Refining the hospitalization rate: A mixed methods approach to differentiate primary COVID-19 from incidental cases.

Purpose: Until now, the Hospitalization Rate (HR) served as an indicator (among others) for the COVID-19 associated healthcare burden. To ensure that the HR accomplishes its full potential, hospitalizations caused by COVID-19 (primary cases) and hospitalizations of patients with incidental positive SARS-CoV-2 test results (incidental cases) must be differentiated. The aim of this study was to synthesize the existing evidence on differentiation criteria between hospitalizations of primary cases and incidental cases. Methods: An online survey of the members of the German Network University Medicine (NUM) was conducted. Additionally, senior clinicians with expertise in COVID-19 care were invited for qualitative, semi-structured interviews. Furthermore, a rapid literature review was undertaken on publications between 03/2020 and 12/2022. Results: In the online survey (n=30, response rate 56%), pneumonia and acute upper respiratory tract infections were the most indicative diagnoses for a primary case. In contrast, malignant neoplasms and acute myocardial infarctions were most likely to be associated with incidental cases. According to the experts (n=6), the diagnosis, ward, and type of admission (emergency or elective), low oxygen saturation, need for supplemental oxygen, and initiation of COVID-19 therapy point to a primary case. The literature review found that respiratory syndromes and symptoms, oxygen support, and elevated levels of inflammatory markers were associated with primary cases. Conclusion: There are parameters for the differentiation of primary from incidental cases to improve the objective of the HR. Ultimately, an updated HR has the potential to serve as a more accurate indicator of the COVID-19 associated healthcare burden.

Quality of life gains in frail and intermediate-fit patients with multiple Myeloma: Findings from the prospective HOVON123 clinical trial.

BACKGROUND: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. METHODS: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). RESULTS: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. CONCLUSION: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.

High-risk pooling for mitigating risk selection incentives in health insurance markets with sophisticated risk equalization: an application based on health survey information.

BACKGROUND: Despite sophisticated risk equalization, insurers in regulated health insurance markets still face incentives to attract healthy people and avoid the chronically ill because of predictable differences in profitability between these groups. The traditional approach to mitigate such incentives for risk selection is to improve the risk-equalization model by adding or refining risk adjusters. However, not all potential risk adjusters are appropriate. One example are risk adjusters based on health survey information. Despite its predictiveness of future healthcare spending, such information is generally considered inappropriate for risk equalization, due to feasibility challenges and a potential lack of representativeness. METHODS: We study the effects of high-risk pooling (HRP) as a strategy for mitigating risk selection incentives in the presence of sophisticated- though imperfect- risk equalization. We simulate a HRP modality in which insurers can ex-ante assign predictably unprofitable individuals to a 'high risk pool' using information from a health survey. We evaluate the effect of five alternative pool sizes based on predicted residual spending post risk equalization on insurers' incentives for risk selection and cost control, and compare this to the situation without HRP. RESULTS: The results show that HRP based on health survey information can substantially reduce risk selection incentives. For example, eliminating the undercompensation for the top-1% with the highest predicted residual spending reduces selection incentives against the total group with a chronic disease (60% of the population) by approximately 25%. Overall, the selection incentives gradually decrease with a larger pool size. The largest marginal reduction is found moving from no high-risk pool to HRP for the top 1% individuals with the highest predicted residual spending. CONCLUSION: Our main conclusion is that HRP has the potential to considerably reduce remaining risk selection incentives at the expense of a relatively small reduction of incentives for cost control. The extent to which this can be achieved, however, depends on the design of the high-risk pool.

Ultrastructural characterization of maturing iPSC-derived nephron structures upon transplantation.

Pluripotent stem cell-derived kidney organoids hold great promise as a potential auxiliary transplant tissue for individuals with end-stage renal disease and as a platform for studying kidney diseases and drug discovery. To establish accurate models, it is crucial to thoroughly characterize the morphological features and maturation stages of the cellular components within these organoids. Nephrons, the functional units of the kidney, possess distinct morphological structures that directly correlate with their specific functions. High spatial resolution imaging emerges as a powerful technique for capturing ultrastructural details that may go unnoticed with other methods such as immunofluorescent imaging and scRNA sequencing. In our study, we have applied software capable of seamlessly stitching virtual slides generated from electron microscopy, resulting in high-definition overviews of tissue slides. With this technology, we can comprehensively characterize the development and maturation of kidney organoids when transplanted under the renal capsule of mice. These organoids exhibit advanced ultrastructural developments upon transplantation, including the formation of the filtration barrier in the renal corpuscle, the presence of microvilli in the proximal tubule, and various types of cell sub-segmentation in the connecting tubule similarly to those seen in the adult kidney. Such ultrastructural characterization provides invaluable insights into the structural development and functional morphology of nephron segments within kidney organoids and how to advance them by interventions such as a transplantation. Research Highlights High-resolution imaging is crucial to determine morphological maturation of hiPSC-derived kidney organoids. Upon transplantation, refined ultrastructural development of nephron segments was observed, such as the development of the glomerular filtration barrier.

