Browsing by Subject "GUIDELINES"

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  • 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.
  • Andersen-Ranberg, Nina; Poulsen, Lone M.; Perner, Anders; Hästbacka, Johanna; Morgan, Matthew P. G.; Citerio, Giuseppe; Oxenboll-Collet, Marie; Weber, Sven-Olaf; Andreasen, Anne Sofie; Bestle, Morten H.; Uslu, Bulent; Pedersen, Helle B. S.; Nielsen, Louise G.; Damgaard, Kjeld; Jensen, Troels B.; Sommer, Trine; Dey, Nilanjan; Mathiesen, Ole; Granholm, Anders (2022)
    Background Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. Methods This protocol describes the secondary, pre-planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID-ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile-based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. Discussion The results of this secondary, pre-planned Bayesian analysis will complement the primary frequentist analysis of the AID-ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.
  • Sousa-Pinto, Bernardo; Azevedo, Luis Filipe; Sa-Sousa, Ana; Vieira, Rafael Jose; Amaral, Rita; Klimek, Ludger; Czarlewski, Wienczyslawa; Anto, Josep M.; Bedbrook, Anna; Kvedariene, Violeta; Ventura, Maria Teresa; Ansotegui, Ignacio J.; Bergmann, Karl-Christian; Brussino, Luisa; Canonica, G. Walter; Cardona, Victoria; Carreiro-Martins, Pedro; Casale, Thomas; Cecchi, Lorenzo; Chivato, Tomas; Chu, Derek K.; Cingi, Cemal; Costa, Elisio M.; Cruz, Alvaro A.; De Feo, Giulia; Devillier, Philippe; Fokkens, Wytske J.; Gaga, Mina; Gemicioglu, Bilun; Haahtela, Tari; Ivancevich, Juan Carlos; Ispayeva, Zhanat; Jutel, Marek; Kuna, Piotr; Kaidashev, Igor; Kraxner, Helga; Larenas-Linnemann, Desiree E.; Laune, Daniel; Lipworth, Brian; Louis, Renaud; Makris, Michael; Monti, Riccardo; Morais-Almeida, Mario; Moesges, Ralph; Mullol, Joaquim; Odemyr, Mikaela; Okamoto, Yoshitaka; Papadopoulos, Nikolaos G.; Patella, Vincenzo; Nhan Pham-Thi; Regateiro, Frederico S.; Reitsma, Sietze; Rouadi, Philip W.; Samolinski, Boleslaw; Sova, Milan; Todo-Bom, Ana; Taborda-Barata, Luis; Tomazic, Peter Valentin; Toppila-Salmi, Sanna; Sastre, Joaquin; Tsiligianni, Ioanna; Valiulis, Arunas; Wallace, Dana; Waserman, Susan; Yorgancioglu, Arzu; Zidarn, Mihaela; Zuberbier, Torsten; Fonseca, Joao Almeida; Bousquet, Jean; Pfaar, Oliver (2022)
    Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air(R) app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK-air(R) data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales-VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season. Results We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT-tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = -12.1;-2.8), lower VAS Work (average difference = 5.0; 95%CrI = -8.5;-1.5), and a lower CSMS (average difference = 3.7; 95%CrI = -9.3;2.2). When compared to SCIT, SLIT-tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = -17.2;-2.8), lower VAS Work (average difference = 7.8; 95%CrI = -15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = -18.5;0.2). Conclusion In patients with grass pollen allergy, SLIT-tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally-harmonised standards for performing and reporting real-world data in AIT are needed to better understand its 'real-world' effectiveness.
  • 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.
  • Heinonen, Kari; Puolakka, Tuukka; Salmi, Heli; Boyd, James; Laiho, Mia; Porthan, Kari; Harve-Rytsälä, Heini; Kuisma, Markku (2022)
    Background Ambulance patients are usually transported to the hospital in the emergency medical service (EMS) system. The aim of this study was to describe the non-conveyance practice in the Helsinki EMS system and to report mortality following non-conveyance decisions. Methods All prehospital patients >= 16 years attended by the EMS but not transported to a hospital during 2013-2017 were included in the study. EMS mission- and patient-related factors were collected and examined in relation to patient death within 30 days of the EMS non-conveyance decision. Results The EMS performed 324,207 missions with a patient during the study period. The patient was not transported in 95,909 (29.6%) missions; 72,233 missions met the study criteria. The patient mean age (standard deviation) was 59.5 (22.5) years; 55.5% of patients were female. The most common dispatch codes were malaise (15.0%), suspected decline in vital signs (14.0%), and falling over (12.9%). A total of 960 (1.3%) patients died within 30 days after the non-conveyance decision. Multivariate logistic regression analysis revealed that mortality was associated with the patient's inability to walk (odds ratio 3.19, 95% confidence interval 2.67-3.80), ambulance dispatch due to shortness of breath (2.73, 2.27-3.27), decreased level of consciousness (2.72, 1.75-4.10), decreased blood oxygen saturation (2.64, 2.27-3.06), and abnormal systolic blood pressure (2.48, 1.79-3.37). Conclusion One-third of EMS missions did not result in patient transport to the hospital. Thirty-day mortality was 1.3%. Abnormalities in multiple respiratory-related vital signs were associated with an increased likelihood of death within 30 days.
  • 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.
