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The article focuses on the systematic reviews of diagnostic test evaluations. Systematic reviews synthesise data from existing primary research and bring some order and sanity to the otherwise stressful process of sorting out a plethora of studies and staying up to date. Systematic reviews are done on a range of clinical questions, such as therapy, diagnosis, prognosis, aetiology, harm, and disease prevalence. All systematic reviews follow the same critical steps. These steps resemble those of the evidence-based medicine process, but are more thorough.

The article presents an overview of systematic reviews of diagnostic test evaluations. Systematic reviews are done on a range of clinical questions, such as therapy, diagnosis, prognosis, etiology, harm, and disease prevalence. The core steps of the systematic review process can be broken down further into more discrete steps. Although not as common as systematic reviews on therapeutic questions, an increasing number of diagnostic reviews are being published in the medical literature. The final steps in the systematic review process are interpretation of the results, including discussion of such issues as applicability, and writing the report for publication.

A response from the authors of the article "Acute gastroenteritis and recreational water: Highest burden among young U.S. children" which was published in a previous article is presented.

A major challenge in tuberculosis control is the diagnosis and treatment of latent tuberculosis infection. Until recently, there were no alternatives to the tuberculin skin test (TST) for diagnosing latent tuberculosis. However, an alternative has now emerged in the form of a new in-vitro test: the interferon-γ assay. We did a systematic review to assess the performance of interferon-γ assays in the immunodiagnosis of tuberculosis. By searching databases, contacting experts and test manufacturers, we identified 75 relevant studies. The results suggest that interferon-γ assays that use Mycobacterium tuberculosis-specific region of difference 1 (RD1) antigens (such as early secretory antigenic target 6 and culture filtrate protein 10) may have advantages over the TST, in terms of higher specificity, better correlation with exposure to M tuberculosis, and less cross-reactivity due to BCG vaccination and non-tuberculous mycobacterial infection. However, interferon-γ assays that use RD1 antigens in isolation may maximise specificity at the cost of sensitivity. Assays that use cocktails of RD1 antigens seem to overcome this problem, and such assays have the highest accuracy. RD1-based interferon-γ assays can potentially identify those with latent tuberculosis who are at high risk for developing active disease, but this requires confirmation. There is inadequate evidence on the value of interferon-γ assays in the management of immunocompromised individuals, children, patients with extrapulmonary or non-tuberculous mycobacterial disease, and populations in countries where tuberculosis is endemic. Current evidence suggests that interferon-γ assays based on cocktails of RD1 antigens have the potential to become useful diagnostic tools. Whether this potential can be realised in practice remains to be confirmed in well designed, long-term studies. [Copyright &y& Elsevier]

Background: Acute encephalitis syndrome (AES) is a constellation of symptoms that includes fever and altered mental status. Most cases are attributed to viral encephalitis (VE), occurring either in outbreaks or sporadically. We conducted hospital-based surveillance for sporadic adult-AES in rural Central India in order to describe its incidence, spatial and temporal distribution, clinical profile, etiology and predictors of mortality. Methods: All consecutive hospital admissions during the study period were screened to identify adult- AES cases and were followed until 30-days of hospitalization. We estimated incidence by administrative sub-division of residence and described the temporal distribution of cases. We performed viral diagnostic studies on cerebrospinal fluid (CSF) samples to determine the etiology of AES. The diagnostic tests included RT-PCR (for enteroviruses, HSV 1 and 2), conventional PCR (for flaviviruses), CSF IgM capture ELISA (for Japanese encephalitis virus, dengue, West Nile virus, Varicella zoster virus, measles, and mumps). We compared demographic and clinical variables across etiologic subtypes and estimated predictors of 30-day mortality. Results: A total of 183 AES cases were identified between January and October 2007, representing 2.38% of all admissions. The incidence of adult AES in the administrative subdivisions closest to the hospital was 16 per 100,000. Of the 183 cases, a non-viral etiology was confirmed in 31 (16.9%) and the remaining 152 were considered as VE suspects. Of the VE suspects, we could confirm a viral etiology in 31 cases: 17 (11.2%) enterovirus; 8(5.2%)flavivirus; 3 (1.9%) Varicella zoster; 1 (0.6%) herpesvirus; and 2 (1.3%) mixed etiology); the etiology remained unknown in remaining 121 (79.6%) cases. 53 (36%) of the AES patients died; the case fatality proportion was similar in patients with a confirmed and unknown viral etiology (45.1 and 33.6% respectively). A requirement for assisted ventilation significantly increased mortality (HR 2.14 (95% CI 1.0-4.77)), while a high Glasgow coma score (HR 0.76 (95% CI 0.69-0.83)), and longer duration of hospitalization (HR 0.88 (95% CI 0.83-0.94)) were protective. Conclusion: This study is the first description of the etiology of adult-AES in India, and provides a framework for future surveillance programs in India. [ABSTRACT FROM AUTHOR]

