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Older Adult Perspectives on Statin Continuation and Discontinuation in Primary Cardiovascular Disease Prevention: A Mixed-Methods Study.
Get PDFBackground and Purpose: Evidence for statin use for primary cardiovascular disease prevention in older adults is limited. When evidence on risk-benefit profile of a medication is uncertain, using it or not becomes a preference-sensitive decision. We aimed to assess and explore patient perspectives on continuation and discontinuation of statins used for primary cardiovascular prevention in older adults.
Patients and Methods: We used a convergent mixed-methods design, conducting in parallel a survey among 47 patients and three focus groups (FGs) with 14 patients total. We recruited patients aged ≥ 65 years and taking a statin for primary cardiovascular prevention. The survey and FGs aimed to assess and explore patient experiences of statin use, and views on statin continuation and discontinuation, including patient decision-making. Quantitative and qualitative data were first analyzed separately – descriptive statistics for quantitative data and thematic analysis for qualitative data – and then integrated to create metainferences, using joint displays.
Results: Forty-one percent of patients (N=19) were reluctant to discontinue the statin, whereas 22% (N=10) were willing to try discontinuing it. A reason to continue the statin was its perceived necessity, while self-estimated low cardiovascular risk and wish to reduce medication burden were given as reasons to discontinue it. Lack of expertise assumed by the patients to decide about statin continuation or discontinuation, uncertainty about statin indication, and fear of having a cardiovascular event after discontinuation made many patients uncertain about deciding to continue or discontinue the statin. In this context, 70% (N=33) would rather have their physician choose for them, and 94% (N=44) would continue taking the statin for as long as their physician told them to do so.
Conclusion: This study highlights factors that influence patient willingness to continue or discontinue statins, patient uncertainty about statin continuation or discontinuation, and the important role physicians play in the decision-making process
Enzymatic debridement with bromelain and development of bacteremia in burn injuries: A retrospective cohort study.
Get PDFBACKGROUND
Debridement is crucial for effective wound management in patients with severe burn injuries, and bromelain, a proteolytic enzyme from pineapple stems, has emerged as a promising alternative for surgery. However, potential links of bromelain use to fever and sepsis have raised some concerns. Given the uncertainty as to whether this was caused by infection or other inflammatory sources, we aimed to investigate if the use of topical bromelain was associated with bacteremia.
METHODS
This single-centre retrospective cohort study included critically ill adult patients with severe burn injuries hospitalised at the Burn Center of the University Hospital Zurich between January 2017 and December 2021. Data were collected from two in-hospital electronic medical records databases. Our primary outcome, the association between topical bromelain treatment and the development of bacteremia, was investigated using a competing risk regression model, taking into account the competing risk of death. As a secondary outcome, the relationship between bromelain treatment and overall ICU mortality was examined using a Cox proportional hazards model.
RESULTS
The study included 269 patients with a median age of 50 years and median burnt total body surface area of 19%. A first bacteremia occurred in 61 patients (23%) after a median time of 6 days. Bromelain treatment was given to 83 (31%) of patients, with 22 (27%) of these developing bacteremia. In the fully adjusted competing risk regression model, no evidence for an association between bromelain treatment and bacteremia was found (SHR 0.79, 95%CI 0.42-1.48, p = 0.47). During hospital stay, 40 (15%) of patients died. There was no significant difference in mortality between patients treated with bromelain and those who were not (HR 0.55, 95%CI 0.26-1.20, p = 0.14). Among the five multidrug-resistant (MDR) pathogens identified, three were found in patients with bromelain treatment.
CONCLUSION
Our study did not confirm an association between topical bromelain and bacteremia in patients with severe burn injuries. This finding can inform evidence-based practices by addressing concerns about potential risks of bromelain use, contributing to the development of more effective and safe burn wound management strategies
Unilateral intraindividual comparison and bilateral performance of a monofocal spherical and diffractive extended depth of field intraocular lens mix-and-match approach
Get PDFBackground: To evaluate the intraindividual visual performance of a spherical and extended depth of field (EDOF) IOL used in a mix-and-match approach.
Methods: Single centre (tertiary care centre), retrospective consecutive case series. Included patients had uneventful cataract surgery with implantation of a spherical monofocal IOL (CT Spheris 204) in the dominant eye and a diffractive EDOF IOL (AT LARA 829) in the non-dominant eye. Monocular and binocular defocus curves and visual acuity at various distances were assessed. In addition, binocular reading speed, contrast sensitivity, and patient satisfaction using QOV, Catquest 9SF, and glare/halo questionnaires are reported.
