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Reporting Standard for describing First Responder Systems, Smartphone Alerting Systems, and AED Networks.
No full textStandardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/ algorithm/ strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice
Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project.
Get PDFINTRODUCTION AND OBJECTIVE
The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework.
METHODS
Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available.
RESULTS
The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs).
CONCLUSIONS
Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible
Wie geht es LGBTQ+ Jugendlichen in Deutschschweizer Schulen? Kurzfassung des Forschungsberichts. Projekt SOGUS – Sexuelle Orientierung, Geschlecht und Schule.
Get PDFGadolinium-Based Contrast Agents and Free Gadolinium Inhibit Differentiation and Activity of Bone Cell Lineages.
Get PDFOBJECTIVES
Administration of gadolinium-based contrast agents (GBCA) in magnetic resonance imaging results in the long-term retention of gadolinium (Gd) in tissues and organs, including the bone, and may affect their function and metabolism. This study aims to investigate the effects of Gd and GBCA on the proliferation/survival, differentiation, and function of bone cell lineages.
MATERIALS AND METHODS
Primary murine osteoblasts (OB) and osteoclast progenitor cells (OPC) isolated from C57BL/6J mice were used to test the effects of Gd3+ (12.5-100 μM) and GBCA (100-2000 μM). Cultures were supplemented with the nonionic linear Gd-DTPA-BMA (gadodiamide), ionic linear Gd-DTPA (gadopentetic acid), and macrocyclic Gd-DOTA (gadoteric acid). Cell viability and differentiation were analyzed on days 4-6 of the culture. To assess the resorptive activity of osteoclasts, the cells were grown in OPC cultures and were seeded onto layers of amorphous calcium phosphate with incorporated Gd.
RESULTS
Gd3+ did not affect OB viability, but differentiation was reduced dose-dependently up to 72.4% ± 6.2%-73.0% ± 13.2% (average ± SD) at 100 μM Gd3+ on days 4-6 of culture as compared with unexposed controls (P < 0.001). Exposure to GBCA had minor effects on OB viability with a dose-dependent reduction up to 23.3% ± 10.2% for Gd-DTPA-BMA at 2000 μM on day 5 (P < 0.001). In contrast, all 3 GBCA caused a dose-dependent reduction of differentiation up to 88.3% ± 5.2% for Gd-DTPA-BMA, 49.8% ± 16.0% for Gd-DTPA, and 23.1% ± 8.7% for Gd-DOTA at 2000 μM on day 5 (P < 0.001). In cultures of OPC, cell viability was not affected by Gd3+, whereas differentiation was decreased by 45.3% ± 9.8%-48.5% ± 15.8% at 100 μM Gd3+ on days 4-6 (P < 0.05). Exposure of OPC to GBCA resulted in a dose-dependent increase in cell viability of up to 34.1% ± 11.4% at 2000 μM on day 5 of culture (P < 0.001). However, differentiation of OPC cultures was reduced on day 5 by 24.2% ± 9.4% for Gd-DTPA-BMA, 47.1% ± 14.0% for Gd-DTPA, and 38.2% ± 10.0% for Gd-DOTA (P < 0.001). The dissolution of amorphous calcium phosphate by mature osteoclasts was reduced by 36.3% ± 5.3% upon incorporation of 4.3% Gd/Ca wt/wt (P < 0.001).
CONCLUSIONS
Gadolinium and GBCA inhibit differentiation and activity of bone cell lineages in vitro. Thus, Gd retention in bone tissue could potentially impair the physiological regulation of bone turnover on a cellular level, leading to pathological changes in bone metabolism
Interventions Based on Acceptance and Commitment Therapy for Stress Reduction in Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
No full textINTRODUCTION
Recently, acceptance- and commitment therapy (ACT) gained increasing interest. Studies show good efficacy in the treatment of patients presenting with several psychologic and somatic complaints. The present systematic review and meta-analysis addresses effectiveness of ACT-based interventions to reduce stress in children, adolescents, and young adults compared to control conditions.
METHODS
The meta-analysis was pre-registered at PROSPERO (CRD42019117440). Randomized controlled trials (RCTs) and quasi-randomized controlled trials (qRCT) in German or English language comparing the effects of ACT-based interventions to control conditions (e.g., treatment as usual, waitlist control) on stress-related outcome measures in youth were considered for inclusion. The target population was subjects 0-18 years of age. The databases PubMed, PsychInfo, Cochrane Database, CINAHL, and Web of Science were searched systematically up to July 2023. A random effect meta-analysis and a risk of bias assessment according to the procedure outlined in the Cochrane Handbook of Systematic Reviews were conducted.
RESULTS
The search resulted in 187 studies, of which eight studies with 976 participants were finally subjected to meta-analysis. Studies implemented ACT both in school-based group settings and in single settings and both as a universal and indicated prevention. Analyses yielded a significant main effect (Hedges' g = -0.20; 95% confidence interval [-0.36; -0.05]), indicating that interventions based on ACT resulted in greater reduction of stress compared to control conditions.
