Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

An international assessment of surgeon practices in abdominal wound closure and surgical site infection prevention by the European Society for Coloproctology.

AIM: The burden of abdominal wound failure can be profound. Recent clinical guidelines have highlighted the heterogeneity of laparotomy closure techniques. The aim of this study was to investigate current midline closure techniques and practices for prevention of surgical site infection (SSI). METHOD: An online survey was distributed in 2021 among the membership of the European Society of Coloproctology and its partner societies. Surgeons were asked to provide information on how they would close the abdominal wall in three specific clinical scenarios and on SSI prevention practices. RESULTS: A total of 561 consultants and trainee surgeons participated in the survey, mainly from Europe (n = 375, 66.8%). Of these, 60.6% identified themselves as colorectal surgeons and 39.4% as general surgeons. The majority used polydioxanone for fascial closure, with small bite techniques predominating in clean-contaminated cases (74.5%, n = 418). No significant differences were found between consultants and trainee surgeons. For SSI prevention, more surgeons preferred the use of mechanical bowel preparation (MBP) alone over MBP and oral antibiotics combined. Most surgeons preferred 2% alcoholic chlorhexidine (68.4%) or aqueous povidone-iodine (61.1%) for skin preparation. The majority did not use triclosan-coated sutures (73.3%) or preoperative warming of the wound site (78.5%), irrespective of level of training or European/non-European practice. CONCLUSION: Abdominal wound closure technique and SSI prevention strategies vary widely between surgeons. There is little evidence of a risk-stratified approach to wound closure materials or techniques, with most surgeons using the same strategy for all patient scenarios. Harmonization of practice and the limitation of outlying techniques might result in better outcomes for patients and provide a stable platform for the introduction and evaluation of further potential improvements.

T6SS and ExoA of flesh-eating Aeromonas hydrophila in peritonitis and necrotizing fasciitis during mono- and polymicrobial infections.

An earlier report described a human case of necrotizing fasciitis (NF) caused by mixed infection with 4 Aeromonas hydrophila strains (NF1-NF4). While the NF2, NF3, and NF4 strains were clonal and possessed exotoxin A (ExoA), the NF1 strain was determined to be phylogenetically distinct, harboring a unique type 6 secretion system (T6SS) effector (TseC). During NF1 and NF2 mixed infection, only NF1 disseminated, while NF2 was rapidly killed by a contact-dependent mechanism and macrophage phagocytosis, as was demonstrated by using in vitro models. To confirm these findings, we developed 2 NF1 mutants (NF1ΔtseC and NF1ΔvasK); vasK encodes an essential T6SS structural component. NF1 VasK and TseC were proven to be involved in contact-dependent killing of NF2 in vitro, as well as in its elimination at the intramuscular injection site in vivo during mixed infection, with overall reduced mouse mortality. ExoA was shown to have an important role in NF by both NF1-exoA (with cis exoA) and NF2 during monomicrobial infection. However, the contribution of ExoA was more important for NF2 than NF1 in the murine peritonitis model. The NF2∆exoA mutant did not significantly alter animal mortality or NF1 dissemination during mixed infection in the NF model, suggesting that the ExoA activity was significant at the injection site. Immunization of mice to ExoA protected animals from NF2 monomicrobial challenge, but not from polymicrobial infection because of NF2 clearance. This study clarified the roles of T6SS and ExoA in pathogenesis caused by A. hydrophila NF strains in both mouse peritonitis and NF models in monomicrobial and polymicrobial infections.

Friendship selection and influence processes for popularity in early and mid-adolescents.

INTRODUCTION: This study examined the effect of popularity levels on friendship selection and friends' influence on popularity levels in early and mid-adolescence. METHODS: Participants were 4205 Spanish adolescents (Mage = 13.1 years at Wave 1; 48% girls) belonging to 160 classrooms in two waves. Adolescents were asked about their friendships and the popularity of their classmates. RESULTS: Longitudinal social network analyses showed that adolescents preferred similarly popular peers as friends. High popular classmates were more attractive as friends, particularly in early adolescence. Popular adolescents were more selective in their friendship nominations and adolescents with popular friends became more popular over time. These two effects were only significant in mid-adolescents, although comparative analyses showed a similar tendency at both age groups. CONCLUSIONS: This study highlights the importance of popularity levels in adolescents' friendship selection and suggests that popularity, at the individual and group level, plays a relevant role in social development. Implications adapted to the different selection and influence processes in early and mid-adolescence are discussed.

