bluuebunny/crossref_metadata_2025 huggingface dataset:
Open science at the science–policy interface: bringing in the evidence?
Authors: Reichmann Stefan , Wieser Bernhard
Published: June 2022

Part of the current enthusiasm about open science stems from its promises to reform scientific practice in service of the common good, to ensure that scientific outputs will be found and reused more easily, and to enhance scientific impact on policy and society. With this article, we question this optimism by analysing the potential for open science practices to enhance research uptake at the science–policy interface. Science advice is critical to help policy-makers make informed decisions. Likewise, some interpretations of open science hold that making research processes and outputs more transparent and accessible will also enhance the uptake of results by policy and society at large. However, we argue that this hope is based on an unjustifiably simplistic understanding of the science–policy interface that leaves key terms (“impact”, “uptake”) undefined. We show that this understanding—based upon linear models of research uptake—likewise grounds the influential “evidence–policy gap” diagnosis which holds that to improve research uptake, communication and interaction between researchers and policy-makers need to be improved. The overall normative stance of both discussions has sidelined empirical description of the science–policy interface, ignoring questions about the underlying differences between the policy domain and academia. Importantly, both open science and literature on closing the evidence–policy gap recommend improving communication (in terms of either the content or the means) as a viable strategy. To correct some of these views, we combine insights from policy theory with a narrative review of the literature on the evidence–policy gap in the health domain and find that removing barriers to access by itself will not be enough to foster research uptake.
Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury
Authors: Li Qiao-Yun , Chen Shao-Xia , Liu Jin-Yu , Yao Pei-Wen , Duan Yi-Wen , Li Yong-Yong , Zang Ying
Published: June 2022

Background

Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus result in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first-order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain.

Methods

The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC glutamatergic neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling.

Results

Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC glutamatergic neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6.

Conclusions

The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.
Promoting respectful maternity care using a behavioral design approach in Zambia: results from a mixed-methods evaluation
Authors: Smith Jana , Schachter Allison , Banay Rachel , Zimmerman Emily , Vargas Ariadna , Sellman Abigail , Kamanga Ameck
Published: June 2022

Background

Respectful maternity care (RMC) has been elevated in the global discourse, however, instances of disrespect and abuse remain prevalent. While several studies have highlighted promising approaches to promote RMC, this body of literature is still limited and few approaches have been scaled outside the initial study sites. Building on formative research conducted through a behavioral science lens, we sought to develop and test evidence-based, low-cost solutions to promote RMC which would be well-positioned for scale-up. Our study highlights the effectiveness of the solution package on provider provision of respectful care and client satisfaction, as well as intermediary outcomes and behavioral mechanisms.

Methods

A quasi-experimental evaluation, informed by the behavioral design approach, was completed to test the effectiveness of a 5-component solution package in Chipata, Zambia. Quantitative surveys were collected from health facility providers and postpartum clients at baseline and endline in intervention and comparison facilities. Additional qualitative interviews were conducted with health facility providers and postpartum clients at endline. We also conducted interviews with health facility in-charges and observed labor and delivery practices at intervention facilities over the course of implementation.

Results

Evidence suggested that at endline, clients at implementation facilities were less likely to experience disrespect and abuse compared to clients at comparison facilities (ß = − 0.15 p = 0.01). Clients at intervention facilities were more likely to request pain management compared to clients at comparison facilities (ß = 0.33, p = 0.003). The solutions were simple for providers to implement and were easily integrated into existing services by providers during labor and delivery. Providers at intervention facilities also described the pain management toolkit as helpful in expanding the types of pain management techniques used during labor.

Conclusions

The results of this small-scale study act as a proof of concept, demonstrating that the behavioral design approach can lead to solutions that show potential for impact. In other settings where providers face similar barriers to providing RMC, an adaptation of this solution package might lead to similarly positive results. Given the global scale of disrespectful care, these low-cost solutions hold promise for improving the quality of care women receive during labor and delivery.
The impact of training on self-reported performance in reproductive, maternal, and newborn health service delivery among healthcare workers in Tanzania: a baseline- and endline-survey
Authors: Mwansisya Tumbwene , Mbekenga Columba , Isangula Kahabi , Mwasha Loveluck , Mbelwa Stewart , Lyimo Mary , Kisaka Lucy , Mathias Victor , Pallangyo Eunice , Edwards Grace , Mantel Michaela , Konteh Sisawo , Rutachunzibwa Thomas , Mrema Secilia , Kidanto Hussein , Temmerman Marleen
Published: June 2022

Background

Delivery of quality reproductive health services has been documented to depend on the availability of healthcare workers who are adequately supported with appropriate training. However, unmet training needs among healthcare workers in reproductive, maternal, and newborn health (RMNH) in low-income countries remain disproportionately high. This study investigated the effectiveness of training with onsite clinical mentorship towards self-reported performance in RMNH among healthcare workers in Mwanza Region, Tanzania.

