Although the link between social factors and health-related outcomes has long been widely acknowledged, the mechanisms characterizing this link are relatively less known and remain a subject of continued investigation across disciplines. In this study, drawing on the structural influence model of health communication, the hypothesis that differences in concern about and information needs on HIV/AIDS, HIV/AIDS-related media use, and perceived salience of HIV/AIDS-related information, characterized as communication inequality, can at least partially mediate the impacts of socioecological  and socioeconomic (education) disparities on inequalities in HIV/AIDS knowledge and risk perception was tested.Data were collected from a random sample of 986 urban and rural respondents in northwest Ethiopia. Structural equation modeling, using the maximum likelihood method, was used to test the mediation models.β = 0.28, p = .001; education: β = 0.08, p = .001) and HIV/AIDS risk perception .The models showed an adequate fit of the data and hence supported the hypothesis that communication inequality can at least partially explain the causal mechanism linking socioeconomic and socioecological factors with HIV/AIDS knowledge and risk perception. Both urbanity versus rurality and education were found to have significant mediated effects on HIV/AIDS knowledge (urbanity vs. rurality: It was concluded that communication inequality might form part of the socioecologically and socioeconomically embedded processes that affect HIV/AIDS-related outcomes. The findings suggest that the media and message effects that are related to HIV/AIDS behavior change communication can be viewed from a structural perspective that moves beyond the more reductionist behavioral approaches upon which most present-day HIV/AIDS communication campaigns seem to be based. The fact that social factors affect health-related outcomes directly or indirectly has garnered considerable evidence over the past several decades. Most of the factors referred to as the social determinants of health might well be seen in terms of and/or subsumed by the three most notable and widely studied factors: socioeconomic status (SES), social capital, and socioecological factors. The role of social factors in health has become increasingly apparent in recent years; however, our understanding of the mechanisms through which such factors exert influences is relatively incomplete,2 and reIn a review synthesizing knowledge about SES and health, Adler and Ostrove observedcommunication inequality seems to have acquired currency in the realm of health communication in recent years. Communication inequality “may be defined as differences in the generation, manipulation, and distribution of information among social groups; and differences in (a) access and use, (b) attention, (c) retention, and (d) capacity to act on relevant information among individuals” duals” duals”  play important roles. Previous research in the region has shown that people with better educations generally tend to have better HIV/AIDS-related outcomes  compared with less-educated individuals-24. SuchWhile the impacts of education and area of residence on HIV/AIDS-related outcomes appear to be well documented, the evidence addressing the mechanisms through which such impacts could be exerted is limited. In an attempt to respond to this paucity of information and to contribute to current understanding of the role of communication inequality, we hypothesized that HIV/AIDS-related communication might be patterned by education level and area of residence and might thereby be a pathway through which these factors affect HIV/AIDS-related outcomes. To test our hypothesis, we developed two structural models in which HIV/AIDS communication inequality was expected to somewhat mediate the effects of area of residence and education on HIV/AIDS knowledge and HIV/AIDS risk perception . In sub-Saharan Africa, HIV is mainly transmitted via heterosexual intercourse[A household survey was conducted between March and June 2011 in two urban towns (Bahir Dar and Debre Markos) and two rural villages (Jajirab and Kurfa) in northwest Ethiopia. Data were gathered from 986 respondents  aged 15 to 34 years  and willing to participate and were the same gender as the enumerators. College-educated enumerators were recruited, trained, and deployed to administer the questionnaire by reading it aloud to all of the participants, as the majority of the rural respondents were illiterate, and we wished to ensure high response and return rates. We attempted to address a possible social desirability bias by selecting enumerators who were not known locally but were familiar with the local dialect and customs and by using same-gender enumerator-respondent combinations. The stuYes, No, and Don’t Know. The most commonly accentuated problem in most knowledge measures is the confounding of knowledge with belief[M = 22.67, SD = 13.14).A detailed measure of HIV/AIDS knowledge was prepared based on previous measures-40. The h belief. Often, M = 3.22, SD = 0.83). The perception of susceptibility was measured by four items: (1) I am at risk for getting HIV/AIDS; (2) I may have had sex with someone who is at risk for HIV; (3) My sexual experiences do not put me at risk for HIV (inversely scored); and (4) There is a possibility that I have HIV. The scale had good reliability . The HIV/AIDS risk perception was calculated by averaging the two measures .This variable measured the participants’ perceptions of severity and susceptibility. The perception of severity was measured by three items: (1) Getting HIV is a sure death sentence; (2) Getting HIV/AIDS is nothing special and is like any other disease (inversely scored); and (3) Getting HIV/AIDS is the worst thing that could happen to me. The scale had a good internal consistency .This variable refers to an individual’s deliberate and/or nondeliberate use of mass media  for HIV/AIDS-related information over the previous month. Three items with seven-point response categories were used: In the last month, how often, on average, did you (1) read HIV/AIDS-related articles/stories in newspapers, pamphlets, or brochures?; (2) listen to HIV/AIDS-related messages on radio? (3) watch HIV/AIDS-related messages/shows on television? The response categories were 1 = Not at all; 2 = Once a week; 3 = 2–3 times a week; 4 = 4–5 times a week; 5 = 6–7 times a week; 6 = 8–9 times a week; and 7 = 10 or more times a week. The overall HIV/AIDS-related media use was calculated by averaging the three items .This variable was measured using the following items: (1) HIV/AIDS is the disease I am currently most concerned about and would like to get information about; (2) HIV/AIDS is the disease that concerns most people in my community and they would like to obtain more information about it; and (3) HIV/AIDS is the most common cause of poor health and death in my community. The respondents were asked to indicate their agreement on a five-point scale that ranged from 1 (strongly disagree) to 5 (strongly agree). The measure had good internal consistency .This variable was assessed using a measure that consisted of three items: (1) I feel that the HIV/AIDS-related information that is being disseminated via different channels is relevant to me, (2) I feel that the HIV/AIDS-related information that is being disseminated via different channels is relevant to residents of my community, and (3) I feel that the HIV/AIDS-related information that is being disseminated via different channels is applicable to my current situation. The response categories ranged from 1 (strongly disagree) to 5 (strongly agree). The scale had good internal consistency , 2 = primary (32.0%), 3 = secondary (13.4%), and 4 = tertiary (8.2%).The analysis began by calculating descriptives and zero-order correlations to create an overview of the relationships between the variables. To obtain preliminary evidence about whether urbanity versus rurality and education affected HIV/AIDS knowledge and HIV/AIDS risk perception, two linear regression models were performed, with demographics (age and gender) included as controls. The hypothesized model was then tested with structural equation modeling (Amos) using the maximum likelihood method. Two models were tested: one with HIV/AIDS knowledge as an endogenous variable and the other with HIV/AIDS risk perception as an endogenous variable. As indicated in the model, communication inequality  has been hypothesized to mediate the relationships only partially. To test whether there was full or partial mediation, two constrained models were tested, and their fit indices were compared with those of the unconstrained models.Following the recommendations of Bollen and Long, the modFurther, following Aish and Jöreskog, insigniZero-order correlations indicated that the variables have strong positive relationships  and education  were significant predictors of HIV/AIDS knowledge, which explained 57.5% of the variance  = 334.11, p < .001) when age and gender were controlled. Similarly, both predictors  were significant in predicting HIV/AIDS risk perception, explaining 40.8% of the variance  = 170.63, p < .001) when demographics were controlled.The regression analysis showed that both urbanity versus rurality (2(3) = 12.06, p = .007, CMIN/DF = 4.02, CFI = .99, RMSEA = .05, GFI = .99, AGFI = .97.The model shown in Figure β = 0.53, SE = .03, p = .001; HIV/AIDS-related media use, β = 0.51, SE = .03, p = .001; and the perceived salience of HIV/AIDS-related information, β = 0.64, SE = .03, p = .001), education was significantly related to only two of these components . Moreover, all three components were found to be significantly related to HIV/AIDS knowledge: HIV/AIDS concern and information needs, β = 0.36, SE = .03, p = .001; HIV/AIDS-related media use, β = 0.05, SE = .02, p = .03; and the perceived salience of HIV/AIDS-related information, β = 0.10, SE = .03, p = .001.The model indicated that while urbanity versus rurality was significantly related to all three components of HIV/AIDS communication inequality  was stronger than that of education . Removing the insignificant path connecting education with perceived salience of HIV/AIDS-related information did indeed slightly improve the overall indirect effect of education, but the effect was still not as strong as that of urbanity versus rurality. A comparison of the fit indices of the constrained model, in which the path coefficients of the direct effects of urbanity versus rurality and education were constrained  and the unconstrained model  further confirmed that the mediation was indeed partial; the unconstrained model yielded better fit indices than the constrained model.Consistent with our prediction, the model showed that HIV/AIDS communication inequality mediated the impacts of urbanity versus rurality and education on HIV/AIDS knowledge. The total indirect effect of urbanity versus rurality through the three components of communication inequality (ained (χ2) = 248.4β = 5.0, p = .001) and education  had their strongest effects on HIV/AIDS knowledge through HIV/AIDS concern and information needs. The second most important indirect effects of urbanity versus rurality  and education  on HIV/AIDS knowledge were through the perceived salience of the HIV/AIDS-related information