Health Economic Evaluation of Patients With Colorectal Liver Metastases Randomized to ALPPS or TSH: Analysis From the LIGRO Trial.

Objective: This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant <30% were randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or two-staged hepatectomy (TSH). Summary Background Data: TSH, is an established method in advanced CRLM. ALPPS has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health-related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared. Methods: Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy, and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Nonparametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs. Results: The mean cost difference between ALPPS and TSH was 12,662€, [95% confidence interval (CI): -10,728-36,051; P = 0.283]. Corresponding mean difference in life years and QALYs was 0.1296 (95% CI: -0.12-0.38; P = 0.314) and 0.1285 (95% CI: -0.11-0.36; P = 0.28), respectively. The ICER was 93,186 and 92,414 for QALYs and life years as outcomes, respectively. Conclusions: Based on the 2-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 years is needed.

Subcutaneous Vedolizumab Treatment in a Real-World Inflammatory Bowel Disease Cohort Switched From Intravenous Vedolizumab: Eighteen-Month Prospective Follow-up Study.

Background: Vedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment. Methods: Eligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment. Data on preferred route of administration, adverse events, drug dosing, serum-vedolizumab, disease activity, fecal calprotectin, and C-reactive protein were collected. Persistence was described using Kaplan-Meier analysis. The impact of clinical and biochemical variables on persistence was analyzed with Cox proportional hazard models. Results: We included 108 patients, and the estimated 18-month drug persistence was 73.6% (95% CI [64.2-80.1]). Patients in clinical remission at switch were less likely to discontinue SC treatment (HR = 0.34, 95% CI [0.16-0.73], P = .006), and patients favoring intravenous treatment at switch were almost 3 times more likely to discontinue (HR = 2.78, 95% CI [1.31-5.90], P = .008). Four patients discontinued subcutaneous vedolizumab due to injection site reactions. At 18 months, 88% of patients administered subcutaneous vedolizumab with an interval of ≥ 14 days, and serum-vedolizumab was 39.1 mg/L. Disease activity was stable during follow-up. Conclusions: Three of the four patients remained on subcutaneous vedolizumab after 18 months, a large proportion received treatment at standard dosing intervals, and disease activity remained stable. This indicates that switching from intravenous to subcutaneous vedolizumab treatment is convenient and safe.

Estimated summer abundance and krill consumption of fin whales throughout the Scotia Sea during the 2018/2019 summer season.

Among large cetaceans in the Southern Hemisphere, fin whales were the most heavily exploited in terms of numbers taken during the period of intense industrial whaling. Recent studies suggest that, whilst some humpback whale populations in the Southern Hemisphere appears to have almost completely recovered to their estimated pre-whaling abundance, much less is known about the status of Southern Hemisphere fin whales. Circumpolar estimates in the 1990s suggest an abundance of about 5500 animals south of 60° S, while the IDCR/SOWER-2000 survey for the Scotia Sea and Antarctic Peninsula areas estimated 4670 fin whales within this region in the year 2000. More recent studies in smaller regions indicate higher densities, suggesting that previous estimates are overly conservative and/or that fin whales are undergoing a substantial increase. Here we report findings from a recent multi-vessel single-platform sightings survey carried out as part of the 2019 Area 48 Survey for Antarctic krill. While fin whales were encountered throughout the entire survey area, which covered the majority of CCAMLR Management Area 48, they were particularly abundant around the South Orkney Islands and the eastern Bransfield Strait. Large feeding aggregations were also encountered within the central Scotia Sea between South Orkney Islands and South Georgia. Distance sampling analyses suggest an average fin whale density throughout the Scotia Sea of 0.0256 ( CV = 0.149 ) whales per km2, which agrees well with recent density estimates reported from smaller sub-regions within the Scotia Sea. Design-based distance sampling analyses resulted in an estimated total fin whale abundance of 53,873 (CV = 0.15, 95% CI 40,233-72,138), while a density surface model resulted in a slightly lower estimate of 50,837 (CV: 0.136, 95% CI 38,966-66,324). These estimates are at least an order of magnitude greater than the previous estimate from the same region based on the IDCR/SOWER-2000 data, suggesting that fin whales are undergoing a substantial abundance increase in the South Atlantic. This may have important implications for the assessment of cetacean population trends, but also for CCAMLRs spatial overlap analysis process and efforts to implement a Feedback Management system for Antarctic krill. Our abundance estimate suggests an annual summer krill consumption by fin whales in the Antarctic Peninsula and Scotia Sea area of 7.97 (95% CI 4.94-11.91) million tonnes, which would represent around 20 times the total krill catch taken by the commercial fishery in Area 48 in the same season, or about 12.7% of the 2019 summer krill standing stock estimated from data collected during the same survey. This highlights the crucial importance of including cetacean krill predators in assessment and management efforts for living marine resources in the Southern Ocean, and particularly stresses the urgent need for a re-appraisal of abundance, distribution and ecological role of Southern Hemisphere fin whales.

Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Current Guidelines for the Implementation of Flywheel Resistance Training Technology in Sports: A Consensus Statement.

BACKGROUND: Flywheel resistance training has become more integrated within resistance training programs in a variety of sports due to the neuromuscular, strength, and task-specific enhancements reported with this training. OBJECTIVE: This paper aimed to present the consensus reached by internationally recognized experts during a meeting on current definitions and guidelines for the implementation of flywheel resistance training technology in sports. METHODS: Nineteen experts from different countries took part in the consensus process; 16 of them were present at the consensus meeting (18 May 2023) while three submitted their recommendations by e-mail. Prior to the meeting, evidence summaries were developed relating to areas of priority. This paper discusses the available evidence and consensus process from which recommendations were made regarding the appropriate use of flywheel resistance training technology in sports. The process to gain consensus had five steps: (1) performing a systematic review of systematic reviews, (2) updating the most recent umbrella review published on this topic, (3) first round discussion among a sample of the research group included in this consensus statement, (4) selection of research group members-process of the consensus meeting and formulation of the recommendations, and (5) the consensus process. The systematic analysis of the literature was performed to select the most up-to-date review papers available on the topic, which resulted in nine articles; their methodological quality was assessed according to AMSTAR 2 (Assessing the Methodological Quality of Systematic Review 2) and GRADE (Grading Recommendations Assessment Development and Evaluation). Statements and recommendations scoring 7-9 were considered appropriate. RESULTS: The recommendations were based on the evidence summary and researchers' expertise; the consensus statement included three statements and seven recommendations for the use of flywheel resistance training technology. These statements and recommendations were anonymously voted on and qualitatively analyzed. The three statements reported a score ranging from 8.1 to 8.8, and therefore, all statements included in this consensus were considered appropriate. The recommendations (1-7) had a score ranging from 7.7 to 8.6, and therefore, all recommendations were considered appropriate. CONCLUSIONS: Because of the consensus achieved among the experts in this project, it is suggested that practitioners and researchers should adopt the guidelines reported in this consensus statement regarding the use of flywheel resistance technology in sports.

Seasonal acoustic presence of marine mammals at the South Orkney Islands, Scotia Sea.

Increased knowledge about marine mammal seasonal distribution and species assemblage from the South Orkney Islands waters is needed for the development of management regulations of the commercial fishery for Antarctic krill (Euphausia superba) in this region. Passive acoustic monitoring (PAM) data were collected during the autumn and winter seasons in two consecutive years (2016, 2017), which represented highly contrasting environmental conditions due to the 2016 El Niño event. We explored differences in seasonal patterns in marine mammal acoustic presence between the two years in context of environmental cues and climate variability. Acoustic signals from five baleen whale species, two pinniped species and odontocete species were detected and separated into guilds. Although species diversity remained stable over time, the ice-avoiding and ice-affiliated species dominated before and after the onset of winter, respectively, and thus demonstrating a shift in guild composition related to season. Herein, we provide novel information about local marine mammal species diversity, community structure and residency times in a krill hotspot. Our study also demonstrates the utility of PAM data and its usefulness in providing new insights into the marine mammal habitat use and responses to environmental conditions, which are essential knowledge for the future development of a sustainable fishery management in a changing ecosystem.

Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography.

OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities. CONCLUSION: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone. CLINICAL RELEVANCE STATEMENT: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic. KEY POINTS: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders.

Relationship Between Arm Path, Ball Velocity, and Elbow Varus Torque in Professional Baseball Pitchers.

