bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung ultrasound response to awake prone positioning predicts the need for intubation in patients with COVID-19 induced acute hypoxemic respiratory failure: an observational study
Authors: Ibarra-Estrada Miguel , Gamero-Rodríguez María J. , García-de-Acilu Marina , Roca Oriol , Sandoval-Plascencia Laura , Aguirre-Avalos Guadalupe , García-Salcido Roxana , Aguirre-Díaz Sara A. , Vines David L. , Mirza Sara , Kaur Ramandeep , Weiss Tyler , Guerin Claude , Li Jie 
Published: June 2022

Abstract
Background
Awake prone positioning (APP) reduces the intubation rate in COVID-19 patients treated by high-flow nasal cannula (HFNC). However, the lung aeration response to APP has not been addressed. We aimed to explore the lung aeration response to APP by lung ultrasound (LUS).

Methods
This two-center, prospective, observational study enrolled patients with COVID-19-induced acute hypoxemic respiratory failure treated by HFNC and APP. LUS score was recorded 5–10 min before, 1 h after APP, and 5–10 min after supine in the first APP session within the first three days. The primary outcome was LUS score changes in the first three days. Secondary outcomes included changes in SpO2/FiO2 ratio, respiratory rate and ROX index (SpO2/FiO2/respiratory rate) related to APP, and the rate of treatment success (patients who avoided intubation).

Results
Seventy-one patients were enrolled. LUS score decreased from 20 (interquartile range [IQR] 19–24) to 19 (18–21) (p < 0.001) after the first APP session, and to 19 (18–21) (p < 0.001) after three days. Compared to patients with treatment failure (n = 20, 28%), LUS score reduction after the first three days in patients with treatment success (n = 51) was greater (− 2.6 [95% confidence intervals − 3.1 to − 2.0] vs 0 [− 1.2 to 1.2], p = 0.001). A decrease in dorsal LUS score > 1 after the first APP session was associated with decreased risk for intubation (Relative risk 0.25 [0.09–0.69]). APP daily duration was correlated with LUS score reduction in patients with treatment success, especially in dorsal lung zones (r =  − 0.76; p < 0.001).

Conclusions
In patients with acute hypoxemic respiratory failure due to COVID-19 and treated by HFNC, APP reduced LUS score. The reduction in dorsal LUS scores after APP was associated with treatment success. The longer duration on APP was correlated with greater lung aeration.
Trial registration This study was prospectively registered on clinicaltrials.gov on April 22, 2021. Identification number NCT04855162.
Preemptive analgesia for hemorrhoidectomy: study protocol for a prospective, randomized, double-blind trial
Authors: Kazachenko Ekaterina , Garmanova Tatiana , Derinov Alexander , Markaryan Daniil , Lee Hanjoo , Magbulova Sabrina , Tsarkov Petr 
Published: June 2022

Abstract
Background
Hemorrhoidectomy is associated with intense postoperative pain that requires multimodal analgesia. It includes nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and local anesthetics to reach adequate pain control. There are data in literature preemptive analgesia could decrease postoperative pain after hemorrhoidectomy. The aim of this study is to assess the efficacy of preemptive analgesia with ketoprofen 100 mg 2 h before procedure per os with spinal anesthesia to decrease postoperative pain according to visual analog scale and to reduce the opioids and other analgesics consumption.

Methods
Patients of our clinic who meet the following inclusion criteria are included: hemorrhoids grade III–IV and the planned Milligan-Morgan hemorrhoidectomy. After signing the consent all participants are randomly divided into 2 groups: the first one gets a tablet with 100 mg ketoprofen, the second one gets a tablet containing starch per os 2 h before surgery (72 participants per arm). Patients of both arms receive spinal anesthesia and undergo open hemorrhoidectomy. Following the procedure the primary and secondary outcomes are evaluated: opioid administration intake, the pain at rest and during defecation, duration, and frequency of other analgesics intake, readmission rate, overall quality of life, time from the procedure to returning to work, and the complications rate.

