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Supplemental Digital Content is available in the text., Background and Purpose: Randomized patent foramen ovale closure trials have used open-label end point ascertainment which increases the risk of bias and undermines confidence in the conclusions. The Gore REDUCE trial prospectively performed baseline and follow-up magnetic resonance imaging (MRIs) for all subjects providing an objective measure of the effectiveness of closure. Methods: We performed blinded evaluations of the presence, location, and volume of new infarct on diffusion-weighted imaging of recurrent clinical stroke or new infarct (>3 mm) on T2/fluid attenuated inversion recovery from baseline to follow-up MRI at 2 years, comparing closure to medical therapy alone. We also examined the effect of shunt size and the development of atrial fibrillation on infarct burden at follow-up. Results: At follow-up, new clinical stroke or silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) medication-only patients (relative risk, 0.44 [95% CI, 0.24–0.81], P=0.02). Clinical strokes were less common in closure patients compared with medically treated patients, 5 (1.3%) versus 12 (6.8%), P=0.001, while silent MRI infarcts were similar, 13 (3.4%) versus 7 (4.0%), P=0.81. There were no differences in number, volumes, and distribution of new infarct comparing closure patients to those treated with medication alone. There were also no differences of number, volumes, and distribution comparing silent infarcts to clinical strokes. Infarct burden was also similar for patients who developed atrial fibrillation and for those with large shunts. Conclusions: The REDUCE trial demonstrates that patent foramen ovale closure prevents recurrent brain infarction based on the objective outcome of new infarcts on MRI. Only clinical strokes were reduced by closure while silent infarctions were similar between study arms, and there were no differences in infarct volume or location comparing silent infarcts to clinical strokes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00738894.

Background: Due to lack of validated body contouring-specific patient-reported outcome (PRO) instruments, the outcomes of abdominoplasty after massive weight loss have been evaluated rather rarely and mainly using generic health-related quality of life (HRQoL) instruments. The aim of the current study was to examine, using body contouring-specific (BODY-Q) and generic (15D) HRQoL instruments, the HRQoL, and key factors related to HRQoL among patients having undergone massive weight loss and abdominoplasty. Methods: Altogether 52 patients who underwent abdominoplasty due to massive weight loss completed the BODY-Q and the 15D HRQoL instruments. The 15D scores were compared to those of age-, gender-, and BMI-adjusted control sample of the general population. Results: The mean score of the BODY-Q Abdomen scale was 50.7 out of 100 (SD 24.4). The HRQoL of abdominoplasty patients was lower than that of age-, gender-, and BMI-adjusted general population (p = 0.001). Sleeping, discomfort and symptoms, depression, excretion, and sexual activity were the patients' main concerns. Body image and psychological well-being were strongly associated with the perceived HRQoL. The satisfaction with appearance of the abdominal area was not associated with generic HRQoL. Conclusions: The HRQoL of abdominoplasty patients is lower than that of general population with similar age, gender and BMI. The most important factors associated with the HRQoL of the patients were body image, psychological well-being, and physical function. (C) 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

We compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA).The predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3 - 6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory.The predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62-0.84), total N-acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68 - 0.88)), or NSE at 72 h (0.85 (0.76 - 0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80-0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85-0.98) vs 0.98 (0.96-1.00), p = 0.037).None of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use.ClinicalTrials.gov NCT00879892, April 13, 2009.

Background We wanted to understand how patients with different modified Rankin Scale (mRS) grades differ regarding their health-related quality of life (HRQoL) and how this affects the interpretation and dichotomization of the grade. Methods In 2016, all adult patients in our brain arteriovenous malformation (AVM) database (n = 432) were asked to fill in mailed letters including a questionnaire about self-sufficiency and lifestyle and the 15D HRQoL questionnaire. The follow-up mRS was defined in 2016 using the electronic patient registry and the questionnaire data. The 15D profiles of each mRS grade were compared to those of the general population and to each other, using ANCOVA with age and sex standardization. Results Patients in mRS 0 (mean 15D score = 0.954 ± 0.060) had significantly better HRQoL than the general population (mean = 0.927 ± 0.028), p p Conclusions Using 15D, we were able to find significant differences in the HRQoL between mRS 0 and mRS 1 AVM patients, against the recent findings on stroke patients using EQ-5D in their analyses. Although the dichotomization cut point is commonly set between mRS 1 and 2, patients in these grades had a similar HRQoL and a decreased ability to continue their premorbid lifestyle, in contrast to patients in mRS 0.

OBJECTIVES: To describe the occurrence of postprocedural atrial fibrillation (AF) among patients with cryptogenic stroke undergoing patent foramen ovale (PFO) closure in the REDUCE clinical study and analyze for potential risk factors for the development of postprocedural AF.BACKGROUND: AF is an adverse event that might potentially counterbalance the stroke prevention benefit from PFO closure. Data on AF after transcatheter PFO closure are sparse.METHODS: We evaluated data from patients having PFO closure (Gore HELEX or Gore Cardioform Septal Occluder) in the REDUCE clinical trial (n = 408) in at post hoc explorative analysis. Median follow-up was 5.0 years.RESULTS: AF occurred in 30 patients (7.4%) after PFO closure with a total of 34 AF events. Most were reported as non-serious (68%), detected within 45 days post-procedure (79%), and resolved within 2 weeks of onset (63%). One subject with AF had recurrent stroke. Postprocedural AF occurred more frequently among subjects with higher age and large device sizes. Male sex was the only independent predictor of postprocedural AF. We found no association between the type of occluder (HELEX or Gore Cardioform Septal Occluder) or PFO anatomical characteristics and post-procedural AF.CONCLUSION: In the REDUCE clinical study, postprocedural atrial fibrillation was mostly early onset, transient and with no later recurrence. Postprocedural AF occurred more frequently among patients with higher age and larger devices. Male sex was the only independent predictor of postprocedural AF.

