An index of cancer survival to measure progress in cancer control: A tutorial.

BACKGROUND: Cancer survival is a key component to assess the overall effectiveness of healthcare systems in their cancer management efforts. A key supporting tool for planning and decision making was introduced with the development of an index of cancer survival that summarises survival for all adults and cancer types into one single estimate, but the implementation details have not been previously described. METHODS: We detail the construction of the index, including the structure, the calculation of 'sex-age-cancer' specific weights and our proposed modelling strategy to estimate net survival. We provide some practical recommendations through an illustration using a synthetic dataset ('Replica') that we generated for this purpose. An example of R code usage to estimate the index using our approach is provided. RESULTS: The 'Replica' contains 500 000 artificial cancer records that mimic a cohort of adult cancer patients diagnosed with cancer in England between 1980 and 2004. Using this dataset, we estimated an index of cancer survival at one, five, and ten years after diagnosis for five selected periods of diagnosis, and provide an example of interpretation of these results. DISCUSSION: We propose a flexible penalised regression modelling strategy to estimate the index's 'sex-age-cancer' specific cancer survival components that minimises the estimation challenge of these components. This tutorial will support researchers in constructing an index of cancer survival for their own setting, facilitating the enrichment of existing toolkits of cancer indicators to more effectively measure progress against cancer in their respective regions/countries.

Increased tolerance to low K+, and to cationic stress of Arabidopsis plants by expressing the F130S mutant version of the K+ transporter AtHAK5.

Potassium (K+) selectivity of high-affinity K+ uptake systems is crucial for plant growth under low K+ and in the presence of inhibitors of K+ uptake that are toxic to plants such as Na+ or Cs+. Here, we express a mutated version of the Arabidopsis AtHAK5 high-affinity K+ transporter consisting on a change of phenylalanine 130 to serine (F130S) in athak5 akt1 double mutant plants. F130S-expressing plants show better growth, increased K+ uptake from low external concentrations and higher K+ contents when grown at low K+ (10 µM) and when grown at low K+ in the presence of Na+ (15 mM) or Cs+ (1 µM). In addition, these plants accumulate less Na+ and Cs+, resulting in lower Na+/K+ and Cs+/K+ ratios, which are important determinants of plant tolerance to salt stress and to Cs+-polluted soils. Structure analysis of AtHAK5 suggest that the F130 residue approaches the intracellular gate of the K+ tunnel of AtHAK5, affecting somehow its ionic selectivity. Modification of transport systems has a large potential to face challenges of future agriculture such as sustainable production under abiotic stress conditions imposed by climate change.

What can hospital emergency admissions prior to cancer diagnosis tell us about socio-economic inequalities in cancer diagnosis? Evidence from population-based data in England.

BACKGROUND: More deprived cancer patients are at higher risk of Emergency Presentation (EP) with most studies pointing to lower symptom awareness and increased comorbidities to explain those patterns. With the example of colon cancer, we examine patterns of hospital emergency admissions (HEAs) history in the most and least deprived patients as a potential precursor of EP. METHODS: We analysed the rates of hospital admissions and their admission codes (retrieved from Hospital Episode Statistics) in the two years preceding cancer diagnosis by sex, deprivation and route to diagnosis (EP, non-EP). To select the conditions (grouped admission codes) that best predict emergency admission, we adapted the purposeful variable selection to mixed-effects logistic regression. RESULTS: Colon cancer patients diagnosed through EP had the highest number of HEAs than all the other routes to diagnosis, especially in the last 7 months before diagnosis. Most deprived patients had an overall higher rate and higher probability of HEA but fewer conditions associated with it. CONCLUSIONS: Our findings point to higher use of emergency services for non-specific symptoms and conditions in the most deprived patients, preceding colon cancer diagnosis. Health system barriers may be a shared factor of socio-economic inequalities in EP and HEAs.

The impact of anatomic alignment on radiocapitellar pressure following radial head arthroplasty.