Methods

The study used a quasi-experimental design with pre-and post-intervention evaluation strategy. The baseline was compared with two endline groups: those with intervention (training and onsite mentorship) and those without. The differences among the three groups in the sociodemographic characteristics were analyzed by using chi-square test for categorical variables, independent-sample t-test for continuous variables and Mann–Whitney U test for ordinal or skewed continuous data. The independent sample t-test was used to determine the effect of the intervention by comparing the computed self-reported performance on RMNH services between the intervention and control groups. The paired-samples t-test was used to measure the differences between before and after intervention groups. Significance was set at a 95% confidence interval with p ≤ 0.05.

Results

The study included a sample of 216 participants with before and after intervention groups comprising of 95 (44.0%) and 121 (56.0%) in the control group. The comparison between before and after intervention groups revealed a statistically significant difference (p ≤ 0.05) in all the dimensions of the self-reported performance scores. However, the comparison between intervention groups and controls indicated a statistical significant difference on intra-operative care (t = 3.10, df = 216, p = 0.002), leadership skills (t = 1.85, df = 216, p = 0.050),
Comprehensive emergency obstetric and newborn care (CEMONC) (t = 34.35, df = 216, p ≤ 0.001), and overall self-reported performance in RMNH (t = 3.15, df = 216, p = 0.002).

Conclusions

This study revealed that the training and onsite clinical mentorship to have significant positive changes in self-reported performance in a wide range of RMNH services especially on intra-operative care, leadership skills and CEMONC. However, further studies with rigorous designs are warranted to evaluate the long-term effect of such training programs on RMNH outcomes.
Rethinking the tools in the toolbox
Authors: George Hornby T.
Published: June 2022

The commentary by Dr. Labruyere on the article by Kuo et al. (J Neuroeng Rehabil. 2021; 18:174) posits that randomized trials evaluating the comparative efficacy of robotic devices for patients with neurological injury may not be needed. The primary argument is that researchers and clinicians do not know how to optimize training parameters to maximize the benefits of this therapy, and studies vary in how they deliver robotic-assisted training. While I concur with the suggestion that additional trials using robotic devices as therapeutic tools are not warranted, an alternative hypothesis is that future studies will yield similar equivocal results regardless of the training parameters used. Attempts are made to detail arguments supporting this premise, including the notion that the original rationale for providing robotic-assisted walking training, particularly with exoskeletal devices, was flawed and that the design of some of the more commonly used devices places inherent limitations on the ability to maximize neuromuscular demands during training. While these devices arrived nearly 20 years ago amid substantial enthusiasm, we have since learned valuable lessons from robotic-assisted and other rehabilitation studies on some of the critical parameters that influence neuromuscular and cardiovascular activity during locomotor training, and different strategies are now needed to optimize rehabilitation outcomes.
Leveraging WHO’s Global Benchmarking Tool to strengthen capacity in clinical trials oversight for public health emergencies: the GHPP VaccTrain model
Authors: Owusu Sekyere Solomon , Škrnjug-Yudov Ivana , Ateba Ngoa Ulysse , Juárez Hernández Marcela , Abiri Onome T. , Komeh James P. , Janneh Kaira Markieu , Marenah Essa , Kercula Juwe Darnuwele , Smith Keturah , Rassokhina Olga , Meyer Heidi , Conrad Christoph
Published: June 2022

Background

A stable, well-functioning and integrated national medicines regulatory system is a core component of health systems resilient against infectious disease outbreaks. In many low- and middle-income countries, however, sizable gaps exist in the emergency preparedness framework of national regulatory authorities (NRAs). RegTrain-VaccTrain is a project of Germany Ministry of Health’s Global Health Protection Programme that contributes to global efforts aimed at strengthening such regulatory systems by providing technical support and advice to partner NRAs. In this study, we probed the outputs of our capacity-strengthening activities for clinical trials oversight (CTO) to take stock of progress made and examine remaining priorities in order to provide specialized technical assistance in addressing them to improve operational readiness for emergencies.

Method

Data validated from NRA self-benchmarking results in 2017 and worksheet records of November 2021 were utilized to assess the emergency preparedness capacity for CTO in three VaccTrain partner NRAs (Liberia, Sierra Leone, The Gambia) before and after interventional capacity-strengthening partnership, using specific public health emergency-related (sub-)indicators of the WHO Global Benchmarking Tool.

