Regionalization and morphological integration in the vertebral column of Eurasian small-bodied newts (Salamandridae: Lissotriton).

Serially homologous structures may have complex patterns of regionalization and morphological integration, influenced by developmental Hox gene expression and functional constraints. The vertebral column, consisting of a number of repeated, developmentally constrained, and highly integrated units-vertebrae-is such a complex serially homologous structure. Functional diversification increases regionalization and modularity of the vertebral column, particularly in mammals. For salamanders, three concepts of regionalization of the vertebral column have been proposed, recognizing one, two, or three presacral regions. Using three-dimensional geometric morphometrics on vertebra models acquired with microcomputerized tomography scanning, we explored the covariation of vertebrae in four closely related taxa of small-bodied newts in the genus Lissotriton. The data were analyzed by segmented linear regression to explore patterns of vertebral regionalization and by a two-block partial least squares method to test for morphological integration. All taxa show a morphological shift posterior to the fifth trunk vertebra, which corresponds to the two-region concept. However, morphological integration is found to be strongest in the mid-trunk. Taken jointly, these results indicate a highly integrated presacral vertebral column with a subtle two-region differentiation. The results are discussed in relation to specific functional requirements, developmental and phylogenetic constraints, and specific requirements posed by a biphasic life cycle and different locomotor modes (swimming vs. walking). Further research should be conducted on different ontogenetic stages and closely related but ecologically differentiated species.

Variation in vertebrae shape across small-bodied newts reveals functional and developmental constraints acting upon the trunk region.

The salamander vertebral column is largely undifferentiated with a series of more or less uniform rib-bearing presacral vertebrae traditionally designated as the trunk region. We explored regionalization of the salamander trunk in seven species and two subspecies of the salamander genus Lissotriton by the combination of microcomputed tomography scanning and geometric morphometrics. The detailed information on trunk vertebral shape was subjected to a multidimensional cluster analysis and a phenotypic trajectory analysis. With these complementary approaches, we observed a clear morphological regionalization. Clustering analysis showed that the anterior trunk vertebrae (T1 and T2) have distinct morphologies that are shared by all taxa, whereas the subsequent, more posterior vertebrae show significant disparity between species. The phenotypic trajectory analysis revealed that all taxa share a common pattern and amount of shape change along the trunk region. Altogether, our results support the hypothesis of a conserved anterior-posterior developmental patterning which can be associated with different functional demands, reflecting (sub)species' and, possibly, regional ecological divergences within species.

Is seniority of emergency physician associated with the weekend mortality effect? An exploratory analysis of electronic health records in the UK.

OBJECTIVE: Admission to hospital over a weekend is associated with increased mortality, but the underlying causes of the weekend effect are poorly understood. We explore to what extent differences in emergency department (ED) admission and discharge processes, severity of illness and the seniority of the treating physician explain the weekend effect. METHODS: We analysed linked ED attendances to hospital admissions to Cambridge University Hospital over a 7-year period from 1 January 2007 to 31 December 2013, with 30-day in-hospital death as the primary outcome and discharge as a competing risk. The primary exposure was day of the week of arrival. Subdistribution hazards models controlled for multiple confounders, including physician seniority, calendar year, mode of arrival, triage category, referral from general practice, sex, arrival time, prior attendances and admissions, diagnosis group and age. RESULTS: 229 401 patients made 424 845 ED attendances, of which 158 396 (37.3%) were admitted to the hospital. The case-mix of admitted patients was more ill at weekends: 2530 (6.4%) admitted at a weekend required immediate resuscitation compared with 6450 (5.4%) admitted on a weekday (p<0.0001). Senior doctors admitted 24.8% of patients on weekdays and 24.0% at weekends, but junior doctors admitted 61.7% of patients on weekdays and 44.2% at weekends. 3947 (3.3%) patients admitted on a weekday and 1454 (3.7%) patients admitted at a weekend died within 30 days. In the adjusted subdistribution hazards model, the HR of in-hospital death was 1.11 (95% CI 1.04 to 1.18) for weekend arrivals. After controlling for confounders, the in-hospital mortality of patients admitted by junior doctors was greater at the weekend (adjusted HR (aHR) 1.15, 95% CI 1.06 to 1.24). In-hospital mortality for patients admitted by senior doctors was not statistically different at the weekend (aHR 1.08, 95% CI 0.98 to 1.19). CONCLUSIONS: Our findings suggest that the weekend effect was driven by a higher proportion of admitted patients requiring immediate resuscitation at the weekend. Junior doctors admitted a lower proportion of relatively healthy patients at the weekend compared with the weekday, thus diluting the risk pool of weekday admissions and contributing to the weekend effect. Senior doctors' admitting behaviour did not change at the weekend, and the corresponding weekend effect was reduced.

Medial compartment knee osteoarthritis: age-stratified cost-effectiveness of total knee arthroplasty, unicompartmental knee arthroplasty, and high tibial osteotomy.

