Search

Latest advances in non-small cell lung cancer (NSCLC) therapies have revolutionized the treatment regimens utilized for NSCLCs with or without a driver mutation. Molecular targeted treatments such as tyrosine kinase inhibitors (TKIs) are utilized to prevent tumor progression and improve survival. Despite the great benefit of immunotherapy in NSCLC tumors with no driver mutation, the use of immune checkpoint inhibitors (ICIs) in NSCLC tumors harboring a driver mutation has been under debate. Furthermore, several trials have been conducted investigating the use of these therapies with TKIs. A few trials were halted due to growing concerns of increased toxicity with the combination of TKI and immunotherapy. The adverse events ranged from low grade dermatologic complaints to fatal interstitial lung diseases. These toxicities occur with both concurrent and sequential administration of treatment. Thus, recommendations for the safest method of combination treatment have not yet been described. This review paper discusses recent views on combination treatment, previous clinical trials reporting grade 3-4 toxicities, and guidelines for a safe timeline of administration of treatment based on past evidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Systematic reviews rank at the top of the evidence hierarchy. Concise writing implies drafting the systematic review article succinctly, i.e. using as few words to express as full an extent of the research effort as possible. Precise writing means drafting the text with accuracy especially with respect to the methodological and statistical aspects. The Abstract ought to be succinct and structured to allow for editors, peer reviewers and readers to get the gist of the key aspects of the systematic review with a quick read. The readership needs to be able to critically appraisal systematic reviews for their internal and external validity rapidly. The Abstract also needs to be standalone, representing an independent summary that can be fully understood without the need for reading the full paper. The standard structure of the main text of a scientific article called IMRaD (Introduction, Methods, Results and Discussion) applies equally to systematic reviews in the same way as it does to any other kinds of research manuscripts whether related to laboratory experiments or clinical trials. Restricting the word count limits to those imposed by journals may at first seem difficult, even unfair, to systematic reviewers. However, with the availability of online appendices to transparently and fully report the details of the methods, results and other aspects of the work undertaken allows for a succinct print or PDF article. Writing a shorter manuscript is more effortful than writing a longer report. This commentary is aimed at novice systematic reviewers to help them learn the written and unwritten writing rules in order to assist them in producing impactful publications to support evidence-based medicine. [ABSTRACT FROM AUTHOR]

Background Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective. Methods A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021. Results Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded "severe" were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database. Conclusions HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218. [ABSTRACT FROM AUTHOR]

Background: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. Methods: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. Discussion: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. Trial registration: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772) [ABSTRACT FROM AUTHOR]

In the era of social media, journalism is no longer the preserve of journalists. In specialised fields, such as law, the public in general and lawyers and legal academics specifically are able to "push in" and report and comment publicly on legal matters including trials, commissions, acts of law passed in parliament and other legal processes. These contributions, as this paper explores, are reshaping the contours and content of public discussions of legal matters and of legal journalism in South Africa. This paper suggests that recent theorising of journalism role theory can help understand not just the motivations of these legal interlopers in the journalism space but also how they are shaping a new informational ecosystem in which legal issues, including human rights, administrative and criminal law, and other topics, are brought into the public domain. The paper explores what some South African lawyers understand about the roles they are playing in digital public spaces and how they perceive their contributions and their relationship to the journalism profession and to journalists within that profession. The paper suggests that these lawyers' practices challenge our understanding about how digital media informational ecosystems work and explores how this is impacting journalism in South Africa. [ABSTRACT FROM AUTHOR]

Introduction: Registering study protocols in a trial registry is important for methodologic transparency and reducing selective reporting bias. The objective of this investigation was to determine whether published studies of intimate partner violence (IPV) that had been registered matched the registration record on key study design elements. Methods: We systematically searched three trial registries to identify registered IPV studies and the published literature for the associated publication. Two authors independently determined for each study whether key study elements in the registry matched those in the published paper. Results: We included 66 studies published between 2006 and 2017. Nearly half (29/66, 44%) were registered after study completion. Many (26/66, 39%) had discrepancies regarding the primary outcome, and nearly two-thirds (42/66, 64%) had discrepancies in secondary outcomes. Discrepancies in study design were less frequent (13/66, 20%). However, large changes in sample size (26/66, 39%) and discrepancies in funding source (28/66, 42%) were frequently observed. Conclusions: Trial registries are important tools for research transparency and identifying and preventing outcome switching and selective outcome reporting bias. Published IPV studies often differ from their records in trial registries. Researchers should pay close attention to the accuracy of trial registry records. [ABSTRACT FROM AUTHOR]

Non-timely reporting, selective reporting, or non-reporting of clinical trial results are prevalent and serious issues. WHO mandates that summary results be available in registries within 12 months of study completion and published in full text within 24 months. However, only a limited number of clinical trials in infectious diseases, including those done during the COVID-19 pandemic, have their results posted on ClinicalTrials.gov. An analysis of 50 trials of eight antiviral drugs tested against COVID-19 with a completion date of at least 2 years ago revealed that only 18% had their results published in the registry, with 40% not publishing any results. Non-timely and non-reporting practices undermine patient participation and are ethically unacceptable. Strategies should include obligatory reporting of summary results within 12 months in clinical trial registries, with progress towards peer-reviewed publication within 24 months indicated. Timely publication of research papers should be encouraged through an automated flagging mechanism in clinical trial registries that draws attention to the status of results reporting, such as a green tick for trials that have reported summary results within 12 months and a red tick in case of failure to do so. We propose the inclusion of mandatory clinical trial reporting standards in the International Conference on Harmonization Good Clinical Practice guidelines, which should prohibit sponsor contract clauses that restrict reporting (referred to as gag clauses) and require timely reporting of results as part of the ethics committees' clearance process for clinical trial protocols. [ABSTRACT FROM AUTHOR]

