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

A review of methods for the analysis of diagnostic tests performed in sequence

Background: Many clinical pathways for the diagnosis of disease are based on diagnostic tests that are performed in sequence. The performance of the full diagnostic sequence is dictated by the diagnostic performance of each test in the sequence as well as the conditional dependence between them, given true disease status. Resulting estimates of performance, such as the sensitivity and specificity of the test sequence, are key parameters in health-economic evaluations. We conducted a methodological review of statistical methods for assessing the performance of diagnostic tests performed in sequence, with the aim of guiding data analysts towards classes of methods that may be suitable given the design and objectives of the testing sequence. Methods: We searched PubMed, Scopus and Web of Science for relevant papers describing methodology for analysing sequences of diagnostic tests. Papers were classified by the characteristics of the method used, and these were used to group methods into themes. We illustrate some of the methods using data from a cohort study of repeat faecal immunochemical testing for colorectal cancer in symptomatic patients, to highlight the importance of allowing for conditional dependence in test sequences and adjustment for an imperfect reference standard. Results: Five overall themes were identified, detailing methods for combining multiple tests in sequence, estimating conditional dependence, analysing sequences of diagnostic tests used for risk assessment, analysing test sequences in conjunction with an imperfect or incomplete reference standard, and meta-analysis of test sequences. Conclusions: This methodological review can be used to help researchers identify suitable analytic methods for studies that use diagnostic tests performed in sequence

Frequencies and patterns of microbiology test requests from primary care in Oxfordshire, UK, 2008-2018: a retrospective cohort study of electronic health records to inform point of care testing

Objectives: To inform point-of-care test (POCT) development, we quantified the primary care demand for laboratory microbiology tests by describing their frequencies overall, frequencies of positives, most common organisms identified, temporal trends in testing and patterns of cotesting on the same and subsequent dates. Design: Retrospective cohort study. Setting: Primary care practices in Oxfordshire. Participants :393 905 patients (65% female; 49% aged 18–49). Primary and secondary outcome measures The frequencies of all microbiology tests requested between 2008 and 2018 were quantified. Patterns of cotesting were investigated with heat maps. All analyses were done overall, by sex and age categories. Results: 1 596 752 microbiology tests were requested. Urine culture±microscopy was the most common of all tests (n=673 612, 42%), was mainly requested without other tests and was the most common test requested in follow-up within 7 and 14 days. Of all urine cultures, 180 047 (27%) were positive and 172 651 (26%) showed mixed growth, and Escherichia coli was the most prevalent organism (132 277, 73% of positive urine cultures). Antenatal urine cultures and blood tests in pregnancy (hepatitis B, HIV and syphilis) formed a common test combination, consistent with their use in antenatal screening. Conclusions: The greatest burden of microbiology testing in primary care is attributable to urine culture ± microscopy; genital and routine antenatal urine and blood testing are also significant contributors. Further research should focus on the feasibility and impact of POCTs for these specimen types

Infections diagnosed in children and young people screened for malaria in UK emergency departments: a retrospective multi-centre study

Background: Data on imported infections in children and young people (CYP) are sparse. Aims: To describe imported infections in CYP arriving from malaria-endemic areas and presenting to UK emergency departments (ED) who were screened for malaria. Methods: This is a retrospective, multi-centre, observational study nested in a diagnostic accuracy study for malaria rapid diagnostic tests. Any CYP less than 16 years presenting to a participating ED with a history of fever and travel to a malaria-endemic area between 1 January 2016 and 31 December 2017 and who had a malaria screen as a part of standard care were included. Geographical risk was calculated for the most common tropical infections. Results: Of the 1414 CYP screened for malaria, 44.0% (n = 622) arrived from South Asia and 33.3% (n = 471) from sub-Saharan Africa. Half (50.0%) had infections common in both tropical and non-tropical settings such as viral upper respiratory tract infection (URTI); 21.0% of infections were coded as tropical if gastro-enteritis is included, with a total of 4.2% (60) cases of malaria. CYP diagnosed with malaria were 7.44 times more likely to have arrived from sub-Saharan Africa than from South Asia (OR 7.44, 3.78–16.41). Conclusion: A fifth of CYP presenting to participating UK EDs with fever and a history of travel to a malaria-endemic area and who were screened for malaria had a tropical infection if diarrhoea is included. A third of CYP had no diagnosis. CYP arriving from sub-Saharan Africa had the greatest risk of malaria. Abbreviations: CYP: children and young people; ED: emergency department; PERUKI: Paediatric Emergency Research in the UK and Ireland; RDT: rapid diagnostic test; VFR: visiting friends and relatives