Results

A generally weak and vulnerable structural framework for CTO characterized the emergency preparedness capacity in all three partner NRAs at baseline, thus putting their operational readiness for public health emergencies at risk. VaccTrain’s collaborative work was successful at supporting individual NRAs to develop the full spectrum of operational structures (including (draft) regulations, guidelines, and standard operating procedures) required to improve regulatory preparedness. A gap in the formal approval and implementation of developed legal documents in two of three NRAs still remains. Notwithstanding, a robust emergency framework now exists and the NRAs stand better prepared to respond to (future) locally-concerning health emergencies, during which time clinical trials activity was observed to heighten.

Conclusions

These results exemplify a north-south capacity-strengthening partnership model that effectively contributes in developing structures to enhance regulatory oversight and support expeditious product development in response to crises. They further underscore the equally critical role local/national processes play in facilitating the full implementation of developed structures.
Management of people with low back pain: a survey of opinions and beliefs of Dutch and Belgian chiropractors
Authors: De la Ruelle Lobke P. , de Zoete Annemarie , de Boer Michiel R. , van Tulder Maurits W. , Ostelo Raymond , Rubinstein Sidney M.
Published: June 2022

Background

Chiropractors commonly provide care to people with low-back pain (LBP). The aim of this survey was to determine the opinions and beliefs of chiropractors regarding the support and management of LBP. We also investigated whether their management is in accordance with the three most commonly recommended approaches to LBP based upon international guidelines (i.e. advice regarding return-to-work, limit bedrest, and stay active).

Methods

A web-based survey was sent out in 2013 to collect data from registered Dutch and Belgian chiropractors. In addition to providing a description of their sociodemographic and practice characteristics, chiropractors were asked to complete six patient vignettes representing people with LBP who typically present to a chiropractor. The respondents indicated which intervention(s) they would recommend or undertake. Based upon these vignettes, we were able to determine whether their management approach adhered to clinical guidelines. Generalized mixed models were used to explore guidelines adherence and their relationship to chiropractors’ characteristics.

Results

In total, 60% (n = 203/340) of the chiropractors who were invited, chose to participate. Chiropractors reported applying a chiropractic adjustment in 90% of all vignettes, while the advice to exercise varied from one-third in the chronic cases to approximately half of those with acute LBP. More than 75% of the chiropractors would initially treat LBP 1–2 times a week. More than 90% of the chiropractors advised against bedrest. Overall, self-reported adherence to clinical guidelines for all six vignettes was [64.5% (CI 58.7–70.0)]. Adherence in the chronic vignettes [73.4% (CI 66.7–79.2)] was better than in the acute vignettes [55.9% (CI 50.5–61.1)]. Importantly, regarding recommended approaches to LBP, chiropractors more consistently followed guidelines regarding advice to limit bedrest [98.5% (CI 97.3–99.1)] than advice to stay active [77.5% (CI 72.3–81.9)] or return-to-work [59.4% (CI 55.2–63.4)]. Finally, Dutch chiropractors were more likely to adhere to the guidelines than Belgian chiropractors.

Conclusions

Chiropractic adjustments were the most common self-reported treatment modalities supplemented by exercise in the management of LBP patients. Two-thirds of the chiropractors reported adhering to the guidelines regarding management and advice for LBP patients. Practitioners should improve guideline adherence, particularly for acute LBP cases, and when advising on return-to-work.
Glycogen storage diseases with liver involvement: a literature review of GSD type 0, IV, VI, IX and XI
Authors: Massese Miriam , Tagliaferri Francesco , Dionisi-Vici Carlo , Maiorana Arianna
Published: June 2022

Background

Glycogen storage diseases (GSDs) with liver involvement are classified into types 0, I, III, IV, VI, IX and XI, depending on the affected enzyme. Hypoglycemia and hepatomegaly are hallmarks of disease, but muscular and renal tubular involvement, dyslipidemia and osteopenia can develop. Considering the paucity of literature available, herein we provide a narrative review of these latter forms of GSDs.

Main body

Diagnosis is based on clinical manifestations and laboratory test results, but molecular analysis is often necessary to distinguish the various forms, whose presentation can be similar. Compared to GSD type I and III, which are characterized by a more severe impact on metabolic and glycemic homeostasis, GSD type 0, VI, IX and XI are usually known to be responsive to the nutritional treatment for achieving a balanced metabolic homeostasis in the pediatric age. However, some patients can exhibit a more severe phenotype and an important progression of the liver and muscular disease. The effects of dietary adjustments in GSD type IV are encouraging, but data are limited.

