Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection: A systematic review and meta-analysis

BackgroundChikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is needed. Serological tests are commonly used to diagnose CHIKV infection, but their accuracy is questionable due to varying degrees of reported sensitivities and specificities. Herein, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serological tests currently available for CHIKV.Methodology and principal findingsA literature search was performed in PubMed, CINAHL Complete, and Scopus databases from the 1^st December 2020 until 22^nd April 2021. Studies reporting sensitivity and specificity of serological tests against CHIKV that used whole blood, serum, or plasma were included. QUADAS-2 tool was used to assess the risk of bias and applicability, while R software was used for statistical analyses.Thirty-five studies were included in this meta-analysis; 72 index test data were extracted and analysed. Rapid and ELISA-based antigen tests had a pooled sensitivity of 85.8% and 82.2%, respectively, and a pooled specificity of 96.1% and 96.0%, respectively. According to our meta-analysis, antigen detection tests serve as a good diagnostic test for acute-phase samples. The IgM detection tests had more than 90% diagnostic accuracy for ELISA-based tests, immunofluorescence assays, in-house developed tests, and samples collected after seven days of symptom onset. Conversely, low sensitivity was found for the IgM rapid test (42.3%), commercial test (78.6%), and for samples collected less than seven of symptom onset (26.2%). Although IgM antibodies start to develop on day 2 of CHIKV infection, our meta-analysis revealed that the IgM detection test is not recommended for acute-phase samples. The diagnostic performance of the IgG detection tests was more than 93% regardless of the test formats and whether the test was commercially available or developed in-house. The use of samples collected after seven days of symptom onset for the IgG detection test suggests that IgG antibodies can be detected in the convalescent-phase samples. Additionally, we evaluated commercial IgM and IgG tests for CHIKV and found that ELISA-based and IFA commercial tests manufactured by Euroimmun (Lübeck, Germany), Abcam (Cambridge, UK), and Inbios (Seattle, WA) had diagnostic accuracy of above 90%, which was similar to the manufacturers’ claim.ConclusionBased on our meta-analysis, antigen or antibody-based serological tests can be used to diagnose CHIKV reliably, depending on the time of sample collection. The antigen detection tests serve as a good diagnostic test for samples collected during the acute phase (≤7 days post symptom onset) of CHIKV infection. Likewise, IgM and IgG detection tests can be used for samples collected in the convalescent phase (>7 days post symptom onset). In correlation to the clinical presentation of the patients, the combination of the IgM and IgG tests can differentiate recent and past infections.     

Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis

BackgroundPredictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue.MethodologyWe performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495).Principal findingsOf 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window.ConclusionThe findings suggest that alterations of platelet count and AST level—in the first 72 hours of fever onset—are independent markers predicting the development of severe dengue.     

Diagnostic test accuracy for detecting Schistosoma japonicum and S. mekongi in humans: A systematic review and meta-analysis

