To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world ...context of clinical practice.
Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis.
Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18.
209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years.
The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis.
Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4
16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1
6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9
7.7; 0.60, 0.54 to 0.67), heart failure (3.1
7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7
17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6
3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87).
In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors.
ClinicalTrials.gov NCT03939624.
3D Food Printing has unprecedented ambitions but for its practical use the increase of the speed of material deposition is a challenge to tackle. We have extended the information on this aspect by ...using a workflow that analyzes the screw-based deposition, at medium-high speed and the effect of some undervalued variables on the quality of 3D printed cereal-based structure. The most familiar approach utilized to compute the right extrusion rate for a good replica of the 3D virtual model completely fails at high print speed. Improvements would be possible only by using a flow of 300% or by changing, as input data, the diameter of filament at 1.0 mm. However, additional irregularities are caused by undervalued variables such as retraction distance being the most important for the printing quality while the travel speed and retraction speed are crucial to reduce printing time. Finally, desirability approach was able to define the conditions capable to get a maximum desirability of 0.85 at speed of 200 mm/s.
•Experiments of 3DFP at high speed were studied by using a screw-based system.•Low fidelity was caused for the lack of equilibrium between movements and deposition.•Better structures were obtained by a flow of 300% or by a filament diameter of 1.0 mm.•Non-printing movements affect the fidelity of printing.•The best printing conditions allowed a desirability of 0.85.
The overarching purpose of this article is to provide an introduction to the use of rigorous single-case research designs (SCRDs) in special education and related fields. Authors first discuss basic ...design types and research questions that can be answered with SCRDs, examine threats to internal validity and potential ways to control for and detect common threats, and provide guidelines for selection of specific designs. Following, contemporary standards regarding rigor, measurement, description, and outcomes are presented. Then, authors discuss data analytic techniques, differentiating rigor, positive outcomes, functional relations, and magnitude of effects.
Interventions designed to decrease problem behavior for students with ASD are critical and may be differentially important for students from minority groups as those students tend to be assigned more ...negative outcomes related to problem behavior (e.g., suspensions). School-based interventions intended to decrease problem behavior for individuals with ASD were reviewed; 46 articles including 84 single case designs and 87 participants were analyzed regarding participant demographics, settings and implementers, intervention components, and study characteristics. We assessed outcomes for 55 demonstration designs with adequate rigor. Most research was conducted with students in segregated settings and, although race and ethnicity were rarely reported, proportions were different from other reviews in that children from some minority groups were overrepresented.
Aim
To compare urosepsis rates in patients with type 2 diabetes treated using sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) with dipeptidyl peptidase‐4 inhibitors (DPP4i) in a real‐world ...setting.
Methods
We conducted a matched cohort study using a prevalent new‐user design with time‐conditional propensity scores. New users of SGLT2i from seven Canadian provinces and the UK were matched to DPP4i users. The primary outcome was hospitalization with a diagnosis of urosepsis and the secondary outcome was Fournier's gangrene. Site‐specific hazard ratios for urosepsis comparing SGLT2i with DPP4i were estimated using Cox proportional hazards models and pooled using a random effects meta‐analysis.
Results
We included 208 244 users of SGLT2i and 208 244 users of DPP4i. Among SGLT2i users, 42% initiated canagliflozin, 31% dapagliflozin and 27% empagliflozin. During a mean follow‐up of 0.9 years, patients initiating SGLT2i had a lower rate of urosepsis compared with those receiving DPP4i. The pooled adjusted hazard ratio was 0.58 (95% confidence interval CI: 0.42‐0.80). The incidence rates of Fournier's gangrene were numerically similar in SGLT2i (0.08 per 1000 person‐years; 95% CI: 0.05‐0.13) and DPP4i users (0.14; 95% CI: 0.09‐0.21).
Conclusions
In this large, multi‐site study, we did not observe an increased risk for urosepsis associated with SGLT2i compared with DPP4i among patients with type 2 diabetes in a real‐world setting.
The present study shows the results of laboratory experiments addressing the effects of different water qualities on E. americana's fecundity and survival. The study was carried out with cultured ...females, incubated under different water qualities and controlled conditions during ten days (7 ± 2 °C, 14 h light, salinity of 32 ± 2, Tetraselmis sp. and Nannochloropsis sp. as food). Four treatments were established: P = subsurface water from sewage plume of Bahía Blanca city, D = the dissolved phase of P, I = bottom water in the sewage discharge point of Bahía Blanca city, and C = water from the low-impacted area of Monte Hermoso, used as a control treatment. Egg production, number of nauplii, number of faecal pellets, survival and fertility-state of females were evaluated. The differences and relationships among copepod factors, environmental variables and pollutants levels (cadmium, lead, copper, zinc, chrome and ammonium-phosphate dissolved), were analysed among treatment using non-parametric multivariate analysis. The copepod factors showed a negative association with pollutants levels and the turbidity. No mortality was observed in C, P and D treatments, whereas 100% mortality was observed in treatment I. Females from C, showed the highest egg production (22.6 ± 6.5 egg/female.clutch), as well as gonads regeneration and a second egg laying. Egg production, number of nauplli and faecal pellets were similar for P and D treatments, but significantly lower than those registered in C. In P treatment, only 40% of females showed regeneration of their gonads for a second egg laying (12.4 ± 2.9 egg/female.clutch) and in D treatment, no female regenerated their gonads for a second egg laying (12.5 ± 3 egg/female.clutch). The results indicate that bioavailable contaminants from dissolved phase of sewage effluent reduce the fertility in Eurytemora americana, while the bottom water at the sewage discharge site is undoubtedly lethal for this species.
Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well ...known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8
T cells expressing CD69
CD103
increase in number ~12 days following the first and second doses, by 0.31 and 0.43 log
cells per swab respectively (p = 0.058 and p = 0.009 in adjusted linear mixed models). CD69
CD103
CD8
T cells in the blood decrease post-vaccination. Similar increases in nasal CD8
CD69
CD103
T cells are observed, particularly following the second dose. CD4
cells co-expressing CCR6 and CD161 are also increased in abundance following both doses. Stimulation of nasal CD8
T cells with SARS-CoV-2 spike peptides elevates expression of CD107a at 2- and 6-months (p = 0.0096) post second vaccine dose, with a subset of donors also expressing increased cytokines. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.
Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to hypomethylation of D4Z4 repeats on chromosome 4q causing expression of the DUX4 transcription factor. ...However, DUX4 is difficult to detect in FSHD muscle biopsies and it is debatable how robust changes in DUX4 target gene expression are as an FSHD biomarker. PAX7 is a master regulator of myogenesis that rescues DUX4-mediated apoptosis. Here, we show that suppression of PAX7 target genes is a hallmark of FSHD, and that it is as major a signature of FSHD muscle as DUX4 target gene expression. This is shown using meta-analysis of over six FSHD muscle biopsy gene expression studies, and validated by RNA-sequencing on FSHD patient-derived myoblasts. DUX4 also inhibits PAX7 from activating its transcriptional target genes and vice versa. Furthermore, PAX7 target gene repression can explain oxidative stress sensitivity and epigenetic changes in FSHD. Thus, PAX7 target gene repression is a hallmark of FSHD that should be considered in the investigation of FSHD pathology and therapy.
PDF
