Chemokine ligand 18 predicts all-cause mortality in patients hospitalized with chest pain of suspected coronary origin.

Introduction: Chemokines mediate recruitment and activation of leucocytes. Chemokine ligand 18 (CCL18) is mainly expressed by monocytes/macrophages and dendritic cells. It is highly expressed in chronic inflammatory diseases, and locally in atherosclerotic plaques, particularly at sites of reduced stability, and systemically in acute coronary syndrome patients. Reports on its prognostic utility in the latter condition, including myocardial infarction (MI), are scarce. Aim: To assess the utility of CCL18 as a prognostic marker of recurrent cardiovascular events in patients hospitalized with chest pain of suspected coronary origin. Methods: The population consisted of 871 consecutive chest-pain patients, of whom 386 were diagnosed with acute myocardial infarction (AMI) based on Troponin-T (TnT) levels >50 ng/L. Stepwise Cox regression models, applying normalized continuous loge/SD values, were fitted for the biomarkers with cardiac mortality within 2 years and total mortality within 2 and 7 years as the dependent variables. Results: Plasma samples from 849 patients were available. By 2 years follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. Univariate analysis showed a positive, significant association between CCL18 and total death [HR 1.55 (95% 1.30-1.83), p < 0.001], and for cardiac death [HR 1.32 (95% 1.06-1.64), p = 0.013]. Associations after adjustment were non-significant. By 7 years follow-up, 332 (38.1%) patients had died. CLL18 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.01-1.29), p = 0.030], but not with MI (n = 203) or stroke (n = 55). Conclusion: CCL18 independently predicts long-term all-cause mortality but had no independent prognostic bearing on short-term cardiac death and CVD events.

α1-antichymotrypsin complex (SERPINA3) is an independent predictor of all-cause but not cardiovascular mortality in patients hospitalized for chest pain of suspected coronary origin.

INTRODUCTION: SERPINA3 is an acute phase protein triggered by inflammation. It is upregulated after an acute myocardial infarction (AMI). Data on its long-term prognostic value in MI patients are scarce. We aimed to assess the utility of SERPINA3 as a prognostic marker in patients hospitalized for chest pain of suspected coronary origin. METHODS: A total of 871 consecutive patients, 386 diagnosed with AMI, were included. Stepwise Cox regression models, applying continuous loge-transformed values, were fitted for the biomarker with all-cause mortality and cardiac death within 2-years or all-cause mortality within median 7 years as dependent variables. An analysis of MI and stroke, and combined endpoints, respectively, was added. The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model. RESULTS: Plasma samples from 847 patients were available. By 2 years follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. The univariate analysis showed a significant association between SERPINA3 and all-cause mortality [HR 1.41 (95% 1.19-1.68), p<0.001], but not for cardiac death. Associations after adjustment were non-significant. By 7 years follow-up, 332 (38.1%) patients had died. SERPINA3 was independently associated with all-cause mortality from the third year onwards. The HR was 1.14 (95% CI, 1.02-1.28), p=0.022. Similar results applied to combined endpoints, but not for MI and stroke, respectively. The prognostic value of SERPINA3 was limited to non-AMI patients. No independent associations were noted among AMI patients. CONCLUSIONS: SERPINA3 predicts long-term all-cause mortality, but failed to predict outcome in AMI patients.

Early outcomes of open anterior versus posterior components separation with transversus abdominis release for large median incisional hernias: a retrospective stepwise analysis.