When a lien is established by entry in a specific public register (registry), it is a registered lien – a mortgage. According to the method of establishment, the right of lien, which is established by entry in the public register (registry), is called a mortgage. In modern real law insurance systems, an important place is occupied by lien law insurance, which allows the creditor, upon maturity of the claim, if it is not settled, to be settled from the value of the pledged thing, regardless of whether the thing at the time of settlement is owned by the pledge debtor or not. In this sense, the arrangement of lien insurance on things that are restricted in circulation for social, political and security reasons is particularly important. Thus, for weapons, a special regulation has determined the regime of legal circulation characterized by various restrictions, approvals and records of possession and ownership. Possession of weapons in the Republic of Croatia is governed by the Act on the Acquisition and Possession of Weapons by Citizens. However, the assumptions, effects and procedure for registration of a registered lien on weapons as movable property are governed by the Act on the Register of Court and Public Notary Security of Claims on Movable Property and Rights. In this regard, there are various registers in which different actual rights to weapons are registered, and which are kept by different state bodies. The paper analyses the actual legal significance (declaratory and constitutive) of the registration of weapons in various registers, the procedure and legal consequences of the registration. Open issues of establishment and transfer of lien rights, satisfaction of the lien creditor, right to possession and use of weapons as pledge are highlighted. The adequacy of the existing types of entries in the Register of Court and Public-Notary Security of Claims on Movable Property and Rights is analysed. The paper offers to provide guidelines and possible solutions for the regulation of these issues de lege ferenda that would meet the general, political and legal interests, as well as interests in private law of real rights holders on weapons. [ABSTRACT FROM AUTHOR]

Increasing farmers' income has always been the core task of China's land reform. In 2017, a nationwide pilot project on the use of collective construction land for the construction of rental housing was launched. This study employed the synthetic difference-in-differences method to examine whether the reform contributed to the growth of farmers' property income. It was found that, compared with non-pilot areas, the property income of farmers in the pilot reform of collective construction land rental housing has increased by about 0.4334% on average, and this conclusion is still valid after a series of robustness tests. The role of the reform in promoting farmers' property income is more evident in Western China, Southern China and non-major grain-producing areas. By revealing the impact of the reform on farmers' property income, this paper enriches the literature related to the field of farmers' income increase and provides a policy reference for narrowing the urban–rural gap and achieving the development of rural revitalization and common prosperity. [ABSTRACT FROM AUTHOR]

Background: Selective publication of studies has important scientific, ethical, and public health implications. Aim: We studied selective publication among mood disorder research protocols registered in the Clinical Trials Registry of India (CTRI) database. We also examined the frequency and nature of protocol deviations among the published articles. Methods: Using a systematic search strategy, we examined the publication status of all mood disorder-related research protocols registered in the CTRI database from inception till December 31, 2019. Logistic regression analysis was used to identify variables associated with selective publication. Results: Of 129 eligible protocols identified, only a third (n = 43, 33.3%) were published in literature; among those published, only 28 (21.7%) were placed in MEDLINE indexed journals. Protocol deviations were observed in more than half of the published papers (n = 25, 58.1%); many of these (41.9%) were related to sample size deviations, though, importantly, deviations in primary and secondary outcomes were also noted (16.2%). Retrospective registration of trials (odds ratio, 2.98, 95% confidence interval, 1.32--6.71) was significantly associated with publication; other variables, such as funding status or multicentric sampling, were not associated with eventual publication. Conclusions: Two out of three mood disorder research protocols registered in India do not translate into published research. These findings from a low- and middle-income country with limited spending on health care research and development represent wastage of resources and raise scientific and ethical concerns about unpublished data and futile patient participation in research. [ABSTRACT FROM AUTHOR]

The systematic cadastral work in Romania involves the identification and measurement of buildings and their owners, their registration in the technical cadastral documents and their representation on cadastral plans, in order to be entered in the land register. Theseworks are carried out within the National Program, a program whose purpose is the free registration of buildings in the integrated cadastre and land book system, the realization of the cadastral plan of buildings and the opening of land books at the level of all UATs. The paper presents the situation of the systematic registration of properties in Mure county. [ABSTRACT FROM AUTHOR]

Background: Nasal High Flow (NHF) therapy delivers flows of heated humidified gases up to 60 LPM (litres per minute) via a nasal cannula. Particles of oral/nasal fluid released by patients undergoing NHF therapy may pose a cross-infection risk, which is a potential concern for treating COVID-19 patients. Methods: Liquid particles within the exhaled breath of healthy participants were measured with two protocols: (1) high speed camera imaging and counting exhaled particles under high magnification (6 participants) and (2) measuring the deposition of a chemical marker (riboflavin-5-monophosphate) at a distance of 100 and 500 mm on filter papers through which air was drawn (10 participants). The filter papers were assayed with HPLC. Breathing conditions tested included quiet (resting) breathing and vigorous breathing (which here means nasal snorting, voluntary coughing and voluntary sneezing). Unsupported (natural) breathing and NHF at 30 and 60 LPM were compared. Results: Imaging: During quiet breathing, no particles were recorded with unsupported breathing or 30 LPM NHF (detection limit for single particles 33 μm). Particles were detected from 2 of 6 participants at 60 LPM quiet breathing at approximately 10% of the rate caused by unsupported vigorous breathing. Unsupported vigorous breathing released the greatest numbers of particles. Vigorous breathing with NHF at 60 LPM, released half the number of particles compared to vigorous breathing without NHF. Chemical marker tests: No oral/nasal fluid was detected in quiet breathing without NHF (detection limit 0.28 μL/m3). In quiet breathing with NHF at 60 LPM, small quantities were detected in 4 out of 29 quiet breathing tests, not exceeding 17 μL/m3. Vigorous breathing released 200–1000 times more fluid than the quiet breathing with NHF. The quantities detected in vigorous breathing were similar whether using NHF or not. Conclusion: During quiet breathing, 60 LPM NHF therapy may cause oral/nasal fluid to be released as particles, at levels of tens of μL per cubic metre of air. Vigorous breathing (snort, cough or sneeze) releases 200 to 1000 times more oral/nasal fluid than quiet breathing (p < 0.001 with both imaging and chemical marker methods). During vigorous breathing, 60 LPM NHF therapy caused no statistically significant difference in the quantity of oral/nasal fluid released compared to unsupported breathing. NHF use does not increase the risk of dispersing infectious aerosols above the risk of unsupported vigorous breathing. Standard infection prevention and control measures should apply when dealing with a patient who has an acute respiratory infection, independent of which, if any, respiratory support is being used. Clinical trial registration: ACTRN12614000924651 [ABSTRACT FROM AUTHOR]

PHOTO (COLOR): A study of the health benefits of a Mediterranean diet was rewritten after a statistical analysis set off alarm bells. Drazen was unsettled enough by what his own journal found to give his manuscript editors a statistics course, and implement extra scrutiny of statistics in accepted papers. [Extracted from the article]