Electronic cigarettes and subsequent cigarette smoking in young people

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the evidence on the relationship between the use and availability of e-cigarettes and subsequent cigarette smoking in young people (aged 29 years or less), and whether the relationship differs by socioeconomic status, gender, or other demographic characteristics

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Associations between circadian rhythm instability, appraisal style and mood in bipolar disorder

Background Internal appraisal styles, in addition to circadian and social rhythm instability, have been implicated in the development of mood experiences in bipolar disorder (BD), yet potential interactions between these variables remain under researched. Methods This study used online questionnaires to examine relationships between social and circadian rhythm instability, appraisal style and mood within populations at varying vulnerability for BD. Results Participants with BD (n=51), and those at behavioural high-risk (BHR; n=77), exhibited poor sleep quality and a stronger tendency to form internal appraisals of both positive and negative experiences compared to non-clinical controls (n=498) and participants with fibromyalgia (n=80). Participants with BD also exhibited a stronger tendency to adopt an internal, negative appraisal style compared to individuals at BHR. Sleep disturbance and internal appraisal styles were significantly associated with low mood in BD. Limitations Sleep quality and social rhythm stability were assessed using self-report measures only, which may differ from objective measures. Causal relationships between constructs could not be examined due to the cross-sectional design. Conclusions The findings suggest the importance of attending to internal appraisal styles and sleep quality when working therapeutically with individuals diagnosed with BD. Potential differences in the effect of appraisal style at the state and trait level warrant further exploration

Diagnostic accuracy evaluation of a point-of-care antigen test for SARS-CoV-2 and influenza in UK primary care (RAPTOR-C19)

Objectives: To evaluate the diagnostic accuracy of the Roche SARS-CoV-2 & Flu A/B Rapid Antigen Test at the point of care. Design: Prospective diagnostic accuracy study. Setting: 17 primary care practices in England. Participants: 500 individuals with symptoms consistent with possible SARS-CoV-2 or influenza infection identified upon presentation to primary care or via medical note review. Primary and secondary outcome measures: Sensitivity, specificity and predictive values, compared to a laboratory reference standard of real-time reverse transcription PCR, using samples collected using a combined nasal and oropharyngeal swab. Results: Of 481 participants with available index and reference test results, 5.6% (27/481) were reference standard-positive for SARS-CoV-2, 11.4% (55/481) for Influenza A and 1.9% (9/481) for Influenza B. The sensitivity of the antigen test to detect SARS-CoV-2 was 70.4% (19/27, 95% CI 49.6–86.2%) and specificity was 99.3% (451/454, 95%CI 98.1–99.9%). For Influenza A, sensitivity was 29.1% (16/55, 95% CI 17.6–42.9%) and specificity 98.6% (420/426, 97.0–99.5%), and for Influenza B, sensitivity was 22.2% (2/9, 2.8–60.0%) and specificity 98.1% (463/472, 96.4–99.1%). Conclusions: In a primary care population of symptomatic individuals, the assay was highly specific and had moderate sensitivity to detect SARS-CoV-2, but did not detect the majority of influenza infections. Registration: ISRCTN14226970

Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19)

Background and objective Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care. Methods Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups. Results Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms. Conclusions Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile’s minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced. Registration ISRCTN142269

Relationship between microbiology of throat swab and clinical course among primary care patients with acute cough: a prospective cohort study.

BACKGROUND: Acute lower respiratory tract infections (ALRTIs) account for most antibiotics prescribed in primary care despite lack of efficacy, partly due to clinician uncertainty about aetiology and patient concerns about illness course. Nucleic acid amplification tests could assist antibiotic targeting. METHODS: In this prospective cohort study, 645 patients presenting to primary care with acute cough and suspected ALRTI, provided throat swabs at baseline. These were tested for respiratory pathogens by real-time polymerase chain reaction and classified as having a respiratory virus, bacteria, both or neither. Three hundred fifty-four participants scored the symptoms severity daily for 1 week in a diary (0 = absent to 4 = severe problem). RESULTS: Organisms were identified in 346/645 (53.6%) participants. There were differences in the prevalence of seven symptoms between the organism groups at baseline. Those with a virus alone, and those with both virus and bacteria, had higher average severity scores of all symptoms combined during the week of follow-up than those in whom no organisms were detected [adjusted mean differences 0.204 (95% confidence interval 0.010 to 0.398) and 0.348 (0.098 to 0.598), respectively]. There were no differences in the duration of symptoms rated as moderate or severe between organism groups. CONCLUSIONS: Differences in presenting symptoms and symptoms severity can be identified between patients with viruses and bacteria identified on throat swabs. The magnitude of these differences is unlikely to influence management. Most patients had mild symptoms at 7 days regardless of aetiology, which could inform patients about likely symptom duration