and HIV/AIDS-related media use, respectively. While the least significant indirect effect of urbanity versus rurality  occurred through HIV/AIDS-related media use, education had an insignificant indirect effect  through the perceived salience of the HIV/AIDS-related information.When we assessed individual indirect effects, both urbanity versus rurality (2(3) = 12.06, p = .007, CMIN/DF = 4.02, CFI = .99, RMSEA = .05, and GFI = .99; AGFI = .97.Figure β = 0.22, SE = .03, p = .001; HIV/AIDS-related media use, β = 0.24, SE = .03, p = .001) and the perceived salience of HIV/AIDS-related information .The effects of urbanity versus rurality and education on the three components of communication inequality were of the same direction and magnitude as those derived from Model 1. While urbanity versus rurality was significantly related to all three components of HIV/AIDS communication inequality, education was significantly related to only two of the three components. Moreover, all three of the components were significantly related to HIV/AIDS risk perception: HIV/AIDS concern and information needs  was stronger than the total indirect effect of education . Removing the insignificant path that connected education with the perceived salience of HIV/AIDS-related information slightly improved the overall indirect effect of education, but it was still weaker than that of urbanity versus rurality. Similar to Model 1, the comparison of the fit indices of the constrained model  and the unconstrained model  further confirmed that the mediation was indeed partial; the unconstrained model yielded much better fit indices than the constrained model.As with Model 1, Model 2 showed the mediating role of HIV/AIDS communication inequality. The total indirect effect of urbanity versus rurality through the three components of communication inequality  on HIV/AIDS risk perception through HIV/AIDS-related media use, education exerted equally strong effects through HIV/AIDS concern and information needs  and HIV/AIDS-related media use . The second most important indirect effect of urbanity versus rurality occurred through HIV/AIDS concern and information needs , and the weakest indirect effect occurred through the perceived salience of HIV/AIDS-related information ; education had an insignificant effect  through the perceived salience of the HIV/AIDS-related information.Individual indirect effects showed that although urbanity versus rurality had its strongest effects  might well be seen from a structural point of view, moving beyond the more reductionist behavioral approaches upon which most present-day HIV/AIDS communication interventions seem to be based ,49. The The findings may also contribute to research and theories that have followed the knowledge gap hypothesis for decades. ResearcThis study may also help to advance SIM of health communication. More spApart from these theoretical implications, the findings may have several practical applications. First, in line with the theoretical implications that we have drawn, identifying the mechanisms through which socioeconomic and socioecological factors affect health-related outcomes could be valuable when designing prevention interventions. In line with SIM, we argue that the structural aspects of the environments (characterized by poor or no communication technology infrastructure) where the rural populace and people with low education levels live and the social roles that these people inhabit may place them in positions that prevent them from benefiting from ongoing HIV/AIDS communication efforts compared with their urban and better-educated counterparts. This disparity may require a re-examination of our tacit assumptions that communication interventions based on the use of mass media can be used to address the “masses” across the board. More specifically, communication interventions may need to identify the communication needs of disadvantaged groups  to move beyond the traditional biases of generalizing effects.Second, and more specifically, our findings indicated that the rural populace and people with low education levels seem to be unconcerned or have little concern about HIV/AIDS; consequently, their overall use of the mass media to obtain prevention information was relatively low. Therefore, BCC efforts in the region might need to alert the poorly educated rural populace about the danger of infection.Third, research has shown that concern about a given health problem affects the effectiveness of the prevention messages about that health problem. SpecifiFinally, our findings suggest that low levels of perceived salience of HIV/AIDS-related information among the rural populace might have contributed to their reduced levels of HIV/AIDS-related media use. The rural populace could thus be motivated to use the mass media for HIV/AIDS information if the content was more relevant and appealing to them. In practice, this would mean that programmatic adjustments must be made in such a way that mass media HIV/AIDS campaigns could include contents more relevant to the rural populace while also providing messages that are relevant to urbanites. Indeed, it is conceivable that there could be various other factors that contribute to the overall lack of HIV/AIDS-related media use among the rural populace and the low SES population sub-group. For instance, previous research in sub-Saharan Africa has suggested that non-HIV life expectancy, which could vary by SES and area of residence, could be one of the factors importantly related to behavioral responses to the infection. It coulAs any study, the merits of the present paper should be evaluated based on a contributions-to-limitations assessment. The stuBecause we live in an era whose main distinctive feature is arguably the increased vitality of information and communication, the control of information is power, and people and/or population subgroups with the capacity to generate, access, use, and redistribute information clearly possess the social power and the privileges that accrue from it,15,63. TThe authors declare that they have no competing interests.Both authors contributed to the manuscript equally. Both authors conceived and designed the study. MAB collected, analyzed and interpreted the data. SE contributed to the analysis and interpretation of the data. MAB drafted and revised the manuscript. SE was involved in drafting and revising the manuscript. Both have given final approval of the version to be published.MAB is a doctoral student at the University of Leuven, Belgium. He is affiliated to Bahir Dar University, Ethiopia. His research focuses on behavior change communication. He is currently at the Harvard School of Public Health to finalize his doctoral research. SE is an associate professor at the University of Leuven. He is the director of the communication sciences program at the faculty of social sciences, University of Leuven.


The aim of the present study was to standardize [11C]MET positron emission tomography (PET) by optimizing the timing of initiation of the scan and applying correction to the plasma concentrations of neutral amino acids (NAAs), where necessary.[Sequential whole-body MET PET/computed tomography (CT) was performed in 11 normal adults after they had fasted for at least 4 h. After whole-body CT for attenuation correction and intravenous bolus injection of MET, the subjects were scanned from the parietal to the groin. The scanning was repeated six to seven times. Decay of radioactivity during the PET scan was corrected to the time of initiation of the first scan. The standardized uptake values (SUVs) were evaluated in various organs by setting regions of interest on the tomographic images. Plasma concentrations of NAAs were examined in relation to the SUV values.The SUVs in the pancreas reached their plateau from 6.5 to 11 min after the MET injection, and in the brain, lung, and myocardium, they reached their plateau from 19.6 to 24.1 min. The MET uptake in the spleen and kidney peaked early after the injection and steadily decreased thereafter. The SUVs in the liver and stomach wall rapidly increased during the first 0 to 4.5 min and gradually elevated thereafter during the scan period. Urinary radioactivity in the bladder reached its plateau from 26.1 to 30.6 min after the MET injection. There were no correlations between the plasma concentrations of NAAs and the maximal SUV in any organs.The present study revealed the times taken to reach the plateau of MET uptake in various important organs, and little effects of the plasma neutral amino acid concentrations on the SUVs in PET studies conducted after the patients had fasted for at least 4 h. In the MET PET study, 4 h fasting period before MET administration and the scan initiation 20 min after MET administration provide the SUV values independent of scan initiation time and the plasma neutral amino acid concentrations. Therefore, it is important to initiate the scanning at a consistent time-point after the FDG injection. The SNM procedure guidelines for tumor PET imaging recommended that emission images should be obtained at least 45 min after injection of the radiopharmaceutical MET is transported through the NAA transporter from the plasma to the tissues. Therefore, plasma NAA concentrations could affect the uptake of [11C]MET in a competitive fashion. Ito et al. reported that brain uptake of the NAA tracer [18F]fluorophenylalanine was inversely correlated with the plasma NAA concentrations [11C]MET accumulation in the target tissues. In this study, we did not find a significant effect of the plasma methionine-equivalent concentrations on the MET uptake. This is considered to be due to the fact that in our subjects, the NAA concentrations in the plasma returned within normal range after a fasting period of 4 h . On the other hand, Ito et al. did not set a fasting period prior to the study [Another factor influencing the SUVs of MET is the plasma concentrations of NAAs. [trations . Howeverhe study . Four of18F]fluorophenylalanine mainly recognizes amino acid transport but is not metabolized in the cell, while MET is metabolized in the cells after transportation. The difference may affect the effect of NAA on tissue MET uptake.There are two limitations to this study. First, though blood clearance was one of the important factors for determining the best timing of scan initiation, we did not take blood samples and measure their radioactivities during the scan. We carefully set and measured ROI in the left ventricle blood pool instead and confirmed that blood clearance was rapid. Second, [The present study demonstrated that the SUVs of MET in normal tissues can be measured by starting the PET imaging 20 min or later after MET infusion, during the plateau phase of accumulation, and by requesting a 4-h fasting period prior to the study. These conditions for the procedure are expected to provide the SUVs of MET in the target tissues independent of the scan initiation timing or the plasma NAA concentrations.The authors declare that they have no competing interests.KI, ES, and JH participated in the design of the study and performed the statistical analysis. Data acquisition was done by KI, ES, YK, SN, and KF. Data analysis was done by KI, HK, and HW. The manuscript was prepared by KI. All authors read and approved the final manuscript.


