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1.
Chembiochem ; 25(5): e202300661, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38224131

RESUMO

PET hydrolases are an emerging class of enzymes that are being heavily researched for their use in bioprocessing polyethylene terephthalate (PET). While work has been done in studying the binding of PET oligomers to the active site of these enzymes, the dynamics of PET hydrolases binding to a bulk PET surface is an unexplored area. Here, methods were developed for total internal reflection fluorescence (TIRF) microscopy and fluorescence recovery after photobleaching (FRAP) microscopy to study the adsorption and desorption dynamics of these proteins onto a PET surface. TIRF microscopy was employed to measure both on and off rates of two of the most commonly studied PET hydrolases, PHL7 and LCC, on a PET surface. It was found that these proteins have a much slower off rates on the order of 10-3  s-1 , comparable to non-productive binding in enzymes such as cellulose. In combination with FRAP microscopy, a dynamic model is proposed in which adsorption and desorption dominates over lateral diffusion over the surface. The results of this study could have implications for the future engineering of PET hydrolases, either to target them to a PET surface or to modulate interaction with their substrate.


Assuntos
Hidrolases , Polietilenotereftalatos , Microscopia de Fluorescência , Adsorção , Celulose
2.
Arch Toxicol ; 97(4): 1033-1045, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36717398

RESUMO

The solvent 1,3-dichlorobenzene (1,3-DCB) is formed during thermal decomposition of the initiator 2,4-dichlorobenzoylperoxide in the production of silicone rubber with potential exposure of production workers as shown in previous works. Despite a threshold limit value (MAK value) of 2 ppm in air, there are currently no data about the corresponding internal exposure that would allow for the derivation of a biological limit value. In the present study, we have investigated the absorption of 1,3-DCB and urinary kinetics of its metabolites in 10 human volunteers after controlled inhalative exposure. Due to the strong odour of 1,3-DCB, a subjective evaluation of odour nuisance was also performed. Ten male human volunteers (23-36 yrs.) were exposed 6 h/day to a concentration of 0.7 ppm and 1.5 ppm in the Aachen workplace simulation laboratory (AWSL) with one week between each experiment. In order to investigate potential dermal absorption, the volunteers were exposed to 1.5 ppm wearing a suitable filter mask that prevented inhalative exposure in a third exposure. 1,3-DCB in blood was measured after 3 and 6 h exposure and the urinary metabolites 3,5-dichlorocatechol (3,5-DCC), 2,4-dichlorophenol (2,4-DCP) and 3,5-dichlorophenol (3,5-DCP) were measured over 24 h after exposure via LC/MS/MS. There were clear dose-response relations for all investigated parameters. The maximum excretion of the metabolites was reached at the end of exposure and corresponded to 5.2 ± 0.7 mg/g crea, 1.5 ± 0.35 mg/g crea and 0.07 ± 0.011 mg/g crea at 0.7 ppm and to 12.0 ± 3 mg/g crea, 3.5 ± 1.1 mg/g crea and 0.17 ± 0.05 mg/g crea at 1.5 ppm for 3,5-DCC, 2,4-DCP and 3,5-DCP, respectively. The use of filter masks decreased the internal exposure for about 85-90%, indicating substantial dermal absorption. Odour perception did not show a dose-response, probably due to fast olfactory adaption. The human study presented here provides an excellent basis for deriving a biological limit value for 1,3-DCB.


Assuntos
Clorofenóis , Exposição Ocupacional , Humanos , Masculino , Voluntários Saudáveis , Espectrometria de Massas em Tandem , Exposição Ocupacional/análise
3.
BMC Vet Res ; 17(1): 379, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879836

