Application of mixture distributions for identifying thresholds of frequent and high inpatient mental health service use in longitudinal data.

BACKGROUND: There is a need for greater understanding about frequent and high use of inpatient mental health services, and those with ongoing increased needs. Most studies employ a threshold of frequent use (e.g. numbers of admissions) and high use (e.g. lengthy stays) without justification. AIMS: To identify model-driven thresholds for frequent/high inpatient mental health service use and contrast characteristics of patients identified using various models and thresholds. METHOD: Retrospective population-based study using 12 years of longitudinal data for 5631 patients admitted with a mental health diagnosis. Two-component negative binomial and poisson mixture (truncated/untruncated) models identified thresholds for frequent/high use in a 12-month period. RESULTS: The two-component negative binomial mixture model resulted in the best model fit. Using negative binomial-derived thresholds, 5.3% of patients had a period of frequent use (admitted six or more times), 15.8% of high use (hospitalised for 45 or more days) and 3.5% of heavy use (both frequent and high use). The prevalence of specific mental health disorders (e.g. mood disorder and schizophrenia) among frequent and high use cohorts varied across thresholds. CONCLUSIONS: This model-driven approach can be applied to identify thresholds in other cohorts. Threshold choice may depend on the magnitude and focus of potential interventions.

Penicillin versus anti-staphylococcal beta-lactams for penicillin-susceptible Staphylococcus aureus blood stream infections: a retrospective cohort study.

The objective of the study is to assess the efficacy and tolerability of penicillins compared to anti-staphylococcal beta-lactams for treatment of penicillin-susceptible Staphylococcus aureus bloodstream infections (PSSA BSI). A retrospective cohort study was conducted of 140 sequential PSSA BSI presenting to a local health district (90 cases included). Penicillin susceptibility was confirmed by disc diffusion, Vitek® and Nitrocefin beta-lactamase methods. Clinical information regarding comorbidities and infection complexity was recorded. Antibiotic choice, dosage and duration were reviewed. Outcomes were compared according to the definitive treatment with either penicillin or ASBLs. The primary outcome was 30-day mortality. Secondary outcomes included renal injury, microbiological relapse and treatment tolerability. Ninety patients met inclusion criteria and were included in subsequent analysis. Of PSSA BSI, 69% were community acquired. Eighty-two percent had complex PSSA infections. The average duration of bacteraemia was 2.8 days (SD = 1.8 days). Sixty-six patients received definitive penicillin treatment, with a mean of 3.5 days of empiric antibiotics prior to penicillin. Twenty-four patients received definitive ASBL treatment (11 cefazolin, 13 flucloxacillin). There was no difference in 30-day mortality between groups (p = 1). There was no difference in renal injury (p > 0.5), hospital length of stay (p = 0.59) or microbiological relapse within 1 year (p = 0.17). Penicillin treatment was well tolerated. Our data supports penicillin as a suitable and well-tolerated alternative to ASBL in managing complex PSSA BSI.

Diagnostic accuracy of brief cognitive screening tools to diagnose vascular cognitive impairment in Peru.

