Browsing by Subject "GUIDELINES"

Sort by: Order: Results:

Now showing items 1-20 of 163
  • Olasveengen, Theresa M.; de Caen, Allan R.; Mancini, Mary E.; Maconochie, Ian K.; Aickin, Richard; Atkins, Dianne L.; Berg, Robert A.; Bingham, Robert M.; Brooks, Steven C.; Castren, Maaret; Chung, Sung Phil; Considine, Julie; Couto, Thomaz Bittencourt; Escalante, Raffo; Gazmuri, Raul J.; Guerguerian, Anne-Marie; Hatanaka, Tetsuo; Koster, Rudolph W.; Kudenchuk, Peter J.; Lang, Eddy; Lim, Swee Han; Lofgren, Bo; Meaney, Peter A.; Montgomery, William H.; Morley, Peter T.; Morrison, Laurie J.; Nation, Kevin J.; Ng, Kee-Chong; Nadkarni, Vinay M.; Nishiyama, Chika; Nuthall, Gabrielle; Ong, Gene Yong-Kwang; Perkins, Gavin D.; Reis, Amelia G.; Ristagno, Giuseppe; Sakamoto, Tetsuya; Sayre, Michael R.; Schexnayder, Stephen M.; Sierra, Alfredo F.; Singletary, Eunice M.; Shimizu, Naoki; Smyth, Michael A.; Stanton, David; Tijssen, Janice A.; Travers, Andrew; Vaillancourt, Christian; Van de Voorde, Patrick; Hazinski, Mary Fran; Nolan, Jerry P.; ILCOR Collaborators (2017)
    The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 paediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have pri-oritised and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question. (C) 2017 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.
  • Ottka, Claudia; Vapalahti, Katariina; Puurunen, Jenni; Vahtera, Laura; Lohi, Hannes (2021)
    Background Metabolomics has been proven to be an invaluable research tool by providing comprehensive insight into systemic metabolism. However, the lack of scalable and quantitative methods with known reference intervals (RIs) and documented reproducibility has prevented the use of metabolomics in the clinical setting. Objective The objective of this study was to validate the developed quantitative nuclear magnetic resonance (NMR) spectroscopy-based metabolomics platform for canine serum and plasma samples and determine optimal sample handling conditions for its use. Methods Altogether, 8247 canine samples were analyzed using a Bruker's 500 MHz NMR spectrometer. Using statistical approaches derived from international guidelines, we studied method precision, measurand stability in various long- and short-term storage conditions, as well as the effect of prolonged contact with red blood cells (RBCs), and differences among blood collection tubes. We also screened interferences with lipemia, hemolysis, and bilirubinemia. The results were compared against routine clinical chemistry methods, and RIs were defined for all measurands. Results We determined RIs for 123 measurands, most of which were previously unpublished. The reproducibility of the results of the NMR platform appeared generally outstanding, and the integrity of the results can be ensured by following standard blood drawing and processing guidelines. Conclusions Owing to the advantages of quantitative results, high reproducibility, and scalability, this canine metabolomics platform holds great potential for numerous clinical and research applications to improve canine health and well-being.