BACKGROUND: The incidence of radial head fractures is increasing, and radial head arthroplasty (RHA) is being more frequently used as treatment for irreparable fractures. Our objective was to compare radiocapitellar pressure between the native joint and 2 radial head prosthesis conditions: (1) a prosthetic head that was aligned to the forearm axis of rotation and (2) the same prosthesis with an axisymmetric nonaligned head. METHODS: Ten cadaveric specimens received a pressfit radial head prosthesis (Align; Skeletal Dynamics) for both prosthetic testing conditions. Anatomic alignment (AL) was defined as the prosthetic head aligned to the forearm axis of rotation. Axisymmetric alignment (AX) was defined as the prosthetic radial head aligned to the axis of the prosthetic stem. Axial load was applied with the elbow in extension and the forearm pronated. Data were collected using a Tekscan 4000 sensor. RESULTS: The mean pressure in the AL and AX groups were significantly higher than the mean pressure in the native joint. Compared with the native joint, the mean pressure was 19% higher in the AL group and 56% higher in the AX group. Peak pressure beyond 5 MPa occurred in 0 specimens in the native joint group, in 1 specimen (10%) in the AL group, and in 5 specimens (50%) in the AX group. DISCUSSION: Our results demonstrated that a pressfit radial head prosthesis aligned with the forearm axis of rotation yields capitellar pressures that were more similar to the native condition than a nonaligned pressfit prosthesis. These findings suggest that anatomic alignment may optimize capitellar wear properties, improving the long-term durability of radial head arthroplasty.

Extended excess hazard models for spatially dependent survival data.

Relative survival represents the preferred framework for the analysis of population cancer survival data. The aim is to model the survival probability associated with cancer in the absence of information about the cause of death. Recent data linkage developments have allowed for incorporating the place of residence into the population cancer databases; however, modeling this spatial information has received little attention in the relative survival setting. We propose a flexible parametric class of spatial excess hazard models (along with inference tools), named "Relative Survival Spatial General Hazard," that allows for the inclusion of fixed and spatial effects in both time-level and hazard-level components. We illustrate the performance of the proposed model using an extensive simulation study, and provide guidelines about the interplay of sample size, censoring, and model misspecification. We present a case study using real data from colon cancer patients in England. This case study illustrates how a spatial model can be used to identify geographical areas with low cancer survival, as well as how to summarize such a model through marginal survival quantities and spatial effects.

Relevance of the SlCIPK23 kinase in Na+ uptake and root morphology in K+-starved tomato plants.

The beneficial effects of Na+ as a substitute for K+ have been well-documented at the physiological level. However, the transport systems and regulatory mechanisms that allow Na+ acquisition under K+ deficiency remain poorly understood in the majority of land plants. In tomato, SlCIPK23 kinase was involved in Na+ accumulation in K+-starved plants, in addition to activating the LKT1 K+ channel and the K+ transporter SlHAK5. We used the central role of SlCIPK23 in K+ and Na+ acquisition to study which molecular entities mediate Na+ uptake with knockout tomato mutants and expression in heterologous systems. Two main pathways for Na+ uptake were deduced in tomato plants: an NH4+-sensitive pathway dependent on SlCIPK23, and a second one sensitive to Ba2+, Ca2+, La3+, and Li+. The addition of Na+ (10 mM) to lkt1, slhak5, or slcipk23 mutant KO lines produced interesting changes in root morphology. In particular, the roots of slcipk23 plants were longer and lighter than those of the WT under K+-deficient conditions and this effect was reversed by the addition of 10 mM Na+. These results provide a stimulating perspective for the study of the beneficial effects of Na+ in crops.

Acute-on-Chronic Liver Failure Triggered by Cutaneous Loxoscelism.

Acute-on-chronic liver failure is a syndrome associated with a high short-term mortality rate. Severe systemic inflammation and single- and multiple-organ failure are a hallmark of this syndrome, with pro-inflammatory precipitating events occurring in the liver or extrahepatic regions. We report a case of a 69-year-old man with a previous diagnosis of alcohol-induced liver cirrhosis who presented with a poorly defined, erythematous-purplish, and edematous plaque with multiple hemorrhagic blisters over the left leg, one day after receiving a spider bite. During the following hours, the skin lesion progressed, and the patient developed hepatic encephalopathy, respiratory failure, and arterial hypotension, requiring the administration of vasopressors; blood analysis revealed hypercreatininemia, an elevated international normalized ratio (INR) value, and hyperbilirubinemia. The patient was diagnosed with acute-on-chronic liver failure caused by cutaneous loxoscelism. There was no hemolytic anemia, rhabdomyolysis, or disseminated intravascular coagulation in the patient, thus excluding the possibility of visceral loxoscelism.

Multiobjective optimization framework for designing a steering system considering structural features and full vehicle dynamics.