Conclusions

Early diagnosis allows a good metabolic control, with improvement of quality of life and prognosis, therefore we underline the importance of building a proper knowledge among physicians about these rare conditions. Regular monitoring is necessary to restrain disease progression and complications.
What role can decentralized trial designs play to improve rare disease studies?
Authors: Moore J. , Goodson N. , Wicks P. , Reites J.
Published: June 2022

People affected by rare diseases want to be involved in research and the search for new treatments. Randomized controlled trials remain the best way of finding new interventions, but many elements of traditional study design are not best suited for rare diseases. Barriers to patients and families include the use of specialist hospital sites for recruitment, requiring frequent site-based study visits for data collection, and a high burden of tests and outcome measures in research. While decentralized clinical trial (DCT) designs have been developed in some rare disease trials, changes necessitated by the COVID-19 pandemic present an opportunity for them to become a standard approach. DCT approaches have been shown to be more resilient to changes in enrolment and attrition during COVID-19 than traditional designs and offer benefits in terms of patient burden, convenience, inclusion, and data quality. Digital tools such as wearable devices and electronic clinical outcome assessments may also provide more convenient and environmentally valid measures of how a condition affects the life of an individual in their regular environment (e.g. mobility around the home versus a hospital corridor). Digital solutions have greater ability to support language localization, accessibility, and may lead to increase access to global rare disease trials. In parallel, challenges exist, such as the technical support, the digital divide, ensuring high quality data, and delivering safe trials.
Twenty years of the Fabry Outcome Survey (FOS): insights, achievements, and lessons learned from a global patient registry
Authors: Beck Michael , Ramaswami Uma , Hernberg-Ståhl Elizabeth , Hughes Derralynn A. , Kampmann Christoph , Mehta Atul B. , Nicholls Kathleen , Niu Dau-Ming , Pintos-Morell Guillem , Reisin Ricardo , West Michael L. , Schenk Jörn , Anagnostopoulou Christina , Botha Jaco , Giugliani Roberto
Published: June 2022

Background

Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the effects of treatment on large patient populations with rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of affected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS studies have made in understanding FD.

Results

FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confirmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been published in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term effectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its effects on morbidity and mortality, as well as the benefits of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agalsidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specific populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies.

Conclusion

FOS over the last 20 years has substantially increased the scientific knowledge around improved patient management of FD and continues to expand our understanding of this rare disease.
Increase in admission rates and symptom severity of childhood and adolescent anorexia nervosa in Europe during the COVID-19 pandemic: data from specialized eating disorder units in different European countries
Authors: Gilsbach Susanne , Plana Maria Teresa , Castro-Fornieles Josefina , Gatta Michela , Karlsson Gunilla Paulson , Flamarique Itziar , Raynaud Jean-Philippe , Riva Anna , Solberg Anne-Line , van Elburg Annemarie A. , Wentz Elisabet , Nacinovich Renata , Herpertz-Dahlmann Beate
Published: June 2022

Background

The COVID-19 pandemic, associated with confinement and social isolation, seems to have impacted the course of many mental disorders in children and adolescents. An increase in hospital admission rates for juvenile anorexia nervosa (AN) has been documented in many regions of the world. However, data from Europe are scarce.

Methods

We asked clinicians in specialized eating disorder units in hospitals of maximum care in France, Germany, Italy, Spain, Sweden, and the Netherlands to report on (i) overall (inpatient and outpatient) and (ii) inpatient admission rates for adolescents with AN during 2019 and 2020. Additionally, a modified version of the COVID Isolation Eating Scale (CIES) was used to assess the child and adolescent psychiatrists’ estimations of a possible increase in symptom severity in children and adolescents with AN during the COVID-19 pandemic and to (iii) inquire about the contributing factors perceived by the caring professionals.

Results

Four out of six representatives of European hospitals described a higher rate of overall admissions during the pandemic. Three hospitals out of six reported an increase in inpatient admissions, and two centres had constant high numbers of admissions of both outpatients and inpatients. The clinicians perceived a higher symptom severity in 2020 than in 2019, especially involving more frequent use of social media, longer duration of exercising, and more restrictive eating. They supposed an increase in social media consumption, a perceived “loss of control”, and a lack of in-person assessments and weight controls as the main contributing factors for the deterioration in AN numbers and symptomatology.

Conclusions

The COVID-19 pandemic seems to have had a deep impact on symptom severity in AN, which is mirrored by a large increase in admission rates across Europe. An increase in exercise, social media consumption, a perceived “loss of control”, and a lack of face-to-face health care seem to have contributed to this development. Further investigation is required to identify which factors may lead to the increase in incidence and deterioration of childhood and adolescent AN. Possible preventive means for the future could include educating paediatricians and health care workers about AN, regular weight assessment, and home-based treatments.
A Delphi study of rescue and clinical subject matter experts on the extrication of patients following a motor vehicle collision
Authors: Nutbeam Tim , Fenwick Rob , Smith Jason E. , Dayson Mike , Carlin Brian , Wilson Mark , Wallis Lee , Stassen Willem
Published: June 2022

Background

Approximately 1.3 million people die each year globally as a direct result of motor vehicle collisions (MVCs). Following an MVC some patients will remain trapped in their vehicle; these patients have worse outcomes and may require extrication. Following new evidence, updated multidisciplinary guidance for extrication is needed.

