Browsing by Subject "PROPHYLAXIS"

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  • 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.
  • Bos, Nick; Kankaanpää-Kukkonen, Viljami; Freitak, Dalial; Stucki, Dimitri; Sundström, Liselotte (2019)
    Eusocial insects, such as ants, have access to complex disease defenses both at the individual, and at the colony level. However, different species may be exposed to different diseases, and/or deploy different methods of coping with disease. Here, we studied and compared survival after fungal exposure in 12 species of ants, all of which inhabit similar habitats. We exposed the ants to two entomopathogenic fungi (Beauveria bassiana and Metarhizium brunneum), and measured how exposure to these fungi influenced survival. We furthermore recorded hygienic behaviors, such as autogrooming, allogrooming and trophallaxis, during the days after exposure. We found strong differences in autogrooming behavior between the species, but none of the study species performed extensive allogrooming or trophallaxis under the experimental conditions. Furthermore, we discuss the possible importance of the metapleural gland, and how the secondary loss of this gland in the genus Camponotus could favor a stronger behavioral response against pathogen threats.
  • Moller, Morten Hylander; Skrifvars, Markus B.; Azoulay, Elie (2017)
  • Duivenvoorden, Wilhelmina C. M.; Daneshmand, Siamak; Canter, Daniel; Lotan, Yair; Black, Peter C.; Abdi, Hamidreza; van Rhijn, Bas W. G.; van de Putte, Elisabeth E. Fransen; Zareba, Piotr; Koskinen, Ilmari; Kassouf, Wassim; Traboulsi, Samer L.; Kukreja, Janet E.; Bostrom, Peter J.; Shayegan, Bobby; Pinthus, Jehonathan H. (2016)
    Purpose: Neoadjuvant chemotherapy and pelvic surgery are significant risk factors for thromboembolic events. Our study objectives were to investigate the timing, incidence and characteristics of thromboembolic events during and after neoadjuvant chemotherapy and subsequent radical cystectomy in patients with muscle invasive bladder cancer. Materials and Methods: We performed a multi-institutional retrospective analysis of 761 patients who underwent neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer from 2002 to 2014. Median followup from diagnosis was 21.4 months (range 3 to 272). Patient characteristics included the Khorana score, and the incidence and timing of thromboembolic events (before vs after radical cystectomy). Survival was calculated using the Kaplan-Meier method. The log rank test and multivariable Cox proportional hazards regression were used to compare survival between patients with vs without thromboembolic events. Results: The Khorana score indicated an intermediate thromboembolic event risk in 88% of patients. The overall incidence of thromboembolic events in patients undergoing neoadjuvant chemotherapy was 14% with a wide variation of 5% to 32% among institutions. Patients with thromboembolic events were older (67.6 vs 64.6 years, p = 0.02) and received a longer neoadjuvant chemotherapy course (10.9 vs 9.7 weeks, p = 0.01) compared to patients without a thromboembolic event. Of the thromboembolic events 58% developed preoperatively and 72% were symptomatic. On multivariable regression analysis the development of a thromboembolic event was not significantly associated with decreased overall survival. However, pathological stage and a high Khorana score were adverse risk factors for overall survival. Conclusions: Thromboembolic events are common in patients with muscle invasive bladder cancer who undergo neoadjuvant chemotherapy before and after radical cystectomy. Our results suggest that a prospective trial of thromboembolic event prophylaxis during neoadjuvant chemotherapy is warranted.
  • Pirilä, Satu Maaria; Taskinen, Mervi; Viljakainen, Heli; Kajosaari, Merja; Turanlahti, Maila; Saarinen-Pihkala, Ulla M.; Mäkitie, Outi (2011)
  • Tapaninen, Tuija; Olkkola, Aleksi M.; Tornio, Aleksi; Neuvonen, Mikko; Elonen, Erkki; Neuvonen, Pertti J.; Niemi, Mikko; Backman, Janne T. (2020)
    The oral bioavailability of ibrutinib is low and variable, mainly due to extensive first-pass metabolism by cytochrome P450 (CYP) 3A4. The unpredictable exposure can compromise its safe and effective dosing. We examined the impact of itraconazole on ibrutinib pharmacokinetics. In a randomized crossover study, 11 healthy subjects were administered itraconazole 200 mg or placebo twice on day 1, and once on days 2-4. On day 3, 1 hour after itraconazole (placebo) and breakfast, ibrutinib (140 mg during placebo; 15 mg during itraconazole) was administered. Itraconazole increased the dose-adjusted geometric mean area under the concentration-time curve from zero to infinity (AUC(0-infinity)) of ibrutinib 10.0-fold (90% confidence interval (CI) 7.2-13.9; P <0.001) and peak plasma concentration (C-max) 8.8-fold (90% CI 6.3-12.1; P <0.001). During itraconazole, the intersubject variation for the AUC(0-infinity) (55%) and C-max (53%) was around half of that during placebo (104%; 99%). In conclusion, itraconazole markedly increases ibrutinib bioavailability and decreases its interindividual variability, offering a possibility to improved dosing accuracy and cost savings.