  • Violette, Philippe D.; Vernooij, Robin W. M.; Aoki, Yoshitaka; Agarwal, Arnav; Cartwright, Rufus; Arai, Yoichi; Tailly, Thomas; Novara, Giacomo; Baldeh, Tejan; Craigie, Samantha; Breau, Rodney H; Guyatt, Gordon H.; Tikkinen, Kari (2021)
    Background: The use of perioperative thromboprophylaxis in urological surgery is common but not standardized. Objective: To characterize international practice variation in thromboprophylaxis use in urological surgery. Design, setting, and participants: We conducted a scenario-based survey addressing the use of mechanical and pharmacological thromboprophylaxis in urological cancer procedures (radical cystectomy [RC], radical prostatectomy [RP], and radical nephrectomy [RN]) among practicing urologists in Canada, Finland, and Japan. The survey presented patient profiles reflecting a spectrum of risk for venous thromboembolism; the respondents described their clinical practice. Outcome measurements and statistical analysis: The proportion of respondents who routinely used (1) mechanical, (2) pharmacological, and (3) extended pharmacological prophylaxis was stratified by procedure. A logistic regression identified characteristics associated with thromboprophylaxis use. Results and limitations: Of 1051 urologists contacted, 570 (54%) participated in the survey. Japanese urologists were less likely to prescribe pharmacological prophylaxis than Canadian or Finnish urologists (p < 0.001 for all procedures). Canadian and Finnish urologists exhibited large variation for extended pharmacological prophylaxis for RP and RN. Finnish urologists were most likely to prescribe extended prophylaxis versus Canadian and Japanese urologists (RC 98%, 84%, and 26%; Open RP 25%, 8%, and 3%; robotic RP 11%, 9%, and 0%; and RN 43%, 7%, and 1%, respectively; p < 0.001 for each procedure). Less variation was found regarding the prescription of mechanical prophylaxis, which was most commonly used until ambulation or discharge. The length of hospital stay was longer in Japan and may bias estimates of extended prophylaxis in Japan.
  • 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.
  • Johansson, Katarina; Mustonen, Harri; Seppänen, Hanna; Lehtimäki, Tiina E. (2022)
    Background No previous studies have examined the possible relationship between intraductal papillary mucinous neoplasm (IPMN) and the developmental ductal variations of the pancreas, such as an ansa pancreatica and a meandering main pancreatic duct (MMPD). Methods This retrospective cross-sectional study enrolled 214 patients, 108 with IPMN disease and 106 subjects from a community at the tertiary care unit. The main pancreatic duct (MPD) was evaluated in the head of the pancreas by its course, which were non-MMPD: descending, vertical, and sigmoid, or MMPD including loop types, reverse-Z subtypes, and an N-shape, which was identified for the first time in this study. IPMN patients were also evaluated for worrisome features (WF) or high-risk stigmata (HRS), and the extent of IPMN cysts. Results Among IPMN patients, 18.4% had MMPD, which we observed in only 3.0% of the control group (P < 0.001). Patients with MMPD were more likely to belong to the IPMN group compared with non-MMPD patients [odds ratio (OR) 6.4, 95% confidence interval (CI) 2.2-24.9]. Compared with a descending shape MPD, IPMN patients with an N-shaped MPD were more likely to have a cystic mural nodule (OR 5.9, 95% CI 1.02-36.0). The presence of ansa pancreatica associated with more extent IPMN disease (OR 12.8, 95% CI 2.6-127.7). Conclusions IPMN patients exhibited an MMPD more often than control patients. Ansa pancreatica associated with multiple cysts. Furthermore, an N-shape in IPMN patients associated with cystic mural nodules, suggesting that this shape serves as a risk factor for more severe IPMN.
  • Sillanpaa, Heidi; Skogman, Barbro H.; Sarvas, Heikki; Seppala, Ilkka J. T.; Lahdenne, Pekka (2014)
  • Harve-Rytsälä, Heini; Ångerman, Susanne; Kirves, Hetti; Nurmi, Jouni (2021)
    Background Normoventilation is crucial for many critically ill patients. Ventilation is routinely guided by end-tidal capnography during prehospital anaesthesia, based on the assumption of the gap between arterial partial pressure of carbon dioxide (PaCO2) and end-tidal carbon dioxide partial pressure (PetCO(2)) of approximately 0.5 kPa (3.8 mmHg). Methods We retrospectively analysed the airway registry and patient chart data of patients who had been anaesthetised and intubated endotracheally by the prehospital critical care team and had their prehospital arterial blood gases analysed. Bland-Altman analysis was used to estimate the bias and limits of agreement. Results Altogether 502 patients were included in the study, with a median age of 58 years. The most common patient groups were post-resuscitation (155, 31%), neurological emergencies (96, 19%), intoxication (75, 15%) and trauma (68, 14%). The median of the gap between PaCO2 and PetCO(2) was 1.3 kPa (interquartile range 0.7 to 2.2) (9.8 (5.3-16.5) mmHg). Mean bias of PetCO(2) was -1.6 kPa/12.0 mmHg (standard deviation 1.7 kPa/12.8 mmHg) with 95% confidence limits of agreement -4.9 to 1.9 kPa (-36.8 to 14.3 mmHg). The gap was >= 1.0 kPa (>7.5 mmHg) in 297 (66%, 95% confidence interval 55 to 63) patients. Conclusion Our results suggest that end-tidal capnography alone might not be an adequate method to achieve normoventilation for critically ill patients intubated and mechanically ventilated in prehospital setting. Thus, an arterial blood gas analysis might be useful to recognize patients with an increased gap between PaCO2 and PetCO(2).
  • 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.