The prevalence of patellofemoral pain in the Rugby League World Cup (RLWC) 2021 spectators: A protocol of a cross-sectional study

Patellofemoral pain (PFP) can cause significant pain leading to limitations in societal participation and physical activity. PFP is usually associated with athletes undergoing intensive physical training, or military recruits; but recent evidence shows that PFP is common in the general population. The relationship of PFP with physical activity is not entirely clear. Our aim is to provide a better estimate of the general population prevalence of PFP and to relate this to the level of physical activity, and demographic characteristics. The Survey instrument for Natural history, Aetiology and Prevalence of Patellofemoral pain Studies (SNAPPS) was developed as a PFP screening tool to be used in the community. The electronic version of the SNAPPS (eSNAPPS) has recently been validated and was used to survey attendees at mass-participation running events. We will use an electronic survey to collect data from a sample of 1100 Rugby League World Cup spectators. The survey will have four sections: i) general and demographic; ii) knee pain (eSNAPPS); iii) level of physical activity; and iv) quality of life in relation to knee pain. The primary analytic approach will be descriptive of PFP prevalence. Secondary analyses will explore the relationships of the presence of PFP and the other variables. We will disseminate this work by publication of peer-reviewed papers in scientific journals, presentations at scientific conferences, and on the dedicated SNAPPS website https://www.snappspfp.com/

Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers

Genomic alterations; Mutated cancers; Immuno-oncologyAlteraciones genómicas; Cánceres mutados; Inmuno-oncologíaAlteracions genòmiques; Càncers mutats; Immuno-oncologiaPURPOSE Promising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking. MATERIALS AND METHODS Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers. RESULTS Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants (KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR-P] = .0006), current or prior smokers (85% v 56%, FDR-P 60 years (73% v 63%, FDR-P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non–small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR-P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR-P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR-P < .01). CONCLUSION This study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status

Laparoscopy versus open adrenalectomy in patients with solid tumor metastases: results of a multicenter European study

Background: The outcome of adrenalectomy carried out by laparoscopy or open surgery for solid tumor metastases was assessed. Methods: A total of 317 patients with histologically confirmed adrenal metastatic disease collected from 30 centres in Europe underwent adrenalectomy by laparoscopy (n=146) or open laparotomy (n=171). Differences between laparoscopic and open adrenalectomy were assessed by a single Cox analysis for both procedures. Results: The median overall survival was 24.0 [95% confidence interval (CI): 21.4-26.6] months for open adrenalectomy and 45.0 (95% CI: 22.6-67.4) for laparoscopic adrenalectomy (P=0.008). Survival rates were 68%, 49%, 35% and 29% at 1, 2, 3 and 5 years for open surgery vs. 88%, 62%, 52% and 46% for laparoscopy, respectively. In the subgroup of R0 resections, the difference in survival in favor of laparoscopy (median 46 vs. 27 months) was marginally significant (P=0.073). Renal cancer [hazard ratio (HR) 0.42; 95% CI: 0.23-0.76, P=0.005], surgery of the primary tumor (HR 0.33; 95% CI: 0.19-0.54), and use of chemotherapy (HR 0.62; 95% CI: 0.43-0.88) were associated with a better survival, whereas type of resection (R1/R2 vs. R0) was associated with a worse prognosis (HR 2.29; 95% CI: 1.52-3.44, P<0.001). Conclusions: Laparoscopic adrenalectomy patients showed a longer survival than open adrenalectomy individuals, as minimally invasive approach was attempted more common in less advanced disease which led to higher number of R0 resections

Desigualdades sociais e uso de serviços de saúde: evidências de análise estratificada

OBJECTIVE: The study aims to identify children who are not benefited by local health programs, looking for to characterize the excluded segment of the population in order to broaden the access to and use of the main actions provided by local health programs. METHODS: A sample of 465 children aged less than 1 year was studied, living in the year of 1996 in Embu, a city of the metropolitan area of S. Paulo, Brazil. Our hypothesis was that there is a higher availability of private health care resources among families who haven't been using the local health program. The statistical analysis consisted of stratified association analysis to study the heterogeneity between and intra four strata of families defined by different socialeconomic conditions. RESULTS: Although only 85.4% of the study children were enrolled in local health services, 91.2% of them were being benefited by main health care actions. The analysis of differences intra strata revealed that our hypothesis was only corroborated in one stratum. It is in the stratum 3, which concentrates the peripheral population, where we could find children who have not been using the local health program in Embu city. CONCLUSIONS: In the same social segment it was detected some inner heterogeneity among families related to the availability of private resources for their children health care.OBJETIVO: Identificar os grupos populacionais não alcançados pelo programa local de saúde materno-infantil, buscando caracterizar os possíveis pontos de exclusão, com vistas ao estudo de intervenções capazes de ampliar o acesso e a utilização das principais ações de saúde oferecidas pelo programa. MÉTODOS: Estudou-se uma amostra de 465 menores de um ano residentes no Município de Embu, SP (Brasil). A análise estatística, orientada pela hipótese que esperava maior disponibilidade de planos de saúde entre as famílias que não usavam o programa local de saúde infantil, consistiu em análises de associação estratificadas que buscaram detectar heterogeneidade entre os quatro estratos de famílias e no interior deles, definidos segundo diferentes padrões de condições de vida. RESULTADOS: Apesar de apenas 85,4% das crianças estudadas serem matriculadas nas unidades básicas de saúde, 91,2 % eram assistidas pelas principais ações de saúde. No estrato 3, onde reside a população periférica, estão concentradas as crianças não alcançadas pelo programa. O estudo de diferenças dentro dos estratos revelou que também no estrato 3 encontra-se a possibilidade de que algumas famílias estejam usando convênios ou planos de saúde como alternativa ao programa local de saúde. Os resultados apontam ainda que a população com piores condições de vida (favelas) dispõe do sistema público do município como única alternativa para cuidar de sua saúde. CONCLUSÕES: É na população residente na periferia do município que se concentram as crianças não assistidas pelo programa local de saúde infantil e existe maior heterogeneidade entre as famílias quanto à disponibilidade de outros recursos para os cuidados de saúde de suas crianças