Cartesian constraints in QM/MM optimizations.

With the rise of quantum mechanical/molecular mechanical (QM/MM) methods, the interest in the calculation of molecular assemblies has increased considerably. The structures and dynamics of such assemblies are usually governed to a large extend by intermolecular interactions. As a result, the corresponding potential energy surfaces are topological rich and possess many shallow minima. Therefore, local structure optimizations of QM/MM molecular assemblies can be challenging, in particular if optimization constraints are imposed. To overcome this problem, structure optimization in normal coordinate space is advocated. To do so, the external degrees of freedom of a molecule are separated from the internal ones by a projector matrix in the space of the Cartesian coordinates. Here we extend this approach to Cartesian constraints. To this end, we devise an algorithm that adds the Cartesian constraints directly to the projector matrix and in this way eliminates them from the reduced coordinate space in which the molecule is optimized. To analyze the performance and stability of the constrained optimization algorithm in normal coordinate space, we present constrained minimizations of small molecular systems and amino acids in gas phase as well as water employing QM/MM constrained optimizations. All calculations are performed in the framework of auxiliary density functional theory as implemented in the program deMon2k.

Barriers and enablers of vigorous intermittent lifestyle physical activity (VILPA) in physically inactive adults: a focus group study.

BACKGROUND: Vigorous Intermittent Lifestyle Physical Activity (VILPA) refers to brief bouts of vigorous intensity physical activity performed as part of daily living. VILPA has been proposed as a novel concept to expand physical activity options among the least active. As a nascent area of research, factors which impede or encourage VILPA in physically inactive adults are yet to be explored. Such information is pertinent in the design of future interventions. We examined the barriers and enablers of VILPA among physically inactive adults using the Capability, Opportunity, Motivation, Behavior (COM-B) model as a conceptual framework. METHODS: We recruited a sample of self-identified physically inactive middle-aged and older adults (N = 78) based in Australia to take part in 19 online focus groups across three age groups: young-middle (age 35-44), middle (age 45-59) and old (age 60-76). We analyzed interviews using a critical realist approach to thematic analysis. Identified barriers and enablers were subsequently mapped onto the COM-B model components. RESULTS: The data generated 6 barriers and 10 enablers of VILPA that corresponded to COM-B concepts. Barriers included physical limitations (physical capability), perceptions of aging, need for knowledge (psychological capability), environmental constraints (physical opportunity), perceptions of effort and energy, and fear (automatic motivation). Enablers included convenience, reframing physical activity as purposeful movement, use of prompts and reminders (physical opportunity), normalization of taking the active option, gamification (social opportunity), sense of achievement, health improvements, personally salient rewards (reflective motivation), identity fit, and changing from effortful deliberation to habitual action (automatic motivation). CONCLUSION: The barriers and enablers of VILPA span capability, opportunity, and motivation beliefs. Promoting the time-efficient nature and simplicity of VILPA requiring no equipment or special gym sessions, the use of prompts and reminders at opportune times, and habit formation strategies could capitalize on the enablers. Addressing the suitability of the small bouts, the development of specific guidelines, addressing safety concerns, and explicating the potential benefits of, and opportunities to do, VILPA could ameliorate some of the barriers identified. Future VILPA interventions may require limited age customization, speaking to the potential for such interventions to be delivered at scale.

Accelerometer-derived physical activity and sedentary time and cardiac biomarkers: The Maastricht Study.