Discussion
Multimodality pain management has been shown to improve pain control and decrease opioid intake in patients after hemorrhoidectomy in several studies. Gabapentin can be considered as an alternative approach to pain control as NSAIDs have limitative adverse effects. Systemic admission of ketorolac with local anesthetics also showed significant efficacy in patients undergoing anorectal surgery. We hope to prove the efficacy of multimodal analgesia including preemptive one for patients undergoing excisional hemorrhoidectomy that will help to hold postoperative pain levels no more than 3–4 points on VAS with minimal consumption of opioid analgesics.

Trial registration
ClinicalTrial.govNCT04361695. Registered on April 24, 2020, version 1.0.
Empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia: study protocol for a multicenter, open-label randomized controlled clinical trial
Authors: Rojo Pablo , Moraleda Cinta , Tagarro Alfredo , Domínguez-Rodríguez Sara , Castillo Lola Madrid , Tato Luis Manuel Prieto , López Aranzazu Sancho , Manukyan Lilit , Marcy Olivier , Leroy Valeriane , Nardone Alessandra , Burger David , Bassat Quique , Bates Matthew , Moh Raoul , Iroh Tam Pui-Ying , Mvalo Tisungane , Magallhaes Justina , Buck W. Chris , Sacarlal Jahit , Musiime Victor , Chabala Chishala , Mujuru Hilda Angela 
Published: June 2022

Abstract
Background
Pneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35–40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and undertreated.
The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children with HIV. CMV and TB may also co-infect the same child.
The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia.

Methods
This is a Phase II-III, open-label randomized factorial (2 × 2) clinical trial, conducted in six African countries. The trial has four arms. Infants from 28 to 365 days of age HIV-infected and hospitalized with severe pneumonia will be randomized (1:1:1:1) to (i) SoC, (ii) valganciclovir, (iii) TB-T, and (iv) TB-T plus valganciclovir. The primary endpoint of the study is all-cause mortality, focusing on the short-term (up to 15 days) and long-term (up to 1 year) mortality. Secondary endpoints include repeat hospitalization, duration of oxygen therapy during initial admission, severe and notable adverse events, adverse reactions, CMV and TB prevalence at enrolment, TB incidence, CMV viral load reduction, and evaluation of diagnostic tests such as GeneXpert Ultra on fecal and nasopharyngeal aspirate samples and urine TB-LAM.

Discussion
Given the challenges in diagnosing CMV and TB in children and results from previous autopsy studies that show high rates of poly-infection in HIV-infected infants with respiratory disease, this study aims to evaluate a new approach including empirical treatment of CMV and TB for this patient population. The potential downsides of empirical treatment of these conditions include toxicity and medication interactions, which will be evaluated with pharmacokinetics sub-studies.

Trial registration
ClinicalTrials.gov, NCT03915366, Universal Trial Number U111-1231-4736, Pan African Clinical Trial Registry PACTR201994797961340.
Getting it wrong most of the time? Comparing trialists’ choice of primary outcome with what patients and health professionals want
Authors: Treweek Shaun , Miyakoda Viviane , Burke Dylan , Shiely Frances 
Published: June 2022

Abstract
Background
Randomised trials support improved decision-making through the data they collect. One important piece of data is the primary outcome — so called because it is what the investigators decide is the most important. Secondary outcomes provide additional information to support decision-making. We were interested in knowing how important patients and healthcare professionals consider the outcomes (especially the primary outcome) measured in a selection of published trials.

Methods
The work had three stages: (1) We identified a body of late-stage trials in two clinical areas, breast cancer management and nephrology. (2) We identified the primary and secondary outcomes for these trials. (3) We randomly ordered these outcomes and presented them to patients and healthcare professionals (with experience of the clinical area), and we asked them to rank the importance of the outcomes. They were not told which outcomes trial authors considered primary and secondary.