Background: Even though considered as studies with high methodological power, many RCTs in paediatric dentistry do not have essential quality items in their design, development, and report, making results' reliability questionable, replication challenging to conduct, wasting time, money, and efforts, and even exposing the participants to research for no benefit. Aim: We addressed the main topics related to transparency in clinical research, with an emphasis in paediatric dentistry. Design: We searched for all controlled clinical trials published from January 2019 up to July 2020 in the three paediatric dentistry journals with high journal Impact Factor, indexed on Medline. These papers were assessed for transparency according to Open Science practices and regarding reporting accuracy using some items required by CONSORT. Results: 53.6% of the studies declared registration, 75% had sample size calculation, 98.2% reported randomisation, and from those, 65.4% explained the randomisation method. Besides that, no study shared their data, and 6.8% were published in open access format. Conclusions: Unfortunately, a large proportion of RCTs in paediatric dental research show a lack of transparency and reproducibility. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of removable partial dentures (RPDs) on masticatory performance (MP) of partially edentulous subjects. Materials and Methods: Electronic database and hand searches were conducted to explore clinical trials reporting the evidence of the effect of metal- and acrylic-based RPDs on mastication. The validated objective and subjective measures of assessment of mastication were included. The article selection, data extraction, and assessment of risk of bias were conducted by two reviewers independently. Results: Out of 11,200 studies, 1 randomized controlled trial and 23 clinical trials met the inclusion criteria. Positive impact on different parameters of masticatory function after RPD treatment was reported in 14 studies. Subjective evaluation of chewing ability (CA) displayed an improvement in 83.3% of studies, while improvement was evidenced only in 69.5% of studies upon objective evaluation. Most studies reported data on free-end saddles. Of the 13 studies associated with bilateral free-end saddle dentures, 9 studies showed a positive effect on masticatory efficiency. Various factors were found to have an impact on the MP of RPDs. Conclusions: Subjective evaluation displays higher positive impact of RPDs in MP than objective evaluation. Assessment of patients' perspectives is important in clinical decision-making. Multiple factors affect the MP with RPD treatment. [ABSTRACT FROM AUTHOR]

Background: Herein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized antidepressant therapy. Methods: Adults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity [ i.e. , Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥ 20] were treated with open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. The previously validated THINC-it tool was the primary dependent measure. The THINC-it tool was validated against the paper and pencil version of the Digit Symbol Substitution Test (DSST) and the Trails Making Test B (TMTB). Results: After 8 weeks of treatment, adults with MDD exhibited improvement in cognitive function relative to healthy controls (e.g. , processing speed) (p = 0.031). A subdomain measure of working memory (i.e. , symbol check; SC) exhibited significant improvement at Weeks 2 and 8 in latency (p = 0.032), SC accuracy (p = 0.046), and objective z-score (p = 0.001) independent of depressive symptoms. A linear regression analysis determined that the THINC-it tool measures of processing speed, as well as executive function were significantly associated with changes observed on the pencil and paper version the Digit Symbol Substitution Test (DSST) (p = 0.002) and in Trails Making Test B (TMTB) (p = 0.003), respectively. Conclusion: The THINC-it tool demonstrates sensitivity to change in adults with MDD and is highly correlated with improvements on pencil and paper versions of DSST and TMTB. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03053362. [ABSTRACT FROM AUTHOR]

Background: Despite efforts to improve the accuracy and transparency of the design, conduct, and reporting of randomised controlled trials (RCTs), deficiencies remain. Such deficiencies contribute to significant, avoidable waste of health research investment and impede reproducibility. This study aimed to synthesise and critically analyse changes over time in the conduct and reporting of internationally published evidence on patient and/or population health-oriented RCTs conducted in one country.Methods: This observational study drew on systematic review methods. We searched six databases for published RCTs (database inception to December 2018) where ≥ 80% of participants were recruited in the Republic of Ireland. RCTs of interventions targeted at patients, providers and/or policy makers intended to improve health, healthcare or health research were included. For each study, screening, data extraction and methodological quality appraisal were conducted by one member of the author team.Results: From 17,560 titles and abstracts, 752 unique RCTs were published in 745 papers between 1968 and 2018, with a steady year-on-year increase since 1968. The number of participants was in the range of 2-8628. The majority were parallel design (86%) and classified as treatment evaluation. Of the 418 RCTs published since the introduction of mandatory clinical trial registration by the International Committee of Medical Journal Editors in 2005, 32% (n = 134) provided a trial registration number. This increased to 47% when taking studies published between 2013 and 2018 (n = 232). Since the 1996 publication of the CONSORT statement, 16% of included RCTs made specific reference to a standardised reporting guideline and this increased to 31% for more recent studies published between 2013 and 2018. Overall, 7% (n = 53) of studies referred to a published study protocol, increasing to 20% for studies published between 2013 and 2018.Conclusion: Evidence from this single-country study of RCTs published in the international literature suggests that both the number overall, the number registered and the number referencing reporting guidelines have increased steadily over time. Despite widespread endorsement of reporting standards, reporting of RCTs remains suboptimal in domains such as compliance with the CONSORT statement and prospective trial registration. Researchers, funders and journal editors, nationally and internationally, should continue to focus on improving reporting and examining avoidable waste of health research investment. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus on controlling for disease symptoms and maintaining high quality of life. Information on individual needs of patients and their relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or are not routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adapted for these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. Methods: The concept for patient-centered "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germany comprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information including routine data from established Cancer Registries in different federal states, treating physicians in hospital as well as in outpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancer registry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-based questionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitor needs, progression, and therapy change of individual patients. Patient's acceptance and feasibility of data collection in clinical routine was assessed within a proof-of-concept study. Results: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018. In total n = 31 patients were included in the pilot study, n = 22 patients were followed up after 1 month. Record linkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n = 7 participants. The feasibility of the registry concept in clinical routine was positively evaluated by the participating hospitals. Conclusion: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needs of family members, and raising clinical parameters from primary and secondary data sources as well as m-health applications are feasible and accepted in an incurable cancer collective. [ABSTRACT FROM AUTHOR]

Background: The occurrence of postoperative cognitive deficits, especially after heart surgery, has been demonstrated in several studies. These deficits can clearly be noticed by the patients and by their close relatives in daily life. Furthermore, postoperative cognitive deficits can decrease quality of life in social functioning and earning capacity. The aim of this study is to investigate whether early postoperative cognitive training can reduce subjective and objective postoperative cognitive deficits.Methods: The proposed study is a multicenter, two-arm, randomized controlled trial involving 144 elderly patients undergoing elective heart-valve surgery with extracorporeal circulation. Patients will be assigned to either a training group or a control group. The intervention involves paper-and-pencil-based cognitive training, which is conducted for 36 min over a period of 18 days. The training starts about 1 week after surgery and is carried out during the hospitalized rehabilitation phase. The control group will not receive cognitive training or a placebo intervention. A detailed assessment of psychological functions and health-related quality of life prior to surgery at discharge from rehabilitation and 3 and 12 months after discharge will be performed. The primary outcome of this trial is the training effect on objective cognitive functions at discharge from rehabilitation. Secondary outcomes are the training effect on objective and subjective cognitive functions (3 and 12 months after discharge), depression, health-related quality of life, and the impact of perioperative cerebral ischemia on the training effect. Perioperative cerebral ischemia will be measured with postoperative magnetic resonance imaging including diffusion-weighted sequences.Discussion: Should it be shown that our cognitive training can improve postoperative cognitive deficits and quality of life, one possibility could be to integrate this intervention into early rehabilitation. Furthermore, we hope that the investigation of perioperative ischemia by diffusion-weighted magnetic resonance imaging will improve our understanding of neurobiological factors influencing the course of postoperative cognitive plasticity.Trial Registration: German Clinical Trials Register (DRKS), DRKS00015512. Retrospectively registered on 21 September 2018. [ABSTRACT FROM AUTHOR]