BACKGROUND: Complex incisional hernia is still a debatable topic, with increasing incidence and an increased local and systemic postoperative morbidity and mortality. The size of the defect is a risk factor for both difficult closure and 30-day readmission due to complications. The main option for closure such defect is a mesh augmented component separation technique. The goal was to evaluate 30-day wound events and general complications including 90 days mortality. MATERIAL AND METHODS: We present a retrospective study that includes patients from two different university hospitals who underwent open incisional hernia repair with anterior component or posterior component separation between January 2015 and December 2021. Only non-contaminated adult patients (over 18 years old) with postoperative primary or recurrent median abdominal wall defects larger than 6 cm and with complete fascial closure were included. Demographics (age, gender, Body Mass Index-BMI, American Society of Anesthesiologists Classification-ASA score), recurrence rank, and co-morbidities), operative details, patient outcomes complications were collected. A native abdomen/pelvis computerized tomography (CT) scan was performed preoperatively in all patients and the anatomy of the defect and volumetry (abdominal cavity volume, incisional hernia volume and peritoneal volume) were evaluated. One of the component separation technique was performed according to Carbonell's equation. RESULTS: Two hundred and two patients (101 from each group) were included. The patients with posterior component separation were more comorbid and with larger defects. The procedure was longer with 80 min but overall length of hospital stay shorter (p < 0.001) for posterior component separation. Seroma, hematoma and skin necrosis were equally distributed for both group of patients and there was no direct relation to surgery (OR 0.887, 95% CI 0.370-2.125, p = 0.788; OR 1.50, 95% CI 0.677-3.33, p = 0.318 and OR 0.386, 95% CI 0.117-1.276, p = 0.119). Surgical Site Infection rate was increased for anterior component separation (p =0.004). CONCLUSION: Complex incisional hernia repair is a challenge given by a large amount of wound complications. Choosing between anterior and posterior component separation is still a source of significant debate. We were not able to depict significant different rates of complications between the procedures and we couldn't find any specific factor related to complications.

Practical use of apomorphine infusion in Parkinson's disease: lessons from the TOLEDO study and clinical experience.

Subcutaneous apomorphine infusion is a device-aided therapy for Parkinson's disease that can be considered when motor fluctuations become persistent and are no longer adequately controlled by oral/transdermal medication. Apomorphine infusion is less invasive than enteral levodopa, deep brain stimulation or focused ultrasound, and is often indicated even when neurosurgical approaches are contraindicated. This article aims to provide practical guidance for doctors and nurses initiating and treating patients with apomorphine infusion, and is based on both trial data and clinical experience from movement disorders specialists. A post hoc analysis of data from the TOLEDO randomized clinical trial of apomorphine infusion was conducted along with an analysis of 'real world' experience from 13 movement disorders specialists using a questionnaire that focused on starting patients on apomorphine infusion. Practical guidelines for starting treatment with apomorphine infusion are provided taking into consideration the regional disparities in healthcare. Apomorphine infusion is straightforward to administer but to be successful it requires concordance from the patient and family, and clinical support from an experienced team of doctors and nurses, particularly in the early months of treatment.

Procollagen type 1 N-terminal propeptide is associated with adverse outcome in acute chest pain of suspected coronary origin.

Background: Extracellular matrix (ECM) is an integral player in the pathophysiology of a variety of cardiac diseases. Cardiac ECM is composed mainly of collagen, of which type 1 is the most abundant with procollagen type 1 N-terminal Propeptide (P1NP) as a formation marker. P1NP is associated with mortality in the general population, however, its role in myocardial infarction (MI) is still uncertain, and P1NP has not been investigated in acute chest pain. The objective of the current study was to assess the role of P1NP in undifferentiated acute chest pain of suspected coronary origin. Methods and results: 813 patients from the Risk in Acute Coronary Syndromes study were included. This was a single-center study investigating biomarkers in consecutively enrolled patients with acute chest pain of suspected coronary origin, with a follow-up for up to 7 years. Outcome measures were a composite endpoint of all-cause death, new MI or stroke, as well as its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. In multivariable Cox regression analysis, quartiles of P1NP were significantly associated with the composite endpoint at 1 year of follow-up with a hazard ratio for Q4 of 1.82 (95% CI, 1.12-2.98). There was no other significant association with outcomes at any time points. Conclusion: P1NP was found to be an independent biomarker significantly associated with adverse clinical outcome at one year in patients admitted to hospital for acute chest pain of suspected coronary origin. This is the first report in the literature on the prognostic value of P1NP in this clinical setting. Clinicaltrialsygov Identifier: NCT00521976.

Performance of bedside tools for predicting infection-related mortality and administrative data for sepsis surveillance: An observational cohort study.

