17-Alpha-Hydroxyprogesterone vs. Placebo for Preventing of Recurrent Preterm Birth: A Systematic Review and Meta-Analysis of Randomized Trials

Background: Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality.Objective: To estimate the effect of 17-alpha-hydroxyprogesterone caproate (17-OHPC) compared to placebo in singleton gestations for reducing the risk of recurrent PTB and neonatal morbidity and mortality.Work Design: Systematic review and meta-analysis.Search Strategy: Searching MEDLINE, Embase, Web of Science, SCOPUS, Cochrane Library, and clinical trial registries.Selection Criteria: Randomized controlled trials of singleton gestations with a history of PTB and treated with a weekly intramuscular injection of 17-OHPC or placebo.Data Collection and Analysis: A random meta-analysis model was performed for the PTB outcomes (<32, <35, and <37 weeks) and neonatal outcomes (neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, and sepsis). Effect estimates were measured by relative risk ratio (RR) with a 95% confidence interval (CI).Main Results: Six works were included. There were no statistically significant reductions in the PTB risk following the use of 17-OHPC at <32 weeks (RR = 0.61, 95% CI: 0.13–2.77, and I2 = 39%), <35weeks (RR = 0.60, 95% CI: 0.10–3.67, and I2 = 51%), and <37 weeks (RR = 0.68, 95% CI: 0.46–1, and I2 = 75%). Furthermore, all the neonatal outcomes were statistically similar between the two groups.Conclusion: Treatment with 17-OHPC is not associated with reducing the risk of PTB or neonatal outcomes compared to placebo.

Persistent and Emergent Clinical Sequelae of Mild COVID-19

BACKGROUND: Knowledge of the clinical course and consequences of COVID-19 initially evolved in the context of severe presentations and among those with comorbidities. However, understanding the outcomes of milder infections in healthy individuals is important for safe return-to-duty in extreme environments or to occupations requiring significant fitness. We reviewed the literature to characterize the nature and timing of persistent and emergent clinical sequelae in milder COVID-19 cases to facilitate development of post-COVID-19 screening and surveillance protocols.METHODS: We searched databases including EMBASE, MEDLINE, Cochrane COVID-19 study register, gray literature, clinical trial registries, and relevant health and disease prevention sources for publications from 2019 to February 18th, 2021, documenting COVID-19 sequelae. Articles were included if the COVID-19 severity was mild and there were no, or only minor, pre-existing comorbidities. Persistent and emergent sequelae were then stratified based on time since diagnosis.RESULTS: Among those with mild COVID-19, sequelae were shown to emerge or persist for months following presumed recovery. Among those with no comorbidities, cardiac, hematological, and respiratory sequelae emerged after 1-2 mo, and primarily cardiac abnormalities persisted at ≥ 3 mo. Among those with minor comorbidities, persistent respiratory abnormalities, fatigue, dyspnea, and headache were common, and mental health symptoms emerged by 1-2 mo postinfection.DISCUSSION: After presumed recovery from mild COVID-19, a range of symptoms can persist and later emerge. Whether these are new or previously unrecognized is unclear. Under-recognized COVID-19 sequelae may increase the risk of subtle or sudden incapacitation and have implications for return-to-work (RTW) screening and surveillance for safety-critical roles.Tucci V, Saary J. Persistent and emergent clinical sequelae of mild COVID-19. Aerosp Med Hum Perform. 2021; 92(12):962–969.

PP94 Pandemic Preparedness: EUnetHTA COVID-19 Rapid Response With “Rolling Collaborative Reviews (RCR)”

IntroductionPotential therapies and interventions for COVID-19 are emerging and developing rapidly. In a response to this public health emergency, the European Network for Health Technology Assessment (EUnetHTA) aims to support health policy in preparation for evidence-based purchasing. To monitor the emerging evidence, a new EUnetHTA product was created: Rolling Collaborative Reviews (RCRs).MethodsRCRs are living documents that are descriptive in nature, updated monthly, and centrally coordinated. They are based on the following three sources of information: (i) published randomized controlled trials (RCTs) presented as a summary of efficacy and safety data (synthesized for a network meta-analysis conducted by the Department of Epidemiology Lazio Regional Health Service, Italy); (ii) published prospective observational studies for safety results, provided by the Map of COVID-19 Evidence conducted by the Norwegian Institute of Public Health, Norway; and (iii) RCTs registered in clinical trial registries (ClinicalTrials.gov, EudraCT Register, and the ISRCTN registry). Additionally, detailed stopping and starting rules were defined.ResultsAs of November 2020, 14 RCRs were ongoing. From the initial list of RCRs, one was suspended due to lacking effectiveness and two moved on to rapid collaborative reviews due to European Medicines Agency approvals. Four RCRs are updated on a bimonthly basis due to a lack of high-quality evidence, and five new RCRs will be started because of promising clinical studies.ConclusionsRCRs can be a means of providing timely and continuous policy support, but they require a high level of coordinated effort.

