Browsing by Subject "RANDOMIZED-TRIAL"

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  • Loupakis, Fotios; Stein, Alexander; Ychou, Marc; Hermann, Frank; Salud, Antonieta; Osterlund, Pia (2016)
    Colorectal cancer is the third most common cancer worldwide. A significant proportion of patients presents with unresectable metastatic disease or develops metachronous metastases following surgical resection of the primary tumor. The prognosis of the disease has improved over the past two decades, with extended multimodality treatment options and the development of increasingly intensified chemotherapy regimens that now typically include targeted biologics. A recent advance in therapy is a treatment regimen composed of three chemotherapeutic agents (i.e., triplet chemotherapy: 5-fluorouracil [5-FU]/leucovorin [LV], oxaliplatin, and irinotecan; FOLFOXIRI) in combination with the vascular endothelial growth factor inhibitor bevacizumab. This regimen has been shown to elicit significantly improved objective response rates and median progression-free survival compared with 5-FU/LV and irinotecan in combination with bevacizumab. However, triplet chemotherapy has been associated with increased rates of chemotherapy-related adverse events, and treatment-emergent adverse events should be properly managed to minimize treatment interruption or discontinuation. We present herein a review of clinical studies evaluating the safety and efficacy of FOLFOXIRI with bevacizumab in metastatic colorectal cancer, and propose a practical guide for the management of adverse events associated with the regimen.
  • Baron, Frederic; Galimard, Jacques-Emmanue; Labopin, Myriam; Yakoub-Agha, Ibrahim; Niittyvuopio, Riitta; Kroeger, Nicolaus; Griskevicius, Laimonas; Wu, Depei; Forcade, Edouard; Richard, Carlos; Aljurf, Mahmoud; Helbig, Grzegorz; Labussiere-Wallet, Helene; Mohty, Mohamad; Nagler, Arnon (2020)
    We compared severe graft-versus-host-disease GyHD) free and relapse-free survival and other transplantation outcomes of acute myeloid leukemia (AML) patients given bone marrow (BM) without and-thymocyte globulin (ATG) versus peripheral blood stem cells (PBSC) with ATG after myeloablative conditioning. In the cohort of patients receiving grafts from a human leukocyte antigen (HLA)-matched sibling donor, patients given PBSC with ATG (n=1,021) and those given BM without ATG (n=1,633) presented comparable severe GvHD-free relapse-free survival (GRSF)(hazard ratio [HR]=0.9, 95% confidence interval [CI]: 0.8-1.1, P=0.5) and overall survival (HR=1.0, 95% CI: 0.8-1.2, P=0.8). They had however, a lower incidence of chronic GvHD (cGvHD) (HR=0.7, 95% CI: 0.6-0.9, P=0.01). In the cohort of patients receiving grafts from HLA-matched unrelated donor , patients given PBSC with ATG (n=2,318) had better severe GvHD-free and relapse-free survival (GRFS) than those given BM without ATG (n=303) (HR=0.8, 95% CI: 0.6-0.9, P=0.001). They also had a lower incidence of cGvHD (HR=0.6, 95% CI: 0.5-0.8, P=0.0006) and better overall survival (HR=0.8, 95% CI: 0.6-1.0, P=0.04). In summary, these data suggest that PBSC with ATG results in comparable (in the case of sibling donor) or significantly better (in the case of unrelated donor) severe GRFS than BM without ATG in patients with AML in complete remission receiving grafts after myeloablative conditioning.
  • FIDELITY Finnish Degenerative Meni; Sihvonen, Raine; Paavola, Mika; Malmivaara, Antti; Itälä, Ari; Joukainen, Antti; Kalske, Juha; Nurmi, Heikki; Kumm, Jaanika; Sillanpää, Niko; Kiekara, Tommi; Turkiewicz, Aleksandra; Toivonen, Pirjo; Englund, Martin; Taimela, Simo; Järvinen, Teppo L. N. (2020)
    Objectives To assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up. Design Multicentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial. Setting Orthopaedic departments in five public hospitals in Finland. Participants 146 adults, mean age 52 years (range 35-65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised. Interventions APM or placebo surgery (diagnostic knee arthroscopy). Main outcome measures We used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade >= 1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function ( Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale). Results There was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade >= 1 of 13%, 95% CI -2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), -1.7 (95% CI -7.7 to 4.3) in WOMET, -2.1 (95% CI -6.8 to 2.6) in Lysholm knee score, and -0.04 (95% CI -0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar. Conclusions APM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery.