Methods

This Delphi study has been developed, conducted and reported to CREDES standards. A literature review identified areas of expertise and appropriate individuals were recruited to a Steering Group. The Steering Group formulated initial statements for consideration. Stakeholder organisations were invited to identify subject matter experts (SMEs) from a rescue and clinical background (total 60). SMEs participated over three rounds via an online platform. Consensus for agreement / disagreement was set at 70%. At each stage SMEs could offer feedback on, or modification to the statements considered which was reviewed and incorporated into new statements or new supporting information for the following rounds. Stakeholders agreed a set of principles based on the consensus statements on which future guidance should be based.

Results

Sixty SMEs completed Round 1, 53 Round 2 (88%) and 49 Round 3 (82%). Consensus was reached on 91 statements (89 agree, 2 disagree) covering a broad range of domains related to: extrication terminology, extrication goals and approach, self-extrication, disentanglement, clinical care, immobilisation, patient-focused extrication, emergency services call and triage, and audit and research standards. Thirty-three statements did not reach consensus.

Conclusion

This study has demonstrated consensus across a large panel of multidisciplinary SMEs on many key areas of extrication and related practice that will provide a key foundation in the development of evidence-based guidance for this subject area.
Impact of the first COVID-19 lockdown on the relationship with parents and peers in a cohort of adolescents with somatic symptom disorder
Authors: Trombetta Andrea , De Nardi Laura , Cozzi Giorgio , Ronfani Luca , Bigolin Lara , Barbi Egidio , Bramuzzo Matteo , Abbracciavento Giuseppe
Published: June 2022

To investigate the coping strategies of a group of adolescents with somatic symptom disorder compared to non-somatic symptom disorder peers during the COVID-19 related lockdown.

This cross-sectional study is the second part of a previously published study showing an improved trend in depression and anxiety in a group of patients with somatic symptom disorder compared to non-somatic symptom disorder peers. An anonymous semi-structured survey was distributed to two groups of Italian adolescents to measure the impact of quarantine on their daily life and coping strategies.

We recruited 115 adolescents, 58 (50.4%) mean age 15.3, with a recent diagnosis of somatic symptom disorder and 57 (49.6%) mean age 15.8, control peers.

The aim of this study was to detect differences in coping strategies and relationships with parents and peers, during the lockdown period in a group of adolescents with somatic symptom disorder and low disease burden when compared with a non-somatic symptom disorder group.

The relationship with parents significantly worsened in 4 (6.9%) of adolescents with somatic symptom disorder compared to 12 (21.1%) adolescents in the non-somatic symptom disorder group (p = 0.048). The relationship with peers significantly improved in 13 (22.4%) of adolescents with symptom disorder versus 3 (5.3%) of peers of the non- somatic symptom disorder group (p = 0.013).

Adolescents with somatic symptom disorder with a low burden of physical symptoms experienced less deterioration in their relationships with parents and peers than the non-somatic symptom disorder group.
Advanced interventions in the pre-hospital resuscitation of patients with non-compressible haemorrhage after penetrating injuries
Authors: ter Avest E. , Carenzo L. , Lendrum R. A. , Christian M. D. , Lyon R. M. , Coniglio C. , Rehn M. , Lockey D. J. , Perkins Z. B.
Published: June 2022

Early haemorrhage control and minimizing the time to definitive care have long been the cornerstones of therapy for patients exsanguinating from non-compressible haemorrhage (NCH) after penetrating injuries, as only basic treatment could be provided on scene. However, more recently, advanced on-scene treatments such as the transfusion of blood products, resuscitative thoracotomy (RT) and resuscitative endovascular balloon occlusion of the aorta (REBOA) have become available in a small number of pre-hospital critical care teams. Although these advanced techniques are included in the current traumatic cardiac arrest algorithm of the European Resuscitation Council (ERC), published in 2021, clear guidance on the practical application of these techniques in the pre-hospital setting is scarce. This paper provides a scoping review on how these advanced techniques can be incorporated into practice for the resuscitation of patients exsanguinating from NCH after penetrating injuries, based on available literature and the collective experience of several helicopter emergency medical services (HEMS) across Europe who have introduced these advanced resuscitation interventions into routine practice.