Background: Falls are common among older people, and General Practitioners (GPs) could play an important role in implementing strategies to manage fall risk. Despite this, fall prevention is not a routine activity in general practice settings. The iSOLVE cluster randomised controlled trial aimed to evaluate implementation of a fall prevention decision tool in general practice. This paper sought to describe the strategies used and reflect on the enablers and barriers relevant to successful recruitment of general practices, GPs and their patients.Methods: Recruitment was conducted within the geographical area of a Primary Health Network in Northern Sydney, Australia. General practices and GPs were engaged via online surveys, mailed invitations to participate, educational workshops, practitioner networks and promotional practice visits. Patients 65 years or older were recruited via mailed invitations, incorporating the practice letterhead and the name(s) of participating GP(s). Observations of recruitment strategies, results and enabling factors were recorded in field notes as descriptive and narrative data, and analysed using mixed-methods.Results: It took 19 months to complete recruitment of 27 general practices, 75 GPs and 560 patients. The multiple strategies used to engage general practices and GPs were collectively useful in reaching the targeted sample size. Practice visits were valuable in engaging GPs and staff, establishing interest in fall prevention and commitment to the trial. A mix of small, medium and large practices were recruited. While some were recruited as a whole-practice, other practices had few or half of the number of GPs recruited. The importance of preventing falls in older patients, simplicity of research design, provision of resources and logistic facilitation of patient recruitment appealed to GPs. Recruitment of older patients was successfully achieved by mailed invitations which was a strategy that was familiar to practice staff and patients. Patient response rates were above the expected 10% for most practices. Many practices (n = 17) achieved the targeted number of 20 or more patients.Conclusions: Recruitment in general practice settings can be successfully achieved through multiple recruitment strategies, effective communication and rapport building, ensuring research topic and design suit general practice needs, and using familiar communication strategies to engage patients.Trial Registration: The trial was prospectively registered on 29 April 2015 with the Australian New Zealand Clinical Trial Registry www.anzctr.org.au (trial ID: ACTRN12615000401550). [ABSTRACT FROM AUTHOR]

Copyright of Journal of Advanced Nursing (John Wiley & Sons, Inc.) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: A bone fracture is a break in the continuity of bone tissue, caused by the action of an external or internal force on the bone. Ankle sprains are one of the most common injuries among athletes. Physically active people who participate in activities that require jumping, changing direction, and turning have an increased risk of ankle sprains. Ankle sprains and the repetitive trauma often associated with this condition can lead to long-term disability, lost time from activity, and financial burdens for athletes. Methods: The work is non-experimental (qualitative research), i.e. a review of scientific literature. The search included an overview of the relevant databases: Medline, PubMed, Google Scholar, Research Gate. The literature review includes 4 randomized clinical trials and 1 randomized single-blind trial. The mentioned databases were searched with the help of keywords: athletes, injury, ankle joint, rehabilitation. Results: Through a scientific review of the literature, the results of the significance and productivity of the application of rehabilitation in athletes with an ankle injury are presented. The results include the presentation and analysis of five published scientific papers in the period 2018-2020. The studies used for this review were published in India, Saudi Arabia, Iran, United States, Austria. Conclusion: By reviewing the scientific literature, it can be concluded that there are improvements in the quality of life of athletes after an ankle injury. The greatest improvements were noted in strength, balance and functional task performance. The application of the rehabilitation program plays an important role in reducing pain and stabilizing the knee joint. [ABSTRACT FROM AUTHOR]

Background: Digital health technologies (DHTs) can facilitate the execution of de-centralized trials that can offer opportunities to reduce the burden on participants, collect outcome data in a real-world setting, and potentially make trial populations more diverse and inclusive. However, DHTs can also be a significant source of electronic waste (e-waste). In recognition of the potential health and environmental impact from DHT use in trials, private and public institutions have recently launched initiatives to help measure and manage this e-waste. But in order to develop sound e-waste management policies, it will be necessary to first estimate the current volume of e-waste that results from the use of DHTs in trials. Materials and Methods: A Web Ontology Language (OWL)-compliant ontology of DHTs was created using a list of 500 DHT device names derived from a mixture of public and private sources. The U.S. clinical trials registry, ClinicalTrials.gov, was then queried to identify and classify trials using any of the devices in the ontology. The ClinicalTrials.gov records from this search were then analyzed to characterize the volume and properties of trials using DHTs, as well as estimating the total volume of individual DHT units that have been provisioned (or are planned to be provisioned) for clinical research. Results: Our ontology-driven search identified 2326 unique clinical trials with a reported "actual" enrollment of 200,947 participants and a "planned" enrollment of an additional 4,094,748 participants. The most-used class of DHTs in our ontology was "wearables," (1852 trials), largely driven by the use of smart watches and other wrist-worn sensors (estimated to involve 149,391 provisioned devices). The most-used subtype of DHTs in trials was "subcutaneous" devices (367 trials), driven by the prevalent use and testing of glucose monitors (estimated to involve 17,666 provisioned devices). Conclusion: Thousands of trials, involving hundreds of thousands of devices, have already been completed, and many more trials (potentially involving millions more devices) are planned. Despite the great opportunities that are afforded by DHTs to the clinical trial enterprise, if the industry lacks the ability to track DHT use with sufficient resolution, the result is likely to be a great deal of e-waste. A new ontology of DHTs, combined with rigorous data science methods like those described in this paper, can be used to provide better information across the industry, and in turn, help create a more sustainable and equitable clinical trials enterprise. [ABSTRACT FROM AUTHOR]