RESUMO

BACKGROUND: Quantitative bacterial culture (QBC) is the gold standard for diagnosing canine urinary tract infection. Current guidelines recommend QBC within 24 h of urine collection and that unpreserved urine is refrigerated until culture. However, temperature-controlled transport is rarely feasible, indicating a need for alternative storage during transport of urine from primary veterinary practices to the microbiology laboratory. The objective was to investigate the effect of storage temperature and boric acid sponge-preservation on quantitative bacterial culture of canine urine. RESULTS: Significant bacteriuria was detected in 72 out of 179 samples (40%) collected from 141 dogs. Overall accuracy was 94-98% for both storage conditions and time points. Non-inferiority (15% margin) to reference quantitative bacterial culture was evident for sensitivity, specificity and predictive values for both storage methods and time points, except for the negative predictive value for 48 h boric acid preservation (NPV: 89, 95% CI [79;95]). There was no significant difference between the sensitivity and specificity for either of the time-points (p-value = 0.07-1). CONCLUSIONS: Boric acid sponge-preservation using Uriswab™ is a useful alternative to refrigeration of urine samples during transport. Reliable quantitative bacterial culture results can be obtained from canine urine up to 48 h after collection if urine is refrigerated, and for at least 24 h if urine is stored using a boric acid-containing urine transport system.


Assuntos
Doenças do Cão , Preservação Biológica , Manejo de Espécimes/veterinária , Infecções Urinárias , Urina/microbiologia , Animais , Bactérias , Ácidos Bóricos , Doenças do Cão/diagnóstico , Doenças do Cão/microbiologia , Cães , Preservação Biológica/veterinária , Temperatura , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia , Infecções Urinárias/veterinária
4.
Acta Anaesthesiol Scand ; 65(6): 834-845, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33583034

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.


Assuntos
Anti-Inflamatórios/administração & dosagem , Tratamento Farmacológico da COVID-19 , Dexametasona/administração & dosagem , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , SARS-CoV-2 , Anti-Inflamatórios/efeitos adversos , COVID-19/complicações , Dinamarca , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Mortalidade Hospitalar , Humanos , Hidrocortisona/uso terapêutico , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Índia , Cuidados para Prolongar a Vida/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Qualidade de Vida , Análise de Sobrevida , Suécia , Suíça
5.
Diabet Med ; 37(9): 1561-1568, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32353914

RESUMO

AIM: Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. METHODS: Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. RESULTS: Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. CONCLUSION: Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo/fisiologia , Exercícios Respiratórios , Diabetes Mellitus Tipo 1/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Frequência Cardíaca/fisiologia , Hiperóxia , Oxigenoterapia , Idoso , Albuminúria/etiologia , Sistema Nervoso Autônomo/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Acta Anaesthesiol Scand ; 63(8): 1098-1101, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31032881

RESUMO

BACKGROUND: An increasing number of trials are stopped earlier than originally planned. It has been suggested that trials stopped pre-maturely overestimate the treatment effect. With the outlined observational study, we aim to simulate the results of stopping trials before they reach their planned sample size to assess the effects on mortality estimates. METHODS AND STATISTICS: Based on 3 international, randomised clinical trials (RCTs) in critical care: Scandinavian Starch for Severe Sepsis and Septic Shock (6S) trial, the Transfusion Requirements in Septic Shock (TRISS) trial and the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial, we will estimate relative risks with 95% confidence intervals for the primary outcome 90-day mortality after the inclusion of each individual patient in each RCT. This will be presented graphically with the primary outcome as a function of the number of included patients. DISCUSSION: The outlined study will provide important knowledge about the effects of stopping critical care trials early. This may have important implications for patients, relatives, clinicians, researchers, guideline committee members and policy makers. ETHICS AND DISSEMINATION: We will use data from consenting patients enrolled in RCTs approved by the relevant ethical committees; this study requires no further permissions. We will report the results in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and submit the final approved manuscript to a peer-reviewed journal.


Assuntos
Protocolos Clínicos , Unidades de Terapia Intensiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Choque Séptico/mortalidade , Idoso , Cuidados Críticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Allergy ; 73(1): 230-238, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28662309