Results: A total of 29 patients (58 eyes) were included. We observed significant intra-individual differences for monocular DCIVA, DCNVA, UIVA, and UNVA. There were no differences in monocular BCDVA or UDVA. The monocular defocus curves for the two IOLs significantly differed at defocus steps between -1.0 and -3.5 D. 93.10% of patients reported they would opt for the same combination of IOLs.
Conclusion: Excellent uncorrected and corrected distance visual acuity was demonstrated in both groups. The mix-and-match approach described in this study yielded good intermediate vision and improved near vision with high-patient satisfaction
Effects of transport age (14 d vs. 28 d of age) on blood total cholesterol, insulin and IGF-1 concentrations of veal calves.
Get PDFThe main aim of the current study was to find biomarkers of health in calves transported at different ages. The selected blood parameters were total cholesterol, insulin and IGF-1 and the longitudinal study investigated whether or not these concentrations were different between calves that were transported from the dairy farm to the veal farm at 14 d or 28 d of age. Relationships between these blood variables and health characteristics of veal calves were investigated. In a 34-wk study period, a total of 683 calves originating from 13 Dutch dairy farms were transported at an age of 14 or 28 d to 8 Dutch veal farms. Calves were blood sampled the first wk after birth (mean and SD: 4.4 ± 2.1 d), a day before transport (mean and SD: 25.8 ± 7.3 d) and in wk 2 post-transport (mean and SD: 36.7 ± 12.2 d). In these samples, insulin, IGF-1 and total cholesterol were determined and analyzed with a linear mixed model (LMM). Individual medical treatments were recorded from birth until the day of transport at the dairy farm, and from the moment of arrival at the veal farm until slaughter, and analyzed as a binary response variable (calf treated or not) with a generalized linear mixed model. Fecal (calf with or without loose or liquid manure) and navel (calves with or without swollen and inflamed navel) scores measured during a single visit in wk 2 post-transport were also analyzed as binary response variables, whereas carcass weights at slaughter age were analyzed with a LMM. Cholesterol, insulin and IGF-1 were included as covariates in the previous models to test their relationships with the likelihood of calves being medically treated, fecal and navel scores, and carcass weights. One day before transport 28 d-old calves had higher blood cholesterol (Δ = 0.40 mmol/l) and IGF-1 (Δ = 53.6 ng/ml) concentrations, and evidence of higher insulin (Δ = 12.2 µU/ml) compared with 14 d-old calves. In wk 2 post-transport, 28-d old calves had higher blood IGF-1 (Δ = 21.1 ng/ml), with evidence of higher insulin (Δ = 12.2 µU/ml) concentrations compared with 14-d old calves. Cholesterol concentration measured one day before transport and in wk 2 post-transport had a positive relationship with carcass weight at slaughter (β = 4.8 and 7.7 kg/mmol/l, respectively). Blood cholesterol concentration in wk 2 post-transport was negatively associated with the fecal score measured at the same sampling moment (β = -0.55/mmol/l), with the likelihood of a calf of being treated with antibiotics (β = -0.36/mmol/l) and other medicines (β = -0.45/mmol/l) at the veal farm. Blood IGF-1 concentration in wk 2 post-transport was negatively associated with the likelihood of a calf of being treated with antibiotics and other medicines (both β = -0.01/ng/ml) at the veal farm, and with fecal score recorded in wk 2 post-transport (β = -0.004/ng/ml). When looking at the blood indicators, it appeared that calves transported at 28 d of age were more developed compared with 14 d old calves, thus transport at an older age might be more beneficial for the animals. It can be concluded that both blood cholesterol and IGF-1 concentrations seemed to be valuable biomarkers of health and energy availability in veal calves
Membrane damage by MBP-1 is mediated by pore formation and amplified by mtDNA.
Get PDFEosinophils play a crucial role in host defense while also contributing to immunopathology through the release of inflammatory mediators. Characterized by distinctive cytoplasmic granules, eosinophils securely store and rapidly release various proteins exhibiting high toxicity upon extracellular release. Among these, major basic protein 1 (MBP-1) emerges as an important mediator in eosinophil function against pathogens and in eosinophil-associated diseases. While MBP-1 targets both microorganisms and host cells, its precise mechanism remains elusive. We demonstrate that formation of small pores by MBP-1 in lipid bilayers induces membrane permeabilization and disrupts potassium balance. Additionally, we reveal that mitochondrial DNA (mtDNA) present in eosinophil extracellular traps (EETs) amplifies MBP-1 toxic effects, underscoring the pivotal role of mtDNA in EETs. Furthermore, we present evidence indicating that absence of CpG methylation in mtDNA contributes to the regulation of MBP-1-mediated toxicity. Taken together, our data suggest that the mtDNA scaffold within extracellular traps promotes MBP-1 toxicity
The Safety and Outcome of Minimally Invasive Staged Segmental Artery Coil Embolization (MIS2ACE) Prior Thoracoabdominal Aortic Aneurysm Repair: A Single-Center Study, Systematic Review, and Meta-Analysis.