Background: Research on clinical trials that employ stem cells to treat children's diseases is limited. The clinical trial registry database provides a unique window to us to get known about clinical trial researches with different statuses. However, few studies aimed to perform a comprehensive and thorough analysis of those registered trials in the aforementioned field based on ClinicalTrials.gov and the ICTRP portal site. Methods: Our study covered the clinical researches about stem cell therapy enrolling subjects aged under 18 years old registered on ClinicalTrials.gov and WHO ICTRP before May 18, 2021. A cross-sectional study was implemented to comprehensively describe and analyze the included trials that met the criteria. Results were available on ClinicalTrials.gov, and publications related to the included trials were identified. All analyses were performed utilizing the SPSS 25.0 software. Results: Eventually, 202 clinical trials were included and evaluated. The participant number of trials tended to be small; 71.3% were enrolled < 50. And 93.5% of the subjects were without gender restrictions. Till May 2020, 112 trials had been preliminary completed, of which only 39 trials had published papers or uploaded results. Most (73.6%) of 186 interventional trials were in phase 1 and phase 2, where 131 (70.4%) trials were conducted without masking, and 26.3% trials were randomized; 55.4% trials were performed single group assignment. Of 16 observational trials, case-only/series took up 37.5%. Hematopoietic stem cells (37.1%) and mesenchymal stem cells (36.1%) were mostly employed, while umbilical cord blood (UCB)-derived cells (24.3%) and bone marrow (BM)-derived cells (20.8%) were the major sources. Conclusions: This study provided an overall picture of utilizing stem cells for treatment and management of childhood diseases. Since clinical trials in this area are insufficient in quantity and quality, there is an urgent need of larger, better-designed trials. Increased investment in clinical research of stem cell treatment products should be carried out to achieve the transformation of results as soon as possible. Moreover, it is important to optimize the management of the registration platform and shorten the time it takes for research results to be published. [ABSTRACT FROM AUTHOR]

Copyright of Tarih İncelemeleri Dergisi is the property of Tarih Incelemeleri Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In emergency response and disaster rescue, unmanned aerial vehicles (UAVs) onboard thermal infrared (TIR) sensors are an essential means of acquiring ground information in the nighttime working environment. To enable field personnel to make better decisions based on TIR video streams returned from a UAV, the geographic information enhancement of TIR video streams is required. At present, it is difficult for low-cost UAVs to carry high-precision attitude sensors and thus obtain high-precision camera attitude information to meet the enhanced processing requirements of UAV TIR video streams. To this end, this paper proposes an improved Kalman filter algorithm to improve the geographic registration (geo-registration) accuracy by fusing the positioning and heading data from the dual-antenna real-time kinematic global positioning system (RTK-GPS) with onboard internal measurement unit (IMU) data. This method can yield high-precision position and attitude data in real time based on low-cost UAV hardware, based on which high-precision geo-registration results can be obtained. The computational complexity can be reduced compared with video stream feature tracking algorithms. Furthermore, the problem of unstable matching due to the low resolution and texture level of TIR video streams can be avoided. The experimental results prove that the proposed method can reduce the registration error by 66.15%, and significantly improve the geo-registration accuracy of UAV TIR video streams. Thus, it can strongly support the popularization and practicality of the application of augmented reality (AR) technology to low-cost UAV platforms. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS‐CoV‐2 lifecycle and COVID‐19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID‐19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as "pivotal clinical trials" (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data. [ABSTRACT FROM AUTHOR]

Goal. Stroke patients are usually accompanied by motor dysfunction, which greatly affects daily life. Electroacupuncture is a kind of nondrug therapy that can effectively improve motor function. However, the effect of electroacupuncture is hard to be measured immediately in clinic. This paper is aimed to reveal the instant changes in brain activity of three groups of stroke patients before, during, and after the electroacupuncture treatment by the EEG analysis in the alpha band and beta band. Methods. Seven different functional connectivity indicators including Pearson correlation coefficient, spectral coherence, mutual information, phase locking value, phase lag index, partial directed coherence, and directed transfer function were used to build the BCI-based brain network in stroke patients. Results and Conclusion. The results showed that the brain activity based on the alpha band of EEG decreased after the electroacupuncture treatment, while in the beta band of EEG, the brain activity decreased only in the first two groups. Significance. This method could be used to evaluate the effect of electroacupuncture instantly and quantitatively. The study will hopefully provide some neurophysiological evidence of the relationship between changes in brain activity and the effects of electroacupuncture. The study of BCI-based brain network changes in the alpha and beta bands before, during, and after electroacupuncture in stroke patients of different periods is helpful in adjusting and selecting the electroacupuncture regimens for different patients. The trial was registered on the Chinese clinical trial registry (ChiCTR2000036959). [ABSTRACT FROM AUTHOR]

We read with interest the paper by Koda I et al i .[1] entitled 'Randomized trial of granulocyte colony-stimulating factor for spinal cord injury'. However, the manner in which the results are presented - and I post hoc i subgroup analyses performed - would suggest that the mixed-effect model described in the protocol was not used. Study participants, who were in the acute phase of their spinal cord injury, enrolled in the trial in the hope that, in the future, others who sustain a spinal cord injury would have improved outcomes. [Extracted from the article]

Featured Application: In this paper, we propose a lightweight key-value store for managing various types of data, which are generated from Big data applications, in a very simple form. The proposed technique can be used in any environments where Windows operating systems are running, which encompass from client environments (e.g., Windows 10) to server environments (e.g., Windows Server 2016), with the minimum effort for the installation. For the other environments without Windows operating systems, we can easily migrate data to the other any environments that support existing key-value stores by using the ETL (Extract-Transform-Load) method proposed by this paper. In this paper, we propose a method to construct a lightweight key-value store based on the Windows native features. The main idea is providing a thin wrapper for the key-value store on top of a built-in storage in Windows, called Windows registry. First, we define a mapping of the components in the key-value store onto the components in the Windows registry. Then, we present a hash-based multi-level registry index so as to distribute the key-value data balanced and to efficiently access them. Third, we implement basic operations of the key-value store (i.e., Get, Put, and Delete) by manipulating the Windows registry using the Windows native APIs. We call the proposed key-value store WR-Store. Finally, we propose an efficient ETL (Extract-Transform-Load) method to migrate data stored in WR-Store into any other environments that support existing key-value stores. Because the performance of the Windows registry has not been studied much, we perform the empirical study to understand the characteristics of WR-Store, and then, tune the performance of WR-Store to find the best parameter setting. Through extensive experiments using synthetic and real data sets, we show that the performance of WR-Store is comparable to or even better than the state-of-the-art systems (i.e., RocksDB, BerkeleyDB, and LevelDB). Especially, we show the scalability of WR-Store. That is, WR-Store becomes much more efficient than the other key-value stores as the size of data set increases. In addition, we show that the performance of WR-Store is maintained even in the case of intensive registry workloads where 1000 processes accessing to the registry actively are concurrently running. [ABSTRACT FROM AUTHOR]