INTRODUCTION: To evaluate the diagnostic accuracy of three brief cognitive screening (BCS) tools, Peruvian version of Addenbrooke's Cognitive Examination (ACE-Pe), of INECO Frontal Screening (IFS-Pe) and of the Mini-Mental State Examination (MMSE-Pe), for the diagnosis of vascular cognitive impairment (VCI) and its non-dementia stages (VCI-ND) and vascular dementia (VD) in patients with cerebral stroke in Lima-Peru. MATERIALS AND METHODS: A cohort analysis to evaluate the diagnostic accuracy of three BCS for VCI. RESULTS: Two hundred and four patients were evaluated: 61% Non-VCI, 30% VCI-ND and 9% VD. To discriminate patients with VCI from controls, the area under the curve (AUC) of ACE-Pe, IFS-Pe and MMs-Pe were 0.99 (95% confidence interval [CI] 0.98-0.99), 0.99 (95%CI 0.98-0.99) and 0.87 (95%CI 0.82-0.92), respectively. Of the three BCS, the IFS-Pe presented a larger AUC to discriminate VCI-ND from VD (AUC = 0.98 [95%CI 0.95-1]) compared to ACE-Pe (AUC = 0.84 [95%CI 0.74-0.95]) and MMSE-Pe (0.92 [95%CI 0.86-0.99]). The IFS-Pe presented a higher sensitivity (S), specificity (Sp), and positive (+LR) and negative likelihood ratios (-LR) (S = 96.72%, Sp = 89.47%, +LR = 9.1 and -LR = 0.03) than ACE-Pe (S = 96.72%, Sp = 63.16%, +LR = 2.62 and -LR = 0.05) and MMSE-Pe (S = 90.16%, Sp = 78.95%, +LR = 4.28 and -LR = 0.12). In the multiple regression analysis, the IFS-Pe was not affected by age, sex or years of schooling. CONCLUSION: The IFS-Pe has the best diagnostic accuracy for detecting VCI and discriminating between pre-dementia (VCI-ND) and dementia (VD) stages.

How to streamline the low and negligible research ethics and governance review process from 80 to 10 days: submission to decision.

Most clinicians find research ethics and governance difficult and time consuming. This study aimed to develop a better local review process for low-risk research. We used real-time processing, leveraged local expertise and streamlined paperwork. As a result, turnaround times decreased from more than 80 days to 10 days, creating an efficient review process for low-risk projects.

Evaluation of the geriatrician in the practice model of care for dementia assessment and management in rural Australia.

OBJECTIVES: To evaluate an integrated care program expanding the physician in the practice model into geriatrics, focussing on dementia assessment and management. DESIGN: Observational descriptive study. SETTING: The rural section of a local health district in New South Wales, Australia. PARTICIPANTS: Patients attending eight general practices, in addition to practice nurses and general practitioners. INTERVENTIONS: Self-report questionnaires completed by patients, specialist general practitioners and practice nurses. Responses to open-ended questions were analysed using content analysis. Routinely collected health data of patients who took part in the program were compared with data of patients from the same institution who did not take part in the program. MAIN OUTCOME MEASURES: A number of planned reviews, actual reviews and emergency department presentations for participating patients, self-efficacy amongst general practitioners and practice nurses, and patient satisfaction and comfort levels. RESULTS: The GIP program was well received by most patients, GPs and practice nurses. Almost 90% of patients found it easier to see the specialist at their general practice. They were less likely to have planned reviews, actual reviews and emergency department presentations than patients who did not take part in the program. GPs and practice nurses expressed increased confidence in and knowledge of dementia assessment and management. CONCLUSIONS: Dementia assessment and management programs based on the physician in the practice model may be well received in similar rural settings. Larger prospective studies are needed to further examine the relationship between programs and patients' health outcomes.

Predisposing, enabling and need factors associated with increased use and ongoing increased use of inpatient mental health care: A population-based longitudinal study.

OBJECTIVE: The study investigated factors associated with frequent (admissions), high (total length of stay) or heavy (frequent and high) hospital use, and with ongoing increased hospital use, for mental health conditions in a regional health district. METHODS: A retrospective population-based study using longitudinal hospital, emergency department and community service use data for people admitted with a mental health condition between 1 January 2012 and 31 December 2016. Multivariate logistic regression models assessed the association of predisposing, enabling and need factors with increased, and ongoing increased, hospital use. RESULTS: A total of 5,631 people had at least one mental health admission. Frequent admission was associated with not being married (odds ratio = 2.3, 95% confidence interval = [1.5, 3.3]), no private hospital insurance (odds ratio = 2.2, 95% confidence interval = [1.2, 3.8]), previous mental health service use (community, emergency department, lengthy admissions) and a history of a substance use disorder, childhood trauma, self-harm or chronic obstructive pulmonary disease. High and heavy hospital use was associated with marital status, hospital insurance, admission for schizophrenia, previous mental health service use and a history of self-harm. Ongoing frequent use was less likely among those aged 65 and older (odds ratio = 0.2, 95% confidence interval = [0.1, 1.0]) but more likely among those with a history of depression (odds ratio = 2.2, 95% confidence interval = [1.1, 4.4]). Ongoing high use was also associated with admissions for schizophrenia and a history of self-harm. CONCLUSION: Interventions targeted at younger people hospitalised with schizophrenia, a history of depression or self-harm, particularly with evidence of social and or health disadvantage, should be considered to improve long-term consumer and health system outcomes. These data can support policymakers to better understand the context and need for improvements in stepped or staged care for people frequently using inpatient mental health care.