Results
In our sample of 44 trials with 46 primary outcomes, 29 patients, one patient representative and 12 healthcare professionals together ranked the primary outcome as the most important outcome 13/46 times or 28%. Breast cancer patients and healthcare professionals considered the primary outcome to be the most important outcome for 8/21 primary outcomes chosen by trialists. For nephrology, the equivalent figure was 5/25. The primary outcome appeared in a respondent’s top 5 ranked outcomes 151/178 (85%) times for breast cancer and 225/259 (87%) times for nephrology even if the primary was not considered the most important outcome.

Conclusions
The primary outcome in a trial is the most important piece of data collected. It is used to determine how many participants are required, and it is the main piece of information used to judge whether the intervention is effective or not. In our study, patients and healthcare professionals agreed with the choice of the primary outcome made by trial teams doing late-stage trials in breast cancer management and nephrology 28% of the time.
A multicomponent family support intervention in intensive care units: study protocol for a multicenter cluster-randomized trial (FICUS Trial)
Authors: Naef Rahel , Filipovic Miodrag , Jeitziner Marie-Madlen , von Felten Stefanie , Safford Judith , Riguzzi Marco , Rufer Michael 
Published: June 2022

Abstract
Background
Family members of critically ill patients face considerable uncertainty and distress during their close others’ intensive care unit (ICU) stay. About 20–60% of family members experience adverse mental health outcomes post-ICU, such as symptoms of anxiety, depression, and posttraumatic stress. Guidelines recommend structured family inclusion, communication, and support, but the existing evidence base around protocolized family support interventions is modest and requires substantiation.

Methods
To test the clinical effectiveness and explore the implementation of a multicomponent, nurse-led family support intervention in ICUs, we will undertake a parallel, cluster-randomized, controlled, multicenter superiority hybrid-type 1 trial. It will include eight clusters (ICUs) per study arm, with a projected total sample size of 896 family members of adult, critically ill patients treated in the German-speaking part of Switzerland. The trial targets family members of critically ill patients with an expected ICU stay of 48 h or longer. Families in the intervention arm will receive a family support intervention in addition to usual care. The intervention consists of specialist nurse support that is mapped to the patient pathway with follow-up care and includes psycho-educational and relationship-focused family interventions, and structured, interprofessional communication, and shared decision-making with families. Families in the control arm will receive usual care. The primary study endpoint is quality of family care, operationalized as family members’ satisfaction with ICU care at discharge. Secondary endpoints include quality of communication and nurse support, family management of critical illness (functioning, resilience), and family members’ mental health (well-being, psychological distress) measured at admission, discharge, and after 3, 6, and 12 months. Data of all participants, regardless of protocol adherence, will be analyzed using linear mixed-effects models, with the individual participant as the unit of inference.

Discussion
This trial will examine the effectiveness of the family support intervention and generate knowledge of its implementability. Both types of evidence are necessary to determine whether the intervention works as intended in clinical practice and could be scaled up to other ICUs. The study findings will make a significant contribution to the current body of knowledge on effective ICU care that promotes family participation and well-being.

Trial registration
ClinicalTrials.gov NCT05280691. Prospectively registered on 20 February 2022.
Blinding of study statisticians in clinical trials: a qualitative study in UK clinical trials units
Authors: Iflaifel Mais , Partlett Christopher , Bell Jennifer , Cook Andrew , Gamble Carrol , Julious Steven , Juszczak Edmund , Linsell Louise , Montgomery Alan , Sprange Kirsty 
Published: June 2022

Abstract
Background
Blinding is an established approach in clinical trials which aims to minimise the risk of performance and detection bias. There is little empirical evidence to guide UK clinical trials units (CTUs) about the practice of blinding statisticians. Guidelines recommend that statisticians remain blinded to allocation prior to the final analysis. As these guidelines are not based on empirical evidence, this study undertook a qualitative investigation relating to when and how statisticians should be blinded in clinical trials.

Methods
Data were collected through online focus groups with various stakeholders who work in the delivery and oversight of clinical trials. Recordings of the focus groups were transcribed verbatim and thematic analysis was used to analyse the transcripts.