Analysis of Intensities Using Inertial Motion Devices in Female Soccer: Do You Train like You Compete?

Intensity research in female soccer is limited. This study aimed to investigate whether female professional soccer players train with external and internal intensities similar to those recorded in real competition. The specific players' position, the game situation and training task type were analyzed in a total of 18 female players (26.25 ± 3.89 years). The empirical, descriptive and associative study was structured into two parts. Part 1: characterizing the training sessions (n = 13) and official matches (n = 3) using the Integral Analysis System of Training Tasks. The association between sports planning variables was evaluated using adjusted standardized residuals from contingency tables, Chi-Square and Fisher tests, as well as the Phi and Cramer's V coefficients. The main findings show that the coach and/or physical trainer predominantly planned training sessions using small-sided games, which integrate physical fitness and tactical-technical behaviors of the game and imply a medium-high subjective external intensity (20.63 ± 5.79 points). The subjective external intensity of the matches was very high (30.00 ± 0.00 points). Part 2: quantifying the external and internal intensity through the inertial motion devices and heart rate monitors. Differences in the intensities according to the type of session (training session and match), specific position of the players, game situation and type of the training task were assessed through different statistical tests. By specific position (Kruskal-Wallis H and one-factor ANOVA tests), defenders performed fewer accelerations/min and decelerations/min, while they recorded higher heart rates in training sessions and official matches. In contrast, the wingbacks performed higher accelerations/min and decelerations/min in training sessions and official matches. The wingers had the lowest heart rate in official matches. Regarding the game situation (Kruskal-Wallis H test) measured during training sessions, the unopposed tasks recorded higher accelerations/min and decelerations/min, while the small-sided games and full games recorded higher values in the rest of the intensities (both subjective and objective). With regard to the type of training task (Kruskal-Wallis H test), the simple application exercises recorded higher accelerations/min and decelerations/min. Distance in meters/min was greater in the complex application exercises. High-intensity activity/min and player load/min were higher in the simple specific game. In addition, modified sport and real game recorded higher subjective external intensity*min, sprints/min and heart rate. Furthermore, training sessions differed statistically (Mann-Whitney U test) from official matches in terms of subjective intensity and the objective external and internal intensity variables weighted by minutes. For all these reasons, female players do not train (training sessions) as they compete (official matches). The use of inertial motion devices has made it possible to quantify intensities during training sessions and real competition in soccer.

Infectious complications after allogeneic hematopoietic stem cell transplantation in children in a bone marrow transplant unit in Colombia.

OBJECTIVE: There is a relative lack of information about infections occurring in children following allogeneic hematopoietic stem cell transplants (allo-HSCT) in developing countries. Herein, we describe the incidence rates of different infections according to the transplant period and baseline condition in Colombia. METHODS: In a retrospective cohort study of all children who underwent allo-HSCTs from 2012 to 2017 in a hospital in Cali, Colombia, we reviewed medical records from the first post-transplant day until day + 365 to describe microbiologically confirmed incidence rates of infections and deaths during three post-transplant periods and according to baseline condition. RESULTS: Most allo-HSCT (n = 144, 96%) were followed by infections over the following year, mostly due to bacteria and cytomegalovirus (4.3 and 3.3 per 1000 patient-days, respectively). Children were at the highest risk for infection in the first 30 days post-HSTC, but mortality was highest after 100 days. Overall, high mortality (n = 44, 31.7%) was associated with infections, especially from extensively drug-resistant bacteria, adenovirus, and aspergillosis. Infection rates were similar independent of the baseline condition. CONCLUSION: Almost all children in this cohort developed infections post allo-HSCT. Describing the distribution of infections throughout the first post allo-HSCT year allows clinicians to narrow the differential diagnosis of infections according to the post-transplant period. This is especially useful when prioritizing interventions in children receiving HSCT in stringent healthcare systems in developing countries.