The authors have requested that this preprint be removed from Research Square.

Background Patient-reported outcome (PRO) instruments measure health gains, including changes in health-related quality of life (HRQoL). Previous studies have assessed the reliability and relationship of multiple HRQoL instruments in search of the optimal instrument for feasible measurement of PROs. Although the 15D instrument was shown to have the best sensitivity and construct validity among cardiac patients, it is unknown how well it captures relevant disease-specific information scores compared to instruments included in the International Consortium for Health Outcomes Measurement (ICHOM) standard set. The aim of this study was to investigate whether the disease-specific PRO instruments and a generic HRQoL instrument capture disease related symptoms in coronary artery disease (CAD) patients. Methods Health status and HRQoL were assessed with the instruments included in the ICHOM standard set: Seattle Angina Questionnaire short-form (SAQ-7), Rose Dyspnea Scale (RDS), two-item Patient Health Questionnaire (PHQ-2), and with the 15D HRQoL instrument at baseline and 1 year from the treatment in a university hospital setting. Spearman correlation and explanatory factor analysis were used to assess the relationship of baseline scores and 1-year change in scores of 297 patients. Results At baseline, the overall 15D score and SAQ-physical limitation (SAQ-PL), 15D “breathing” and SAQ-PL, as well as “breathing” and RDS showed moderately strong correlations. The factor interpreted to reflect “Breathing-related physical activity”, based on high loadings of “breathing”, RDS, SAQ-PL, “mobility”, “vitality”, and “usual activities”, explained 19.2% of the total variance. Correlations between 1-year changes in scores were fair. The factor of “Breathing-related physical activity”, with significant loading of RDS, SAQ-PL, “breathing, “usual activities”, “vitality”, “sexual activity”, “mobility”, and disease-specific quality of life explained 20.5% of the total variance in 1-year change in scores. The correlation of angina frequency measured by SAQ-7 and the 15D instrument was poor. Conclusions The 15D detects dyspnea and depression similarly to RDS and PHQ-2 but not angina similarly to the SAQ-7. This may call for supplementing the 15D instrument with a disease-specific instrument when studying CAD patients.

Aim: To assess health-related quality of life (HRQoL) of patients with benign gynecological disorders. Materials & methods: Prospective 2-year follow-up with the 15D HRQoL-instrument of 311 women treated in Helsinki-area hospitals in 2012–2013. Results: The initially impaired HRQoL regarding excretion, discomfort and symptoms, and vitality and sexual activity improved after treatment. However, only sexual activity reached similar levels as in the general population. Treatment of endometriosis, fibroids and polyps resulted in best and that of unspecific pelvic pain and bleeding disorders in worst HRQoL scores. Results were independent of hospital size. Conclusion: The impaired HRQoL dimensions were improved by treatment but HRQoL still remained poorer than in the general female population. Treatment of unspecific pelvic pain and bleeding disorders needs further evaluation.

Extended 5-Year Follow-up of the PFO Closure Trial In the initial report of the Gore REDUCE trial of patent foramen ovale closure, with a median follow-up of 3.2 years, 18 patients had stroke recur...

BackgroundGuidelines recommend brain imaging for neurological prognostication after out-of-hospital cardiac arrest (OHCA). We aimed to evaluate the predictive accuracy of early phase diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H-MRS) combined with neuron-specific enolase (NSE) and selected clinical variables for poor neurological outcome after OHCA.MethodsIn 92 patients with complete data set, the predictive accuracy of DTI, 1H-MRS, and NSE at 72h for poor neurological outcome (mRS 3-6) at six months were assessed by area under the receiver operating characteristic (ROC) curve as predetermined in the protocol. Additional post-hoc analyses were also performed to find a model with the best predictive power for poor neurological outcome. The brain imaging was performed in a median (IQR) time of 53 hours (47-64) after OHCA.ResultsAt six-months, 31 patients had mRS 3-6, considered to reflect a poor neurological outcome. There was no significant difference between area under ROC curve of 0.73 (95% CI 0.62-0.84) for DTI, 0.78 (0.68-0.88) for 1H-MRS and 0.85 (0.76-0.93) for NSE at 72h for predicting poor outcome at 6 months. In the post-hoc analysis, the combination of DTI, 1H-MRS, and NSE with motor score at 72 hours and epileptic seizures provided the best predictive power with area under ROC curve of 0.98 (95% CI 0.96 – 1.00) as compared to 0.92 (0.86 − 0.97) for DTI, 1H-MRS and NSE at 72 hours alone (p = 0.009).ConclusionsNeither early stage DTI nor 1H-MRS imaging was better than NSE at 72h in predicting poor outcome in this patient group. Although the addition of neuroimaging to the best model using current clinical and laboratory parameters improved the diagnostic performance, the costs and challenges of MR imaging of critically ill patients may outweigh this small benefit. Trial registrationClinicalTrials.gov NCT00879892. Registered on 13 April 2009.