RESUMO

BACKGROUND: Patients with systemic mastocytosis (SM) may suffer from mast cell (MC) mediator-related symptoms insufficiently controlled by conventional therapy. Omalizumab is an established treatment in other MC-driven diseases, but experiences in SM are limited. OBJECTIVE: To assess the efficacy and safety of omalizumab in SM. METHODS: In our patient cohort, we evaluated all SM patients treated with omalizumab. A physician global assessment of type and severity of symptoms was performed at baseline, at 3 and 6 months and at latest follow-up. Quality of life was assessed by visual analogue scale. S-tryptase and KIT D816V allele burden were monitored. RESULTS: A total of 14 adult SM patients (10 ISM, 2 BMM, 1 SSM, and 1 ASM-AHN) received omalizumab with a median duration of 17 months (range: 1-73 months). One patient was excluded due to concomitant cytoreductive therapy. In the remaining 13 patients, we observed a significant reduction in symptoms, with complete symptom control in five (38.5%), major response in three (23.1%), and a partial response in three (23.1%) patients, whereas two patients (15.4%) withdrew due to subjective side-effects at first dose. The treatment was most effective for recurrent anaphylaxis and skin symptoms, less for gastrointestinal, musculoskeletal, and neuropsychiatric symptoms. Patient-reported quality of life showed significant improvement. No significant changes in s-tryptase/KIT D816V allele burden were observed. No severe adverse events were recorded. CONCLUSIONS: Omalizumab appears to be a promising treatment option in SM, effectively preventing anaphylaxis and improving chronic MC mediator-related symptoms, insufficiently controlled by conventional therapy. Controlled studies are needed to substantiate findings.


Assuntos
Anafilaxia/prevenção & controle , Antialérgicos/uso terapêutico , Mastocitose Sistêmica/tratamento farmacológico , Omalizumab/uso terapêutico , Adulto , Anafilaxia/etiologia , Antialérgicos/administração & dosagem , Antialérgicos/efeitos adversos , Biomarcadores , Feminino , Humanos , Masculino , Mastocitose Sistêmica/diagnóstico , Pessoa de Meia-Idade , Omalizumab/administração & dosagem , Omalizumab/efeitos adversos , Qualidade de Vida , Pele/patologia , Avaliação de Sintomas , Resultado do Tratamento , Adulto Jovem
8.
Diabet Med ; 35(10): 1375-1382, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29781558

RESUMO

AIM: To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high- or low-risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional risk factors for diabetic kidney disease were evaluated using univariate and logistic regression analysis. RESULTS: A total of 1777 participants from 15 centres were included, with 12.3% of these having a high-risk proteomic pattern. Participants in the high-risk group (n=218), were more likely to be men, were older, had longer diabetes duration, a lower estimated GFR and a higher urinary albumin:creatinine ratio than those in the low-risk group (n=1559, P<0.02). Numerical differences were small and univariate regression analyses showed weak associations (R2 < 0.04) of CKD273 with each baseline variable. In a logistic regression model including clinical variables known to be associated with diabetic kidney disease, estimated GFR, gender, log urinary albumin:creatinine ratio and use of renin-angiotensin system-blocking agents remained significant determinants of the CKD273 high-risk group: area under the curve 0.72 (95% CI 0.68-0.75; P<0.01). CONCLUSIONS: In this population of individuals with Type 2 diabetes and normoalbuminuria, traditional diabetic kidney disease risk factors differed slightly between participants at high risk and those at low risk of diabetic kidney disease, based on CKD273. These data suggest that CKD273 may provide additional prognostic information over and above the variables routinely available in the clinic. Testing the added value will be subject to our ongoing study. (European Union Clinical Trials Register: EudraCT 2012-000452-34 and Clinicaltrials.gov: NCT02040441).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/urina , Hipoglicemiantes/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Proteoma/análise , Adolescente , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteoma/metabolismo , Proteômica/métodos , Medição de Risco , Urinálise/métodos , Adulto Jovem
9.
Vox Sang ; 113(2): 185-197, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29214632