  • Järvinen, Teppo L. N.; Sihvonen, Raine; Englund, Martin (2014)
  • Nykänen, Taina; Udd, Marianne; Peltola, Erno; Leppaniemi, Ari; Kylänpää, Marja-Leena (2017)
    Bleeding pancreatic pseudocysts (PPCs) are a rare but lethal complication of pancreatitis. Transcatheter arterial embolization (TAE) is the first-line treatment of acute hemorrhage, but consensus on the definitive management of bleeding PPCs is lacking. The aim of this study was to evaluate the safety and efficacy of the combination of TAE and therapeutic endoscopy in the treatment of bleeding PPCs. Patients with acute or chronic pancreatitis treated for bleeding PPCs in Helsinki University Hospital during 2004-2014 comprised the study group. Inpatients with acute necrotizing pancreatitis were excluded. Patients underwent TAE as the primary treatment to control the bleeding. Therapeutic endoscopy performed on an outpatient visit after TAE allowed the definitive treatment of PPCs. A total of 58 patients underwent TAE. Re-bleeding rate (<30 days) was 15.5 %, necessitating re-embolization on seven and surgical intervention on two patients. Overall, TAE success rate was 96.6 %. Mortality rate (<30 days) was 3.4 %. Of the 58, 47 patients were followed up for their PPCs in our unit. PPCs resolved spontaneously in 13 (27.1 %). The remaining 34 had an endoscopic treatment attempt with endoscopic draining performed on 32 and unsuccessful cannulation on two (5.9 %). Of the 32 patients with initially successful endoscopy, 7 (21.9 %) needed an additional drainage procedure (six non-surgical and one surgical). Overall success rate of non-surgical management was 91.5 %. Post-endoscopy mortality rate (<30 days) was 2.9 %. Our follow-up continued for 15 (1-75) months. By the time of data retrieval, 35 of 58 patients had died with alcohol liver disease being the most common cause of death. Five-year survival estimate was 63 %. Bleeding pancreatic pseudoaneurysms require non-surgical management. We need more data on the optimal timing of therapeutic endoscopy and on the role of empirical embolizations.
  • Järvinen, Teppo L. N.; Sihvonen, Raine; Bhandari, Mohit; Sprague, Sheila; Malmivaara, Antti; Paavola, Mika; Schuenemann, Holger J.; Guyatt, Gordon H. (2014)
  • Tainio, Karoliina; Athanasiou, Antonios; Tikkinen, Kari A. O.; Aaltonen, Riikka; Cardenas Hernandes, Jovita; Glazer-Livson, Sivan; Jakobsson, Maija; Joronen, Kirsi; Kiviharju, Mari; Louvanto, Karolina; Oksjoki, Sanna; Tähtinen, Riikka; Virtanen, Seppo; Nieminen, Pekka; Kyrgiou, Maria; Kalliala, Ilkka (2018)
    OBJECTIVE To estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016. ELIGIBILITY CRITERIA Studies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months. DATA SYNTHESIS Two reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I-2 statistics. MAIN OUTCOME MEASURES Rates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months). RESULTS 36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I-2= 77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I-2= 82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I-2= 90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I-2= 0%), 23% (two studies, 226/938 women, 20% to 26%; I-2= 97%), and 11% (three studies, 163/1033 women, 5% to 19%; I-2= 67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%. CONCLUSIONS Most CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring.
  • Tarvasmäki, Tuukka; Lassus, Johan; Varpula, Marjut; Sionis, Alessandro; Sund, Reijo; Kober, Lars; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Cardoso, Jose Silva; Carubelli, Valentina; Di Somma, Salvatore; Mebazaa, Alexandre; Harjola, Veli-Pekka; CardShock Study Investigators (2016)
    Background: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. Methods: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Results: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. Conclusion: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.
  • Rainio, Mia; Lindström, Outi; Udd, Marianne; Louhimo, Johanna; Kylänpää, Leena (2017)
    Background Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications. Aims Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit. Methods The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP. Results PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder. Conclusions In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.
