Predefined Outcome Measures Research Articles

Improving Admission Temperature in Infants ≥34 Weeks' Gestation: A Quality Improvement Initiative.

NICU admission for hypothermia is a problem worldwide, with associated morbidity, mortality, and financial costs. Many interventions have been studied for smaller infants, but there has been little focus on infants born ≥34 weeks' gestational age (GA), though most deliveries occur at this gestation. Our primary aim was to improve the proportion of infants ≥34 weeks' GA with normal NICU admission temperature. Secondary outcomes included improvement of the proportion of normal first temperature in all infants ≥34 weeks' GA, independent of NICU admission, and improvement of predefined outcome measures. We completed a root cause analysis, using fishbone and process mapping to determine what factors were contributing to hypothermia. A series of changes were trialed using plan-do-study-act cycles to develop a standard operating procedure, covering both vaginal and cesarean section births. Outcome measures were analyzed using a P-chart as well as traditional statistical tests. We successfully increased the proportion of infants ≥34 weeks' GA with normothermia on NICU admission from 62% to 80% without increasing hyperthermia. In addition, the interventions improved the proportion of delivery room normothermia in all infants born ≥34 weeks' GA and were associated with a decreased need for intravenous therapy for hypoglycemia and the incidence of metabolic acidosis. This quality improvement initiative was successful at improving our institution's rates of normal infant temperature. The methodology used can be applied to other similar centers to improve this common problem.

Association of Indoleamine 2,3-Dioxygenase (IDO) Activity with Outcome after Cardiac Surgery in Adult Patients.

Indoleamine 2,3-deoxygenase (IDO) plays an important role in the catabolism of the amino acid tryptophan. Tryptophan and its metabolites are key immune modulators. Increased IDO activity has been observed in various diseases and is associated with worse clinical outcomes. However, comprehensive research regarding its role in cardiac surgery remains limited. Therefore, we aimed to investigate perioperative changes in IDO activity and pathway metabolites, along with their impact on clinical outcomes in adult patients undergoing cardiac surgery. As an observational cohort study conducted at the Inselspital in Bern from January to December 2019, we retrospectively analyzed the data of prospectively collected biobank samples of patients undergoing cardiac surgery with the use of cardiopulmonary bypass. IDO pathway metabolite analysis was conducted by mass spectrometry. Perioperative dynamics were descriptively assessed and associated with pre-defined clinical outcome measures (30-day mortality, 1-year mortality, incidence of stroke and myocardial infarction, and length of hospital stay) through a multi-step exploratory regression analysis. A cohort of 192 adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass were included (median age 67.0, IQR 60.0-73.0, 75.5% male). A significant perioperative decrease in the kynurenine/tryptophan (Kyn/Trp) ratio (-2.298, 95% CI -4.028 to -596, p = 0.009) and significant perioperative dynamics in the associated metabolites was observed. No association of perioperative changes in IDO activity and pathway metabolites with clinical outcomes was found. A significant decrease in the Kyn/Trp ratio among adult patients undergoing cardiac surgery indicates a perioperative downregulation of IDO, which stands in contrast to other pro-inflammatory conditions. Further studies are needed to investigate IDO in the setting of perioperative immunomodulation, which is a key driver of postoperative complications in cardiac surgery patients.

Study protocol of a national multicentre prospective evaluation study assessing the validity and impact of the Dutch Paediatric Early Warning Score (PEWS) in the Netherlands

IntroductionEarly recognition of clinical deterioration and timely intervention are important to improve morbidity and mortality in paediatric care. The Paediatric Early Warning Score (PEWS) is a scoring system aiming to...

Evaluation of the impact of a health-system specialty pharmacy patient management program on achieving predefined clinical outcome measures.