Graphical Abstract
Bringing rehabilitation home with an e-health platform to treat stroke patients: study protocol of a randomized clinical trial (RGS@home)
Authors: Mura Anna , Maier Martina , Ballester Belén Rubio , De la Torre Costa Javier , López-Luque Judit , Gelineau Axelle , Mandigout Stephane , Ghatan Per Hamid , Fiorillo Raffaele , Antenucci Fabrizio , Coolen Ton , Chivite Iñigo , Callen Antonio , Landais Hugo , Gómez Olga Irina , Melero Cristina , Brandi Santiago , Domenech Marc , Daviet Jean-Christophe , Zucca Riccardo , Verschure Paul F. M. J.
Published: June 2022

Background

There is a pressing need for scalable healthcare solutions and a shift in the rehabilitation paradigm from hospitals to homes to tackle the increase in stroke incidence while reducing the practical and economic burden for patients, hospitals, and society. Digital health technologies can contribute to addressing this challenge; however, little is known about their effectiveness in at-home settings. In response, we have designed the RGS@home study to investigate the effectiveness, acceptance, and cost of a deep tech solution called the Rehabilitation Gaming System (RGS). RGS is a cloud-based system for delivering AI-enhanced rehabilitation using virtual reality, motion capture, and wearables that can be used in the hospital and at home. The core principles of the brain theory-based RGS intervention are to deliver rehabilitation exercises in the form of embodied, goal-oriented, and task-specific action.

Methods

The RGS@home study is a randomized longitudinal clinical trial designed to assess whether the combination of the RGS intervention with standard care is superior to standard care alone for the functional recovery of stroke patients at the hospital and at home. The study is conducted in collaboration with hospitals in Spain, Sweden, and France and includes inpatients and outpatients at subacute and chronic stages post-stroke. The intervention duration is 3 months with assessment at baseline and after 3, 6, and 12 months. The impact of RGS is evaluated in terms of quality of life measurements, usability, and acceptance using standardized clinical scales, together with health economic analysis. So far, one-third of the patients expected to participate in the study have been recruited (N = 90, mean age 60, days after stroke ≥ 30 days). The trial will end in July 2023.

Discussion

We predict an improvement in the patients’ recovery, high acceptance, and reduced costs due to a soft landing from the clinic to home rehabilitation. In addition, the data provided will allow us to assess whether the prescription of therapy at home can counteract deterioration and improve quality of life while also identifying new standards for online and remote assessment, diagnostics, and intervention across European hospitals.

Trial registration

ClinicalTrials.gov NCT04620707. Registered on November 3, 2020
Pulmonary artery acceleration time accuracy for systolic pulmonary artery pressure estimation in critically ill patients
Authors: Dammassa Valentino , Corradi Francesco , Colombo Costanza Natalia Julia , Mojoli Francesco , Price Susanna , Tavazzi Guido
Published: June 2022

Background

Estimation of pulmonary pressures is of key importance in acute cardiovascular and respiratory failure. Pulmonary artery acceleration time (PAAT) has emerged as reliable parameter for the estimation of systolic pulmonary artery pressure (sPAP) in cardiological population with preserved right ventricular function. We sought to find whether PAAT correlates with sPAP in critically ill patients with and without right ventricular (RV) systolic dysfunction.

Methods

Observational study. We measured sPAP using continuous-wave Doppler analysis of tricuspid regurgitation velocity peak method and we assessed the validity of PAAT in estimating sPAP in patients admitted to adult intensive care unit (ICU) for acute cardiovascular and respiratory failure.

Results

We enrolled 236 patients admitted to cardiothoracic ICU for cardiovascular and respiratory failure (respectively: 129, 54.7% and 107, 45.3%). 114 (48.3%) had preserved RV systolic function (defined as TAPSE ≥ 17 mm), whilst 122 (51.7%) had RV systolic impairment (defined as TAPSE < 17 mm). A weak inverse correlation between PAAT and sPAP (ρ–0.189, p 0.0035) was observed in overall population, which was confirmed in those with preserved RV systolic PAAT and sPAP (ρ–0.361, p 0.0001). In patients with impaired RV systolic function no statistically significant correlation between PAAT and sPAP was demonstrated (p 0.2737). Adjusting PAAT values for log10, heart rate and RV ejection time did not modify the abovementioned correlations.

Conclusions

PAAT measurement to derive sPAP is not reliable in cardiothoracic critically ill patients, particularly in the coexistence of RV systolic impairment.
Profiling the absolute and relative strength of a special operations police unit
Authors: Talaber Kimberly A. , Orr Robin M. , Maupin Danny , Schram Ben , Hasanki Ksaniel , Roberts Adam , Robinson Jeremy
Published: June 2022

Background

Specialist police perform high-risk tasks and are required to have, and maintain, a high level of fitness. The aims of this study were to profile the strength of a specialist police unit and to investigate whether this profile remained constant over an 18-month period.