  • IN.PACT Global Study Investigators; Venermo, Maarit (2018)
    OBJECTIVES The IN. PACT Global Study is the largest prospective, multicenter, independently adjudicated trial to evaluate a paclitaxel drug-coated balloon in patients with lifestyle-limiting claudication and/or ischemic rest pain due to atherosclerotic disease of the femoropopliteal artery and includes complex lesions beyond what are typically included in randomized controlled trials. BACKGROUND Randomized controlled trials have demonstrated the safety and efficacy of drug-coated balloons for the treatment of Trans-Atlantic Inter-Society Consensus Document II A and B lesions, but there is a need for large-scale prospective studies to evaluate a broader range of lesions. METHODS The IN. PACT Global Study enrolled 1,535 subjects, and 1,406 (1,773 lesions) were included in the pre-defined clinical cohort analysis. Freedom from clinically driven target lesion revascularization was evaluated at 24 months. The safety composite endpoint was freedom from device-and procedure-related death through 30 days and freedom from target limb major amputation and clinically driven target vessel revascularization within 24 months. RESULTS Mean lesion length was 12.1 cm, 35.5% were total occlusions, and 18.0% had in-stent restenosis. Freedom from clinically driven target lesion revascularization at 24 months was 83.3%, the composite safety endpoint was met in 81.7%, the 2-year all-cause mortality rate was 7.0%, and the major target limb amputation rate was 0.7%. Increased lesion length and the presence of de novo in-stent restenosis or coronary artery disease were associated with increased risk for clinically driven target lesion revascularization by 24 months. CONCLUSIONS This real-world study of femoropopliteal artery disease treatment with drug-coated balloons confirmed positive findings reported from more strictly designed randomized controlled trials and showed that outcomes are durable in this population up to 2 years after treatment. (c) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Lindfors, Olavi; Knekt, Paul; Lehtonen, Johannes; Virtala, Esa; Maljanen, Timo; Härkänen, Tommi (2019)
    The evidence on potentially greater benefits of psychoanalysis (PA) vs. long-term psychodynamic psychotherapy (LPP) is scarce. This study compared the effectiveness of PA and LPP on personality and social functioning during a 10-year follow-up from the beginning of the treatments. The eligible patients, 41 self-selected for PA and 128 assigned to LPP, were 20–45 years of age and had anxiety or mood disorder. Outcomes were analyzed using ten standard measures of personality and social functioning, carried out 5-9 times during the follow-up. Different change patterns by time in PA and LPP emerged, suggesting less benefit of PA during the first years of follow-up and more benefit in most outcomes thereafter. Greater post-treatment improvement in PA than in LPP was seen up to 1-2 years after PA had ended in more mature defense style (DSQ), level of personality organization (LPO), more positive self-concept (SASB), more improved social adjustment (SAS-SR) and sense of coherence (SOC). However, at the 10-year follow-up the differences were non-significant. In conclusion, PA may give some additional benefits when long-term aims are linked to personality and social functioning. The relatively small differences and higher costs in comparison to LPP may restrict the feasibility of PA.
  • Bauer, Sebastian; Joensuu, Heikki (2015)
    Imatinib is strongly positioned as the recommended first-line agent for most patients with advanced gastrointestinal stromal tumor (GIST) due to its good efficacy and tolerability. Imatinib-resistant advanced GIST continues to pose a therapeutic challenge, likely due to the frequent presence of multiple mutations that confer drug resistance. Sunitinib and regorafenib are approved as second- and third-line agents, respectively, for patients whose GIST does not respond to imatinib or who do not tolerate imatinib, and their use is supported by large randomized trials. ATP-mimetic tyrosine kinase inhibitors provide clinical benefit even in heavily pretreated GIST suggesting that oncogenic dependency on KIT frequently persists. Several potentially useful tyrosine kinase inhibitors with distinct inhibitory profiles against both KIT ATP-binding domain and activation loop mutations have not yet been fully evaluated. Agents that have been found promising in preclinical models and early clinical trials include small molecule KIT and PDGFRA mutation-specific inhibitors, heat shock protein inhibitors, histone deacetylase inhibitors, allosteric KIT inhibitors, KIT and PDGFRA signaling pathway inhibitors, and immunological approaches including antibody-drug conjugates. Concomitant or sequential administration of tyrosine kinase inhibitors with KIT signaling pathway inhibitors require further evaluation, as well as rotation of tyrosine kinase inhibitors as a means to suppress drug-resistant cell clones.
  • EVA-TRISP Investigators; Nordanstig, Annika; Curtze, Sami; Gensicke, Henrik; Lappalainen, Kimmo; Strbian, Daniel; Tatlisumak, Turgut (2021)
    Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
  • Cenzato, Marco; Boccardi, Edoardo; Beghi, Ettore; Vajkoczy, Peter; Szikora, Istvan; Motti, Enrico; Regli, Luca; Raabe, Andreas; Eliava, Shalva; Gruber, Andreas; Meling, Torstein R.; Niemela, Mika; Pasqualin, Alberto; Golanov, Andrey; Karlsson, Bengt; Kemeny, Andras; Liscak, Roman; Lippitz, Bodo; Radatz, Matthias; La Camera, Alessandro; Chapot, Rene; Islak, Civan; Spelle, Laurent; Debernardi, Alberto; Agostoni, Elio; Revay, Martina; Morgan, Michael K. (2017)
    In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.
  • Moore, Andrew; Derry, Sheena; Eccleston, Christopher; Kalso, Eija (2013)
  • Huttunen, Henri J.; Palva, J. Matias; Lindberg, Laura; Palva, Satu; Saarela, Ville; Karvonen, Elina; Latvala, Marja-Leena; Liinamaa, Johanna; Booms, Sigrid; Castren, Eero; Uusitalo, Hannu (2018)
    Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: -0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (-0.167 logMAR; 95% CI: -0.226 to -0.108; p <0.001) and placebo (-0.194 logMAR; 95% CI: -0.254 to -0.133; p <0.001) groups. While this study failed to provide evidence that fluoxetine enhances neuroplasticity, our data support other recent clinical studies suggesting that improvement of vision can be accomplished in adults with amblyopia.