Procalcitonin (PCT)-protocols to guide antibiotic treatment in severe infections are known to be effective. But less is known about the long-term effects of such protocols on antibiotic consumption under real life conditions. This retrospective study analyses the effects on antibiotic use in patients with severe sepsis and septic shock after implementation of a PCT-protocol.We conducted a retrospective ICU-database search for adult patients between 2005 and 2009 with sepsis and organ dysfunction who where treated accordingly to a PCT-guided algorithm as follows: Daily measurements of PCT . Antibiotic therapy was discontinued if 1) clinical signs and symptoms of infection improved and PCT decreased to ≤1 ng/ml, or 2) if the PCT value was >1 ng/ml, but had dropped to 25-35% of the initial value within three days. The primary outcome parameters were: antibiotic days on ICU, ICU re-infection rate, 28-day mortality rate, length of stay (LOS) in ICU, mean antibiotic costs (per patient) and ventilation hours. Data from 141 patients were included in our study. Primary outcome parameters were analysed using covariance analyses (ANCOVA) to control for effects by gender, age, SAPS II, APACHE II and effective cost weight.From baseline data of 2005, duration of antibiotic therapy was reduced by an average of 1.0 day per year from 14.3 ±1.2 to 9.0 ±1.7 days in 2009 (p=0.02). ICU re-infection rate was decreased by yearly 35.1%  just as ventilation hours by 42 hours per year . ICU-LOS was reduced by 2.7 days per year (p<0.001). Trends towards an average yearly reduction of 28-day mortality by −22.4%  and mean cost for antibiotic therapy/ patient by −14.3 Euro (95% CI −55.7 to 27.1) did not reach statistical significance.In a real-life clinical setting, implementation of a PCT-protocol was associated with a reduced duration of antibiotic therapy in septic ICU patients without compromising clinical or economical outcomes.DRKS00003490 There is a dramatic increase in antibiotic-resistant infections -3, leadiBut, shortening the length of antibiotic courses seems to play an important role in reducing antibiotic resistance  and its Although the effectiveness of PCT-guided antibiotic therapy has been proven in several randomised clinical trials, so far less is known about implementation and effects of such protocols under out-of-study conditions. For patients with respiratory infections outside the ICU, two studies demonstrated that following a PCT algorithm significantly reduces antibiotic use without increasing the risk of complications ,23. But Ethics commission approval was obtained from the Medical Faculty at Christian Albrecht University of Kiel (D409/10) for our trial in the surgical intensive care ward at the West Coast Hospital in Heide. The informed consent was waived in view of the retrospective and anonymous nature of the study.In 2005 we introduced a PCT-guided algorithm as follows: Daily measurements of PCT  with the daily routine blood samples. Antibiotic therapy was discontinued if 1) clinical signs and symptoms of infection improved and PCT decreased to ≤1 ng/ml, or 2) if the PCT value was >1 ng/ml, but had dropped to 25-35% of the initial value within three days /fraction of inspired oxygen (FiO2) < 300 mmHg), acute renal dysfunction (2-fold baseline creatinine increase or urine output < 0.5 ml/kg for at least two hours), platelet count below 100,000 cells/mm3, lactate blood concentration above 2 mmol/l or sepsis induced impaired mental status. Patients with sepsis induced mean arterial pressure below 65 mmHg for ≥ 1 hour despite adequate fluid resuscitation were classified as having septic shock).We conducted a retrospective ICU-database search for adult patients from our surgical ICU between 2005 and 2009 with a) sepsis and b) organ dysfunction on presentation as defined by the ACCP/SCCM Consensus Conference Committee   and do-not-resuscitate orders. Also, patients with an incomplete data set were excluded.Data were collected for gender, age, Simplified Acute Physiology Score (SAPS) II, Acute Physiology And Chronic Health Evaluation (APACHE) Score II, German Diagnosis Related Groups (G-DRG)-effective cost weight and for the primary outcome parameters: antibiotic days on ICU, ICU re-infection rate, LOS in ICU, ventilation hours, 28-day mortality, and antibiotic costs per patient. Re-infection was defined as the growth of the initial causative bacterial strains, taken from the same infection site after ≥ 48 h of stopping antibiotics, in addition to clinical signs or symptoms of infection. Mean antibiotic costs per patient (Euro) were calculated by means of the hospital’s wholesale prices without costs of administration.Descriptive statistics are mean ± standard deviation for patient characteristics or mean ± standard error or 95% confidence intervals (CI) for outcome. Chi-squared test was employed for comparison of infection sites over the years. Number of PCT-measurements per patient for trend significance over the years was analysed with Kruskal-Wallis test. Annual means/ percentages of patient characteristics were first compared for any difference by analysis of variance (ANOVA) for continuous characteristics and by logistic regression for categorical characteristics. P values of the corresponding F tests and Wald chi-square tests are reported. In a second step, polynomial contrasts and Cochran-Armitage tests were applied to test whether linear trends were to be observed in patient characteristics over the total study period. Since in observational studies of moderate size even non-significant imbalances may bias the results to a relevant extent, outcome analysis was exclusively performed by statistical control of the baseline characteristics. Thus, outcome parameters were tested for linear trends by analysis of covariance (ANCOVA) or logistic regression models with adjustment for the covariates gender, age, SAPS II, APACHE II and effective G-DRG cost weight. A p < 0.05 was considered statistically significant.This method proves to be useful when a retrospective comparison between different treatment groups is performed as it compensates for imbalances in important prognostic variables, which may lead to biases in treatment effect, and additionally reduces the residual variability in the statistical models, thus increasing the precision of the estimates and the power of the applied statistical tests.The statistical software package SPSS 15.0  and STATA 11.0  were used for statistical analysis.Data of 4212 ICU-patients from 2005 to 2009 were screened. Through our data filter, we identified 146 patients with severe sepsis or septic shock. Of these, 5 patients were excluded from the study because of incomplete data set. In total, 141 patients were included in the final analysis set  from 14.3 ±1.2 to 9.0 ±1.7 days, rate of re-infection on ICU , ICU-LOS  and ventilation time . Trends towards reduction of 28-day mortality by 22.4% per year  and total cost for antibiotic therapy  per patient did not reach statistical significance  to 9.0 ± 1.7 days (2009). This reduction was associated with a significant reduction in ICU re-infection rate, ICU-LOS and ventilation hours and non-significant reduction of 28-day mortality and mean costs of antibiotics per patient. Thus, shortening antibiotic therapy did not have negative effects on clinical or economical outcome.The length of antibiotic therapy was effectively reduced in several randomised controlled trials using PCT-guided algorithms. Thus, it was concluded that implementation of a PCT-based algorithm may reduce antibiotic exposure in critically ill, septic patients without compromising clinical outcomes . Hence, However, little is known about transfer of such protocols into clinical practice and development of antibiotic use after implementation of a PCT-guided algorithm. Implementation of new protocols in an ICU is complex, multi-professional, and transfer to clinical practice and optimisation of adherence is time-consuming and develops over a long period. For example, variability in compliance with sepsis resuscitation bundles has recently been shown . And in Interestingly, we found a yearly reduction of 35.1% in ICU re-infection rate. To our knowledge, so far, six randomised controlled trials assessed the utility of PCT in tailoring antibiotic therapy in septic ICU individuals ,15-17,28Furthermore, an average yearly mortality reduction of 22.4% and decreased ventilation hours cannot be solely explained by implementation of a PCT algorithm. In 2004, sepsis guidelines for management of severe sepsis and septic shock were published and extensively implemented in clinical practice . Impact PCT-algorithms for guidance of antibiotic treatment may enhance adherence to guidelines since clinicians may be reassured in their decision to discontinue antibiotics by an objective parameter. It must be emphasised that PCT-algorithms are only a single component in strategies for optimising antibiotic treatment. Antimicrobial stewardship programs are important concepts for a more rational utilisation of antibiotics . Most elOur study revealed no significant antibiotic cost reduction. But there seems to be a trend to lower costs over the years. In our hospital, cost amounted to 14 Euros per PCT-test. But, a final assessment of cost effectiveness of a PCT-guided antibiotic therapy cannot be made with the present study design since there are numerous variables influencing clinical processes of care, many of which are difficult to quantify. For example, multi-resistant microorganisms significantly increase treatment expenses due to requirement of isolation procedures and use of costly reserve antibiotics. Shortening antibiotic treatment may have potential to reduce the incidence of multi-resistant microorganisms and therefore consequential costs. Also, possibly reduced incremental cost of antibiotic related adverse effects were not considered in our study. Furthermore, in times of shortage of ICU beds, a reduction in ICU-LOS leads to economical advantages. An average yearly reduction of 2.7 days in ICU-LOS like in our study has potential to conserve resources and enhance ICU capacity and thus may increase the hospital’s refund. A previous study confirmed that under certain, assumptions managing antibiotic treatment with PCT-guided algorithms may reduce overall cost of care  and a daAlthough antibiotic use has been reduced by PCT-guided strategies, a corresponding reduction in isolation of antibiotic-resistant organisms has not yet been demonstrated . Data foNumerous PCT-algorithms with different cut-off values for starting or discontinuing antibiotic therapy have been evaluated ,28,36-39Nonetheless, our data and the results of several studies and meta-analyses provide that PCT-guided algorithms seem to be a useful and safe tool in clinical practice to discontinue antibiotic treatment without negative effects on clinical or economical outcomes.The main shortcoming of our study is that we did not compare our results with data from a historical control group. Thus, it remains unclear to which extent reductions in antibiotic consumption and improvements in outcomes are exactly related to the PCT protocol. However, data from 2005, when the PCT-algorithm was implemented and number of PCT-measurements per patient was low, were used as baseline, showing how antibiotic use improved over the years when the program was transferred into clinical practice.In our study 3.4% of all patients were reported to have severe sepsis whereas prevalence for severe sepsis including septic shock in Germany’s ICUs is about 11% . A retroThis is the first study that analyses the long-term effects on antibiotic consumption after implementation of a PCT-guided algorithm to discontinue antibiotic treatment under real-life clinical conditions in ICU-patients. In a real-life clinical setting, implementation of a PCT-protocol was associated with a reduced duration of antibiotic therapy in septic ICU patients without compromising clinical or economical outcomes. Further studies to assess the impact of PCT-protocols on reduction of resistant organisms are required. Also, algorithm-adherence and cost-effectiveness of a procalcitonin-guided strategy should be fully evaluated in a real-life setting of an ICU.ACCP: American college of chest physicians; ANCOVA: Analysis of covariance; ANOVA: Analysis of variance; APACHE: Acute physiology and chronic health evaluation score; CI: Confidence interval; FiO2: Fraction of inspired oxygen; G-DRG: German diagnosis related group; ICU: Intensive care unit; LOS: Length of stay; PaO2: Partial pressure of arterial oxygen; PCT: Procalcitonin; RCT: Randomised controlled trial; SAPS: Simplified acute physiology score; SCCM: Society of critical care medicineSS served as consultant and has received payments from BRAHMS AG for speaking engagements. KW has received funding from BRAHMS AG for performing the statistical analysis. All other authors declare no competing interests.AH, SS and MH carried out data collection, contributed to the design of the study and drafted the manuscript. BB participated in the design of the study. KW participated in the design of the study, performed the statistical analysis and drafted the manuscript. AG and KB participated in the design of the study and data collection. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/158/prepub


It is well documented that prophylactic antibiotic could reduce surgical site infection significantly providing that it is given timely with right drug and right dose. However, administering prophylactic antibiotic in a timely manner is not easy. Several factors such as low awareness of importance of timing on prophylactic antibiotic given, the workflow, ease of administration and perception of individual responsibility toward the administration could all contribute to the failure of given timely antibiotic to reduce surgical infection.To investigate how these problems were tackled in an elective surgical hospital in order to achieve timely administering surgical prophylactic antibiotic.During the period 2009 to 2012, all anesthetic records of orthopedic operation performed at the Duchess of Kent Children’s Hospital at Sandy Bay were reviewed. Data on time, administrator of prophylactic antibiotic, logistic of antibiotics being issued, methods of safety guide for administration and infection control rate were collected.- Total 6061 cases were reviewed.- 99.9% of the prophylactic antibiotics were given within 15-45 minutes interval before operation.- 100% cases went through the safety check list by nurse.- Anesthesiologist administered all the antibiotics while surgeon prescribed all prophylactic antibiotics.- All prophylactic antibiotics were given in operating theater except Vancomycin.- However, 99% antibiotics went through their regular route to OT.- Infection rate was 0.13% over these 4 years.Clearly defined roles and responsibility in the process of prophylactic antibiotic administration were essential. Safety check list helped to enforce the guidelines. Monitoring the outcome alerted stakeholders to take necessary action. Successful transfer evidence-based guidelines into daily practice required multiple interventions and support from top management to frontline staff were vital.None declared.