Methods

Retrospective data for 47 special operations police officers (mean initial weight = 88.84 ± 8.25 kg) were provided. Officers were tested five times over 18 months for 1 repetition maximum: bench press, squat, deadlift, and pull-up. All officers continued to participate in their typical physical conditioning programs. Repeated-measures ANOVAs with Bonferroni post-hoc adjustments or Friedman tests with Wilcoxon signed-rank tests were used to compare strength values across all five time points (TPs). Alpha levels were set at 0.05.

Results

All strength values increased significantly over the 18-month period. Over the five TPs, absolute squat increased the most (+ 9%: initial mean = 125.79 ± 24.53 kg), followed by absolute bench press (+ 8%: initial mean = 109.67 ± 19.80 kg), absolute deadlift (+ 7%: initial mean = 151.64 ± 26.31 kg) and absolute pull-up (+ 4%: initial mean = 121.43 ± 14.91 kg). Relatively, the highest increase was found with the squat (+ 8%: initial mean = 1.42 ± 0.25%), followed by the bench press (+ 7%: initial mean = 1.24 ± 0.20%), deadlift (+ 6%: initial mean = 1.71 ± 0.25%) then pull-up (+ 4%: initial mean = 1.37 ± 0.15%). The period between TP3 and TP4 yielded the fewest significant increases compared with other TP differences with only absolute bench press (+ 1.7%), absolute squat (+ 1.1%) and relative bench press (+ 1.6%) changing significantly (p < 0.05).

Conclusions

Specialist police can maintain, even increase strength, while serving in specialist units if provided with a Strength and Conditioning coach and time to train. Given changes over time, constant monitoring is required and a single timepoint may not be optimal to establish normative data.
Intranasal budesonide for rhinitis during a high airborne pollution period: a randomized controlled trial
Authors: Zhang Yuan , Shan Chunguang , Liu Weiwei , Han Yaozhong , Shi Guanggang , Ma Yongjian , Wagner Kerstin , Tian Xiaoyan , Zhang Lili , Larona Allan Joseph , Sacavage Steven , Franklin Kathleen , Wang Chengshuo , Zhang Luo
Published: June 2022

Background

Air pollution may induce or reinforce nasal inflammation regardless of allergy status. There is limited direct clinical evidence informing the treatment of airborne pollution-related rhinitis.

Objective

To assess the effectiveness of intranasal budesonide in adults with self-reported rhinitis symptoms triggered/worsened by airborne pollution.

Methods

Adults in northern China with self-reported rhinitis symptoms triggered or worsened by airborne pollution were randomized to budesonide 256 µg/day or placebo for 10 days in pollution season (October 2019 to February 2020). The primary endpoint was the mean change from baseline in 24-h reflective total nasal symptom score (rTNSS) averaged over 10 days. The secondary endpoints were subject-assessed Global Impression of Change (SGIC), mean change from baseline in individual nasal symptom severity, and mean change from baseline in individual non-nasal symptoms of cough and postnasal drip severity. One-sided P < 0.0125 was considered statistically significant.

Results

After an interruption by COVID-19, an interim analysis showed that the study could be ended for efficacy with n = 206 participants (103/group) since the primary efficacy endpoint demonstrated significant results. The final efficacy results showed that the 10-day-averaged rTNSS change in the budesonide group was greater than with placebo (− 2.20 vs − 1.72, P = 0.0107). Budesonide also significantly improved 10-day-averaged itching/sneezing change (− 0.75 vs − 0.51, P = 0.0009). Results for SGIC and all other individual symptoms did not show significant differences between the two groups.

Conclusions

Intranasal budesonide 256 µg once daily improved the total nasal symptoms and itching/sneezing over 10 days in adults with rhinitis triggered/worsened by airborne pollution.
Massive adrenocortical carcinoma presenting as peripheral edema: a case report
Authors: Goodkin David A.
Published: June 2022

Background

Adrenocortical carcinoma is a rare, but potentially lethal, malignancy that is usually detected as an incidental finding on abdominal imaging studies or owing to hormonal complications. This report recounts an unusual presentation with leg edema due to compression of the inferior vena cava. The dearth of proven effective treatment is also addressed.