  • Mikkola, Ilona; Hagnäs, Maria; Hartsenko, Jelena; Kaila, Minna; Winell, Klas (2020)
    Aims To investigate whether the use of a personalized care plan is associated with clinical outcomes of type 2 diabetes (T2D) treatment in real-world. Methods Quality of treatment was assessed using data from a yearly sample of patients with T2D visiting primary care health centres in 2012–2016. Patients were divided into three groups: 1) patient has a copy of their personalized care plan, 2) care plan exists in the patient record only or 3) patient has no care plan. Data on smoking, laboratory tests, systolic blood pressure (sBP) and statin use were collected. We compared the outcomes between the three groups in terms of proportions of patients achieving the clinical targets recommended by international guidelines. Results Evaluable data were available for 10,403 patients. Of these, 1,711 (16%) had a copy of their personalized care plan, and 3,623 (35%) had no care plan. Those who had a copy of their care plan were significantly more likely than those without to achieve the sBP target (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.29–1.51, p
  • Li, Xia; Frechen, Sebastian; Moj, Daniel; Lehr, Thorsten; Taubert, Max; Hsin, Shih-hsuan; Mikus, Gerd; Neuvonen, Pertti J; Olkkola, Klaus; Saari, Teijo; Fuhr, Uwe (2020)
    Background Voriconazole, a first-line antifungal drug, exhibits nonlinear pharmacokinetics (PK), together with large interindividual variability but a narrow therapeutic range, and markedly inhibits cytochrome P450 (CYP) 3A4 in vivo. This causes difficulties in selecting appropriate dosing regimens of voriconazole and coadministered CYP3A4 substrates. Objective This study aimed to investigate the metabolism of voriconazole in detail to better understand dose- and time-dependent alterations in the PK of the drug, to provide the model basis for safe and effective use according to CYP2C19 genotype, and to assess the potential of voriconazole to cause drug-drug interactions (DDIs) with CYP3A4 substrates in more detail. Methods In vitro assays were carried out to explore time-dependent inhibition (TDI) of CYP3A4 by voriconazole. These results were combined with 93 published concentration-time datasets of voriconazole from clinical trials in healthy volunteers to develop a whole-body physiologically based PK (PBPK) model in PK-Sim(R). The model was evaluated quantitatively with the predicted/observed ratio of the area under the plasma concentration-time curve (AUC), maximum concentration (C-max), and trough concentrations for multiple dosings (C-trough), the geometric mean fold error, as well as visually with the comparison of predicted with observed concentration-time datasets over the full range of recommended intravenous and oral dosing regimens. Results The result of the half maximal inhibitory concentration (IC50) shift assay indicated that voriconazole causes TDI of CYP3A4. The PBPK model evaluation demonstrated a good performance of the model, with 71% of predicted/observed aggregate AUC ratios and all aggregateC(max)ratios from 28 evaluation datasets being within a 0.5- to 2-fold range. For those studies reporting CYP2C19 genotype, 89% of aggregate AUC ratios and all aggregateC(max)ratios were inside a 0.5- to 2-fold range of 44 test datasets. The results of model-based simulations showed that the standard oral maintenance dose of voriconazole 200 mg twice daily would be sufficient for CYP2C19 intermediate metabolizers (IMs; *1/*2, *1/*3, *2/*17, and *2/*2/*17) to reach the tentative therapeutic range of > 1-2 mg/L to <5-6 mg/L forC(trough), while 400 mg twice daily might be more suitable for rapid metabolizers (RMs; *1/*17, *17/*17) and normal metabolizers (NMs; *1/*1). When the model was integrated with independently developed CYP3A4 substrate models (midazolam and alfentanil), the observed AUC change of substrates by voriconazole was inside the 90% confidence interval of the predicted AUC change, indicating that CYP3A4 inhibition was appropriately incorporated into the voriconazole model. Conclusions Both the in vitro assay and model-based simulations support TDI of CYP3A4 by voriconazole as a pivotal characteristic of this drug's PK. The PBPK model developed here could support individual dose adjustment of voriconazole according to genetic polymorphisms of CYP2C19, and DDI risk management. The applicability of modeling results for patients remains to be confirmed in future studies.
  • Övermark, Meri; Koskenmies, Sari; Pitkanen, Sari (2016)
    Squamous cell carcinoma in situ is an intra-epidermal malignancy of the skin with potential to progress to invasive carcinoma. Commonly used treatments are surgical excision, cryotherapy, photodynamic therapy, laser ablation, curettage with cautery, radiotherapy, topical 5-fluorouracil, and topical imiquimod. The efficacies of these different treatment modalities are compared in this retrospective study of 239 patients with squamous cell carcinoma in situ diagnosed and treated at our hospital during a period of 1 year. A total of 263 histologically confirmed in situ lesions were followed up for approximately 8 years. The overall recurrence rate was 6.5%. Surgical excision had the lowest recurrence rate, at 0.8%. Recurrence rates with the less-invasive treatment modalities were markedly higher; cryotherapy 4.7% and photodynamic therapy 18%. Of all recurrences, 65% were carcinoma in situ and 35% squamous cell carcinomas. Twenty-three patients had actinic keratosis in the area treated, but these were not counted as recurrences. In conclusion, excisional surgery is the gold standard treatment for squamous cell carcinoma in situ, although it has limitations. Less invasive methods may sometimes be preferred.