BackgroundMost of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular transmission monitoring. However, the Kato-Katz technique has shown low sensitivity for the detection of light-intensity infections, and therefore highly sensitive diagnostic tools are urgently required to monitor prevalence of infection in low transmission settings. The objective of this systematic review was to evaluate and synthesize the performance of diagnostic tests for detecting Schistosoma japonicum and S. mekongi infection in people living in endemic areas.Methodology/Principal findingsWe comprehensively searched these nine electronic databases and other resources until July 2019, with no language or publication limits: PubMed, EMBASE, MEDLINE, Web of Science, BIOSIS Citation Index, HTA, CINAHL PLUS, The Cochrane Library, and PsycINFO. We included original studies that assessed diagnostic performance using antibody, antigen, and molecular tests with stool examination test as a reference standard. Two reviewers independently extracted a standard set of data and assessed study quality. We estimated the pooled estimates of sensitivity and specificity for each index test. We used diagnostic odds ratio to determine the overall accuracy and hierarchical summary receiver operating characteristics (HSROC) curve to assess the index tests performance.Fifteen studies (S. japonicum [n = 13] and S. mekongi [n = 2]) testing 15,303 participants were included in the review. Five studies reported performance of enzyme-linked immunosorbent assay (ELISA), seven studies reported indirect hemagglutination assay (IHA), and four studies reported polymerase chain reaction (PCR) for detecting S. japonicum. The pooled sensitivity and specificity were 0.93 (95% CI: 0.84–0.98) and 0.40 (95% CI: 0.29–0.53) for ELISA, 0.97 (95% CI: 0.90–0.99) and 0.66 (95% CI: 0.58–0.73) for IHA, and 0.89 (95% CI: 0.71–0.96) and 0.49 (95% CI: 0.29–0.69) for PCR respectively. A global summary indicated the best performance for IHA, closely followed by ELISA. We were unable to perform meta-analysis for S. mekongi due to insufficient number of studies.Conclusions/SignificanceIHA showed the highest detection accuracy for S. japonicum. Further studies are needed to determine the suitable diagnostic methods to verify the absence of transmission of S. mekongi and also to compare detection accuracy against more sensitive reference standards such as PCR.     

Diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin: a systematic review and meta-analysis

Background

Proteolysis of matrix components, in particular elastin, is a major contributing factor to the development of lung diseases such as emphysema and chronic obstructive pulmonary disease (COPD). MMP-12 (macrophage elastase) is a protease known to be involved in the progression of lung disease. The relatively low abundance of MMP-12 has precluded the development of quantitative assays that can accurately measure MMP-12 protein levels and activity across cohorts of healthy and diseased individuals.

Methods

Commercial antibodies were screened for performance in sandwich ELISA and capture FRET activity assay formats. Precision, accuracy, sensitivity, dilution linearity, and spike recovery were evaluated using sputum samples.

Results

Total protein and capture FRET activity assays were developed that were sensitive enough to detect MMP-12 in 37 of 38 donor sputum samples. A comparison of results between the two assays shows that a majority of sputum MMP-12 is in the active form. No differences were seen between normal, asthmatic, and COPD donors.

Conclusion

Sensitive and quantitative assays for both MMP-12 activity and total protein in human induced sputum have been developed. These assays can be used to evaluate MMP-12 as a biomarker for lung disease, and to monitor efficacy of potential therapeutic compounds.     

Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and meta-analysis

Background

Lymph node status is the key to determining the prognosis and treatment of cervical cancer. However, it cannot be assessed clinically, and testing for nodal metastasis is controversial. We sought to systematically review the diagnostic accuracy literature on sentinel node biopsy, positron emission tomography, magnetic resonance imaging and computed tomography to evaluate the accuracy of each index test in determining lymph node status in patients with cervical cancer.

Methods

We searched MEDLINE (1966–2006), EMBASE (1980–2006), Medion (1980–2006) and the Cochrane library (Issue 2, 2006) for relevant articles. We also manually searched the reference lists from primary articles and reviews, and we contacted experts in the field for conference abstracts and unpublished studies. We performed random-effects meta-analysis of accuracy indices, and we performed meta-regression analysis to test the effect of study quality on diagnostic accuracy and to identify other sources of heterogeneity.

Results

We included 72 relevant primary studies, involving a total of 5042 women, in our analysis. We found that, in determining lymph node status, sentinel node biopsy had a pooled positive likelihood ratio of 40.8 (95% confidence interval [CI] 24.6–67.6) and a pooled negative likelihood ratio of 0.18 (95% CI 0.14–0.24). The pooled positive likelihood ratios (and 95% CI) were 15.3 (7.9–29.6) for positron emission tomography, 6.4 (4.9–8.3) for magnetic resonance imaging and 4.3 (3.0–6.2) for computed tomography. The pooled negative likelihood ratios (and 95% CIs) were 0.27 (0.11–0.66) for positron emission tomography, 0.50 (0.39–0.64) for magnetic resonance imaging and 0.58 (0.48–0.70) for computed tomography. Using a 27% pretest probability of lymph node metastasis among all cases (regardless of stage), we found that a positive sentinel node biopsy result increased post-test probability to 94% (95% CI 90%–96%), whereas a positive finding on positron emission tomography increased it to 85% (75%–92%).