CONCLUSION
ACT appears effective at reducing stress in youth. Further research is needed due to methodological shortcomings of existing studies. Small sample sizes, heterogenous studies, methodological shortcomings, and evidence of publication bias limit the conclusions that can be drawn from this meta-analysis
Dosimetrically motivated beam-angle optimization for non-coplanar arc radiotherapy with and without dynamic collimator rotation.
Get PDFBACKGROUND
Non-coplanar techniques have shown to improve the achievable dose distribution compared to standard coplanar techniques for multiple treatment sites but finding optimal beam directions is challenging. Dynamic collimator trajectory radiotherapy (colli-DTRT) is a new intensity modulated radiotherapy technique that uses non-coplanar partial arcs and dynamic collimator rotation.
PURPOSE
To solve the beam angle optimization (BAO) problem for colli-DTRT and non-coplanar VMAT (NC-VMAT) by determining the table-angle and the gantry-angle ranges of the partial arcs through iterative 4π fluence map optimization (FMO) and beam direction elimination.
METHODS
BAO considers all available beam directions sampled on a gantry-table map with the collimator angle aligned to the superior-inferior axis (colli-DTRT) or static (NC-VMAT). First, FMO is performed, and beam directions are scored based on their contributions to the objective function. The map is thresholded to remove the least contributing beam directions, and arc candidates are formed by adjacent beam directions with the same table angle. Next, FMO and arc candidate trimming, based on objective function penalty score, is performed iteratively until a desired total gantry angle range is reached. Direct aperture optimization on the final set of colli-DTRT or NC-VMAT arcs generates deliverable plans. colli-DTRT and NC-VMAT plans were created for seven clinically-motivated cases with targets in the head and neck (two cases), brain, esophagus, lung, breast, and prostate. colli-DTRT and NC-VMAT were compared to coplanar VMAT plans as well as to class-solution non-coplanar VMAT plans for the brain and head and neck cases. Dosimetric validation was performed for one colli-DTRT (head and neck) and one NC-VMAT (breast) plan using film measurements.
RESULTS
Target coverage and conformity was similar for all techniques. colli-DTRT and NC-VMAT plans had improved dosimetric performance compared to coplanar VMAT for all treatment sites except prostate where all techniques were equivalent. For the head and neck and brain cases, mean dose reduction-in percentage of the prescription dose-to parallel organs was on average 0.7% (colli-DTRT), 0.8% (NC-VMAT) and 0.4% (class-solution) compared to VMAT. The reduction in D2% for the serial organs was on average 1.7% (colli-DTRT), 2.0% (NC-VMAT) and 0.9% (class-solution). For the esophagus, lung, and breast cases, mean dose reduction to parallel organs was on average 0.2% (colli-DTRT) and 0.3% (NC-VMAT) compared to VMAT. The reduction in D2% for the serial organs was on average 1.3% (colli-DTRT) and 0.9% (NC-VMAT). Estimated delivery times for colli-DTRT and NC-VMAT were below 4 min for a full gantry angle range of 720°, including transitions between arcs, except for the brain case where multiple arcs covered the whole table angle range. These times are in the same order as the class-solution for the head and neck and brain cases. Total optimization times were 25%-107% longer for colli-DTRT, including BAO, compared to VMAT.
CONCLUSIONS
We successfully developed dosimetrically motivated BAO for colli-DTRT and NC-VMAT treatment planning. colli-DTRT and NC-VMAT are applicable to multiple treatment sites, including body sites, with beneficial or equivalent dosimetric performances compared to coplanar VMAT and reasonable delivery times
Long Term Survival and Quality of Life Following Transcatheter Aortic Valve Replacement in Nonagenarians.
