Comparative efficacy of drugs for treating giardiasis: a systematic update of the literature and network meta-analysis of randomized clinical trials

Background: Giardiasis is the commonest intestinal protozoal infection worldwide. The current first-choice therapy is metronidazole. Recently, other drugs with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing the many treatment options available. Network meta-analysis (NMA) is a useful tool to compare multiple treatments when there is limited or no direct evidence available. Objectives: To compare the efficacy and side effects of all available drugs for the treatment of giardiasis. Methods: We selected all RCTs included in systematic-reviews and expert reviews of all treatments for giardiasis published until 2014, extended the systematic literature search until 2016, and identified new studies by scanning reference lists for relevant studies. We then conducted a NMA of all available treatments of giardiasis by comparing parasitological cure (efficacy) and side effects. Results: We identified 60 RCTs from 58 reports (46 from published systematic-reviews, 8 from reference lists and 4 from the updated systematic search). Data from 6,714 patients, 18 treatments and 42 treatment comparisons were available. Tinidazole was associated with higher parasitological cure than metronidazole (RR: 1.23, 95% CI: 1.12-1.35) and albendazole (RR: 1.35, 95% CI: 1.21-1.50). Taking into consideration clinical efficacy, side effects and size of the evidence, tinidazole was found to be the most effective drug. Conclusions: We provide additional evidence that tinidazole single dose is the best available treatment of giardiasis in symptomatic and asymptomatic children and adults

Diagnostic value of symptoms and signs for identifying urinary tract infection in older adult outpatients: systematic review and meta-analysis

Objectives To critically appraise and evaluate the diagnostic value of symptoms and signs in identifying UTI in older adult outpatients, using evidence from observational studies. Methods We searched Medline and Medline in process, Embase and Web of Science, from inception up to September 2017. We included studies assessing the diagnostic accuracy of symptoms and/or signs in predicting UTI in outpatients aged 65 years and above. Study quality was assessed using the QUADAS-2 tool. Results We identified 15 eligible studies of variable quality, with a total of 12,039 participants (range 65–4259), and assessed the diagnostic accuracy of 66 different symptoms and signs in predicting UTI. A number of symptoms and signs typically associated with UTI, such as nocturia, urgency and abnormal vital signs, were of limited use in older adult outpatients. Inability to perform a number of acts of daily living were predictors of UTI: For example, disability in feeding oneself, + ve LR: 11.8 (95% CI 5.51–25.2) and disability in washing one's hands and face, + ve LR: 6.84 (95% CI 4.08–11.5). Conclusions The limited evidence of varying quality shows that a number of symptoms and signs traditionally associated with UTI may have limited diagnostic value in older adult outpatients

Diagnostic value of symptoms and signs for identifying urinary tract infection in older adult outpatients: systematic review and meta-analysis

Objectives To critically appraise and evaluate the diagnostic value of symptoms and signs in identifying UTI in older adult outpatients, using evidence from observational studies. Methods We searched Medline and Medline in process, Embase and Web of Science, from inception up to September 2017. We included studies assessing the diagnostic accuracy of symptoms and/or signs in predicting UTI in outpatients aged 65 years and above. Study quality was assessed using the QUADAS-2 tool. Results We identified 15 eligible studies of variable quality, with a total of 12,039 participants (range 65–4259), and assessed the diagnostic accuracy of 66 different symptoms and signs in predicting UTI. A number of symptoms and signs typically associated with UTI, such as nocturia, urgency and abnormal vital signs, were of limited use in older adult outpatients. Inability to perform a number of acts of daily living were predictors of UTI: For example, disability in feeding oneself, + ve LR: 11.8 (95% CI 5.51–25.2) and disability in washing one's hands and face, + ve LR: 6.84 (95% CI 4.08–11.5). Conclusions The limited evidence of varying quality shows that a number of symptoms and signs traditionally associated with UTI may have limited diagnostic value in older adult outpatients

Interactive visualisation for interpreting diagnostic test accuracy study results