  • Mattila, Kalle E.; Laajala, Teemu D.; Tornberg, Sara V.; Kilpeläinen, Tuomas P.; Vainio, Paula; Ettala, Otto; Bostrom, Peter J.; Nisen, Harry; Elo, Laura L.; Jaakkola, Panu M. (2021)
    After surgery of localized renal cell carcinoma, over 20% of the patients will develop distant metastases. Our aim was to develop an easy-to-use prognostic model for predicting metastasis-free survival after radical or partial nephrectomy of localized clear cell RCC. Model training was performed on 196 patients. Right-censored metastasis-free survival was analysed using LASSO-regularized Cox regression, which identified three key prediction features. The model was validated in an external cohort of 714 patients. 55 (28%) and 134 (19%) patients developed distant metastases during the median postoperative follow-up of 6.3 years (interquartile range 3.4-8.6) and 5.4 years (4.0-7.6) in the training and validation cohort, respectively. Patients were stratified into clinically meaningful risk categories using only three features: tumor size, tumor grade and microvascular invasion, and a representative nomogram and a visual prediction surface were constructed using these features in Cox proportional hazards model. Concordance indices in the training and validation cohorts were 0.755 +/- 0.029 and 0.836 +/- 0.015 for our novel model, which were comparable to the C-indices of the original Leibovich prediction model (0.734 +/- 0.035 and 0.848 +/- 0.017, respectively). Thus, the presented model retains high accuracy while requiring only three features that are routinely collected and widely available.
  • Tirkkonen, Joonas; Hellevuo, Heidi; Olkkola, Klaus T.; Hoppu, Sanna (2016)
    Aim: Aetiology of in-hospital cardiac arrests (IHCAs) on general wards has not been studied. We aimed to determine the underlying causes for IHCAs by the means of autopsy records and clinical judgement of the treating consultants. Furthermore, we investigated whether aetiology and preceding vital dysfunctions are associated with long-term survival. Design and setting: Prospective observational study between 2009-2011 including 279 adult IHCA patients attended by medical emergency team in a Finnish university hospital's general wards. Results: The median age of the patients was 72 (64, 80) years, 185 (66%) were male, 178 (64%) of events were monitored/witnessed, first rhythm was shockable in 42 (15%) cases and 53 (19%) patients survived six months. Aetiology was determined as cardiac in 141 events, 73 of which were due to acute myocardial infarction. There were 138 non-cardiac IHCAs; most common causes were pneumonia (39) and exsanguination (16). No statistical difference was observed in the incidence of objective vital dysfunctions preceding the event between the cardiac and non-cardiac groups (40% vs. 44%, p = 0.448). Subjective antecedents were more common in the cardiac cohort (47% vs. 32%, p = 0.022), chest pain being an example (11% vs. 0.7%, p <0.001). Reviewing all 279 IHCAs, only shockable primary rhythm, monitored/witnessed event and low comorbidity score were independently associated with 180-day survival. Conclusions: Cardiac aetiology underlies half of the IHCAs on general wards. Both objective and subjective antecedents are common. However, neither the cardiac aetiology nor the absence of preceding deterioration of vital signs were factors independently associated with a favourable outcome. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Mobile Airways Sentinel Network M; Bousquet, Jean; Hellings, Peter W.; Agache, Ioana; Haahtela, T.; Toppila-Salmi, S.; Kuitunen, M.; Valovirta, E.; Salimäki, Johanna; Vasankari, Tuula; Eklund, P.; Karjalainen, J.; Zuberbier, Torsten (2019)
    Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
  • Dimitri, Paul; Fernandez-Luque, Luis; Banerjee, Indraneel; Bergada, Ignacio; Calliari, Luis Eduardo; Dahlgren, Jovanna; de Arriba, Antonio; Lapatto, Risto; Reinehr, Thomas; Senniappan, Senthil; Thomas-Teinturier, Cecile; Tsai, Meng-Che; Zaini, Azriyanti Anuar; Bagha, Merat; Koledova, Ekaterina (2021)