No full textTranscatheter aortic valve replacement (TAVR) has emerged as a successful treatment option for severe aortic stenosis (AS). However, the long term outcomes of TAVR in nonagenarians is lacking. We aimed to examine the long-term mortality and quality-of-life in nonagenarians after TAVR. This is a multi-center retrospective analysis on patients with severe AS undergoing TAVR. Patients were divided into two groups: Nonagenarians (age ≥ 90 years) and age < 90 years. Kansas city cardiomyopathy questionnaires (KCCQ) and New York Heart Associated (NYHA) scores were compared pre- and post-TAVR. All-cause mortality was compared between both groups at 30 days, 1-year and 5-years post-TAVR using Cox-proportional hazard model. A total of 6896 patients were included, of which 591 were nonagenarians. Nonagenarians had a higher STS perioperative risk of mortality (8.1 ± 4.6% vs 5.4 ± 4.2%, p<0.001) pre-TAVR. Both groups were similar in baseline KCCQ and NYHA scores. At one year post-TAVR, there was no significant difference in improvement in the KCCQ overall score between age < 90 and nonagenarians (-4.76, 95% CI: -11.4 - 1.9, p = 0.161). Similarly, there was no statistically significant difference in improvement in NYHA class between the two groups at 1-year (OR: 1.07, 95% CI: 0.85 - 1.25), p = 0.526). The unadjusted 30-day (3.2% vs 2.7%; HR:1.11, 95% CI: 0.70-1.80, p=0.667) and 5-year (28.0% vs 26.6%, HR: 1.05, 95% CI:0.89-1.24, p=0.60) all-cause mortality were similar between the two groups. In conclusion, this study demonstrates an excellent long-term mortality rate at 5 years following TAVR in nonagenarians, comparable to patients younger than 90 years old. There is a significant and enduring improvement in functional status in nonagenarians, observed up to 1 year following TAVR
Optimal detection protocol of Tetracapsuloides bryosalmonae by environmental DNA : A comparison of qPCR and ddPCR approaches
Get PDFInvestigation of environmental DNA (eDNA) is increasingly used to precisely and non-invasively
detect and monitor pathogens. Among these, Tetracapsuloides bryosalmonae
is a myxozoan endoparasite that causes proliferative kidney disease (PKD) in salmonid
fish. Although the detection of T. bryosalmonae DNA in water samples has been shown
to be promising and successful, method comparison and cross-validation
are currently
lacking. This study aims to directly compare the sensitivity of different eDNA-based
methods in field and laboratory applications, and to develop an easy-to-
apply
and
sensitive protocol to monitor T. bryosalmonae occurrence non-invasively
by its eDNA
in water samples. First, we tested three existing probe-based
T. bryosalmonae-specific
detection assays in parallel by comparing the limit of detection (LOD) and limit of
quantification (LOQ) using quantitative PCR (qPCR) and digital droplet PCR (ddPCR)
platforms. Second, the impact of different filter types and water volumes on the
detection probability was tested by sampling water directly from riverbanks with a
syringe-based
protocol. The most sensitive detection protocol was the combination
of the probe-based
assay published by Bettge et al. run via ddPCR, resulting in a LOD
of 1.65 copies/μL input (6.6 copies/reaction) and a LOQ of 3.66 copies/μL input (14.67
copies/reaction). The type of filter (Sterivex™ compared to Millex®) did not significantly
influence detection probability, however, the volume of water sampled (600 mL
compared to 300 mL) significantly affected the probability of capturing eDNA in a
sample. Based on modeled probabilities of eDNA capture and detection, we calculated
that using the Bettge et al. assay via the ddPCR platform for data collection,
95% overall detection probability could be achieved with three replicates of 600 mL
filtered water with Sterivex™ filters. Based on this cross-validation
of assays and detection
platforms, we provide a cost-effective,
straightforward, and highly sensitive
laboratory analysis workflow to detect DNA of T. bryosalmonae from water samples
Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation.
Get PDFThe intracellular ATP-ribosyltransferases PARP1 and PARP2, contribute to DNA base excision repair (BER) and DNA demethylation and have been implicated in epigenetic programming in early mammalian development. Recently, proteomic analyses identified BER proteins to be covalently poly-ADP-ribosylated by PARPs. The role of this posttranslational modification in the BER process is unknown. Here, we show that PARP1 senses AP-sites and SSBs generated during TET-TDG mediated active DNA demethylation and covalently attaches PAR to each BER protein engaged. Covalent PARylation dissociates BER proteins from DNA, which accelerates the completion of the repair process. Consistently, inhibition of PARylation in mESC resulted both in reduced locus-specific TET-TDG-targeted DNA demethylation, and in reduced general repair of random DNA damage. Our findings establish a critical function of covalent protein PARylation in coordinating molecular processes associated with dynamic DNA methylation
Evaluation of Triple Whammy Prescriptions After the Implementation of a Drug Safety Algorithm.
Get PDFBACKGROUND AND OBJECTIVE
The term triple whammy (TW) refers to the concomitant use of non-steroidal anti-inflammatory drugs, diuretics, and angiotensin system inhibitors; this combination significantly increases the risk of acute kidney injury (AKI). To prevent this serious complication, we developed an electronic algorithm that detects TW prescriptions in patients with additional risk factors such as old age and impaired kidney function. The algorithm alerts a clinical pharmacist who then evaluates and forwards the alert to the prescribing physician.
METHODS
We evaluated the performance of this algorithm in a retrospective observational study of clinical data from all adult patients admitted to the Cantonal Hospital of Aarau in Switzerland in 2021. We identified all patients who received a TW prescription, had a TW alert, or developed AKI during TW therapy. Algorithm performance was evaluated by calculating the sensitivity and specificity as a primary endpoint and determining the acceptance rate among clinical pharmacists and physicians as a secondary endpoint.
RESULTS
Among 21,332 hospitalized patients, 290 patients had a TW prescription, of which 12 patients experienced AKI. Overall, 216 patients were detected by the alert algorithm, including 11 of 12 patients with AKI; the algorithm sensitivity is 88.3% with a specificity of 99.7%. Physician acceptance was high (77.7%), but clinical pharmacists were reluctant to forward the alerts to prescribers in some cases.
CONCLUSION
The TW algorithm is highly sensitive and specific in identifying patients with TW therapy at risk for AKI. The algorithm may help to prevent AKI in TW patients in the future
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