Interpretation

Sentinel node biopsy has greater accuracy in determining lymph node status among women with primary cervical cancer than current commonly used imaging methods.In the United States and European Union it is estimated that cervical cancer is diagnosed in about 42 000 women each year.^1,2 The International Federation of Gynecology and Obstetrics criteria currently used to stage cervical cancer do not account for lymph node involvement, but the lymphatic spread of the disease is key to determining prognosis and appropriate treatment.The primary treatment options for early cervical cancer (stage 1B1 or less advanced) are surgery and chemoradiotherapy, which have similar survival rates.³ Surgical treatment offers some degree of fertility preservation and may not have the long-term complications associated with chemoradiotherapy. However, because it is not possible to clinically detect pelvic and para-aortic lymph node metastasis, surgery typically includes lymphadenectomy, which may reveal metastatic spread. In such cases, chemoradiotherapy is required, which would make the initial surgical procedure unnecessary in retrospect. There has been considerable interest in using a preoperative, noninvasive test to determine lymph node status in order to select the most appropriate treatment option. Such a test could avoid unnecessary surgical intervention, reduce morbidity and correctly direct choice of treatment.In recent years, the use of magnetic resonance imaging and computed tomography to determine lymph node status has increased; however, neither method has been formally included as part of International Federation of Gynecology and Obstetrics staging of cervical cancer. Sentinel node biopsy and positron emission tomography have emerged as competitors to magnetic resonance imaging and computed tomography. The accuracy of magnetic resonance imaging, computed tomography and positron emission tomography has been assessed previously in reviews,^4–6 but updates are required because recent studies have reported on their diagnostic accuracy⁷ and on quality assessment in diagnostic reviews.⁸ Given this background, we performed a systematic review of the literature to compare the accuracy of these 4 methods in determining lymph node status in patients with cervical cancer.     

Diagnostic and prognostic value of circulating miR-21 for cancer: A systematic review and meta-analysis

Background

MicroRNAs (miRNAs) have been reported to be aberrantly expressed in patients with cancer. Many studies have shown that circulating miRNAs could play potential roles as diagnostic and prognostic biomarkers of cancers. The aim of this meta-analysis is to summarize the role of circulating miR-21 as a biomarker in patients with a variety of carcinomas.

Material and methods

Eligible studies were identified and assessed for quality through multiple search strategies. For diagnostic meta-analysis, the sensitivity, specificity, and other measures of miR-21 in the diagnosis of cancer were pooled using bivariate random-effects approach models. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated.

Results

A total of 36 studies dealing with various carcinomas were included for the systemic review. Among them, 23 studies were finally enrolled in the global meta-analysis (17 studies for diagnosis and 6 studies for prognosis). For diagnostic meta-analysis, the overall pooled results for sensitivity, specificity, positive likelihood ratio (LRP), negative likelihood ratios (LRN) and diagnostic odds ratio (DOR) were 75.7% (95% CI: 67.1%–82.6%), 79.3% (95% CI: 74.2%–83.5%), 3.65 (95% CI: 2.83–4.70), 0.31 (95% CI: 0.22–0.43), and 11.88 (95% CI: 6.99–20.19), respectively. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 2.37 (95% CI: 1.83–3.06, P < 0.001), which could significantly predict poorer survival in general carcinomas. Importantly, subgroup analysis suggested that higher expression of miR-21 correlated with worse overall survival (OS) significantly in carcinomas of digestion system (HR, 5.77 [95% CI: 2.65–12.52]).

Conclusions

Our findings suggest that circulating miR-21 may not suitable to be a diagnostic biomarker, but it has a prognostic value in patients with cancer.     