    Background: The use of technology to support health and health care has grown rapidly in the last decade across all ages and medical specialties. Newly developed eHealth tools are being implemented in long-term management of growth failure in children, a low prevalence pediatric endocrine disorder. Objective: Our objective was to create a framework that can guide future implementation and research on the use of eHealth tools to support patients with growth disorders who require growth hormone therapy. Methods: A total of 12 pediatric endocrinologists with experience in eHealth, from a wide geographical distribution, participated in a series of online discussions. We summarized the discussions of 3 workshops, conducted during 2020, on the use of eHealth in the management of growth disorders, which were structured to provide insights on existing challenges, opportunities, and solutions for the implementation of eHealth tools across the patient journey, from referral to the end of pediatric therapy. Results: A total of 815 responses were collected from 2 questionnaire-based activities covering referral and diagnosis of growth disorders, and subsequent growth hormone therapy stages of the patient pathway, relating to physicians, nurses, and patients, parents, or caregivers. We mapped the feedback from those discussions into a framework that we developed as a guide to integration of eHealth tools across the patient journey. Responses focused on improved clinical management, such as growth monitoring and automation of referral for early detection of growth disorders, which could trigger rapid evaluation and diagnosis. Patient support included the use of eHealth for enhanced patient and caregiver communication, better access to educational opportunities, and enhanced medical and psychological support during growth hormone therapy management. Given the potential availability of patient data from connected devices, artificial intelligence can be used to predict adherence and personalize patient support. Providing evidence to demonstrate the value and utility of eHealth tools will ensure that these tools are widely accepted, trusted, and used in clinical practice, but implementation issues (eg, adaptation to specific clinical settings) must be addressed. Conclusions: The use of eHealth in growth hormone therapy has major potential to improve the management of growth disorders along the patient journey. Combining objective clinical information and patient adherence data is vital in supporting decision-making and the development of new eHealth tools. Involvement of clinicians and patients in the process of integrating such technologies into clinical practice is essential for implementation and developing evidence that eHealth tools can provide value across the patient pathway.
  • Lek, Monkol; Karczewski, Konrad J.; Minikel, Eric V.; Samocha, Kaitlin E.; Banks, Eric; Fennell, Timothy; O'Donnell-Luria, Anne H.; Ware, James S.; Hill, Andrew J.; Cummings, Beryl B.; Tukiainen, Taru; Birnbaum, Daniel P.; Kosmicki, Jack A.; Duncan, Laramie E.; Estrada, Karol; Zhao, Fengmei; Zou, James; Pierce-Hollman, Emma; Berghout, Joanne; Cooper, David N.; Deflaux, Nicole; DePristo, Mark; Do, Ron; Flannick, Jason; Fromer, Menachem; Gauthier, Laura; Goldstein, Jackie; Gupta, Namrata; Howrigan, Daniel; Kiezun, Adam; Kurki, Mitja I.; Moonshine, Ami Levy; Natarajan, Pradeep; Orozeo, Lorena; Peloso, Gina M.; Poplin, Ryan; Rivas, Manuel A.; Ruano-Rubio, Valentin; Rose, Samuel A.; Ruderfer, Douglas M.; Shakir, Khalid; Stenson, Peter D.; Stevens, Christine; Thomas, Brett P.; Tiao, Grace; Tusie-Luna, Maria T.; Weisburd, Ben; Palotie, Aarno; Tuomilehto, Jaakko; Daly, Mark J.; Exome Aggregation Consortium (2016)
    Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.
