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BACKGROUND: Allergic sensitization and low lung function in early childhood are risk factors for subsequent wheezing and asthma. However, it is unclear how allergic sensitization affects lung function over time. OBJECTIVE: We sought to test whether allergy influences lung function and whether these factors synergistically increase the risk of continued wheezing in childhood. METHODS: We analyzed longitudinal measurements of lung function (spirometry and impulse oscillometry) and allergic sensitization (aeroallergen skin tests and serum allergen-specific IgE) throughout early childhood in the Urban Environmental and Childhood Asthma study, which included high-risk urban children living in disadvantaged neighborhoods. Intraclass correlation coefficients were calculated to assess lung function stability. Cluster analysis identified low, medium, and high allergy trajectories, which were compared with lung function and wheezing episodes in linear regression models. A variable selection model assessed predictors at age 5 years for continued wheezing through age 12 years. RESULTS: Lung function adjusted for growth was stable (intraclass correlation coefficient, 0.5-0.7) from age 5 to 12 years and unrelated to allergy trajectory. Lung function and allergic sensitization were associated with wheezing episodes in an additive fashion. In children with asthma, measuring lung function at age 5 years added little to the medical history for predicting future wheezing episodes through age 12 years. CONCLUSIONS: In high-risk urban children, age-related trajectories of allergic sensitization were not associated with lung function development; however, both indicators were related to continued wheezing. These results underscore the importance of understanding early-life factors that negatively affect lung development and suggest that treating allergic sensitization may not alter lung function development in early to mid-childhood.
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Pulmão , Sons Respiratórios , População Urbana , Humanos , Sons Respiratórios/fisiopatologia , Sons Respiratórios/imunologia , Masculino , Feminino , Pré-Escolar , Criança , Pulmão/fisiopatologia , Pulmão/imunologia , Asma/fisiopatologia , Asma/epidemiologia , Asma/imunologia , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Testes de Função Respiratória , Fatores de Risco , Alérgenos/imunologia , Testes CutâneosRESUMO
BACKGROUND: Chronic rhinitis symptoms cause significant health burden among children and can have a heterogeneous presentation. Defining phenotypes of childhood chronic rhinitis and associated pathobiology may lead to prevention or improved treatments. OBJECTIVES: We sought to identify longitudinal patterns of rhinitis symptoms in childhood and determine their associations with early life risk factors, allergic comorbidities, and nasal epithelial cell gene expression. METHODS: Chronic rhinitis symptoms were evaluated from ages 1 through 11 years in 485 urban children at high risk for allergic disease in the URECA (Urban Environment and Childhood Asthma) birth cohort. We identified longitudinal rhinitis phenotypes and their relationships to early life exposures, atopic comorbidities, and patterns of nasal epithelial gene expression at age 11 years. RESULTS: Chronic rhinitis symptoms started early in many children and were a risk factor for developing aeroallergen sensitization. We identified 4 longitudinal rhinitis phenotypes: low/minimal, persistent, persistent decreasing, and late increasing. Persistent rhinitis was most closely linked to allergic sensitization and asthma. Risk factors for persistent rhinitis included frequent colds (P < .001), antibiotic use (P < .001), and reduced exposure to common indoor aeroallergens (P = .003). Compared to low/minimal rhinitis phenotype, the other rhinitis phenotypes were associated with increased expression of canonical type 2 genes and decreased expression of immune response genes. CONCLUSIONS: In urban children, rhinitis symptoms often precede aeroallergen sensitization. Rhinitis phenotypes based on symptoms had distinct risk factors and nasal transcriptome. These results suggest that focusing on early life risk factors and distinct immune mechanisms may be a target to preventing chronic rhinitis in childhood.
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BACKGROUND: Drowning is the third-leading cause of unintentional injury death worldwide. Although the USA as a whole bears a heavy burden, with approximately 4000 drowning fatalities annually, Texas stands out as a high-risk state for drowning due to its large population, suitable climate for year-round aquatic activities and availability of water-related recreational opportunities. METHODS: Using mortality data from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research online database, this retrospective, cross-sectional study overviews the magnitude and patterns of fatal unintentional drownings among Texans from 1999 to 2020. RESULTS: Over the 22-year period, 7737 Texans died from unintentional drowning. An average of 352 drowning deaths occurred annually, with a rate of 1.4 deaths per 100 000 population. The highest proportion of unintentional drownings occurred in natural water settings (eg, lakes, ponds or rivers), accounting for 40% of fatal drownings. Children aged 1-4 years had the highest drowning death rate compared with all other age groups. Male Texans had a drowning death rate three times higher than that of female Texans. Black Texans had a higher drowning death rate than White Texans and Asian or Pacific Islander Texans. CONCLUSIONS: Drowning remains a significant public health issue in Texas. Data on high-risk groups and settings should be used to strengthen drowning prevention efforts and policy initiatives and encourage more research to address the multifaceted factors contributing to drowning.
