BACKGROUND: Ventilator-associated pneumonia (VAP) is a prevalent and grave hospital-acquired infection that affects mechanically ventilated patients. Diverse diagnostic criteria can significantly affect VAP research by complicating the identification and management of the condition, which may also impact clinical management.
OBJECTIVE: We conducted this review to assess the diagnostic criteria and the definitions of the term \"ventilator-associated\" used in randomised controlled trials (RCTs) of VAP management.
METHODS: Based on the protocol (PROSPERO 2019 CRD42019147411), we conducted a systematic search on MEDLINE/PubMed and Cochrane CENTRAL for RCTs, published or registered between 2010 and 2024.
METHODS: We included completed and ongoing RCTs that assessed pharmacological or non-pharmacological interventions in adults with VAP.
METHODS: Data were collected using a tested extraction sheet, as endorsed by the Cochrane Collaboration. After cross-checking, data were summarised in a narrative and tabular form.
RESULTS: In total, 7,173 records were identified through the literature search. Following the exclusion of records that did not meet the eligibility criteria, 119 studies were included. Diagnostic criteria were provided in 51.2% of studies, and the term \"ventilator-associated\" was defined in 52.1% of studies. The most frequently included diagnostic criteria were pulmonary infiltrates (96.7%), fever (86.9%), hypothermia (49.1%), sputum (70.5%), and hypoxia (32.8%). The different criteria were used in 38 combinations across studies. The term \"ventilator-associated\" was defined in nine different ways.
CONCLUSIONS: When provided, diagnostic criteria and definitions of VAP in RCTs display notable variability. Continuous efforts to harmonise VAP diagnostic criteria in future clinical trials are crucial to improve quality of care, enable accurate epidemiological assessments, and guide effective antimicrobial stewardship.

BACKGROUND: There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta-analysis and best practice advice.
OBJECTIVE: This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis.
METHODS: CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language.
METHODS: Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range.
RESULTS: Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid-luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies.
CONCLUSIONS: This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care.

The purpose of this paper is to systematically sort out and analyze the cutting-edge research on the eligibility criteria of clinical trials. Eligibility criteria are important prerequisites for the success of clinical trials. It directly affects the final results of the clinical trials. Inappropriate eligibility criteria will lead to insufficient recruitment, which is an important reason for the eventual failure of many clinical trials. We have investigated the research status of eligibility criteria for clinical trials on academic platforms such as arXiv and NIH. We have classified and sorted out all the papers we found, so that readers can understand the frontier research in this field. Eligibility criteria are the most important part of a clinical trial study. The ultimate goal of research in this field is to formulate more scientific and reasonable eligibility criteria and speed up the clinical trial process. The global research on the eligibility criteria of clinical trials is mainly divided into four main aspects: natural language processing, patient pre-screening, standard evaluation, and clinical trial query. Compared with the past, people are now using new technologies to study eligibility criteria from a new perspective (big data). In the research process, complex disease concepts, how to choose a suitable dataset, how to prove the validity and scientific of the research results, are challenges faced by researchers (especially for computer-related researchers). Future research will focus on the selection and improvement of artificial intelligence algorithms related to clinical trials and related practical applications such as databases, knowledge graphs, and dictionaries.

OBJECTIVE: To assess the eligibility criteria and trial characteristics among contemporary (2010-2019) randomized clinical trials (RCTs) that included infants born extremely preterm (<28 weeks of gestation) and to evaluate whether eligibility criteria result in underrepresentation of high-risk subgroups (eg, infants born at <24 weeks of gestation).
METHODS: PubMed and Scopus were searched January 1, 2010, to December 31, 2019, with no language restrictions. RCTs with mean or median gestational ages at birth of <28 weeks of gestation were included. The study followed the PRISMA guidelines; outcomes were registered prospectively. Data extraction was performed independently by multiple observers. Study quality was evaluated using a modified Jadad scale.
RESULTS: Among RCTs (n = 201), 32 552 infants were included. Study participant characteristics, interventions, and outcomes were highly variable. A total of 1603 eligibility criteria were identified; rationales were provided for 18.8% (n = 301) of criteria. Fifty-five RCTs (27.4%) included infants <24 weeks of gestation; 454 (1.4%) infants were identified as <24 weeks of gestation.
CONCLUSIONS: The present study identifies sources of variability across RCTs that included infants born extremely preterm and reinforces the critical need for consistent and transparent policies governing eligibility criteria.