Male and female inheritance patterns in tetraploid 'Moncada' mandarin.

KEY MESSAGE: Tetraploid `Moncada´ mandarin, used as male and female in interploidy hybridizations, displays mainly tetrasomic inheritance for most LGs, with slight variations according to the direction of the crossing. Triploid-breeding programs in citrus are key tool to develop seedless cultivars. Obtaining triploid citrus hybrids may be achieved through different strategies, such as the exploitation of female unreduced gamete in crosses between diploid parents and diploid by tetraploid sexual hybridizations, in which tetraploid genotypes can be used as male or female parents. Genetic configuration of triploid populations from interploid crosses greatly depends on the chromosomic segregation mode of the tetraploid parent used. Here, we have analyzed the inheritance of the tetraploid 'Moncada' mandarin and compared the genetic structures of the resulting gametes when used as male and as female parent. The preferential chromosome pairing rate is calculated from the parental heterozygosity restitution (PHR) of codominant molecular markers, indicating the proportion between disomic and tetrasomic segregation. Tetraploid 'Moncada' both as female and male parent largely exhibited tetrasomic segregation. However, as female parent, one linkage group (LG8) showed intermediate segregation with tendency towards tetrasomic inheritance, while another linkage group (LG4) evidenced a clear intermediate segregation. On the other hand, when used as male parent two linkage groups (LG5 and LG6) showed values that fit an intermediate inheritance model with tetrasomic tendency. Significant doubled reduction (DR) rates were observed in five linkage groups as female parent, and in six linkage groups as male parent. The new knowledge generated here will serve to define crossing strategies in citrus improvement programs to efficiently obtain new varieties of interest in the global fresh consumption market.

Critical adjustments in a department of orthopaedics through the COVID-19 pandemic.

PURPOSE: SARS-CoV-2's new scenario has forced health systems to work under extreme stress urging to perform a complete reorganization of the way our means and activities were organized. The orthopaedic and trauma units have rescheduled their activities to help SARS-CoV-2 units, but trauma patients require also treatment, and no standardized protocols have been established. METHODS: A single-centre cross-sectional study was performed in a tertiary hospital. Two different periods of time were analyzed: a two week period of time in March 2019 (pre-SARS-CoV-2) and the same period in March 2020 (SARS-CoV-2 pandemic time). Outpatient's data, emergency activity, surgical procedures, and admissions were evaluated. Surgeons' and patient's opinion was also evaluated using a survey. RESULTS: A total of ~ 16k (15,953) patients were evaluated. Scheduled clinical appointments decreased by ~ 22%. Urgent consultations and discharge from clinics also descended (~ 37% and ~ 20% respectively). Telemedicine was used in 90% of outpatient clinical evaluations. No elective surgical procedures during SARS-CoV-2 time were scheduled, and subtracting the effect of elective surgeries, there was a reduction of inpatient surgeries, from ~ 85% to ~ 59%. Patients delayed trauma assistance more than 48 hours in 13 cases (35%). Pre-operative admission for hip fractures decreased in ten hours on average. Finally, surveys stated that patients were more in favour than surgeons were to this new way to evaluate orthopaedic and trauma patients based strongly on telemedicine. CONCLUSION: Detailed protocols should be standardized for surgical departments during the pandemic. This paper offers a general view in how this virus affects an orthopaedic unit and could serve as a protocol and example for orthopaedic and trauma units. Even in the worst scenario, an orthopaedic and trauma unit could offer an effective, efficient, and quality service. SARS-CoV-2 will set up a new paradigm for health care in orthopaedics and trauma.