Diagnostic accuracy of level 3 portable sleep tests versus level 1 polysomnography for sleep-disordered breathing: a systematic review and meta-analysis

Background:

Greater awareness of sleep-disordered breathing and rising obesity rates have fueled demand for sleep studies. Sleep testing using level 3 portable devices may expedite diagnosis and reduce the costs associated with level 1 in-laboratory polysomnography. We sought to assess the diagnostic accuracy of level 3 testing compared with level 1 testing and to identify the appropriate patient population for each test.

Methods:

We conducted a systematic review and meta-analysis of comparative studies of level 3 versus level 1 sleep tests in adults with suspected sleep-disordered breathing. We searched 3 research databases and grey literature sources for studies that reported on diagnostic accuracy parameters or disease management after diagnosis. Two reviewers screened the search results, selected potentially relevant studies and extracted data. We used a bivariate mixed-effects binary regression model to estimate summary diagnostic accuracy parameters.

Results:

We included 59 studies involving a total of 5026 evaluable patients (mostly patients suspected of having obstructive sleep apnea). Of these, 19 studies were included in the meta-analysis. The estimated area under the receiver operating characteristics curve was high, ranging between 0.85 and 0.99 across different levels of disease severity. Summary sensitivity ranged between 0.79 and 0.97, and summary specificity ranged between 0.60 and 0.93 across different apnea–hypopnea cut-offs. We saw no significant difference in the clinical management parameters between patients who underwent either test to receive their diagnosis.

Interpretation:

Level 3 portable devices showed good diagnostic performance compared with level 1 sleep tests in adult patients with a high pretest probability of moderate to severe obstructive sleep apnea and no unstable comorbidities. For patients suspected of having other types of sleep-disordered breathing or sleep disorders not related to breathing, level 1 testing remains the reference standard.Undiagnosed sleep-disordered breathing places a substantial burden on patients, families, health care systems and society.¹ Sleep fragmentation and recurrent hypoxemia cause daytime sleepiness and impaired concentration, which increase the risk of motor vehicle collisions and occupational accidents.^2–7 In addition, sleep-disordered breathing is associated with hypertension, stroke, cardiovascular disease, obesity and type 2 diabetes,^8–12 all of which involve greater use of health care resources.^13–17Obstructive sleep apnea is the most common type of sleep-disordered breathing. Narrowing of the upper airway during inspiration results in episodes of apnea (breathing cessation for at least 10 seconds), hypopnea (reduced airflow), oxygen desaturation and arousal from sleep due to respiratory effort.¹⁸ Clinical signs and symptoms include snoring, reports of nocturnal apnea, gasping or choking witnessed by a partner, daytime sleepiness, morning headaches and inability to concentrate. Patients with obesity or cardiovascular disease are at increased risk.¹⁹The severity of obstructive sleep apnea is usually graded using the apnea–hypopnea index (the mean number of apneas and hypopneas per hour of sleep) as follows: mild (5–14), moderate (15–29) and severe (≥ 30).^18,20Other, less common types of sleep-disordered breathing include upper airway resistance syndrome, obesity hyperventilation syndrome, central sleep apnea, and nocturnal hypoventilation/hypoxemia secondary to cardiopulmonary or neuromuscular disease. It is not uncommon for patients to have more than 1 type of sleep-disordered breathing.Estimates of the prevalence of sleep-disordered breathing vary depending on the population (e.g., by sex, age and comorbidities).²¹ According to the Wisconsin Sleep Cohort Study, values in American adults (aged 30–60 yr) are 24% for men and 9% for women.¹ A Canadian survey found a self-reported prevalence of sleep apnea of 3% among adults more than 18 years of age, and 5% among those more than 45 years of age.²² As the population ages and rates of obesity increase, the prevalence of sleep-disordered breathing is climbing.^1,19,23,24 Given its clinical implications, accurate diagnosis and treatment of the condition are critical.Level 1 sleep testing, or polysomnography, requires an overnight stay in a sleep laboratory with a technician in attendance. It captures a minimum of 7 channels of data (but typically ≥ 16), including respiratory, cardiovascular and neurologic parameters, to produce a comprehensive picture of sleep architecture. Level 1 is considered the reference standard for diagnosing all types of sleep-disordered breathing and sleep disorders.^19,25–27 However, limited facilities and the growing demand for sleep studies have resulted in long wait times.²⁸ Level 2 sleep testing uses level 1 equipment, but is performed without a technician in attendance.Level 3 testing uses portable monitors that allow sleep studies to be done at the patient’s home or elsewhere. This option was introduced as a more accessible and less expensive alternative to in-laboratory polysomnography. Level 3 devices record at least 3 channels of data (e.g., oximetry, airflow, respiratory effort). Unlike level 1, level 3 testing cannot measure the duration of sleep, the number of arousals or sleep stages, nor can it detect nonrespiratory sleep disorders.^27,29 Level 4 devices are also portable, but they capture less data — usually only 1 or 2 channels.^27,30We conducted a systematic review and meta-analysis to compare the diagnostic accuracy of the widely used level 3 portable monitors to in-laboratory polysomnography, and to determine the subpopulations of patients whose conditions might be most appropriately diagnosed with each test.     