RESUMO

BACKGROUND AND OBJECTIVES: ABO remains the clinically most important blood group system, but despite earlier extensive research, significant findings are still being made. The vast majority of catalogued ABO null alleles are based on the c.261delG polymorphism. Apart from c.802G>A, other mechanisms for O alleles are rare. While analysing the data set from the 1000 Genomes (1000G) project, we encountered two previously uncharacterized deletions, which needed further exploration. MATERIALS AND METHODS: The Erythrogene database, complemented with bioinformatics software, was used to analyse ABO in 2504 individuals from 1000G. DNA samples from selected 1000G donors and African blood donors were examined by allele-specific PCR and Sanger sequencing to characterize predicted deletions. RESULTS: A 5821-bp deletion encompassing exons 5-7 was called in twenty 1000G individuals, predominantly Africans. This allele was confirmed and its exact deletion point defined by bioinformatic analyses and in vitro experiments. A PCR assay was developed, and screening of African samples revealed three donors heterozygous for this deletion, which was thereby phenotypically established as an O allele. Analysis of upstream genetic markers indicated an ancestral origin from ABO*O.01.02. We estimate this deletion as the 3rd most common mechanism behind O alleles. A 24-bp deletion was called in nine individuals and showed greater diversity regarding ethnic distribution and allelic background. It could neither be confirmed by in silico nor in vitro experiments. CONCLUSION: A previously uncharacterized ABO deletion among Africans was comprehensively mapped and a genotyping strategy devised. The false prediction of another deletion emphasizes the need for cautious interpretation of NGS data and calls for strict validation routines.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Deleção de Genes , Genoma Humano , Genótipo , Humanos , Fenótipo , Polimorfismo Genético
10.
Acta Anaesthesiol Scand ; 62(7): 974-982, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29602190

RESUMO

BACKGROUND: Mortality rates in critically ill adult patients admitted to the intensive care unit (ICU) remains high, and numerous patient- and disease-related adverse prognostic factors have been identified. In recent years, studies in a variety of emergency conditions suggested that outcome is dependent on the time of hospital admission. The importance of out-of-hours admission to the ICU has been sparsely evaluated and with ambiguous findings. We assessed the association between out-of-hours (16:00 to 07:00) and weekend admission to the ICU, respectively, and 90-day mortality in a nationwide cohort. METHODS: We included all Danish adult patients admitted to the ICU between 1 January 2011 and 30 June 2014, with an ICU stay > 24 h. The crude and adjusted association between out-of-hours and weekend admission and 90-day mortality was assessed (odds ratio (ORs) with 95% confidence intervals (CI)). RESULTS: A total of 44,797 patients were included, 53.3% were admitted out-of-hours, and 22.6% during weekends. Median age was 67 years (interquartile range (IQR) 55-76), and median SAPS II was 42 (IQR 30-54). Patients admitted in-hours vs. out-of-hours displayed a 90-day mortality rate of 41.0% vs. 44.2%. The adjusted association (OR with 95% CI) between out-of-hours admission and 90-day mortality was 1.07 (1.02-1.11), and the adjusted association (OR with 95% CI) between weekend admission and 90-day mortality was 1.10 (1.05-1.15). CONCLUSION: This nationwide study suggests that critically ill adult patients admitted to the ICU during weekends and out-of-hours, and with an ICU stay > 24 h are at slightly increased risk of mortality.


Assuntos
Plantão Médico , Estado Terminal/mortalidade , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente
11.
Acta Anaesthesiol Scand ; 62(1): 6-18, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29124727

RESUMO

BACKGROUND: Systematic reviews comparing untargeted antifungal treatment with placebo or no treatment in critically ill patients have provided conflicting results. We aimed to assess patient-important benefits and harms of untargeted antifungal therapy vs. placebo or no treatment in adult patients with complicated intra-abdominal infection. METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials assessing untargeted antifungal therapy compared to placebo or no treatment in adults with complicated intra-abdominal infection. We used the Cochrane and GRADE methodologies and exclusively assessed patient-important outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias. We performed conventional meta-analyses, including sensitivity and subgroup analyses, and trial sequential analysis to assess the risk of random errors and to estimate trial sequential analysis adjusted confidence intervals. RESULTS: We included six trials (1,067 patients) in the review, and four trials reported data on the predefined outcome measures and were included in the meta-analysis. Three of the four trials had high risk of bias. We observed no statistically significant difference in mortality (relative risk 0.58, 95% confidence interval 0.24-1.39) or in any of the other patient-important outcomes between untargeted antifungal treatment and placebo or no treatment (low/very low quality of evidence). Trial sequential analysis demonstrated lack of data and high risk of random errors. CONCLUSIONS: The quantity and quality of evidence supporting untargeted antifungal treatment in adult patients with complicated intra-abdominal infection are low to very low with no firm evidence for benefit or harm.