Repair of Late Retrograde Type A Aortic Dissection After TEVAR: Causes and Management.

One of the most feared complications of thoracic endovascular aortic repair (TEVAR) and hybrid arch repair is retrograde type A aortic dissection (RTAD). More than two-thirds of RTAD occurs in the immediate postoperative period and first postoperative month. In presentations beyond that point, progression of the native aortopathy must be considered. We report a late presentation of an RTAD seven months after hybrid repair of an aortic intramural hematoma with an ulcer-like projection, and review the causes and management of this TEVAR complication.

Genetic mapping of centromeres in the nine Citrus clementina chromosomes using half-tetrad analysis and recombination patterns in unreduced and haploid gametes.

BACKGROUND: Mapping centromere locations in plant species provides essential information for the analysis of genetic structures and population dynamics. The centromere's position affects the distribution of crossovers along a chromosome and the parental heterozygosity restitution by 2n gametes is a direct function of the genetic distance to the centromere. Sexual polyploidisation is relatively frequent in Citrus species and is widely used to develop new seedless triploid cultivars. The study's objectives were to (i) map the positions of the centromeres of the nine Citrus clementina chromosomes; (ii) analyse the crossover interference in unreduced gametes; and (iii) establish the pattern of genetic recombination in haploid clementine gametes along each chromosome and its relationship with the centromere location and distribution of genic sequences. RESULTS: Triploid progenies were derived from unreduced megagametophytes produced by second-division restitution. Centromere positions were mapped genetically for all linkage groups using half-tetrad analysis. Inference of the physical locations of centromeres revealed one acrocentric, four metacentric and four submetacentric chromosomes. Crossover interference was observed in unreduced gametes, with variation seen between chromosome arms. For haploid gametes, a strong decrease in the recombination rate occurred in centromeric and pericentromeric regions, which contained a low density of genic sequences. In chromosomes VIII and IX, these low recombination rates extended beyond the pericentromeric regions. The genomic region corresponding to a genetic distance < 5cM from a centromere represented 47% of the genome and 23% of the genic sequences. CONCLUSIONS: The centromere positions of the nine citrus chromosomes were genetically mapped. Their physical locations, inferred from the genetic ones, were consistent with the sequence constitution and recombination pattern along each chromosome. However, regions with low recombination rates extended beyond the pericentromeric regions of some chromosomes into areas richer in genic sequences. The persistence of strong linkage disequilibrium between large numbers of genes promotes the stability of epistatic interactions and multilocus-controlled traits over successive generations but also maintains multi-trait associations. Identification of the centromere positions will allow the development of simple methods to analyse unreduced gamete formation mechanisms in a large range of genotypes and further modelling of genetic inheritance in sexual polyploidisation breeding schemes.

Perceptions of treatment for tics among young people with Tourette syndrome and their parents: a mixed methods study.

BACKGROUND: Tourette syndrome (TS) among young people is associated with psychosocial difficulties and parents play an important role in the management of the condition. Clinical guidelines have been developed for the treatment of TS and tics, but little is known about how young people and their parents perceive their treatment options or their desired outcomes of treatment. The aim of this study is to explore perceptions of treatments for tics among young people with TS and their parents. METHODS: In-depth interviews with 42 young people with TS and a mixed-methods, online survey of 295 parents of young people with TS. Participant recruitment was conducted through Tourettes Action (TA): a non-profit UK organisation for the support of people with TS. Interview transcripts were analysed using thematic analysis and responses to survey open-ended questions were analysed using content analysis. Triangulation of qualitative and quantitative data from the parents' survey and qualitative data from the interviews with young people was used to increase the validity and depth of the findings. RESULTS: A strong theme was the perception that health professionals have limited knowledge of TS and its treatment. Medication was a common treatment for tics and both young people and parents described benefits of medication. However, adverse effects were frequently described and these were a common reason for stopping medication among young people. Aripiprazole was viewed most positively. Access to behavioural interventions for tics was limited and 76% of parents wanted this treatment to be available for their child. Some young people had reservations about the effectiveness or practicality of behavioural interventions. Reduction and abolition of tics were desired outcomes of treatment, but both parents and young people also identified the importance of increasing control over tics and reducing anxiety-related symptoms. For young people, managing the urge to tic was an important outcome of treatment. CONCLUSIONS: The results suggest a need for more training in the identification and management of TS and wider availability of behavioural treatments. Clinical trials could explore the effectiveness of Aripiprazole used in combination with psycho-educational interventions to reduce anxiety and promote a sense of control.