Results
Thirty-seven participants from 19 CTUs participated in one of six focus groups. Four main themes were identified, namely statistical models of work, factors affecting the decision to blind statisticians, benefits of blinding/not blinding statisticians and practicalities. Factors influencing the decision to blind the statistician included available resources, study design and types of intervention and outcomes and analysis.
Although blinding of the statistician is perceived as a desirable mitigation against bias, there was uncertainty about the extent to which an unblinded statistician might impart bias. Instead, in most cases, the insight that the statistician offers was deemed more important to delivery of a trial than the risk of bias they may introduce if unblinded.
Blinding of statisticians was only considered achievable with the appropriate resource and staffing, which were not always available. In many cases, a standard approach to blinding was therefore considered unrealistic and impractical; hence the need for a proportionate risk assessment approach identifying possible mitigations.

Conclusions
There was wide variation in practice between UK CTUs regarding the blinding of trial statisticians. A risk assessment approach would enable CTUs to identify risks associated with unblinded statisticians conducting the final analysis and alternative mitigation strategies. The findings of this study will be used to design guidance and a tool to support this risk assessment process.
Tumor lysis syndrome following ifosfamide monotherapy in metastatic osteosarcoma: a case report and review of the literature
Authors: Luminais Steven N. , Chen Xiao T. , Roman Darwin , Ma Brian , Christ Alexander B. , Hu James S. 
Published: June 2022

Abstract
Background
Tumor lysis syndrome is an oncologic emergency that involves multiple metabolic abnormalities and clinical symptoms such as acute renal failure, cardiac arrhythmias, seizures, and multiorgan failure, and may be fatal if not promptly recognized. Tumor lysis syndrome occurs most often in patients with hematologic malignancies, and relatively few cases have been described in patients with sarcoma.

Case presentation
A 64-year-old male of Asian heritage presented to his primary care physician with a right lower-extremity mass and was ultimately diagnosed with widely metastatic osteosarcoma. He was treated with one cycle of cisplatin and doxorubicin that was complicated by hypervolemia and hypoxic respiratory failure. Given concerns for volume overload, therapy was changed to single-agent, dose-reduced ifosfamide. After receiving one dose of ifosfamide 1 g/m2 (1.8 g total) intravenously over 1 hour, the patient developed renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and lactic acidosis. The patient ultimately died from severe electrolyte abnormalities associated with tumor lysis syndrome.

Conclusion
This is the first instance of tumor lysis syndrome described in a patient with osteosarcoma undergoing ifosfamide monotherapy. Clinicians must be vigilant in identifying tumor lysis syndrome regardless of the malignancy type or chemotherapy regimen in order to prevent potentially fatal complications.
Consideration of sex and gender differences in addiction medication response
Authors: McKee Sherry A. , McRae-Clark Aimee L. 
Published: June 2022

AbstractSubstance use continues to contribute to significant morbidity and mortality in the United States, for both women and men, more so than any other preventable health condition. To reduce the public health burden attributable to substances, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have identified that medication development for substance use disorder is a high priority research area. Furthermore, both Institutes have stated that research on sex and gender differences in substance use medication development is a critical area. The purpose of the current narrative review is to highlight how sex and gender have been considered (or not) in medication trials for substance use disorders to clarify and summarize what is known regarding sex and gender differences in efficacy and to provide direction to the field to advance medication development that is consistent with current NIH ‘sex as a biological variable’ (SABV) policy. To that end, we reviewed major classes of abused substances (nicotine, alcohol, cocaine, cannabis, opioids) demonstrating that, sex and gender have not been well-considered in addiction medication development research. However, when adequate data on sex and gender differences have been evaluated (i.e., in tobacco cessation), clinically significant differences in response have been identified between women and men. Across the other drugs of abuse reviewed, data also suggest sex and gender may be predictive of outcome for some agents, although the relatively low representation of women in clinical research samples limits making definitive conclusions. We recommend the incorporation of sex and gender into clinical care guidelines and improved access to publicly available sex-stratified data from medication development investigations.
Anatomy and the type concept in biology show that ontologies must be adapted to the diagnostic needs of research
Authors: Vogt Lars , Mikó István , Bartolomaeus Thomas 
Published: June 2022