Vehicle handling and stability performance and ride comfort is normally assessed through standard field test procedures, which are time consuming and expensive. However, the rapid development of digital technologies in the automotive industry have enabled to properly model and simulate the full-vehicle dynamics, thus drastically reducing design and manufacturing times and costs while enhancing the performance, safety, and longevity of vehicle systems. This paper focus on a computationally efficient multi-objective optimization framework for developing an optimal design of a vehicle steering system, which is carried out by coupling certain computer-aided design tools (CAD) and computer-aided engineering (CAE) software. The 3D CAD model of the steering system is made using SolidWorks, the Finite Element Analysis (FEA) is modelled using Ansys Workbench, while the multibody kinematic and dynamic is analysed using Adams/Car. They are embedded in a multidisciplinary optimization design framework (modeFrontier) with the aim of determining the optimal hardpoint locations of the suspension and steering systems. This is achieved by minimizing the Ackermann error and toe angle deviations, together with the volume, mass, and maximum stresses of the rack-and-pinion steering mechanism. This enhances the vehicle stability, safety, manoeuvrability, and passengers' comfort, extends the vehicle systems reliability and fatigue life, while reducing the tire wear. The method has been successfully applied to different driving scenarios and vehicle maneuvers to find the optimal Pareto front and analyse the performance and behaviour of the steering system. Results show that the design of the steering system can be significantly improved using this approach.

Fractures of the phalanges.

Fractures of the phalanges encompass a wide range of injury patterns with variable articular and soft tissue involvement. The goals of treatment whether conservative or surgical are the restoration of function while limiting the risk of complications. An armamentarium of fixation options allows the surgeon to appropriately treat these fractures with the intention of initiating early postoperative mobilization. Previous publications report variable rates of complications following internal fixation of phalangeal fractures which represents an unsolved problem. It is incumbent on the surgeon to utilize meticulous surgical technique, achieve anatomic reduction with stable fixation and initiate early postoperative mobilization where indicated. In the following text, we review the management of most types of phalangeal fractures, except fracture-dislocations of the proximal interphalangeal joint. These injuries comprise a wide spectrum of presentation; thus, an understanding of anatomical and mechanical principles is integral to achieving a successful outcome.

A Medial Approach That Provides Ample Exposure of the Coronoid for Fracture Management.

We describe a medial approach to the coronoid where the flexor-pronator mass is released from its humeral origin by creating a proximally based tendinous flap. This technique facilitates access to the coronoid, preservation of the medial collateral ligament origin, and repair of the flexor-pronator mass. This approach has utility for all coronoid fracture variations but especially the O'Driscoll anteromedial subtype 3, which includes fractures of the sublime tubercle, the anteromedial facet, and the coronoid tip.

On near-redundancy and identifiability of parametric hazard regression models under censoring.

We study parametric inference on a rich class of hazard regression models in the presence of right-censoring. Previous literature has reported some inferential challenges, such as multimodal or flat likelihood surfaces, in this class of models for some particular data sets. We formalize the study of these inferential problems by linking them to the concepts of near-redundancy and practical nonidentifiability of parameters. We show that the maximum likelihood estimators of the parameters in this class of models are consistent and asymptotically normal. Thus, the inferential problems in this class of models are related to the finite-sample scenario, where it is difficult to distinguish between the fitted model and a nested nonidentifiable (i.e., parameter-redundant) model. We propose a method for detecting near-redundancy, based on distances between probability distributions. We also employ methods used in other areas for detecting practical nonidentifiability and near-redundancy, including the inspection of the profile likelihood function and the Hessian method. For cases where inferential problems are detected, we discuss alternatives such as using model selection tools to identify simpler models that do not exhibit these inferential problems, increasing the sample size, or extending the follow-up time. We illustrate the performance of the proposed methods through a simulation study. Our simulation study reveals a link between the presence of near-redundancy and practical nonidentifiability. Two illustrative applications using real data, with and without inferential problems, are presented.

Functional forms of socio-territorial inequities in breast cancer screening - A French cross-sectional study using hierarchical generalised additive models.

To reduce the breast cancer burden, the French National Organised Breast Cancer Screening Programme (FNOBCSP) was implemented in 2004. The recommended participation rate has never been achieved and socio-territorial inequities in participation have been reported on several occasions. We investigated the functional forms and consistency of the relationships between neighbourhood deprivation, travel time to the nearest accredited radiology centre and screening uptake. We used two-level hierarchical generalised additive models in 8 types of territories classified by socio-demographic and economic factors. The first level was 368,201 women aged 50-72 invited to the 2013-2014 screening campaign in metropolitan France. They were nested in 41 départements, the level of organisation of the FNOBCSP. The effect of travel time showed two main patterns: it was either linear (with participation decreasing as travel time increased) or participation first increased with increasing travel time to a peak around 5-15 min and decreased afterward. In nearly all types and départements, the probability of participation decreased linearly with increasing deprivation. Territorial inequities in participation were more context-dependent and complex than social inequities. Inequities in participation represent a loss of opportunity for individuals who already have the worst cancer outcomes. Evidence-based public health policies are needed to increase the effectiveness and equity of breast cancer screening.