Objectives Postoperative cognitive dysfunction (POCD) is a common consequence of coronary artery bypass grafting. However, domain‐specific associations between postoperative changes and long‐term performance are poorly known. The aim of this study was to investigate whether domain‐specific cognitive changes after cardiac surgery predict long‐term cognitive outcome. Materials and Methods We assessed 100 patients (86 men, mean age 60) before coronary artery bypass grafting, with re‐examinations after one week, three months, and a mean of 6.7 years. The extensive neuropsychological test battery was organized into seven functional cognitive domains. Cognitive decline and improvement were defined with the reliable change index derived from 17 matching healthy controls. Analyses were adjusted for baseline cognitive performance, age, gender, education and cardiovascular risks factors. Results On group level, one week after surgery 71% patients showed cognitive decline and 9% improvement in any functional domain, as compared to preoperative results. Three months postsurgery, decline was observed in 47% and improvement in 25% of patients. Executive functioning was the most sensitive domain to both decline and improvement. Postoperative dysfunction predicted long‐term cognitive deterioration six years after operation, particularly in the domain of executive functioning. Conclusions POCD after coronary artery bypass grafting is an essential risk factor for long‐term deterioration and an indication for neuropsychological follow‐up. Assessment of change in executive functioning after coronary artery bypass grafting may help to identify patients at risk for unfavorable long‐term outcome., The aim of this study was to investigate whether domain‐specific cognitive changes after cardiac surgery predict long‐term cognitive outcome. We assessed 100 patients before coronary artery bypass grafting, with re‐examinations after one week, three months, and six years. Postoperative dysfunction predicted long‐term cognitive deterioration six years after operation, particularly in the domain of executive functioning.

Aims The REDUCE study demonstrated a reduction in the risk of recurrent stroke with patent foramen ovale closure and antiplatelet therapy compared to antiplatelet therapy alone. The clinicians were allowed to choose among aspirin, clopidogrel, or aspirin/dipyridamole with the expectation that all antiplatelet therapies would have similar efficacy in this population. We tested that presumption by comparing recurrent stroke rates among antiplatelet agents within the control arm of the trial. Methods We evaluated patients in REDUCE study who were randomized to the medical arm. The primary endpoint for this analysis was freedom from clinical ischemic stroke through at least 2 years of follow-up, to a maximum of 5 years. In the primary analysis, antiplatelet treatment was defined as the agent during the week prior to a recurrent stroke or last known contact. Results Of 223 patients in the medical treatment arm, the initial agent was aspirin 52%, clopidogrel 30%, and aspirin/dipyridamole 12%. Patients treated with aspirin were similar to those treated with alternatives, but were more likely to be enrolled in the United States. The last reported agent was aspirin alone in 55%, clopidogrel alone in 31%, aspirin/dipyridamole in 7%, and other/nothing/missing in 7%. Recurrent stroke rates were similar for all 3 antiplatelet regimens in unadjusted and adjusted analyses, with no overall difference among agents (P= .17). Conclusions Among patients with patent foramen ovale-associated stroke who were managed medically, there were no differences among antiplatelet agents in the risk of recurrent stroke, though confidence intervals were wide.

Background: Randomized PFO closure trials have used open-label endpoint ascertainment, which may increase the risk of bias and undermine confidence in the conclusions. The Gore REDUCE Trial prospectively performed baseline and follow-up MRIs for all subjects, thereby providing an objective measure of the effectiveness of closure. Methods: The presence, location, and volume of new infarct, defined as an acute DWI lesion at time of recurrent clinical stroke or new lesion (>3mm) on T2/FLAIR from baseline to follow up MRI at 2 years, was evaluated using a semi-automated methodology blinded to treatment assignment, comparing patients randomized to undergo closure to those assigned medical therapy. Results: There were no differences in total new infarct volume, new large infarct (>3cm diameter), or new infarct location, comparing patients who underwent closure to those treated with medication (Table). New clinical stroke or clinically silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) of medically treated patients, RR 0.44, 95% CI 0.24-0.82, p=0.008. Recurrent clinical ischemic stroke occurred in 5/383 (1.3%) vs 12/177 (6.8%), RR 0.19, 95% CI 0.07-0.54, p=0.005, and silent brain infarction in 13/383 (3.3%) vs 7/177 (4.0%), RR 0.86, 95% CI 0.34-2.11, p=0.74. Conclusions: New MRI infarcts were generally small and the volumes and distribution of injury were similar between patients randomized to closure and those assigned to aspirin alone. The finding that silent infarcts were not smaller in volume than clinical ischemic strokes and that only clinical strokes were reduced by closure suggests that there may be ascertainment bias in clinical outcomes during open label studies. Nevertheless, as MRI is an objective outcome assessed blinded to randomization assignment, the REDUCE trial provides the highest level of evidence that PFO closure prevents recurrent ischemic brain injury, reducing new infarcts by more than half.

Background and Purpose— Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods— We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results— Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0–1.2]; P =0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions— In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.

Background The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). Objectives A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population. Methods A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33°C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release. Results Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean ± SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 ± 1.54 in the xenon group and 1.56 ± 1.38 in the control group (adjusted mean difference −0.66; 95% confidence interval: −1.16 to −0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively). Conclusions Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T.