Field studies often use caregiver-reported diarrhoea and related symptoms to measure child morbidity. There are various vernacular terms to define diarrhoea that vary across the local cultural contexts. The relationship between vernacular definitions of diarrhoea and symptoms-based definitions is not well-documented. This paper describes the association of the vernacular Quechua term k'echalera with the symptoms-based standard definition of diarrhoea in rural Bolivian settings. During a cluster randomized trial in rural Bolivia, both signs and symptoms of diarrhoea and reports of k'echalera were collected for children aged less than five years. Reported k'echalera were found to be associated with important changes in stool frequency, consistency, and presence of blood and mucus. Reported k'echalera were highly related to three of four recorded categories of watery stool. The intermediate (milk-rice) stool consistency, which fits into the definition of watery stool, was not strongly related to k'echalera. Mucus in the stool was also associated with k'echalera; however, its presence in k'echalera-free days accounted for at least 50% of the possible false negatives. The sensitivity and specificity of the term k'echalera were estimated by Bayesian methods, allowing for both symptoms of diarrhoea and reports of k'echalera to be subject to diagnosis error. An average specificity of at least 97% and the sensitivity of at least 50% were obtained. The findings suggest that the use of k'echalera would identify fewer cases of diarrhoea than a symptom-based definition in rural Bolivia. [ABSTRACT FROM AUTHOR]

Many studies have reported the results of interventions to reduce illness through improvements in drinking water, sanitation facilities, and hygiene practices in less developed countries. There has, however, been no formal systematic review and meta-analysis comparing the evidence of the relative effectiveness of these interventions. We developed a comprehensive search strategy designed to identify all peer-reviewed articles, in any language, that presented water, sanitation, or hygiene interventions. We examined only those articles with specific measurement of diarrhoea morbidity as a health outcome in non-outbreak conditions. We screened the titles and, where necessary, the abstracts of 2120 publications. 46 studies were judged to contain relevant evidence and were reviewed in detail. Data were extracted from these studies and pooled by meta-analysis to provide summary estimates of the effectiveness of each type of intervention. All of the interventions studied were found to reduce significantly the risks of diarrhoeal illness. Most of the interventions had a similar degree of impact on diarrhoeal illness, with the relative risk estimates from the overall meta-analyses ranging between 0·63 and 0·75. The results generally agree with those from previous reviews, but water quality interventions (point-of-use water treatment) were found to be more effective than previously thought, and multiple interventions (consisting of combined water, sanitation, and hygiene measures) were not more effective than interventions with a single focus. There is some evidence of publication bias in the findings from the hygiene and water treatment interventions. [Copyright &y& Elsevier]

This systematic review summarises the evidence for treatment efficacy and tolerability of highly active antiretroviral therapies containing two nucleoside reverse transcriptase inhibitors (NRTI) with a protease inhibitor (PI), compared with two NRTIs alone for the treatment of HIV-1 infection in randomised controlled trials. Three electronic databases (Medline, Embase, and the Cochrane Library) were searched up to December 2003. 16 randomised controlled trials met the inclusion criteria and were included in the analysis from 328 articles screened. The pooled analysis indicated that treatment with two NRTIs with a PI is more effective in achieving viral suppression than two NRTIs alone (relative risk [RR] 3·44, 95% confidence interval [CI] 2·43–4·87). However, the RR for discontinuation of treatment due to adverse events of treatment with two NRTIs with a PI compared with two NRTIs alone was 1·81 (95% CI 1·17–2·79). The benefits of treatment with two NRTIs and a PI are substantial among those who can tolerate the regimen in comparison with treatment with two NRTIs alone. [Copyright &y& Elsevier]

Conventional tests are not always helpful in making a diagnosis of tuberculous meningitis. We did a systematic review and meta-analysis to establish the summary accuracy of nucleic acid amplification (NAA) tests for tuberculous meningitis. We searched six electronic databases and contacted authors, experts, and manufacturers. Measures of diagnostic accuracy were pooled using a random effects model. 49 studies met our inclusion criteria. The summary estimates in 14 studies with commercial NAA tests were: sensitivity 0·56 (95% CI 0·46, 0·66), specificity 0·98 (0·97, 0·99), positive likelihood ratio 35·1 (19·0, 64·6), negative likelihood ratio 0·44 (0·33, 0·60), and diagnostic odds ratio 96·4 (42·8, 217·3). In the 35 studies with in-house (“home-brew”) tests, the summary accuracy could not be established with confidence because of wide variability in test accuracy. On current evidence, commercial NAA tests show a potential role in confirming tuberculous meningitis diagnosis, although their overall low sensitivity precludes the use of these tests to rule out tuberculous meningitis with certainty. [Copyright &y& Elsevier]