Post-stroke infection: A systematic review and meta-analysis

Background  

stroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.     

Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review

BackgroundBreast cancer (BC) is the most common cancer for women all over the world. Great interests have been paid to discover accurate and noninvasive methods for breast cancer diagnosis and prognosis. Although the diagnostic and prognostic value of microRNA-200 (miRNA- 200, miR-200) family has been revealed in many studies, the results were inconsistent. Thus, this meta-analysis aims to assess the overall value of miRNA-200 family in breast cancer diagnosis and prognosis.MethodRelevant studies were searched from the following databases: PubMed, PMC, EMBASE, and ScienceDirect using key words: ("miRNA-200 family" or "miR-141" or "miR-200a" or "miR-200b" or "miR-200c" or "miR-429") and (“HER2” or “Luminal A” or “Luminal B” or “TNBC”) and ("breast cancers" or "breast carcinoma" or "breast malignancy" or "breast tumor"). The sensitivity, specificity, AUC were then calculated to estimate the diagnostic accuracy of the miR-200 family. As for the prognostic value of the miR-200 family, the pooled hazard ratio (HR) was assessed. Heterogeneity among individual studies was also examined by subgroup analyses.ResultA total of 24 articles were included in the meta-analysis. The diagnostic value of miR-200s in BC was presented by the pooled sensitivity was 0.86 (95% CI: 0.83-0.88); the pooled specificity was 0.82 (95% CI: 0.72-0.89); the pooled AUC was 0.931 (95% CI: 0.919-0.942). Besides, expression of miR-200s in metastatic breast cancer has sensitivity, specificity and AUC of 0.70 (95%CI: 0.56-0.81), 0.72 (95%CI: 0.61-0.81), and 0.814 (95%CI: 0.741-0.903), respectively. The meta-analysis then revealed that high expression of miR-200 family corresponded to poor OS (HR: 1.63, 95% CI: 1.03-2.52), poor DFS (HR: 1.55, 95% CI: 0.95-2.56) in BC patients while downregulation of miRNA-200s corresponded to poor OS (HR= 0.84, 95%CI: 0.46-1.63) in TNBC patients and poor OS (HR=0.49; 95%CI: 0.27-0.88) in luminal BC patient.ConclusionThe MiR-200 family has high diagnostic accuracy and can be used as an important biomarker to prognosticate breast cancer.     

Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis

BackgroundNeonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR.Methods and findingsAll studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria.ConclusionsGram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.

Sophie Wen and co-workers report a meta-analysis on bacterial isolates and antimicrobial resistance in neonatal sepsis in low- and lower-middle-income countries.     