Patient-Reported Outcome Measures in Colorectal Surgery: Construction of Core Measures Using Open-Source Research Method.

Purpose. The primary aim of the study was to review the existing literature about patient-reported outcome measures (PROMs) in colorectal cancer and IBD. The secondary aim was to present a road map to develop a core outcome set via opinion gathering using social media. Method. This study is the first step of a three-step project aimed at constructing simple, applicable PROMs in colorectal surgery. This article was written in a collaborative manner with authors invited both through Twitter via the #OpenSourceResearch hashtag. The 5 most used PROMs were presented and discussed as slides/images on Twitter. Inputs from a wide spectrum of participants including researchers, surgeons, physicians, nurses, patients, and patients' organizations were collected and analyzed. The final draft was emailed to all contributors and 6 patients' representatives for proofreading and approval. Results. Five PROM sets were identified and discussed: EORTC QLQ-CR29, IBDQ short health questionnaire, EORTC QLQ-C30, ED-Q5-5L, and Short Form-36. There were 315 tweets posted by 50 tweeters with 1458 retweets. Awareness about PROMs was generally limited. The general psycho-physical well-being score (GPP) was suggested and discussed, and then a survey was conducted in which more than 2/3 of voters agreed that GPP covers the most important aspects in PROMs. Conclusion. Despite the limitations of this exploratory study, it offered a new method to conduct clinical research with opportunity to engage patients. The general psycho-physical well-being score suggested as simple, applicable PROMs to be eventually combined procedure-specific, disease-specific, or symptom-specific PROMs if needed.

One Health Interdisciplinary Collaboration in Veterinary Education Establishments in Europe: Mapping Implementation and Reflecting on Promotion.

One Health recognizes the interconnection of people, animals, and the environment and encourages a multidisciplinary approach. Several high-level European and global policy recommendations call for close intersectoral collaboration to better understand and manage health challenges faced today. Academic education has a fundamental role in preparing all health professionals in that respect. Our research investigates whether, and how, European Veterinary Education Establishments (VEEs) implement interdisciplinarity. We collected data on undergraduate education, post-graduate programs, and academic research through a pan-European survey. Our aim was to identify policy actions that could encourage cross-sectoral education and a culture of One Health at universities. Input from 41 VEEs showed that interdisciplinary education for undergraduates is still in the early stages. The models of academic structure, undergraduate curricula, and education policies established so far hinder interdisciplinarity. One Health interdisciplinary post-graduate education is easier, at least in some countries, while research successfully integrates multidisciplinary interdisciplinary and transdisciplinary approaches . To conclude, we propose five recommendations to promote interdisciplinary education in veterinary and other curricula and to further encourage the intersectoral cooperation in research: (1) the need for the development of One Health transdisciplinary competencies across different discipline curricula in the European Union (EU); (2) the need for an integrated strategy of university structures and policies (for undergraduates and post-graduates) to encourage and support interdisciplinarity; (3) the need for a harmonized approach to academic education via accreditation; (4) the need for appropriate legislation to facilitate interdisciplinary training; and (5) the need to encourage One Health research.

Structure-based domain assignment in Leishmania infantum EndoG: characterization of a pH-dependent regulatory switch and a C-terminal extension that largely dictates DNA substrate preferences.

