Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes.
To determine whether the combination of vasopressin and ...methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation.
Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021.
Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses.
The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2).
Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean SD age, 71 13 years; 322 men 64%). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 95% CI, 1.03-1.63; risk difference, 9.6% 95% CI, 1.1%-18.0%; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 95% CI, 0.50-1.37; risk difference: -2.0% 95% CI, -7.5% to 3.5%; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 95% CI, 0.55-1.83; risk difference, 0.0% 95% CI, -4.7% to 4.9%; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively.
Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival.
ClinicalTrials.gov Identifier: NCT03640949.
Implants of bioresorbable materials combined with osteoconductive calcium phosphate ceramics show promising results to replace and repair damaged bone tissue. Here we present additive manufacturing ...of patient-specific porous scaffolds of poly(trimethylene carbonate) (PTMC) including high amounts of β-tricalcium phosphate (β-TCP). Tensile testing of composite networks showed that addition of β-tricalcium phosphate reinforces the composites significantly. Three-dimensional structures containing up to 60 wt % β-TCP could be built by stereolithography. By lowering the content to 51 wt %, manufacturing of a large-sized patient-specific prototype was possible at high resolution. Closer examination revealed that the created scaffolds contained more β-TCP on the surface of the builds. Stereolithography therefore provides a manufacturing technique where the bioactive agent is directly available for creating an enhanced microenvironment for cell growth. The biocompatibility and bioresorption of PTMC coupled with the osteoconductivity of β-TCP are an important candidate to consider in additive manufacturing of bone regeneration implants.
Abstract
Aims
Direct-current cardioversion is one of the most commonly performed procedures in cardiology. Low-escalating energy shocks are common practice but the optimal energy selection is ...unknown. We compared maximum-fixed and low-escalating energy shocks for cardioverting atrial fibrillation.
Methods and results
In a single-centre, single-blinded, randomized trial, we allocated elective atrial fibrillation patients to cardioversion using maximum-fixed (360-360-360 J) or low-escalating (125-150-200 J) biphasic truncated exponential shocks. The primary endpoint was sinus rhythm 1 min after cardioversion. Safety endpoints were any arrhythmia, myocardial injury, skin burns, and patient-reported pain after cardioversion. We randomized 276 patients, and baseline characteristics were well-balanced between groups (mean ± standard deviation age: 68 ± 9 years, male: 72%, atrial fibrillation duration >1 year: 30%). Sinus rhythm 1 min after cardioversion was achieved in 114 of 129 patients (88%) in the maximum-fixed energy group, and in 97 of 147 patients (66%) in the low-escalating energy group (between-group difference; 22 percentage points, 95% confidence interval 13–32, P < 0.001). Sinus rhythm after first shock occurred in 97 of 129 patients (75%) in the maximum-fixed energy group compared to 50 of 147 patients (34%) in the low-escalating energy group (between-group difference; 41 percentage points, 95% confidence interval 30–51). There was no significant difference between groups in any safety endpoint.
Conclusion
Maximum-fixed energy shocks were more effective compared with low-escalating energy shocks for cardioverting atrial fibrillation. We found no difference in any safety endpoint.
Aims
To examine the nationwide trends in antidiabetic drug utilization and expenditure in Denmark over the past 22 years.
Methods
Data on antidiabetic use and expenditure from 1996 to 2017 were ...retrieved from the Register of Medicinal Product Statistics. Antidiabetic drug use is reported as defined daily dose (DDD) in total counts and per 1000 inhabitants/d. Expenditure is reported as volume sold in total counts per 1000 inhabitants and as annual mean expenditure.
