BACKGROUND: In 2016, WHO estimated there were roughly 374 million new infections among adults of the following four curable sexually transmitted infections (STIs): chlamydia (caused by Chlamydia trachomatis (CT)), gonorrhoea (Neisseria gonorrhoeae (NG)), syphilis (Treponema pallidum) and trichomoniasis (Trichomonas vaginalis (TV)). Accurate point-of-care tests (POCTs) for screening of genital and extragenital CT, NG and TV infections are of great value and have been developed during recent decade. Several tests are commercially available and have shown encouraging performance compared with \'gold-standard\' reference tests in laboratory-based studies. However, there is limited data on their clinical performance, including at the POC. Key populations, such as men who have sex with men (MSM), are at higher risk of these STIs at genital and extragenital sites and these STIs are often asymptomatic, especially in extragenital sites and in women. We will conduct a clinical-based evaluation to assess the performance characteristics and acceptability to end-users of molecular-based diagnostic technology for POC/near patient use of the Xpert CT/NG (Cepheid, Sunnyvale, California, USA) test for screening of genital, anorectal and pharyngeal CT and NG infections in MSM and the Xpert CT/NG and Xpert TV (Cepheid, Sunnyvale, California, USA) for screening of genital CT, NG and TV among women at risk for these STIs compared with gold-standard reference nucleic acid amplification tests. This master protocol outlines the overall research approach that will be used in seven countries.
METHODS: Consecutive MSM and women at risk presenting at the clinical sites in high, and low- and middle-income countries will be enrolled. The POCTs to be evaluated are Xpert CT/NG and Xpert TV. All procedures will be carried out by trained healthcare staff and tests performed in strict accordance with the manufacturer\'s instructions. The sensitivity, specificity, positive and negative predictive values for each POCT will be calculated. The study is ongoing with recruitment expected to be completed in all countries by mid-2022 to late-2022.
BACKGROUND: Prior to enrolment, this core protocol was independently peer-reviewed and approved by the research project review panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The core protocol has been slightly adapted accordingly to individual countries and adaptations approved by both RP2 and ERC, as well as all relevant institutional review boards at each participating site. Results will be disseminated through peer-reviewed journals and presented at relevant national/international conferences.

OBJECTIVE: This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF).
METHODS: Single-centre retrospective study.
METHODS: The Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital.
METHODS: We enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023.
METHODS: We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM.
RESULTS: Among these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively.
CONCLUSIONS: The diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM.

Central nervous system tuberculosis (CNSTB) is a severe condition, sometimes associated with a poor prognosis. Early diagnosis of CNSTB remains challenging, considering that conventional methods lack sensitivity or might lead to certain side effects. Herein, we presented a protocol for a systematic review and meta-analysis to assess the diagnostic efficacy of MRI for CNSTB.
SinoMed, Wanfang database, China National Knowledge Infrastructure, Embase, the Cochrane Library and PubMed will be searched to identify studies reporting on the use of MRI in the diagnosis of CNSTB from database inception to December 2023. The following keywords will be applied: \'Intracranial tuberculosis\', \'Cerebral tuberculosis\', \'Central nervous system tuberculosis\', \'Spinal tuberculous arachnoiditis\' and \'Magnetic Resonance Imaging\'. Studies that evaluate the diagnostic accuracy of MRI for the diagnosis of CNSTB and report clear reference criteria will be included. Studies from which full true positive, false positive, false negative and true negative values cannot be extracted, those published in languages other than English or Chinese, abstracts not reporting the full text, and case reports will be excluded. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used to evaluate the methodological quality of each included study. Stata V.15.0 and RevMan V.5.3 will be used to perform a meta-analysis and generate forest plots and summary receiver operating characteristic curves. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and meta-regression analyses.
This research is based on public databases and does not require ethical approval. Results will be submitted for publication in a peer-reviewed journal.
CRD42023415690.

Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at both urogenital and extragenital sites has been recommended in many countries. Testing of the infections using pooled specimens from urogenital and extragenital sites offer the opportunity to shorten the testing time and reduce the testing cost. Ex-ante pooling is placing the original single-site specimens in a tube with transport media, while ex-post pooling is making a pool of the transport media from both anorectal and oropharyngeal specimens and the urine. This study aimed to conduct a multisite performance evaluation of two pool-specimen approaches (ex-ante and ex-post) in detection of CT and NG using the Cobas 4800 platform among men who have sex with men (MSM) in China.
Diagnostic accuracy study.
Participants were recruited from MSM communities at six cities in China. Two oropharyngeal and anorectal swabs collected by clinical staff and 20 mL first-void urine collected by the participant himself were used for evaluating sensitivity and specificity.
A total of 1311 specimens were collected from 437 participants in six cities. The sensitivities of ex-ante pooling approach as compared with single-specimen approach (reference standard) were 98.7% (95% CI, 92.7% to 100.0%) for detection of CT and 89.7% (95% CI, 75.8% to 97.1%) for NG, and the specificities were 99.5% (95% CI, 98.0% to 99.9%) and 98.7% (95% CI, 97.1% to 99.6%), respectively. The sensitivities of ex-post pooling approach were 98.7% (95% CI, 92.7% to 100.0%) for CT and 100.0% (95% CI, 91.0% to 100.0%) for NG, and the specificities were 100.0% (95% CI, 99.0% to 100.0%) and 100.0% (95% CI, 99.1% to 100.0%), respectively.
The ex-ante and ex-post pooling approaches show good sensitivity and specificity in detecting urogenital and extragenital CT and/or NG, indicating that these approaches can be used in epidemiological surveillance and clinical management of CT and NG infections, particularly among MSM population.