  • Singh, Sonal; Warren, Helen R.; Hiltunen, Timo P.; McDonough, Caitrin W.; El Rouby, Nihal; Salvi, Erika; Wang, Zhiying; Garofalidou, Tatiana; Fyhrquist, Frej; Kontula, Kimmo K.; Glorioso, Valeria; Zaninello, Roberta; Glorioso, Nicola; Pepine, Carl J.; Munroe, Patricia B.; Turner, Stephan T.; Chapman, Arlene B.; Boerwinkle, Eric; Johnson, Julie A.; Gong, Yan; Cooper-DeHoff, Rhonda M. (2019)
    Background-There exists a wide interindividual variability in blood pressure (BP) response to beta(1)-blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome-wide meta-analysis of genetic variants beta(1)-influencing blocker BP response. Methods and Results-Genome-wide association analysis for systolic BP and diastolic BP response to beta(1)-blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta-analysis and single nucleotide polymorphisms (SNPs) with P Conclusions-Data from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with beta(1)-blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.
  • Knittle, Keegan Phillip; Gellert, Paul; Moore, Clair; Bourke, Natalie; Hull, Victoria (2019)
    This study investigates the extent to which achieving goals during behavioral activation (BA) treatment predicts depressive symptom improvement, and whether goal-related cognitions predict goal achievement or treatment response. Patients (n = 110, mean age 37.6, 54% female) received low-intensity cognitive behavioral therapy for depression, which included setting up to three behavioral goals in each of three BA-focused sessions (i.e., 9 goals per patient). Patients completed items from the Self-Regulation Skills Battery to assess goal-related cognitions and goal achievement for these goals, and depressive symptoms were assessed weekly with the PHQ-9. Multilevel models investigated the relationships between goal-related cognitions, goal achievement and depressive symptoms. Depressive symptoms improved curve-linearly during treatment (B = 0.12, p <.001), but were not predicted by contemporaneous or time-lagged goal achievement. While cumulative goal achievement predicted end-of-treatment depressive symptoms (r= -.23; p <.01), this relationship became nonsignificant after controlling for depressive symptoms at baseline. Readiness, planning and action control predicted greater goal achievement, whereas greater goal ownership predicted less goal achievement (all p <.05). Motivation and outcome expectancy were related to subsequent, but not contemporaneous, improvements in depressive symptoms (all p<.05). This study indicates the importance of goal-related cognitions in BA treatments, and future research should investigate potential moderators of the relationships between goal-related cognitions, goal achievement, and improvements in depressive symptoms.
  • Keski-Nisula, Juho; Pesonen, Eero; Olkkola, Klaus T.; Ahlroth, Terri; Puntila, Juha; Andersson, Sture; Neuvonen, Pertti J.; Suominen, Pertti K. (2016)
    Background. The optimal dose of methylprednisolone during pediatric open heart surgical procedures is unknown. This study compared the antiinflammatory and cardioprotective effects of high and lower doses of methylprednisolone in children undergoing cardiac operations. Methods. Thirty children, between 1 and 18 months old and undergoing total correction of tetralogy of Fallot, were randomized in double-blind fashion to receive either 5 or 30 mg/kg of intravenous methylprednisolone after anesthesia induction. Plasma concentrations of methylprednisolone, interleukin-6 (IL-6), IL-8, and IL-10, troponin T, and glucose were measured at anesthesia induction before administration of the study drug, at 30 minutes on cardiopulmonary bypass (CPB), just after weaning from CPB, and at 6 hours after CPB. Troponin T and blood glucose were also measured on the first postoperative morning. Results. Significantly higher methylprednisolone concentrations were measured in patients receiving 30 mg/kg of methylprednisolone at 30 minutes on CBP, after weaning from CPB and at 6 hours after CPB (p <0.001). No differences were detected in IL-6, IL-8, IL-10, or troponin concentrations at any time point. Blood glucose levels were significantly higher in patients receiving 30 mg/kg of methylprednisolone at 6 hours after CPB (p = 0.04) and on the first postoperative morning (p = 0.02). Conclusions. Based on the measured concentrations of interleukins or troponin T, a 30 mg/kg dose of methylprednisolone during pediatric open heart operations does not offer any additional antiinflammatory or cardioprotective benefit over a 5 mg/kg dose. Higher dose of methylprednisolone exposes patients more frequently to hyperglycemia. (C) 2016 by The Society of Thoracic Surgeons