| 1. |
- Axfors, Cathrine, et al.
(author)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Research review (peer-reviewed)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 2. |
- Gill, Dipender, et al.
(author)
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ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels : a Mendelian randomization study
- 2020
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In: Royal Society Open Science. - : ROYAL SOC. - 2054-5703. ; 7:11
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Journal article (peer-reviewed)abstract
- Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 x 10(-4)) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.
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| 3. |
- Orejas, C, et al.
(author)
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Cold-water corals in aquaria: advances and challenges. A focus on the Mediterranean
- 2019
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In: Mediterranean Cold-Water Corals: Past, Present and Future. - : Springer. - 2213-719X. - 9783319916071
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Book chapter (peer-reviewed)abstract
- Knowledge on basic biological functions of organisms is essential to understand not only the role they play in the ecosystems but also to manage and protect their populations. The study of biological processes, such as growth, reproduction and physiology, which can be approached in situ or by collecting exemplars and rearing them in aquaria, is particularly challenging for deep-sea organisms such as cold-water corals (CWCs). Present experimental work and monitoring of deep-sea populations is still a chimera. Only a handful of research institutes or companies have been able to install in situ marine observatories in the Mediterranean Sea or elsewhere, which facilitate for a continuous monitoring of deep-sea ecosystems. Hence, today’s best way to obtain basic biological information on these organisms is (1) working with collected samples and analysing them post-mortem and / or (2) cultivating corals in aquaria in order to monitor biological processes and investigate coral behaviour and physiological responses under different experimental treatments. The first challenging aspect is the collection process, which implies the use of oceanographic research vessels in most occasions, since these organisms inhabit areas between ca. 150 m to more than 1,000 m depth, and specific sampling gears. The next challenge is the maintenance of the animals on board (in situations where cruises may take weeks) and their transport to home laboratories. Maintenance in the home labs is also extremely challenging since special conditions and set ups are needed to conduct experimental studies to obtain information on the biological processes of these animals. The complexity of the natural environment from which the corals were collected cannot be exactly replicated within the laboratory setting; a fact which has led some researchers to question the validity of work and conclusions drawn from such undertakings. It is evident that aquaria experiments cannot perfectly reflect the real environmental and trophic conditions where these organisms occur, but: (1) in most cases we do not have the possibility to obtain equivalent in situ information and (2) even with limitations, they produce relevant information about 117 the biological limits of the species, which is especially valuable when considering potential future climate change scenarios. This chapter includes many contributions from different authors and it intends to be both, a practical “handbook” for conducting CWC aquaria work, while at the same time, to offer an overview on the CWC research conducted in Mediterranean labs equipped with aquaria infrastructure. Experiences from Atlantic and Pacific laboratories with extensive experience with CWC work have also contributed to this chapter, as their procedures are valuable to any researcher interested in conducting experimental work with CWC in aquaria. It was impossible to include contributions from all labs in the world currently working experimentally with CWCs in the laboratory, but at the conclusion of the chapter we attempt, to our best of our knowledge, to supply a list of laboratories with operational CWC aquaria facilities.
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| 4. |
- Papadopoulos, Nikolaos G, et al.
(author)
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Research needs in allergy: an EAACI position paper, in collaboration with EFA.
- 2012
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Journal article (peer-reviewed)abstract
- ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
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| 5. |
- Roberts, Daniel N., et al.
(author)
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Perioperative water and electrolyte balance and water homeostasis regulation in children with acute surgery
- 2023
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 94:4, s. 1373-1379
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Journal article (peer-reviewed)abstract
- Background: Hospital-acquired hyponatremia remains a feared event in patients receiving hypotonic fluid therapy. Our objectives were to assess post-operative plasma-sodium concentration and to provide a physiological explanation for plasma-sodium levels over time in children with acute appendicitis. Methods: Thirteen normonatremic (plasma-sodium ≥135 mmol/L) children (8 males), median age 12.3 (IQR 11.5–13.5) years participated in this prospective observational study (ACTRN12621000587808). Urine was collected and analyzed. Blood tests, including renin, aldosterone, arginine-vasopressin, and circulating nitric oxide substrates were determined on admission, at induction of anesthesia, and at the end of surgery. Results: On admission, participants were assumed to be mildly dehydrated and were prescribed 50 mL/kg of Ringer’s acetate intravenously followed by half-isotonic saline as maintenance fluid therapy. Blood tests, urinary indices, plasma levels of aldosterone, arginine-vasopressin, and net water-electrolyte balance indicated that participants were dehydrated on admission. Although nearly 50% of participants still had arginine-vasopressin levels that would have been expected to produce maximum antidiuresis at the end of surgery, electrolyte-free water clearance indicated that almost all participants were able to excrete net free water. No participant became hyponatremic. Conclusions: The use of moderately hypotonic fluid therapy after correction of extracellular fluid deficit is not necessarily associated with post-operative hyponatremia. Impact: Our observations show that in acutely ill normonatremic children not only the composition but also the amount of volume infused influence on the risk of hyponatremia.Our observations also suggest that perioperative administration of hypotonic fluid therapy is followed by a tendency towards hyponatremia if extracellular fluid depletion is left untreated.After correcting extracellular deficit almost all patients were able to excrete net free water. This occurred despite nearly 50% of the cohort having high circulating plasma levels of arginine-vasopressin at the end of surgery, suggesting a phenomenon of renal escape from arginine-vasopressin-induced antidiuresis.
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| 6. |
- Schiele, Miriam A., et al.
(author)
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Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders : A meta-analysis
- 2021
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In: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 44, s. 105-120
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Journal article (peer-reviewed)abstract
- There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.
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