Assuntos
Antifúngicos/uso terapêutico , Infecções Intra-Abdominais/tratamento farmacológico , Adulto , Antifúngicos/efeitos adversos , Humanos , Tempo de Internação , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Acta Anaesthesiol Scand ; 62(5): 724-730, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29520759

RESUMO

INTRODUCTION: Anaerobic bacteria are believed to be common pathogens in severe infections. Yet, they are difficult to culture and consequently often unrecognised in clinical infections. Metronidazole is often used empirically for potential anaerobic infections, as the resistance to metronidazole is low. However, disadvantages of metronidazole use exist, including drug interactions, side effects and economical expenses. Currently, the balance between the benefits and harms of empirical metronidazole for severe bacterial infections is unknown. We aim to assess patient-important benefits and harms of empirical metronidazole vs. placebo or no treatment in adult patients with severe bacterial infection of any origin in a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. METHODS AND ANALYSIS: This protocol provides details on the planned systematic review, which will be prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, the Cochrane Handbook, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. The primary outcome is all-cause mortality. Secondary outcomes include adverse events, secondary infections, use of life support, antibiotic resistance and hospital length of stay. We will conduct conventional meta-analyses, including predefined subgroup- and sensitivity analyses. Additionally, we will assess the risk of random errors by trial sequential analysis. ETHICS AND DISSEMINATION: Ethical approval is not needed, as the outlined review exclusively will include previously published data. We aim to publish in an international, peer-reviewed journal.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Metronidazol/uso terapêutico , Humanos , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Acta Anaesthesiol Scand ; 62(9): 1321-1326, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29797714

RESUMO

BACKGROUND: Corticosteroids are frequently prescribed to critically ill patients. However, their use may increase the risk of gastrointestinal (GI) bleeding, which is associated with morbidity and mortality. Accordingly, we aim to assess whether continued administration of corticosteroids for >24 hours increases the rate of GI bleeding in adult critically ill patients compared to placebo or no treatment. METHODS/DESIGN: We will conduct a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis. The participants will be adult (as defined in the included trials) critically ill patients. The intervention will be any corticosteroid administered systematically for >24 hours and the comparator will be placebo or no treatment. The primary outcome will be rate of clinically important GI bleeding. We will systematically search EMBASE, MEDLINE, Medline In-Process, Cochrane Library, Epistemonikos and trial registries for relevant literature, as well as perform a hand search. We will follow the recommendations by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors (bias) and random errors will be assessed and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION: The risk of GI bleeding in adult critically ill patients treated with corticosteroids is unknown. Hence, there is need for a robust systematic review to assess this risk and provide clinicians with a clearer understanding of the strength and limitations of existing data.


Assuntos
Corticosteroides/efeitos adversos , Estado Terminal , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Cuidados Críticos , Humanos , Risco
14.
Acta Anaesthesiol Scand ; 62(6): 744-755, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29577238

RESUMO

BACKGROUND: In the intensive care unit (ICU), stress ulcer prophylaxis with proton pump inhibitors or histamine-2-receptor antagonists is standard of care although gastrointestinal bleeding remains uncommon. It remains unknown whether its use is associated with benefits or harms and the quality of evidence supporting the use of stress ulcer prophylaxis has been questioned. Accordingly, the objective of this systematic review was to critically assess the evidence from randomized clinical trials on the benefits and harms of stress ulcer prophylaxis vs. placebo or no prophylaxis in adult ICU patients. METHODS: We will systematically search for randomized clinical trials in major international databases. Two authors will independently screen and select trials for inclusion, extract data and assess the methodological quality using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will perform conventional meta-analyses using Review Manager, and STATA 15, and we will assess the risk of random errors using Trial Sequential Analysis. Also, we will assess and report the overall quality of evidence for all outcomes according to GRADE. DISCUSSION: The evidence on the benefits and harms of stress ulcer prophylaxis in adult ICU patients is unclear and an updated systematic review is warranted as new trials have been published. To control risks of systematic and random errors, we will use Cochrane and GRADE methodology and Trial Sequential Analysis. Our ambition with this systematic review is to provide updated, reliable and precise data to better inform decision makers on the use of stress ulcer prophylaxis in adult ICU patients.