Background: Cardiac troponins and NT-proBNP are biomarkers of cardiac injury that are used clinically in the diagnosis of myocardial infarction and heart failure. It is not known whether the amount, types and patterns of physical activity (PA) and sedentary behaviour are associated with levels of cardiac biomarkers. Methods: In the population-based Maastricht Study (n = 2,370, 51.3% male, 28.3% T2D) we determined cardiac biomarkers hs-cTnI, hs-cTnT, and NT-proBNP. PA and sedentary time were measured by activPAL and divided into quartiles [quartile 1 (Q1) served as reference]. The weekly pattern of moderate-to-vigorous PA (insufficiently active; regularly actives; weekend warriors) and coefficient of variation (CV) was calculated. Linear regression analyses were conducted with adjustment for demographic, lifestyle, and cardiovascular risk factors. Results: There was no consistent pattern between physical activity (different intensities: total, light, moderate-to-vigorous and vigorous) and sedentary time on the one hand and hs-cTnI and hs-cTnT on the other. Those with the highest levels of vigorous intensity PA had significantly lower levels of NT-proBNP. With regard to PA patterns, weekend warriors and regularly actives had lower levels of NT-proBNP but not with hs-cTnI and hs-cTnT (reference:insufficiently actives). A higher weekly moderate-to-vigorous PA CV (indicating more irregular activity) was associated with lower levels of hs-cTnI and higher levels of NT-proBNP, but not with hs-cTnT. Conclusions: In general, there was no consistent association between PA and sedentary time and cardiac troponins. In contrast, vigorous and possibly moderate-to-vigorous intensity PA, especially if done regularly, were associated with lower levels of NT-proBNP.

Infection prevention and control between legal requirements and German Society for Hygiene and Microbiology expert assessments: a cross-sectional study in September-November 2022.

BACKGROUND: In contrast to the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), pandemic, more and more hospital issues are now regulated by policy. AIM: To identify differences between expert recommendations and legal requirements regarding infection prevention and control (IPC) strategies. METHODS: A cross-sectional study was conducted between 29th September 2022 and 3rd November 2022 addressing 1319 members of the German Society for Hygiene and Microbiology. The response rate was 12%. This paper reports the expert recommendations on different IPC strategies. FINDINGS: The majority (66%) of experts recommended universal mask usage, with 34% recommending it seasonally, even after the SARS-CoV-2 pandemic. Medical microbiology (MM) experts were more likely to recommend continuing to wear the masks indefinitely compared with IPC experts. Concerning the mask type, medical masks were recommended more frequently by IPC experts (47.3%), while FFP2 masks were preferred by MM experts (31.8%). The majority (54.7%) of experts recommended universal screening of employees, mainly in settings with extremely vulnerable patients and if regional incidence rates were high, at a frequency of twice per week. The dominant advice (recommended by at least 50% of experts) for employees exposed to SARS-CoV-2 was daily testing and wearing a mask, regardless of the length of exposure. CONCLUSIONS: Expert recommendations deviate from the legal requirements and appear to be more differentiated and proportional. The influence of specific experience and expertise on mask recommendations should be investigated in more detail. For relevant policy decisions, a quick, focused and broad-based consultation of expertise could be of added value.

Selection tools and student diversity in health professions education: a multi-site study.

Student diversity in health professions education (HPE) can be affected by selection procedures. Little is known about how different selection tools impact student diversity across programs using different combinations of traditional and broadened selection criteria. The present multi-site study examined the chances in selection of subgroups of applicants to HPE undergraduate programs with distinctive selection procedures, and their performance on corresponding selection tools. Probability of selection of subgroups (based on gender, migration background, prior education, parental education) of applicants (N = 1935) to five selection procedures of corresponding Dutch HPE undergraduate programs was estimated using multilevel logistic regression. Multilevel linear regression was used to analyze performance on four tools: prior-education grade point average (pe-GPA), biomedical knowledge test, curriculum-sampling test, and curriculum vitae (CV). First-generation Western immigrants and applicants with a foreign education background were significantly less likely to be selected than applicants without a migration background and with pre-university education. These effects did not vary across programs. More variability in effects was found between different selection tools. Compared to women, men performed significantly poorer on CVs, while they had higher scores on biomedical knowledge tests. Applicants with a non-Western migration background scored lower on curriculum-sampling tests. First-generation Western immigrants had lower CV-scores. First-generation university applicants had significantly lower pe-GPAs. There was a variety in effects for applicants with different alternative forms of prior education. For curriculum-sampling tests and CVs, effects varied across programs. Our findings highlight the need for continuous evaluation, identifying best practices within existing tools, and applying alternative tools.