The current overriding thought in HIV/AIDS communication in developing countries is the need for a shift from the cognitive model, which emphasises the decision-making of the individual, to the activity model, which emphasises the context of the individual. In spite of the acknowledged media shift from the cognitive to the activity model in some developing countries, some HIV/AIDS communication scholars have felt otherwise. It was against this background that this study examined the content of some selected Nigerian newspapers to ascertain the attention paid to HIV/AIDS cognitive and activity information. Generally, the study found that Nigerian newspapers had shifted from the cognitive to the activity model of communication in their coverage of HIV/AIDS issues. The findings of the study seem inconsistent with the theoretical argument of some scholars that insufficient attention has been paid by mass media in developing countries to the activity model of HIV/AIDS communication. It is suggested that future research replicate the study for Nigerian and other developing countries’ mass media. In response to the overwhelming burden of new cases of HIV infections in Africa, Asia, Latin America, and the Caribbean, the UNAIDS in 1997 initiated a project to examine the application of existing communication theories/models to HIV/AIDS prevention and care in those regions. Consequently, 103 leading global researchers were invited by UNAIDS to participate in one of five consultative workshops to review the theories/models and rethink their adequacy for Africa, Asia, Latin America, and the Caribbean. Accordingly, a new communications framework for HIV/AIDS was developed to redirect focus on the cognitive approach, which emphasises individual reason, to the activity approach, which emphasises contextual factors. The redirection came up as a response to the deficiencies of the cognitive models/theories, which are narrowly focused on the individual with insignificant consideration to critical contextual factors such as economic circumstances, political climate, and cultural environment among others  is a nationally driven agenda that involves the response of relevant sectors, organisations, and stakeholders .Consequently, some countries in Africa, including Nigeria, have responded by drawing up HIV/AIDS communication strategies to strengthen their national response capacities to the epidemic. Out of the estimated 33.2 million people worldwide living with the virus in 2007, Nigeria has the third-largest number after India and South Africa, with an estimated figure of 2.9 million. An estimated 168,474 people in the country became newly infected in this year  culture, 2) politics, 3) economics, 4) gender, and 5) spiritual/religion , 11, 20.A number of studies analysing media coverage of HIV/AIDS in developing countries –27 have A number of studies on Nigeria media coverage of HIV/AIDS , 28–30 hFor the most part, the empirical studies in the literature have been limited to the general analysis of 1) incidences of HIV/AIDS information, 2) depth of HIV/AIDS information, 3) focus of HIV/AIDS information, and 4) nature of HIV/AIDS in the mass media. A number of studies have focused on one or more of the above, with tangential comparisons of the individual and contextual information that define the character of the epidemic, but none have systematically offered a comparison of the attention paid to HIV/AIDS cognitive and activity information.In general, most Nigerian newspapers cover HIV/AIDS issues. However, eight daily newspapers were purposively chosen for the study. Several reasons guided the selection of the newspapers.The GuardianThe PunchThe VanguardNew NigeriaNigerian TribuneThisDayDaily TrustDaily ChampionFirst, their popularity and consistency on the newsstand justify their use. They are among the newspapers in the country that have been published consistently since their founding. This might have increased the validity of the study, as the editions of the newspaper that were sampled for the study were available. Second, with a network of national correspondents, the newspapers have earned respect for their in-depth coverage of national issues, including HIV/AIDS. This means that the newspapers cover areas where HIV/AIDS prevalence rate is both low and high. Third, the newspapers are famous for their coverage of health issues. For instance, they have been widely cited in workshops, seminars, and training sessions on health communications in the country. Fourth, the eight newspapers are among the most widely distributed in the country and by implication the most widely read. Hence, they have the capability of attracting wider feedback on national developmental issues, including health. Fifth, the newspapers are English language dailies. The selection of only English language newspapers is because they have wider readership in Nigeria than indigenous newspapers, which are limited to particular geo-ethnic areas. The readership encompasses the elites who not only influence government policies  but are themselves policy-makers. The newspapers are:The aim of the study is to ascertain the attention accorded to HIV/AIDS cognitive and activity information in selected Nigerian newspapers. Data were obtained by content analysis of the selected newspapers over a specified period of time. Content analysis was selected because it is the most appropriate method of providing indicators of the explicit character of Nigerian media in addressing HIV/AIDS as a development problem. The study was based on two-stage sampling: first, a sample of newspapers was taken, then a sample of newspaper editions. The units of analysis were all newspaper items . The categories for coding content related to HIV/AIDS in the newspapers were based on those developed by JAAIDS, Nigeria,  on the cAwareness/preventionTreatment/careAdvocacy and campaignCure claimsPolicy pronouncementsLitigationStatistics/trendsResearchThe content categories are:The Guardian, 0.891; The Punch, 0.918; Tribune, 0.903; ThisDay, 0.927; Trust, 0.944; Champion, 0.915; New Nigerian, 0.936; Vanguard, 0.954). Krippendorff's α for all the newspapers put together was 0.928. Given these high results, the coding sheet as well as the coders were considered reliable for the study. The Statistical Package for the Social Sciences (SPSS) was employed to analyse the study data with the aid of a computer. Descriptive statistics was used to highlight the frequency and percentage of HIV/AIDS cognitive and activity information in the selected newspapers on tables. Subsequently, the SPSS Sub-program t-test (independent samples) was used to test the hypotheses. The data were analysed to ascertain the attention paid to HIV/AIDS cognitive-oriented information and HIV/AIDS activity-oriented information in terms of frequency, prominence, and space.To maximise consistency in coding and formally assess the intercoder reliability, the coding sheet was pilot tested. Krippendorff's alpha (α) statistic was used to verify the intercoder reliability. To compute α, the SPSS macro (KALPHA) produced by Hayes and Krippendorff  was emplCoders identified a total of 779 HIV/AIDS information leading to 908 attention scores of information location and 41365.7 col.cms of information space. Daily Trust newspaper, which published an equal amount of activity and cognitive information, all of the other newspapers published more activity than cognitive information.The findings show that in terms of frequency, information on HIV/AIDS activity predominate in Nigerian newspapers. The data in Count within newspapers suggests that HIV/AIDS activity-oriented news stories significantly dominated HIV/AIDS cognitive-oriented news stories across all of the newspapers. As shown in The results of this study also suggest that, in terms of page placement, Nigerian newspapers give more prominence to HIV/AIDS activity news stories than HIV/AIDS cognitive news stories in their coverage of HIV/AIDS issues, although the difference is not statistically significant.In all of the newspapers, there was no news story on HIV/AIDS that made front and back pages lead. There were equal proportions of news stories of HIV/AIDS activity and cognitive orientations among the news stories that appeared on the front page. Activity news stories accounted for 50% (or 20), as did cognitive news stories, which also accounted for 50% (or 20). However, among the news stories which constituted the back page, page 2, and other inside pages, activity-oriented news stories had more attention scores than cognitive-oriented news stories.Vanguard.Analysis of the study findings further shows that HIV/AIDS activity news stories predominate in terms of space occupation. As shown in Daily Trust, New Nigerian, Tribune, and Daily Champion) did not publish HIV/AIDS editorials at all during the period studied  with the exception of The Punch paid more attention to HIV/AIDS activity editorials than to HIV/AIDS cognitive editorials. The total number of HIV/AIDS activity editorials was seven (or 63.6%) while the total number of HIV/AIDS cognitive editorials was four (or 3.4%).With regard to frequency of HIV/AIDS editorials, the findings show that although Nigerian newspapers carry more HIV/AIDS activity editorials than HIV/AIDS cognitive editorials in their coverage of HIV/AIDS issues, they carry insignificant number of editorials of activity orientation compared to editorials of cognitive orientation. Four of the eight newspapers  have the capacity to stimulate debate and foster a social environment in which AIDS is addressed in the spirit of openness and communality.It can be observed that straight news stories dominated the HIV/AIDS information items studied see . It is aThe insignificant difference in prominence between HIV/AIDS activity-oriented news stories and HIV/AIDS cognitive-oriented news stories is suggestive of the editorial value Nigerian newspapers attach to HIV/AIDS activity-oriented new stories in particular and HIV/AIDS stories in general. As pointed out earlier, it may be that Nigerian newspapers were still withdrawing from the cognitive model or better still, it could be as a result of the unimportant editorial value they attach to HIV/AIDS information generally. It is noteworthy that none of the newspapers sampled used an HIV/AIDS story as front or back page lead. Furthermore, both HIV/AIDS activity and cognitive stories have low attention scores on the front and back pages see . A numbeFor page placement of information, the insignificant difference between HIV/AIDS activity-oriented feature articles and HIV/AIDS cognitive-oriented feature articles is indicative of the social significance Nigerian newspapers attach to HIV/AIDS activity-oriented feature articles. Perhaps, this is because print space dedicated to one topic invariably displaces another and editors might not have the ‘see value’ in dedicating scarce and valuable column centimetres to activity feature articles. In other words, activity feature articles were not given the required contextual depth. This seems consistent with the argument of Projecthope  that HIVFor a country that has the third largest HIV infection rate in the world, one would have expected the mass media to deliberately play an instrumental and a more active role in the battle against the disease by setting the agenda for in-depth contextual discourse. Nigerian newspapers have the greatest challenge by becoming more responsive.Generally, this study shows that Nigerian newspapers have shifted from the cognitive to the activity model of HIV/AIDS communication. Their gatekeeping, agenda setting, and agenda-building roles underscore the likelihood that the mass media in other developing countries may not be grounded in the cognitive model of HIV/AIDS communication, as observed by some scholars. They may be involved in HIV/AIDS communication using the activity model. It is therefore suggested that this study be replicated for the mass media of other developing countries, the Nigerian radio, television, magazines, and weekly/monthly newspapers to ascertain their level of response to the global call for a shift from the cognitive model to the activity model of HIV/AIDS communication.