Transcatheter closure of patent foramen ovale (PFO) has been demonstrated in clinical trials and meta-analyses to reduce the risk of subsequent stroke in patients who present with cryptogenic strokes [(1)][1]. In the REDUCE trial, PFO closure with the septal occluders (W.L. Gore, Newark, Delaware)

IntroductionWe assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke.Patients and methodsIn this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were randomised to cooling to a target body temperature of 34.0–35.0°C, started within 6 h after stroke onset and maintained for 12 or 24 h , versus standard treatment. The primary outcome was the score on the modified Rankin Scale at 91 days, as analysed with ordinal logistic regression.ResultsThe trial was stopped after inclusion of 98 of the originally intended 1500 patients because of slow recruitment and cessation of funding. Forty-nine patients were randomised to hypothermia versus 49 to standard treatment. Four patients were lost to follow-up. Of patients randomised to hypothermia, 15 (31%) achieved the predefined cooling targets. The primary outcome did not differ between the groups (odds ratio for good outcome, 1.01; 95% confidence interval, 0.48–2.13; p = 0.97). The number of patients with one or more serious adverse events did not differ between groups (relative risk, 1.22; 95% confidence interval, 0.65–1.94; p = 0.52).DiscussionIn this trial, cooling to a target of 34.0–35.0°C and maintaining this for 12 or 24 h was not feasible in the majority of patients. The final sample was underpowered to detect clinically relevant differences in outcomes.ConclusionBefore new trials are launched, the feasibility of cooling needs to be improved.

Purpose To analyse costs related to the diagnosis and treatment of patients with sialolithiasis and sialadenitis managed with sialendoscopy, and to prospectively evaluate the impact of sialendoscopy on health-related quality of life (HRQoL) in a longitudinal follow-up study. Methods All patients undergoing sialendoscopy or sialendoscopy-assisted surgery at a tertiary care university hospital between January 2014 and May 2016 were identified from a surgical database, and the direct hospital costs were retrospectively evaluated from 1 year before to 1 year after the sialendoscopy. The 15D HRQoL questionnaire and a questionnaire exploring the use of health care services during the preceding 3 months were mailed to the patients before sialendoscopy as well as at 3 and 12 months after the operation. Results A total of 260 patients were identified. Mean total hospital costs, costs related to the sialendoscopy, and complications were significantly higher in sialolithiasis patients than in patients with other diagnoses. 74 patients returned the baseline 15D questionnaire, and 51 patients all three 15D questionnaires. At baseline, the dimensions “discomfort and symptoms” and “distress” were lower in patients than in age- and gender-standardised general population, but the total 15D score did not differ significantly. The dimension “discomfort and symptoms” improved significantly at 3 and 12 months postoperatively, and the mean total HRQoL score improved in patients with sialolithiasis at 3 months postoperatively. Conclusions The costs related to sialendoscopy are substantial and the cost-effectiveness of sialendoscopy warrants further studies. However, sialendoscopy seems to reduce patients’ discomfort and ailments and to improve HRQoL at least in patients with sialolithiasis.

Objectives Stroke case fatality is decreasing over time. Less, however, is known about patients’ health-related quality of life (HRQoL), quality-adjusted life years (QALYs), and costs. We studied all these with two data sets collected in Finland 10 years apart. Methods A total of 468 and 355 first-ever ischemic stroke patients were followed up 1 year in two studies (Study 1 in 1989–1991 and Study 2 in 2001–2003). Case fatality, HRQoL measured by the 15D, QALYs, costs, and first-year cost/QALY were compared. Regression analysis was used to examine the effects of various factors on QALYs. Results In the later study, the case fatality rates were lower and the mean 15D scores higher. During the follow-up year, patients experienced on average 0.519 (95% CI 0.453–0.555) and 0.646 (95% CI 0.613–0.680) QALYs in Study 1 and Study 2, respectively (P < 0.001). Age, modified Rankin Scale before stroke onset, acute phase Scandinavian Stroke Scale, and the study group explained the variance of QALYs. The first-year mean total costs were 10 626 € and 14 603 € and the mean cost/QALY 20 474 € and 22 605 € in Study 1 and Study 2, respectively. The incremental cost-effectiveness ratio of Study 2 compared with Study 1 was 31 315 € without and 60 684 € with patient characteristics standardization. Conclusions Stroke patients’ improved outcome is clear, but it remains uncertain to what extent it is attributable to the development of care. More research is needed to study the cost-effectiveness of stroke care.

Author(s): Laitio, Timo; Koskensalo, Kalle; Virtanen, Sami; Saunavaara, Jani; Parkkola, Riitta; Laitio, Ruut; Arola, Olli; Hynninen, Marja; Silvasti, Paivi; Nukarinen, Eija; Martola, Juha; Silvennoinen, Heli M; Tiainen, Marjaana; Roine, Risto O; Scheinin, Harry; Maze, Mervyn; Vahlberg, Tero

Background: The Gore REDUCE Clinical Study (REDUCE) demonstrated superiority of PFO closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients with cryptogenic stroke. Methods: We randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus PFO closure (with Gore HELEX Septal Occluder or Gore CARDIOFORM Septal Occluder) or antiplatelet therapy alone. Co-primary endpoints were freedom from recurrent clinical ischemic stroke through ≥2 years and incidence of new brain infarct (defined as the composite of clinical ischemic stroke and silent brain infarct) at 2 years. Primary analyses were performed on the intention-to-treat (ITT) population. Per-protocol (PP) analysis included only subjects randomized and treated according to critical protocol requirements (excluding those who violated key eligibility criteria, did not receive the therapy to which they were randomized, or did not comply with protocol-required medical regimen). As-treated (AT) analysis assessed all subjects based on treatment received, regardless of study assignment. Results: PFO closure was associated with a highly consistent reduction in risk compared to medical therapy alone in all three analytic cohorts (Table). Conclusions: Among selected patients with cryptogenic stroke and PFO, closure of the PFO plus antiplatelet therapy was superior to antiplatelet therapy alone for reducing the risk of subsequent ischemic stroke.