Serotonergic dysfunction, including reduced central serotonin levels, is associated with different psychiatric syndromes, including depression. As a serotonin precursor, 5-hydroxytryptophan has long been used as a nonpharmacological treatment for depression.
A systematic review and meta-analysis was conducted to determine the antidepressant effects of 5-hydroxytryptophan in depressed patients.
MEDLINE (via PubMed) and Google Scholar were searched from inception to May 2018.
Thirteen investigations were included in the systematic review (using PRISMA guidelines), and 7 in the full meta-analysis (pre-registered on PROSPERO: CRD42018104415).
Analyses revealed a depression remission rate of 0.65 (95% confidence interval [CI], 0.55-0.78; remission rate [k] = 13), and this was confirmed by the questionnaire results, which revealed a large Hedges\' g (1.11; 95%CI, 0.53-1.69). Methodological variability (in treatment duration, type of depression studied, experimental design, 5-hydroxytryptophan dosage) contributes to heterogeneity in the results (I2 = 76%, τ2 = 0.379). In addition, the OHAT (Office of Health Assessment and Translation risk of bias rating) tool suggested that, on the whole, current studies are relatively weak (few include placebo groups).
Further trials should overcome these limitations by using placebo-controlled studies that include patients with well-defined depression diagnoses, along with strong characterization of psychological and physiological patient characteristics.

OBJECTIVE: PsA is a heterogeneous disease with various subtypes of joint manifestations, which can affect the homogeneity of randomized controlled trials (RCTs). The aim of this systematic literature review was to evaluate the inclusion criteria, demographics and outcomes of RCTs to see whether the whole spectrum of PsA was represented.
METHODS: Medline, EMBASE and Cochrane databases were screened for RCTs on the efficacy of any treatment for PsA up to 4 October 2016 to investigate the inclusion criteria, demographics, outcomes and efficacy.
RESULTS: Two thousand and sixty-eight abstracts were identified at screening; 76 articles and 52 conference proceedings were included in the final analysis. The main inclusion criteria always included the number of active joints and never axial symptoms, enthesitis nor dactylitis. Only 10 studies provided information about subtypes, of which symmetrical polyarthritis was the main subtype. Mean (s.d.) tender and swollen joints were between 7.8 and 35.8 (1.8-22.1) and between 5.2 and 25.2 (1.5-16.2), respectively. All studies had responses in joint counts as their primary outcome. Responses in enthesitis and dactylitis were usually secondary or tertiary outcomes. Response in BASDAI was among the outcomes in four studies. The comparison of efficacy in polyarticular vs oligoarticular disease was given in three studies, whereas no information was available for DIP joint disease or arthritis mutilans.
CONCLUSIONS: There is evidence in the literature to guide clinicians on how to treat PsA patients with polyarticular disease, but there is a gap in knowledge about the other subtypes.
BACKGROUND: The study protocol is registered at PROSPERO (CRD42017053907).

Low back pain is a common health complaint resulting in substantial economic burden. Each year, upwards of 20 randomised controlled trials (RCTs) evaluating interventions for non-specific low back pain are published. Use of the term non-specific low back pain has been criticised on the grounds of encouraging heterogeneity and hampering interpretation of findings due to possible heterogeneous causes, challenging meta-analyses. We explored selection criteria used in trials of treatments for nsLBP.
A systematic review of English-language reports of RCTs in nsLBP population samples, published between 2006 and 2012, identified from MEDLINE, EMBASE, and the Cochrane Library databases, using a mixed-methods approach to analysis. Study inclusion and exclusion criteria were extracted, thematically categorised, and then descriptive statistics were used to summarise the prevalence by emerging category.
We included 168 studies. Two inclusion themes (anatomical area, and symptoms and signs) were identified. Anatomical area was most reported as between costal margins and gluteal folds (n = 8, 5%), while low back pain (n = 150, 89%) with or without referred leg pain (n = 27, 16%) was the most reported symptom. Exclusion criteria comprised 21 themes. Previous or scheduled surgery (n = 84, 50%), pregnancy (n = 81, 48%), malignancy (n = 78, 46%), trauma (n = 63, 37%) and psychological conditions (n = 58, 34%) were the most common. Sub-themes of exclusion criteria mostly related to neurological signs and symptoms: nerve root compromise (n = 44, 26%), neurological signs (n = 34, 20%) or disc herniation (n = 30, 18%). Specific conditions that were most often exclusion criteria were spondylolisthesis (n = 35, 21%), spinal stenosis (n = 31, 18%) or osteoporosis (n = 27, 16%).
RCTs of interventions for non-specific low back pain have incorporated diverse inclusion and exclusion criteria. Guidance on standardisation of inclusion and exclusion criteria for nsLBP trials will increase clinical homogeneity, facilitating greater interpretation of between-trial comparisons and meta-analyses. We propose a template for reporting inclusion and exclusion criteria.