The increasing prevalence of diabetes and its inadequate management results in a heavy burden of the disease for the patients, the health and the productive system and the overall community. Consequently, it is necessary to have new effective drugs to treat people with diabetes to decrease such burden. DPP-4 inhibitors can help to cope with this demand, but its usage is challenged by its apparent high cost. The aim of the current study was to compare a simulated cost-effectiveness ratio of metformin (MET) plus one drug of the DPP-4 inhibitors family, saxagliptin (SAXA) or sulfonylurea (SU) treatment during a 20-year period, from the perspective of the social security system, in a cohort of people with Type 2 diabetes (T2DM) who did not attain glycosylated hemoglobin treatment target values only with MET.A discrete event simulation model (Cardiff diabetes model) based on UKPDS 68 was used to simulate disease progression and to estimate the economic and health treatment consequences in people with T2DM. The clinical efficacy parameters for SAXA administration were obtained from the literature; local standard costs were considered for drug acquisition, adverse events (AEs), and micro/macrovascular complications. Costs were expressed in US dollars (2009) with an annual 3.5% discount and a 20-year time horizon.vs. 152.8). The total cost of the SAXA + MET cohort was 15% higher than that of the SU + MET cohort. Treatment with SAXA + MET resulted in a higher number of quality-adjusted life years (QALYs) (9.54 vs. 9.32) and life-years gained (LYGs) (20.84 vs. 20.76) compared to those treated with SU + MET. The incremental cost per QALY and LYG gained was $7,374 and $20,490, respectively.The SAXA + MET treated group had a lower number of non-fatal events than the SU + MET treated group. The model also predicted a lower number of fatal macrovascular events for the SAXA + MET group (149.6 According to the criteria proposed by the Commission on Macroeconomics and Health, the use of the combination SAXA + MET is highly cost-effective in Argentina. The QALY gain with SAXA + MET compared with SU + MET treatment was 0.22 per patient. There was only a small difference in LYG (0.08 LYG per patient).On the other hand, the number of QALYs per patient for SAXA + MET was larger than that of SU + MET  per QALY.The cost-effectiveness acceptability curve illustrates a probability of less than 58% that SAXA + MET is cost-effective compared with SU + MET Figure , conside1c, earlier and more frequent prescription has been recommended for the treatment of people with T2DM [versus addition of SU in a cohort of people with T2DM who did not attain, in Argentina, treatment target values of HbA1c with MET alone. The results indicate that the combination SAXA + MET produced a greater number of LYG and QALYs than that of SU + MET, with an incremental cost-effective ratio (ICER) equal to $ 7,374.Based on the overall safety and effectivity of incretin-based therapies to achieve the treatment target value of HbAith T2DM . Even whith T2DM , as any ith T2DM ,37. Therith T2DM ,39. Thisith T2DM ,41. In tper capita, and as "very cost-effective" if the ICER was less than the GDP per capita[Since in Argentina there is not an accepted universal criterion to define a threshold for cost-effectiveness ratio, we used guidelines specifically intended for international comparisons, as proposed by the Commission on Macroeconomics and Health . This crer capita,43. Sincer capita, our SAXet al. in a European population [1c > 6.5% while on MET in six European countries, using a discrete event simulation model which employed the UKPDS Outcomes Model risk equations for predicting risks of diabetes-related complications. They found that the discounted ICERs associated with the addition of SITA to MET, compared with adding a SU, the values ranging from €5,949 to €20,350 per QALY across countries. The sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycemia.Although in Latin America there are no similar studies to compare with, our results are similar to those reported by Schwarz pulation . These ai.e., more effective and less costly than rosiglitazone), with or without considering complications at baseline [On the other hand, the NICE assessment group compared the rosiglitazone plus MET and a SU with sitagliptin plus MET treatment using the acquisition cost of the combined rosiglitazone/MET formulation for the analysis. They noted that the comparison of sitagliptin and rosiglitazone as well as that of vildagliptin and pioglitazone did not consider side effects associated with the use of thiazolidinediones. It was found that the sitagliptin intervention was the dominant option  it only considered direct costs from a third party payer´s perspective; 2) it does not include nonmedical costs such as productivity lost and consequently it likely underestimates costs from a societal perspective; 3) the costs included in the analysis were obtained from a single institutional source (IOMA), no matter that IOMA is one of the most important institutions of social security system of Argentina and it is a reference for other institution. However, the update of the model results with additional sources of costs will improve its external validity; 4) data regarding utilities came from European population, which could be different for Argentinean one and thus it could have biased our results. In this regard we could argue that utility values were varied in the sensitivity analysis to show the impact on the outcomes of the model, and all the results of such sensitivity analysis variations confirmed those of our base case analysis. On the other hand, despite great efforts have been currently made to use the most accurate and up-to-date data sources to provide a realistic simulation of T2DM in Argentina, the model has a limitation shared by most modeling studies, namely, the uncertainty around projecting long-term outcomes based on clinical input data from a short-term study. This situation is conditioned by the absence of lifetime follow-up data from a well-designed clinical or epidemiological study. All these concerns suggest that the current results might be used with caution to avoid misleading conclusions rather than to deny their real value for decision makers and administrators.In brief, the data currently obtained using a stochastic simulation model designed to evaluate the impact of new therapies in people with T2DM -17 and lThe authors declare that JEC, JFE, JJG and LG have no competing interests, while EA and MW are employees of Bristol Myers Squibb.JJG conceived the study and coordinated the project. JEC, JFE, JJG and LG were responsible for literature review, real world-data acquisition, data analysis and manuscript writing. EA and MW cooperate in the literature search and access to as well as in the final revision of the manuscript. All authors read and approved the final version of the manuscript.


Groesbeck Parham and colleagues describe their Cervical Cancer Prevention Programin Zambia, which has provided services to over 58,000 women over the past fiveyears, and share lessons learned from the program's implementation andintegration with existing HIV/AIDS programs. Invasive cervical cancer is a leading cause of cancer-related death andmorbidity among women in the developing world.Screening coverage rates are very low in developing countries despitethere being proven, simple, “screen and treat” approachesfor cervical cancer prevention.In 2006 we initiated a partnership with the public health system inZambia and created the Cervical Cancer Prevention Program in Zambia(CCPPZ), targeting the highest risk HIV-infected women, and haveprovided services to over 58,000 women (regardless of HIV status) overthe past 5 years.We have demonstrated a strategy for using the availability, momentum, andcapacity-building efforts of vertical HIV/AIDS care and treatmentprograms to implement a setting-appropriate protocol for cervical cancerprevention within public health infrastructures.We report our lessons learned to help other cervical cancer preventioninitiatives succeed in the developing world and to avoid additionalburdens on health systems.Invasive cervical cancer (ICC) is a leading cause of cancer-related mortality andmorbidity among women in the developing world CCPPZ is a unique partnership between Zambian and United States partner institutionsfrom the academic , research (Centre forInfectious Disease Research in Zambia [CIDRZ]), and governmental  sectors. Prevention efforts have been rapidly scaled up, takingadvantage of a historical circumstance of increased attention and funding in theHIV/AIDS sector through the US President's Emergency Plan for AIDS Relief(PEPFAR) program The dearth of adequately trained cytotechnologists and pathologists, and therequirement for multiple patient visits, preclude successful utilization of cervicalcytology (“Pap smears”) in most of the developing world The increasing expansion, over the past decade, of bilateral  andmultilateral  donor funding for HIV/AIDS programs has transformedhealth care delivery in resource limited settings, particularly in sub-SaharanAfrica One of the most enabling and transforming aspects of the program involves utilizinginformation technology tools for enhancing the program's operations andenabling quality assurance. Telemedicine consultation through the “electroniccervical cancer control” model The program is, by design, integrated with the operations of the public health systemrun and operated by the Zambian Ministry of Health, a model that has helped itstransition from being a foreign-funded/led project to a locally/nationally“owned” program. Program nurses are recruited from the public sectorhealth care system, with add-on financial incentives to facilitate retention. Theprogram also employs community-based volunteers to serve as “peereducators” to facilitate community awareness, counteract misconceptions andmyths, and serve patient support functions For cancer prevention initiatives to succeed in the developing world, programs mustavoid placing additional burdens on health systems already stretched thin due tocompeting priorities. We have demonstrated a strategy for using the availability,momentum, and capacity-building efforts of vertical HIV/AIDS care and treatmentprograms to implement other disease-specific initiatives such as cervical cancerprevention