Background The efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions. Methods In this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet-only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction detected on imaging. Results We enrolled 664 patients (mean age, 45.2 years), of whom 81% had moderate or large interatrial shunts. During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 95% confidence interval [CI], 0.09 to 0.62; P=0.002). The incidence of new brain infarctions was significantly lower in the PFO closure group than in the antiplatelet-only group (22 patients [5.7%] vs. 20 patients [11.3%]; relative risk, 0.51; 95% CI, 0.29 to 0.91; P=0.04), but the incidence of silent brain infarction did not differ significantly between the study groups (P=0.97). Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet-only group (P=0.22). Serious device-related adverse events occurred in 6 patients (1.4%) in the PFO closure group, and atrial fibrillation occurred in 29 patients (6.6%) after PFO closure. Conclusions Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation. (Funded by W.L. Gore and Associates; Gore REDUCE ClinicalTrials.gov number, NCT00738894 .).

Background Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged Key hypotheses/aims (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

IntroductionTelerehabilitation shows promise in many fields though strong evidence of benefit has been limited. We reviewed progress in the use of telerehabilitation for persons with chronic obstructive pulmonary disease (COPD). A challenge in caring for persons with this condition is the ability to achieve high levels of patient participation and compliance with rehabilitation processes.MethodsRelevant publications were identified through literature searches from November 2009 to May 2018. We selected those that described studies of telerehabilitation in the management of COPD and reported clinical or administrative outcomes. Study quality was assessed using an approach that considers both study performance and study design. Judgments were made on whether the telerehabilitation application had been successful, if reported outcomes were clinically significant, and if further data were needed to establish the application as suitable for routine use.ResultsTwenty-five publications, on 26 studies, were selected. Twelve were of high or good quality. In 11 studies the telemedicine application was successful. Nine studies had unsuccessful applications, and for six studies success was unclear. Further data before routine use would be required or desirable for all successful applications. In many studies there were difficulties associated with availability of skilled mentors, motivational support for patients and access to reliable remote monitoring and communication technology.ConclusionsVarious types of telerehabilitation are potentially helpful in the management of COPD. Availability and access to these technologies should improve. However, in management of this clinically challenging condition their use must be linked to suitable training and education of patients with COPD and timely support for them from healthcare professionals.

Objective To investigate the quality of life of men who had been treated for posterior urethral valves (PUV) in childhood. Patients and methods Questionnaires were mailed to 108 patients with PUV treated at the Children's Hospital, University of Helsinki, and 67 (62%) of them responded. Three different questionnaires (15D, LSS, and RAND) were used to evaluate the quality of life. Results The total quality of life in PUV patients was reported as good compared to the general population in the RAND and LSS surveys. However, in the 15D analysis the PUV patients reported lower scores in sleeping, eating, and sexual activity. Those PUV patients who had been treated for renal insufficiency reported lower scores in several dimensions in all three surveys. Patients with urinary incontinence reported more sleeping problems and regarded themselves physically more disabled. Conclusions The PUV patients with renal insufficiency or urinary incontinence had impaired quality of life in several dimensions.

The health-related quality of life (HRQoL) is significantly impaired among urinary incontinent women and the effectiveness of urinary incontinence (UI) treatment should be measured using an HRQoL instrument.A prospective, observational study evaluating the HRQoL of 178 non-selected UI patients referred for routine treatment at the Helsinki University Central Hospital between the years 2004 and 2010. HRQoL was assessed using the generic 15D questionnaire on four occasions: before treatment, 6 and 18 months after treatment, and after a median follow-up of 5 years. The HRQoL of the patients was compared with that of an age-standardized Finnish female population.Compared with the general population, the baseline total HRQoL score of the patients was significantly impaired (p 0.001). It was worse among the urge or mixed (UUI (±SUI)) incontinence patients than among the stress incontinence (SUI) patients (p = 0.035). During follow-up, HRQoL improved and the improvement was more substantial among the operatively than among the conservatively treated patients (p = 0.027). Statistically significant improvement was only seen in the SUI group (Δ + 0.021, 95 % CI 0.005-0.036), but clinically relevant improvement was also found in the operatively treated UUI (±SUI) group. The maximum benefit of treatment was reached between at 2 and 3 years.15D is a sensitive tool for monitoring the change in HRQoL and could be implemented into clinical practice. Operative treatment of UI is effective when measured by improved HRQoL. Not only SUI patients, but also selected patients with an urgency component may benefit from surgery.

Objective To evaluate health-related quality of Life (HRQoL) in patients with abnormal cervical cytology referred for colposcopy. Study design An observational study with prospective and retrospective cohorts. In the prospective arm 240 women referred for colposcopy filled in the 15D HRQoL and the State Anxiety Inventory (STAI) questionnaires and were followed up for 12 months. In the retrospective arm 208 patients who had been treated for cervical dysplasia eight years earlier filled in the 15D HRQoL questionnaire. Results were compared with the age- and sex-standardized general population. Results In the prospective part of the study, the mean 15D score of the patients did not differ from that of the general population. On the dimensions of sleeping, distress and sexual activity, however, the patients scored lower than the general population (p

Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients.An open controlled and randomized single-centre clinical drug trial (clinicaltrials.gov NCT00879892).A multipurpose ICU in university hospital.Thirty-six adult out-of-hospital cardiac arrest patients (18-80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm.Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33°C (mild therapeutic hypothermia group, n=18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon+mild therapeutic hypothermia group, n=18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n=17; Xenon+mild therapeutic hypothermia group, n=16).Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group=5.30 mg vs Xenon+mild therapeutic hypothermia group=2.95 mg, p=0.06). Heart rate was significantly lower in Xenon+mild therapeutic hypothermia patients during hypothermia (p=0.04). Postarrival incremental change in troponin-T at 72 hours was significantly less in the Xenon+mild therapeutic hypothermia group (p=0.04).Xenon treatment in combination with hypothermia is feasible and has favorable cardiac features in survivors of out-of-hospital cardiac arrest.