Results
Throughout the study period, the total use of antidiabetic drugs increased from 16.4 to 55.8 DDDs per 1000 inhabitants/d, while total expenditure increased from €59 to €286 m. The introduction of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), dipeptidyl peptidase‐4 inhibitors and sodium‐glucose co‐transporter‐2 inhibitors has, since 2005, led to considerable variation in the proportional use of the different drug classes. Use of insulin and insulin analogues accounted for the majority of the cost of antidiabetic drugs, peaking at 75% in 2008; however, its proportional impact on overall antidiabetic drug expenditure decreased to ~44% in 2017. In contrast, a steep increase in GLP‐1RA expenditure was observed from 2010 to 2017, reaching an annual cost of €85 m (~29% of all antidiabetic expenditure).
Conclusion
Antidiabetic drug utilization and cost in Denmark has increased considerably over the last 22 years, in accordance with the increased incidence of type 2 diabetes and changes in treatment guidelines. The release of several novel antidiabetic drugs seems to be responsible for the increase in antidiabetic drug expenditure.
•The evolution of droplet penetration correlates with oil transport mechanisms in the filter media.•The formation of channels leads to an increase in overall penetration.•The formation of the film ...causes a drop of overall penetration.•Filtration velocity and oil loading rate affect the evolution of overall penetration.•For highly efficient oleophilic media, entrainment is the dominant factor for clean gas concentration in steady state.
The operating conditions of oil mist filters along with the filter media properties are the decisive factors for the evolution of separation efficiency and pressure drop during filter operation. Experimental studies were carried out to determine the evolution of clean gas concentration of oil mist filters with different media properties with regard to the oil transport mechanisms and its dependence on the operating conditions of the filters. The experiments were carried out using two types of glass fiber filter media, one oleophilic and one oleophobic. The effects of filter face velocity and oil loading rate were investigated for both filter media. The effect of media thickness was explored by varying the number of layers. It was found that filter overall separation efficiency can be correlated with the oil transport mechanisms analogously to the correlation to pressure drop proposed by the Film–and-Channel model by Kampa et al. (2004). Decreasing velocities led to a stronger increase in overall penetration when liquid channels are formed in both types of media, which can be attributed to a loss of efficiency for droplets smaller than the MPPS in the size range of 0.1 µm and below, while increasing the oil loading rate had the same effect, however not as distinct. Increasing filter thickness by adding filter layers also caused a stronger increase of penetration during this channel section. The formation of an oil film caused a drop in penetration. The effect of the oil film on penetration was found to be independent of loading rate, but not of velocity, due to its significance for inertial deposition. For highly efficient oleophilic filters, entrainment was found to be the dominant factor for clean gas concentration in steady state.
The "wet pressure drop" of oil mist filters (i.e. the increase in differential pressure of the air flow due to loading of the filter with liquid) is presented as a function of two mechanisms by which ...coalesced oil is transported through the filter. These mechanisms operate in separate regions of the filter and make separate (and separately measurable) contributions to the overall wet pressure drop. This new concept, which was first formulated qualitatively in a phenomenological model by Kampa et al. (2014), leads to semi-quantitative predictions regarding the dependence of pressure drop Delta p and saturation S on filter operating conditions, filter properties and liquid properties. These predictions are first formulated and then validated for a range of wettable and non-wettable filter media in combination with 4 mineral oils of different viscosity. The key findings, summarized below, are consistent with the model and apply to both wettable and non-wettable media. Oil transport across media interfaces (i.e. transitions between regions of different porosity and/or wettability) was associated with a relatively sharp increase in pressure drop Delta p and oil saturation S over a very thin layer of the filter (a " Delta p jump"). The magnitude of this Delta p jump was determined by the media properties. It correlated well with the respective static break-through pressures for oil or air, but did not depend on the oil viscosity and loading rate of the filter (at constant air velocity). Oil transport through channel regions of the filter (i.e. the regions connecting interfaces) was associated with a linear increase in Delta p with channel length and liquid throughput. The corresponding saturation level S was relatively flat throughout the channel region and lower than at an interface. (Both quantities are media dependent, of course.) An increase in oil viscosity mu (at constant oil throughput) led to different responses depending on filter wettability.
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