  • INOSS Collaboration; McCall, S. J.; Bonnet, M-P; Äyräs, O.; Knight, M. (2020)
    Anaphylaxis in pregnancy is a rare but severe complication for both mother and infant. Population-based data on anaphylaxis in pregnancy are lacking from mainland European countries. This multinational study presents the incidence, causative agents, management and maternal and infant outcomes of anaphylaxis in pregnancy. This descriptive multinational study used a combination of retrospective (Finnish medical registries) and prospective population-based studies (UK, France, Belgium and the Netherlands) to identify cases of anaphylaxis. Sixty-five cases were identified among 4,446,120 maternities (1.5 per 100,000 maternities; 95%CI 1.1-1.9). The incidence did not vary between countries. Approximately three-quarters of reactions occurred at the time of delivery. The most common causes were antibiotics in 27 women (43%), and anaesthetic agents in 11 women (17%; including neuromuscular blocking drugs, 7), which varied between countries. Anaphylaxis had very poor outcomes for one in seven mothers and one in seven babies; the maternal case fatality rate was 3.2% (95%CI 0.4-11.0) and the neonatal encephalopathy rate was 14.3% (95%CI 4.8-30.3). Across Europe, anaphylaxis related to pregnancy is rare despite having a multitude of causative agents and different antibiotic prophylaxis protocols.
  • Sillanpaa, Heidi; Skogman, Barbro H.; Sarvas, Heikki; Seppala, Ilkka J. T.; Lahdenne, Pekka (2014)
  • Sihvonen, Raine; Paavola, Mika; Malmivaara, Antti; Itälä, Ari; Joukainen, Antti; Nurmi, Heikki; Kalske, Juha; Ikonen, Anna; Järvelä, Timo; Järvinen, Tero A. H.; Kanto, Kari; Karhunen, Janne; Knifsund, Jani; Kröger, Heikki; Kääriäinen, Tommi; Lehtinen, Janne; Nyrhinen, Jukka; Paloneva, Juha; Päiväniemi, Outi; Raivio, Marko; Sahlman, Janne; Sarvilinna, Roope; Tukiainen, Sikri; Välimäki, Ville-Valtteri; Äärimaa, Ville; Toivonen, Pirjo; Järvinen, Teppo L. N.; FIDELITY Finnish Degenerative (2018)
    Objective To assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus. Methods In this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35-65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out. Results In the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, -4.3; 95% CI, -11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (-3.2; -8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (-0.4; -1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups. Conclusions In this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.
  • Öhman, Jonas; Harjola, Veli-Pekka; Karjalainen, Pasi; Lassus, Johan (2018)
    Background: It is unclear how to optimally monitor acute heart failure (AHF) patients. We evaluated the timely interplay of cardiac filling pressures, brain natriuretic peptides (BNPs), lung ultrasound (LUS) and symptoms during AHF treatment. Methods: We enrolled 60 patients who had been hospitalised for AHF. Patients were examined with a rapid cardiothoracic ultrasound (CaTUS) protocol, combining LUS and focused echocardiographic evaluation of cardiac filling pressures (i.e. medial E/e' and inferior vena cava index [IVCi]). CaTUS was done at 0, 12, 24 and 48 hours (3 hours) and on the day of discharge, alongside clinical evaluation and laboratory samples. Patients free of congestion (Blines or pleural fluid) on LUS at discharge were categorised as responders, whereas the rest were categorised as non-responders. Improvement in congestion parameters was evaluated separately in these groups. The effect of congestion parameters on prognosis was also analysed. Results: Responders experienced a significantly larger decline in E/e' (2.58 vs. 0.38, p=0.037) and dyspnoea visual analogue scale (1-10) score (7.68 vs. 3.57, p=0.007) during the first 12 hours of treatment, while IVCi and BNPs declined later without no such rapid initial decline. Among patients experiencing a >3 U decline in E/e' during the first 12 hours of treatment, 18/21 were to become responders (p Conclusion: E/e' seemed like the most useful congestion parameter for monitoring early treatment response, predicting prognostically beneficial resolution of pulmonary congestion.