BACKGROUND: Measuring sepsis incidence and associated mortality at scale using administrative data is hampered by variation in diagnostic coding. This study aimed first to compare how well bedside severity scores predict 30-day mortality in hospitalised patients with infection, then to assess the ability of combinations of administrative data items to identify patients with sepsis. METHODS: This retrospective case note review examined 958 adult hospital admissions between October 2015 and March 2016. Admissions with blood culture sampling were matched 1:1 to admissions without a blood culture. Case note review data were linked to discharge coding and mortality. For patients with infection the performance characteristics of Sequential Organ Failure Assessment (SOFA), National Early Warning System (NEWS), quick SOFA (qSOFA), and Systemic Inflammatory Response Syndrome (SIRS) were calculated for predicting 30-day mortality. Next, the performance characteristics of administrative data (blood cultures and discharge codes) for identifying patients with sepsis, defined as SOFA ≥2 because of infection, were calculated. RESULTS: Infection was documented in 630 (65.8%) admissions and 347 (55.1%) patients with infection had sepsis. NEWS (Area Under the Receiver Operating Characteristic, AUROC 0.78 95%CI 0.72-0.83) and SOFA (AUROC 0.77, 95%CI 0.72-0.83), performed similarly well for prediction of 30-day mortality. Having an infection and/or sepsis International Classification of Diseases, Tenth Revision (ICD-10) code (AUROC 0.68, 95%CI 0.64-0.71) performed as well in identifying patients with sepsis as having at least one of: an infection code; sepsis code, or; blood culture (AUROC 0.68, 95%CI 0.65-0.71), Sepsis codes (AUROC 0.53, 95%CI 0.49-0.57) and positive blood cultures (AUROC 0.52, 95%CI 0.49-0.56) performed least well. CONCLUSIONS: SOFA and NEWS best predicted 30-day mortality in patients with infection. Sepsis ICD-10 codes lack sensitivity. For health systems without suitable electronic health records, blood culture sampling has potential utility as a clinical component of a proxy marker for sepsis surveillance.

The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease.

BACKGROUND: Vorapaxar has been shown to reduce cardiovascular mortality in post-myocardial infarction (MI) patients. Pharmacodynamic biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has short follow-up (FU) duration and is mainly focused on platelets rather than endothelial cells. AIM: This article assesses systemic changes in endothelial-related biomarkers during vorapaxar treatment compared with placebo at 30 days' FU and beyond, in patients with coronary heart disease. METHODS: Local substudy patients in Norway were included consecutively from two randomized controlled trials; post-MI subjects from TRA2P-TIMI 50 and non-ST-segment elevation MI (NSTEMI) patients from TRACER. Aliquots of citrated blood were stored at -80°C. Angiopoietin-2, angiopoietin-like 4, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, von Willebrand factor, thrombomodulin, and plasminogen activator inhibitor-1 and -2 were measured at 1-month FU and at study completion (median 2.3 years for pooled patients). RESULTS: A total of 265 consecutive patients (age median 62.0, males 83%) were included. Biomarkers were available at both FUs in 221 subjects. In the total population, angiopoietin-2 increased in patients on vorapaxar as compared with placebo at 1-month FU (p = 0.034). Angiopoietin-like 4 increased (p = 0.028) and plasminogen activator inhibitor-2 decreased (p = 0.025) in favor of vorapaxar at final FU. In post-MI subjects, a short-term increase in E-selectin favoring vorapaxar was observed, p = 0.029. Also, a short-term increase in von Willebrand factor (p = 0.032) favoring vorapaxar was noted in NSTEMI patients. CONCLUSION: Significant endothelial biomarker changes during PAR-1 inhibition were observed in post-MI and NSTEMI patients.

Podocan and Adverse Clinical Outcome in Patients Admitted With Suspected Acute Coronary Syndromes.

Background: Markers of bone and extracellular matrix (ECM) remodeling may be associated with adverse outcomes in atherosclerotic cardiovascular disease. Podocan is a newly discovered ECM glycoprotein, previously not studied in a chest pain population. We wanted to study the association between Podocan levels on admission and the risk of adverse outcomes in a chest pain population with suspected acute coronary syndromes. Methods: A total of 815 patients from the Risk markers in Acute Coronary Syndrome (RACS) trial with suspected coronary chest pain were followed for 7 years. Blood samples were taken immediately after inclusion and stored in the biobank. Associations between Podocan and endpoints were assessed with Cox proportional hazards analyses. Results: The median admission level of Podocan was 0.674 ng/ml (0.566-0.908 ng/ml). No significant association was found between Podocan quartile levels and all-cause death, neither at 1 year nor 2- or 7-years follow-up (p > 0.05 for all). Furthermore, no significant association could be shown between Podocan and cardiac death, myocardial infarction (MI), stroke, or the composites of all-cause death/MI/stroke or cardiac death/MI/stroke (p > 0.05 for all). Similarly, in a subgroup of patients with Troponin T-positive (n = 432) there was no significant association between Podocan and any of the outcome measures (p > 0.05 for all endpoints and points in time). Conclusion: Podocan, a novel ECM biomarker, is not associated with all-cause mortality or other major cardiovascular adverse events in patients admitted with acute chest pain suspected to be of coronary origin. Clinical Trialsgov Identifier: NCT00521976.