Specialty medications often have high costs, pose difficulties with payor approval, and require additional monitoring. Earlier articles have defined various examples of clinical outcome measures (COMs); however, goals and benchmarks have not been well defined, and a gap in the literature exists. This study evaluated the effectiveness of our health-system specialty pharmacy (HSSP) patient management program (PMP) in achieving predefined COM goals. Disease state protocols were developed within the HSSP, and clinical and adherence goals were created for each COM based on primary literature. This retrospective, single-center review examined outcomes and adherence data on patients enrolled in the PMP during 2022. The primary outcome was the number of predefined disease state COM goals met. Secondary outcomes included the number of predefined adherence goals met and annual financial impact. Of 1,431 patients whose records were reviewed, 1,053 met criteria for inclusion. The primary outcome analysis showed that 85% (33 of 39) of the predefined disease state goals were met. Predefined adherence goals were met, with an average proportion of days covered (PDC) for all specialty medications of >90%. The PMP yielded $5,167,043 in direct patient cost savings and $167,260 in cost avoidance. The PMP yielded positive results in meeting goals set for the COMs in the disease states managed within the HSSP. COMs will remain a focus for HSSPs to help patients achieve desired clinical outcomes and HSSPs adhere to accreditation standards. More research in this field and standardization of COM goals may benefit the larger HSSP community.

Patient perspectives on same-day discharge following catheter ablation for atrial fibrillation: Results from a patient survey as part of the monocentric FAST AFA trial.

Same-day discharge (SDD) following catheter ablation (CA) of atrial fibrillation (AF) was already introduced in selected facilities in Europe but a widespread implementation has not yet succeeded. Data on patients' perspectives is lacking. Therefore, we conducted a survey to address patients' beliefs towards SDD and identify variables that are associated with their evaluation. As part of the prospective, monocentric FAST AFA trial, patients aged ≥20 years undergoing left atrial CA for AF were asked to participate in the survey consisting of a study-specific questionnaire, the AF knowledge scale and pre-defined PROMs. The study cohort was stratified based on SDD willingness and a logistic regression analysis was used to identify predictors for patients' valuation. Between 07/26/2021-07/01/2022, 256 of 376 screened patients consented to study participation of whom 248 (mean age 61.8 years, 33.9% female) completed the SDD survey. Of them, 50.0% were willing to have SDD concepts integrated into their clinical course with increased patient comfort (27.5%), shorter waiting times (14.6%) and a cost-efficient treatment (14.0%) being imaginable benefits. In contrast, expressed concerns included uncertainties with occurring complaints (50.6%), and the insufficient recognition (47.8%) and treatment (48.9%) of complications. EHRA class at baseline and inpatient treatments within the preceding year were predictors for SDD willingness whereas comorbidity burden or AF knowledge were not. We provide a detailed survey expressing patients' beliefs towards SDD following left atrial CA. Our findings may facilitate adequate patient selection to improve the future implementation of SDD programs in suitable cohorts.

Comparison Between Burden of Care Partners of Individuals with Alzheimer's Disease Versus Individuals with Other Chronic Diseases.

Caregiving in Alzheimer's disease (AD) is often provided by informal care partners, who spend more hours per week on average than care partners of individuals with conditions other than AD. However, the burden of care in partners of individuals with AD has not been systematically compared to that of other chronic diseases. The current study therefore aims to compare the care partner burden of AD to that of other chronic diseases through a systematic literature review. Data was collected from journal articles published in the last 10years, using two unique search strings in PubMed and analysed using pre-defined patient-reported outcome measures (PROMs) including the EQ-5D-5L, GAD-7, GHQ-12, PHQ-9, WPAI and the ZBI. The data was grouped according to the included PROMs and the diseases studied. The number of participants in the studies reporting burden of caregiving in AD was adjusted to reflect the number of participants in studies reporting care partner burden in other chronic diseases. All results in this study are reported as a mean value and standard deviation (SD). The ZBI measurement was the most frequently used PROM to collect care partner burden (15 studies) and showed a moderate burden (mean 36.80, SD 18.35) on care partners of individuals with AD, higher than most of the other included diseases except for those characterized by psychiatric symptoms (mean scores 55.92 and 59.11). Other PROMs such as PHQ-9 (six studies) and GHQ-12 (four studies) showed a greater burden on care partners of individuals with other chronic diseases such as heart failure, haematopoietic cell transplantations, cancer and depression compared to AD. Likewise, GAD-7 and EQ-5D-5L measurements showed a lesser burden on care partners of individuals with AD compared to care partners of individuals with anxiety, cancer, asthma and chronic obstructive pulmonary disease. The current study suggests that care partners of individuals with AD experience a moderate burden, but with some variations depending on the PROMs used. The results of this study were mixed with some PROMs indicating a greater burden for care partners of individuals with AD versus other chronic diseases, and other PROMs showing a greater burden for care partners of individuals with other chronic diseases. Psychiatric disorders imposed a greater burden on care partners compared to AD, while somatic diseases in the musculoskeletal system resulted in a significantly smaller burden on care partners compared to AD.