Information about the performance of diagnostic tests is typically presented in the form of measures of test accuracy such as sensitivity and specificity. These measures may be difficult to translate directly into decisions about patient treatment, for which information presented in the form of probabilities of disease after a positive or a negative test result may be more useful. These probabilities depend on the prevalence of the disease, which is likely to vary between populations. This article aims to clarify the relationship between pre-test (prevalence) and post-test probabilities of disease, and presents two free, online, interactive tools to illustrate this relationship. These tools allow probabilities of disease to be compared to decision thresholds above and below which different treatment decisions may be indicated. They are intended to help those involved in communicating information about diagnostic test performance and are likely to be of benefit when teaching these concepts. A substantive example is presented using C-reactive protein as a diagnostic marker for bacterial infection in the older adult population. The tools may also be useful for manufacturers of clinical tests in planning product development, for authors of test evaluation studies to improve reporting, and for users of test evaluations to facilitate interpretation and application of the results

Body mass index and survival in people with heart failure

Background People with obesity are twice as likely to develop heart failure (HF) compared to people with a healthy body mass index (BMI) [1]. However, among people with HF a higher BMI has been linked to a reduced risk of all-cause mortality, a concept known as the “obesity paradox” [2]. Purpose To examine the association between BMI and survival in patients with chronic HF among a large primary care cohort. Methods We extracted data from the Clinical Practice Research Datalink of primary care records from 1st January 2000 to 31st December 2017 and included 47,531 patients with an incident diagnosis of HF, who were aged 45 years and over and who had a recorded BMI. Patients were stratified into categories of baseline BMI as underweight (BMI <18.5 kg/m2), healthy weight (BMI 18.5 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2) or obese, with obesity split into class I (30.0–34.9 kg/m2), class II (35.0–39.9 kg/m2) and class III (40 kg/m2 and over). The primary outcome was all-cause mortality. We used Kaplan-Meier curves and log rank tests to compare survival in people with HF, based on baseline BMI. We also report a Cox regression model for risk of all-cause mortality among people with HF comparing BMI categories. Results There were 25,013 deaths during the study follow-up. The average age of participants was 77.1 years (SD 10.6) and mean BMI was 27.9 (SD 6.1). In an age- and sex-adjusted analysis, people who were underweight were at increased risk of all-cause mortality compared to people with healthy weight (HR 1.52, 95% CI 1.41 to 1.64). People with overweight (HR 0.81, 95% CI 0.79 to 0.84), obesity class I (HR 0.79, 95% CI 0.76 to 0.82) and obesity class II (HR 0.78, 95% CI 0.74 to 0.82) were at decreased risk of all-cause mortality. People with obesity class III had no difference in risk of death compared to people with healthy weight (HR 0.95, 95% CI 0.88 to 1.02). In a Kaplan-Meier analysis, there was an inverse relationship between body weight and risk of death, even within the first year of follow-up. Conclusion In our large community cohort of people with HF, we found an inverse relationship between BMI and survival. Underweight people with HF have the poorest prognosis and should be identified as high-risk. Conversely, people with HF who are overweight or obese (class I and II) are at lower risk of death confirming the obesity paradox in a real-world primary care population. These findings suggest a more cautious approach to weight management in overweight and obese patients may be needed for people with HF in primary care. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The SurviveHF study was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Oxford at Oxford Health NHS Foundation Trust and the Wellcome Institutional Strategic Fund. The funders did not have any role in the design of the study, analysis and interpretation of the data, or writing of the results for publication

Interactive visualisation for interpreting diagnostic test accuracy study results

Information about the performance of diagnostic tests is typically presented in the form of measures of test accuracy such as sensitivity and specificity. These measures may be difficult to translate directly into decisions about patient treatment, for which information presented in the form of probabilities of disease after a positive or a negative test result may be more useful. These probabilities depend on the prevalence of the disease, which is likely to vary between populations. This article aims to clarify the relationship between pre-test (prevalence) and post-test probabilities of disease, and presents two free, online, interactive tools to illustrate this relationship. These tools allow probabilities of disease to be compared to decision thresholds above and below which different treatment decisions may be indicated. They are intended to help those involved in communicating information about diagnostic test performance and are likely to be of benefit when teaching these concepts. A substantive example is presented using C-reactive protein as a diagnostic marker for bacterial infection in the older adult population. The tools may also be useful for manufacturers of clinical tests in planning product development, for authors of test evaluation studies to improve reporting, and for users of test evaluations to facilitate interpretation and application of the results

Frequencies and patterns of laboratory test requests from general practice: a service evaluation to inform point of care testing