Factors Associated with Polyp Detection Rate in European Colonoscopy Practice: Findings of The European Colonoscopy Quality Investigation (ECQI) Group.

Background: The European Colonoscopy Quality Investigation (ECQI) Group aims to raise awareness for improvement in colonoscopy standards across Europe. We analysed data collected on a sample of procedures conducted across Europe to evaluate the achievement of the polyp detection rate (PDR) target. We also investigated factors associated with PDR, in the hope of establishing areas that could lead to a quality improvement. Methods: 6445 form completions from 12 countries between 2 June 2016 and 30 April 2018 were considered for this analysis. We performed an exploratory analysis looking at PDR according to European Society of Gastrointestinal Endoscopy (ESGE) definition. Stepwise multivariable logistic regression analysis was conducted to determine the most influential associated factors after adjusting for the other pre-specified variables. Results: In our sample there were 3365 screening and diagnostic procedures performed in those over 50 years. The PDR was 40.5%, which is comparable with the ESGE minimum standard of 40%. The variables found to be associated with PDR were in descending order: use of high-definition equipment, body mass index (BMI), patient gender, age group, and the reason for the procedure. Use of HD equipment was associated with a significant increase in the reporting of flat lesions (14.3% vs. 5.7%, p < 0.0001) and protruded lesions (34.7% vs. 25.4%, p < 0.0001). Conclusions: On average, the sample of European practice captured by the ECQI survey meets the minimum PDR standard set by the ESGE. Our findings support the ESGE recommendation for routine use of HD colonoscopy.

Factors Associated with Withdrawal Time in European Colonoscopy Practice: Findings of the European Colonoscopy Quality Investigation (ECQI) Group.

The European Colonoscopy Quality Investigation (ECQI) Group aims to raise awareness for improvement in colonoscopy standards across Europe. We analyzed data collected on a sample of procedures conducted across Europe to evaluate the achievement of the European Society of Gastrointestinal Endoscopy (ESGE) mean withdrawal time (WT) target. We also investigated factors associated with WT, in the hope of establishing areas that could lead to a quality improvement. METHODS: 6445 form completions from 12 countries between 2 June 2016 and 30 April 2018 were considered for this analysis. We performed an exploratory analysis looking at WT according to the ESGE definition. Stepwise multivariable logistic regression analysis was conducted to determine the most influential associated factors after adjusting for the other pre-specified variables. RESULTS: In 1150 qualifying colonoscopies, the mean WT was 7.8 min. Stepwise analysis, including 587 procedures where all inputs were known, found that the variables most associated with mean WT were a previous total colonoscopy in the last five years (p = 0.0011) and the time of day the colonoscopy was performed (p = 0.0192). The main factor associated with a WT < 6 min was the time of day that a colonoscopy was performed. Use of sedation was the main factor associated with a higher proportion of WT > 10 min, along with a previous colonoscopy. CONCLUSIONS: On average, the sample of European practice captured by the ECQI survey met the minimum standard set by the ESGE. However, there was variation and potential for improvement.

Complement component 7 is associated with total- and cardiac death in chest-pain patients with suspected acute coronary syndrome.

BACKGROUND: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease. AIM: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information. METHODS: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death. RESULTS: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population. CONCLUSIONS: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976.

Colonoscopy quality across Europe: a report of the European Colonoscopy Quality Investigation (ECQI) Group.

Background and study aims The European Colonoscopy Quality Investigation (ECQI) Group comprises expert colonoscopists and investigators with the aim of raising colonoscopy standards. We assessed the levels of monitoring and achievement of European Society of Gastrointestinal Endoscopy (ESGE) performance measures (PMs) across Europe using responses to the ECQI questionnaires. Methods The questionnaire comprises three forms: institution and practitioner questionnaires are completed once; a procedure questionnaire is completed on multiple occasions for individual total colonoscopies. ESGE PMs were approximated as closely as possible from the data collected via the procedure questionnaire. Procedure data could provide rate of adequate bowel preparation, cecal intubation rate (CIR), withdrawal time, polyp detection rate (PDR), and tattooing resection sites. Results We evaluated ECQI questionnaire data collected between June 2016 and April 2018, comprising 91 practitioner and 52 institution questionnaires. A total of 6445 completed procedure forms were received. Institution and practitioner responses indicate that routine recording of PMs is not widespread: adenoma detection rate (ADR) is routinely recorded in 29 % of institutions and by 34 % of practitioners; PDR by 42 % and 47 %, CIR by 62 % and 64 %, bowel preparation quality by 56 % and 76 %, respectively. Procedure data showed a rate of adequate bowel preparation of 84.2 %, CIR 73.4 %, PDR 40.5 %, mean withdrawal time 7.8 minutes and 12.2 % of procedures with possible removal of a non-pedunculated lesion ≥ 20 mm reporting tattooing. Conclusions Our findings clearly show areas in need of quality improvement and the importance of promoting quality monitoring throughout the colonoscopy procedure.