PURPOSE: To compare the age-based cost-effectiveness of total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), and high tibial osteotomy (HTO) for the treatment of medial compartment knee osteoarthritis (MCOA). METHODS: A Markov model was used to simulate theoretical cohorts of patients 40, 50, 60, and 70 years of age undergoing primary TKA, UKA, or HTO. Costs and outcomes associated with initial and subsequent interventions were estimated by following these virtual cohorts over a 10-year period. Revision and mortality rates, costs, and functional outcome data were estimated from a systematic review of the literature. Probabilistic analysis was conducted to accommodate these parameters' inherent uncertainty, and both discrete and probabilistic sensitivity analyses were utilized to assess the robustness of the model's outputs to changes in key variables. RESULTS: HTO was most likely to be cost-effective in cohorts under 60, and UKA most likely in those 60 and over. Probabilistic results did not indicate one intervention to be significantly more cost-effective than another. The model was exquisitely sensitive to changes in utility (functional outcome), somewhat sensitive to changes in cost, and least sensitive to changes in 10-year revision risk. CONCLUSIONS: HTO may be the most cost-effective option when treating MCOA in younger patients, while UKA may be preferred in older patients. Functional utility is the primary driver of the cost-effectiveness of these interventions. For the clinician, this study supports HTO as a competitive treatment option in young patient populations. It also validates each one of the three interventions considered as potentially optimal, depending heavily on patient preferences and functional utility derived over time.

How artificial intelligence and machine learning can help healthcare systems respond to COVID-19.

The COVID-19 global pandemic is a threat not only to the health of millions of individuals, but also to the stability of infrastructure and economies around the world. The disease will inevitably place an overwhelming burden on healthcare systems that cannot be effectively dealt with by existing facilities or responses based on conventional approaches. We believe that a rigorous clinical and societal response can only be mounted by using intelligence derived from a variety of data sources to better utilize scarce healthcare resources, provide personalized patient management plans, inform policy, and expedite clinical trials. In this paper, we introduce five of the most important challenges in responding to COVID-19 and show how each of them can be addressed by recent developments in machine learning (ML) and artificial intelligence (AI). We argue that the integration of these techniques into local, national, and international healthcare systems will save lives, and propose specific methods by which implementation can happen swiftly and efficiently. We offer to extend these resources and knowledge to assist policymakers seeking to implement these techniques.

Incorporating efficiency in hospital-capacity planning in Germany.

Hospital occupancy is a key metric in hospital-capacity planning in Germany, even though this metric neglects important drivers of economic efficiency, for example treatment costs and case mix. We suggest an alternative metric, which incorporates economic efficiency explicitly, and illustrate how this metric can be used in the hospital-capacity planning cycle. The practical setting of this study is the hospital capacity planning process in the German federal state of Rheinland-Pfalz. The planning process involves all 92 acute-care hospitals of this federal state. The study is based on standard hospital data, including annual costs, number of cases--disaggregated by medical departments and ICD codes, respectively--length-of-stay, certified beds, and occupancy rates. Using the developed metric, we identified 18 of the 92 hospitals as inefficient and targets for over-proportional capacity cuts. On the upside, we identified 15 efficient hospitals. The developed model and analysis has affected the federal state's most recent medium term planning cycle.

Physicians in leadership: the association between medical director involvement and staff-to-patient ratios.

In a hospital environment that demands a careful balance between commercial and clinical interests, the extent to which physicians are involved in hospital leadership varies greatly. This paper assesses the influence of the extent of this involvement on staff-to-patient ratios. Using data gathered from 604 hospitals across Germany, this study evidences the positive relationship between a full-time medical director (MD) or heavily involved part-time MD and a higher staff-to-patient ratio. The data allows us to control for a range of confounding variables, such as size, rural/urban location, ownership structure, and case-mix. The results contribute to the sparse body of empirical research on the effect of clinical leadership on organizational outcomes.

Screening of healthcare workers for tuberculosis: development and validation of a new health economic model to inform practice.

BACKGROUND: Methods for determining cost-effectiveness of different treatments are well established, unlike appraisal of non-drug interventions, including novel diagnostics and biomarkers. OBJECTIVE: The authors develop and validate a new health economic model by comparing cost-effectiveness of tuberculin skin test (TST); blood test, interferon-gamma release assay (IGRA) and TST followed by IGRA in conditional sequence, in screening healthcare workers for latent or active tuberculosis (TB). DESIGN: The authors focus on healthy life years gained as the benefit metric, rather than quality-adjusted life years given limited data to estimate quality adjustments of life years with TB and complications of treatment, like hepatitis. Healthy life years gained refer to the number of TB or hepatitis cases avoided and the increase in life expectancy. The authors incorporate disease and test parameters informed by systematic meta-analyses and clinical practice. Health and economic outcomes of each strategy are modelled as a decision tree in Markov chains, representing different health states informed by epidemiology. Cost and effectiveness values are generated as the individual is cycled through 20 years of the model. Key parameters undergo one-way and Monte Carlo probabilistic sensitivity analyses. SETTING: Screening healthcare workers in secondary and tertiary care. RESULTS: IGRA is the most effective strategy, with incremental costs per healthy life year gained of £10 614-£20 929, base case, £8021-£18 348, market costs TST £45, IGRA £90, IGRA specificities of 99%-97%; mean (5%, 95%), £12 060 (£4137-£38 418) by Monte Carlo analysis. CONCLUSIONS: Incremental costs per healthy life year gained, a conservative estimate of benefit, are comparable to the £20 000-£30 000 NICE band for IGRA alone, across wide differences in disease and test parameters. Health gains justify IGRA costs, even if IGRA tests cost three times TST. This health economic model offers a powerful tool for appraising non-drug interventions in the market and under development.