Severity Assessment of Lower Respiratory Tract Infection in Malawi: Derivation of a Novel Index (SWAT-Bp) Which Outperforms CRB-65

OBJECTIVE: To assess the validity of CRB-65 (Confusion, Respiratory rate >30 breaths/min, BP<90/60 mmHg, age >65 years) as a pneumonia severity index in a Malawian hospital population, and determine whether an alternative score has greater accuracy in this setting. DESIGN: Forty three variables were prospectively recorded during the first 48 hours of admission in all patients admitted to Queen Elizabeth Central Hospital, Malawi, for management of lower respiratory tract infection over a two month period (N = 240). Calculation of sensitivity and specificity for CRB-65 in predicting mortality was followed by multivariate modeling to create a score with superior performance in this population. RESULTS: Median age 37, HIV prevalence 79.9%, overall mortality 18.3%. CRB-65 predicted mortality poorly, indicated by the area under the ROC curve of 0.649. Independent predictors of death were: Male sex, “S” (AOR 2.6); Wasting, “W” (AOR 6.6); non-ambulatory, “A” (AOR 2.5); Temp >38°C or <35°C, “T” (AOR 3.2); BP<100/60, “Bp” (AOR 3.7). Combining these factors to form a severity index (SWAT-Bp) predicted mortality with high sensitivity and specificity (AUC: 0.867). Mortality for scores 0–5 was 0%, 3.3%, 7.4%, 29.2%, 61.5% and 87.5% respectively. A score ≥3 was 84% sensitive and 77% specific for mortality prediction, with a negative predictive value of 95.8%. CONCLUSION: CRB-65 performs poorly in this population. The SWAT-Bp score can accurately stratify patients; ≤2 indicates non-severe infection (mortality 4.4%) and ≥3 severe illness (mortality 45%)

Cost of increasing access to artemisinin combination therapy: the Cambodian experience

BACKGROUND: Malaria-endemic countries are switching antimalarial drug policy from cheap ineffective monotherapies to artemisinin combination therapies (ACTs) for the treatment of Plasmodium falciparum malaria and the global community are considering setting up a global subsidy to fund their purchase. However, in order to ensure that ACTs are correctly used and are accessible to the poor and remote communities who need them, specific interventions will be necessary and the additional costs need to be considered. METHODS: This paper presents an incremental cost analysis of some of these interventions in Cambodia, the first country to change national antimalarial drug policy to an ACT of artesunate and mefloquine. These costs include the cost of rapid diagnostic tests (RDTs), the cost of blister-packaging the drugs locally and the costs of increasing access to diagnosis and treatment to remote communities through malaria outreach teams (MOTs) and Village Malaria Workers (VMW). RESULTS: At optimum productive capacity, the cost of blister-packaging cost under $0.20 per package but in reality was significantly more than this because of the low rate of production. The annual fixed cost (exclusive of RDTs and drugs) per capita of the MOT and VMW schemes was$0.44 and $0.69 respectively. However because the VMW scheme achieved a higher rate of coverage than the MOT scheme, the cost per patient treated was substantially lower at$5.14 compared to $12.74 per falciparum malaria patient treated. The annual cost inclusive of the RDTs and drugs was$19.31 for the MOT scheme and $11.28 for the VMW scheme given similar RDT positivity rates of around 22% and good provider compliance to test results. CONCLUSION: In addition to the cost of ACTs themselves, substantial additional investments are required in order to ensure that they reach the targeted population via appropriate delivery systems and to ensure that they are used appropriately. In addition, differences in local conditions, in particular the prevalence of malaria and the pre-existing infrastructure, need to be considered in choosing appropriate diagnostic and delivery strategies

A methodological framework to distinguish spectrum effects from spectrum biases and to assess diagnostic and screening test accuracy for patient populations: Application to the Papanicolaou cervical cancer smear test

<p>Abstract</p> <p>Background</p> <p>A spectrum effect was defined as differences in the sensitivity or specificity of a diagnostic test according to the patient's characteristics or disease features. A spectrum effect can lead to a spectrum bias when subgroup variations in sensitivity or specificity also affect the likelihood ratios and thus post-test probabilities. We propose and illustrate a methodological framework to distinguish spectrum effects from spectrum biases.</p> <p>Methods</p> <p>Data were collected for 1781 women having had a cervical smear test and colposcopy followed by biopsy if abnormalities were detected (the reference standard). Logistic models were constructed to evaluate both the sensitivity and specificity, and the likelihood ratios, of the test and to identify factors independently affecting the test's characteristics.</p> <p>Results</p> <p>For both tests, human papillomavirus test, study setting and age affected sensitivity or specificity of the smear test (spectrum effect), but only human papillomavirus test and study setting modified the likelihood ratios (spectrum bias) for clinical reading, whereas only human papillomavirus test and age modified the likelihood ratios (spectrum bias) for "optimized" interpretation.</p> <p>Conclusion</p> <p>Fitting sensitivity, specificity and likelihood ratios simultaneously allows the identification of covariates that independently affect diagnostic or screening test results and distinguishes spectrum effect from spectrum bias. We recommend this approach for the development of new tests, and for reporting test accuracy for different patient populations.</p

Clustering More than Two Million Biomedical Publications: Comparing the Accuracies of Nine Text-Based Similarity Approaches

We investigate the accuracy of different similarity approaches for clustering over two million biomedical documents. Clustering large sets of text documents is important for a variety of information needs and applications such as collection management and navigation, summary and analysis. The few comparisons of clustering results from different similarity approaches have focused on small literature sets and have given conflicting results. Our study was designed to seek a robust answer to the question of which similarity approach would generate the most coherent clusters of a biomedical literature set of over two million documents.We used a corpus of 2.15 million recent (2004-2008) records from MEDLINE, and generated nine different document-document similarity matrices from information extracted from their bibliographic records, including titles, abstracts and subject headings. The nine approaches were comprised of five different analytical techniques with two data sources. The five analytical techniques are cosine similarity using term frequency-inverse document frequency vectors (tf-idf cosine), latent semantic analysis (LSA), topic modeling, and two Poisson-based language models--BM25 and PMRA (PubMed Related Articles). The two data sources were a) MeSH subject headings, and b) words from titles and abstracts. Each similarity matrix was filtered to keep the top-n highest similarities per document and then clustered using a combination of graph layout and average-link clustering. Cluster results from the nine similarity approaches were compared using (1) within-cluster textual coherence based on the Jensen-Shannon divergence, and (2) two concentration measures based on grant-to-article linkages indexed in MEDLINE.PubMed's own related article approach (PMRA) generated the most coherent and most concentrated cluster solution of the nine text-based similarity approaches tested, followed closely by the BM25 approach using titles and abstracts. Approaches using only MeSH subject headings were not competitive with those based on titles and abstracts

TRPA1 is essential for the vascular response to environmental cold exposure

This work was supported by the British Heart Foundation and a Capacity Building Award in Integrative Mammalian Biology. It was also supported by Arthritis Research UK and XK is supported by a British Pharmacological Society AJ Clark studentship

Pneumocystis jirovecii pneumonia in tropical and low and middle income countries: a systematic review and meta-regression

Objective: Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings. Design Systematic review and meta-regression. METHODS: Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies). RESULTS: The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×10 3/ ml. CONCLUSIONS: There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii , ubiquitous in all settings, then becomes a greater relative threat