The Success Rate of Glaucoma Drainage Device Revision.

We report the survival of surgical revision to glaucoma drainage devices for several indications in a large cohort of patients, with an overall success rate of 45% at 36 months. To evaluate the outcomes of surgical revision for complications of glaucoma drainage devices. Three hundred thirty-five eyes of 318 patients who underwent tube revision or removal at University of California Los Angeles (UCLA) Jules Stein Eye Institute between 1997 and 2019 were included. The pre-defined primary outcome measure was surgical success of the initial revision, defined as resolution of the condition with no additional revisions required, no functionally significant change in vision, and no instances of intraocular pressure > 21mmHg at 2 consecutive visits postoperatively. Kaplan-Meier survival analysis was applied to evaluate survival at 36 months based on these criteria. The Wilcoxon paired test was used to compare mean preoperative and postoperative intraocular pressure, medication usage, and visual acuity. Overall, survival of revised tubes at 36 months was 45%. The 4 most common indications for revision were exposure of the implant (42% of all revisions), occlusion (14%), corneal failure or threat of failure (12%), and hypotony (11%). Survival at 36 months for each of these indications was 44%, 45%, 52%, and 37%, respectively. These results suggest that eyes with glaucomatous damage with long-term glaucoma drainage device complications can still have a reasonably successful outcome when a revision is performed. However, with substantial rates of vision loss and a frequent need for additional revisions to manage complications, managing patient expectations for success and making them aware of the likelihood of additional surgeries or failure is important.

Baseline serum vitamin A and vitamin C levels and their association with disease severity in COVID-19 patients.

We aimed to investigate the association between the serum concentrations of Vitamin A and Vitamin C and the severity of the COVID-19. Methods:Fifty-three consecutive PCR (+) COVID-19 patients admitted to a dedicated ward were enrolled in this study. Blood samples for serum Vitamin A and C measurements were drawn from all participants upon admission. All subjects underwent thoracic CT imaging prior to hospitalization. CT severity score (CT-SS) was then calculated for determining the extent of pulmonary involvement. A group of healthy volunteers, in whom COVID-19 was ruled out, were assigned to the control group (n=26). These groups were compared by demographic features and serum vitamin A and C levels. The relationship between serum concentrations of these vitamins and pre-defined outcome measures, CT-SS and length of hospitalization (LOH), was also assessed. Results:In COVID-19 patients, serum Vitamin A (ng/ml, 494±96 vs. 698±93; p<0.001) and Vitamin C (ng/ml, 2961 [1991-31718] vs. 3953 [1385-8779]; p=0.007) levels were significantly lower with respect to healthy controls. According to the results of correlation analyses, there was a significant negative association between Vitamin A level and outcome measures (LOH, r=-0.293; p=0.009 and CT-SS, r=-0.289; p=0.010). The negative correlations between Vitamin C level and those measures were even more prominent (LOH, r=-0.478; p<0.001 and CT-SS, r=-0.734: p<0.001). COVID-19 patients had lower baseline serum Vitamin A and Vitamin C levels as compared to healthy controls. In subjects with COVID-19, Vitamin A and Vitamin C levels were negatively correlated with CT-SS and LOH.

Listening to music for insomnia in adults.