This paper provides a thorough analysis of the storage structure of hive files and then proposes a new method for processing hive files independently of the Windows registry API and for achieving direct access. The method has the advantages of high priority and of preserving the computing environment. In particular, it is suitable for occasions when the hive files of the target operating system cannot be copied or directly loaded. This paper also presents a set of algorithms for key operations associated with hive files such as access, deletion, creation, and expansion. These operations are designed to be independent of the Windows API. Third-party developers can develop other specialized applications on the basis of this set of algorithms. A complete hivedit program to carry out the operations described above has been implemented. This program can be executed before loading the operating system with the assistance of the ECM-XDP3 emulator, and the correctness of all the algorithms has been verified. [ABSTRACT FROM AUTHOR]

The Internet Corporation for Assigned Names and Numbers (ICANN) coordinates web address identifiers worldwide. Any individual, business, or organization that registers a domain name must provide names, addresses, emails, and phone numbers for the registration service called WHOIS. This data is managed by "registries", which are under contract with ICANN to operate top level domains like.com,.org, or new ones now in operation (.consult, for example). Anyone can use WHOIS to search and identify the registered name holder of a domain name. The WHOIS Accuracy Reporting System (ARS) is a formal examination of the accuracy of contact information provided to registries and registrars. This project examines syntax (does the email contain an "@" symbol; does the phone number have the correct number of digits; does the mailing address have the required fields?) and operability (does the email bounce; does the phone number connect; is the postal address deliverable?) accuracy. This paper will provide statistics on Internet domains worldwide as well as the accuracy of domain contact information based on four studies over two years. [ABSTRACT FROM AUTHOR]

The historic place of Meycauayan was derived from the term 'makawayan' where it is believed that the church made from nipa and bamboo was established here. Because of its historical geographic development, as it is being nailed as the first province before it became Bulacan, it could spring enriched experiences and cultural narratives shared through its language. The jewelry industry serves as the heart of livelihood, aside from leather, handicrafts, forge welding, etc. Even though Meycauayan was named as the jewelry capital, there is a decline over the years. Only a few were still pursuing it, since it is their livelihood, particularly at Brgy. Calvario. The aim of this study is to examine the initial existing language register from the glossary of words embedded in the jewelry-making process, as well as explore the situation of it in this modern age. Value Chain Process and Systemic Functional Linguistic by M.A.K. Halliday will be served as a framework, the words that come from the jewelry-making process were analyzed and its meaning aligned to the industry. This paper also discussed some concepts related to sociolinguistics that strengthened the domain of the jewelry industry in the city of Meycauayan and would contribute to the local and provincial industries. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Residency Review is the property of Journal of Medical Residency Review and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Gastroenterology has been an early leader in bridging the gap between artificial intelligence (AI) model development and clinical trial validation, and in recent years we have seen the publication of several randomized clinical trials examining the role of AI in gastroenterology. As AI applications for clinical medicine advance rapidly, there is a clear need for guidance surrounding AI‐specific study design, evaluation, comparison, analysis and reporting of results. Several initiatives are in the publication or pre‐publication phase including AI‐specific amendments to minimum reporting guidelines for clinical trials, society task force initiatives aimed at priority use cases and research priorities, and minimum reporting guidelines that guide the reporting of clinical prediction models. In this paper, we examine applications of AI in clinical trials and discuss elements of newly published AI‐specific extensions to the Consolidated Standards of Reporting Trials and Standard Protocol Items: Recommendations for Interventional Trials statements that guide clinical trial reporting and development. We then review AI applications at the pre‐trial level in both endoscopy and other subfields of gastroenterology and explore areas where further guidance is needed to supplement the current guidance available at the pre‐trial level. [ABSTRACT FROM AUTHOR]

Background: Juvenile drug treatment courts (JDTC) have struggled to define themselves since their inception in 1995. Early courts followed a format similar to adult drug courts, but these did not address the unique needs of juveniles, which led to the creation of 16 Strategies by a consensus panel of practitioners and researchers. But, like the first JDTCs, research with courts following these strategies failed to provide convincing evidence that this "model" was associated with significant reductions in recidivism or drug use. More recently, a new set of evidence-based guidelines were developed through meta-analyses commissioned by the Office of Juvenile Justice and Delinquency Prevention (OJJDP, 2016). Method: OJJDP provided funding for a rigorous multi-site evaluation of the guidelines. This study protocol paper for the Juvenile Drug Treatment Court (JDTC) Guidelines Cross-Site Evaluation presents research designs for the comparison of youth outcomes from 10 JDTCs compared with 10 Traditional Juvenile Courts (TJCs) in the same jurisdictions. Two sites opted into a randomized controlled trial (RCT) and eight sites chose to follow a regression discontinuity design (RDD). Youth data are captured at baseline, and at 6- and 12-month follow-ups using an interview comprised of several standardized assessments. The youths' official records also are abstracted for recidivism and substance use information. The degree to which the evidence-based guidelines are implemented at each site is assessed via an in-depth court self-assessment collected at baseline and again 2 years later and via structured site visits conducted once during implementation. Discussion: As a field-based trial, using both RCT and RDD designs, findings will provide important, policy-relevant information regarding the implementation of the OJJDP evidence-based guidelines, including the degree to which JDTCs adopted and/or modified these practices, their relative impact on recidivism and substance use, as well as the degree to which JDTCs differ from TJCs. Specific inferences may be drawn about whether following or not following specific guidelines differentially impact youth outcomes, yielding recommendations about the translation of this information from research-to-practice for potentiating the broader adoption of these guidelines by JDTCs nationwide. Clinical trials registration: This was not an NIH supported trial. The funder, OJJDP/NIJ, instead required publishing the design with even more information at https://www.ojp.gov/ncjrs/virtual-library/abstracts/juvenile-drug-treatment-court-jdtc-guidelines-cross-site-evaluation. [ABSTRACT FROM AUTHOR]

