Hindsight judgement on ambiguous episodes of suspected infection in critically ill children: poor consensus amongst experts?

Few episodes of suspected infection observed in paediatric intensive care are classifiable without ambiguity by a priori defined criteria. Most require additional expert judgement. Recently, we observed a high variability in antibiotic prescription rates, not explained by the patients' clinical data or underlying diseases. We hypothesised that the disagreement of experts in adjudication of episodes of suspected infection could be one of the potential causes for this variability. During a 5-month period, we included all patients of a 19-bed multidisciplinary, tertiary, neonatal and paediatric intensive care unit, in whom infection was clinically suspected and antibiotics were prescribed ( n=183). Three experts (two senior ICU physicians and a specialist in infectious diseases) were provided with all patient data, laboratory and microbiological findings. All experts classified episodes according to a priori defined criteria into: proven sepsis, probable sepsis (negative cultures), localised infection and no infection. Episodes of proven viral infection and incomplete data sets were excluded. Of the remaining 167 episodes, 48 were classifiable by a priori criteria ( n=28 proven sepsis, n= 20 no infection). The three experts only achieved limited agreement beyond chance in the remaining 119 episodes (kappa = 0.32, and kappa = 0.19 amongst the ICU physicians). The kappa is a measure of the degree of agreement beyond what would be expected by chance alone, with 0 indicating the chance result and 1 indicating perfect agreement. CONCLUSION: agreement of specialists in hindsight adjudication of episodes of suspected infection is of questionable reliability.

Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts.

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

Knowledge as a factor in vulnerability to tuberculosis among nursing students and professionals

The objective of this study was to identify vulnerability to tuberculosis (TB) related to knowledge about the disease among 76 nursing students and professionals. A quantitative descriptive study was conducted using a closed questionnaire for the collection of data regarding transmission, preventive and biosafety measures, diagnosis, and prejudice regarding the disease. The SAS software version 9.1.3 was used for data analysis, with the level of significance set at 5% (p < 0.05). Nursing students and professionals showed a vulnerability to TB related to knowledge about transmission, preventive and biosafety measures, and diagnosis of the disease. With respect to transmission, vulnerability was higher among nursing professionals. The results indicate the need for investment by healthcare institutions surrounding this topic in view of the important role of nursing in the establishment of strategies for prevention and control of the disease.

The discourse of health managers on aspects related to the delay in tuberculosis diagnosis

The aim of this study was to analyze the discourse of health managers on aspects related to delay in tuberculosis diagnosis. This was a qualitative research study, conducted with 16 Family Health Unit managers. The empirical data were obtained through semi-structured interviews. The analysis was based on the theoretical framework of the French school of discourse analysis. According to the managers’ statements, the delay in tuberculosis diagnosis is related to patient and health service aspects. As for patient aspects, managers report fear, prejudice and lack of information as factors that may promote a delayed diagnosis. Regarding health service aspects, structural problems and lack of professional skills were reported. The discourse of managers should be considered to qualify tuberculosis control actions and to prevent delays in diagnosis.

Nursing performance in the policy transfer of directly observed treatment of tuberculosis

Objective Analyzing the policy transfer of directly observed treatment of tuberculosis from the perspective of nursing. Method This is a descriptive study with qualitative approach, which had 10 nurses of the Family Health Strategy in São Paulo as subjects. The interviews were carried out between May and June 2013, and were adopted the technique of thematic content analysis and the referential of policy transfer. Results On the signification of this treatment, are related the senses of disciplinary monitoring, the bond and approximation to the context of patients’ lives. Operationally, nurses, community health agents and nursing technicians stand out as agents of implementation of this policy, developing multiple actions of user embracement. The nurse is evidenced as an educator in health, leader in the family health team, and capable of creating emotional bond with users. Conclusion It was found that the innovations proposed in the treatment are incipient in the daily work of nurses.

The distribution of tuberculosis in Porto Alegre: analysis of the magnitude and tuberculosis-HIV coinfection

Objective Analyzing the geographical distribution of the tuberculosis (TB), its incidence and prevalence and TB-HIV coinfection in the districts of Porto Alegre from 2007 to 2011. Method An ecological, descriptive study of time series that used descriptive and geoprocessing techniques. Results In total, were recorded 3,369 incident cases and 3,998 prevalent cases of pulmonary TB. In both contexts, there was predominance of cases in males and in Caucasians. Seventeen districts showed prevalence rates above 79.2 cases/100,000 inhabitants, considering that 15 of them had incidence rates above 73.7 cases/100,000 inhabitants. The TB-HIV coinfection rates reached 67% in some districts, which is above the city average value (30%). Conclusion The distribution analysis showed that the reformulation and restructuring of policies and health services in Porto Alegre are essential.