  • Vähämurto, Pauli; Pollari, Marjukka; Clausen, Michael R.; d'Amore, Francesco; Leppä, Sirpa; Mannisto, Susanna (2020)
    Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267-3.086,p= 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175-0.757,p= 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.
  • Brissot, Eolia; Labopin, Myriam; Moiseev, Ian; Cornelissen, J. J.; Meijer, Ellen; Van Gorkom, Gwendolyn; Rovira, Montserrat; Ciceri, Fabio; Griskevicius, Laimonas; Blaise, Didier; Forcade, Edouard; Mistrik, Martin; Mielke, Stephan; Bulabois, Claude Eric; Niittyvuopio, Riitta; Deconinck, Eric; Ruggeri, Annalisa; Sanz, Jaime; Spyridonidis, Alexandros; Savani, Bipin; Giebel, Sebastian; Nagler, Arnon; Mohty, Mohamad (2020)
    Background Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. Methods Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis Results No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. Conclusion These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.
  • Tikkinen, Kari A. O.; Craigie, Samantha; Agarwal, Arnav; Violette, Philippe D.; Novara, Giacomo; Cartwright, Rufus; Naspro, Richard; Siemieniuk, Reed A. C.; Ali, Bassel; Eryuzlu, Leyla; Geraci, Johanna; Winkup, Judi; Yoo, Daniel; Gould, Michael K.; Sandset, Per Morten; Guyatt, Gordon H. (2018)
    Context: Pharmacological thromboprophylaxis involves balancing a lower risk of venous thromboembolism (VTE) against a higher risk of bleeding, a trade-off that critically depends on the risks of VTE and bleeding in the absence of prophylaxis (baseline risk). Objective: To provide estimates of the baseline risk of symptomatic VTE and bleeding requiring reoperation in urological cancer surgery. Evidence acquisition: We identified contemporary observational studies reporting symptomatic VTE or bleeding after urological procedures. We used studies with the lowest risk of bias and accounted for use of thromboprophylaxis and length of follow-up to derive best estimates of the baseline risks within 4wk of surgery. We used the GRADE approach to assess the quality of the evidence. Evidence synthesis: We included 71 studies reporting on 14 urological cancer procedures. The quality of the evidence was generally moderate for prostatectomy and cystectomy, and low or very low for other procedures. The duration of thromboprophylaxis was highly variable. The risk of VTE in cystectomies was high (2.6-11.6% across risk groups) whereas the risk of bleeding was low (0.3%). The risk of VTE in prostatectomies varied by procedure, from 0.2-0.9% in robotic prostatectomy without pelvic lymph node dissection (PLND) to 3.9-15.7% in open prostatectomy with extended PLND. The risk of bleeding was 0.1-1.0%. The risk of VTE following renal procedures was 0.7-2.9% for low-risk patients and 2.6-11.6% for high-risk patients; the risk of bleeding was 0.1-2.0%. Conclusions: Extended thromboprophylaxis is warranted in some procedures (eg, open and robotic cystectomy) but not others (eg, robotic prostatectomy without PLND in low-risk patients). For "close call'' procedures, decisions will depend on values and preferences with regard to VTE and bleeding. Patient summary: Clinicians often give blood thinners to patients to prevent blood clots after surgery for urological cancer. Unfortunately, blood thinners also increase bleeding. This study provides information on the risk of clots and bleeding that is crucial in deciding for or against giving blood thinners. (C) 2017 European Association of Urology. Published by Elsevier B.V.