Get PDFBACKGROUND
Minimally Invasive Staged Segmental Artery Coil Embolization (MIS2ACE) is a novel technique of spinal cord preconditioning used to reduce the risk of paraplegia in thoracoabdominal aortic aneurysm (TAAA) repair. In this study, we report our experience with MIS2ACE, including both degenerative and post-dissection TAAA, while we attempt to systematically summarize relevant data available in the literature.
DESIGN
single-center observational study with systematic review of the literature and meta-analysis.
METHODS
Initial retrospective analysis of 7 patients undergoing MIS2ACE over 12 sessions with a subsequent systematic review of the literature and meta-analysis of the available published data (PROSPERO protocol number: CRD42023477411). Baseline patient and aneurysm characteristics, along with procedural technique and outcomes, were analyzed. One-arm pooling of proportions was used to summarize available published data.
RESULTS
We treated seven patients (5 males, 71%) with a median age of 69 years (IQR 55,69). According to the Crawford classification, five patients (1%) had extent II TAAA, and two (29%) had extent III TAAA. Five patients (71%) had post-dissection -TAAA; four of them were after Stanford type A dissection, and one had a chronic type B dissection. Three patients (43%) had connective tissue disease. Of the seven patients, six (86%) underwent previous aortic surgery, while the median aneurysm diameter was 58 mm (IQR 55,58). MIS2ACE was successful in 11 sessions (92%). The median number of embolized arteries was 4 (IQR 1,4). There were no periprocedural complications in any embolization. The median embolization-operation time interval was 37.0 days (IQR 31,78). Two patients had open and five endovascular treatment. There were no events of spinal cord ischemia either after MIS2ACE or after the aortic repair. Out of the 432 initially retrieved articles, we included two studies in the meta-analysis, including patients with MIS2ACE for spinal cord preconditioning in addition to our cohort. The prevalence of pooled postoperative spinal cord ischemia among MIS2ACE patients is 1.9% (95% CI -0.028 to 0.066, p = 0.279; 3 studies; 81 patients, 127 coiling sessions).
CONCLUSIONS
While the current published data is limited, our study further confirms that MIS2ACE is a technically feasible and safe option for spinal cord preconditioning
Comparison of ultrasonography, tenography, and cone beam computed tomographic tenography with tenoscopy for lesion detection within the digital flexor tendon sheath – a prospective clinical trial
No full textMachine Learning-Based Analysis Reveals Triterpene Saponins and Their Aglycones in Cimicifuga racemosa as Critical Mediators of AMPK Activation.
Get PDFCimicifuga racemosa (CR) extracts contain diverse constituents such as saponins. These saponins, which act as a defense against herbivores and pathogens also show promise in treating human conditions such as heart failure, pain, hypercholesterolemia, cancer, and inflammation. Some of these effects are mediated by activating AMP-dependent protein kinase (AMPK). Therefore, comprehensive screening for activating constituents in a CR extract is highly desirable. Employing machine learning (ML) techniques such as Deep Neural Networks (DNN), Logistic Regression Classification (LRC), and Random Forest Classification (RFC) with molecular fingerprint MACCS descriptors, 95 CR constituents were classified. Calibration involved 50 randomly chosen positive and negative controls. LRC achieved the highest overall test accuracy (90.2%), but DNN and RFC surpassed it in precision, sensitivity, specificity, and ROC AUC. All CR constituents were predicted as activators, except for three non-triterpene compounds. The validity of these classifications was supported by good calibration, with misclassifications ranging from 3% to 17% across the various models. High sensitivity (84.5-87.2%) and specificity (84.1-91.4%) suggest suitability for screening. The results demonstrate the potential of triterpene saponins and aglycones in activating AMP-dependent protein kinase (AMPK), providing the rationale for further clinical exploration of CR extracts in metabolic pathway-related conditions
Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland.
Get PDFOBJECTIVES
In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial.
DESIGN
This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial.
SETTING
10 Swiss paediatric hospitals (secondary and tertiary care) participated.
PARTICIPANTS
Paediatric patients hospitalised with PIMS-TS.
INTERVENTIONS
All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event.
RESULTS
Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like).
CONCLUSION
The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future.
TRIAL REGISTRATION NUMBERS
SNCTP000004720 and NCT04826588
Data sources:
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