AIDS-associated cholangiopathy is a form of biliary tract inflammation with stricture formation seen in AIDS patients who are severely immunosuppressed. It is no longer common in countries in which HAART therapy is widely employed but is still seen in underdeveloped countries. The majority of patients are symptomatic at the time of presentation. Herein, we describe a seventy-four-year-old woman who presented with unilateral leg swelling after a prolonged airplane flight. She was otherwise entirely asymptomatic. Routine laboratory testing was notable for a hypochromic microcytic anemia, slight leukopenia, and mild hypoalbuminemia. Liver enzymes were all elevated. Deep venous thrombosis was confirmed, and a CT scan of the chest disclosed no pulmonary emboli. However, the visualized portion of the abdomen showed dilatation of the common bile and pancreatic ducts. This was confirmed on ultrasonography and MRCP, and no obstructive lesions were noted. An ERCP revealed a dilated common bile duct without filling defects or strictures. A balloon occlusion cholangiogram showed strictures and beading of the intrahepatic ducts. Shortly thereafter, serology for HIV returned positive along with a depressed CD4 cell count, and the patient was diagnosed with AIDS-associated cholangiography. A seventy-four-year-old Kenyan woman was admitted to the hospital with bilateral lower extremity edema. Three days earlier, she had arrived to the United States after a sixteen hour flight. Past medical history included a stroke with no residual deficits and chronic low-back pain. Her family history was unremarkable. The patient had a 30 pack-year history of smoking but had quit 3 years earlier. She neither drank nor used illicit drugs. Review of systems was notable for generalized pruritus without rash, a periodic nonproductive cough, dysphagia with globus sensation, and a recent unintended weight loss of 14 kg. She had not been sexually active in more than thirty years. 2 saturation 98% on room air. The initial physical exam was only remarkable for 2+ edema in the left lower extremity as well as bilaterally diminished lung sounds with occasional faint late inspiratory crackles at the bases. Her vital signs included a temperature of 36°C, blood pressure 104/68 mmHg, respiratory rate of 16 per minute, heart rate 80 per minute, and OAbnormal “routine” laboratory tests included hemoglobin 99 g/L, hematocrit 0.32 vol RBC/vol whole blood, WBC count 3,400/cc, 8% eosinophils, MCV 66 fL, and albumin 32 g/L; liver enzyme panel revealed an AST of 79 U/L , ALT of 67 U/L , alkaline phosphatase of 252 U/L , and GGTP of 287 U/L . The bilirubin and prothrombin time were normal. A venous duplex of the lower extremities revealed a thrombus in the left superficial femoral vein extending into the left popliteal vein. She was placed on heparin and warfarin.An initial chest X-ray evealed a right lower lobe patchy infiltrate versus atelectasis. Given her history of cough and weight loss, the patient was treated with ceftriaxone and azithromycin for possible pneumonia and placed on droplet precautions while a PPD was placed and a QuantiFERON Gold lab test was obtained. Written consent was also obtained to complete an HIV test. A CT scan of the chest showed no significant pulmonary pathology or embolism. The visualized portion of the abdomen showed dilatation of the common bile and pancreatic ducts. An abdominal ultrasound later confirmed dilatation of the common bile duct and showed central intrahepatic duct dilatation as well. No stones were visualized, but the distal portion of the common bile duct was obscured by overlying bowel gas. Magnetic resonance cholangiopancreatography (MRCP) showed pancreatic and biliary ductal dilatation without identification of any obstructive lesions. . An ERCPShortly thereafter, the patient's HIV test came back positive. The CD count was 124 per cubic millimeter with an HIV viral load of 2.6 million copies/mL. As it was suspected that the patient suffered from AIDS cholangiopathy, further laboratory studies were obtained. A stool study for Isospora ova and parasites and a direct stool study for Cyclospora were negative. An electroimmunofluroscent assay for cryptospora was also negative. The IgM level of CMV antibody was 0.34 , but the IgG level of CMV antibody was elevated at 4.74 antibody index.3 [The term “AIDS cholangiopathy” (aka AIDS-related cholangitis) was first coined in 1986 by Margulis et al. who described biliary tract abnormalities in patients with AIDS . That sa3 .The etiology of AIDS cholangiopathy is unknown, but it is believed to be related to opportunistic infections in the biliary tract where pathogens have often been detected. These infections likely cause a secondary sclerosing cholangitis due to the associated continual inflammation. It is theorized that enteric infection leads to portal bacteremia which, in turn, leads to subsequent bile duct injury and destruction . HIV itsThe pathogens associated with AIDS cholangiopathy are listed in Cryptosporidium was the first opportunistic infection reported in the bile ducts of AIDS patients in 1983 by two independent groups, Pitlik et al. . It is aEnterocytozoon bieneusi can be detected with hematoxylin and eosin stain, but is more apparent with Giemsa stain. In some cases, electron microscopy may be necessary [Before the introduction of HAART therapy, cytomegalovirus was detected in up to two-thirds of autopsies in AIDS patients. These patients often had coinfection with Cryptosporidium and Candida albicans. Common bile duct dilatation and a mural thickening of an acalculous gallbladder were often noted . It has ecessary , 20. Isoecessary . Mycobacecessary . Malignaecessary , 21. FinAffected patients often present with right upper quadrant abdominal pain (99%) and, less commonly, with fever and jaundice (10%) . AbdominLaboratory examination is helpful but not specific in the diagnosis of AIDS cholangiopathy. The classic laboratory profile in AIDS cholangiopathy is an alkaline phosphatase that is five- to seven-times the upper limit of normal and a moderate increase in transaminase levels. Alkaline phosphatase elevation may be the sole laboratory abnormality in some patients. Jaundice in AIDS cholangiopathy is usually mild with a total bilirubin less than twice the upper limit of normal indicating incomplete obstruction. In approximately 20% of patients with AIDS cholangiopathy, however, all aforementioned lab tests are within normal limits even with diagnostic findings on ERCP . AmylaseUltrasonography is useful in the initial screening of AIDS cholangiopathy as it can provide the intraluminal caliber, thickness of the gallbladder wall and bile ducts, the presence of stones, sludge and/or pericholecystic fluid . It is aCT is more useful than ultrasound in identifying intrahepatic strictures . It is aFour subcategories of AIDS cholangiopathy have been described: (1) papillary stenosis 15%), (2) intrahepatic sclerosing cholangitis-like lesions (20%), (3) a combination of papillary stenosis and intrahepatic sclerosing lesions (50%), and 4) long extrahepatic bile duct strictures with or without intrahepatic lesions (15%)  long ext. The com%, (2) inThe intrahepatic findings in AIDS cholangiopathy are comparable to those seen in primary sclerosing cholangitis (PSC) with a beaded appearance and a diminished arborization or pruning of peripheral branches. However, the extrahepatic manifestations of AIDS cholangiopathy are quite different from PSC . DivertiIn addition to imaging features, biopsy will often show an inflammatory infiltrate that is rich in T4 lymphocytes in primary sclersoing cholangitis while these cells are depleted in AIDS patients. The characteristic finding on biopsy in AIDS cholangiopathy is prominent mucosal folds which indicate inflammation and edema. This mucosal thickening can be diffuse or it can be focal in which case it is fine and nodular . ApproxiTreatment of AIDS cholangiopathy is primarily endoscopic sphincterotomy for papillary stenosis and stenting for dominant common bile duct strictures. Sphincterotomy provides persistent pain relief, but unfortunately has not been shown to prolong survival or improve transaminase elevation . AlkalinUrsodeoxycholic acid has been used in patients with AIDS cholangiopathy, given that the intrahepatic changes are similar to those found in primary sclerosing cholangitis. It has been shown to improve liver biochemistry. The recommended dose is 300 mg three times daily primarily for patients with intrahepatic ductal disease and elevated liver function tests. Patients with pain refractory to ECP may experience relief with ursodeoxycholic acid . In the pre-HAART era, the survival of patient with AIDS cholangiopathy had been generally dictated by the natural course of AIDS rather than the cholangiopathy since this disease tends to occur in patients with advanced AIDS. AIDS cholangiopathy was, itself, rarely fatal as other AIDS-related illnesses were usually the cause of death in these patients. In patients diagnosed with AIDS cholangiopathy before the introduction of HAART, the median survival time was 5–8 months compared to the 14 months median survival for those diagnosed with AIDS cholangiopathy after 1996 , 19, 29.Finally, it is recommended that patients with AIDS cholangiopathy intermittently have abdominal ultrasonography and CA 19-9 levels screening for cholangiocarcinoma. An early diagnosis might allow for complete resection of the tumor .


One consensus in discussions on HIV/AIDS communication in low and middle income countries (LMICs) is the need for communication models to focus on activity rather than cognitive indicators in order to achieve desired improvements in health behaviors and outcomes. Past failures of HIV/AIDS communication efforts in LMICs have been attributed to emphasis on cognitive indicators. This study analyses HIV/AIDS communication models in Nigerian newspapers.Data were obtained through analysis of manifest content of four Nigerian papers issued between 2002 and 2004. Frequency, prominence and space dedicated to HIV/AIDS-related topics were measured. Descriptive statistics were used to highlight the frequency and percentage of cognitive- and activity-oriented informationon HIV/AIDS.A total of 464 HIV/AIDS-related articles were identified. Fifty-nine percent (274) of articles were activity-oriented. Over half of articles were news stories. No news story made front and back pages lead. There were only nine editorials on HIV/AIDS.This study shows that the activity model of HIV/AIDS communication dominates the four Nigerian mainstream newspapers studied. However, it is worth noting the limited number of editorials and feature articles, which have the capacity to stimulate debate and foster a social environment in which AIDS is addressed in a spirit of openness. For a country that has thethird largest number of people living with HIV/AIDS globally, one would expect the mass media to deliberately play an instrumental and a more active role in the battle against the disease by engaging in in-depth contextual discourse on HIV/AIDS. Current thought in HIV/AIDS communication in low and middle income countries foregrounds the need to move beyond the cognitive approach to the activity approach .CognitivAlthough, cognitive models have been effective in western contexts , some scHowever, a dominant view in the literature is that the mass media in low and middle income countries are yet to transition from cognitive models to the activity model of HIV communication . PresentUsing data from a recent comparative study on HIV/AIDS cognitive and activity-oriented information content in four mainstream Nigerian newspapers, this paper examines; (a) the number of HIV/AIDS cognitive and activity information carried by Nigerian newspapers (b) amount of space devoted to HIV/AIDS cognitive and activity information by Nigerian newspapers, and (c) the location of HIV/AIDS cognitive and activity information in Nigerian newspapers. In other words, three variables  were measured in this study which covered a three-year period (2002– 2004).Although HIV was first reported in Nigeria in 1986, the study period coincided with the implementation of the first phase of Nigeria'smulti-sectoral and community-based national