Potential uses of cytisine for smoking cessation in menopausal women - literature summary.

Introduction: Menopause is a vital stage in which the risk of the appearance of metabolic syndrome and cardiovascular diseases is increased. Cardiovascular risk in menopausal women must be monitored because it is one of the most common causes of mortality in these women. Smoking is an important risk factor for the development of many diseases, including cardiovascular diseases, so promoting smoking cessation in these women is important for the maintenance of cardiovascular health. Material and methods: Current smoking cessation programs mainly include nicotine and varenicline as therapeutic agents, due to their history of success, safety, and efficacy in aiding in cessation, but they do not include "new" agents such as cytisine as coadjuvant in the elimination of the habit of smoking. Results: Cytisine is a therapeutic agent traditionally used in Eastern Europe, which has demonstrated efficacy and safety in smoking cessation, also showing other new pharmacological actions. It has been widely used since World War II as a nicotine substitute. Conclusions: These pharmacological actions, together with their efficacy in smoking cessation, should be explored to evaluate the convenience of the use of cytisine in premenopausal and postmenopausal women, so that cytisine can be identified as a useful therapeutic tool in smoking cessation programs and in particular in menopausal women.

Inhibition of SlSKOR by SlCIPK23-SlCBL1/9 uncovers CIPK-CBL-target network rewiring in land plants.

Transport of K+ to the xylem is a key process in the mineral nutrition of the shoots. Although CIPK-CBL complexes have been widely shown to regulate K+ uptake transport systems, no information is available about the xylem ones. Here, we studied the physiological roles of the voltage-gated K+ channel SlSKOR and its regulation by the SlCIPK23-SlCBL1/9 complexes in tomato plants. We phenotyped gene-edited slskor and slcipk23 tomato knockout mutants and carried out two-electrode voltage-clamp (TEVC) and BiFC assays in Xenopus oocytes as key approaches. SlSKOR was preferentially expressed in the root stele and was important not only for K+ transport to shoots but also, indirectly, for that of Ca2+ , Mg2+ , Na+ , NO3 - , and Cl- . Surprisingly, the SlCIPK23-SlCBL1/9 complexes turned out to be negative regulators of SlSKOR. Inhibition of SlSKOR by SlCIPK23-SlCBL1/9 was observed in Xenopus oocytes and tomato plants. Regulation of SKOR-like channels by CIPK23-CBL1 complexes was also present in Medicago, grapevine, and lettuce but not in Arabidopsis and saltwater cress. Our results provide a molecular framework for coordinating root K+ uptake and its translocation to the shoot by SlCIPK23-SlCBL1/9 in tomato plants. Moreover, they evidenced that CIPK-CBL-target networks have evolved differently in land plants.

[Analysis of the legal framework on food supplements for menopause in Spanish community pharmacies]. / Análisis del marco legal sobre complementos alimenticios para la menopausia en farmacias comunitarias españolas.

OBJECTIVE: To analyze the legal framework for the marketing of specific food supplements prescribed and indicated for menopause symptoms, so that it is verified if according to the effects on health that they produce, should be considered in the category of food supplements, or in others included in our legal system. METHOD: An exhaustive review of the legal frameworks applicable to food supplements used both in Spain and in Europe, collecting those aspects that are related to legal concepts such as the definition of medicine for human use, medicine based on medicinal plants, or the so-called "frontier products". RESULTS: There is a large number of products that can be called "frontier products", they can fit into different product categories, they can fit into different product categories, since some of the plants in their formulation are also authorized for use as industrial medicines or medicines based on traditional medicinal plants. CONCLUSIONS: There are currently specific food supplements for menopause that raise reasonable doubts about their inclusion in other legal categories, both as medicines for human use, or as herbal medicines, so the legislator would need to enable more agile mechanisms and more frequent reviews of the new certainties that science finds, and that can change the status of these products.

Flexor Carpi Radialis Tendon Insertion Onto the Trapezial Ridge: An Anatomic Description.