Performance evaluation of primary care services for the treatment of tuberculosis

Objective Evaluating the performance of primary care services for the treatment of tuberculosis according to the assessment referential of health services (structure/process) in Cabedelo, a port city in the state of Paraíba. Method An evaluation quantitative, cross-sectional study, in which were carried out 117 interviews with health professionals using a structured instrument. The analysis was based on the construction of indicators using a standardized value for the reduced variable (z=1). Results The structural indicators showed regular performance for the following variables: professional training, access to record instruments and coordination with other services. The process indicators related to external actions and information about the disease had unsatisfactory performance. The directly observed treatment and the flows of reference/counter-reference had regular performance. Conclusion The focused professional qualification, the fragmentation of practices and the unsystematic home care constitute obstacles for carrying out actions aimed at providing expanded, continuous and resolute care.



Understanding the experiences of caregivers of children with tuberculosis in directly observed therapy

Objective To understand the situations and communications experienced by caregivers of children with tuberculosis (TB) with regard to directly observed therapy (DOT). Method A descriptive exploratory study with a qualitative approach was applied and developed in the ambulatory of Programa Einstein na Comunidade de Paraisópolis (PECP). The data were collected using semi-structured interviews of 13 caregivers of children with TB in DOT. The Collective Subject Discourse (CSD) method was used to analyze the data. Results Seven CSDs were identified and grouped into four categories: "Living in a difficult situation", "Changing the family routine", "Responsibility almost always fall son the mother", and "Adapting to the DOT". Conclusions The difficulties faced by the caregiver of the child at the beginning of DOT significantly changed the familiar routine. The responsibility for its continuity was assigned to the mother, who must adapt to the demands of the treatment and face the situation.

La tuberculose extrapulmonaire [Extrapulmonary tuberculosis].

Extrapulmonary tuberculosis represents an increasing proportion of all cases of tuberculosis reaching 20 to 40% according to published reports. Extrapulmonary TB is found in a higher proportion of women, black people and immunosuppressed individuals. A significant proportion of cases have a normal chest X-Ray at the time of diagnosis. The most frequent clinical presentations are lymphadenitis, pleuritis and osteoarticular TB. Peritoneal, urogenital or meningeal tuberculosis are less frequent, and their diagnosis is often difficult due to the often wide differential diagnosis and the low sensitivity of diagnostic tests including cultures and genetic amplification tests. The key clinical elements are reported and for each form the diagnostic yield of available tests. International therapeutic recommendations and practical issues are reviewed according to clinical presentation.

Similarities and dissimilarities between the Movement ABC-2 and the Zurich Neuromotor Assessment in children with suspected developmental coordination disorder.

An established tool for the assessment of motor performance in children with developmental coordination disorder (DCD) is the Movement-ABC-2 (M-ABC-2). The Zurich Neuromotor Assessment (ZNA) is also widely used for the evaluation of children's motor performance, but has not been compared with the M-ABC-2. Fifty-one children (39 males) between 5 and 7 years of age with suspected DCD were assessed using the M-ABC-2 and the ZNA. Rank correlations between scores of different test components were calculated. The structure of the tests was explored using canonical-correlation analysis. The correlation between total scores of the two motor tests was reasonable (0.66; p<0.001). However, ZNA scores were generally lower than those of M-ABC-2, due to poor performance in the fine motor adaptive component and increased contralateral associated movements (CAM). The canonical-correlation analysis revealed that ZNA measures components like pure motor skills and CAM that are not represented in the M-ABC-2. Furthermore, there was also no equivalent for the aiming and catching items of the M-ABC-2 in ZNA. The two tests measure different motor characteristics in children with suspected DCD and, thus, can be used complementary for the diagnosis of the disorder.

Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease.

Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.

Prevalence of positive tuberculosis skin tests during 5 years of screening in a Swiss remand prison

BACKGROUND: Tuberculosis (TB) screening in prisons is recommended, but the appropriate methods remain controversial. Studies evaluating screening in remand prisons arc scarce. METHOD: Between 1997 and 2001, voluntary screening based on the tuberculin skin test (TST) was offered to all prisoners on entry into the largest remand prison in Switzerland. Prisoners with positive results underwent chest X-rays. We analysed this information collected in an anonymous database. RESULTS: A total of 4890 prisoners entered the prison and were eligible for screening; 3779 (77.3%) had TST performed on average 9 days after arrival: 46.9% were positive (induration >= 10 mm). Positive TST rates were similar over the 5 years. Women were more likely to have a negative TST (60.4%) than men (47.7%; P < 0.001, Pearson's chi(2) 16.5). Positive TSTs varied according to the prisoner's country of origin (64% for sub-Saharan Africa, 57% for Eastern Europe, 56% for North Africa, 51% for Asia and 34% for North and West Europe). CONCLUSION: The percentage of TST-positive subjects was high, and most did not receive preventive treatment for latent TB. The usefulness of systematic TST for all prisoners on entry is limited, as diagnosis of TB disease usually remains the priority in prisons. Keywords

Comparison of the diagnostic performance of the original and modified Wells score in inpatients and outpatients with suspected deep vein thrombosis.