In clinical research, longitudinal trials are frequently conducted to evaluate the treatment effect by comparing trends in repeated measurements among different intervention groups. For such longitudinal trials, many researchers have developed the sample size estimation methods for comparison between two groups measurements. In contrast, relatively less attention has been paid to trials with K-group (K ≥ 3) comparison. Jung and Ahn (2004) and Lou et al. (2017) derived the sample size formulas for comparing trends among K groups using the generalized estimating equations approach for repeated continuous and count outcomes, respectively. However, to the best of our knowledge, there has been no development in sample size calculation for binary outcomes in multi-arms trials. In this paper, we present a sample size formula for comparing trends in K-group repeated binary measurements that accommodates various missing patterns and correlation structures. Simulation results show that the proposed method performs well under a wide range of design parameter settings. We illustrate the proposed method through an example. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper is to describe the utility of various recruitment modalities utilized in the Working to Increase Stability through Exercise (WISE) study. WISE is a pragmatic randomized trial that is testing the impact of a 3-year, multicomponent (strength, balance, aerobic) physical activity program led by trained volunteers or delivered via DVD on the rate of serious fall-related injuries among adults 65 and older with a past history of fragility fractures (e.g., vertebral, fall-related). The modified goal was to recruit 1130 participants over 2 years in three regions of Pennsylvania.Methods: The at-risk population was identified primarily using letters mailed to patients of three health systems and those over 65 in each region, as well as using provider alerts in the health record, proactive recruitment phone calls, radio advertisements, and presentations at community meetings.Results: Over 24 months of recruitment, 209,301 recruitment letters were mailed, resulting in 6818 telephone interviews. The two most productive recruitment methods were letters (72% of randomized participants) and the research registries at the University of Pittsburgh (11%). An average of 211 letters were required to be mailed for each participant enrolled. Of those interviewed, 2854 were ineligible, 2,825 declined to enroll and 1139 were enrolled and randomized. Most participants were female (84.4%), under age 75 (64.2%), and 50% took an osteoporosis medication. Not having a prior fragility fracture was the most common reason for not being eligible (87.5%). The most common reason provided for declining enrollment was not feeling healthy enough to participate (12.6%).Conclusions: The WISE study achieved its overall recruitment goal. Bulk mailing was the most productive method for recruiting community-dwelling older adults at risk of serious fall-related injury into this long-term physical activity intervention trial, and electronic registries are important sources and should be considered. [ABSTRACT FROM AUTHOR]

Background: Clinical trial registries allow assessment of deviations of published trials from their protocol, which may indicate a considerable risk of bias. However, since entries in many registries can be updated at any time, deviations may go unnoticed. We aimed to assess the frequency of changes to primary outcomes in different historical versions of registry entries, and how often they would go unnoticed if only deviations between published trial reports and the most recent registry entry are assessed. Methods and findings: We analyzed the complete history of changes of registry entries in all 1746 randomized controlled trials completed at German university medical centers between 2009 and 2017, with published results up to 2022, that were registered in ClinicalTrials.gov or the German WHO primary registry (German Clinical Trials Register; DRKS). Data were retrieved on 24 January 2022. We assessed deviations between registry entries and publications in a random subsample of 292 trials. We determined changes of primary outcomes (1) between different versions of registry entries at key trial milestones, (2) between the latest registry entry version and the results publication, and (3) changes that occurred after trial start with no change between latest registry entry version and publication (so that assessing the full history of changes is required for detection of changes). We categorized changes as major if primary outcomes were added, dropped, changed to secondary outcomes, or secondary outcomes were turned into primary outcomes. We also assessed (4) the proportion of publications transparently reporting changes and (5) characteristics associated with changes. Of all 1746 trials, 23% (n = 393) had a primary outcome change between trial start and latest registry entry version, with 8% (n = 142) being major changes, that is, primary outcomes were added, dropped, changed to secondary outcomes, or secondary outcomes were turned into primary outcomes. Primary outcomes in publications were different from the latest registry entry version in 41% of trials (120 of the 292 sampled trials; 95% confidence interval (CI) [35%, 47%]), with major changes in 18% (54 of 292; 95% CI [14%, 23%]). Overall, 55% of trials (161 of 292; 95% CI [49%, 61%]) had primary outcome changes at any timepoint over the course of a trial, with 23% of trials (67 of 292; 95% CI [18%, 28%]) having major changes. Changes only within registry records, with no apparent discrepancy between latest registry entry version and publication, were observed in 14% of trials (41 of 292; 95% CI [10%, 19%]), with 4% (13 of 292; 95% CI [2%, 7%]) being major changes. One percent of trials with a change reported this in their publication (2 of 161 trials; 95% CI [0%, 4%]). An exploratory logistic regression analysis indicated that trials were less likely to have a discrepant registry entry if they were registered more recently (odds ratio (OR) 0.74; 95% CI [0.69, 0.80]; p<0.001), were not registered on ClinicalTrials.gov (OR 0.41; 95% CI [0.23, 0.70]; p = 0.002), or were not industry-sponsored (OR 0.29; 95% CI [0.21, 0.41]; p<0.001). Key limitations include some degree of subjectivity in the categorization of outcome changes and inclusion of a single geographic region. Conclusions: In this study, we observed that changes to primary outcomes occur in 55% of trials, with 23% trials having major changes. They are rarely transparently reported in the results publication and often not visible in the latest registry entry version. More transparency is needed, supported by deeper analysis of registry entries to make these changes more easily recognizable. Protocol registration: Open Science Framework (https://osf.io/t3qva; amendment in https://osf.io/qtd2b). In this meta-research study, Martin Holst and colleagues investigate changes to prespecified primary outcomes in the historic registries of clinical trials. Author summary: Why was this study done?: Clinical trial registries are a key tool to increase the trustworthiness of clinical trials. They allow assessment of how closely a published trial follows its original plan. However, registry entries can be updated at any time, which creates a trail of historical versions. If the latest registry entry version matches with the published trial report, important preceding changes might thus be unapparent to assessors at first glance. Our objective was to investigate how often primary outcomes are changed in the trial registry over the course of a trial, and how often outcome changes are unapparent if one compares only the latest registry entry version to the publication. What did the researchers do and find?: We assessed all 1746 randomized controlled trials completed at German university medical centers between 2009 and 2017, that have a results publication. We determined the frequency of outcome changes between different versions of a registry entry, as well as the latest registry entry and the results publication. We defined adding or dropping primary outcomes, changing them to secondary outcomes, or turning secondary outcomes into primary outcomes, as major changes. We found that approximately 55% of trials had primary outcome changes at any timepoint over the course of a trial; 23% of trials had major changes. We observed changes that can be easily identified by comparing the published results to the latest registry entry in 41% of trials. In 14% of trials, however, the changes would require an in-depth look within the historical versions of that trial's registry entry. Only 1% of trials with changes (2 trials) reported this in the corresponding publications. What do these findings mean?: Our analysis suggests that changes to primary outcomes of a clinical trial are common, are often major, and have a potential to go unnoticed. More transparency is needed, supported by deeper analysis of registry entries to reveal these outcome changes. [ABSTRACT FROM AUTHOR]

The article focuses on the relaunch of EMA (European Medicines Agency) Clinical Data Publication Policy 0070, effective from September 2023. It provides key details such as scope, early preparation recommendations for sponsors, the new Q&A document, and the use of a structured Anonymisation Report template. It also highlights the continuation of COVID-19 and public health emergency clinical data publication.