Purpose: The flexor carpi radialis (FCR) tendon is often involved in surgical procedures of the hand and wrist. The FCR tendon may be mobilized from the trapezium during distal radius fracture fixation, for tendon transfer, and during carpometacarpal joint procedures. There is a paucity of literature describing the anatomy of the FCR insertion onto the trapezial ridge. We analyzed the insertional characteristics of the FCR onto the trapezium. Methods: Forty-two fresh-frozen cadaveric wrists were dissected using the extended FCR approach through the FCR tendon sheath. The length of the fibrous portion of the FCR insertion onto the trapezial ridge was measured from proximal to distal using a digital caliper. Results: FCR insertion onto the trapezium was present in all specimens. The mean length of the FCR insertion was 11.8 ± 4.14 mm. The character of the tissue quality varied across specimens. Conclusions: These results demonstrate the commonality of the FCR fibers that insert onto the trapezium. The length and tissue quality of this insertion varied across specimens. Clinical relevance: Understanding the complex anatomy of the hand and wrist facilitates surgical planning and intraoperative techniques. The FCR tendon insertion onto the trapezium is an important component of exposure for the volar approach to the distal radius and surgical management of thumb carpometacarpal joint arthritis.

Correction: Bullous Pilomatrixoma After COVID-19 Vaccination.

[This corrects the article DOI: 10.7759/cureus.32370.].

Individual frailty excess hazard models in cancer epidemiology.

Unobserved individual heterogeneity is a common challenge in population cancer survival studies. This heterogeneity is usually associated with the combination of model misspecification and the failure to record truly relevant variables. We investigate the effects of unobserved individual heterogeneity in the context of excess hazard models, one of the main tools in cancer epidemiology. We propose an individual excess hazard frailty model to account for individual heterogeneity. This represents an extension of frailty modeling to the relative survival framework. In order to facilitate the inference on the parameters of the proposed model, we select frailty distributions which produce closed-form expressions of the marginal hazard and survival functions. The resulting model allows for an intuitive interpretation, in which the frailties induce a selection of the healthier individuals among survivors. We model the excess hazard using a flexible parametric model with a general hazard structure which facilitates the inclusion of time-dependent effects. We illustrate the performance of the proposed methodology through a simulation study. We present a real-data example using data from lung cancer patients diagnosed in England, and discuss the impact of not accounting for unobserved heterogeneity on the estimation of net survival. The methodology is implemented in the R package IFNS.

Avoiding articular breakthrough in screw fixation of radial head fractures.

Background: The radial head is anatomically complex, making fracture fixation challenging because of the difficult visualization of the articular surface. As a result, screw penetration into the radiocapitellar joint can often occur. To facilitate safe placement of screws tangential to the joint surface, we define an approximate and reliable distance from the articular rim of the radial head that can minimize the risk of articular breach. Methods: A Kirschner wire for cannulated drilling was placed tangential to the articular surface in 15 cadaveric proximal radii. The distance from the wire to the articular rim was measured 3 times. After insertion of a 3.5-mm compression screw, the radial head was divided in the coronal plane, bisecting the screw track, to visualize the cross section of the screw's position. Headless compression screws of 3.5 mm were placed the distance from the most proximal edge of the screw track to the radial head's articular surface was measured 3 times. Results: The average distance from the articular rim to the distal surface of the Kirschner wire was 5.1 mm. The average distance from the articular rim to the proximal edge of the cavity was 1.7 mm. The screw placement was subchondral and extra-articular in all cases. Conclusion: When fixing Mason type 2 articular radial head fractures with 3.5-mm headless compression screws placed tangential to the articular surface, maintaining a screw entry point about 5 mm distal to the articular surface of the radial head will minimize the possibility of articular screw breach. This position also places the screw into subchondral bone, providing the best bone quality for mechanical support.

MEGH: A parametric class of general hazard models for clustered survival data.

In many applications of survival data analysis, the individuals are treated in different medical centres or belong to different clusters defined by geographical or administrative regions. The analysis of such data requires accounting for between-cluster variability. Ignoring such variability would impose unrealistic assumptions in the analysis and could affect the inference on the statistical models. We develop a novel parametric mixed-effects general hazard (MEGH) model that is particularly suitable for the analysis of clustered survival data. The proposed structure generalises the mixed-effects proportional hazards and mixed-effects accelerated failure time structures, among other structures, which are obtained as special cases of the MEGH structure. We develop a likelihood-based algorithm for parameter estimation in general subclasses of the MEGH model, which is implemented in our R package MEGH. We propose diagnostic tools for assessing the random effects and their distributional assumption in the proposed MEGH model. We investigate the performance of the MEGH model using theoretical and simulation studies, as well as a real data application on leukaemia.