  • Jokelainen, Jarno; Mustonen, Harri; Kylänpää, Leena; Udd, Marianne; Lindström, Outi; Pöyhiä, Reino (2018)
    Background and aims: There is no consensus on how to assess the depth of sedation for endoscopic retrograde cholangiopancreatography (ERCP). This study was carried out in order to evaluate different methods of assessment of depth of sedation: bispectral index (BiS), modified Richmond Agitation/Sedation Scale (mRASS), modified Ramsay Sedation Scale (mRSS) and modified Observer Assessment of Alertness and Sedation (mOAAS) and their applicability to clinical practice.Methods: Two hundred patients were recruited. Sedation was given by standard clinical practice using propofol sedation or patient controlled sedation. Sedation was assessed on all patients using the above-mentioned methods. BiS was considered the reference point for sedation scales. Cronbach's alpha was calculated to determine the consistency of different scales in respect to each other and prediction probability and Spearman's correlation coefficients of sedation scales were calculated to show the relationship between sedation scales and BiS.Results: All scales showed high reliability with overall Cronbach's alpha 0.943. Dropping scales suggested better consistency between mOAAS, mRSS and mRASS than with BiS. Spearman's correlation and prediction probability showed similar results with all tested scales: mOAAS (0.695, 0.739), mRSS (0.673, 0.735), mRASS (0.683, 0.738), p
  • GREAT Global Res Acute Conditions; INI-CRCT Invest Network Initiative; Legrand, Matthieu; Lassus, Johan; Harjola, Veli-Pekka (2018)
    Background The interaction between chronic medications on admission and the association between serum potassium level and outcome in patients with acute heart failure (AHF) are unknown. Methods Observational intercontinental study of patients admitted with AHF. 15954 patients were included from 12 cohorts in 4 continents. Main outcome was 90-day mortality. Clinical presentation (medication use, hemodynamics, comorbidities), demographic, echocardiographic, and biochemical data on admission were recorded prospectively in each cohort, with prospective adjudication of outcomes. Results Positive and negative linear relationships between 90-day mortality and sK+ above 4.5 mmol/L (hyperkalemia) and below 3.5 mmol/L (hypo-kalemia) were observed. Hazard ratio for death was 1.46 [1.34-1.58] for hyperkalemia and 1.22 [1.06-1.40] for hypokalemia. In a fully adjusted model, only hyperkalemia remained associated with mortality (HR 1.03 [1.02-1.04] for each 0.1 mmol/l change of sK+ above 4.5 mmol/L). Interaction tests revealed that the association between hyperkalemia and outcome was significantly affected by chronic medications. The association between hyperkalemia and mortality was absent for patients treated with beta blockers and in those with preserved renal function. Conclusions In patients with AHF, sK+ > 4.5 mmol/L appears to be associated with 90-day mortality. B-blockers have potentially a protective effect in the setting of hyperkalemia.
  • FINNAKI Study Grp (2019)
    Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p <0.001) and IL-6 increased (p <0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p <0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI(>12 h)). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI(>12 h) with OR (95% CI) of 12.71 (2.96-54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31-3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29-23.57], p <0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44-4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67-11.79; p <0.001) for 90-day mortality. Conclusions VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality.