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Purpose: Data on the use of transesophageal echocardiography (TEE) by intensivist physicians (IP) and emergency physicians (EP) are limited. This study aims to characterize the use of TEE by IPs and EPs in critically ill patients at a single center in the United States. Materials and Methods: Retrospective chart review of all critical care TEEs performed from January 1, 2016 to January 31, 2021. The personnel performing the exams, location of the exams, characteristics of exams, complications, and outcome of the patients were reviewed. Results: A total of 396 examinations was reviewed. TEE was performed by IPs (92%) and EPs (9%). The location of TEE included: intensive care unit (87%), emergency department (11%), and prehospital (2%) settings. The most common indications for TEE were: hemodynamic instability/shock (44%), cardiac arrest (23%), and extracorporeal membrane oxygenation (ECMO) facilitation, adjustment, or weaning (21%). The most common diagnosis based on TEE were: normal TEE (25%), left ventricular dysfunction (19%), and vasodilatory shock (15%). A management change resulted from 89% of exams performed. Complications occurred in 2% of critical care TEEs. Conclusion: TEE can be successfully performed by IPs and EPs on critically ill patients in multiple clinical settings. TEE frequently informed management changes with few complications.
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Estado Terminal , Médicos , Cuidados Críticos , Estado Terminal/terapia , Ecocardiografia Transesofagiana/efeitos adversos , Humanos , Estudos RetrospectivosRESUMO
Recent statistics show an increasing trend of electronic cigarette usage among adolescents. Despite common misconceptions, electronic cigarette use does not reduce cigarette use among adolescents and can potentially increase cigarette dependence via nicotine addiction and modeling of smoking behaviors. Pediatric nurses and health care providers should be aware of the popularity and safety concerns of electronic cigarettes so that they can properly provide education regarding the possible negative health effects of adolescent electronic cigarette use, raise awareness of this public health concern, and impact policies in their communities.
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Comportamento do Adolescente , Sistemas Eletrônicos de Liberação de Nicotina/efeitos adversos , Enfermagem Pediátrica , Assunção de Riscos , Adolescente , HumanosRESUMO
BACKGROUND: Drowning is a worldwide problem. Scholarly publications about drowning prevention play a crucial role in bringing data to policy makers and prevention specialists. This study presents a bibliometric analysis of published articles related to unintentional drowning prevention included in the comprehensive, curated injury literature database, SafetyLit®. METHODS: Thorough searches of drowning-related search terms in English and non- English translations identified articles published in journals between 2000 and 2022. RESULTS: There was a 3-fold increase in publications between 2000 and 2022, with 2,937 articles published in 941 journals. Articles were published in 20 different languages. Five journals published 16% of the articles and sixty-one top journals published 50% of the articles. Eighty-nine percent of the top journals were included in PubMed; 82% were indexed in MEDLINE®; and professional areas of expertise of article authors spanned 18 categories. CONCLUSIONS: This study can facilitate journal selection for drowning researchers to ultimately increase the publication of scientific literature globally.
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BACKGROUND: Sport-related injuries and illnesses can negatively impact athlete welfare at all standards of participation in team sports. Injury and illness surveillance (IIS), and the development of monitoring systems, initiates the sequence of injury and illness prevention. Operational IIS monitoring systems help to appraise epidemiological estimates of injury and illness incidence and burden in various athlete populations. However, the methodological underpinnings of various monitoring systems are not harmonized or widely documented, with the presence of efficient and successful programmes rarely showcased at non-elite levels. The aim is to provide a framework that guides the development of IIS, which will enhance overall surveillance, to indirectly inform injury prevention strategies. METHODS: The process involved all members of the research group initially discussing the research gaps, scope of the project, and the aims of the article. Unique experiences were shared, and specific and global challenges and barriers to IIS at all standards of team sport participation were identified. A tiered system of data collection with corresponding content were produced, with experiences and guidance provided throughout the article. RESULTS: The literature has been reviewed and using first-hand experience in conducting IIS programmes in complex and diverse sport settings, the authors have identified key enablers and barriers for best practise as time, technological and human resources, reporter/practitioner training, and medical expertise. Areas of greatest importance regarding the conducting of IIS have been outlined, providing guidance and recommendations across all levels of team sport participation. These areas include definitions, data context, collection procedures, handling, security, ethics, storage, dissemination, quality, compliance, and analysis. Given the barriers to IIS, 3-tiered levels of data collection and content have been proposed. The levels indicate data collection variables, with a focus on sufficiency and achievability, aiming to support the successful conducting of IIS in team sports across all standards of participation. Future opportunities in IIS have been discussed, with several predictive measures and analytical techniques expanded upon. CONCLUSIONS: The framework provides universal guidance for implementing IIS monitoring systems, facilitating athletes, coaches, parents/guardians, governing bodies and practitioners to implement IIS processes, identify challenges, complete analysis, and interpret outcomes at all standards of participation.
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BACKGROUND: A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption. METHODS: Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months. RESULTS: We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 µg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 µg/l. Adverse events were uncommon, and the majority were related to the food challenge. CONCLUSIONS: Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).
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Arachis , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/prevenção & controle , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/epidemiologia , Seguimentos , Arachis/imunologia , Feminino , Masculino , Pré-Escolar , Lactente , Adolescente , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Criança , Tolerância ImunológicaRESUMO
ABSTRACT: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the Center for International Blood and Marrow Transplant Research registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART therapy between 2018 and 2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range, 1-7) prior therapies and were treated with axicabtagene ciloleucel (69%). At median follow-up of 23 months after CART therapy, 2-year overall and progression-free survival were 42% (95% confidence interval [CI], 27-57) and 29% (95% CI, 17-43), respectively. In univariable analysis, poor performance status before CART therapy was associated with higher mortality (hazard ratio, 2.35; 95%CI, 1.02-5.5). The 2-year cumulative incidences of relapse/progression and nonrelapse mortality were 69% and 2%, respectively. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurologic syndrome occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART therapy for R/R THRLBCL, â¼30% of patients were alive and progression free 2 years after CART therapy. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CARTs.
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Antígenos CD19 , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Antígenos CD19/imunologia , Antígenos CD19/uso terapêutico , Adulto , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Idoso , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Histiócitos/patologia , Resultado do Tratamento , Receptores de Antígenos Quiméricos/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Drowning is the leading cause of death for toddlers. When caregivers are knowledgeable about water safety, they can provide the best protection against drowning. The aim of this study is to survey caregivers of toddlers to better understand factors associated with water safety knowledge, attitudes about pool supervision, and toddler water competency skills. METHODS: An online survey of 650 parents/caregivers of 1-4-year-old toddlers asked about the caregiver's water safety and swimming background and views on pool supervision. Surveys included a true/false section of ten basic water safety knowledge questions. Caregivers also reported on toddler swim lesson history and whether their toddler could perform six standard water competency skills. Linear regression identified factors predictive of water safety knowledge. RESULTS: On average, caregivers selected the correct answer on six out of ten water safety knowledge questions. Water safety knowledge was predicted by the relationship of the caregiver to the toddler, gender, race, education, prior CPR training, caregiver swim capability, and reported pool supervision style. On average, caregivers reported that their toddler could perform half of the water competency skills. The majority of the toddlers had taken swimming lessons. One third of caregivers believed that after a toddler has had swimming lessons, they don't need to be watched as closely when they are in a pool. CONCLUSIONS: Findings suggest that water safety knowledge is poor and that there are misconceptions about toddler supervision needs. Efforts are needed to improve water safety knowledge and to change perceptions about supervision among caregivers of toddlers.
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Deterioration in movement and posture often occurs with aging. Yet there may be approaches to movement training that can maintain posture and movement coordination patterns as we age. The Alexander Technique is a non-exercise-based approach that aims to improve everyday movement and posture by increasing awareness and modulating whole-body postural muscle activity. This study assessed whether nineteen 55-72-year-old Alexander Technique teachers showed different posture and movement coordination patterns than twenty age-matched controls during a standing and walking protocol using 3D inertial sensors. During upright stance, Alexander Technique teachers showed lower centroidal sway frequency at the ankle (p = .04) and lower normalized jerk at the sternum (p = .05) than controls. During gait, Alexander Technique teachers had more symmetrical gait cycles (p = .04), more symmetrical arm swing velocity (p = .01), greater arm swing velocity (p < .01), greater arm swing range of motion (p = .02), and lower range of acceleration of the torso in the frontal plane (p = .03) than controls. Smoother control of upright posture, more stable torso motion, and less restrained arm mobility suggest that Alexander Technique training may counter movement degradation that is found with aging. Results highlight the important balance between mobility and stability within the torso and limbs.
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Drowning is a major public health issue internationally. In August 2022, a report was released by members of the Central Texas Drowning Prevention Action Team that provided data on drowning fatalities in Texas between 2006 and 2020 and offered recommendations for drowning prevention actions. The information in the Texas drowning report is an important contribution to the field of injury prevention. The aim of this editorial is to allow the information in the report to be available to a wider audience and potentially used as a model for other states.
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We tested whether Shoshone pupfish Cyprinodon nevadensis shoshone and Amargosa River pupfish C. n. amargosae respond behaviourally to conspecific chemical alarm cues released when epidermal tissue is damaged by a predator. We found that both subspecies reduced activity and vertical position in the water column in response to alarm cues. We then tested if pupfish can use alarm cue to acquire recognition of a novel predator. We trained pupfish with (1) water + odour of largemouth bass fed a diet of earthworms, (2) alarm cues from skin extract (epidermal alarm cues) + odour of bass fed a diet of earthworms, or (3) water + odour of bass fed a diet of pupfish (dietary alarm cues). Pupfish responded to epidermal alarm cues but not to dietary alarm cues. Pupfish were retested with the odour of bass that were fed an earthworm diet. Pupfish that had previously received epidermal alarm cues reduced vertical position and activity relative to the other two treatments. This is the first demonstration of acquired recognition of a novel predator by a pupfish, the first report of partial predator naiveté, and opens the possibility of predator-recognition training as a tool for management and conservation of endangered desert fishes.
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Implementing an effective clinical integration program requires deliberate investment of time and resources in five key areas: Physician leadership, Physician-led care management, Quality monitoring, Patient information and data sharing, Payer engagement.
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Organizações de Assistência Responsáveis , Integração de Sistemas , Gestão da Informação/organização & administração , Reembolso de Seguro de Saúde , Liderança , Registro Médico Coordenado , Inovação Organizacional , Papel do Médico , Controle de Qualidade , Estados UnidosRESUMO
Background: Groups of children swimming during summer camp or child care are generally monitored by a small number of lifeguards and staff. The high child-to-staff ratio can make pool monitoring less effective, increasing drowning risk. The aim of this study is to evaluate novel drowning detection technology that could supplement pool monitoring. Methods: The WAVE™ Drowning Detection System was deployed at a camp pool for 8 weeks. The WAVE™ Drowning Detection System entails headbands worn by swimmers that send alerts to vibrating staff bracelets and audible alarms when submerged for a period of time. Data on the number of alerts were collected, and staff were surveyed. Results: One or two alerts were initiated every hour. Staff reported that risky underwater play and exiting the pool area were top reasons for alerts. Staff found the awareness brought to risky pool behavior useful and had a neutral attitude about false alarms. Staff found the system easy to learn and use but suggested headband fit and comfort could be improved. Staff believed the system could help save someone's life. Conclusions: The WAVE system is low-risk, easy-to-use technology that may supplement lifeguard monitoring of large groups of children in pools.
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BACKGROUND: Drowning is a leading cause of unintentional injury-related death for toddlers within the USA. Keeping toddlers within arm's reach while swimming is recommended, yet many caregivers do not. Possibly, caregivers' attitudes are shaped by their expectations about whether they could quickly save a child. The aims of this study are to 1) explore caregivers' views of arm's reach pool supervision in various scenarios and 2) understand whether perceptions of arm's reach pool supervision are impacted by the caregiver's self-reported capability to swim the length of a standard pool. RESULTS: Caregivers generally showed agreement with arm's reach pool supervision; however, arm's reach supervision was viewed as less necessary when a toddler was in shallow water, wearing a flotation device, or with an older child or teen. There was a significant effect of caregiver swimming capability on perceptions of arm's reach pool supervision, with non-swimmers and the strongest swimmers showing more positive perceptions of arm's reach pool supervision than caregivers reporting poor swimming capability. Female caregivers showed significantly more agreement with arm's reach pool supervision compared with male caregivers. Grandparents and parents showed significantly more agreement with arm's reach pool supervision than siblings. CONCLUSIONS: Caregivers' views about what constitutes appropriate supervision are impacted by gender, the relationship to the toddler, and the caregiver's swimming capability. Findings suggest that a caregiver's ability to offer close supervision or respond in an emergency may influence their attitudes about what constitutes appropriate supervision. Caregivers may view arm's reach pool supervision as less necessary when additional layers of protection are in place.
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Gene therapy is a rapidly developing field, and adeno-associated viruses (AAVs) are a leading viral-vector candidate for therapeutic gene delivery. Newly engineered AAVs with improved abilities are now entering the clinic. It has proven challenging, however, to predict the translational potential of gene therapies developed in animal models due to cross-species differences. Human retinal explants are the only available model of fully developed human retinal tissue and are thus important for the validation of candidate AAV vectors. In this study, we evaluated 18 wild-type and engineered AAV capsids in human retinal explants using a recently developed single-cell RNA sequencing (RNA-seq) AAV engineering pipeline (scAAVengr). Human retinal explants retained the same major cell types as fresh retina, with similar expression of cell-specific markers except for a photoreceptor population with altered expression of photoreceptor-specific genes. The efficiency and tropism of AAVs in human explants were quantified with single-cell resolution. The top-performing serotypes, K91, K912, and 7m8, were further validated in non-human primate and human retinal explants. Together, this study provides detailed information about the transcriptome profiles of retinal explants and quantifies the infectivity of leading AAV serotypes in human retina, accelerating the translation of retinal gene therapies to the clinic.
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While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett's esophagus compared to 40 Barrett's patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett's tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures. The critical distinction between stable Barrett's versus those who progress to cancer is acquisition and expansion of TP53-/- cell populations having complex structural variants and high-level amplifications, which are detectable up to six years prior to a cancer diagnosis. These findings reveal the timing of common somatic genome dynamics in stable Barrett's esophagus and define key genomic features specific to progression to esophageal adenocarcinoma, both of which are critical for cancer prevention and early detection strategies.
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Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Adenocarcinoma/patologia , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , HumanosRESUMO
OBJECTIVE: To examine sex differences in lumbopelvic motion and symptom behavior during hip medial rotation in people with low back pain (LBP). We hypothesized that men would demonstrate greater and earlier lumbopelvic motion and would be more likely to report increased symptoms compared with women. DESIGN: Cross-sectional observational study. SETTING: University musculoskeletal analysis laboratory. PARTICIPANTS: Persons with chronic LBP (N=59; 30 men, 29 women) were recruited from the community and a university-based physical therapy clinic. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lumbopelvic rotation range of motion, amount of hip rotation completed before the start of lumbopelvic motion, and provocation of LBP symptoms during the test of prone hip medial rotation were measured. RESULTS: Men demonstrated significantly more lumbopelvic rotation (men, 10.0°±5.1°; women, 4.5°±3.9°; P<.001) and completed less hip rotation before the start of lumbopelvic motion (men, 5.4°±3.8°; women, 16.0°±13.2°; P<.001) compared with women. Additionally, a significantly greater percentage of men (60.0%) than women (34.5%; P=.050) reported increased symptoms with hip medial rotation. CONCLUSIONS: Men could be at greater risk than women for experiencing LBP symptoms related to hip medial rotation as a result of greater and earlier lumbopelvic motion.
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Dor Lombar/fisiopatologia , Movimento/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Doença Crônica , Estudos Transversais , Feminino , Articulação do Quadril/fisiologia , Humanos , Dor Lombar/reabilitação , Região Lombossacral/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pelve/fisiopatologia , Rotação , Fatores SexuaisRESUMO
When assessing the financial implications of a physician alignment and clinical integration initiative, a hospital should measure the initiative's potential ROI, perhaps best using a combination of net present value and payback period. The hospital should compare its own historical and projected performance with rating agency median benchmarks for key financial indicators of profitability, debt service, capital and cash flow, and liquidity. The hospital should also consider potential indirect benefits, such as retained outpatient/ancillary revenue, increased inpatient revenue, improved cost control, and improved quality and reporting transparency.