Importance Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. Objective To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). Design, Setting, and Participants A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. Interventions Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). Main Outcomes and Measures The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. Results Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). Conclusions and Relevance Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. Trial Registration clinicaltrials.gov Identifier:NCT00879892

Purpose The aim of the study was to evaluate mental health and quality of life (QoL) aspects in women operated on because of disorders of sexual differentiation (DSDs) in childhood. Methods Questionnaires were mailed to 45 women older than 15 years who had been operated on because of DSD, of which 24 patients (53%) responded. Of these, 16 had been prenatally exposed to androgens. Eight females had 46,XY karyotype. Mental health was measured with the 90-item Symptom Checklist, QoL with the 20-item Life Situation Survey questionnaire, and health-related QoL (HRQoL) with the 15D questionnaire. Results The QoL and HRQoL scores appeared normal in most of the patients. Furthermore, mental health of the patients was similar or better compared with previously published scores of a Finnish community sample in all dimensions (somatization, obsessive compulsivity, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism). However, 5 patients had poorer scores in some of the 3 questionnaires. These 5 had either distressful memories because of a too-late operation, the operative treatment itself, or current poor sexual function. Conclusions The QoL, HRQoL, and overall mental health of female patients with DSD are usually normal.

Evaluation of the severity of disease and the effectiveness of operative treatment is commonly done by registering pre- and postoperative symptoms. During the preceding decade, greater awareness has focused not only on the symptoms but also on patients' quality of life (QoL). The aim of the study was to determine the effect of septoplasty, as measured by generic and disease-specific QoL questionnaires. The generic 15D and disease-specific SNOT-22 questionnaires were given to patients before the operation and 6 months after the operation. Data analysis consisted originally of 188 septoplasty patients. One-hundred and twenty-six patients (67%) answered the SNOT-22 questions, and in the 15D, the response rate was 76%. In the post-operative SNOT-22, the need to blow the nose, sneezing, runny nose, nasal obstruction, loss of smell or taste, post-nasal discharge, facial pain/pressure, difficulty in falling asleep and waking up at night improved significantly. However in the 15D the mean QoL, i.e., general well-being, became significantly poorer. The QoL became increasingly poor especially in the older age groups and among the patients in which the improvement achieved in nasal symptoms postoperatively was minor. The more nasal symptoms the patients had pre- or postoperatively, the poorer the QoL was in general. Based on our results, critical evaluation of the symptoms and findings in the patients is essential in deciding whether surgery or other treatment should be given to individual patients having nasal blockage symptoms. Especially in patients with mild symptoms or among older patients, adequate medical treatment has to be tried before even considering surgery. The results also encourage the use of a systematic questionnaire to estimate the severity of symptoms in daily clinical practice.

To describe health-related quality of life (HRQoL), quality-adjusted life years (QALYs) gained and school performance in subjects having received either bystander or emergency medical service personnel initiated cardiopulmonary resuscitation (CPR) after a drowning incident in childhood.64 children admitted to pediatric intensive care (PICU) after successful CPR between 1985 and 2007. Eleven died in the PICU, 9 other within 6 months. In 2009 all long-term survivors, except for two, lived at home. Of the 40 patients eligible for the study, 29 (73%) responded to a questionnaire. HRQoL was assessed with the generic 15D, or its versions for adolescents (16D) or children (17D), and compared to that of general population. These HRQoL scores, age-specific survival probabilities, and HRQoL scores of the general population were used in a Markov model to estimate the number of QALYs gained.Median age of the respondents was 17.3 (range: 3.0-28.4) years and 62% were male. At the time of drowning their median age had been 3.0 (range: 1.2-15.7) years. The drowning incident was associated with a significant loss in HRQoL in the oldest age group (total HRQoL total score 0.881 compared to 0.971 in the general population, P0.01) but not in children (HRQoL score 0.944 vs. 0.938). When submersion time exceeded 10min mean HRQoL score was significantly lower than in patients with a shorter submersion (0.844 vs. 0.938, P=0.032). The mean undiscounted and discounted (at 3%) number of QALYs gained by treatment were 40.8 and 17.0, respectively.A good HRQoL will be achieved in the majority of patients surviving long-term after a drowning incident in childhood, although HRQoL is affected by the submersion time.

BackgroundThe threshold to secondary health care should be similar for all patients independent of the underlying disease. This study compared, using a validated health-related quality of life (HRQoL)-instrument, whether the perceived burden of illness is similar in patients admitted for secondary care treatment into a university hospital because of one of six common conditions.MethodsHRQoL, assessed by the generic 15D instrument before elective treatment, was compared in six groups: operative treatment of cataract (n = 219), operative treatment of cervical or lumbar radicular pain (n = 270), hysterectomy due to benign uterine conditions (n = 337), hip or knee replacement surgery (n = 223), coronary angiography due to suspected coronary artery disease (n = 261), and secondary care treatment of depression (n = 89).ResultsMean (±SD) HRQoL score was clearly highest in patients with benign uterine conditions (0.908 ± 0.071) and lowest in patients with depression (0.729 ± 0.120) (P < 0.001 between the groups). Also all the other groups had a significantly (P < 0.001) higher baseline HRQoL score (ranging from 0.802 to 0.824) than patients with depression. Outcome of treatment, in terms of HRQoL improvement, was in depressive patients at least equal, and in some cases even better, than that in the other groups.DiscussionOur results imply that, at least concerning perceived burden of illness, patients with depression are worse off when admitted to secondary care treatment than patients with many somatic conditions. That may be a consequence of poor motivation of depressive patients to seek treatment or that, contradictory to guidelines, the health care system does nor give priority to those worst off and sets a higher threshold for specialized care of patients with depression than of those with common somatic disorders.