Angiopoietin-2 and angiopoietin-like 4 protein provide prognostic information in patients with suspected acute coronary syndrome.

BACKGROUND: Plasma levels of angiopoietin-2 (ANGPT2) and angiopoietin-like 4 protein (ANGPTL4) reflect different pathophysiological aspects of cardiovascular disease. We evaluated their association with outcome in a hospitalized Norwegian patient cohort (n = 871) with suspected acute coronary syndrome (ACS) and validated our results in a similar Argentinean cohort (n = 982). METHODS: A cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for ANGPT2 and ANGPTL4, respectively, with all-cause mortality and cardiac death within 24 months and all-cause mortality within 60 months as the dependent variables. RESULTS: At 24 months follow-up, 138 (15.8%) of the Norwegian and 119 (12.1%) of the Argentinian cohort had died, of which 86 and 66 deaths, respectively, were classified as cardiac. At 60 months, a total of 259 (29.7%) and 173 (17.6%) patients, respectively, had died. ANGPT2 was independently associated with all-cause mortality in both cohorts at 24 months [hazard ratio (HR) 1.27 (95% confidence interval (CI), 1.08-1.50) for Norway, and HR 1.57 (95% CI, 1.27-1.95) for Argentina], with similar results at 60 months [HR 1.19 (95% CI, 1.05-1.35) (Norway), and HR 1.56 (95% CI, 1.30-1.88) (Argentina)], and was also significantly associated with cardiac death [HR 1.51 (95% CI, 1.14-2.00)], in the Argentinean population. ANGPTL4 was significantly associated with all-cause mortality in the Argentinean cohort at 24 months [HR 1.39 (95% CI, 1.15-1.68)] and at 60 months [HR 1.43 (95% CI, 1.23-1.67)], enforcing trends in the Norwegian population. CONCLUSIONS: ANGPT2 and ANGPTL4 were significantly associated with outcome in similar ACS patient cohorts recruited on two continents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00521976. ClinicalTrials.gov Identifier: NCT01377402.

Continuous Subcutaneous Apomorphine Infusion in Parkinson's Disease: A Single-Center, Long-Term Follow-Up Study of the Causes for Discontinuation.

(1) Background: Subcutaneous apomorphine infusion (SCAI) is one of the three main treatment options for motor fluctuations in advanced Parkinson's disease (PD). The adherence to SCAI is generally considered to be low due to adverse events and because it is perceived as a treatment option to be used for a limited period only. We evaluated the reasons for discontinuation of SCAI in relation to when patients stopped treatment. (2) Methods: We reviewed the medical records of PD patients treated with SCAI at a single center, capturing patient demographics and the reasons for cessation of SCAI. (3) Results: 101 patients were included in the analysis, with a median time on treatment of 6.34 years. The main reasons for stopping SCAI were adverse events, death, and dissatisfaction with treatment. In the first 6 years of treatment, the predominant side effects leading to discontinuation were somnolence and hallucinations. (4) Conclusions: We suggest that SCAI can be an effective long-term treatment option for advanced PD, but it requires careful patient selection, a high level of communication with the patient and carer, and rigorous monitoring of the effects of treatment and for any adverse events so they can be promptly managed.

Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study.