Assuntos
Protocolos Clínicos , Úlcera Péptica/prevenção & controle , Estresse Psicológico/complicações , Adulto , Humanos , Unidades de Terapia Intensiva , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Acta Anaesthesiol Scand ; 62(3): 336-346, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29210058

RESUMO

BACKGROUND: Intensive care unit (ICU) mortality prediction scores deteriorate over time, and their complexity decreases clinical applicability and commonly causes problems with missing data. We aimed to develop and internally validate a new and simple score that predicts 90-day mortality in adults upon acute admission to the ICU: the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU). METHODS: We used data from an international cohort of 2139 patients acutely admitted to the ICU and 1947 ICU patients with severe sepsis/septic shock from 2009 to 2016. We performed multiple imputations for missing data and used binary logistic regression analysis with variable selection by backward elimination, followed by conversion to a simple point-based score. We assessed the apparent performance and validated the score internally using bootstrapping to present optimism-corrected performance estimates. RESULTS: The SMS-ICU comprises seven variables available in 99.5% of the patients: two numeric variables: age and lowest systolic blood pressure, and five dichotomous variables: haematologic malignancy/metastatic cancer, acute surgical admission and use of vasopressors/inotropes, respiratory support and renal replacement therapy. Discrimination (area under the receiver operating characteristic curve) was 0.72 (95% CI: 0.71-0.74), overall performance (Nagelkerke's R2 ) was 0.19 and calibration (intercept and slope) was 0.00 and 0.99, respectively. Optimism-corrected performance was similar to apparent performance. CONCLUSIONS: The SMS-ICU predicted 90-day mortality with reasonable and stable performance. If performance remains adequate after external validation, the SMS-ICU could prove a valuable tool for ICU clinicians and researchers because of its simplicity and expected very low number of missing values.


Assuntos
Estado Terminal/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
16.
Acta Anaesthesiol Scand ; 62(4): 420-450, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29479665

RESUMO

BACKGROUND: Adult critically ill patients often suffer from acute circulatory failure and those with low cardiac output may be treated with inotropic agents. The aim of this Scandinavian Society of Anaesthesiology and Intensive Care Medicine guideline was to present patient-important treatment recommendations on this topic. METHODS: This guideline was developed according to GRADE. We assessed the following subpopulations of patients with shock: (1) shock in general, (2) septic shock, (3) cardiogenic shock, (4) hypovolemic shock, (5) shock after cardiac surgery, and (6) other types of shock, including vasodilatory shock. We assessed patient-important outcome measures, including mortality and serious adverse reactions. RESULTS: For all patients, we suggest against the routine use of any inotropic agent, including dobutamine, as compared to placebo/no treatment (very low quality of evidence). For patients with shock in general, and in those with septic and other types of shock, we suggest using dobutamine rather than levosimendan or epinephrine (very low quality of evidence). For patients with cardiogenic shock and in those with shock after cardiac surgery, we suggest using dobutamine rather than milrinone (very low quality of evidence). For the other clinical questions, we refrained from giving any recommendations or suggestions. CONCLUSIONS: We suggest against the routine use of any inotropic agent in adult patients with shock. If used, we suggest using dobutamine rather than other inotropic agents for the majority of patients, however, the quality of evidence was very low, implying high uncertainty on the balance between the benefits and harms of inotropic agents.


Assuntos
Anestesiologia , Cardiotônicos/uso terapêutico , Guias de Prática Clínica como Assunto , Choque/tratamento farmacológico , Doença Aguda , Cuidados Críticos , Dobutamina/uso terapêutico , Humanos , Sociedades Médicas
17.
Artigo em Inglês | MEDLINE | ID: mdl-29761482

RESUMO

BACKGROUND: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. METHODS: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. CONCLUSIONS: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.

