Care Seeking Behavior of Chest Symptomatics: A Community Based Study Done in South India after the Implementation of the RNTCP

INTRODUCTION: With the creation of the Revised National TB Control Programme (RNTCP), tuberculosis services have become decentralized and more accessible. A 1997 study prior to RNTCP implementation reported that most chest symptomatics accessed first private health care facilities and a general dissatisfaction with government health facilities. The study was repeated post-RNTCP implementation to gain insight into the current care seeking behavior of chest symptomatics. METHODOLOGY: A cross-sectional community-based study carried out between March-August 2008 in 4 sites (2 rural [R] and 2 urban [U]) from the same two districts of Chennai and Madurai, southern India, as in the 1997 study. Six hundred and forty chest symptomatics were identified (R 314; U 326), and detailed interviews were done for 606 (R311; U295). RESULTS: Prevalence of chest symptomatics in the urban and rural areas were 2.7% and 4.9% respectively (p<0.01), and was found to increase with age (Chi-square for trend, p<0.01). Longer delays in seeking care were seen amongst symptomatics above 45 years of age (p 0.01), and those who had taken previous TB treatment (p=0.05). Overall, 50% (222/444) of the chest symptomatics approached a government health care facility first (R 142 (61%); U 80 (38%), p=or  <0.001). This was significantly (p<0.001) more than were observed in the 1997 study, where only 38.4% approached a government facility first. Sixty two (28%) of the 222 made a second visit to a government facility (R26%; U31%), while 17% shifted to a private facility (R14%; U21%). Dissatisfaction with the health care facility was one of the major reasons expressed. CONCLUSIONS: It appears that the RNTCP has had an impact in the community with regard to the availability and accessibility of TB services in government health facilities. However the relatively high levels of subsequent shifting to private health facilities calls for urgent action to make government facilities more patients friendly with quality care facilities in the delivery of RNTCP services

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Diagnosis and treatment delay among pulmonary tuberculosis patients identified using the Taiwan reporting enquiry system, 2002–2006

<p>Abstract</p> <p>Background</p> <p>The tuberculosis reporting enquiry system was launched in Taiwan in 2001. Tuberculosis has been categorized as the third most important notifiable disease in Taiwan and the time required for reporting has been shortened to 7 days.</p> <p>Methods</p> <p>A total of 114,827 cases were reported using the Taiwan enquiry system between 2002 and 2006; of these, 26,027 (22.7%) were finally diagnosed as not being tuberculosis, 7,005 (8.2%) were diagnosed as extra-pulmonary tuberculosis and 3,677 (3.2%) were not a first-time diagnosis of tuberculosis, and these cases were hence excluded. Diagnosis time was defined as the length of time between the first medical examination (including chest radiography, sputum smear or sputum culture) to the diagnosis of PTB; treatment time was defined as the period from the diagnosis of PTB to the initiation of treatment. Using the cut-off at the 75^thpercentile, a period of longer than 9 days was defined as a <it>diagnosis delay </it>and a period of longer than 2 days as a <it>treatment delay</it>. Multiple logistic regression analysis was applied to analyze the risk factors associated with these delays.</p> <p>Results</p> <p>During the five-year study period, among the 78,118 new PTB patients reported in Taiwan, the mean diagnosis and treatment times were 12 and 5 days and the median times 1 day and 0 days, respectively. In total, 24.9% of the new PTB patients' diagnosis time delays were longer than 9 days and 20.3% of the patients' treatment time delays were longer than 2 days. The main factors associated with diagnosis delay included age, reporting year, living with family and a positive sputum culture (<it>p </it>< 0.0001); the risk factors significantly associated with treatment delay were increased age, an aboriginal ethnic background, a positive sputum culture and diagnosis at a non-medical center (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>The Taiwan TB reporting enquiry system has successfully increased the confirmed PTB reporting rate from 64.4% to 71.5%. Greater age and a positive sputum culture were both found to significantly increase both diagnosis and treatment delays; treatment delay is also significantly affected by the patient having an aboriginal ethnic background and being diagnosed at a non-medical center.</p

The Effect of Diagnostic Delays on the Drop-Out Rate and the Total Delay to Diagnosis of Tuberculosis

Background: Numerous patient and healthcare system-related delays contribute to the overall delay experienced by patients from onset of TB symptoms to diagnosis and treatment. Such delays are critical as infected individuals remain untreated in the community, providing more opportunities for transmission of the disease and adversely affecting the epidemic. Methodology/Principal Findings: We present an analysis of the factors that contribute to the overall delay in TB diagnosis and treatment, in a resource-poor setting. Impact on the distribution of diagnostic delay times was assessed for various factors, the sensitivity of the diagnostic method being found to be the most significant. A linear relationship was found between the sensitivity of the test and the predicted mean delay time, with an increase in test sensitivity resulting in a reduced mean delay time and a reduction in the drop-out rate. Conclusions/Significance: The results show that in a developing country a number of delay factors, particularly the low sensitivity of the initial sputum smear microscopy test, potentially increase total diagnostic delay times experienced by TB patients significantly. The results reinforce the urgent need for novel diagnostic methods, both for smear positive an

