Aim To assess predictors of in‐hospital mortality in people with prediabetes and diabetes hospitalized for COVID‐19 infection and to develop a risk score for identifying those at the greatest risk of a fatal outcome. Materials and Methods A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID‐19. The primary outcome was in‐hospital mortality and the predictor variables upon admission included clinical data, co‐morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in‐hospital mortality. Results The mean age of people hospitalized (n = 238) for COVID‐19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance ( P = .128). A score including age, arterial occlusive disease, C‐reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in‐hospital mortality with a C‐statistic of 0.889 (95% CI: 0.837‐0.941) and calibration of 1.000 ( P = .909). Conclusions The in‐hospital mortality for COVID‐19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in‐hospital mortality.
Parkinson disease (PD) compromises oropharyngeal swallowing, which negatively affects quality of life and contributes to aspiration pneumonia. Dysphagia often begins early in the disease process, and does not improve with standard therapies. As a result, swallowing deficits are undertreated in the PD population. The Pink1 −/− rat is used to model PD, and demonstrates widespread brainstem neuropathology in combination with early-onset sensorimotor dysfunction; however, to date, swallowing behaviors have not been evaluated. To test the hypothesis that Pink1 −/− rats demonstrate early-onset differences in swallowing, we analyzed within-subject oropharyngeal swallowing using videofluoroscopy. Pink1 −/− and wildtype (WT) controls at 4 (Pink1 −/− n = 16, WT = 16) and 8 (Pink1 −/− n = 12, WT = 12) months of age were tested. The average and maximum bolus size was significantly increased in Pink1 −/− rats at both 4 and 8 months. Bolus average velocity was increased at 8 months for all animals; yet, Pink1 −/− animals had significantly increased velocities compared to WT at 8 months. The data show a significant reduction in mastication rate for Pink1 −/− rats at 8 months suggesting the onset of oromotor dysfunction begins at this time point. Relationships among swallowing variables and neuropathological findings, such as increased alpha-synuclein protein in the nucleus ambiguus and reductions in noradrenergic cells in the locus coeruleus in the Pink1 −/− rats, were determined. The presence of early oropharyngeal swallowing deficits and relationships to brainstem pathology in Pink1−/− rat models of PD indicate that this may be a useful model of early swallowing deficits and their mechanisms. These findings suggest clinical implications for early detection and management of dysphagia in PD.
In Parkinson disease (PD), a complex neurodegenerative disorder that affects nearly 10 million people worldwide, motor skills are significantly impaired. However, onset and progression of motor deficits and the neural correlates of these deficits are poorly understood. We used a genetic mouse model of PD (Pink1-/-), with phenotypic similarities to human PD, to investigate the manifestation of early-onset sensorimotor deficits. We hypothesized this mouse model would show early vocalization and gross motor dysfunction that would be progressive in nature. Pink1-/- mice, compared to wild type (WT) controls, were evaluated at 2, 3, 4, 5, and 6 months of age. To quantify deficit progression, ultrasonic vocalizations and spontaneous locomotor activity (cylinder test and pole test) were analyzed. Although somewhat variable, in general, Pink1-/- mice produced significantly more simple calls with reduced intensity as well as a larger percentage of cycle calls compared to WT counterparts. However, there were no significant differences in duration, bandwidth, or peak frequency for any of the ultrasonic call types between genotypes. Pink1-/- mice showed a significant impairment in limb motor skills with fewer hindlimb steps, forelimb steps, and rears and lands in the cylinder test compared to WT. Additionally, Pink1-/- mice took significantly longer to turn and traverse during the pole test. Immunohistochemical staining showed no significant difference in the number of tyrosine hydroxylase (TH) positive cells in the substantia nigra or density of TH staining in the striatum between genotypes. These data suggest the Pink1-/- mouse model may be instrumental in defining early motor biomarkers of PD in the absence of nigrostriatal dopamine loss.
Levodopa does not improve dysarthria in patients with Parkinson Disease (PD), although vocal exercise therapy, such as “LSVT/LOUD®”, does improve vocal communication. Most patients receive vocal exercise therapy while concurrently being treated with levodopa, although the interaction between levodopa and vocal exercise therapy on communication in PD is relatively unknown. Further, carryover of vocal exercise therapy to novel situations is critical for successful outcomes, but the influence of novel situations on rehabilitated vocal communication is not well understood. To address the influence of exercise, medications, and environment on vocal communication with precise experimental control, we employed the widely used 6-OHDA rat neurotoxin model of PD (infusion to the medial forebrain bundle), and assessed ultrasonic vocalizations after: vocal exercise, vocal exercise with levodopa, levodopa alone, and control conditions. We tested USVs in the familiar training environment of the home cage and a novel cage. We hypothesized that parkinsonian rats that undergo vocal exercise would demonstrate significant improvement of ultrasonic vocalization (USV) acoustic parameters as compared to the control exercise and levodopa-only treatment groups. We further hypothesized that vocal exercise in combination with levodopa administration, similar to what is common in humans, would lead to improvement in USV outcomes, particularly when tested in a familiar versus a novel environment. We found that the combination of exercise and levodopa lead to some improvement in USV acoustic parameters and these effects were stronger in a familiar vs. a novel environment. Our results suggest that although treatment can improve aspects of communication, environment can influence the benefits of these effects.
Background: This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. Methods: This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or prediabetes hospitalized for COVID-19 in 11 hospitals in Austria. The primary outcome of this study was in-hospital mortality. The predictor variables included demographic characteristics, clinical parameters, comorbidities, use of medication, disease severity, and laboratory measurements of biomarkers. The association between biomarkers and in-hospital mortality was assessed using simple and multiple logistic regression analyses. The predictive performance of biomarkers was assessed using discrimination and calibration. Results: In our analysis, 70.8% had type 2 diabetes mellitus, 5.8% had type 1 diabetes mellitus, 14.9% had prediabetes, and 8.6% had other types of diabetes mellitus. The mean age was 70.3 ± 13.3 years, and 69.3% of patients were men. A total of 19.0% of patients died in the hospital. In multiple logistic regression analysis, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. The discrimination of NT-proBNP was 74%, and that of Troponin T was 81%. The calibration of NT-proBNP was adequate (p = 0.302), while it was inadequate for Troponin T (p = 0.010). Conclusion: Troponin T showed excellent predictive performance, while NT-proBNP showed good predictive performance for assessing in-hospital mortality in patients with diabetes mellitus hospitalized with COVID-19. Therefore, these cardiac biomarkers may be used for prognostication of COVID-19 patients.
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