AbstractBackgroundIn times of exponential data growth in the life sciences, machine-supported approaches are becoming increasingly important and with them the need for FAIR (Findable, Accessible, Interoperable, Reusable) and eScience-compliant data and metadata standards. Ontologies, with their queryable knowledge resources, play an essential role in providing these standards. Unfortunately, biomedical ontologies only provide ontological definitions that answerWhat is it?questions, but no method-dependent empirical recognition criteria that answerHow does it look?questions. Consequently, biomedical ontologies contain knowledge of the underlying ontological nature of structural kinds, but often lack sufficient diagnostic knowledge to unambiguously determine the reference of a term.ResultsWe argue that this is because ontology terms are usually textually defined and conceived as essentialistic classes, while recognition criteria often require perception-based definitions because perception-based contents more efficiently document and communicate spatial and temporal information—a picture is worth a thousand words. Therefore, diagnostic knowledge often must be conceived as cluster classes or fuzzy sets. Using several examples from anatomy, we point out the importance of diagnostic knowledge in anatomical research and discuss the role of cluster classes and fuzzy sets as concepts of grouping needed in anatomy ontologies in addition to essentialistic classes. In this context, we evaluate the role of the biological type concept and discuss its function as a general container concept for groupings not covered by the essentialistic class concept.ConclusionsWe conclude that many recognition criteria can be conceptualized as text-based cluster classes that use terms that are in turn based on perception-based fuzzy set concepts. Finally, we point out that only if biomedical ontologies model also relevant diagnostic knowledge in addition to ontological knowledge, they will fully realize their potential and contribute even more substantially to the establishment of FAIR and eScience-compliant data and metadata standards in the life sciences.
Fuelwood use and carbon emission reduction of improved biomass cookstoves: evidence from kitchen performance tests in Tigray, Ethiopia
Authors: Manaye Ashenafi , Amaha Selemawit , Gufi Yirga , Tesfamariam Berihu , Worku Adefires , Abrha Haftu 
Published: June 2022

Abstract
Background
In Ethiopia, biomass contributes to about 92% of the household fuel consumption. As a result, deforestation rate has alarmingly increased associated with greenhouse gas (GHG) emissions and land degradation. The concerned government agencies have been widely making concerted efforts to reverse the situation by of promotion of improved cookstoves (ICS). However, the performance of these technologies in terms of saving fuelwood and their contribution to CO2 emission reduction in a real kitchen was not studied systematically. Thus, this research was initiated to address the knowledge gap.

Methods
The study was conducted in Tigray region in northern Ethiopia. The study households were selected following cross-sectional and longitudinal study designs. A kitchen performance test (KPT) was carried out based on 3 days of repeated fuelwood use measurements to compare the wood-saving performance of ICS in comparison with the traditional cookstove (TCS). The emission reduction potential of both ICS and TCS was calculated based on the Clean Development Mechanism and United Nation’s Framework of Convention on Climate Change and presented in CO2 equivalent (CO2e).

Results
The result suggests significant differences in total and per capita wood consumption (p < 0.05) between improved and TCS. The use of Mirt and Tikikil compared to the traditional stove has reduced the household wood consumption by 35% and 18%, respectively. Furthermore, ICS stoves also reduced CO2e emission per stove per year by 0.65 and 0.27 tons, respectively.

Conclusion
The study deals with the significant contribution that the shift from TCS to the ICS brought in terms of reducing the amount of fuelwood used at household level and the carbon emission per capita. It addresses the crucial roles of such technologies in reducing forest degradation and the associated ecosystem loss. Therefore, policy aimed at reducing greenhouse gas emissions in developing countries at household level should at least start via promotions of ICS.