OP218 Searching Preprint Repositories For COVID-19 Therapeutics Using A Semi-Automated Text-Mining Tool

IntroductionThe COVID-19 pandemic led to a significant surge in clinical research activities in the search for effective and safe treatments. Attempting to disseminate early findings from clinical trials in a bid to accelerate patient access to promising treatments, a rise in the use of preprint repositories was observed. In the UK, NIHR Innovation Observatory (NIHRIO) provided primary horizon-scanning intelligence on global trials to a multi-agency initiative on COVID-19 therapeutics. This intelligence included signals from preliminary results to support the selection, prioritisation and access to promising medicines.MethodsA semi-automated text mining tool in Python3 used trial IDs (identifiers) of ongoing and completed studies selected from major clinical trial registries according to pre-determined criteria. Two sources, BioRxiv and MedRxiv are searched using the IDs as search criteria. Weekly, the tool automatically searches, de-duplicates, excludes reviews, and extracts title, authors, publication date, URL and DOI. The output produced is verified by two reviewers that manually screen and exclude studies that do not report results.ResultsA total of 36,771 publications were uploaded to BioRxiv and MedRxiv between March 3 and November 9 2020. Approximately 20–30 COVID-19 preprints per week were pre-selected by the tool. After manual screening and selection, a total of 123 preprints reporting clinical trial preliminary results were included. Additionally, 50 preprints that presented results of other study types on new vaccines and repurposed medicines for COVID-19 were also reported.ConclusionsUsing text mining for identification of clinical trial preliminary results proved an efficient approach to deal with the great volume of information. Semi-automation of searching increased efficiency allowing the reviewers to focus on relevant papers. More consistency in reporting of trial IDs would support automation. A comparison of accuracy of the tool on screening titles/abstract or full papers may help to support further refinement and increase efficiency gains.This project is funded by the NIHR [(HSRIC-2016-10009)/Innovation Observatory]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Antimalarial drug candidates in phase I and II drug development: a scoping review

The emergence and spread of parasite resistance to currently available antimalarials has highlighted the importance of developing novel antimalarials. This scoping review provides an overview of antimalarial drug candidates undergoing phase I and II studies between 1 January 2016 and 28 April 2021. PubMed, Web of Science, Embase, clinical trial registries and reference lists were searched for relevant studies. Information regarding antimalarial compound details, clinical trial characteristics, study population, drug pharmacokinetics and pharmacodynamics (PK-PD) were extracted. A total of 50 studies were included of which 24 had published their results and 26 were unpublished. New antimalarial compounds were evaluated as monotherapy (28 studies, 14 drug candidates) and combination therapy (9 studies, 10 candidates). Fourteen active compounds were identified in the current antimalarial drug development pipeline together with 11 compounds that are inactive; six due to insufficient efficacy. PK-PD data were available from 24 studies published as open-access articles. Four unpublished studies have made their results publicly available on clinical trial registries. The terminal elimination half-life of new antimalarial compounds ranged from 14.7 to 483 hours. The log 10 parasite reduction ratio over 48 hours and parasite clearance half-life for P. falciparum following a single dose monotherapy were 1.55–4.1 and 3.4–9.4 hours, respectively. The antimalarial drug development landscape has seen a number of novel compounds, with promising PK-PD properties, evaluated in phase I and II studies over the past 5 years. Timely public disclosure of PK-PD data is crucial for informative decision-making and drug development strategy.

Utilization of Innovative Medical Technologies In German Inpatient Care: Does Evidence Matter?

Background: The reimbursement of new technologies in inpatient care is not always linked to a requirement for evidence-based evaluation of patient benefit. In Germany, every new technology approved for market was until recently reimbursable unless explicitly excluded. It was therefore unclear whether the implementation of innovative technologies is guided by scientific evidence. This work aimed to explore the relationship between clinical evidence and utilization for 25 selected technologies in German inpatient care.Methods: Different methods were applied. A systematic search for evidence published between 2003 and 2017 was conducted in four bibliographic databases; clinical trial registries; resources for clinical guidelines; and health technology assessment - databases. Information was also collected on funding mechanisms and safety notices. Utilization was measured by hospital cases captured in claims data. The body of evidence, funding and safety notices per technology were analysed descriptively. The relationship between utilization and evidence was explored empirically using a multilevel regression analysis.Results: The number of included publications per technology ranges from two to 498. For all technologies, non-comparative studies form the bulk of the evidence. The number of randomised controlled clinical trials per technology ranges from zero to 19. Some technologies were utilized for several years without an adequate evidence base. A relationship between evidence and utilization could be shown for several but not all technologies.Conclusions: This study reveals a mixed picture regarding the evidence available for new technologies, and the relationship between the development of evidence and the use of technologies over time. Although the influence of funding and safety notices requires further investigation, these results re-emphasize the need for strengthening market approval standards and HTA pathways as well as approaches such as “coverage with evidence development”.