BACKGROUND: Since 2010, the use of Tranexamic Acid (TXA) in trauma has been brought to the forefront of severe hemorrhage treatment. However, the mixed literature illustrates the need for additional proof of efficacy and determining which patients may benefit from TXA. The purpose of this retrospective study was to evaluate a more stringent TXA inclusion criterion (heart rate ≥ 120 beats per minute (BPM) with a systolic blood pressure (SBP) ≤ 90 mmHg) as compared to the standard CRASH-2 inclusion criteria.
METHODS: From 2013-2016 a total of 115 patients (control, n = 62; TXA, n = 53) were included in the analysis. These patients adhered to the standard CRASH-2 and more stringent inclusion criteria; they also survived at least 8.5 hrs (minimum amount of time required for full TXA dose) from the initiation. Basic characteristics of the patients were summarized. The mortality rates between TXA and control groups were compared using two proportion z-tests. All p values <0.05 were considered statistically significant.
RESULTS: There was no statistical significant difference in patient characteristics between the two treatment groups, making them more comparable (p value >0.05). This study found a significant reduction of percent mortality at the 24 hr time point against the control (p = 0.007). Additionally, utilizing the more strict inclusion criteria (BPM ≥ 120 and SBP ≤ 90) substantially extended time to stabilize patients to 48 hrs (p = 0.029).
CONCLUSIONS: By imposing the more strict criteria, TXA appears to be a better treatment option in reducing mortality rates and potentially extends the treatment time-frame for stabilizing the patient up to 48 hours.

BACKGROUND: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) are often selected for randomized clinical trials (RCTs) aiming at new drug approval. Guidelines for the design of such RCTs have been repeatedly updated by regulatory agencies. We hypothesized that large variability in the enrolled populations, the endpoints assessed and the HAP/VAP definition criteria may impact the results of these studies, and addressed this through a systematic review of HAP/VAP RCTs.
METHODS: A search (Pubmed-Embase-ICAAC-ECCMID) of all RCTs published between 1994 and 2016 comparing antimicrobial treatment for HAP/VAP in the intensive care unit was conducted. The populations enrolled, inclusion/exclusion criteria, statistical design and endpoints assessed were recorded. All unpublished RCTs recorded on the ClinicalTrials.gov registry were also screened.
RESULTS: From the 93 abstracts reviewed, 39 potentially relevant studies were inspected, leading to 27 studies being included. As expected, illness severity or the proportion with VAP (27-100%) differed greatly among the enrolled populations. The HAP/VAP definition used various clinical and biological criteria, and only 55% of studies required a microbiological sample. The mandatory duration of prior hospital stay was variable; the mechanical ventilation duration was an inclusion criterion in only 41% of VAP studies. Nine studies had non-inferiority design, but nine studies (33%) did not have a pre-specified statistical hypothesis. Clinical cure was the primary endpoint in 24 studies, but was recorded in several populations or as the co-primary endpoint in 13 studies. The definition of clinical cure and the timing of its assessment greatly differed. This variability slightly improved over time but remained significant in the 13 registered but currently unpublished RCTs that we screened.
CONCLUSIONS: Our study provides a description of populations and endpoints of RCTs evaluating antimicrobials for treatment of HAP/VAP in the ICU. There was significant heterogeneity in enrollment criteria, endpoints and statistical design, which may influence the ability of studies to demonstrate differences between studied drugs.