How progress evaluations are used in postgraduate education with longitudinal supervisor-trainee relationships: a mixed method study.

The combination of measuring performance and giving feedback creates tension between formative and summative purposes of progress evaluations and can be challenging for supervisors. There are conflicting perspectives and evidence on the effects supervisor-trainee relationships have on assessing performance. The aim of this study was to learn how progress evaluations are used in postgraduate education with longitudinal supervisor-trainee relationships. Progress evaluations in a two-year community-pharmacy specialization program were studied with a mixed-method approach. An adapted version of the Canadian Medical Education Directives for Specialists (CanMEDS) framework was used. Validity of the performance evaluation scores of 342 trainees was analyzed using repeated measures ANOVA. Semi-structured interviews were held with fifteen supervisors to investigate their response processes, the utility of the progress evaluations, and the influence of supervisor-trainee relationships. Time and CanMEDS roles affected the three-monthly progress evaluation scores. Interviews revealed that supervisors varied in their response processes. They were more committed to stimulating development than to scoring actual performance. Progress evaluations were utilized to discuss and give feedback on trainee development and to add structure to the learning process. A positive supervisor-trainee relationship was seen as the foundation for feedback and supervisors preferred the roles of educator, mentor, and coach over the role of assessor. We found that progress evaluations are a good method for directing feedback in longitudinal supervisor-trainee relationships. The reliability of scoring performance was low. We recommend progress evaluations to be independent of formal assessments in order to minimize roles-conflicts of supervisors.

Selection Incentives in the Dutch Basic Health Insurance: To What Extent Does End-of-Life Spending Contribute to Predictable Profits and Losses for Selective Groups?

Existing risk-equalization models in individual health insurance markets with premium-rate restrictions do not completely compensate insurers for predictable profits/losses, confronting insurers with risk selection incentives. To guide further improvement of risk-equalization models, it is important to obtain insight into the drivers of remaining predictable profits/losses. This article studies a specific potential driver: end-of-life spending (defined here as spending in the last 1-5 years of life). Using administrative (N = 16.9 m) and health survey (N = 384 k) data from the Netherlands, we examine the extent to which end-of-life spending contributes to predictable profits/losses for selective groups. We do so by simulating the predictable profits/losses for these groups with and without end-of-life spending while correcting for the overall spending difference between these two situations. Our main finding is that-even under a sophisticated risk-equalization model-end-of-life spending can contribute to predictable losses for specific chronic conditions.

ScipionTomo: Towards cryo-electron tomography software integration, reproducibility, and validation.

Image processing in cryogenic electron tomography (cryoET) is currently at a similar state as Single Particle Analysis (SPA) in cryogenic electron microscopy (cryoEM) was a few years ago. Its data processing workflows are far from being well defined and the user experience is still not smooth. Moreover, file formats of different software packages and their associated metadata are not standardized, mainly since different packages are developed by different groups, focusing on different steps of the data processing pipeline. The Scipion framework, originally developed for SPA (de la Rosa-Trevín et al., 2016), has a generic python workflow engine that gives it the versatility to be extended to other fields, as demonstrated for model building (Martínez et al., 2020). In this article, we provide an extension of Scipion based on a set of tomography plugins (referred to as ScipionTomo hereafter), with a similar purpose: to allow users to be focused on the data processing and analysis instead of having to deal with multiple software installation issues and the inconvenience of switching from one to another, converting metadata files, managing possible incompatibilities, scripting (writing a simple program in a language that the computer must convert to machine language each time the program is run), etcetera. Additionally, having all the software available in an integrated platform allows comparing the results of different algorithms trying to solve the same problem. In this way, the commonalities and differences between estimated parameters shed light on which results can be more trusted than others. ScipionTomo is developed by a collaborative multidisciplinary team composed of Scipion team engineers, structural biologists, and in some cases, the developers whose software packages have been integrated. It is open to anyone in the field willing to contribute to this project. The result is a framework extension that combines the acquired knowledge of Scipion developers in close collaboration with third-party developers, and the on-demand design of functionalities requested by beta testers applying this solution to actual biological problems.

Association of physical activity and sedentary time with structural brain networks-The Maastricht Study.