Insomnia is a common problem in modern society. It is associated with reduced quality of life and impairments in physical and mental health. Listening to music is widely used as a sleep aid, but it remains unclear if it can actually improve insomnia in adults. This Cochrane Review is an update of a review published in 2015. To assess the effects of listening to music on sleep in adults with insomnia and to assess the influence of specific variables that may moderate the effect. For this update, we searched CENTRAL, MEDLINE, Embase, nine other databases and two trials registers up to December 2021. In addition, we handsearched reference lists of included studies, and contacted authors of published studies to identify additional studies eligible for inclusion, including any unpublished or ongoing trials. Randomised controlled trials comparing the effects of listening to music with no treatment or treatment as usual (TAU) in adults complaining of sleep difficulties. Two review authors independently screened records for eligibility, selected studies for inclusion, extracted data and assessed risk of bias of the included studies. We assessed the certainty of the evidence using GRADE. The primary outcomes were sleep quality, insomnia severity, sleep-onset latency, total sleep time, sleep interruption, sleep efficiency and adverse events. Data on the predefined outcome measures were included in meta-analyses when consistently reported by at least two studies that were homogeneous in terms of participants, interventions and outcomes. We undertook meta-analyses using random-effects models. We included 13 studies (eight studies new to this update) comprising 1007 participants. The studies examined the effect of listening to prerecorded music daily, for 25 to 60 minutes, for a period of three days to three months. The risk of bias within the studies varied, with all studies being at high risk of performance bias, because of limited possibilities to blind participants to the music intervention. Some studies were at high risk of detection bias or other bias. Four studies reported funding from national research councils, three studies reported financial support from university sources and one study reported a grant from a private foundation. Five studies did not report any financial support. At the end of the intervention, we found moderate-certainty evidence for improved sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI) in themusic groups compared to no intervention or TAU (mean difference (MD) -2.79, 95% confidence interval (CI) -3.86 to -1.72; 10 studies, 708 participants). The PSQI scale ranges from 0 to 21 with higher scores indicating poorer sleep. The size of the effect indicates an increase in sleep quality of the size of about one standard deviation in favour of the intervention. We found no clear evidence of a difference in the effects of listening to music compared to no treatment or TAU on insomnia severity (MD -6.96, 95% CI -15.21 to 1.28; 2 studies, 63 participants; very low-certainty evidence). We found low-certainty evidence that, compared to no treatment or TAU, listening to music may reduce problems with sleep-onset latency (MD -0.60, 95% CI -0.83 to -0.37; 3 studies, 197 participants), total sleep time (MD -0.69, 95% CI -1.16 to -0.23; 3 studies, 197 participants) and sleep efficiency (MD -0.96, 95% CI -1.38 to -0.54; 3 studies, 197 participants), but may have no effect on perceived sleep interruption (MD -0.53, 95% CI -1.47 to 0.40; 3 studies, 197 participants). In addition, three studies (136 participants) included objective measures of sleep-onset latency, total sleep time, sleep efficiency and sleep interruption and showed that listening to music may not improve these outcomes compared to no treatment or TAU. None of the included studies reported any adverse events. The findings of this review provide evidence that music may be effective for improving subjective sleep quality in adults with symptoms of insomnia. More research is needed to establish the effect of listening to music on other aspects of sleep as well as the daytime consequences of insomnia.

The Influence of Wearables on Health Care Outcomes in Chronic Disease: Systematic Review.

BackgroundChronic diseases contribute to high rates of disability and mortality. Patient engagement in chronic disease self-management is an essential component of chronic disease models of health care. Wearables provide patient-centered health data in real time, which can help inform self-management decision-making. Despite the perceived benefits of wearables in improving chronic disease self-management, their influence on health care outcomes remains poorly understood.ObjectiveThis review aimed to examine the influence of wearables on health care outcomes in individuals with chronic diseases through a systematic review of the literature.MethodsA narrative systematic review was conducted by searching 6 databases for randomized and observational studies published between January 1, 2016, and July 1, 2021, that included the use of a wearable intervention in a chronic disease group to assess its impact on a predefined outcome measure. These outcomes were defined as any influence on the patient or clinician experience, cost-effectiveness, or health care outcomes as a result of the wearable intervention. Data from the included studies were extracted based on 6 key themes, which formed the basis for a narrative qualitative synthesis. All outcomes were mapped against each component of the Quadruple Aim of health care. The guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement were followed in this study.ResultsA total of 30 articles were included; studies reported 2446 participants (mean age: range 10.1-74.4 years), and the influence of 14 types of wearables on 18 chronic diseases was presented. The most studied chronic diseases were type 2 diabetes (4/30, 13%), Parkinson disease (3/30, 10%), and chronic lower back pain (3/30, 10%). The results were mixed when assessing the impact on a predefined primary outcome, with 50% (15/30) of studies finding a positive influence on the studied outcome and 50% (15/30) demonstrating a nil effect. There was a positive effect of 3D virtual reality systems on chronic pain in 7% (2/30) of studies that evaluated 2 distinct chronic pain syndromes. Mixed results were observed in influencing exercise capacity; weight; and biomarkers of disease, such as hemoglobin A1c, in diabetes. In total, 155 outcomes were studied. Most (139/155, 89.7%) addressed the health care outcomes component. This included pain (11/155, 7.5%), quality of life (7/155, 4.8%), and physical function (5/155, 3.4%). Approximately 7.7% (12/155) of outcome measures represented the patient experience component, with 1.3% (2/155) addressing the clinician experience and cost.ConclusionsGiven their popularity and capability, wearables may play an integral role in chronic disease management. However, further research is required to generate a strong evidence base for safe and effective implementation.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42021244562; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=244562