Aims The demand for test requests from general practice to laboratory services remains high. Tests performed at the point of care could reduce turnaround time and speed up clinical decision making. Replicating laboratory testing in the community would require panels of tests to be performed simultaneously, which is now approaching technological feasibility. We assessed frequencies and combinations of test requests from community settings to inform the potential future development of multiplex point of care panels. Methods We assessed all laboratory test requests made from general practice in Oxfordshire, UK, January 2014-March 2017. We summarised test request frequency overall and in combination, using heat maps and hierarchical cluster analysis. Results are also presented by age/sex subgroups. We further assessed patterns of tests requested within 7 and 14 days after an initial test request. Results 11,763,473 test requests were made for 413,073 individuals (28% age>65). Of more than 500 test types, 62 were requested at least 5,000 times, most commonly Renal Function Tests (approximately 296,000/year), Full Blood Count (278,000/year) and Liver Function Tests (237,000/year). Cluster analysis additionally identified a clear grouping of tests commonly used to investigate anaemia. Follow-up test frequency was much lower than the frequency of multiple tests ordered at initial presentation. Conclusions The current high volume of single and combination test requests highlights an opportunity for reliable multiplex point of care panels to cover a core set of frequently requested tests. The impact on test use of introducing such panels to general practice requires additional research.</p

Frequencies and patterns of laboratory test requests from general practice: a service evaluation to inform point of care testing

Aims The demand for test requests from general practice to laboratory services remains high. Tests performed at the point of care could reduce turnaround time and speed up clinical decision making. Replicating laboratory testing in the community would require panels of tests to be performed simultaneously, which is now approaching technological feasibility. We assessed frequencies and combinations of test requests from community settings to inform the potential future development of multiplex point of care panels. Methods We assessed all laboratory test requests made from general practice in Oxfordshire, UK, January 2014-March 2017. We summarised test request frequency overall and in combination, using heat maps and hierarchical cluster analysis. Results are also presented by age/sex subgroups. We further assessed patterns of tests requested within 7 and 14 days after an initial test request. Results 11,763,473 test requests were made for 413,073 individuals (28% age&gt;65). Of more than 500 test types, 62 were requested at least 5,000 times, most commonly Renal Function Tests (approximately 296,000/year), Full Blood Count (278,000/year) and Liver Function Tests (237,000/year). Cluster analysis additionally identified a clear grouping of tests commonly used to investigate anaemia. Follow-up test frequency was much lower than the frequency of multiple tests ordered at initial presentation. Conclusions The current high volume of single and combination test requests highlights an opportunity for reliable multiplex point of care panels to cover a core set of frequently requested tests. The impact on test use of introducing such panels to general practice requires additional research.</p

Solarium use and risk for malignant melanoma: meta-analysis and evidence-based medicine systematic review

Background: There is an ongoing debate whether solarium use (indoor tanning/artificial UV) may increase the risk for primary cutaneous malignant melanoma. Aim: A systematic literature search was conducted using MEDLINE and ISI Web of Science. Included studies were critically assessed regarding their risk of bias, and methodological shortcomings. Levels of evidence and grades of recommendation were determined according to guidelines of the Oxford Centre for Evidence-Based Medicine. Summary risk estimates and 95% confidence intervals for four different outcomes (ever exposure, exposure at younger age, high/low exposure vs. non-exposure) were derived from random-effects meta-analyses to account for possible heterogeneity across studies. Results: Two cohort and twenty-nine case–control studies were eligible. Overall, quality of included studies was poor as a result of severe limitations, including possible recall and selection bias, and due to lack of interventional trials. Summary risk estimates suggested a weak association (odds ratio (OR)=1.19, 95% confidence interval (CI)=1.04-1.35, p=0.009) for ever-exposure to UV radiation from a solarium with melanoma risk. However, sensitivity analyses did not show an association for studies from Europe (OR=1.10; 95%CI=0.95-1.27, p=0.218), studies with low risk of bias (OR=1.15; 95%CI=0.94-1.41, p=0.179), and studies conducted after 1990 (OR 1.09; 95%CI=0.93-1.29, p=0.295). Moreover, moderate associations were found for first exposure to UV radiation from a solarium at younger age (10 sessions in lifetime) with melanoma risk. However, for all outcomes analyzed, overall study quality and resulting levels of evidence (3a–) and grades of recommendation (D) were low due to lack of interventional studies and severe limitations including unobserved or unrecorded confounding. Conclusion: Current scientific knowledge is mainly based on observational studies with poor quality data, which report associations but do not prove causality. At present, there is no convincing evidence that moderate/responsible solarium use increases melanoma risk