Improving the FAIRness of Health Studies in Germany: The German Central Health Study Hub COVID-19

The German Central Health Study Hub COVID-19 is an online service that offers bundled access to COVID-19 related studies conducted in Germany. It combines metadata and other information of epidemiologic, public health and clinical studies into a single data repository for FAIR data access. In addition to study characteristics the system also allows easy access to study documents, as well as instruments for data collection. Study metadata and survey instruments are decomposed into individual data items and semantically enriched to ease the findability. Data from existing clinical trial registries (DRKS, clinicaltrails.gov and WHO ICTRP) are merged with epidemiological and public health studies manually collected and entered. More than 850 studies are listed as of September 2021.

Defining difficult intravenous access (DIVA): A systematic review

Background: The term “difficult intravenous access” (DIVA) is commonly used but not clearly defined. Repeated attempts at peripheral intravenous catheter (PIVC) insertion can be a traumatic experience for patients, leading to sub-optimal clinical and economic outcomes. We conducted a systematic literature review (SLR) to collate literature definitions of DIVA, with the aim of arriving at an evidence-driven definition. Methods: The SLR was designed to identify clinical, cost, and quality of life publications in patients requiring the insertion of a PIVC in any setting, including studies on US-guidance and/or guidewire, and studies with no specific intervention. The search was restricted to English language studies published between 1st January 2010 and 30th July 2020, and the Ovid platform was used to search several electronic databases, in addition to hand searching of clinical trial registries. Results: About 121 studies were included in the SLR, of which 64 reported on the objectives relevant to this manuscript. Prevalence estimates varied widely from 6% to 87.7% across 19 publications, reflecting differences in definitions used. Of 43 publications which provided a definition of DIVA, six key themes emerged. Of these, themes 1–3 (failed attempts at PIV access using traditional technique; based on physical examination findings for example no visible or palpable veins; and personal history of DIVA) were covered by all but one publication. Following a failed insertion attempt, the most common number of subsequent attempts was 3, and it was frequently reported that a more experienced clinician would attempt to gain access after multiple failed attempts. Conclusions: Considering the themes identified, an evidence-driven definition of DIVA is proposed: “when a clinician has two or more failed attempts at PIV access using traditional techniques, physical examination findings are suggestive of DIVA (e.g. no visible or palpable veins) or the patient has a stated or documented history of DIVA.”

How effective are devices in the management of Onychomycosis? A protocol for a systematic review

Review question / Objective: To compile evidence and determine the utility of various device-based treatments for the treatment of onychomycosis, and improve the appearance of afflicted toenails. Condition being studied: Toenail onychomycosis, also known as tinea unguium. Information sources: A systematic literature search will be conducted in Scopus, MEDLINE and PubMed. The bibliographies of relevant articles will also be searched to ensure a comprehensive review is presented. Clinical trial registries (such as clinicaltrials.gov) will also be searched for complete, or incomplete trials.

Mobile devices and wearable technology for measuring patient outcomes after surgery: a systematic review

Complications following surgery are common and frequently occur the following discharge. Mobile and wearable digital health interventions (DHI) provide an opportunity to monitor and support patients during their postoperative recovery. Lack of high-quality evidence is often cited as a barrier to DHI implementation. This review captures and appraises the current use, evidence base and reporting quality of mobile and wearable DHI following surgery. Keyword searches were performed within Embase, Cochrane Library, Web of Science and WHO Global Index Medicus databases, together with clinical trial registries and Google scholar. Studies involving patients undergoing any surgery requiring skin incision where postoperative outcomes were measured using a DHI following hospital discharge were included, with DHI defined as mobile and wireless technologies for health to improve health system efficiency and health outcomes. Methodological reporting quality was determined using the validated mobile health evidence reporting and assessment (mERA) guidelines. Bias was assessed using the Cochrane Collaboration tool for randomised studies or MINORS depending on study type. Overall, 6969 articles were screened, with 44 articles included. The majority (n = 34) described small prospective study designs, with a high risk of bias demonstrated. Reporting standards were suboptimal across all domains, particularly in relation to data security, prior patient engagement and cost analysis. Despite the potential of DHI to improve postoperative patient care, current progress is severely restricted by limitations in methodological reporting. There is an urgent need to improve reporting for DHI following surgery to identify patient benefit, promote reproducibility and encourage sustainability.