Prothrombin A19911G polymorphism and the risk of venous thromboembolism.

BACKGROUND: The A > G polymorphism at position 19911 of the prothrombin gene is associated with increased plasma prothrombin levels but its role as a risk factor for venous thromboembolism (VTE) is not established. OBJECTIVE: To investigate the role of prothrombin 19911 A > G polymorphism in the risk of VTE in patients with heterozygous prothrombin 20210GA or factor (F) V Leiden and in those without thrombophilia. PATIENTS AND METHODS: Case-control study of 793 patients with prothrombin 20210 GA (n = 167) or FV Leiden (n = 198), and without thrombophilia (n = 428), and of 795 healthy individuals with the corresponding coagulation profile, investigated for the presence of prothrombin 19911 A > G. Plasma prothrombin levels were measured in 342 individuals. RESULTS: Prothrombin 19911 A > G did not increase the risk of VTE in carriers of prothrombin 20210 GA [odds ratio (OR) 1.2, 95% CI (95% CI) 0.8-1.8] but significantly increased the risk in carriers of FV Leiden (OR 2.1, 95% CI 1.3-3.4) and in patients without thrombophilia (OR 1.5, 95% CI 1.0-2.2). Higher plasma prothrombin levels in carriers of prothrombin 19911 A > G polymorphism than in non-carriers were found among individuals without thrombophilia (P =0.05) and with FV Leiden (P = 0.07), but not in carriers of prothrombin 20210 GA (P = 0.2). CONCLUSIONS: Prothrombin 19911 A > G polymorphism was independently associated with a 1.5-fold increased risk of VTE and increased 2-fold the risk of VTE associated with FV Leiden, both increases statistically significant. No effect was observed in carriers of prothrombin 20210 GA, perhaps because this polymorphism has a stronger influence on plasma prothrombin levels than the prothrombin 19911 polymorphism.

Cigarette smoking and alcohol consumption as determinants of survival in non-Hodgkin's lymphoma: a population-based study.

BACKGROUND: The risk of non-Hodgkin's lymphoma (NHL) seems to be enhanced by cigarette smoking and lowered by alcohol drinking. PATIENTS AND METHODS: To assess whether cigarette smoking and alcohol drinking affect NHL survival, a population-based prospective study on 1138 Italian patients, diagnosed in 1991-1993, followed-up until 2002, was carried out. At diagnosis, clinical and socio-demographic data were recorded and lifestyle habits were assessed through a validated questionnaire. Survival analysis was performed with Kaplan-Meier methods. Hazard ratios (HR) were estimated by Cox regression. RESULTS: The mean follow-up was 6.6 years (standard deviation (SD) 4.3). The mean survival time was 7.56 years (SD 0.155). At both univariate and multivariate analysis heavy cigarette smoking and alcohol drinking were associated with poor survival. Compared with those with a lower cumulative exposure to tobacco smoking, those who had smoked>31 pack-years had a worse survival (HR=1.60, 95%CI=1.18-2.18). Drinkers had a higher risk of death compared with non-drinkers (HR=1.41, 95%CI=1.10-1.81). Considering only those who had NHL as cause of death, the HR for the higher category of pack-years smoked, compared with the lowest, was 1.63 (95% CI=1.15-2.33) and for drinkers, compared with non-drinkers, it was 1.33 (95% CI=1.01-1.80). CONCLUSIONS: cigarette smoking and alcohol drinking may influence NHL survival.