Background: Currently, most pitching instructors suggest a shorter arm path-the total distance the arm travels during pitching. Theoretically, this combination allows for better body segment sequencing, a more efficient energy transfer through the kinetic chain, and increased ball velocity, while limiting elbow varus torque. Hypothesis: Shorter arm paths would be associated with increased ball velocity and decreased elbow varus torque. Study Design: Descriptive laboratory study. Methods: A total of 182 professional pitchers threw 8 to 12 fastball pitches while evaluated by 3-dimensional motion capture (480 Hz). The arm path was calculated as the total distance the hand marker traveled during the pitch. The pitch was divided into early, late, and total arm paths. A linear regression model assessed the interpitcher relationship between arm path, elbow varus torque, and ball velocity. A linear mixed-effects model with random intercepts assessed intrapitcher relationships. Results: Interpitcher comparison showed that total arm path weakly correlated with greater elbow varus torque (P = .025). Strong correlations were found between ball velocity and early (R2 = 0.788; P < .001), late (R2 = 0.787; P = .024), and total arm paths (R2 = 0.792; P < .001). Strong positive intrapitcher correlations were found between elbow varus torque and early (R2 = 0.962; P < .001) and total arm path (R2 = 0.964; P < .001). For individual pitchers, there was a large variation in the early (30.1 ± 15.7 cm) and late (21.4 ± 12.1 cm) arm path. For every 30-cm (11.8-inch) increase in early arm path (the mean range for an individual pitcher), there was a 1.29-N (ß = 0.0429) increase in elbow varus torque and a 0.354 m/s (0.79 mph) (ß = 0.0118) increase in ball velocity. Conclusion: A shorter arm path correlated with decreased elbow varus torque and decreased ball velocity in intrapitcher comparisons. Determining the individual mechanics that decrease elbow varus torque may help coaches and trainers correct these patterns. Clinical Significance: A shorter arm path during the pitch can decrease elbow varus torque, which limits the load on the medial elbow but also has a detrimental effect on ball velocity. An improved understanding of the impact of shortening arm paths on stresses on the throwing arm may help minimize injury risk.

eHealth usage among parents to premature or surgically treated neonates: associations with eHealth literacy, healthcare satisfaction or satisfaction with an eHealth device.

BACKGROUND: A specific eHealth device, a surf tablet, was developed for bridging between advanced in-hospital care and children's homes. Since little is known about determinators for parental eHealth usage, the study's aim was to explore if parents' usage of the device was associated with their eHealth literacy, or their satisfaction with their child's healthcare or with the specific surf tablet. METHODS: In this explorative usage and questionnaire study, parents to neonates who were discharged home after advanced in-hospital care were included. Their surf tablet usage at maximum 30 days after discharge was reported as frequency (%) of active days (usage days/days having the device) and median number of tablet activities (chat and photo) per usage day. eHealth literacy (eHealth Literacy Questionnaire; eHLQ), healthcare satisfaction (PedsQL Healthcare Satisfaction Generic Module), and satisfaction with the surf tablet were explored regarding tablet usage. Statistics were described in median (range) and (%) using non-parametric and regression models (p < 0.05). RESULTS: Parents to 32 children (11 premature, 21 operated) were included. Active days with eHealth communication using the device was 39% (9.0/29.5), with 2.0 (1.0-4.2) usage occasions per active day. Activity on the tablet was higher among parents reporting to be very satisfied or satisfied with the device (n = 25) compared with neutral/dissatisfied parents (n = 7) (2.8 vs. 2.2 vs. 1.6 activities) (p = 0.030), while their frequency of active days did not differ (31.6% vs. 38.3% vs. 40%) (p = 0.963). A higher eHealth literacy was not associated with frequency of active days (0.926 (0.652-1.317); p = 0.659) or number of eHealth activities (0.973 (0.758-1.250); p = 0.825). Healthcare satisfaction was not associated with higher frequency of active days 0.996 (0.983-1.009; p = 0.519); neither was number of eHealth activities 1.001 (0.991-1.011; p = 0.883). CONCLUSION: In this study, eHealth usage was associated with parental satisfaction with the specific eHealth device, but not with eHealth literacy or healthcare satisfaction. To assure equal access to healthcare when using eHealth, the user-friendliness of the device seems to be crucial, and technical support needs to be in place. GOV REGISTRATION IDENTIFIER: NCT04150120 (04/11/2019).

Relation between increasing attachment security and weight gain: a clinical study of adolescents and their parents at an outpatient ward.