Introduction: The original and modified Wells score are widely used prediction rules for pre-test probability assessment of deep vein thrombosis (DVT). The objective of this study was to compare the predictive performance of both Wells scores in unselected patients with clinical suspicion of DVT.Methods: Consecutive inpatients and outpatients with a clinical suspicion of DVT were prospectively enrolled. Pre-test DVT probability (low/intermediate/high) was determined using both scores. Patients with a non-high probability based on the original Wells score underwent D-dimers measurement. Patients with D-dimers <500 mu g/L did not undergo further testing, and treatment was withheld. All others underwent complete lower limb compression ultrasound, and those diagnosed with DVT were anticoagulated. The primary study outcome was objectively confirmed symptomatic venous thromboembolism within 3 months of enrollment.Results: 298 patients with suspected DVT were included. Of these, 82 (27.5%) had DVT, and 46 of them were proximal. Compared to the modified score, the original Wells score classified a higher proportion of patients as low-risk (53 vs 48%; p<0.01) and a lower proportion as high-risk (17 vs 15%; p=0.02); the prevalence of proximal DVT in each category was similar with both scores (7-8% low, 16-19% intermediate, 36-37% high). The area under the receiver operating characteristic curve regarding proximal DVT detection was similar for both scores, but they both performed poorly in predicting isolated distal DVT and DVT in inpatients.Conclusion: The study demonstrates that both Wells scores perform equally well in proximal DVT pre-test probability prediction. Neither score appears to be particularly useful in hospitalized patients and those with isolated distal DVT. (C) 2011 Elsevier Ltd. All rights reserved.

Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guérin and Mycobacterium tuberculosis clearance.

Interleukin (IL)-12p40, a subunit of IL-12p70 and IL-23, has previously been shown to inhibit IL-12p70 activity and interferon-gamma (IFN-gamma) production. However, recent evidence has suggested that the role of IL-12p40 is more complex. To study the contribution of IL-12p40 to immune responses against mycobacterial infections, we have used transgenic (tg) mice overexpressing IL-12p40 under the control of a major histocompatibility complex-II promoter. The IL-12p40 transgene was expressed during steady state at concentrations of 129 +/- 25 ng/ml of serum and 75 +/- 13 ng per spleen, while endogenous IL-12p40 was hardly detectable in control littermates. Bacille Calmette-Guérin (BCG) infection strongly induced the expression of IL-12p40 transgene in infected organs, and IL-12p40 monomeric and dimeric forms were identified in spleen of IL-12p40 tg mice. Excessive production of IL-12p40 resulted in a 14-fold increase in IL-12p70 serum levels in tg mice versus non-transgenic mice. IL-23 was also strongly elevated in the serum and spleens of IL-12p40 tg mice through BCG infection. While IFN-gamma and tumour necrosis factor protein levels were similar in IL-12p40 tg and non-transgenic mice, Th2 type immune responses were reduced in IL-12p40 tg mice. The number of BCG granulomas and macrophage expressing inducible nitric oxide synthase were similar in IL-12p40 tg and non-transgenic mice. IL-12p40 tg mice were as resistant as non-transgenic mice to BCG and Mycobacterium tuberculosis infections as they could efficiently control bacillary growth. These data show that high amounts of IL-12p40 promotes IL-12p70 and IL-23 formation, but that does not affect T helper 1 type immune responses and granuloma function, thus leading to normal mycobacterial clearance in infected organs.

Undocumented migrants in Switzerland: geographical origin versus legal status as risk factor for tuberculosis.

Undocumented migrants, meaning migrants without a legal residency permit, come to Geneva from countries with high tuberculosis (TB) incidence. We estimate here whether being undocumented is a determinant of TB, independently of origin. Cross-sectional study including undocumented migrants in a TB screening program in 2002; results were compared to 12,904 age and frequency matched participants in a general TB screening program conducted at various workplaces in Geneva, Switzerland from 1992 to 2002. A total of 206 undocumented migrants (36% male, 64% female, mean age 37.8 years (SD 11.8), 82.5% from Latin America) participated in the TB screening program. Compared to legal residents, undocumented migrants had an adjusted OR for TB-related fibrotic signs of 1.7 (95% CI 0.8;3.7). The OR of TB-related fibrotic signs for Latin American (vs. other) origin was 2.7 (95% CI 1.6;4.7) among legal residents and 5.5 (95% CI 2.8;10.8) among undocumented migrants. Chest X-ray screening identified a higher proportion of TB-related fibrotic signs among Latin Americans, independently of their residency status.