The purpose of this study was systematically and quantitatively to assess the value of the neutrophil-to-lymphocyte ratio (NLR) for the diagnosis of neonatal sepsis by systematic review and meta-analysis.
Systematic review and meta-analysis.
Eight major databases, including The Cochrane, PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature Database and VIP Database, were systematically searched for NLR diagnoses of neonatal sepsis from inception to June 2022. Two investigators independently conducted the literature search, screening, data extraction and quality evaluation with the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Statistical analysis was performed using Review Manager V.5.3, Stata V.16.0, R (V.3.6.0) and Meta-DISC V.1.4.
A total of 14 studies comprising 1499 newborns were included in this meta-analysis. With a cut-off value ranging from 0.1 to 9.4, the pooled sensitivity of the NLR in the diagnosis of neonatal sepsis was 0.74 (95% CI: 0.61 to 0.83), the pooled specificity was 0.88 (95% CI: 0.73 to 0.95), the positive likelihood ratio (LR+) was 6.35 (95% CI: 2.6 to 15.47), the negative likelihood ratio (LR-) was 0.30 (95% CI: 0.19 to 0.46), the diagnostic OR (DOR) was 12.88 (95% CI: 4.47 to 37.08), area under the curve (AUC) was 0.87 (95% CI: 0.84 to 0.89). In the subgroup analysis of early-onset neonatal sepsis, the pooled sensitivity was 0.75 (95% CI: 0.47 to 0.91), the pooled specificity was 0.99 (95% CI: 0.88 to 1.00), the LR+ was 63.3 (95% CI: 5.7 to 696.8), the LR- was 0.26 (95% CI: 0.10 to 0.63), the DOR was 247 (95% CI: 16 to 3785) and the AUC was 0.97 (95% CI: 0.95 to 0.98).
Our findings suggest that the NLR is a helpful indicator for the diagnosis of early neonatal sepsis, but it still needs to be combined with other laboratory tests and specific clinical manifestations.

To explore the outcomes of Helicobacter pylori infection treatments for naïve patients in the real-world settings.
A retrospective observational study.
Single tertiary level academic hospital in China.
We identified patients initially receiving quadruple therapy for H. pylori infection from 2017 to 2020 in whom eradication was confirmed (n=23 470).
Efficacy of different initial H. pylori infection treatments.
Results of urea breath test (UBT) after H. pylori eradication.
Among 23 470 patients who received initial H. pylori treatment, 21 285 (90.7%) were treated with amoxicillin-based regimens. The median age of the patients decreased from 2017 to 2020 (45.0 vs 39.0, p<0.0001). The main treatments were therapies containing amoxicillin and furazolidone, which had an eradication rate of 87.6% (14 707/16 784); those containing amoxicillin and clarithromycin had an eradication rate of 85.5% (3577/4182). The date of treatment, age, antibiotic regimen and duration of treatment showed correlations with the failure of H. pylori eradication in a multivariable logistic regression analysis. Finally, positive UBT results after eradication clustered around the cut-off value, in both the 13C-UBT and 14C-UBT.
The major H. pylori infection treatments for naïve patients were those containing amoxicillin and furazolidone, which offered the highest eradication rate. The date of treatment, age, antibiotic regimen and duration of treatment were risk factors for the failure of H. pylori eradication. Additionally, positive UBT results after eradication clustered around the cut-off value.

Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-β-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases.
Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2).
This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal.
CRD42021241820.