Case presentation

A 65-year-old White male physician presented with severe, bilateral pitting edema that extended from the toes to the thighs. It progressed over several months. He also experienced paroxysmal dyspnea. Evaluation of cardiac, hepatic, and renal function failed to determine a cause. Computed tomography revealed a tumor above the right kidney, with compression of the intrahepatic inferior vena cava and upstream distension. Serum cortisol and dehydroepiandrosterone sulfate concentrations were elevated, 24-hour urinary cortisol level was elevated, and serum adrenocorticotropic hormone and testosterone concentrations were suppressed. A 27-cm tumor, the right lobe of the liver, the right kidney, and 26 lymph nodes were resected. Histological study confirmed the diagnosis of adrenocortical carcinoma. Ki67 proliferation index was 26.7% (worse prognosis associated with index > 10%). Lymph nodes were negative for malignancy, but a separate 2.7-cm tumor was found near the renal hilum. Adjuvant mitotane chemotherapy was prescribed. Serum testosterone concentration returned to normal. High-dose hydrocortisone administration was needed because of adrenal suppression and CYP 3A4 induction by mitotane.

Conclusion

Imaging of the abdomen and pelvis should be conducted in cases of unexplained leg edema. In this case, a large adrenal cancer compressed the vena cava. Iron deficiency followed resection of the large tumor. Advanced stages of adrenocortical carcinoma are associated with poor prognosis. Mitotane chemotherapy is a standard but unproven adjuvant treatment that is associated with many complications, and its induction of hepatic CYP 3A4 enzymes necessitates adjustment of other medications.
Preparation and identification of a single domain antibody specific for adenovirus vectors and its application to the immunoaffinity purification of adenoviruses
Authors: Cheng Yi , Hao Yanxia , Bao Fuxiang , Zhang Huimin , Liu Yanlong , Ao Kexin , Fu Shan , Wu Qiyao , Wang Zhi
Published: June 2022

Adenovirus belongs to the family of Adenoviridae. As a vaccine carrier, it has high safety and stimulates the body to produce cellular immunity and humoral immunity. This study prepared an adenoviral vector-specific single-domain antibody for use in adenovirus identification and purification. We successfully constructed a single domain antibody phage display library with a capacity of 1.8 × 109 by immunizing and cloning the VHH gene from Bactrian camel. After the second round of biopanning, clones specific for adenovirus were screened using phage ELISA. Twenty-two positive clones were obtained, and two clones with the highest binding affinity from ELISA were selected and named sdAb 5 and sdAb 31 for further application. The recombinant single-domain antibody was solublely expressed in E. coli and specifically bound to adenoviruses rAd26, ChAd63 and HAd5 in ELISA and live cell immunofluorescence assays. We established an effective method for immunoaffinity purification of adenovirus by immobilizing the single domain antibody to Sepharose beads, and it may be used to selectively capture adenoviruses from cell culture medium. The preparation of the adenovirus-specific single-domain antibody lays a foundation for the one-step immunoaffinity purification and identification of adenoviruses.
Blockade of the Arid5a/IL-6/STAT3 axis underlies the anti-inflammatory effect of Rbpjl in acute pancreatitis
Authors: Lv Jiachen , Fang Min , Sun Shijie , Wang Gang , Fu Songbin , Sun Bei , Tong Jinxue
Published: June 2022

Background

The microarray data analysis predicted that Rbpjl is poorly expressed in acute pancreatitis (AP). Activated IL-6/STAT3 signaling is further known to contribute to the progression of AP through immune regulation, and both IL-6 and STAT3 were bioinformatically predicted to interact with Arid5a. Accordingly, we aimed to investigate the potential involvement of the Arid5a/IL-6/STAT3 axis in the regulatory role of Rbpjl in the inflammation of AP.

Methods

Pancreatic acinar cells were exposed to lipopolysaccharide (LPS) to induce the pancreatic cell damage, and mice were subjected to supramaximal cerulein stimulation to induce AP. Expression patterns of Rbpjl and the Arid5a/IL-6/STAT3 axis were measured in mouse and cell models. Their expression was further manipulated to explore their effects on pancreatic cell injury and inflammation, as reflected by cell viability and apoptosis as well as reactive oxygen species (ROS) accumulation and proinflammatory cytokine secretion. Moreover, ChIP, EMSA, and dual-luciferase reporter assays were carried out to identify the interactions between Rbpjl and Arid5a.

Results

Rbpjl was found to be down-regulated in pancreatic tissues of AP mice and LPS-induced pancreatic acinar cells, while re-expression of Rbpjl led to enhanced cell viability, suppressed LPS-induced inflammation and ROS accumulation, and alleviation of AP-induced damage. Mechanistically, Rbpjl could bind to the promoter region of Arid5a and down-regulated its expression, thus repressing the activation of the IL-6/STAT3 signal axis. Furthermore, Rbpjl impaired Arid5a-dependent IL-6/STAT3 activation, hence alleviating pancreatic acinar cell inflammation. Furthermore, these effects were validated with in vivo experiments.

Conclusion

Collectively, our findings highlight that Rbpjl attenuates AP by down-regulating Arid5a and inactivating the IL-6/STAT3 pathway.