Background and Purpose— Treatment of stroke consumes a significant portion of all healthcare expenditure. We developed a system for monitoring costs from individual patient data on a national level in Finland. Methods— Multiple national administrative registers were linked to gain episode-of-care data on all hospital-treated patients with incident stroke over the years 1999 to 2007 (n=94 316). Inpatient and specialist outpatient costs were evaluated with a cost database, long-term care costs with fixed prices, and medication costs with true retail prices. Results— For the patients of Year 2007, the mean 1-year costs after an ischemic stroke were $29 580, after an intracerebral hemorrhage $36 220, and after a subarachnoid hemorrhage $42 570, valued in Year 2008 US dollars. Only part of these costs are attributable to stroke, because the annual costs prior to stroke were significant, $8900 before ischemic stroke, $7600 before intracerebral hemorrhage, and $4200 before subarachnoid hemorrhage. Older patients with ischemic stroke, and, among patients with ischemic stroke and subarachnoid hemorrhage, women, incurred higher costs. The mean estimated lifetime costs were $130 000 after ischemic stroke or intracerebral hemorrhage and $80 000 after subarachnoid hemorrhage. Annually $1.6 billion is spent in the care of Finnish patients with stroke, which equals to 7% of the national healthcare expenditure, or 0.6% of the gross domestic product. Costs of patients with stroke are increasing with prolonged survival and the aging population. Conclusions— Treatment of patients with stroke is a large national investment. Setting up a nationwide system for continuous monitoring of stroke costs is feasible. Cost data should optimally be evaluated in conjunction with effectiveness and performance indicators.

This article in this supplement issue on the Performance, Effectiveness, and Costs of Treatment episodes (PERFECT) project describes trends in Finnish stroke treatment and outcome.The PERFECT Stroke study uses multiple national registry linkages at individual patient level to produce a national stroke database with comprehensive follow-up of all hospital-treated stroke patients in Finland.There were 94,316 incident stroke patients treated in Finnish hospitals from 1999 to 2007. Lengths-of-stays decreased after ischemic stroke (IS), and increased after intracerebral (ICH) and subarachnoid (SAH) hemorrhage. Ten-year survival improved in IS (hazard ratio 0.75; 95% CI 0.71-0.79) and ICH patients (0.88; 0.79-0.97), increasing median survival by 2 and 1 life-years respectively. This has translated into more days spent home among IS patients, but not among ICH patients. Treatment by neurologists improved the survival of IS (odds ratio [OR] 1.77; 95% CI 1.70-1.84) and ICH patients (OR 1.55; 95% CI 1.40-1.69), and treatment by neurosurgeons of SAH patients (OR 2.66; 95% CI 2.25-3.16), the effects were further improved by care in specialized stroke centers.The survival of Finnish IS and ICH patients has improved. Specialized acute care was associated with improved outcome.

Background and Purpose— Early neurological improvement (ENI) after thrombolytic therapy of acute stroke has been linked with recanalization and favorable outcome, although its definition shows considerable variation. We tested the ability of ENI, as defined in previous publications, to predict vessel recanalization and 3-month functional outcome after intravenous thrombolysis recorded in an extensive patient cohort in the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR). Methods— Of 21 534 patients registered between December 2002 and December 2008, 798 patients (3.7%) had CT- or MR angiography-documented baseline vessel occlusion and also angiography data at 22 to 36 hours post-treatment. ENI definitions assessed at 2 hours and 24 hours post-treatment were (1) National Institutes of Health Stroke Scale (NIHSS) score improvement ≥4 points from baseline; (2) NIHSS 0, 1, or improvement ≥8; (3) NIHSS ≤3 or improvement ≥10; (4) improvement by 20%; (5) 40% from baseline; or (6) NIHSS score 0 to 1. Receiver operating curve analysis and multiple logistic regression were performed to evaluate the association of ENI with vessel recanalization and favorable functional outcome (modified Rankin Scale score 0 to 2 at 3 months). Results— ENI at 2 hours had fair accuracy to diagnose recanalization as derived from receiver operating curve analysis. Definitions of improvement based on percent of NIHSS score change from baseline demonstrate better accuracy to diagnose recanalization at 2 hours and 24 hours than the definitions based on NIHSS cutoffs (the best performance at 2 hours was area under the curve 0.633, sensitivity 58%, specificity 69%, positive predictive value 68%, and negative predictive value 59% for 20% improvement; and area under the curve 0.692, sensitivity 69%, specificity 70%, positive predictive value 70%, and negative predictive value 62% for 40% improvement at 24 hours). ENI-predicted functional outcome with OR 2.8 to 6.0 independently from recanalization in the angiography cohort (n=695) and with OR of 6.9 to 9.7 in the whole cohort (n=18 181). Conclusions— Early 20% neurological improvement at 2 hours was the best predictor of 3-month functional outcome and recanalization after thrombolysis, although fairly accurate, and may serve as a surrogate marker of recanalization if only imaging evaluation of vessel status is not available. If recanalization status is required after intravenous thrombolysis, vascular imaging is recommended despite ENI.