INTRODUCTION: The randomized, double-blind phase (DBP) of the TOLEDO study confirmed the efficacy of apomorphine infusion (APO) in reducing OFF time in PD patients with persistent motor fluctuations despite optimized oral/transdermal therapy. Here we report safety and efficacy results including the 52-week open-label phase (OLP). METHODS: All patients completing the 12-week DBP (including those switching early to open-label treatment) were offered OLP entry. The primary objective was the evaluation of long-term safety of APO. RESULTS: Eighty-four patients entered the OLP (40 previously on APO, 44 on placebo) and 59 patients (70.2%) completed the study. The safety profile of APO was consistent with experience from extensive clinical use. Common treatment-related adverse events (AEs) were mild or moderate infusion site nodules, somnolence and nausea. Fourteen (16.7%) patients discontinued the OLP due to AEs, those involving >1 patient were infusion site reactions (n = 4) and fatigue (n = 2); hemolytic anemia occurred in one case. Reduction in daily OFF time and improvement in ON time without troublesome dyskinesia were sustained for up to 64 weeks. Pooled data for week 64 (n = 55) showed a mean (SD) change from DBP baseline in daily OFF time of -3.66 (2.72) hours and in ON time without troublesome dyskinesia of 3.31 (3.12) hours. Mean (±SD) daily levodopa-equivalent dose decreased from DBP baseline to week 64 by 543 mg (±674) and levodopa dose by 273 mg (±515). CONCLUSIONS: The safety and efficacy of APO infusion were demonstrated with long-term use for persistent motor fluctuations, allowing substantial reductions in oral PD medication.

RANIBIZUMAB 0.5 MG TREATMENT IN ADOLESCENTS WITH CHOROIDAL NEOVASCULARIZATION: SUBGROUP ANALYSIS DATA FROM THE MINERVA STUDY.

PURPOSE: To evaluate the efficacy and safety of ranibizumab 0.5 mg in adolescent patients with any choroidal neovascularization etiology enrolled in the 12-month MINERVA study. METHODS: In the open-label, non-randomized study arm, ranibizumab 0.5 mg was administered to five adolescents (aged 13-17 years). The findings were assessed descriptively as individual case reports at Month 12. Best-corrected visual acuity changes, central subfield thickness, treatment exposure, and safety were described over 12 months. RESULTS: Baseline choroidal neovascularization etiologies of the study eye included choroidal neovascularization secondary to Best disease (n = 2), idiopathic chorioretinopathy (n = 2), and optic disk drusen (n = 1). At Months 2, 6, and 12, the observed mean best-corrected visual acuity changes in the study eye from baseline were +9.2, +16.6, and +16.6 letters, respectively, and the observed mean central subfield thickness change from baseline was -31.4, -87.6, and -116.4 µm, respectively. Adolescent patients received a mean of three (range, 2-5) ranibizumab injections in the study eye. No adverse events or serious adverse events related to ranibizumab were reported. CONCLUSION: Ranibizumab 0.5 mg treatment was beneficial in improving visual acuity and stabilizing or reducing central subfield thickness in five adolescents with differing choroidal neovascularization etiologies requiring infrequent injection. No new safety findings were observed over 12 months.

Association of out of hospital paediatric early warning score with need for hospital admission in a Scottish emergency ambulance population.

OBJECTIVE: Physiological derangement, as measured by paediatric early warning score (PEWS) is used to identify children with critical illness at an early point to identify and intervene in children at risk. PEWS has shown some utility as a track and trigger system in hospital and also as a predictor of adverse outcome both in and out of hospital. This study examines the relationship between prehospital observations, aggregated into an eight-point PEWS (Scotland), and hospital admission. METHODS: A retrospective analysis of all patients aged less than 16 transported to hospital by the Scottish Ambulance Service between 2011 and 2015. Data were matched to outcome data regarding hospital admission or discharge and length of stay. RESULTS: Full data were available for 21 202 paediatric patients, of whom 6340 (29.9%) were admitted to hospital. Prehospital PEWS Scotland was associated with an odds ratio for admission of 1.189 [95% confidence interval (CI): 1.176-1.202; P < 0.001]. The area under receiver operating curve of 0.617 (95% CI: 0.608-0.625; P < 0.001) suggests poorly predictive ability for hospital admission. There was no association between prehospital PEWS Scotland and length of hospital stay. CONCLUSION: These data show that a single prehospital PEWS Scotland was a poor predictor of hospital admission for unselected patients in a prehospital population. The decision to admit a child to hospital is not solely based on the physiological derangement of vital signs, and hence physiological-based scoring systems such as PEWS Scotland cannot be used as the sole criteria for hospital admission, from an undifferentiated prehospital population.

N-terminal pro-B-type natriuretic peptide as a prognostic indicator for 30-day mortality following out-of-hospital cardiac arrest: a prospective observational study.