This paper outlines a range of factors associated with extradition and transnational online intellectual property offending by examining the Australian case of Hew Griffiths. In documenting key legal issues from available domestic and international verdicts examining this case, we show how broad legislative drafting in Australia works alongside the decision to initiate conspiracy charges to favour extradition. We also examine how Australian legal requirements that remove the presumption of bail for transnational fugitives limit the prospect of mounting a fair defence against extradition and during a foreign trial, and the limited direct impact of determinations by the United Nations Human Rights Committee on these national processes. We critically discuss the implications of these rulings in the Griffiths case in light of the evolving role of extradition law in a digital age and their implications on theories of criminal jurisdiction founded on the principle of extraterritoriality. [ABSTRACT FROM AUTHOR]

Background: Vertigo and dizziness (VD) are among the most frequently seen symptoms in clinics and are important for medical students, especially for those in Chinese standardized residency training (SRT). The aim of our study was to examine the PAL method's feasibility in the clinical teaching of VD-related diseases for SRT students in China. Methods: This is a randomized, controlled, multicenter study. A total of 228 residents were invited to participate in this study, of which 198 completed the program. The students were randomized into two groups, and VD-related diseases were taught using lecture-based learning (control group) or peer-assisted learning (PAL). An examination paper and a rating scale were used to evaluate students' performance in the mastery of VD-related theoretical knowledge and clinical skills, meanwhile students' perceptions, satisfaction, and risk of burnout were also analyzed using a questionnaire. Independent-samples t-test and chi-square analysis were performed to evaluate statistical significance for continuous variables and categorical variables, respectively, using SPSS 18.0 software. Results: The PAL group performed better in mastering theoretical knowledge and clinical skills than the control group. And more students believed that PAL could help improve their personal qualities such as teamwork skills. However, more students reported that PAL increased the risk of burnout. Conclusions: PAL was a suitable and effective method in the clinical teaching of some specialized diseases, especially it was recommended for students who had gained initial knowledge and skills, such as Chinese SRT students. However, we should draw attention to the increased risk of burnout if PAL is intended to be widely used in clinical teaching. Trial registration: ISRCTN registry, ISRCTN53773239, 05/07/2021, retrospectively registered. [ABSTRACT FROM AUTHOR]

Prospective registration of study protocols in clinical trial registries is a useful way to minimize the risk of publication bias in meta‐analysis, and several clinical trial registries are available nowadays. However, they are mainly used as a tool for searching studies and information submitted to the registries has not been utilized as efficiently as it could. In addressing publication bias in meta‐analyses, sensitivity analysis with the Copas selection model is a more objective alternative to widely‐used graphical methods such as the funnel‐plot and the trim‐and‐fill method. Despite its ability to quantify the potential impact of publication bias, the Copas selection model relies on sensitivity analyses, in which some parameters are varied across a certain range. This may result in some difficulty in interpreting the results. In this paper, we propose an alternative inference procedure for the Copas selection model by utilizing information from clinical trial registries. Our method provides a simple and accurate way to estimate all unknown parameters of the Copas selection model. A simulation study revealed that our proposed method resulted in smaller biases and more accurate confidence intervals than existing methods. Furthermore, three published meta‐analyses were re‐analyzed to demonstrate how to implement the proposed method in practice. [ABSTRACT FROM AUTHOR]

Background: The obstacle of limb motor caused by stroke, especially the decline of motor function of upper limbs, can directly affect the activities of daily living of stroke patients with hemiplegia. Based on long-term clinical practice, the treatment effect of electrical stimulation methods for stroke limb dysfunction has been widely recognized and supported by authoritative guidelines and systematic reviews. However, which electrical stimulation method is the optimum in the treatment of stroke limb dysfunction is still a controversial issue. Objective: In this paper, we adopted Network Meta-Analysis (NMA) to rank the priorities of various electrical stimulation methods, so as to select the optimal electrical stimulation method and discuss its rationality in guiding clinical practice. Methods: We carried out a systematic review by searching a total of 6806 studies from 8 databases and 2 clinical trial registries, and finally screened out 34 studies for further investigation. Then, pairwise meta-analysis and Bayesian network meta-analysis were employed to evaluate the effectiveness and ranking of various interventions. The primary outcome measure was Fugl-Meyer Assessment Upper Extremity (FMA-UE), and the secondary outcome measures were Modified Barthel Index (MBI) and Modified Ashworth Scale (MAS). Finally, the risk of bias, publication bias and sensitivity of the Randomized Controlled Trials (RCTs) were evaluated. Results: On the basis of comprehensive rehabilitation treatment (RT), the Functional Electrical Stimulation (FES) was superior than other electrical stimulation methods in improving both FMA-UE and MBI. Meanwhile, the results indicated that the Transcutaneous Electrical Acupoint Stimulation (TEAS) was the only electrical stimulation method that showed treatment advantages in reducing MAS. Conclusion: The study showed that FES had the optimal overall rehabilitation effect on upper limb dysfunction of stroke patients based on the comprehensive RT, while the treatment effect of TEAS on upper limb spasticity after stroke was the most significant. [ABSTRACT FROM AUTHOR]

Introduction: Previous analysis of registered clinical trials has found a number of protocols result in changes in the registered primary outcome measures. This investigation determined if reported primary outcomes in chiropractic-related clinical trials registered in clinicaltrials.gov match their published results. Additionally, we assessed secondary outcomes, publication status and whether raw data were posted to the registry. Methods: Clinicaltrials.gov was searched for chiropractic-related trials and having a completed status. If the study was published, outcome measures were compared between the clinicaltrials.gov entry and the published paper to assess for consistency. Results: Within clinicaltrials.gov 171 chiropracticrelated protocols were identified with 102 of those published (59.6% publication rate). Ninety-two of the published papers (90.2%) had agreement between their primary outcome and the entry on clinicaltrials.gov and 82 (80.4%) agreed with the secondary outcomes. Conclusion: A modest rate of agreement between clinicaltrails.gov entries and the published papers was found. While chiropractic-related clinical trials are fewer compared to medical trials, chiropractic-related research has a substantially better rate of primary and secondary outcome concordance with registered protocols. [ABSTRACT FROM AUTHOR]