The height premium: A systematic review and meta-analysis

The taller people are, the more money they tend to earn. This phenomenon is widely known as the height premium. However, it is not yet known whether the height premium is universal, or whether it varies by context. To that end, a systematic review of the literature was performed. Five databases were searched until August 2020. Ultimately, a list of 42 studies were included in a narrative synthesis, and 17 studies were included in a meta-analysis. Based on the meta-analysis, we found evidence that the height premium varied by context: the height premium was smaller in the U.S. and Australia, and larger in Latin America and Asia. Within geographies, there appeared to be a larger height premium for men than for women. Cultural factors, labor market structures and biology may play a role in determining the strength of the height premium.     

The diagnostic performance of current tumour markers in surveillance for recurrent testicular cancer: A diagnostic test accuracy systematic review

In this diagnostic test accuracy systematic review we summarise the evidence on the diagnostic accuracy of blood α-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) in surveillance for testicular cancer recurrence in adults. We searched four electronic databases for studies that reported the diagnostic accuracy of HCG, AFP, and/or LDH in sufficient detail for sensitivity and specificity to be calculated by extracting a 2 × 2 table comparing biomarker positivity with testicular cancer recurrence. Screening, data extraction and QUADAS-2 quality assessment were completed by two independent reviewers. From 2406 studies, nine met our inclusion criteria. Eight reported data at the per-patient level. Sample sizes were small (range 5 to 449 patients) and clinical heterogeneity precluded meta-analysis. In most studies the specificity for recurrence with AFP and HCG was high (90–100%) but sensitivity was often relatively low, suggesting that many recurrences would not be detected by tumour markers alone. The diagnostic performance of LDH appears poorer. Studies were methodologically weak, with probable selection, incorporation and partial verification bias, and many studies were excluded for not reporting on recurrence-free patients. Limitations including small sample sizes, high heterogeneity, and inconsistent and incomplete reporting mean these results must be interpreted with caution. Despite inclusion of biomarkers in international surveillance guidance, there remains a lack of high quality evidence about their accuracy, optimal thresholds, and the most effective surveillance strategy in relation to contemporary investigative modalities. Higher quality research using data from modern-day follow-up cohorts is necessary to identify opportunities to reduce unnecessary testing.     

Garlic for hypertension: A systematic review and meta-analysis of randomized controlled trials

BackgroundIn the past decade, garlic has become one of the most popular complementary therapies for blood pressure (BP) control used by hypertensive patients. Numerous clinical studies have focused on the BP-lowering effect of garlic, but results have been inconsistent. Overall, there is a dearth of information available to guide the clinical community on the efficacy of garlic in hypertensive patients.AimTo systematically review the medical literature to investigate the current evidence of garlic for the treatment of hypertension.MethodsPubMed, the Cochrane Library and EMBASE were searched for appropriate articles from their respective inceptions until August 2014. Randomized, placebo-controlled trials comparing garlic vs. a placebo in patients with hypertension were considered. Papers were independently reviewed by two reviewers and were analyzed using Cochrane software Revman 5.2.ResultsA total of seven randomized, placebo-controlled trials were identified. Compared with the placebo, this meta-analysis revealed a significant lowering effect of garlic on both systolic BP (WMD: −6.71 mmHg; 95% CI: −12.44 to −0.99; P = 0.02) and diastolic BP (WMD: −4.79 mmHg; 95% CI: −6.60 to −2.99; P < 0.00001). No serious adverse events were reported in any of the trials.ConclusionThe present review suggests that garlic is an effective and safe approach for hypertension. However, more rigorously designed randomized controlled trials focusing on primary endpoints with long-term follow-up are still warranted before garlic can be recommended to treat hypertensive patients.     

Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review

Objective To review the spot protein:creatinine ratio and albumin:creatinine ratio as diagnostic tests for significant proteinuria in hypertensive pregnant women.Design Systematic review.Data sources Medline and Embase, the Cochrane Library, reference lists, and experts.Review methods Literature search (1980-2007) for articles of the spot protein:creatinine ratio or albumin:creatinine ratio in hypertensive pregnancy, with 24 hour proteinuria as the comparator.Results 13 studies concerned the spot protein:creatinine ratio (1214 women with primarily gestational hypertension). Nine studies reported sensitivity and specificity for eight cut-off points, median 24 mg/mmol (range 17-57 mg/mmol; 0.15-0.50 mg/mg). Laboratory assays were not well described. Diagnostic test characteristics were recalculated for a cut-off point of 30 mg/mmol. No significant heterogeneity in cut-off points was found between studies over a range of proteinuria. Pooled values gave a sensitivity of 83.6% (95% confidence interval 77.5% to 89.7%), specificity of 76.3% (72.6% to 80.0%), positive likelihood ratio of 3.53 (2.83 to 4.49), and negative likelihood ratio of 0.21 (0.13 to 0.31) (nine studies, 1003 women). Two studies of the spot albumin:creatinine ratio (225 women) found optimal cut-off points of 2 mg/mmol for proteinuria of 0.3 g/day or more and 27 mg/mmol for albuminuria.Conclusion The spot protein:creatinine ratio is a reasonable “rule-out” test for detecting proteinuria of 0.3 g/day or more in hypertensive pregnancy. Information on use of the albumin:creatinine ratio in these women is insufficient.     

Effect of dengue vector control interventions on entomological parameters in developing countries: a systematic review and meta-analysis

The aim of this review was to compare the effects of different dengue vector control interventions (i.e. biological control, chemical control, environmental management and integrated vector management) with respect to the following entomological parameters: Breteau index (BI), container index (CI), and house index (HI). We systematically searched PubMed, ISI Web of Science, Science Direct, the Dengue Bulletin of the World Health Organization and reference lists of retrieved articles on dengue vector control interventions in developing countries. We extracted data on the effectiveness of different dengue vector control interventions (defined as the relative reduction of an entomological measure caused by the intervention compared with the control or pre-intervention phase) and calculated a measure of combined relative effectiveness, with 95% confidence intervals (95% c.i.). We identified 56 publications covering 61 dengue vector control interventions. Integrated vector management was found to be the most effective method to reduce the CI, HI and BI, resulting in random combined relative effectiveness values of 0.12 (95% c.i. 0.02-0.62), 0.17 (95% c.i. 0.02-1.28) and 0.33 (95% c.i. 0.22-0.48), respectively. Environmental management showed a relatively low effectiveness of 0.71 (95% c.i. 0.55-0.90) for the BI, 0.49 (95% c.i. 0.30-0.79) for the CI and 0.43 (95% c.i. 0.31-0.59) for the HI. Biological control (relative effectiveness for the CI: 0.18) usually targeted a small number of people (median population size: 200; range 20-2500), whereas integrated vector management focused on larger populations (median: 12 450; range: 210-9 600 000). In conclusion, dengue vector control is effective in reducing vector populations, particularly when interventions use a community-based, integrated approach, which is tailored to local eco-epidemiological and sociocultural settings and combined with educational programmes to increase knowledge and understanding of best practice. New research should assess the density-dependent effectiveness of each control measure in order to estimate whether reducing vector numbers has an impact on dengue transmission when populations are at a critical threshold.     

Efficacy and safety of telavancin in clinical trials: a systematic review and meta-analysis

Introduction

The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens.

Objective

To systematically review and synthesize the available evidence from randomized controlled trials (RCTs) evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis.

Results

Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients) referred to complicated skin and soft tissue infections (cSSTIs) and 2 (1503 patients) to hospital-acquired pneumonia (HAP). Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio [OR] = 1.10 [95% confidence intervals: 0.82–1.48]). Among patients with MRSA infection, telavancin showed higher eradication rates (OR = 1.71 [1.08–2.70]) and a trend towards better clinical response (OR = 1.55 [0.93–2.58]). Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20%) and vancomycin (18.6%). Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (OR = 2.22 [1.38–3.57]), serious adverse events (OR = 1.53 [1.05–2.24]), and adverse event-related withdrawals (OR = 1.49 [1.14–1.95]) among telavancin recipients.

Conclusion

Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.