To date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the leading causes of death in paediatric patients. Therefore, we aimed this retrospective study to analyse medical records of paediatric patients with fever of unknown origin (FUO) to provide a preliminary basis for improving the diagnostic categories and facilitate the treatment outcomes.
A retrospective study.
Beijing Children\'s Hospital.
Clinical data were collected from 1288 children between 1 month and 18 years of age diagnosed with FUO at Beijing Children\'s Hospital between January 2010 and December 2017.
According to the aetiological composition, age, duration of fever and laboratory examination results, the diagnostic strategies were analysed and formulated.
The statistical analyses were carried out using SPSS V.24.0 platform along with the χ2 test and analysis of variance (p<0.05).
The duration of fever ranged from 2 weeks to 2 years, with an average of 6 weeks. There were 656 cases (50.9%) of infectious diseases, 63 cases (4.9%) of non-infectious inflammatory diseases (NIIDs), 86 cases (6.7%) of neoplastic diseases, 343 cases (26.6%) caused by miscellaneous diseases and 140 cases (10.9%) were undiagnosed. With increasing age, the proportion of FUO from infectious diseases gradually decreased from 73.53% to 44.21%. NIID was more common in children over 3 years old, and neoplastic diseases mainly occurred from 1 to 6 years of age. Among miscellaneous diseases, the age distribution was mainly in school-aged children over 6 years. Respiratory tract infection was the most common cause of FUO in children, followed by bloodstream infections. Bacterial infection was the most common cause in children with less than 1 year old, while the virus was the main pathogen in children over 1 year old.
The diagnosis of neoplastic diseases and miscellaneous diseases-related diseases still depends mainly on invasive examination. According to our clinical experience, the diagnostic process was formulated based on fever duration and the type of disease. This process can provide a guide for the diagnosis and treatment of paediatric FUO in the future.

Long-term use of high-dose glucocorticoids can lead to severe immunosuppression and increased risk of treatment-resistant pneumonia and mortality. We investigated the aetiology and prognostic risk factors of mortality in hospitalised patients who developed pneumonia while receiving glucocorticoid therapy alone or glucocorticoid and other immunosuppressant therapies.
Retrospective cohort study.
Six secondary and tertiary academic hospitals in China.
Patients receiving glucocorticoids who were hospitalised with pneumonia between 1 January 2013 and 31 December 2019.
We analysed the prevalence of comorbidities, microbiology, antibiotic susceptibility patterns, 30-day and 90-day mortality and prognostic risk factors.
CONCLUSIONS: A total of 716 patients were included, with pneumonia pathogens identified in 69.8% of patients. Significant morbidities occurred, including respiratory failure (50.8%), intensive care unit transfer (40.8%) and mechanical ventilation (36%), with a 90-day mortality of 26.0%. Diagnosis of pneumonia occurred within 6 months of glucocorticoid initiation for 69.7% of patients with Cytomegalovirus (CMV) pneumonia and 79.0% of patients with Pneumocystis jirovecii pneumonia (PCP). Pathogens, including Pneumocystis, CMV and multidrug-resistant bacteria, were identified more frequently in patients with persistent lymphocytopenia and high-dose glucocorticoid treatment (≥30 mg/day of prednisolone or equivalent within 30 days before admission). The 90-day mortality was significantly lower for non-CMV viral pneumonias than for PCP (p<0.05), with a similar mortality as CMV pneumonias (24.2% vs 38.1% vs 27.4%, respectively). Cox regression analysis indicated several independent negative predictors for mortality in this patient population, including septic shock, respiratory failure, persistent lymphocytopenia, interstitial lung disease and high-dose glucocorticoid use.Patients who developed pneumonia while receiving glucocorticoid therapy experienced high rates of opportunistic infections, with significant morbidity and mortality. These findings should be carefully considered when determining treatment strategies for this patient population.

With a marginally effective vaccine and no significant breakthroughs in new treatments, a sensitive and specific method to distinguish active tuberculosis from latent tuberculosis infection (LTBI) would allow for early diagnosis and limit the spread of the pathogen. The analysis of multiple cytokine profiles provides the possibility to differentiate the two diseases.
Systematic review and meta-analysis.
PubMed, Cochrane Library, Clinical Key and EMBASE databases were searched on 31 December 2019.
We included case-control studies, cohort studies and randomised controlled trials considering IFN-γ, TNF-α, IP-10, IL-2, IL-10, IL-12 and VEGF as biomarkers to distinguish active tuberculosis and LTBI.
Two students independently extracted data and assessed the risk of bias. Diagnostic OR, sensitivity, specificity, positive and negative likelihood ratios and area under the curve (AUC) together with 95% CI were used to estimate the diagnostic value.
Of 1315 records identified, 14 studies were considered eligible. IL-2 had the highest sensitivity (0.84, 95% CI: 0.72 to 0.92), while VEGF had the highest specificity (0.87, 95% CI: 0.73 to 0.94). The highest AUC was observed for VEGF (0.85, 95% CI: 0.81 to 0.88), followed by IFN-γ (0.84, 95% CI: 0.80 to 0.87) and IL-2 (0.84, 95% CI: 0.81 to 0.87).
Cytokines, such as IL-2, IFN-γ and VEGF, can be utilised as promising biomarkers to distinguish active tuberculosis from LTBI.
CRD42020170725.