18.
Scand J Med Sci Sports ; 28(4): 1424-1434, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29286552

RESUMO

Current methods of sports injury surveillance are limited by lack of medical validation of self-reported injuries and/or incomplete information about injury consequences beyond time loss from sport. The aims of this study were to (a) evaluate the feasibility of the SMS, Phone, and medical Examination injury surveillance (SPEx) system (b) to evaluate the proportion of injuries and injury consequences reported by SPEx when compared to outcomes from a modified version of the Oslo Sports Trauma Research Centre (OSTRC) Overuse Injury Questionnaire. We followed 679 elite adolescent handball players over 31 weeks using the SPEx system. During the last 7 weeks, we also implemented a modified OSTRC questionnaire in a subgroup of 271 players via telephone interviews. The weekly response proportions to the primary SPEx questions ranged from 85% to 96% (mean 92%). SMS responses were received from 79% of the participants within 1 day. 95% of reported injuries were classified through the telephone interview within a week, and 67% were diagnosed by medical personnel. Comparisons between reported injuries from SPEx and OSTRC demonstrated fair (κ = 39.5% [25.1%-54.0%]) to substantial prevalence-adjusted bias-adjusted kappa (PABAK = 66.8% [95% CI 58.0%-75.6%]) agreement. The average injury severity score difference between SPEx and the OSTRC approach was -0.2 (95% CI -3.69-3.29) of possible 100 with 95% limits of agreement from(-14.81-14.41). These results support the feasibility and validity of the SPEx injury surveillance system in elite youth sport. Future studies should evaluate the external validity of SPEx system in different cohorts of athletes.


Assuntos
Traumatismos em Atletas/diagnóstico , Exame Físico , Telefone , Envio de Mensagens de Texto , Adolescente , Atletas , Dinamarca , Estudos de Viabilidade , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Inquéritos e Questionários , Esportes Juvenis
19.
Scand J Med Sci Sports ; 28(1): 252-259, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28267868

RESUMO

The accurate measurement of sport exposure time and injury occurrence is key to effective injury prevention and management. Current measures are limited by their inability to identify all types of sport-related injury, narrow scope of injury information, or lack the perspective of the injured athlete. The aims of the study were to evaluate the proportion of injuries and the agreement between sport exposures reported by the SMS messaging and follow-up telephone part of the SMS, Phone, and medical staff Examination (SPEx) sports injury surveillance system when compared to measures obtained by trained on-field observers and medical staff (comparison method). We followed 24 elite adolescent handball players over 12 consecutive weeks. Eighty-six injury registrations were obtained by the SPEx and comparison methods. Of them, 35 injury registrations (41%) were captured by SPEx only, 10 injury registrations (12%) by the comparison method only, and 41 injury registrations (48%) by both methods. Weekly exposure time differences (95% limits of agreement) between SPEx and the comparison method ranged from -4.2 to 6.3 hours (training) and -1.5 to 1.0 hours (match) with systematic differences being 1.1 hours (95% CI 0.7 to 1.4) and -0.2 (95% CI -0.3 to -0.2), respectively. These results support the ability of the SPEx system to measure training and match exposures and injury occurrence among young athletes. High weekly response proportions (mean 83%) indicate that SMS messaging can be used for player measures of injury consequences beyond time-loss from sport. However, this needs to be further evaluated in large-scale studies.


Assuntos
Traumatismos em Atletas/epidemiologia , Sistema de Registros , Telemedicina , Envio de Mensagens de Texto , Adolescente , Atletas , Traumatismos em Atletas/diagnóstico , Dinamarca , Feminino , Humanos , Masculino , Corpo Clínico , Estudos Prospectivos , Esportes , Fatores de Tempo
20.
Opt Express ; 25(3): 1762-1768, 2017 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29519029

RESUMO

We demonstrate a plasmonic Mach-Zehnder (MZ) modulator with a flat frequency response exceeding 170 GHz. The modulator comprises two phase modulators exploiting the Pockels effect of an organic electro-optic material in plasmonic slot waveguides. We further show modulation at 100 GBd NRZ and 60 GBd PAM-4. The electrical drive signals were generated using a 100 GSa/s digital to analog converter (DAC). The high-speed and small-scale devices are relevant for next-generation optical interconnects.

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