Assignment of SNP allelic configuration in polyploids using competitive allele-specific PCR: application to citrus triploid progeny.

BACKGROUND: Polyploidy is a major component of eukaryote evolution. Estimation of allele copy numbers for molecular markers has long been considered a challenge for polyploid species, while this process is essential for most genetic research. With the increasing availability and whole-genome coverage of single nucleotide polymorphism (SNP) markers, it is essential to implement a versatile SNP genotyping method to assign allelic configuration efficiently in polyploids. SCOPE: This work evaluates the usefulness of the KASPar method, based on competitive allele-specific PCR, for the assignment of SNP allelic configuration. Citrus was chosen as a model because of its economic importance, the ongoing worldwide polyploidy manipulation projects for cultivar and rootstock breeding, and the increasing availability of SNP markers. CONCLUSIONS: Fifteen SNP markers were successfully designed that produced clear allele signals that were in agreement with previous genotyping results at the diploid level. The analysis of DNA mixes between two haploid lines (Clementine and pummelo) at 13 different ratios revealed a very high correlation (average = 0·9796; s.d. = 0·0094) between the allele ratio and two parameters [θ angle = tan(-1) (y/x) and y' = y/(x + y)] derived from the two normalized allele signals (x and y) provided by KASPar. Separated cluster analysis and analysis of variance (ANOVA) from mixed DNA simulating triploid and tetraploid hybrids provided 99·71 % correct allelic configuration. Moreover, triploid populations arising from 2n gametes and interploid crosses were easily genotyped and provided useful genetic information. This work demonstrates that the KASPar SNP genotyping technique is an efficient way to assign heterozygous allelic configurations within polyploid populations. This method is accurate, simple and cost-effective. Moreover, it may be useful for quantitative studies, such as relative allele-specific expression analysis and bulk segregant analysis.

Genotyping by Sequencing for SNP-Based Linkage Analysis and the Development of KASPar Markers for Male Sterility and Polyembryony in Citrus.

Polyembryony and male sterility (MS) are essential characters for citrus breeding. MS, coupled with parthenocarpy, allows for addressing the diversification of diploid seedless mandarin varieties, and nucleocytoplasmic MS is the most prevalent system. Polyembryony limits the use of seed parents in scion breeding programs, and the recovery of monoembryonic hybrids to be used as female parents is a crucial pre-breeding component. The objectives of this work were the identification of SNPs closely linked with the genes implied in these traits for marker-assisted selection. Genotyping by sequencing was used to genotype 61 diploid hybrids from an F1 progeny recovered from crossing 'Kiyomi' and 'Murcott' tangors. A total of 6444 segregating markers were identified and used to establish the two parental genetic maps. They consisted of 1374 and 697 markers encompassing 1416.287 and 1339.735 cM for 'Kiyomi' and 'Murcott', respectively. Phenotyping for MS and polyembryony was performed. The genotype-trait association study identified a genomic region on LG8 which was significantly associated with MS, and a genomic region on LG1 which was significantly associated with polyembryony. Annotation of the identified region for MS revealed 19 candidate genes. One SNP KASPar marker was developed and fully validated for each trait.

High Mitochondrial Haplotype Diversity Found in Three Pre-Hispanic Groups from Colombia.