Aim: Impaired health-related quality of life (HRQoL) and an increased risk of psychosocial problems may encounter children and adolescents with inflammatory bowel disease (IBD). Generic HRQoL questionnaires, 15D designed for subjects over 16 years of age, 16D for adolescents aged 12–15 and 17D for younger children, allow comparison to healthy peers and have not been used in children with IBD before. Further, in paediatric IBD patients, HRQoL has not been related to disease activity. We evaluated the applicability of 15D, 16D and 17D questionnaires in the paediatric IBD population and examined how HRQoL is influenced by changes in clinical activity of IBD. Methods: The study subjects recruited at their scheduled, routine appointment in the outpatient clinic of the children's hospital completed the HRQoL questionnaire at baseline and again after 3–5 months. Disease activity was estimated by a three-level scale. The HRQoL of the study population was compared with that of the age-standardised general population. Results: Fifty-five children, aged 7–19 years, were recruited. The HRQoL scores strongly correlated with the activity of the disease (P < 0.001). The two oldest age groups with IBD had lower HRQoL scores than age-standardised peers (P= 0.001/0.04). There was no gender difference in HRQoL scores. Conclusions: IBD has a considerable impact on the HRQoL of children and adolescents. The generic HRQoL instruments used appeared to be promising tools for examining HRQoL in paediatric IBD patients in different age groups, but larger studies to establish their usefulness in the follow-up of young patients are still warranted.

Objectives/Hypothesis: To determine clinical features, health-related quality of life, and adult voice in patients with a history of juvenile-onset recurrent respiratory papillomatosis (JORRP). Study Design: Case-control study. Methods: All 32 patients with JORRP treated at Helsinki University Hospital between 1975 and 1994 were invited to an outpatient visit in spring 2008, and 18 of them (56%) entered the study. Each patient had an age- and gender-matched control subject with similar smoking habits. Videolaryngostroboscopy was performed and voice quality determined by acoustic and perceptual analysis. Voice-quality characteristics of the whole patient group and the recurrence-free patients were examined separately. Subjective voice-related disability was studied with voice handicap index (VHI) and health-related quality of life with a 15D questionnaire. Results: Acoustic analysis showed that patients had statistically significantly higher values in percent jitter, percent shimmer, and noise-to-harmonics ratio. Perceptual analysis indicated higher scores for patients in overall grade, roughness, breathiness, and strain. Acoustic and perceptual values for recurrence-free patients (n = 14) were also significantly higher than those for their matched paired controls. No statistically significant differences emerged for handicap related to voice or to health-related quality of life. Four study patients (22%) had undergone tracheotomy, indicating severity of juvenile-onset disease. Conclusions: JORRP is a risk factor for permanent laryngeal pathology and voice-disturbances in adulthood. Laryngoscope, 2011

We aimed to study the voice, voice-related quality of life (VRQoL) and health-related quality of life (HRQoL) of children who in early infancy underwent a laryngeal split (cotton plasty operation) at the Helsinki University Central Hospital between January 1990 and December 2005.A retrospective review identified 17 children, of whom 10 fulfilled the inclusion criteria and participated in the study. Age- and gender-matched volunteers formed a control group. We used generic 16D and 17D questionnaires to assess HRQoL; the Pediatric Voice Outcomes Survey (PVOS) and the pediatric voice-related quality of life (PVRQoL) instrument served to assess VRQoL. The children underwent indirect laryngoscopy and perceptual voice assessment.HRQoL and PVRQoL scores did not differ between subjects and controls. The subjects had lower PVOS scores than did the controls (P0.01). Perceptual assessment revealed that the subjects' voices were worse off according to the following dimensions: voice is strained, voice is hoarse or husky, and voice is weak/does not resonate (P0.05).This study adds to the knowledge on the long-term effects of laryngeal split on children through assessment of their HRQoL and PVRQoL. The study subjects' lower PVOS scores and findings of perceptual assessment point to the effect of cotton plasty on VRQoL and voice.

Background and aims: Patients with inflammatory bowel diseases (IBD) show increased risk for other immune-mediated diseases such as arthritis, ankylosing spondylitis, and some pulmonary diseases. Less is known about the prevalence of other chronic diseases in IBD, and the impact of comorbidity on health-related quality of life (HRQoL). Methods: The study population comprised 2831 IBD patients recruited from the National Health Insurance register and from a patient-association register. Study subjects completed generic 15D and disease-specific IBDQ questionnaires. The Social Insurance Institution of Finland provided data on other chronic diseases entitling patients to reimbursed medication. For each study subject, two controls, matched for age, sex, and hospital district, were chosen. Results: A significant increase existed in prevalence of connective tissue diseases, pernicious anemia and asthma. Furthermore, coronary heart disease (CHD) occurred significantly more frequently in IBD patients than in their peers ( p = 0.004). The difference was, however, more clearly seen in females ( p = 0.014 versus 0.046 in males). Active and long-lasting IBD were risk factors. Concomitant other chronic diseases appeared to impair HRQoL. Asthma, hypertension and psychological disorders had an especially strong negative impact on HRQoL, as observed with both the generic and disease-specific HRQoL tools. Conclusions: In addition to many immune-mediated diseases, CHD appeared to be more common in IBD than in control patients, especially in females. The reason is unknown, but chronic inflammation may predispose to atherosclerosis. This finding should encourage more efficacious management of underlying cardiovascular risk factors, and probably also inflammatory activity in IBD. * Abbreviations: CHD : coronary heart disease CD : Crohn's disease HRQoL : health-related quality of life IBD : inflammatory bowel disease IBDQ : Inflammatory Bowel Disease Questionnaire IC : indeterminate/unspecified colitis SD : standard deviation UC : ulcerative colitis