Mitochondrial endonuclease G from Leishmania infantum (LiEndoG) participates in the degradation of double-stranded DNA (dsDNA) during parasite cell death and is catalytically inactive at a pH of 8.0 or above. The presence, in the primary sequence, of an acidic amino acid-rich insertion exclusive to trypanosomatids and its spatial position in a homology-built model of LiEndoG led us to postulate that this peptide stretch might act as a pH sensor for self-inhibition. We found that a LiEndoG variant lacking residues 145-180 is indeed far more active than its wild-type counterpart at pH values >7.0. In addition, we discovered that (i) LiEndoG exists as a homodimer, (ii) replacement of Ser211 in the active-site SRGH motif with the canonical aspartate from the DRGH motif of other nucleases leads to a catalytically deficient enzyme, (iii) the activity of the S211D variant can be restored upon the concomitant replacement of Ala247 with Arg and (iv) a C-terminal extension is responsible for the observed preferential cleavage of single-stranded DNA (ssDNA) and ssDNA-dsDNA junctions. Taken together, our results support the view that LiEndoG is a multidomain molecular machine whose nuclease activity can be subtly modulated or even abrogated through architectural changes brought about by environmental conditions and interaction with other binding partners.

The association of major patterns of physical activity, sedentary behavior and sleeping with mortality in older adults.

Objective: To identify major patterns of physical activity (PA), sedentary behavior (SB) and sleeping (all self-reported), and their association with long-term mortality. Methods: Cohort of 2,851 individuals aged ≥ 60 from Spain. Mortality was ascertain from 2003 up to July 2013. Patterns of PA, SB and sleeping were identified by factor analysis. Results: During follow-up, 1,145 deaths occurred. The first pattern, named "sedentary and non-active pattern", was characterized by long sleeping or lying time, and not doing even light PA (household chores or walking). The second pattern was named "active and non-sedentary pattern", and was characterized long time devoted to vigorous activities, long walking time, and short seating time. Compared to those in the first quartile of the "sedentary and non-active pattern", those in the highest quartile showed a 71% higher mortality (HR: 1.71; 95%CI: 1.42-2.07; p-trend:<0.001); it corresponds to being 6-year older. By contrast, being in the highest versus the lowest quartile of the "active and non-sedentary pattern" was associated with a 32% lower mortality (HR: 0.68: 0.57-0.82; p-trend:<0.001); it corresponds to being 4-year younger. Conclusion: The "sedentary and non-active" pattern had a large impact on mortality. The "active and non-sedentary" pattern showed an opposite and slightly lower association.

Mapping the Teaching of Laboratory Animal Science and Medicine in the European Union and European Free Trade Area.

Developing a common market and allowing free movement of goods, services, and people is one of the main objectives of the European Union (EU) and the European Free Trade Area. In the field of scientific research, Directive 2010/63/EU on the protection of animals used for scientific purposes aims to improve the welfare of laboratory animals by following the principle of the 3Rs (replacement, reduction, and refinement). Each breeder, supplier, and user must appoint a designated veterinarian to advise on the well-being and treatment of the animals. In our report we investigate how the undergraduate veterinary curriculum prepares future veterinarians for the role of designated veterinarian, by analyzing data from 77 European veterinary education establishments. Over 80% of them provide training in laboratory animal science and medicine in their curriculum. All countries in the EU and the European Free Trade Area, having national veterinary schools, include such training in the curriculum of at least one of their establishments. Laboratory animal science and medicine courses can be obligatory or elective and are often part of more than one subject in the veterinary curricula. Post-graduate courses or programs are available at more than 50% of those veterinary schools. Most authorities in the European region consider graduate veterinarians ready to seek the role as designated veterinarian immediately after graduation.

Pangenome-wide and molecular evolution analyses of the Pseudomonas aeruginosa species.