PURPOSE: We wanted to evaluate the impact of a relational focus in the treatment of adolescent ED-patients and their parents at an intensive outpatient ward, based on attachment theory, combined with a family approach and psychodynamic principles. Our aim was to investigate the distribution of different attachment styles among the adolescent ED-patients and their parents, and to find out if they could change by the treatment. METHODS: Swedish adolescents (n = 33; 3 boys, 30 girls) and their parents (n = 60; 34 mothers, 26 fathers) participated. MEASURES: Attachment Style Questionnaire (ASQ), Body Mass Index (BMI) and Children's Global Assessment Scale (CGAS) before and after treatment. RESULTS: The adolescents were high on Need for Approval (ASQ4) of the Insecure/Anxious scale before treatment (in contrast to the parents). The patients had a significant decrease in ASQ4 after treatment, which correlated inversely to the increase in BMI but not to CGAS. The mothers showed features of the Secure/Confident style, fathers of the Insecure/Avoidant with elevated Relationships as Secondary (ASQ2). CONCLUSIONS: Treatment with a relational and a family focus has impact on attachment insecurity in adolescent ED-patients and outcomes in terms of BMI. It is important to engage the parents, who need to help the adolescents to separate at that developmental stage. A secure therapeutic context, which enables mentalizations and allows new relational experiences, is essential. The ASQ-instrument is useful in indicating how the treatment of ED-adolescents is proceeding. LEVEL OF EVIDENCE: Level IV: evidence obtained from multiple time series with the intervention.

Alpha-1-acid glycoprotein and its potential impact on local anesthetic dose in neonates.

BACKGROUND: Alpha-1-acid glycoprotein is an acute-phase protein with a high affinity for amide local anesthetics. Compared to adults, neonates have lower concentrations of this glycoprotein in plasma, and are therefore at higher risk of developing local anesthetic toxicity. Alpha-1-acid glycoprotein concentrations rise in adults after surgery as a response to stress as well as in inflammatory conditions. Previous studies have shown that concentrations of alpha-1-acid-glycoprotein in neonates vary postpartum, influenced by gestational age and mode of delivery. AIM: This study aims to determine the concentrations of alpha-1-acid glycoprotein pre- and postoperatively in neonates undergoing major surgery. This information is important for determining safe and effective dosage of local anesthetic in this vulnerable group of patients. METHODS: In this prospective observational study, 25 neonates (median 3 days of age) undergoing major surgery were included. Blood sampling was performed preoperatively and at four occasions postoperatively. Alpha-1-acid-glycoprotein plasma concentrations were analyzed using an immunoturbidimetric assay. Mann-Whitney U test, Kruskal-Wallis and Spearman ranking correlation test were used for the statistical analysis. RESULTS: Higher plasma concentrations of alpha-1-acid-glycoprotein were found 48 h postoperatively compared to preoperatively [median (inter-quartile range) 0.815 g L-1 (0.663-0.983 g L-1 ) vs. 0.300 g L-1 (0.205-0.480 g L-1 p < 0.001)], respectively. It was not possible to detect any influence of sex, postnatal age, gestational age, or delivery mode on alpha-1-acid-glycoprotein concentrations in our data. CONCLUSIONS: Alpha-1-acid-glycoprotein concentrations increase in neonates as a response to surgery regardless of gestational age, sex, or mode of delivery.

Estimation of fat content in soft tissues using dual frequency ultrasound-A phantom study.

This paper presents an initial investigation into the use of dual frequency pulse-echo ultrasound, second order ultrasound field (SURF) imaging, to measure the fat content of soft tissues. The SURF imaging method was used to measure the non-linear bulk elasticity (NBE) of several fatty phantoms that were created by mixing different mass fractions of soybean oil uniformly into agar phantoms. The median of the measured NBE within the estimation region was found to increase linearly with fat mass fraction (R2 = 0.99), from 1.7 GPa-1 at 9.6% fat to 2.52 GPa-1 at 63.6% fat, thus, showing promise as a sensitive parameter for fat content measurement. Comparisons to mixture laws in earlier literature are made, and the most important error sources that need to be considered for the in vivo applications of the method are discussed.

Accuracy of stress perfusion cardiac magnetic resonance imaging in a district hospital.

Background: The European Society of Cardiology has published updated guidelines regarding pathways for diagnosis and management of obstructive coronary artery disease (CAD). Non-invasive functional assessment, for example, by stress perfusion cardiac magnetic resonance (stress pCMR) is recommended in patients with intermediate pretest probability of disease. Previous pCMR studies were mainly performed in high volume university hospitals with experienced radiologists or cardiologists interpreting the images. Purpose: The aim of the present study was to evaluate the feasibility of establishing a stress pCMR imaging service in a district hospital. Material and Methods: One hundred and thirteen patients with intermediate pretest probability of CAD referred for single-photon emission computed tomography (SPECT) at the regional hospital also underwent adenosine stress pCMR locally. The diagnostic analysis was compared to that of an experienced cardiac magnetic resonance (CMR) center serving as a reference. Results: Inter-rater agreement between local readers and the reference reader was substantial to perfect for late gadolinium enhancement (LGE) (weighted kappa = 0.76 and 0.82), but only fair to moderate for pCMR (k = 0.34 and 0.51). No improvement in agreement between reference reader and local reader during the study was demonstrated. Conclusion: CMR is feasible in patients with intermediate pretest probability of obstructive CAD in the setting of a district hospital. However, as opposed to infarct detection with LGE, the interpretation of stress pCMR was more challenging. To establish this method, we suggest obtaining experience in close collaboration with a reference CMR center.