  • Peippo, Maija Helena; Kurki, Samu; Lassila, Riitta; Carpen, Olli Mikael (2018)
    Background The incidence of venous thromboembolism (VTE) is 1-2/1000 individuals. Patients with cancer, especially during chemotherapy, are at enhanced risk, but real-world data on factors associated with VTE events are still scarce. Aim The aim of this retrospective study was to survey the incidence of VTE based on a large hospital database, and to identify comorbidities and features associated with VTE events. We focused on cancer-related VTE events and on factors indicating increased VTE risk during chemotherapy. Methods The cohort included patients treated at Turku University Hospital during years 2005-2013. Health information was derived and analysed from multiple electronic databases. The diagnoses of VTE and all comorbidities, including type of cancer, were based on International Classification of Diseases 10th Revision coding. For further analysis, we focused on 16 common types of cancers treated with chemotherapy. Age, gender, surgery, radiotherapy, distant metastasis, available laboratory values and platinum-based chemotherapy were evaluated for VTE group, and associations were estimated by Cox regression analyses. Results The entire database contained information from 495 089 patients, of whom 5452 (1.1%) had a VTE diagnosis. Among individuals with VTE, 1437 (26.4%) had diagnosis of coronary heart disease and 1467 (26.9%) had cancer diagnosis. Among 7778 patients with cancer treated with chemotherapy, 282 (3.6%) had a VTE, platinum-based chemotherapy being a major risk factor (HR 1.77, 95% CI 1.40 to 2.24, p3.25x10(9) cells/L, HR 1.96, 95% CI 1.33 to 2.89, p62.5 mu mol/L; HR 1.60, 95% CI 1.21 to 2.13, p=0.001) values were independent indicators of increased VTE risk during chemotherapy. Conclusions Longitudinal electronic health record analysis provides a powerful tool to gather meaningful real-world information to study clinical associations, like comorbidities, and to identify markers associated with VTE. The combination of various clinical and laboratory variables could be used for VTE risk evaluation and targeted prevention.
  • Ifversen, Marianne; Meisel, Roland; Sedlacek, Petr; Kalwak, Krzysztof; Sisinni, Luisa; Hutt, Daphna; Lehrnbecher, Thomas; Balduzzi, Adriana; Diesch, Tamara; Jarisch, Andrea; Gungor, Tayfun; Stein, Jerry; Yaniv, Isaac; Bonig, Halvard; Kuhlen, Michaela; Ansari, Marc; Nava, Tiago; Dalle, Jean-Hugues; Diaz-de-Heredia, Cristina; Trigoso, Eugenia; Falkenberg, Ulrike; Hartmann, Mihaela; Deiana, Marco; Canesi, Marta; Broggi, Chiara; Bertaina, Alice; Gibson, Brenda; Krivan, Gergely; Vettenranta, Kim; Matic, Toni; Buechner, Jochen; Lawitschka, Anita; Peters, Christina; Yesilipek, Akif; Yalcin, Koray; Lucchini, Giovanna; Bakhtiar, Shahrzad; Turkiewicz, Dominik; Niinimaki, Riitta; Wachowiak, Jacek; Cesaro, Simone; Dalissier, Arnaud; Corbacioglu, Selim; Willasch, Andre Manfred; Bader, Peter (2021)
    Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.
  • Skrifvars, Markus; Bailey, Michael; Presneill, Jeffrey; French, Craig; Nichol, Alistair; Little, Lorraine; Duranteau, Jacques; Huet, Olivier; Haddad, Samir; Arabi, Yaseen; McArthur, Colin; Cooper, D. James; Bellomo, Rinaldo (2017)
    To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit. A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death. Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2-11) and to PE diagnosis 6.5 days (IQR 2-16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01-1.03), patient weight (HR per kg 1.01, 95% CI 1-1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01-1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51-1.65). Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality.
  • Ratasvuori, Maire; Lassila, Riitta; Laitinen, Minna (2016)
    Introduction and aim: Venous thromboembolism (VTE) is a severe complication associated both with major orthopaedic surgery and cancer. However, survival and postoperative complications of skeletal metastases despite their thrombogenic potential, have received little attention in both the clinical management and research setting. This single-centre observational cohort study aimed to evaluate the incidence and impact of VTE in association with cancer surgery targeted to the management of fractures secondary to skeletal metastases. Methods: Data were collected retrospectively from the medical database. We included consecutive 306 patients operated for 343 non-spinal skeletal metastases during a 15-year period (1999-2014). The incidence of VTE and its risk factors were assessed using binary logistic regression analysis. Kaplan-Meier and Cox regression analyses were used to evaluate variables affecting survival. Results: The rate of symptomatic VTE was 10% (30/306) during the 3-month postoperative period, while 79% received thromboprophylaxis. Fatal pulmonary embolism (PE) rate was high, 3.3% (10/306) after surgery. Intraoperative oxygen saturation drop, pulmonary metastases and intramedullary nailing were independent risk factors for VTE. Indicators of decreased survival were lung cancer, intramedullary nailing, multiple skeletal and pulmonary metastases, anaemia, leukocytosis, and PE. Conclusion: Relationship between fractures secondary to skeletal metastases and VTE needs further clinical attention. Whether the survival of patients with fractures secondary to skeletal metastases can be improved by targeted thromboprophylactic means should be studied further. (C) 2016 Elsevier Ltd. All rights reserved.