BACKGROUND: Drug treatments and vaccine designs against the opportunistic human pathogen Pseudomonas aeruginosa have multiple issues, all associated with the diverse genetic traits present in this pathogen, ranging from multi-drug resistant genes to the molecular machinery for the biosynthesis of biofilms. Several candidate vaccines against P. aeruginosa have been developed, which target the outer membrane proteins; however, major issues arise when attempting to establish complete protection against this pathogen due to its presumably genotypic variation at the strain level. To shed light on this concern, we proposed this study to assess the P. aeruginosa pangenome and its molecular evolution across multiple strains. RESULTS: The P. aeruginosa pangenome was estimated to contain more than 16,000 non-redundant genes, and approximately 15 % of these constituted the core genome. Functional analyses of the accessory genome indicated a wide presence of genetic elements directly associated with pathogenicity. An in-depth molecular evolution analysis revealed the full landscape of selection forces acting on the P. aeruginosa pangenome, in which purifying selection drives evolution in the genome of this human pathogen. We also detected distinctive positive selection in a wide variety of outer membrane proteins, with the data supporting the concept of substantial genetic variation in proteins probably recognized as antigens. Approaching the evolutionary information of genes under extremely positive selection, we designed a new Multi-Locus Sequencing Typing assay for an informative, rapid, and cost-effective genotyping of P. aeruginosa clinical isolates. CONCLUSIONS: We report the unprecedented pangenome characterization of P. aeruginosa on a large scale, which included almost 200 bacterial genomes from one single species and a molecular evolutionary analysis at the pangenome scale. Evolutionary information presented here provides a clear explanation of the issues associated with the use of protein conjugates from pili, flagella, or secretion systems as antigens for vaccine design, which exhibit high genetic variation in terms of non-synonymous substitutions in P. aeruginosa strains.

Spontaneous haematoma of the anterior rectus abdominis muscle. / Hematoma espontáneo del músculo recto anterior del abdomen.

INTRODUCTION: Spontaneous haematoma of the rectus abdominis muscle is an uncommon cause of abdominal pain. It occurs mostly in anticoagulated patients. The objective of this paper is to analyse the onset, diagnosis and treatment in patients under anticoagulant therapy. METHODS: A retrospective analysis of a prospectively maintained database of all patients with a diagnosis of spontaneous hematoma of the abdominal rectus muscle between March 2003 and December 2014. RESULTS: The study included 34 patients, of whom 28 were women, with an average age of 80 years old. All the patients showed a unilateral infraumbilical haematoma. Twenty- 8 patients had received long-term anticoagulant treatment (26 with acenocumarol and 2 low molecular weight heparin); and 6 patients were under anticoagulant prophylaxis with low molecular weight heparin. The diagnosis was performed with ultrasound in 7 cases, computed tomography angiography in 27 patients, and with both methods in 6 cases. The treatment consisted of stopping the anticoagulant drug, correcting haemostasis parameters and blood transfusion when required. Ten patients displayed active bleeding in the computed tomography angiography, and 8 underwent selective arterial embolization. The evolution was successful in 34 patients, however, 2 patients required surgery and, finally, died due to persistent haemorrhage. CONCLUSION: Spontaneous haematoma of the rectus abdominis muscle is more frequent in elderly women under oral anticoagulant treatment. Non-operative treatment is successful in most cases. Computed tomography angiography is useful to determine which patients could benefit from selective arterial embolization.

Expression of an alkane monooxygenase (alkB) gene and methyl tert-butyl ether co-metabolic oxidation in Pseudomonas citronellolis.

Pseudomonas citronellolis UAM-Ps1 co-metabolically transforms methyl tert-butyl ether (MTBE) to tert-butyl alcohol with n-pentane (2.6 mM), n-octane (1.5 mM) or dicyclopropylketone (DCPK) (4.4 mM), a gratuitous inducer of alkane hydroxylase (AlkB) activity. The reverse transcription quantitative real-time PCR was used to quantify the alkane monooxygenase (alkB) gene expression. The alkB gene was expressed in the presence of n-alkanes and DCPK and MTBE oxidation occurred only in cultures when alkB was transcribed. A correlation between the number of alkB transcripts and MTBE consumption was found (ΜΤΒΕ consumption in µmol = 1.44e(-13) x DNA copies, R(2) = 0.99) when MTBE (0.84 mM) was added. Furthermore, alkB was cloned and expressed into Escherichia coli and the recombinant AlkB had a molecular weight of 42 kDa. This is the first report where the expression of alkB is related to the co-metabolic oxidation of MTBE.

The association of major patterns of physical activity, sedentary behavior and sleep with health-related quality of life: a cohort study.