Fetal weight projection model to define growth velocity and validation against pregnancy outcome in a cohort of serially scanned pregnancies.

ABSTRACTObjectiveFetal growth assessment is central to good antenatal care, yet there is a lack of definition of normal and abnormal fetal growth rate which can identify pregnancies at risk of adverse outcome. The aim of this study was to develop and test a model for defining normal limits of growth velocity which are specific to the fetal weight measurement interval.MethodsThe cohort consisted of 102 138 singleton pregnancies which underwent at least two third‐trimester measurements of ultrasound estimated fetal weight (EFW), usually carried out because routine early‐pregnancy risk assessment had indicated an increased risk of fetal growth restriction. We projected the EFW from the first of each consecutive measurement pair along its own centile rank to the gestational age of the second scan. Normal growth was defined as the second EFW being within a weight range based on limits derived by partial receiver‐operating‐characteristics‐curve (pROC) analyses for small‐for‐gestational‐age (SGA; < 10th centile) and large‐for‐gestational‐age (LGA; > 90th centile) birth weight. The limits were measurement‐interval specific and calculated for a fixed false‐positive rate (FPR) of 10%. The resultant normal, slow and accelerated growth rates calculated from consecutive EFW pairs were evaluated against the following predefined perinatal outcome measures: stillbirth, neonatal death, SGA and LGA at birth, 5‐min Apgar score < 7 and admission to the neonatal intensive care unit. Slow growth based on the last two scans was compared with SGA fetal weight (EFW < 10th centile) at the last scan and association with stillbirth risk was assessed, expressed as relative risk (RR) with 95% CI.ResultsThe optimal cut‐off limits for normal growth rate between consecutive scans varied according to the length of the measurement interval, with an average of –8.0% for slow growth and + 9.3% for accelerated growth at a fixed FPR of 10%. Slow growth between random consecutive scan pairs was associated significantly with all predefined outcome measures including stillbirth (RR, 2.19; 95% CI, 1.84–2.53) and neonatal death (RR, 2.28; 95% CI, 1.60–3.13). Accelerated growth was associated with LGA at birth (RR, 2.15; 95% CI, 2.10–2.20), while normal growth was protective of all adverse outcome measures. Slow growth between the last two scans (which were performed at a median gestational age of 33 + 1 to 36 + 4 weeks) and SGA at the last scan were each predictors of stillbirth, and stillbirth risk was highest when both were present (RR, 2.65; 95% CI, 1.67–4.20). However, 66.2% of pregnancies with slow growth were not SGA at the last scan and these cases also had an increased risk of stillbirth (RR, 2.07; 95% CI, 1.40–3.05).ConclusionFetal growth velocity defined by projected, measurement‐interval specific fetal weight limits is associated independently with perinatal outcome and should be used for antenatal surveillance in addition to assessment by fetal size. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

MHealth impact on secondary stroke prevention: a scoping review of randomized controlled trials among stroke survivors between 2010-2020.