response to the epidemic. The four newspapers surveyed in the present study are the Guardian, Punch, New Nigerian and Daily Trust. The Guardian and Punch are published in southern Nigeria while New Nigerian and Daily Trust are published in the North. These papers represent an important outlet for health information. They have been in the forefront of the crusade against HIV/AIDS . In addiCoding: Coders, working in pairs, coded newspaper items independently of one another. Each pair of coders coded all issues of the same newspaper during the study period according to the coding scheme. Coding focused on manifest content. Data extraction and recording were performed manually. All coders were final-year undergraduate students of Mass Communication enrolled in print journalism in three Nigerian tertiary institutions . The coders were carefully recruited and trained to code. The training of coders included one 2-hour session a day for two weeks. The categories for coding HIV/AIDS-related content of the newspapers were based on those developed by Journalists Against AIDS (JAAIDS), Nigeria in 2003 on the coverage of HIV/AIDS in eleven Nigerian newspapers. The JAAIDS categories are similar to those Pratt et al  used in Intercoder Reliability: Intercoder reliability was measured using Krippendorff's alpha . KrippenThe units of analysis were all newspaper items . Each unit of analysis was coded as cognitive- or activity-focused based on the following categories: (1)Awareness/Prevention, (2)Treatment/Care, (3)Advocacy and campaign, (4)Cure claims, (5)Policy pronouncements, (6)Litigation, (7)Statistics/Trends, and (8)Research. As such, the frequency of either HIV/AIDS cognitive or activity information was measured by the number of items about HIV/AIDS in Nigerian newspapers. In terms of space, the items were measured in column centimeters (col. cms). The study quantified how much space is given to HIV/AIDS cognitive and activity information by multiplying the number of published HIV/AIDS items’ columns in the selected newspapers by their length in centimeters. The centimeters were measured by placing vertically a centimeter ruler alongside columns of published HIV/AIDS items.A modification of Budd's  attentioIt is assumed that the most important items are published on the front page with the lead outstanding, while the degree of priority on information items decreases into the inside pages. The back page is also considered critical and strategic because of its external position. For the study therefore, information items which were not published on front and back pages of the newspapers were considered of least attention or priority. Items that continued from the two pages (front and back) to inside pages have been classified as front and back (page).Coders identified a total of 464 pieces of HIV/AIDS-related information in the four newspapers corresponding to a total attention score of 571 and 22293.8 column centimeters of information space. The data were analyzed to ascertain the attention paid to HIV/AIDS cognitive-oriented information and HIV/AIDS activity-oriented information in terms of information frequency, prominence and space. One hundred and forty five (31%) pieces of HIV/AIDS-related information were in The Punch; 116 (25%) in the New Nigerian; 111 (24%) in The Guardian, and 92 (20%) in the Daily Trust. In terms of prominence, The Punch had the highest attention scores, 176 (31%). Daily Trust had 150 (26%); New Nigerian, 131 (23%) and The Guardian, 114 (20%). New Nigerian recorded the highest column centimeters with regards to HIV/AIDS information space, 6771.9 (30%); The Punch, 6023.6 (27%); Daily Trust, 5263.5 (24%) and The Guardian, 4234.8 (19%).The total number of HIV/AIDS activity-oriented information published by the four Nigerian newspapers was more than the total number of HIV/AIDS cognitive-oriented information during the period studied. Two hundred and seventy four (59%) pieces of HIV/AIDS-related information were activity-oriented. Apart from the Daily Trust which published an equal number of activity and cognitive information, all the other newspapers published more activity than cognitive information. The proportions of activity-oriented pieces of HIV/AIDS-related information were 64.7% in the New Nigerian; 61.4% in The Punch; 57.7% in The Guardian and 50% in the Daily Trust.Altogether, the four newspapers devoted a total of 276 news stories to HIV/AIDS (64.9% activity-oriented). The proportions of activity-oriented HIV/AIDS news stories in the Daily Trust was 59.3%; The Guardian 61.7%; New Nigerian, 67.7%, and The Punch 67.1%. Out of the 279 attention scores allotted to all the news stories in the content categories, activity-oriented news stories had more points than cognitive-oriented news stories; 70.6% (197). No news story on HIV/AIDS made front and back pages lead. There were equal numbers of HIV/AIDS activity and cognitive front page news stories. However, among the news stories which constituted the back page, page 2 and other inside pages, activity-oriented news stories had more attention scores than cognitive-oriented news stories. Overall, HIV/AIDS news stories occupied 11637.8 column centimeters. While HIV/AIDS activity-oriented news stories accounted for 59.7% (6951.9col.cms), HIV/AIDS cognitive-oriented news stories accounted for 40.3% (or 4685.9 col.cms).Two of the four newspapers (Daily Trust and New Nigerian) did not publish HIV/AIDS editorials at all during the period studied. There were nine editorials on HIV/AIDS. Eight of these appeared in The Guardian. Of the eight editorials in The Guardian, five were activity-oriented. The only editorial featured in The Punch was cognitive-oriented.There were more HIV/AIDS activity-oriented feature articles (60.7%) than HIV/AIDS cognitive-oriented feature articles. Seventy-one percent of feature articles in the Daily Trust were activity oriented as were 56.4% in The Guardian, 60.0% in the New Nigerian, and 63.6% in the Punch. The ratio of space in col.cms occupied by HIV/AIDS activity-oriented feature articles to HIV/AIDS cognitive-oriented feature articles in all the newspapers put together indicates that HIV/AIDS activity-oriented feature articles occupied more space than HIV/AIDS cognitive feature articles. During the period studied, the four Nigerian newspapers devoted a space of 5341.1 col.cms (or 50.6%) to activity-oriented feature articles and a space of 5221 col.cms (or 49.4%) to cognitive-oriented feature articles. In the New Nigerian and the Punch however, HIV/AIDS cognitive-oriented feature articles occupied more space than HIV/AIDS activity-oriented feature articles. In New Nigerian 44.4% (240col.cms) of space was dedicated to activity-oriented feature articles while 48.6% (2040 col.cms) was dedicated to activity-oriented feature stories. The Guardian and the Daily Trustdevoted more space to HIV/AIDS activity oriented feature articles (56.4% (2640.5 col.cms) and 70% (420.6 col.cms) respectively.There were thirty-five HIV-AIDS-related advertisements in the four newspapers. Overall, there were more cognitive-oriented advertisements (60.0%). However, a greater proportion of advertisement messages in The Guardian and New Nigerian had three and two HIV/AIDS-related advertisements respectively, all of which were activity-oriented. The Daily Trust had 21 advertisements of which 16 (76.2%) were cognitive-oriented. There were nine HIV/AIDS-related advertisements in The Punch of which five were cognitive-oriented.To understand the response of the media in Nigeria to the call for transition from cognitive to activity-oriented models of HIV/AIDS communication, a comparative analysis of HIV/AIDS information in four Nigerian mainstream newspapers was conducted. The predominance in coverage of HIV/AIDS activity-oriented information as identified in the four newspapers suggests that HIV/AIDS contextual issues receive considerable attention. The dominance of activity-oriented HIV/AIDS content information contradicts the view of some scholars , 13–16 tThe dominance of activity information further shows that Nigerian newspapers in their expanded roles may be capable of providing national and international models of strategic responses to diseases. The dominance of HIV/AIDS activity-oriented editorials as well as feature articles is critical because these items, more than news stories, have the capacity to lay bare the ways in which HIV/AIDS exacerbates social prejudices, economic inequalities, discriminatory practices and political injustices. Although, editorials and feature articles have the capacity to stimulate debate and foster a social environment in which AIDS is addressed in a spirit of openness, news stories dominated the HIV/AIDS information items studied. The relative lack of editorials and feature articles may suggest ambivalence occasioned by lack of skill and acknowledge on the part of editorial and feature writers.None of the papers sampled used an HIV/AIDS story as front or back page lead. Furthermore, both HIV/AIDS activity and cognitive stories have very low attention scores on the front and back pages. A number of reasons could be adduced for it. It could be that the urge to sell had conditioned the perception of the newspapers towards considering HIV/AIDS stories less sensational than other news items. It could also be a manifestation of the natural inclination of the papers to follow occurrences that had “greater” social impact. Indeed, the Nigerian mass media within the period covered by this study focused more on intriguing and sensational social, political and economic issues in Nigeria.A striking feature of the four Nigerian newspapers coverage of HIV/AIDS information was the dominance of HIV/AIDS cognitive-oriented advertisement messages. This is not surprising, as advertisers and advertisement copy writers in Nigeria as elsewhere determine the content and space of advertisement messages.Study findings should be interpreted in light of several limitations. First, the sample was not randomized and is based on a small sample of newspapers. Results cannot therefore be generalized to the entire Nigerian newspapers and other mass media. Second, tracing the evolution of newspaper reporting on HIV in Nigeria over a longer period of time would have offered a broader comparative analysis of the transition from cognitive to activity model of communication. These are areas for further research.This study shows that the activity model of HIV/AIDS communication dominates the four Nigerian mainstream newspapers studied. It is possible that this trend is common to other Nigerian mass media outlets. Perhaps, the considerable global review of HIV/AIDS communication practices that have taken place and the relative positive national response have provided broader basis for contextual redirection for the mass media in some developing countries. However, it is worth noting the limited number of editorials and feature articles, which have the capacity to stimulate debate and foster a social environment in which AIDS is addressed in a spirit of openness.For a country that has the third largest number of people living with HIV/AIDS, globally, one would expect the mass media to deliberately play an instrumental and a more active role in the battle against the disease by engaging in more in-depth contextual discourse.