The analysis of mitochondrial DNA (mtDNA) hypervariable region (HVR) sequence data from ancient human remains provides valuable insights into the genetic structure and population dynamics of ancient populations. mtDNA is particularly useful in studying ancient populations, because it is maternally inherited and has a higher mutation rate compared to nuclear DNA. To determine the genetic structure of three Colombian pre-Hispanic populations and compare them with current populations, we determined the haplotypes from human bone remains by sequencing several mitochondrial DNA segments. A wide variety of mitochondrial polymorphisms were obtained from 33 samples. Our results support a high population heterogeneity among pre-Hispanic populations in Colombia.

A reference genetic map of C. clementina hort. ex Tan.; citrus evolution inferences from comparative mapping.

BACKGROUND: Most modern citrus cultivars have an interspecific origin. As a foundational step towards deciphering the interspecific genome structures, a reference whole genome sequence was produced by the International Citrus Genome Consortium from a haploid derived from Clementine mandarin. The availability of a saturated genetic map of Clementine was identified as an essential prerequisite to assist the whole genome sequence assembly. Clementine is believed to be a 'Mediterranean' mandarin × sweet orange hybrid, and sweet orange likely arose from interspecific hybridizations between mandarin and pummelo gene pools. The primary goals of the present study were to establish a Clementine reference map using codominant markers, and to perform comparative mapping of pummelo, sweet orange, and Clementine. RESULTS: Five parental genetic maps were established from three segregating populations, which were genotyped with Single Nucleotide Polymorphism (SNP), Simple Sequence Repeats (SSR) and Insertion-Deletion (Indel) markers. An initial medium density reference map (961 markers for 1084.1 cM) of the Clementine was established by combining male and female Clementine segregation data. This Clementine map was compared with two pummelo maps and a sweet orange map. The linear order of markers was highly conserved in the different species. However, significant differences in map size were observed, which suggests a variation in the recombination rates. Skewed segregations were much higher in the male than female Clementine mapping data. The mapping data confirmed that Clementine arose from hybridization between 'Mediterranean' mandarin and sweet orange. The results identified nine recombination break points for the sweet orange gamete that contributed to the Clementine genome. CONCLUSIONS: A reference genetic map of citrus, used to facilitate the chromosome assembly of the first citrus reference genome sequence, was established. The high conservation of marker order observed at the interspecific level should allow reasonable inferences of most citrus genome sequences by mapping next-generation sequencing (NGS) data in the reference genome sequence. The genome of the haploid Clementine used to establish the citrus reference genome sequence appears to have been inherited primarily from the 'Mediterranean' mandarin. The high frequency of skewed allelic segregations in the male Clementine data underline the probable extent of deviation from Mendelian segregation for characters controlled by heterozygous loci in male parents.

Traumatic aortic injuries associated with major visceral vascular injuries in major blunt trauma patients.

BACKGROUND: The objectives of this study were to report the clinical and radiological characteristics and outcomes of a series of acute traumatic aortic injuries (ATAIs) with associated injury to major aortic abdominal visceral branches (MAAVBs). METHODS: From January 2000 to August 2011, 10 consecutive major blunt trauma patients with associated ATAI and injury to MAAVBs (group A) and 42 major blunt trauma patients presenting only an ATAI without MAAVB injuries (group B) were admitted to our institution. RESULTS: Overall in-hospital mortality was 32.7%. In-hospital mortality in group A was 40% and in group B it was 31% (p = 0.86). Observed in-hospital mortality was slightly lower than the expected in-hospital mortality in both groups. Mean peak creatine phosphokinase was significantly higher in group A than in group B patients (23,008 ± 33,400 vs. 3,970 ± 3,495 IU/L; p < 0.001). Acute renal injury occurred in 50% of group A and in 26.2% of group B patients. Hemodiafiltration was required in 30% of group A and in 9.5% of group B patients. Median follow-up time was 64 months (range = 1-130 months). Group A survival was 60% at 1, 5 and 10 years. Group B survival was 69% at 1 year and 63.3% at 5 and 10 years (p = 0.15). CONCLUSIONS: Aortic injuries associated with MAAVB injuries in major trauma patients seem to present in a different clinical scenario. These patients present increased risk of rhabdomyolysis, visceral ischemia, and acute renal failure, as well as higher in-hospital mortality. A multidisciplinary approach combining endovascular and open surgical techniques for a staged treatment of these life-threatening aortic and MAAVB injuries is mandatory in this critical subset of trauma patients.