We assessed whether objectively measured low- and high-intensity physical activity (LPA and HPA) and sedentary time (ST) were associated with white matter connectivity, both throughout the whole brain and in brain regions involved in motor function. In the large population-based Maastricht Study (n = 1715, age 59.6 ± 8.1 (mean ± standard deviation) years, and 48% women), the amounts of LPA, HPA, and ST were objectively measured during 7 days by an activPAL accelerometer. In addition, using 3T structural and diffusion MRI, we calculated whole brain node degree and node degree of the basal ganglia and primary motor cortex. Multivariable linear regression analysis was performed, and we report standardized regression coefficients (stß) adjusted for age, sex, education level, wake time, diabetes status, BMI, office systolic blood pressure, antihypertensive medication, total-cholesterol-to-HDL-cholesterol ratio, lipid-modifying medication, alcohol use, smoking status, and history of cardiovascular disease. Lower HPA was associated with lower whole brain node degree after full adjustment (stß [95%CI] = - 0.062 [- 0.101, - 0.013]; p = 0.014), whereas lower LPA (stß [95%CI] = - 0.013 [- 0.061, 0.034]; p = 0.580) and higher ST (stß [95%CI] = - 0.030 [- 0.081, 0.021]; p = 0.250) was not. In addition, lower HPA was associated with lower node degree of the basal ganglia after full adjustment (stß [95%CI] = - 0.070 [- 0.121, - 0.018]; p = 0.009). Objectively measured lower HPA, but not lower LPA and higher ST, was associated with lower whole brain node degree and node degree in specific brain regions highly specialized in motor function. Further research is needed to establish whether more HPA may preserve structural brain connectivity.

A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients.

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg-1 . This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg-1 ) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.

Cross-sectional associations of device-measured sedentary behaviour and physical activity with cardio-metabolic health in the 1970 British Cohort Study.

AIMS: This study aimed to examine the cross-sectional associations of thigh accelerometry-assessed sedentary behaviour and moderate-to-vigorous physical activity (MVPA) with cardio-metabolic health markers and prevalent diabetes in a population sample of middle-aged British adults. METHODS: Participants (n = 4892) from the age-46-to-48 wave of the 1970 British Cohort Study were fitted with a waterproofed activPAL3 micro device. Total/prolonged sedentary time, breaks and MVPA were the main exposures. We dichotomized prolonged sedentary time and MVPA based on the corresponding median, generating four combinations as categorical exposures. Outcomes comprised of diabetes and seven cardio-metabolic health markers. We used logistic regression and generalized linear models to examine independent/joint associations, conducting a minimally adjusted model including demographics and contextual covariates, and further adjusted for total sedentary time and/or MVPA as applicable. RESULTS: Each set of 10 sedentary breaks and 1 h of prolonged sedentary time were associated with HbA1c (mmol/mol) [B = -0.18 (-0.33, -0.03) and 2.35 (1.01, 3.69), respectively]. Each set of 10 sedentary breaks and 1 h of MVPA were favourably associated with diabetes [adjusted odds ratio (AOR): 0.80 (0.71, 0.99) and 0.42 (0.26, 0.67), respectively]. Joint analyses showed that only the low MVPA × long sedentary time combination had significantly higher odds for diabetes than the referent high MVPA × short sedentary time combination [AOR: 1.89 (1.17, 3.03)]. CONCLUSIONS: Each set of additional 10 sedentary breaks per day was associated with 20% lower odds for diabetes. A low physical activity level combined with long sedentary time might synergistically deteriorate cardio-metabolic health.

Burden of disease of type 2 diabetes mellitus: cost of illness and quality of life estimated using the Maastricht Study.

AIMS: To estimate the societal costs and quality of life of people with type 2 diabetes and to compare these results with those of people with normal glucose tolerance or prediabetes. METHODS: Data from 2915 individuals from the population-based Maastricht Study were included. Costs were assessed through a resource-use questionnaire completed by the participants; cost prices were based on Dutch costing guidelines. Quality of life was expressed in utilities using the Dutch EuroQol 5D-3L questionnaire and the SF-36 health survey. Based on normal fasting glucose and 2-h plasma glucose values, participants were classified into three groups: normal glucose tolerance (n = 1701); prediabetes (n = 446); or type 2 diabetes (n = 768). RESULTS: Participants with type 2 diabetes had on average 2.2 times higher societal costs than those with normal glucose tolerance (€3,006 and €1,377 per 6 months, respectively) and had lower utilities (0.77 and 0.81, respectively). No significant differences were found between participants with normal glucose tolerance and those with prediabetes. Subgroup analyses showed that higher age, being female and having two or more diabetes-related complications resulted in higher costs (P < 0.05) and lower utilities. CONCLUSIONS: This study showed that people with type 2 diabetes have substantially higher societal costs and lower quality of life than people with normal glucose tolerance. The results provide important input for future model-based economic evaluations and for policy decision-making.