Smear-negative pulmonary tuberculosis (SN-PTB), which is common in HIV-infected patients, is difficult to diagnose using smear microscopy alone. In 2007, the WHO developed an algorithm to improve the diagnosis and management of smear-negative tuberculosis in HIV prevalent and resource constrained settings. Implementation of the algorithm required individuals with presumptive TB to be initially evaluated using two sputum microscopy examinations followed by clinical diagnosis that may include chest X-ray and antibiotic treatment in smear-negative individuals. Since that time, the WHO has endorsed several new tests for diagnosis of tuberculosis. However, it is unclear how the new tests perform when compared to the WHO 2007 algorithm in diagnosis of SN-PTB. Using meta-analysis study design, we summarized and compared the accuracy of Xpert® MTB/Rif assay (GeneXpert) and Microscopic Observation Drug Susceptibility assay (MODS), with the WHO 2007 algorithm in the diagnosis of SN-PTB.A systematic review and meta-analysis of publications on GeneXpert, or MODS, or the WHO 2007 algorithm for diagnosis of SN-PTB, using culture as reference test was performed. Meta-Disc software was used to obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity in the accuracy estimates was tested by reviewing the generated forest plots, sROC curves and the Spearman correlation coefficient of the logit of true positive rate versus the logit of false positive rate.Twenty-four publications on all three diagnostic methods were meta-analyzed. The pooled sensitivity and specificity for detection of smear-negative pulmonary tuberculosis were 67% and 98% for GeneXpert, 73% and 91% for MODS, and 61% and 69% for WHO 2007 algorithm, respectively. The sensitivity of GeneXpert reduced from 67% to 54% when sub-group analysis of studies with patient HIV prevalence ≥30% was performed.The GeneXpert, MODS, and the WHO algorithm have moderate to high accuracy for the diagnosis of SN-PTB. However, the accuracy of the tests is extremely variable. The setting and context under which the tests are conducted in addition to several other factors could explain this variability. There is therefore need to investigate these factors further. The information from these studies would inform the adoption and placement of these new tests. The global burden of tuberculosis (TB) remains high with 8.7 million new TB cases estimated to have occurred in 2012 . In sub In 2007, the WHO issued an algorithm for the diagnosis of SN-PTB for use in resource-limited settings with high HIV infection rates . AdoptioMore recently, the WHO endorsed the Xpert® MTB/Rif assay (GeneXpert) for the diagnosis of TB . The GenAnother new test is the Microscopic Observation Drug Susceptibility assay (MODS). The WHO recently endorsed the test for rapid screening of multidrug-resistant TB . The MODHowever, evidence on the performance of the GeneXpert, MODS assay, and the WHO 2007 algorithm for diagnosis of SN-PTB is scanty. In this study, we did a meta-analysis to summarize and compare the accuracy (sensitivity and specificity) of the GeneXpert (a molecular based assay), the MODS (a rapid culture method) and the WHO 2007 algorithm  for the diagnosis of SN-PTB. We considered all the elements of the WHO 2007 algorithm (its entirety) as one test.A systematic review of publications on GeneXpert, MODS and the WHO 2007 algorithm for the diagnosis of SN-PTB was performed, followed by a meta-analysis.Initially, we performed an electronic search in Pubmed without year restriction for articles in English for each test individually. The search terms used were ‘GeneXpert’, ‘Microscopic observation drug susceptibility’, and ‘WHO TB algorithm’. We then reviewed the retrieved abstracts and selected publications for full text review. After fully reading the selected publications, their bibliographies were also reviewed and relevant additional publications were also retrieved for full text review. To ensure that no relevant publications were missed, we also performed a search in Google Scholar, but no additional publications were found.We selected peer-reviewed articles published until 30th May 2012. The publications should have used the GeneXpert, or MODS, or WHO 2007 algorithm, for diagnosis of pulmonary TB. The inclusion criteria were: i) use of culture as the reference method . ii) Publications should have reported data to allow first hand computation of sensitivity and specificity of the test for SN-PTB. In papers where this was not reported, we contacted the corresponding authors to request provision of the required data.We created an excel spreadsheet and collected data on 20 variables per article, including: index test, author and year of publication, culture method, country of study, study HIV prevalence, sample size, specimen type, culture method, and numbers of true positive, true negative, false positive, and false negative. Numbers of the positive and negative values were extracted either directly or through calculation based on reported measures of accuracy. The obtained data were verified by a second investigator.Publications included in the meta-analysis were assessed for quality using the QUADAS-2 tool . The tooFrom the main spreadsheet we created sub files for GeneXpert, MODS and the WHO 2007 algorithm. Each file was configured to fit into the Meta-Disc software v.1.4 for data analysis . Using tAs study results can be variable (heterogeneous), it is critical to explore this heterogeneity to understand the possible factors that influence the obtained accuracy estimates and whether it is appropriate to pool them. Heterogeneity can either be due to chance or due to differences in the threshold that is used to define positive and negative results of a test.p-values, which are automatically computed by Meta-disc during analysis. A low Chi-square p-value would suggest presence of heterogeneity beyond what could be expected by chance alone and, (iii) the inconsistence index (I-square), which is also automatically computed by Meta-disc software. The inconsistence index is a quantitative measure of the amount of heterogeneity [We explored for heterogeneity due to chance (other than threshold effect) for each diagnostic method by; i) visual inspection of the forest plots for deviation of sensitivity and specificity of each study from the vertical line corresponding to the pooled estimates. Large deviations from this line would indicate possibility of heterogeneity, (ii) Chi-square ogeneity . We inteogeneity .Heterogeneity due to threshold effect was explored by plotting summary receiver operating curves (sROC) for each diagnostic method to assess if the points in the plots had a curvilinear (shoulder arm) pattern or not. A typical “shoulder arm” pattern would suggest presence of threshold effect ,19,20. TThe systematic review based on all the stated strategies retrieved a total of 256 abstracts. After reviewing the abstracts, 125 publications  were fully reviewed. Due to various reasons such as; a test not being evaluated for diagnostic accuracy or data to allow computation of sensitivity and specificity not reported . In addition, 10 of the 24 publications were conducted in countries from sub-Saharan Africa . Further, 6 out of 15 publications on GeneXpert used fluorescent microscopy (FM) as the screening test, while 3 out of 5 publications on MODS used Ziehl-Nielsen microscopy (ZN) as the screening test, and 2 out of 4 publications on the WHO 2007 algorithm used either FM or ZN. A summary of the description of the studies meta-analyzed is presented in Table The results of the sensitivity and specificity of each test are shown in Figure The pooled sensitivity and the 95% confidence interval for GeneXpert was 67% (62% to 71%) while the pooled specificity was 98% (97% to 99%). On visualization of the forest plots, there was large deviation from the pooled estimate for sensitivity by several studies. For specificity, deviation from the pooled estimate was small. However, the I-square values for both sensitivity and specificity were above 40%.The pooled sensitivity and the 95% confidence interval for the MODS test was73% (66% to 79%) while the pooled specificity was 91% (92% to 96%). On visualization of the forest plots, there was large deviation from the pooled estimate for sensitivity by two studies. For specificity, large deviation from the pooled estimate observed for one study. The I-square values for both sensitivity and specificity were above 70%.The pooled sensitivity and the 95% confidence interval for the WHO 2007 algorithm was 61% (55% to 67%) while the pooled specificity was 69% (66% to 72%). On visualization of the forest plots, there was large deviation from the pooled estimate for both sensitivity and specificity by two studies. The I-square values for both sensitivity and specificity were also above 70%.The patterns of the sROC curves are shown in Figure The Spearman rank correlations between the logistic transformations (logit) of the true positive rate (TPR) plotted against the logit of the false positive rate (FPR) for each method is presented in Table Having found indication of possible heterogeneity, we performed the following sub-group analyses.For the GeneXpert, we focused on publications of studies in settings with HIV prevalence ≥ 30%, a typical value for TB patients from sub-Saharan Africa, where the GeneXpert is expected to be of much benefit due to the high levels of HIV-associated TB . There wSince FM microscopy is increasingly becoming an alternative to ZN microscopy for diagnosis of TB in several settings , we alsoLastly, since the WHO 2007 algorithm is widely used for diagnosis of smear-negative TB, but in practice few patients complete all the elements of the algorithm before clinicians exclude or initiate treatment for smear-negative TB, we performed a sub-group analysis of the WHO algorithm, excluding the publication that reported performance of the algorithm based on data of those patients that completed all the elements of the algorithm before clinicians decided if to treat or not . The pooSeventeen out of the 24 meta-analyzed publications (70%) had a low risk of bias. Of the publications at risk of bias, six were on GeneXpert, while one was on WHO 2007 algorithm. The source of risk in these publications arose principally from unclear and flow of patients. However, all the publications matched the review questions, and therefore had low concern for applicability. The overall quality of the 24 publications is shown in Figure We set out to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm, for diagnosis of SN-PTB by doing a meta-analysis of the published literature. To our knowledge, this is the first study done to compare the accuracy of the three methods for the diagnosis of SN-PTB.Overall, the MODS had the highest pooled sensitivity of 73%, followed by the GeneXpert with sensitivity of 67% and the WHO 2007 algorithm with sensitivity of 61%. GeneXpert had the highest pooled specificity of 98%, followed by MODS with 91% and the WHO 2007 algorithm with 69%.2) ranging from 71% to 90% for sensitivity, and 70% to 93% for specificity. Considering the sROC curves in view of the substantial heterogeneity, the GeneXpert had the highest accuracy for detection of SN-PTB with an area under the curve of a constructed sROC curve (AUC) value of 0.94, followed by MODS with 0.88 and the WHO algorithm with 0.69.There was substantial heterogeneity in the accuracy estimates for all the three tests that we evaluated, with the inconsistence indices (ISeveral reasons can explain the heterogeneity that we observed. These include; variations in the HIV prevalence among study patients and the corresponding variation in the severity of TB disease. Additionally use of either FM or ZN as the screening test including operator/technician performance, type of specimen tested, and differences in the culture methods used as reference test can explain the variability.Thus, the observed heterogeneity for the GeneXpert could be due to differences in the severity of HIV and the co-morbidities among the patients evaluated, since the test is fully automated after sample processing, requiring no technician involvement. On the other hand, technician performance could be a major factor in the heterogeneity observed for MODS, since inexperienced technicians could confuse artefacts for M.tb cords.With regard to heterogeneity observed for the WHO 2007 algorithm, few clinicians fully adhere to the algorithm in practice, due to operational difficulties. Therefore, the decision by clinicians if to treat or not for SN-PTB is made variably. For example, of the 4 studies on the WHO 2007 algorithm in our review, only 1 reported results based on full adherence to all the elements of the algorithm . HoweverOur results of the GeneXpert for diagnosis of SN-PTB are similar to those recently reported by the Cochrane Collaboration® . Both ouUnlike in the report by the Cochrane group, where meta-analysis for the effect of HIV on the diagnostic accuracy of GeneXpert for SN-PTB could not be done, due to the small numbers of publications, in our study we found that the sensitivity of GeneXpert reduced from 67% to 54% while specificity remained unchanged. This finding was based on four studies with HIV prevalence ≥ 30%, an HIV rate which is commonly seen in six of the nine TB high burden countries from sub-Sahara Africa .We used a comprehensive search and selection strategy which has been used before . FurtherOur study had the following limitations: There were few publications on MODS and the WHO2007 algorithm on diagnosis of SN-PTB. Moreover a substantial number of the publications on these two tests had to be excluded due to lack of reported data to compute sensitivity and specificity of the tests for diagnosis of SN-PTB. This included 2 large landmark studies on GeneXpert for the same reason ,23. The The GeneXpert, MODS, and the WHO algorithm have moderate to high accuracy for the diagnosis of SN-PTB. However, the accuracy of the tests is extremely variable. The setting and context under which the tests are conducted in addition to several other factors could explain this variability. There is therefore need to investigate these factors further. The information from these studies would inform the adoption and placement of these new tests.The authors declare that they have no competing interests.All the authors planned and designed the study. SW and FB: retrieved and reviewed the study reports, summarized and analysed the data, and prepared the manuscript. MH and ADC: retrieved some of the study reports and critically revised the manuscript versions. MJ and SH: Critically revised the manuscript versions. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/507/prepub