BACKGROUND: Early risk stratification applying cardiac biomarkers may prove useful in sudden cardiac arrest patients. We investigated the prognostic utility of early-on levels of high sensitivity cardiac troponin-T (hs-cTnT), copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a prospective observational unicenter study, including patients with OHCA of assumed cardiac origin from the southwestern part of Norway from 2007 until 2010. Blood samples for later measurements were drawn during cardiopulmonary resuscitation or at hospital admission. RESULTS: A total of 114 patients were included, 37 patients with asystole and 77 patients with VF as first recorded heart rhythm. Forty-four patients (38.6%) survived 30-day follow-up. Neither hs-cTnT (p = 0.49), nor copeptin (p = 0.39) differed between non-survivors and survivors, whereas NT-proBNP was higher in non-survivors (p <  0.001) and significantly associated with 30-days all-cause mortality in univariate analysis, with a hazard ratio (HR) for patients in the highest compared to the lowest quartile of 4.6 (95% confidence interval (CI), 2.1-10.1), p <  0.001. This association was no longer significant in multivariable analysis applying continuous values, [HR 0.96, (95% CI, 0.64-1.43), p = 0.84]. Similar results were obtained by dividing the population by survival at hospital admission, excluding non-return of spontaneous circulation (ROSC) patients on scene [HR 0.93 (95% CI, 0.50-1.73), P = 0.83]. We also noted that NT-proBNP was significantly higher in asystole- as compared to VF-patients, p <  0.001. CONCLUSIONS: Early-on levels of hs-cTnT, copeptin and NT-proBNP did not provide independent prognostic information following OHCA. Prediction was unaffected by excluding on-scene non-ROSC patients in the multivariable analysis. TRIAL REGISTRATION: ClinicalTrials. gov, NCT02886273 .

Development of a high throughput and low cost model for the study of semi-dry biofilms.

The persistence of microorganisms as biofilms on dry surfaces resistant to the usual terminal cleaning methods may pose an additional risk of transmission of infections. In this study, the Centre for Disease Control (CDC) dry biofilm model (DBM) was adapted into a microtiter plate format (Model 1) and replicated to create a novel in vitro model that replicates conditions commonly encountered in the healthcare environment (Model 2). Biofilms of Staphylococcus aureus grown in the two models were comparable to the biofilms of the CDC DBM in terms of recovered log10 CFU well-1. Assessment of the antimicrobial tolerance of biofilms grown in the two models showed Model 2 a better model for biofilm formation. Confirmation of the biofilms' phenotype with an extracellular matrix deficient S. aureus suggested stress tolerance through a non-matrix defined mechanism in microorganisms. This study highlights the importance of conditions maintained in bacterial growth as they affect biofilm phenotype and behaviour.

The relationship between frailty, functional dependence, and healthcare needs among community-dwelling people with moderate to severe dementia.

This paper examines the healthcare needs of community-dwelling older people living in Porto, Portugal, diagnosed with moderate or severe dementia, linked to functional dependency, cognitive decline, limitations in the activities of daily life, and frailty levels. A sample of 83 participants was recruited. Data were collected between 2013 and 2017. A sociodemographic questionnaire, the Clinical Dementia Rating (CDR), the Barthel Index (BI), the Lawton and Brody Instrumental Activities of Daily Living (IADL) Scale, and the Edmonton Frail Scale (EFS) were used. A set of 26 healthcare needs was defined to support the assessment. The Pearson chi-square or Fisher's exact test (as appropriate) was used to examine the association of the needs (unmet and met) with the levels of dementia and frailty. Participants were diagnosed previously with moderate or severe dementia and benefited from a structured home-care program. There was a high number rated as "severe dementia," "fully dependent," "severely or fully dependent in the activities of daily living (ADL)," and "severe frailty." There were statistically significant differences among needs identified in people with moderate or severe dementia and moderate or severe frailty. The most prevalent healthcare needs in the sample were food preparation, medication/taking pills, looking after their home, toilet use, sensory problems, communication/interaction, bladder, bowels, eating and drinking, memory, sleeping, and falls prevention. In particular, the study identifies a set of needs that are present simultaneously in both frailty and dementia stages. This study underlines that despite well-structured home-care programs for people with dementia, unmet health needs remain. Timely healthcare needs assessment may help professionals to avoid fragmented care and to tailor quality-integrated interventions, including the emotional and psychological balance of the caregiver.