A fundamental gap between clinical prevention and self-management awareness heightens the risk for stroke recurrence in approximately one-fourth of the highest risk stroke survivors annually. Secondary stroke prevention has the potential to be promoted by mobile health (mHealth) applications for effective real-world adoption of vascular risk factor mitigation. This scoping review aims to evaluate the impact of mHealth interventions and their effectiveness to reduce recurrent stroke rates among stroke survivors in randomized controlled trials (RCTs). Scoping review in Ovid Medline, Cochrane Library, CINAHL, and Scopus for RCT literature employing mHealth among stroke populations published in English from 2010 to November 19, 2020. Small or pilot studies that included randomized design were included. A total of 352 abstracts met inclusion criteria; 31 full-text articles were assessed and 18 unique RCTs involving 1,453 patients ultimately fulfilled criteria. Twelve of 18 met the pre-defined primary outcome measure, including 2 studies evaluating feasibility. Eight of 18 only addressed recovery from index stroke deficits. Most outcomes focused on self-reported functional status, mood, quality of life or compliance with intervention; primary outcome was an objective metric in 4/18 (blood pressure readings, step number, obstructive sleep apnea support compliance). Intervention duration 2-12 months, with a median 9 weeks. No high-quality evidence supporting mHealth applications to reduce recurrent stroke was found in this scoping review. Overall, most studies were relatively small, heterogenous, and employed subjective primary outcome measures. mHealth's potential as an effective tool for stroke stakeholders to reduce recurrent stroke rates has not been sufficiently demonstrated in this review. Future randomized studies are needed that explicitly evaluate stroke recurrence rate.

A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing.

Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type). A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life). Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27-0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24-0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93-1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66-2.44], p = 0.47). PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response. The study is registered with PROSPERO, registration number CRD42020223768.

Dural tear repair surgery comparative analysis: a stitch in time saves nine

PurposeA dural tear is a common iatrogenic complication of spinal surgery associated with a several post-operative adverse events. Despite their common occurrence, guidelines on how best to repair the defect remain unclear. This study uses five post-operative outcomes to the compare repair methods used to treat 106 dural tears to determine which method is clinically favourable.MethodsData were retrospectively collected from Southampton General Hospital’s online databases. 106 tears were identified and grouped per repair method. MANOVA was used to compare the following five outcomes: Length of stay, numbers of further admissions or revision surgeries, length of additional admissions, post-operative infection rate and dural tear associated neurological symptoms. Sub-analysis was conducted on patient demographics, primary vs non-primary closure and type of patch. Minimal clinically important difference (MCID) was calculated via the Delphi procedure.ResultsAge had a significant impact on patient outcomes and BMI displayed positive correlation with three-fifth of the predefined outcome measures. No significant difference was observed between repair groups; however, primary closure ± a patch achieved an MCID percentage improvement with regards to length of original stay, rate of additional admissions/surgeries and post-operative infection rate. Artificial over autologous patches resulted in shorter hospital stays, fewer readmissions, infections and neurological symptoms.ConclusionThis study reports primary closure ± dural patch as the most efficient repair method with regards to the five reported outcomes. This study provides limited evidence in favour of artificial over autologous patches and recommends that dural patches be used in conjunction with primary closure.Level of evidence IDiagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

P.0713 Effectiveness and safety of vortioxetine in real-world clinical practice in China: results from the prospective RELIEVE China study

Vortioxetine, a novel antidepressant for the treatment of major depressive disorder (MDD), is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and serotonin (5-HT) transporter (SERT) inhibitor. Here we review its preclinical and clinical properties and discuss translational aspects. Vortioxetine increases serotonergic, noradrenergic, dopaminergic, cholinergic, histaminergic and glutamatergic neurotransmission in brain structures associated with MDD. These multiple effects likely derive from its interaction with 5-HT-receptor-mediated negative feedback mechanisms controlling neuronal activity. In particular, 5-HT3 receptors may play a prominent role, since their blockade i) increases pyramidal neuron activity by removing 5-HT3 receptor-mediated excitation of GABA interneurons, and ii) augments SSRI effects on extracellular 5-HT. However, modulation of the other 5-HT receptor subtypes also likely contributes to vortioxetine's pharmacological effects. Preclinical animal models reveal differences from SSRIs and SNRIs, including antidepressant-like activity, increased synaptic plasticity and improved cognitive function. Vortioxetine had clinical efficacy in patients with MDD: 11 placebo-controlled studies (including one in elderly) with efficacy in 8 (7 positive, 1 supportive), 1 positive active comparator study plus a positive relapse prevention study. In two positive studies, vortioxetine was superior to placebo in pre-defined cognitive outcome measures. The clinically effective dose range (5–20 mg/day) spans ~50 to >80% SERT occupancy. SERT and 5-HT3 receptors are primarily occupied at 5 mg, while at 20 mg, all targets are likely occupied at functionally relevant levels. The side-effect profile is similar to that of SSRIs, with gastrointestinal symptoms being most common, and a low incidence of sexual dysfunction and sleep disruption possibly ascribed to vortioxetine's receptor modulation.