  • Hemilä, Harri; Douglas, R M (1999)
  • Hemilä, Harri (1999)
    Placebo-controlled trials have shown that vitamin C supplementation decreases the duration and severity of common cold infections. However, the magnitude of the benefit has substantially varied, hampering conclusions about the clinical significance of the vitamin. In this paper, 23 studies with regular vitamin C supplementation (> or = 1 g/day) were analyzed to find out factors that may explain some part of the variation in the results. It was found that on average, vitamin C produces greater benefit for children than for adults. The dose may also affect the magnitude of the benefit, there being on average greater benefit from > or = 2 g/day compared to 1 g/day of the vitamin. In five studies with adults administered 1 g/day of vitamin C, the median decrease in cold duration was only 6%, whereas in two studies with children administered 2 g/day the median decrease was four times higher, 26%. The trials analyzed in this work used regular vitamin C supplementation, but it is conceivable that therapeutic supplementation starting early at the onset of the cold episode could produce comparable benefits. Since few trials have examined the effects of therapeutic supplementation and their results have been variable, further therapeutic trials are required to examine the role of vitamin C in the treatment of colds.
  • Hemilä, Harri (1996)
    In 1971, Linus Pauling carried out a meta-analysis of four placebo-controlled trials and concluded that it was highly unlikely that the decrease in the "integrated morbidity of the common cold" in vitamin C groups was caused by chance alone (P < 0.00003). Studies carried out since then have consistently found that vitamin C (> or = 1 g/d) alleviates common cold symptoms, indicating that the vitamin does indeed have physiologic effects on colds. However, widespread conviction that the vitamin has no proven effects on the common cold still remains. Three of the most influential reviews drawing this conclusion are considered in the present article. Two of them are cited in the current edition of the RDA nutritional recommendations as evidence that vitamin C is ineffective against colds. In this article, these three reviews are shown to contain serious inaccuracies and shortcomings, making them unreliable sources on the topic. The second purpose is to suggest possible conceptual reasons for the persistent resistance to the notion that vitamin C might have effects on colds. Although placebo-controlled trials have shown that vitamin C does alleviate common cold symptoms, important questions still remain.
  • Bates, Shannon M.; Alonso-Coello, Pablo; Tikkinen, Kari A. O.; Ebrahim, Shanil; Lopes, Luciane Cruz; McDonald, Sarah D.; Zhou, Qi; Akl, Elie A.; Neumann, Ignacio; Jacobsen, Anne Flem; Zhang, Yuqing; Santamara, Amparo; Annichino-Bizzacchi, Joyce Maria; Sandset, Per Morten; Bitar, Wael; Eckman, Mark H.; Guyatt, Gordon H. (2016)
    Background: Pregnant women with prior venous thromboembolism (VTE) are at risk of recurrence. Prophylaxis with low molecular weight heparin (LWMH) reduces that risk but is inconvenient, costly, and may be associated with increased risks of obstetrical bleeding. The views of pregnant women, crucial when making prophylaxis recommendations, are currently unknown. Methods: Cross-sectional international multicenter study. We included women with a history of VTE who were either pregnant or planning pregnancy. We provided information regarding risk of VTE recurrence with and without LMWH and determined participant's willingness to receive LMWH prophylaxis through direct choice exercises, preference-elicitation (utilities) for health states (e.g. burden of LMWH prophylaxis), and a probability trade-off exercise. Results: Of 123 women, more women at high risk than those at low risk of recurrence (86.4% vs. 60.0%; p=0.003) chose to use LMWH. The median threshold reduction in VTE at which women were willing to accept use of LMWH, given a 16% risk of VTE without prophylaxis, was 3% (interquartile range: 1 to 6). Participants' evaluation of the relevant health states varied widely and was unrelated to their direct choices to use or not use LMWH. Conclusions: Although the majority of women with a previous VTE, pregnant or planning pregnancy choose to take LMWH during pregnancy, a minority -and in low risk women, a large minority-do not. Our results highlight the need for individualized shared decision-making (SDM) in the clinical encounter, and for guideline panels to make weak recommendations in favor of LMWH that make clear the need for SDM. (C) 2015 Elsevier Ltd. All rights reserved.