  • Pekkarinen, Pirkka T.; Bäcklund, Minna; Efendijev, Ilmar; Raj, Rahul; Folger, Daniel; Litonius, Erik; Laitio, Ruut; Bendel, Stepani; Hoppu, Sanna; Ala-Kokko, Tero; Reinikainen, Matti; Skrifvars, Markus B. (2019)
    BackgroundOrgan dysfunction is common after cardiac arrest and associated with worse short-term outcome, but its impact on long-term outcome and treatment costs is unknown.MethodsWe used nationwide registry data from the intensive care units (ICU) of the five Finnish university hospitals to evaluate the association of 24-h extracerebral Sequential Organ Failure Assessment (24h-EC-SOFA) score with 1-year survival and healthcare-associated costs after cardiac arrest. We included adult cardiac arrest patients treated in the participating ICUs between January 1, 2003, and December 31, 2013. We acquired the confirmed date of death from the Finnish Population Register Centre database and gross 1-year healthcare-associated costs from the hospital billing records and the database of the Finnish Social Insurance Institution.ResultsA total of 5814 patients were included in the study, and 2401 were alive 1year after cardiac arrest. Median (interquartile range (IQR)) 24h-EC-SOFA score was 6 (5-8) in 1-year survivors and 7 (5-10) in non-survivors. In multivariate regression analysis, adjusting for age and prior independency in self-care, the 24h-EC-SOFA score had an odds ratio (OR) of 1.16 (95% confidence interval (CI) 1.14-1.18) per point for 1-year mortality.Median (IQR) healthcare-associated costs in the year after cardiac arrest were Euro47,000 (Euro28,000-75,000) in 1-year survivors and Euro12,000 (Euro6600-25,000) in non-survivors. In a multivariate linear regression model adjusting for age and prior independency in self-care, an increase of one point in the 24h-EC-SOFA score was associated with an increase of Euro170 (95% CI Euro150-190) in the cost per day alive in the year after cardiac arrest. In the same model, an increase of one point in the 24h-EC-SOFA score was associated with an increase of Euro4400 (95% CI Euro3300-5500) in the total healthcare-associated costs in 1-year survivors.ConclusionsExtracerebral organ dysfunction is associated with long-term outcome and gross healthcare-associated costs of ICU-treated cardiac arrest patients. It should be considered when assessing interventions to improve outcomes and optimize the use of resources in these patients.
  • German HNPCC Consortium; Dutch Lynch Syndrome Collaborative; Finnish Lynch Syndrome Registry; Engel, Christoph; Ahadova, Aysel; Seppälä, Toni T.; Lepistö, Anna; Renkonen-Sinisalo, Laura; Vasen, Hans F. (2020)
    BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P <.001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.
  • Bensch, Frank; Varjonen, Elina A.; Pyhältö, Tuomo T.; Koskinen, Seppo K. (2019)
    Purpose BCVI may lead to ischemic stroke, disability, and death, while being often initially clinically silent. Screening criteria for BCVI based on clinical findings and trauma mechanism have improved detection, with Denver criteria being most common. Up to 30% of patients do not meet BCVI screening criteria. The aim of this study was to analyze the effect of augmented Denver criteria on detection, and to determine the relative risk for ischemic stroke. Methods Denver screening criteria were augmented by any high-energy trauma of the cervical spine, thorax, abdomen, or pelvis. All acute blunt trauma WBCT including CT angiography (CTA) over a period of 38 months were reviewed retrospectively by two Fellowship-trained radiologists, as well as any cerebral imaging after the initial trauma. Results 1544 WBCT studies included 374 CTA (m/f = 271/103; mean age 41.5 years). Most common mechanisms of injury were MVA (51.5%) and fall from a height (22.3%). We found 72 BCVI in 56 patients (15.0%), with 13 (23.2%) multiple lesions. The ICA was affected in 49 (68.1%) and the vertebral artery in 23 (31.9%) of cases. The most common injury level was C2, with Biffl grades I and II most common in ICA, and II and IV in VA. Interobserver agreement was substantial (Kappa = 0.674). Of 215 patients imaged, 16.1% with BCVI and 1.9% of the remaining cases had cerebral ischemic stroke (p <.0001; OR = 9.77; 95% CI 3.3-28.7). Eleven percent of patients with BCVI would not have met standard screening criteria. Conclusions The increase in detection rate for BCVI justifies more liberal screening protocols.