OBJECTIVE: To examine the prospective association of patterns of physical activity, sedentary behavior and sleep with health-related quality of life (HRQL) in the general population of Spain. METHODS: A cohort study with 4271 individuals aged ≥ 18 years was recruited in 2008-2010 and followed-up prospectively through 2012. Activity patterns were derived from factor analysis. HRQL was assessed with the SF-12 questionnaire, and suboptimal HRQL was defined as a score below the sex-specific sample median. RESULTS: Three main activity patterns were identified. A higher adherence to the pattern named "vigorous activity-seated at the computer" was inversely associated with a suboptimal score in the physical-composite summary (PCS) of the SF-12 (multivariate adjusted odds ratio [aOR] for the highest vs. the lowest quartile 0.71; 95% confidence interval [IC] 0.55-0.90; p-trend=0.003). The "light activity-seated for reading" pattern was inversely associated with a suboptimal score in the mental-composite summary (aOR=0.73; 95% CI=0.61-0.89; p-trend=0.002). However, a higher adherence to the "seated for watching TV-daytime sleeping" pattern was directly associated with suboptimal PCS (aOR=1.35; 95% CI=1.10-1.66; p-trend=0.008). CONCLUSION: Patterns including any physical activity were associated with better physical or mental HRQL. However, a pattern defined by sedentary behavior with diurnal sleep showed worse HRQL and should be a priority target of preventive interventions.

RNAi-mediated knockdown of IKK1 in transgenic mice using a transgenic construct containing the human H1 promoter.

Inhibition of gene expression through siRNAs is a tool increasingly used for the study of gene function in model systems, including transgenic mice. To achieve perdurable effects, the stable expression of siRNAs by an integrated transgenic construct is necessary. For transgenic siRNA expression, promoters transcribed by either RNApol II or III (such as U6 or H1 promoters) can be used. Relatively large amounts of small RNAs synthesis are achieved when using RNApol III promoters, which can be advantageous in knockdown experiments. To study the feasibility of H1 promoter-driven RNAi-expressing constructs for protein knockdown in transgenic mice, we chose IKK1 as the target gene. Our results indicate that constructs containing the H1 promoter are sensitive to the presence of prokaryotic sequences and to transgene position effects, similar to RNApol II promoters-driven constructs. We observed variable expression levels of transgenic siRNA among different tissues and animals and a reduction of up to 80% in IKK1 expression. Furthermore, IKK1 knockdown led to hair follicle alterations. In summary, we show that constructs directed by the H1 promoter can be used for knockdown of genes of interest in different organs and for the generation of animal models complementary to knockout and overexpression models.

Quality of death in patients in advanced chronic liver disease and cancer patients managed by gastroenterologists in Portugal: are we doing it right?

INTRODUCTION: The incidence of chronic progressive diseases is rising and investment on quality of death and dying is of utmost importance to minimize physical and emotional suffering. There is still a gap in palliative care (PC) between patients with cancer and those with advanced chronic liver disease (ACLD). Our objectives were to characterize clinical attitudes and therapeutic interventions and to evaluate the differences in end-of-life care between inpatients with cancer and ACLD under gastroenterology care. METHODS: Retrospective cohort study, including patients with cancer or ACLD who died in a Gastroenterology department between 2012 and 2021. Demographic characteristics, clinical and endoscopic procedures and symptom control were compared between the groups. RESULTS: From 150 patients, 118 (78.7%) died with cancer and 32 (21.3%) died from ACLD without concomitant hepatocellular carcinoma. ACLD patients were more frequently male ( P  = 0.001) and younger ( P  = 0.001) than patients with cancer. Median time of hospitalization in the last month of life was 16 days for both groups. Discussion of prognosis with the patient was more frequent for cancer patients (35.6% versus 3.2%, P  < 0.001). Referral to PC occurred in 18.8% and 61% of the patients with ACLD and cancer respectively ( P  < 0.001). Endoscopic procedures were performed in half of the patients and were more likely to be unsuccessful in those with cancer. CONCLUSION: Clinical decisions were different between groups in terms of PC access and discussion of prognostic with the patient. It is urgent to define and implement metrics of quality of death and dying to prevent potentially inappropriate treatment.