A Functional Assessment Tool to Distinguish Controls From Alzheimer's Disease in Lima, Peru.

BACKGROUND: The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale is a versatile functional assessment tool for patients with Alzheimer's disease (ad). We evaluated its performance in controls, Peruvians with MCI or AD. METHODS: A cross-sectional study of older adults attending a neurology institute in Lima (Peru) with mild cognitive impairment (MCI), ad or cognitively healthy. Test-retest reliability (intraclass correlation coefficient, ICC; internal consistency, Cronbach's alpha) and validity were assessed. RESULTS: We enrolled 276 individuals (ad: 113, MCI: 68, controls: 95) with no age, sex, educational level, and depressive symptom differences. Reliability was ideal (ICC: .996), and Cronbach's alpha was adequate (.937). The ADCS-ADL could not differentiate MCI from controls but did differentiate ad severity. The ADCS-ADL correlated highly with nearly all tools. CONCLUSIONS: The ADCS-ADL scale is reliable in a population with ad in Lima, Peru. Future work may validate a tool for Peruvians with lower educational levels.

Match Injuries in the Spanish Rugby Union Division de Honor.

OBJECTIVE: To describe the injury rate, severity, cause, anatomical location (tissue damaged), recurrence, place and time during matches throughout a season in the Spanish Rugby Union Division de Honor. METHODS: Observational, prospective and descriptive study conducted in the competition of the Spanish División de Honor de Rugby with 258 players. The data were reported by the medical services of the previously formed clubs. RESULTS: Total exposure was 4100 h, during which 220 injuries occurred. The average number of sick days was 36.8. The total injury rate was 53.6 injuries/1000 h of exposure. Three quarters suffered 93 injuries and the forwards sustained a total of 127 injuries, with a total of 48.6 and 58.1 injuries/1000 h of exposure, respectively. Moderate injuries were the most frequent. Specifically, ligament injury was the most frequent, and dislocation was the injury that caused the most sick days. The most injuries occurred in the third quarter of the match, and the most serious injuries occurred in the second quarter. CONCLUSIONS: The injury rate of Spanish rugby competitors is 53.6 injuries/1000 match hours, with an average of 36.8 sick days. Contact injuries are the most frequent, taking place especially when tackling or being tackled.

Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease.

CONTEXT: Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse. OBJECTIVES: This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas. METHODS: A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years' follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery. RESULTS: Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P < .001). CONCLUSION: This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas.

Acquired von Willebrand syndrome and mitral valve prosthesis leakage. A pilot study.

BACKGROUND: Of patients with severe aortic stenosis, 15-25% present with bleeding episodes possibly attributable to acquired von Willebrand syndrome (AVWS). AVWS associated with mitral valve prosthesis leakage has not been reported. METHODS AND RESULTS: Five patients receiving appropriate oral anticoagulation showed mitral valve prosthesis leakage and bleeding episodes; all of them required hospitalization and two blood transfusions, and a von Willebrand factor (VWF) analysis was performed. Two patients with normal functioning metallic prosthesis valves were included as controls. Before surgery, after cessation of acenocumarol, the patients had prolonged activated partial thromboplastin time; four had prolonged closure time (CT) from the platelet function analyzer. Factor VIII procoagulant activity (FVIII:C), VWF ristocetin cofactor activity (VWF:RCo), and VWF collagen binding (VWF:CB) were considerably elevated, while VWF antigen (VWF:Ag) was most elevated. Disproportionate VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios were seen with the loss of large VWF multimers. Following surgery, all parameters were markedly increased and the ratios, CT, and multimeric VWF profile became normal. CONCLUSIONS: Acquired VWF qualitative alterations in mitral valve prosthesis leakage may be associated with or contribute to bleeding diathesis. AVWS should be taken into consideration in patients with mitral valve prosthesis leakage with bleeding diathesis not explained by excessive oral anticoagulation.