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  • Frank, Philipp; Jokela, Markus; Batty, David; Cadar, Dorina; Steptoe, Andrew; Kivimäki, Mika (2021)
    Objective: Evidence from anti-inflammatory drug trials for the treatment of depression has been inconsistent. This may be ascribed to the differing symptom-specific effects of inflammation. Accordingly, the authors explored the associations between systemic inflammation and an array of individual symptoms of depression across multiple studies. Methods: This random-effects pooled analysis included 15 population-based cohorts and 56,351 individuals age 18 years and older. Serum or plasma concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured at baseline. Using validated self-report measures, 24 depressive symptoms were ascertained in 15 cross-sectional studies, and, in seven cohorts, were also assessed at follow-up (mean follow-up period, 3.2 years). Results: The prevalence of depressive symptoms ranged from 1.1% (suicidal ideation) to 21.5% (sleep problems). In cross-sectional analyses, higher concentrations of CRP were robustly associated with an increased risk of experiencing four physical symptoms (changes in appetite, felt everything was an effort, loss of energy, sleep problems) and one cognitive symptom (little interest in doing things). These associations remained after adjustment for sociodemographic variables, behavioral factors, and chronic conditions; in sex-and age-stratified analyses; in longitudinal analyses; when using IL-6 as the inflammatory marker of interest; in depressed individuals; and after excluding chronically ill individuals. For four exclusively emotional symptoms (bothered by things, hopelessness about the future, felt fearful, life had been a failure), the overall evidence was strongly against an association with inflammation. Conclusions: These findings suggest symptom-specific rather than generalized effects of systemic inflammation on depression. Future trials exploring anti-inflammatory treatment regimens for depression may benefit from targeting individuals presenting with symptom profiles characterized by distinct inflammation-related physical and cognitive symptoms. Am J Psychiatry 2021; 178:1107-1118; doi: 10.1176/appi.ajp.2021.20121776
  • Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Bovi, Paolo; Carletti, Monica; Cappellari, Manuel; Zedde, Marialuisa; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Silvestrelli, Giorgio; Lanari, Alessia; Ciccone, Alfonso; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Abdul-Rahim, Azmil H.; Lees, Kennedy R.; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Becattini, Cecilia; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Soloperto, Rossana; Masotti, Luca; Vannucchi, Vieri; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Sohn, Sung-Il; Marcheselli, Simona; Mumoli, Nicola; De Lodovici, Maria Luisa; Bono, Giorgio; Furie, Karen L.; Tadi, Prasanna; Yaghi, Shadi; Toni, Danilo; Letteri, Federica; Tassinari, Tiziana; Kargiotis, Odysseas; Lotti, Enrico Maria; Flomin, Yuriy; Mancuso, Michelangelo; Maccarrone, Miriam; Giannini, Nicola; Bandini, Fabio; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Scoditti, Umberto; Denti, Licia; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Gourbali, Vanessa; Orlandi, Giovanni; Giuntini, Martina; Chiti, Alberto; Giorli, Elisa; Gialdini, Gino; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Monaco, Serena; Baronello, Mario Maimone; Karapanayiotides, Theodore; Caso, Valeria (2017)
    Background-The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and theirtiming in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results-Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA(2)DS(2)-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated > 14 days after acute stroke. Conclusions-In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
  • Wardlaw, Joanna M; Debette, Stephanie; Jokinen, Hanna; De Leeuw, Frank-Erik; Pantoni, Leonardo; Chabriat, Hugues; Staals, Julie; Doubal, Fergus; Rudilosso, Salvatore; Eppinger, Sebastian; Schilling, Sabrina; Ornello, Raffaele; Enzinger, Christian; Cordonnier, Charlotte; Taylor-Rowan, Martin; Lindgren, Arne G. (2021)
    'Covert' cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD.
  • Int Liaison Comm Resuscitations IL; Neonatal Life Support Task Force E; Educ mentation Teams Task Force; Dainty, Katie N.; Atkins, Dianne L.; Breckwoldt, Jan; Skrifvars, Markus B.; Furuta, Marie (2021)
    Context: Parent/family presence at pediatric resuscitations has been slow to become consistent practice in hospital settings and has not been universally implemented. A systematic review of the literature on family presence during pediatric and neonatal resuscitation has not been previously conducted. Objective: To conduct a systematic review of the published evidence related to family presence during pediatric and neonatal resuscitation. Data sources: Six major bibliographic databases was undertaken with defined search terms and including literature up to June 14, 2020. Study selection: 3200 titles were retrieved in the initial search; 36 ultimately included for review. Data extraction: Data was double extracted independently by two reviewers and confirmed with the review team. All eligible studies were either survey or interview-based and as such we turned to narrative systematic review methodology. Results: The authors identified two key sets of findings: first, parents/family members want to be offered the option to be present for their child's resuscitation. Secondly, health care provider attitudes varied widely (ranging from 15% to >85%), however, support for family presence increased with previous experience and level of seniority. Limitations: English language only; lack of randomized control trials; quality of the publications. Conclusions: Parents wish to be offered the opportunity to be present but opinions and perspectives on the family presence vary greatly among health care providers. This topic urgently needs high quality, comparative research to measure the actual impact of family presence on patient, family and staff outcomes.