Incorporating self-reported health measures in risk equalization through constrained regression.

Most health insurance markets with premium-rate restrictions include a risk equalization system to compensate insurers for predictable variation in spending. Recent research has shown, however, that even the most sophisticated risk equalization systems tend to undercompensate (overcompensate) groups of people with poor (good) self-reported health, confronting insurers with incentives for risk selection. Self-reported health measures are generally considered infeasible for use as an explicit 'risk adjuster' in risk equalization models. This study examines an alternative way to exploit this information, namely through 'constrained regression' (CR). To do so, we use administrative data (N = 17 m) and health survey information (N = 380 k) from the Netherlands. We estimate five CR models and compare these models with the actual Dutch risk equalization model of 2016 which was estimated by ordinary least squares (OLS). In the CR models, the estimated coefficients are restricted, such that the under-/overcompensation for groups based on self-reported general health is reduced by 20, 40, 60, 80, or 100%. Our results show that CR can improve outcomes for groups that are not explicitly flagged by risk adjuster variables, but worsens outcomes for groups that are explicitly flagged by risk adjuster variables. Using a new standardized metric that summarizes under-/overcompensation for both types of groups, we find that the lighter constraints can lead to better outcomes than OLS.

The role of fibrinogen and fibrinogen concentrate in cardiac surgery: an international consensus statement from the Haemostasis and Transfusion Scientific Subcommittee of the European Association of Cardiothoracic Anaesthesiology.

To date, data regarding the efficacy and safety of administering fibrinogen concentrate in cardiac surgery are limited. Studies are limited by their low sample size and large heterogeneity with regard to the patient population, by the timing of fibrinogen concentrate administration, and by the definition of transfusion trigger and target levels. Assessment of fibrinogen activity using viscoelastic point-of-care testing shortly before or after weaning from cardiopulmonary bypass in patients and procedures with a high risk of bleeding appears to be a rational strategy. In contrast, the use of Clauss fibrinogen test for determination of plasma fibrinogen level can no longer be recommended without restrictions due to its long turnaround time, high inter-assay variability and interference with high heparin levels and fibrin degradation products. Administration of fibrinogen concentrate for maintaining physiological fibrinogen activity in the case of microvascular post-cardiopulmonary bypass bleeding appears to be indicated. The available evidence does not suggest aiming for supranormal levels, however. Use of cryoprecipitate as an alternative to fibrinogen concentrate might be considered to increase plasma fibrinogen levels. Although conclusive evidence is lacking, fibrinogen concentrate does not seem to increase adverse outcomes (i.e., thromboembolic events). Large prospective multi-centre studies are needed to better define the optimal perioperative monitoring tool, transfusion trigger and target levels for fibrinogen replacement in cardiac surgery.

Hybrid ADFT Study of the C104 and C106 IPR Isomers.

This work presents a hybrid auxiliary density functional theory (ADFT) study of the neutral and hexaanionic C104 and C106 fullerenes with the aim to determine their ground state structures. To this end, all C104 and C106 fullerene structures that obey the isolated pentagon rule (IPR) were optimized with the Perdew-Burke-Ernzerhof generalized gradient approximation followed by a single-point energy calculation with the PBE0 hybrid functional. Our studies show that this composite approach yields relative energies of giant fullerenes that are accurate to around 1 kcal/mol. As a result, the ground states of C104, C1046-, and C1066- can be assigned to the isomers 234:Cs, 821:D2, and 891:Cs, respectively. On the other hand, the energetically lowest lying IPR isomers of C106, 331:Cs, 1194:C2, 534:C1 are separated by less than 1 kcal/mol which makes an unequivocal ground state assignment by hybrid DFT methods impossible. To guide future experiments, we also report the simulated IR and Raman spectra of the most stable neutral and hexaanionic C104 and C106 fullerenes.

The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.

In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. INTRODUCTION: To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally-in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. METHODS: Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. RESULTS: After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (- 4%) in prediabetes and smaller cross-sectional area of the tibia (- 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (- 5%), cortical thickness (- 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (- 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. CONCLUSIONS: In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.