A Threshold Value for the Time Delay to TB Diagnosis

The original publication is available at http:/www.plosone.orgIncludes bibliographyBackgound. In many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission. Methodology/Principal Findings. This study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic. Conclusions/Significance. The analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed. © 2007 Uys et al.Publishers' Versio

Identifying Critical Non-Catalytic Residues that Modulate Protein Kinase A Activity

Distal interactions between discrete elements of an enzyme are critical for communication and ultimately for regulation. However, identifying the components of such interactions has remained elusive due to the delicate nature of these contacts. Protein kinases are a prime example of an enzyme with multiple regulatory sites that are spatially separate, yet communicate extensively for tight regulation of activity. Kinase misregulation has been directly linked to a variety of cancers, underscoring the necessity for understanding intramolecular kinase regulation.A genetic screen was developed to identify suppressor mutations that restored catalytic activity in vivo from two kinase-dead Protein Kinase A mutants in S. cerevisiae. The residues defined by the suppressors provide new insights into kinase regulation. Many of the acquired mutations were distal to the nucleotide binding pocket, highlighting the relationship of spatially dispersed residues in regulation.The suppressor residues provide new insights into kinase regulation, including allosteric effects on catalytic elements and altered protein-protein interactions. The suppressor mutations identified in this study also share overlap with mutations identified from an identical screen in the yeast PKA homolog Tpk2, demonstrating functional conservation for some residues. Some mutations were independently isolated several times at the same sites. These sites are in agreement with sites previously identified from multiple cancer data sets as areas where acquired somatic mutations led to cancer progression and drug resistance. This method provides a valuable tool for identifying residues involved in kinase activity and for studying kinase misregulation in disease states

The effect of linking community health centers to a state-level smoker's quitline on rates of cessation assistance

<p>Abstract</p> <p>Background</p> <p>Smoking cessation quitlines are an effective yet largely untapped resource for clinician referrals. The aim of this study was to assess the effect of a fax referral system that links community health centers (CHCs) with the New York State Quitline on rates of provider cessation assistance.</p> <p>Methods</p> <p>This study was conducted in four CHCs using a quasi experimental study design. Two comparison sites offered usual care (expanded vital sign chart stamp that prompted providers to ask about tobacco use, advice smokers to quit, assess readiness, and offer assistance (4As)) and two intervention sites received the chart stamp plus an office-based fax referral link to the New York State Quitline. The fax referral system links patients to a free proactive telephone counseling service. Provider adherence to the 4 As was assessed with 263 pre and 165 post cross sectional patient exit interviews at all four sites.</p> <p>Results</p> <p>Adherence to the 4As increased significantly over time in the intervention sites with no change from baseline in the comparison sites. Intervention sites were 2.4 (p < .008) times more likely to provide referrals to the state Quitline over time than the comparison sites and 1.8 (p < .001) times more likely to offer medication counseling and/or a prescription.</p> <p>Conclusions</p> <p>Referral links between CHCs and state level telephone quitlines may facilitate the provision of cessation assistance by offering clinicians a practical method for referring smokers to this effective service. Further studies are needed to confirm the efficacy of fax referral systems and to identify implementation strategies that work to facilitate the utilization of these systems across a wide range of clinical settings.</p

Risk factors for treatment delay in pulmonary tuberculosis in Recife, Brazil

BACKGROUND: Tuberculosis is still a great challenge to public health in Brazil and worldwide. Early detection followed by effective therapy is extremely important in controlling the disease. Recent studies have investigated reasons for delays in treatment, but there is no agreed definition of what constitutes an "acceptable" delay. This study investigates factors associated with total delay in treatment of tuberculosis. METHODS: A cohort of adult cases of pulmonary tuberculosis diagnosed over a two-year period was studied. Patients were interviewed on entry, reporting the duration of symptoms before the start of treatment, and sputum and blood samples were collected. It was decided that sixty days was an acceptable total delay. Associations were investigated using univariable and multivariable analysis and the population attributable fraction was estimated. RESULTS: Of 1105 patients, 62% had a delay of longer than 60 days. Age, sex, alcoholism and difficulty of access were not associated with delays, but associations were found in the case of unemployment, having given up smoking, having lost weight and being treated in two of the six health districts. The proportion attributable to: not being an ex-smoker was 31%; unemployment, 18%; weight loss, 12%, and going to the two worst health districts, 25%. CONCLUSION: In this urban area, delays seem to be related to unemployment and general attitudes towards health. Although they reflect the way health services are organized, delays are not associated with access to care