  • TRISP Collaborators; Polymeris, Alexandros A.; Curtze, Sami; Erdur, Hebun; Tatlisumak, Turgut; Strbian, Daniel (2019)
    Objective Seizure at onset (SaO) has been considered a relative contraindication for intravenous thrombolysis (IVT) in patients with acute ischemic stroke, although this appraisal is not evidence based. Here, we investigated the prognostic significance of SaO in patients treated with IVT for suspected ischemic stroke. Methods In this multicenter, IVT-registry-based study we assessed the association between SaO and symptomatic intracranial hemorrhage (sICH, European Cooperative Acute Stroke Study II definition), 3-month mortality, and 3-month functional outcome on the modified Rankin Scale (mRS) using unadjusted and adjusted logistic regression, coarsened exact matching, and inverse probability weighted analyses. Results Among 10,074 IVT-treated patients, 146 (1.5%) had SaO. SaO patients had significantly higher National Institutes of Health Stroke Scale score and glucose on admission, and more often female sex, prior stroke, and prior functional dependence than non-SaO patients. In unadjusted analysis, they had generally less favorable outcomes. After controlling for confounders in adjusted, matched, and weighted analyses, all associations between SaO and any of the outcomes disappeared, including sICH (odds ratio [OR](unadjusted) = 1.53 [95% confidence interval (CI) = 0.74-3.14], ORadjusted = 0.52 [95% CI = 0.13-2.16], ORmatched = 0.68 [95% CI = 0.15-3.03], ORweighted = 0.95 [95% CI = 0.39-2.32]), mortality (ORunadjusted = 1.49 [95% CI = 1.00-2.24], ORadjusted = 0.98 [95% CI = 0.5-1.92], ORmatched = 1.13 [95% CI = 0.55-2.33], ORweighted = 1.17 [95% CI = 0.73-1.88]), and functional outcome (mRS >= 3/ordinal mRS: ORunadjusted = 1.33 [95% CI = 0.96-1.84]/1.35 [95% CI = 1.01-1.81], ORadjusted = 0.78 [95% CI = 0.45-1.32]/0.78 [95% CI = 0.52-1.16], ORmatched = 0.75 [95% CI = 0.43-1.32]/0.45 [95% CI = 0.10-2.06], ORweighted = 0.87 [95% CI = 0.57-1.34]/1.00 [95% CI = 0.66-1.52]). These results were consistent regardless of whether patients had an eventual diagnosis of ischemic stroke (89/146) or stroke mimic (57/146 SaO patients). Interpretation SaO was not an independent predictor of poor prognosis. Withholding IVT from patients with assumed ischemic stroke presenting with SaO seems unjustified. ANN NEUROL 2019
  • Tolonen, Hanna M; Airaksinen, Marja; Ruokoniemi, Päivi; Hämeen-Anttila, Katri; Shermock, Kenneth M; Kurki, Pekka (2019)
  • Kiguchi, Tekeyuki; Okubo, Masashi; Nishiyama, Chika; Maconochie, Ian; Ong, Marcus Eng Hock; Kern, Karl B.; Wyckoff, Myra H.; McNally, Bryan; Christensen, Erika; Tjelmeland, Ingvild; Herlitz, Johan; Perkins, Gavin D.; Booth, Scott; Finn, Judith; Shahidah, Nur; Shin, Sang Do; Bobrow, Bentley J.; Morrison, Laurie J.; Salo, Ari; Baldi, Enrico; Burkart, Roman; Lin, Chih-Hao; Jouven, Xavier; Soar, Jasmeet; Nolan, Jerry P.; Iwami, Taku (2020)
    Background Since development of the Utstein style recommendations for the uniform reporting of cardiac arrest, increasing numbers of national and regional out-of-hospital cardiac arrest (OHCA) registries have been established worldwide. The International Liaison Committee on Resuscitation (ILCOR) created the Research and Registries Working Group and aimed to systematically report data collected from these registries. Methods We conducted two surveys of voluntarily participating national and regional registries. The first survey aimed to identify which core elements of the current Utstein style for OHCA were collected by each registry. The second survey collected descriptive summary data from each registry. We chose the data collected for the second survey based on the availability of core elements identified by the first survey. Results Seven national and four regional registries were included in the first survey and nine national and seven regional registries in the second survey. The estimated annual incidence of emergency medical services (EMS)-treated OHCA was 30.0 to 97.1 individuals per 100,000 population. The combined data showed the median age varied from 64 to 79 years and more than half were male in all 16 registries. The provision of bystander cardiopulmonary resuscitation (CPR) and bystander automated external defibrillator (AED) use was 19.1% to 79.0% in all registries and 2.0% to 37.4% among 11 registries, respectively. Survival to hospital discharge or 30-day survival after EMS-treated OHCA was 3.1% to 20.4% across all registries. Favourable neurological outcome at hospital discharge or 30 days after EMS-treated OHCA was 2.8% to 18.2%. Survival to hospital discharge or 30-day survival after bystander witnessed shockable OHCA ranged from 11.7% to 47.4% and favourable neurological outcome from 9.9% to 33.3%. Conclusion This report from ILCOR describes data on systems of care and outcomes following OHCA from nine national and seven regional registries across the world. We found variation in reported survival outcomes and other core elements of the current Utstein style recommendations for OHCA across nations and regions.
  • Remes, Tiina Maria; Suo-Palosaari, Maria Helena; Koskenkorva, Päivi K. T.; Sutela, Anna K.; Toiviainen-Salo, Sanna-Maria; Arikoski, Pekka M.; Arola, Mikko O.; Heikkilä, Vesa-Pekka; Kapanen, Mika; Lähteenmäki, Päivi Maria; Lönnqvist, Tuula R. I.; Niiniviita, Hannele; Pokka, Tytti M-L; Porra, Liisa; Riikonen, V. Pekka; Seppälä, Jan; Sirkiä, Kirsti H.; Vanhanen, Antti; Rantala, Heikki M. J.; Harila-Saari, Arja H.; Ojaniemi, Marja K. (2020)
    Background. Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. Methods. Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients' files. Results. Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. Conclusions. Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.