Accuracy of the fully integrated Insole3's estimates of spatiotemporal parameters during walking.

This study investigated the accuracy of the Insole3 wireless shoe device in estimating several clinically useful spatiotemporal parameters (STPs). Eleven subjects walked at slow (0.8-1.0 m/s) and moderate-paced (1.2-1.4 m/s) speeds. Data were simultaneously recorded using the Insole3 and an industry-standard, three-dimensional motion capture (MOCAP) system. An error analysis compared the resulting STP data from the two systems. The mean bias error (MBE) was generally lower for temporal variables, and somewhat higher, but acceptable, for spatial variables. The MBE for temporally-related cadence and cycle time were the lowest (less than ±0.45%), with 100% (110/110) of slow-paced walking trial values and 99.1% (109/110) of moderate-paced walking trial values within 5% of the MOCAP estimates. The MBE was highest for speed (3.23-4.91%) and stride length (3.68-4.63%), with between 52.7 and 69.1% of trial values falling within the 5% error range. Stance time and swing time ranged between -0.98 and 4.38% error for both walking conditions. The results of this study suggest that the Insole3 is a potential alternative to MOCAP for estimating several STPs, namely cadence, stance time, and cycle time, particularly for use outside of the laboratory setting.

Switching from intravenous to subcutaneous vedolizumab maintenance treatment in patients with inflammatory bowel disease followed by therapeutic drug monitoring.

OBJECTIVE: Vedolizumab (VDZ) for subcutaneous (SC) administration has recently become available. We aimed to assess feasibility, safety and clinical outcome when switching from intravenous (IV) to SC VDZ maintenance treatment in a real world cohort of patients with inflammatory bowel disease (IBD) followed by therapeutic drug monitoring (TDM). METHODS: Eligible IBD patients were switched from IV to SC treatment and assessed six months prior to switch, at baseline and six, twelve and twenty-six weeks after switch. Primary outcome was proportion of patients on SC treatment after 26 weeks. Secondary outcomes included adverse events (AEs), clinical disease activity, biochemical markers, treatment interval, serum-VDZ (s-VDZ), preferred route of administration and health-related quality of life. RESULTS: In total, 108 patients were switched. After 26 weeks, 100 patients (92.6%) were still on SC treatment and median s-VDZ was 47.6 mg/L (IQR 41.3 - 54.6). The most frequent AE was injection site reaction (ISR), reported by 20 patients (18.5%). There were no clinically significant changes in disease activity, biochemical markers and quality of life. The proportion of patients preferring SC administration increased from 28.0% before switch to 59.4% after 26 weeks (p < 0.001). CONCLUSIONS: Nine out of ten patients still received SC treatment after 26 weeks. No change in disease activity occurred, and levels of serum VDZ increased. Although almost one fifth of patients experienced ISRs, a higher proportion favored SC administration at 26 weeks. This study demonstrates that SC maintenance treatment is a safe and feasible alternative to IV treatment.

Catching the Wave: Detecting Strain-Specific SARS-CoV-2 Peptides in Clinical Samples Collected during Infection Waves from Diverse Geographical Locations.

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a major health crisis worldwide with its continuously emerging new strains, resulting in new viral variants that drive "waves" of infection. PCR or antigen detection assays have been routinely used to detect clinical infections; however, the emergence of these newer strains has presented challenges in detection. One of the alternatives has been to detect and characterize variant-specific peptide sequences from viral proteins using mass spectrometry (MS)-based methods. MS methods can potentially help in both diagnostics and vaccine development by understanding the dynamic changes in the viral proteome associated with specific strains and infection waves. In this study, we developed an accessible, flexible, and shareable bioinformatics workflow that was implemented in the Galaxy Platform to detect variant-specific peptide sequences from MS data derived from the clinical samples. We demonstrated the utility of the workflow by characterizing published clinical data from across the world during various pandemic waves. Our analysis identified six SARS-CoV-2 variant-specific peptides suitable for confident detection by MS in commonly collected clinical samples.

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).

Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium.

OBJECTIVES: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). PURPOSE: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. METHODS: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard. RESULTS: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). CONCLUSIONS: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD. KEY POINTS: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.