Cone beam computed tomography for detecting residual stones in percutaneous nephrolithotomy, a randomized controlled trial (CAPTURE) protocol

IntroductionPercutaneous nephrolithotomy (PCNL) is the standard surgical treatment method for large kidney stones. Its aim is to achieve a stone-free status, since any residual fragments (RFs) after PCNL are likely to cause additional morbidity or stone growth. Enhancing intraoperative detectability of RFs could lead to increased stone-free rates and decreased re-intervention rates. Cone beam computed tomography (CBCT) has recently been introduced in urology as a feasible method for intraoperatively imaging RFs. The aim of this trial is to determine the added value of CBCT in percutaneous nephrolithotomy, by measuring differences in stone-related morbidity for patients with procedures in which a CBCT is used versus patients with procedures without the use of CBCT.MethodsThe CAPTURE trial is an investigator-initiated single-center, randomized controlled trial (RCT) in adult patients who have an indication for percutaneous nephrolithotomy. A contemporary percutaneous nephrolithotomy is performed. Once the surgeon is convinced of a stone-free status by means of fluoroscopy and nephroscopy, randomization allocates patients to either the study group in whom an intraoperative CBCT scan is performed or to the control group in whom no intraoperative CBCT scan is performed. The main endpoint is the stone-free status as assessed four weeks postoperatively by low-dose non-contrast abdominal CT, as a standard follow-up procedure. Secondary endpoints include the number of PCNL procedures required and the number of stone-related events (SREs) registered. The total study population will consist of 320 patients that undergo PCNL and are eligible for randomization for an intraoperative CBCT scan.DiscussionWe deem a randomized controlled trial to be the most effective and reliable method to assess the efficacy of CBCT in PCNL. Though some bias may occur due to the impossibility of blinding the urologist at randomization, we estimate that the pragmatic nature of the study, standardized circumstances, and follow-up methods with pre-defined outcome measures will result in a high level of evidence.Trial registrationNetherlands Trial Register (NTR) NL8168, ABR NL70728.042.19. Registered on 15 October 2019. Prospectively registered.

Safe and Efficient Practice of Bronchoscopic Sampling from Mechanically Ventilated Patients: A Structured Evaluation of the Ambu Bronchosampler-Ascope 4 Integrated System

Background: Bronchoscopic sampling of bronchoalveolar fluid (BAL) should be safe and effective. Current sampling practice risks loss of sample to the attached negative flow, aerosolisation, or spillage, due to repeated circuit breaks, when replacing sample containers. Such concerns were highlighted during the recent coronavirus pandemic. Objectives: Evaluation of an alternative integrated sampling solution, with the Ambu Bronchosampler with aScope 4, by an experienced bronchoscopist in ICU. Methods: An observational study of 20 sequential bronchoscopic diagnostic sampling procedures was performed on mechanically ventilated patients with suspected ventilator-associated pneumonia. Mixed methods assessment was done. The predefined outcome measures were (1) ease of set up, (2) ease of specimen collection, (3) ease of protecting specimen from loss or spillage, and (4) overall workflow. The duration of the procedure and the % volume of sample retrieved were recorded. Results: The mean (±standard deviation [SD]) time for collecting 1 sample was 2.5 ± 0.8 min. The mean (±SD) specimen yield for instilled miniBAL was 54.2 ± 17.9%. Compared with standard sampling, the set-up was much easier in 18 (90%), or easier in 2 (10%) of procedures, reducing the connection steps. It was much more intuitive to use in 14 (70%), more intuitive in 4 (20%), and no more intuitive to use in 2 (10%). The overall set-up and workflow was much easier in 69% of the 13 intraprocedural connections and easier or as easy in the remaining 31% procedures. All procedures where pre connection was established were much easier (7, 100%). The Ambu Bronchosampler remained upright in all procedures with no loss or spillage of sample. Obtaining a sample was much easier in 60%, easier in 10%, no different in 20%, and worse in 10%. The ability to protect a sample from start to finish compared to standard procedures was much easier in 80%, easier in 15%, and no different in 5% of procedures. Overall workflow was much easier in 14 (70%), easier in 4 (20%), and no different in 2 (10%) of procedures. Conclusions: The Ambu Bronchosampler unit was a reliable, effective, and possibly safer technique for diagnostic sampling in ICU. It may improve safety standards during the coronavirus pandemic. A randomized control trial against the standard sampling technique is warranted.

Pre-procedural platelet transfusion thresholds in hospitalised children - Protocol for a scoping review.

Thrombocytopenia is a common condition in hospitalised critically ill children and most platelet transfusions are given as prophylaxis to non-bleeding children prior to invasive procedures such as central venous catheterisation and lumbar puncture. Platelet transfusion may reduce bleeding complications but have also been associated with potential adverse effects and variation in clinical practice exist. To direct future research, we aim to assess the current evidence regarding prophylactic platelet transfusion prior to procedures in hospitalised thrombocytopenic children. We will conduct a scoping review of all study designs in accordance with the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) statement. We will include studies on hospitalised children undergoing invasive procedures where the prevalence of thrombocytopenia and the predefined outcome measures, including bleeding, transfusion-related adverse events and use of blood products and life support are reported. We will provide descriptive analyses of the included studies/trials and the quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The outlined scoping review will provide an overview on the benefits and harms of prophylactic platelet transfusion prior to invasive procedures in thrombocytopenic hospitalised children.

Bleomycin for orbital and peri-orbital veno-lymphatic malformations - A systematic review.

Orbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such malformations. The purpose of this systematic review is to synthesize evidence on the safety and efficacy of bleomycin/pingyangmycin sclerotherapy for the treatment of orbital and peri-orbital VLM. We searched Medline, Embase, Scopus and Cochrane database for studies reporting outcomes of bleomycin/pingyangmycin sclerotherapy for orbital and peri-orbital VLM between 1974 to April 5th, 2019. Nine retrospective cohort studies enrolling 132 patients were included. Two reviewers independently screened and extracted data and assessed the risk of bias. Predefined outcome measures were subjective and objective reduction of the lesion and associated complications. Subjective reduction of the lesions was seen in 96.2% of the studies. Objective reduction of the lesion and symptomatic improvement were reported in 91.6 and 95% of the studies respectively. Non responders were 9.0%. Minor adverse events were reported in 18.1% of the studies. Major complications like pulmonary toxicity or pulmonary fibrosis was not encountered in any of the included studies. Quality of evidence was generally low. Bleomycin/pingyangmycin sclerotherapy is very effective and relatively safe for the treatment of orbital and periorbital VLM and is not associated with any major side effects including pulmonary fibrosis.Limitations: The systematic review is limited mainly due to low quality of the included studies with retrospective design.

Effects of post-operative furosemide in adult surgical patients: A systematic review and meta-analysis of randomised clinical trials.

Acute kidney injury (AKI) is associated with increased morbidity and mortality and may present as oliguria in the post-operative phase. Diuretics, including furosemide, are commonly used in post-operative patients. Accordingly, we aimed to assess the balance between benefits and harms of furosemide post-operatively in adult surgical patients. We conducted a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, the Cochrane Handbook and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. We included randomised clinical trials (RCTs) comparing post-operative treatment with furosemide vs no furosemide in adult surgical patients. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by conventional meta-analysis and trial sequential analysis (TSA). Two thousand five hundred and sixty seven records were identified and four trials with 325 patients in total were included. All were adjudicated as having overall high risk of bias. We observed no statistically significant difference between furosemide- vs no furosemide-treated patients in any of the predefined outcome measures, including AKI (RR 1.07, 95% CI 0.43-2.65), all-cause mortality (RR 1.73, 95% CI 0.62-4.80, use of vasopressors post-operatively (RR 1.04, 95% CI 0.74-1.44) or need for renal replacement therapy (RR 3.87, 95% CI 0.44-33.99). TSA highlighted sparse data, and the overall quality of evidence was very low. In this systematic review, we found that the quantity and quality of evidence for using furosemide post-operatively in adult surgical patients were very low with no firm evidence for benefit or harm.