An unexpected role for caspase-2 in neuroblastoma

Caspase-2 has been implicated in various cellular functions, including cell death by apoptosis, oxidative stress response, maintenance of genomic stability and tumor suppression. The loss of the caspase-2 gene (Casp2) enhances oncogene-mediated tumorigenesis induced by E1A/Ras in athymic nude mice, and also in the Eμ-Myc lymphoma and MMTV/c-neu mammary tumor mouse models. To further investigate the function of caspase-2 in oncogene-mediated tumorigenesis, we extended our studies in the TH-MYCN transgenic mouse model of neuroblastoma. Surprisingly, we found that loss of caspase-2 delayed tumorigenesis in the TH-MYCN neuroblastoma model. In addition, tumors from TH-MYCN/Casp2(-/-) mice were predominantly thoracic paraspinal tumors and were less vascularized compared with tumors from their TH-MYCN/Casp2(+/+) counterparts. We did not detect any differences in the expression of neuroblastoma-associated genes in TH-MYCN/Casp2(-/-) tumors, or in the activation of Ras/MAPK signaling pathway that is involved in neuroblastoma progression. Analysis of expression array data from human neuroblastoma samples showed a correlation between low caspase-2 levels and increased survival. However, caspase-2 levels correlated with clinical outcome only in the subset of MYCN-non-amplified human neuroblastoma. These observations indicate that caspase-2 is not a suppressor in MYCN-induced neuroblastoma and suggest a tissue and context-specific role for caspase-2 in tumorigenesis.L Dorstyn, J Puccini, A Nikolic, S Shalini, CH Wilson, MD Norris, M Haber and S Kuma

Caspase-2-mediated cell death is required for deleting aneuploid cells

Caspase-2, one of the most evolutionarily conserved of the caspase family, has been implicated in maintenance of chromosomal stability and tumour suppression. Caspase-2 deficient (Casp2-/-) mice develop normally but show premature ageing-related traits and when challenged by certain stressors, succumb to enhanced tumour development and aneuploidy. To test how caspase-2 protects against chromosomal instability, we utilized an ex vivo system for aneuploidy where primary splenocytes from Casp2-/- mice were exposed to anti-mitotic drugs and followed up by live cell imaging. Our data show that caspase-2 is required for deleting mitotically aberrant cells. Acute silencing of caspase-2 in cultured human cells recapitulated these results. We further generated Casp2C320S mutant mice to demonstrate that caspase-2 catalytic activity is essential for its function in limiting aneuploidy. Our results provide direct evidence that the apoptotic activity of caspase-2 is necessary for deleting cells with mitotic aberrations to limit aneuploidy.S Dawar, Y Lim, J Puccini, M White, P Thomas, L Bouchier-Hayes, D R Green, L Dorstyn and S Kuma

Performance Of A Liquid Argon Time Projection Chamber Exposed To The WANF Neutrino Beam

We present the results of the first exposure of a Liquid Argon TPC to a multi-GeV neutrino beam. The data have been collected with a 50 liters ICARUS-like chamber located between the CHORUS and NOMAD experiments at the CERN West Area Neutrino Facility (WANF). We discuss both the instrumental performance of the detector and its capability to identify and reconstruct low multiplicity neutrino interactions.Comment: 14 pages, 12 figures. Submitted for publication to Physical Review

Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy:a population-based study in six European regions

ObjectiveTo explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases.DesignDescriptive drug utilisation study.SettingSix electronic healthcare databases in Denmark, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK.PopulationAll women with a pregnancy ending in a live or stillbirth starting and ending between 2004 and 2010.MethodsA common protocol was implemented across databases to identify SSRI prescriptions issued (UK) or dispensed (non-UK) in the year before, during or in the year following pregnancy.Main outcome measuresThe percentage of deliveries in which the woman received an SSRI prescription in the year before, during or in the year following pregnancy. We also compared the choice of SSRIs and changes in prescribing over the study period.ResultsIn total, 721 632 women and 862943 deliveries were identified. In the year preceding pregnancy, the prevalence of SSRI prescribing was highest in Wales [9.6%; 95% confidence interval (CI95), 9.4-9.8%] and lowest in Emilia Romagna (3.3%; CI95, 3.2-3.4%). During pregnancy, SSRI prescribing had dropped to between 1.2% (CI95, 1.1-1.3%) in Emilia Romagna and 4.5% (CI95, 4.3-4.6%) in Wales. The higher UK pre-pregnancy prescribing rates resulted in higher first trimester exposures. After pregnancy, SSRI prescribing increased most rapidly in the UK. Paroxetine was more commonly prescribed in the Netherlands and Italian regions than in Denmark and the UK.ConclusionsThe higher SSRI prescribing rates in the UK, compared with other European regions, raise questions about differences in the prevalence and severity of depression and its management in pregnancy across Europe.</p

Systemic antibiotic prescribing to paediatric outpatients in 5 European countries: A population-based cohort study

Background: To describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far.Methods: Outpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008.Results: With 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad s