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Deranged lipid homeostasis has been implicated in neurodegenerative diseases. Cholesterol reducing compounds such as statins have received special attention for the possibility that they may be able to ameliorate or prevent cognitive loss associated with neurodegeneration. However, there is much dissension concerning the actual effect of statins on cognitive function. The aim of this study is to investigate the effects of pitavastatin on hippocampal synaptogenesis because the hippocampus is crucial for memory formation. We also evaluated the effects of pitavastatin on local hippocampal estrogen synthesized in the hippocampus itself and its effect on Brain-Derived Neurotrophic Factor (BDNF). Using a hippocampal cell line, H19-7, we found that hippocampal neurons exposed to pitavastatin demonstrate a significant reduction in the synaptic marker postsynaptic density protein 95 (psd-95). The pitavastatin treated neurons also exhibited decreased production of local estrogen and their expression of BDNF mRNA was decreased. These results suggest that statins reduce the ability of hippocampal neurons to form synapses by restricting the production of local estrogen. Because neural connections in the hippocampus are crucial for memory formation, our findings implicate statins as medications that may compromise cognitive function.
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INTRODUCTION: Given the prevalence and staggering cost of neurological disorders, there is dire need for effective early detection and intervention tools. Emerging evidence suggests that multidisciplinary lifestyle interventions (MLI) may mitigate the risk and progression of neurological disorders. The objectives of this protocol are (1) to test the impact of MLI on the progression of neurological disorders and (2) to identify multi-omic biomarkers for early stages of neurological disease and the impact of MLIs on these biomarkers. METHODS AND ANALYSIS: We present the Multidisciplinary lifestyle Interventions for Neurological Disorders during the Silent phase (MINDS) protocol, a randomized controlled trial of MLI in neurologically healthy older adults (≥ 50 years old) exhibiting elevated risk for common neurological disorders: stroke, epilepsy, Parkinson's Disease, or Alzheimer's disease and related dementias. Participants will be randomly assigned to intervention (n = 100) or control (n = 100) groups. The intervention group will receive 3 months of weekly 2-hour sessions on diet education, yoga, music therapy, and cognitive skills training. The participants' neurological health and engagement in relevant lifestyle practices will be assessed at regular intervals for 12 months. Neuroimaging and samples for multi-omic analyses will be collected at baseline, and at 3 months and 12 months after enrollment. Primary outcomes will be signs of progression of the neurological disorder risk that qualified them for study enrollment or a clinical diagnosis of the disorder. Secondary and exploratory outcomes will be based on self-reported health and multi-omic data. Data analysis will include between-group and longitudinal within-group analyses. PERSPECTIVES: The MINDS protocol and trial aims to clarify the impact of MLI on the progression of neurological disorder risk or diagnosis in older adults and to identify biomarkers that can be used to confirm MLI efficacy. The ability to validate the impact of MLI on neurological disorder progression based on biomarker data allows the identification of individuals most likely to benefit from such therapies in the early stages of neurological disease. TRIAL REGISTRATION: The trial is registered on the National Institutes of Health (NIH) ClinicalTrials.gov (NCT05984056) site. It was registered on August 2nd, 2023. The trial has full approval of the Cleveland Clinic Internal Review Board.
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BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative brain disease with rapid progression and currently limited treatment options. A comprehensive understanding of disease progression, management, and healthcare resource utilization is limited, and further research is challenging due to the small population of patients. To address these challenges in conducting PSP research, individuals with PSP were recruited using a multichannel approach tailored specifically to the PSP community. We performed a retrospective observational study using data abstracted from participant medical records collected from multiple patient care centers. RESULTS: Seventy-two individuals with PSP were eligible for inclusion. On average, 144 medical documents per participant were collected from an average of 2.9 healthcare centers per participant, with a mean study period of 7.9 years. Among participants with a date of symptom onset documented in the medical records, the median time for the onset of the first fall was 2.0 years (IQR 3.2) before diagnosis, the median onset of unsteady gait or gait impairment was 1.2 years (IQR 1.8) before diagnosis, and the median onset of mobility problems was 0.8 years (IQR 1.8) before diagnosis. The most widely utilized healthcare resources, with at least 85% of participants using each of these resources at some point during the disease course, were medications (100%), imaging (99%), assistive devices (90%), supportive care (86%), and surgeries and procedures (85%). CONCLUSIONS: This retrospective study adds to the current understanding of PSP symptoms, comorbidities, and healthcare resource utilization (HRU) across the disease journey. By involving individuals with PSP and their caregivers or legally authorized representatives in the research process, this study was unique in its approach to participant recruitment and enabled individuals to participate in research without the need for travel. We collected medical documents from multiple healthcare centers, allowing for broad data collection covering the entire disease journey. This approach to the collection of real-world data may be used to generate valuable insights into many aspects of disease progression and management in PSP and many other rare diseases.
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Progresión de la Enfermedad , Parálisis Supranuclear Progresiva , Humanos , Parálisis Supranuclear Progresiva/terapia , Estudios Retrospectivos , Femenino , Masculino , Anciano , Canadá , Persona de Mediana Edad , Estados Unidos , Aceptación de la Atención de Salud/estadística & datos numéricos , Anciano de 80 o más AñosRESUMEN
Understanding the clinical characteristics and medical treatment of individuals affected by genetic epilepsies is instrumental in guiding selection for genetic testing, defining the phenotype range of these rare disorders, optimizing patient care pathways and pinpointing unaddressed medical need by quantifying healthcare resource utilization. To date, a matched longitudinal cohort study encompassing the entire spectrum of clinical characteristics and medical treatment from childhood through adolescence has not been performed. We identified individuals with genetic and non-genetic epilepsies and onset at ages 0-5 years by linkage across the Cleveland Clinic Health System. We used natural language processing to extract medical terms and procedures from longitudinal electronic health records and tested for cross-sectional and temporal associations with genetic epilepsy. We implemented a two-stage design: in the discovery cohort, individuals were stratified as being 'likely genetic' or 'non-genetic' by a natural language processing algorithm, and controls did not receive genetic testing. The validation cohort consisted of cases with genetic epilepsy confirmed by manual chart review and an independent set of controls who received negative genetic testing. The discovery and validation cohorts consisted of 503 and 344 individuals with genetic epilepsy and matched controls, respectively. The median age at the first encounter was 0.1 years and 7.9 years at the last encounter, and the mean duration of follow-up was 8.2 years. We extracted 188,295 Unified Medical Language System annotations for statistical analysis across 9659 encounters. Individuals with genetic epilepsy received an earlier epilepsy diagnosis and had more frequent and complex encounters with the healthcare system. Notably, the highest enrichment of encounters compared with the non-genetic groups was found during the transition from paediatric to adult care. Our computational approach could validate established comorbidities of genetic epilepsies, such as behavioural abnormality and intellectual disability. We also revealed novel associations for genitourinary abnormalities (odds ratio 1.91, 95% confidence interval: 1.66-2.20, P = 6.16 × 10-19) linked to a spectrum of underrecognized epilepsy-associated genetic disorders. This case-control study leveraged real-world data to identify novel features associated with the likelihood of a genetic aetiology and quantified the healthcare utilization of genetic epilepsies compared with matched controls. Our results strongly recommend early genetic testing to stratify individuals into specialized care paths, thus improving the clinical management of people with genetic epilepsies.
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Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.
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OBJECTIVE: Idiopathic subglottic stenosis is a rare disease, and time to diagnosis is often prolonged. In the United States, some estimate it takes an average of 9 years for patients with similar rare disease to be diagnosed. Patient experience during this period is termed the diagnostic odyssey. The aim of this study is to use qualitative methods grounded in behavioral-ecological conceptual frameworks to identify drivers of diagnostic odyssey length that can help inform efforts to improve health care for iSGS patients. METHODS: Qualitative study using semi-structured interviews. Setting consisted of participants who were recruited from those enrolled in a large, prospective multicenter trial. We use directed content analysis to analyze qualitative semi-structured interviews with iSGS patients focusing on their pathways to diagnosis. RESULTS: Overall, 30 patients with iSGS underwent semi-structured interviews. The patient-reported median time to diagnosis was 21 months. On average, the participants visited four different health care providers. Specialists were most likely to make an appropriate referral to otolaryngology that ended in diagnosis. However, when primary care providers referred to otolaryngology, patients experienced a shorter diagnostic odyssey. The most important behavioral-ecological factors in accelerating diagnosis were strong social support for the patient and providers' willingness to refer. CONCLUSION: Several factors affected time to diagnosis for iSGS patients. Patient social capital was a catalyst in decreasing time to diagnosis. Patient-reported medical paternalism and gatekeeping limited specialty care referrals extended diagnostic odysseys. Additional research is needed to understand the effect of patient-provider and provider-provider relationships on time to diagnosis for patients with iSGS. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:815-824, 2024.
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Laringoestenosis , Enfermedades Raras , Humanos , Estados Unidos , Constricción Patológica , Estudios Prospectivos , Laringoestenosis/diagnóstico , Derivación y ConsultaRESUMEN
OBJECTIVE: To investigate the effect of isoflurane anesthesia on thermoregulation and peripheral heat loss in dorsally recumbent horses. STUDY DESIGN: Prospective, clinical study. ANIMALS: Seven adult horses (2.6 ± 1.5 years old, 455 ± 70.2 kg). METHODS: Horses underwent elective surgical procedures in dorsal recumbency under general anesthesia (GA) maintained with isoflurane in oxygen. Rectal (TR), intranasal (TN) and fetlock surface temperatures (TF) were measured every 10 minutes for the first 80 minutes following induction of GA. Room temperature (TRO) was monitored during the study. Statistical analysis to determine differences between temperature measurement sites and techniques (TR, TN and TF), and differences over time were completed using a mixed-effects model with Tukey's multiple comparison or Dunnett's multiple comparison testing where appropriate. Significance was set at p < 0.05. RESULTS: Following induction of anesthesia, TF was significantly increased compared with baseline (0 minutes) from 40 to 80 minutes (p < 0.01). No significant differences were detected in TR and TN at any time point compared with baseline (p > 0.05). TF was significantly lower than TN (p < 0.02) at all time points and TR from times 0 to 70 minutes (p < 0.04). There were no significant differences between TR and TN at any time (p > 0.05). CONCLUSIONS: In horses undergoing isoflurane GA, TF increased, indicating peripheral heat loss likely because of vasodilation, whereas TR showed a clinically relevant decrease over time. These findings are suggestive of body heat redistribution during GA in horses in dorsal recumbency. Thermographic imaging of the peripheral limbs in combination with TR and TN monitoring allowed for recognition of peripheral heat redistribution in anesthetized horses. CLINICAL RELEVANCE: Anesthetized horses experience peripheral heat loss through their extremities as a result of vasodilation. Mitigating peripheral heat loss may improve thermoregulation and reduce hypothermic complications in anesthetized horses.
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Anestesia General , Caballos , Isoflurano , Termometría , Animales , Anestesia General/veterinaria , Anestesia General/métodos , Temperatura Corporal , Caballos/cirugía , Isoflurano/farmacología , Estudios Prospectivos , Termometría/métodos , Termometría/veterinariaRESUMEN
OBJECTIVES: Thyroid cancer incidence increased over 200% from 1992 to 2018, whereas mortality rates had not increased proportionately. The increased incidence has been attributed primarily to the detection of subclinical disease, raising important questions related to thyroid cancer control. We developed the Papillary Thyroid Carcinoma Microsimulation model (PATCAM) to answer them, including the impact of overdiagnosis on thyroid cancer incidence. METHODS: PATCAM simulates individuals from age 15 until death in birth cohorts starting from 1975 using 4 inter-related components, including natural history, detection, post-diagnosis, and other-cause mortality. PATCAM was built using high-quality data and calibrated against observed age-, sex-, and stage-specific incidence in the United States as reported by the Surveillance, Epidemiology, and End Results database. PATCAM was validated against US thyroid cancer mortality and 3 active surveillance studies, including the largest and longest running thyroid cancer active surveillance cohort in the world (from Japan) and 2 from the United States. RESULTS: PATCAM successfully replicated age- and stage-specific papillary thyroid cancers (PTC) incidence and mean tumor size at diagnosis and PTC mortality in the United States between 1975 and 2015. PATCAM accurately predicted the proportion of tumors that grew more than 3 mm and 5 mm in 5 years and 10 years, aligning with the 95% confidence intervals of the reported rates from active surveillance studies in most cases. CONCLUSIONS: PATCAM successfully reproduced observed US thyroid cancer incidence and mortality over time and was externally validated. PATCAM can be used to identify factors that influence the detection of subclinical PTCs.
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Carcinoma Papilar , Carcinoma , Neoplasias de la Tiroides , Humanos , Estados Unidos/epidemiología , Adolescente , Cáncer Papilar Tiroideo/epidemiología , Carcinoma/diagnóstico , Carcinoma/patología , Carcinoma Papilar/epidemiología , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patología , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , IncidenciaRESUMEN
Background: The use of thyroid ultrasound increases yearly, adding to costs and overdetection of clinically irrelevant nodules. We investigated which indications most commonly prompt referral for thyroid ultrasound and the diagnostic utility by indication. Methods: We performed a retrospective observational cohort study of adults (≥18 years) undergoing an initial dedicated thyroid ultrasound between 2017 and 2019 at a tertiary academic center. Indicated reasons for referral were categorized into suspected palpable nodule (SPN), compressive symptoms (CS), metabolic symptoms (MS), screening due to high-risk factors, follow-up of incidental finding on other imaging, and combination of factors. Percentage of ultrasounds with an identifiable nodule and with a nodule recommended for biopsy was compared by indication. Separate logistic regression models were used to identify factors associated with finding any nodule and a biopsy-recommended nodule. Results: Among the 1739 patients included, the most common indication for thyroid ultrasound was SPN (40%), followed by incidental imaging (28%), CS (13%), combination (11%), MS (6%), and high-risk factors (2%). Overall, 62% of ultrasounds identified a nodule. Ultrasounds performed for incidental findings had the highest rate of nodule identification (94%), compared with 55%, 39%, and 43%, for SPN, CS, and MS, respectively (p < 0.05). Only 27% of ultrasounds identified a biopsy-recommended nodule. Nodules found incidentally had the highest rate of biopsy-recommended nodules at 55%. Rates of biopsy-recommended nodules for SPN, CS, and MS were 21%, 6%, and 10%, respectively. Logistic regression demonstrated that compared with patients referred for an SPN, those with incidental nodules were 10 times more likely to have a nodule found on ultrasound (odds ratio [OR] = 10.6 [CI 7.0-16.0]), while those referred for CS were half as likely to have a nodule (OR = 0.5 [CI 0.4-0.7]). Similar factors were associated with identification of biopsy-recommended nodules. Conclusions: Of all new dedicated thyroid ultrasounds, only a quarter find biopsy-recommended nodules, and nearly 40% do not identify a nodule at all. Notably, only 55% of ultrasounds done for SPN found a nodule. Ultrasound for CS and MS had the lowest rates of detecting nodules. Providing clear guidance on when to order thyroid ultrasounds can help reduce unnecessary health care utilization and potential overtreatment.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Adulto , Humanos , Nódulo Tiroideo/patología , Neoplasias de la Tiroides/patología , Estudios Retrospectivos , Biopsia , UltrasonografíaRESUMEN
Golden-winged Warblers (Vermivora chrysoptera, Parulidae) are declining migrant songbirds that breed in the Great Lakes and Appalachian regions of North America. Within their breeding range, Golden-winged Warblers are found in early successional habitats adjacent to mature hardwood forest, and previous work has found that Golden-winged Warbler habitat preferences are scale-dependent. Golden-winged Warbler Working Group management recommendations were written to apply to large regions of the breeding range, but there may be localized differences in both habitat availability and preferences. Rapid declines at the southernmost extent of their breeding range in Western North Carolina necessitate investigation into landscape characteristics governing distribution in this subregion. Furthermore, with the increase in availability of community science data from platforms such as eBird, it would be valuable to know if community science data produces similar distribution models as systemic sampling data. In this study, we described patterns of Golden-winged Warbler presence in Western North Carolina by examining habitat variables at multiple spatial scales using data from standardized Audubon North Carolina (NC) playback surveys and community science data from eBird. We compared model performance and predictions between Audubon NC and eBird models and found that Golden-winged Warbler presence is associated with sites which, at a local scale (150m), have less mature forest, more young forest, more herb/shrub cover, and more road cover, and at a landscape scale (2500m), have less herb/shrub cover. Golden-winged Warbler presence is also associated with higher elevations and smaller slopes. eBird and Audubon models had similar variable importance values, response curves, and overall performance. Based on variable importance values, elevation, mature forest at the local scale, and road cover at the local scale are the primary variables driving the difference between Golden-winged Warbler breeding sites and random background sites in Western North Carolina. Additionally, our results validate the use of eBird data, since they produce species distribution modeling results that are similar to results obtained from more standardized survey methods.
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Passeriformes , Pájaros Cantores , Animales , Región de los Apalaches , Ecosistema , Bosques , Passeriformes/fisiología , Pájaros Cantores/fisiologíaRESUMEN
Exposure to tropospheric ozone pollution impairs photosynthesis and growth in plants and this can have consequences for ecosystems. However, exposure-response research in the United States (U.S.) has historically focused on trees and crops, and less attention has been given to non-crop herbaceous species. We combined U.S. Environmental Protection Agency ozone monitoring data from the entirety of 2016 with published exposure-response relationships from controlled exposure experiments for twenty herbaceous plant species occurring in California. The U.S. Department of Agriculture PLANTS database was used to identify county-level occurrence data of these plant species. A kriged ozone exposure surface for 2016 was generated using data from monitoring stations in California and surrounding states, using Accumulated Ozone exposure over a Threshold of 40 ppb (AOT40) as an exposure metric. County-wide ozone exposure estimations were then combined with published exposure response functions for focal plants, and maps were created to estimate ozone-induced growth losses in the counties where the plants occur. Plant species had estimated annual growth losses from <1 % to >20 % based on exposure levels and sensitivity. Of the 20 species, 17 had predicted biomass loss >5 % in at least one county, emphasizing the vulnerability of herbaceous species at recent ozone concentrations. Butte, Nevada, Plumas, San Luis Obispo, and Shasta Counties, an area of about 31,652 km2, had the highest number of species (6) with >10 % estimated biomass loss, the loss threshold for European critical levels. White clover (Trifolium repens L.) was one of the most affected species with more than an estimated 10 % annual estimated growth loss over 59 % of the state. Overall, these estimated growth losses demonstrate potential for shifts in plant communities and negative effects on ecosystems. This study addresses critical policy needs for risk assessments on herbaceous species in a single year of ozone exposure.
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Contaminantes Atmosféricos , Ozono , Trifolium , Ozono/toxicidad , Ozono/análisis , Biomasa , Ecosistema , Productos Agrícolas , California , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisisRESUMEN
BACKGROUND: Access to emergency surgical care has declined as the rural workforce has decreased. Interhospital transfers of patients are increasingly necessary, and care coordination across settings is critical to quality care. We characterize the role of repeated hospital patient sharing in outcomes of transfers for emergency general surgery (EGS) patients. METHODS: A multicenter study of Wisconsin inpatient acute care hospital stays that involved transfer of EGS patients using data from the Wisconsin Hospital Association, a statewide hospital discharge census for 2016 to 2018. We hypothesized that higher proportion of patients transferred between hospitals would result in better outcomes. We examined the association between the proportion of EGS patients transferred between hospitals and patient outcomes, including in-hospital morbidity, mortality, and length of stay. Additional variables included hospital organizational characteristics and patient sociodemographic and clinical characteristics. RESULTS: One hundred eighteen hospitals transferred 3,197 emergency general surgery patients over the 2-year study period; 1,131 experienced in-hospital morbidity, mortality, or extended length of stay (>75th percentile). Patients were 62 years old on average, 50% were female, and 5% were non-White. In the mixed-effects model, hospitals' proportion of patients shared was associated with lower odds of an in-hospital complication; specifically, when the proportion of patients shared between two hospitals doubled, the relative odds of any outcome changed by 0.85. CONCLUSION: Our results suggest the importance of emergent relationships between hospital dyads that share patients in quality outcomes. Transfer protocols should account for established efficiencies, familiarity, and coordination between hospitals. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.
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Servicios Médicos de Urgencia , Cirugía General , Humanos , Femenino , Estados Unidos , Persona de Mediana Edad , Masculino , Hospitales , Tratamiento de Urgencia , Calidad de la Atención de Salud , Pacientes Internos , Mortalidad Hospitalaria , Transferencia de Pacientes , Estudios RetrospectivosRESUMEN
AIMS: To explore the role of transfer centre nurses and how they facilitate communication between referring and accepting providers during calls about interhospital transfers, including their strategies to overcome communication challenges. DESIGN: A qualitative interview study. METHODS: We conducted semi-structured interviews with 17 transfer centre nurses at one tertiary medical centre from March to August 2019, asking participants to describe their work. We performed content analysis, applying codes based on the Relational Coordination Framework and generating emergent codes, then organized codes in higher-order concepts. We followed the COREQ checklist. RESULTS: Transfer centre nurses employed multiple strategies to mitigate communication challenges. When referring providers had misconceptions about the transfer centre nurse's role and the accepting hospital's processes, the nurses informed referring providers why sharing information with them was necessary. If providers expressed frustrations or lacked understanding about their counterpart's caseload, the nurses managed providers' emotions by letting them "vent," explaining the other provider's situational context and describing the hospital's capabilities. Some nurses also mediated conflict and sought to break the tension if providers debated about the best course of action. When providers struggled to share complete and accurate information, the nurses hunted down details and 'filled in the blanks'. CONCLUSION: Transfer centre nurses perform invisible work throughout the lifespan of interhospital transfers. Nurses' expert knowledge of the transfer process and hospitals' capabilities can enhance provider communication. Meanwhile, providers' lack of knowledge of the nurse's role can impede respectful and efficient transfer conversations. Interventions to support and optimize the transfer centre nurses' critical work are needed. IMPACT: This study describes how transfer centre nurses facilitate communication and overcome challenges during calls about interhospital transfers. An intervention that supports this critical work has the potential to benefit nurses, providers and patients by ensuring accurate and complete information exchange in an effective, efficient manner that respects all parties. PATIENT OR PUBLIC CONTRIBUTION: This study was designed to capture the perspectives and experiences of transfer centre nurses themselves through interviews. Therefore, it was not conducted using input or suggestions from the public or the patient population served by the organization.
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Comunicación , Enfermeras y Enfermeros , Humanos , Rol de la Enfermera , Investigación Cualitativa , HospitalesRESUMEN
BACKGROUND: Regionalization of care has been proposed to optimize outcomes in congenital cardiac surgery (CCS). We hypothesized that hospital infrastructure and systems of care factors could also be considered in regionalization efforts. METHODS: Observed-to-expected (O/E) mortality ratio and hospital volumes were obtained between 2015 and 2018 from public reporting data. Using a resource dependence framework, we examined factors obtained from American Hospital Association, Children's Hospital Association, and hospital websites. Linear regression models were estimated with volume only, then with hospital factors, stratified by procedural complexity. Robust regression models were reestimated to assess the impact of outliers. RESULTS: We found wide variation in the volume of congenital cardiac surgeries performed (89-3920) and in the surgical outcomes (O/E ratio range, 0.3-3.1). Six outlier hospitals performed few high-complexity cases with high mortality. Univariate analysis including all cases indicated that higher volume predicted lower O/E ratio (ß = -0.02; SE = 0.008; P = .011). However, this effect was driven by the most complex cases. Models stratified by The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category show that volume is a significant predictor only in category 5 cases (ß = -1.707; SE = 0.663; P = .012). Robust univariate regression accounting for outliers found no effect of volume on O/E ratio (ß = 0.005; SE = 0.002; P = .975). Elimination of outliers through robust multivariate regression decreased the volume-outcome relationship and found a modest relationship between health plan ownership and outcomes. CONCLUSIONS: Systems of care factors should be considered in addition to volume in designing regionalization in CCS. Patient-level data sets will better define these factors.
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Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Cirugía Torácica , Niño , Estados Unidos , Humanos , Cardiopatías Congénitas/cirugía , Hospitales , Mortalidad HospitalariaRESUMEN
Scabies is a dermatological disease found worldwide. Mainly in tropical regions, it is also the cause of significant morbidity and mortality due to its association with potentially severe secondary bacterial infections. Current treatment strategies for scabies do not consider the role of opportunistic bacteria, and here we investigate whether current and emerging scabicides can offer any anti-bacterial protection. Using the broth microdilution method, we examined antimicrobial potential of the current scabicide ivermectin and emerging scabies treatments: abametapir, manuka oil, and its individual ß-triketones. Our results demonstrate that the two novel scabicides abametapir and manuka oil have antimicrobial properties against common scabies-associated bacteria, specifically Staphylococcus aureus, Streptococcus pyogenes, Streptococcus dysgalactiae subsp. equisimilis and Acinetobacter baumannii. The current scabicide ivermectin offers some antimicrobial activity and is capable of inhibiting the growth aforementioned bacteria. This research is important as it could help to inform future best treatment options of scabies, and scabies-related impetigo.
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There is uncertainty among researchers and clinicians about how to best measure autism spectrum dimensional traits in adults. In a sample of adults with high levels of autism spectrum traits and without intellectual disability (probands, n = 103) and their family members (n = 96), we sought to compare self vs. informant reports of autism spectrum-related traits and possible effects of sex on discrepancies. Using correlational analysis, we found poor agreement between self- and informant-report measures for probands, yet moderate agreement for family members. We found reporting discrepancy was greatest for female probands, often self-reporting more autism-related behaviors. Our findings suggest that autism spectrum traits are often underrecognized by informants, making self-report data important to collect in clinical and research settings.
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Importance: Fine-needle biopsy (FNB) became a critical part of thyroid nodule evaluation in the 1970s. It is not clear how diagnostic accuracy of FNB has changed over time. Objective: To conduct a systematic review and meta-analysis estimating the accuracy of thyroid FNB for diagnosis of malignancy in adults with a newly diagnosed thyroid nodule and to characterize changes in accuracy over time. Data Sources: PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched from 1975 to 2020 using search terms related to FNB accuracy in the thyroid. Study Selection: English-language reports of cohort studies or randomized trials of adult patients undergoing thyroid FNB with sample size of 20 or greater and using a reference standard of surgical histopathology or clinical follow-up were included. Articles that examined only patients with known thyroid disease or focused on accuracy of novel adjuncts, such as molecular tests, were excluded. Two investigators screened each article and resolved conflicts by consensus. A total of 36 of 1023 studies met selection criteria. Data Extraction and Synthesis: The MOOSE guidelines were used for data abstraction and assessing data quality and validity. Two investigators abstracted data using a standard form. Studies were grouped into epochs by median data collection year (1975 to 1990, 1990 to 2000, 2000 to 2010, and 2010 to 2020). Data were pooled using a bivariate mixed-effects model. Main Outcomes and Measures: The primary outcome was accuracy of FNB for diagnosis of malignancy. Accuracy was hypothesized to increase in later time periods, a hypothesis formulated prior to data collection. Results: Of 16â¯597 included patients, 12â¯974 (79.2%) were female, and the mean (SD) age was 47.3 (12.9) years. The sensitivity of FNB was 85.6% (95% CI, 79.9-89.5), the specificity was 71.4% (95% CI, 61.1-79.8), the positive likelihood ratio was 3.0 (95% CI, 2.3-4.1), and the negative likelihood ratio was 0.2 (95% CI, 0.2-0.3). The area under the receiver operating characteristic curve was 86.1%. Epoch was not significantly associated with accuracy. None of the available covariates could explain observed heterogeneity. Conclusions and Relevance: Accuracy of thyroid FNB has not significantly changed over time. Important developments in technique, preparation, and interpretation may have occurred too heterogeneously to capture a consistent uptrend over time. FNB remains a reliable test for thyroid cancer diagnosis.