Ependymomas account for nearly 10% of pediatric intracranial tumors. Surgical resection followed by focal radiation constitutes standard management for children older than 1 year when diagnosed. No ...standard therapy exists for the extremely vulnerable population of infants diagnosed under 12 months-old, including those with leptomeningeal disease dissemination, when nervous system development is extraordinarily rapid and complex. Chemotherapy offers a promising strategy to avoid well-documented radiation-induced toxicities, especially marked neurocognitive impairment. This report describes successful chemotherapy that obviated radiation in two infants with ependymoma associated with leptomeningeal dissemination, PF-A molecular subtype in one and C11orf95-RELA gene fusion in the other. It provides a proof of concept that individualized chemotherapy in select patients can minimize radiation-associated adverse neurocognitive disabilities while promoting cure, despite high-risk clinical and molecular features.
Purpose: To document recent trends in visual function among the United States population aged 70+ years and investigate how the trends can be explained by inter-temporal changes in: (1) population ...sociodemographic characteristics, and chronic disease prevalence, including eye diseases (compositional changes); and (2) effects of the above factors on visual function (structural changes).
Methods: Data from the 1995 Asset and Health Dynamics among the Oldest Old (AHEAD) and the 2010 Health and Retirement Study (HRS) were merged with Medicare Part B claims in the interview years and the 2 previous years. Decomposition analysis was performed. Respondents from both studies were aged 70+ years. The outcome measure was respondent self-reported visual function on a 6-point scale (from 6 = blind to 1 = excellent).
Results: Overall, visual function improved from slightly worse than good (3.14) in 1995 to slightly better than good (2.98) in 2010. A decline in adverse effects of aging on vision was found. Among the compositional changes were higher educational attainment leading to improved vision, and higher prevalence of such diseases as diabetes mellitus, which tended to lower visual function. However, compared to compositional changes, structural changes were far more important, including decreased adverse effects of aging, diabetes mellitus (when not controlling for eye diseases), and diagnosed glaucoma.
Conclusion: Although the US population has aged and is expected to age further, visual function improved among elderly persons, especially among persons 80+ years, likely reflecting a favorable role of structural changes identified in this study in mitigating the adverse effect of ongoing aging on vision.
Background
Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient ...populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within‐visit and previsit DAs for localized prostate cancer, and minority men were oversampled.
Methods
The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12‐item measure) assessed immediately after a urology consultation.
Results
Four sites administered the previsit DA (39 patients), 4 sites administered the within‐visit DA (44 patients), 3 sites administered both previsit and within‐visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within‐visit DA study arm, 67% for the previsit DA only arm, 58% for the within‐visit DA only arm, and 58% for the usual‐care arm. Neither the previsit DA nor the within‐visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P = .132 and P = .977, respectively).
Conclusions
DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge.
This study oversamples minority men and evaluates the effect of 2 decision aids on prostate cancer patients' knowledge. Decision aids are not shown to affect knowledge about prostate cancer treatment options.
Summary The aim of this investigation was to describe the quality of prescription and fabrication of single‐unit crowns by general dental practitioners in Wales. One hundred pre‐piloted ...questionnaires were distributed to commercial laboratories in Wales with large catchment areas, and 20 pre‐piloted questionnaires were distributed to the production laboratory at the Cardiff Dental Hospital. Information was collected relating to the quality of prescription and master impressions for single‐unit crowns. One hundred and seven completed questionnaires were returned (response rate = 89%). Sixty per cent (n = 64) of questionnaires related to single‐unit crowns being made in general practice under private funding arrangements, 30% (n = 32) were being made in general dental practice under National Health Service (public) funding arrangements and 10% (n = 11) were collected from the Dental Hospital. Polyvinylsiloxane impression material was used to record the master impression in all cases (n = 107). Plastic stock trays were used to make the master impression in 79% of cases (n = 85), metal stock trays were used in 19% of cases (n = 20) and special trays were used in 2% of cases (n = 2). Eighty‐five per cent (n = 91) of master casts were considered to be adequate for crown fabrication. Less than 50% of written instructions (n = 52) were considered ‘clear’ and of sufficient detail to adequately specify the planned crown. In 21% of cases (n = 22), the technician had to contact the dentist for clarification of the design prior to making the crown. While the quality of impression making for single‐unit crowns was of a reasonable standard, the quality of the accompanying written communication was poor and more than one‐half of written instructions examined failed to meet the requirements of the European Union Medical Devices Directive.
‘Intracranial mesenchymal tumor, FET‐CREB fusion‐positive’ occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or ...intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome‐wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET‐CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1‐ATF1 and EWSR1‐CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1‐CREM or FUS‐CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma‐like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma‐like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression‐free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH‐like neoplasms and IMMT represent histologic variants of a single tumor type (‘intracranial mesenchymal tumor, FET‐CREB fusion‐positive’) that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity.
We studied the epigenomic landscape of intracranial mesenchymal tumor with FET‐CREB fusion, an emerging CNS tumor entity that occurs primarily in children and young adults. These tumors resolved into two epigenetic subgroups with divergent clinical outcomes that were distinct from meningiomas and all analyzed extracranial sarcomas.
Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent ...or aggressive clinical course. Comprehensive profiling of genetic alterations beyond
NF1
inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas. The first harbored biallelic
NF1
inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology “pilocytic astrocytoma, arising in the setting of NF1”. The second subgroup harbored additional oncogenic alterations including
CDKN2A
homozygous deletion and
ATRX
mutation, occurred primarily during adulthood, followed a more aggressive clinical course, and was epigenetically diverse, with most tumors aligning with either high-grade astrocytoma with piloid features or various subclasses of IDH-wildtype glioblastoma. Several patients were treated with small molecule MEK inhibitors that resulted in stable disease or tumor regression when used as a single agent, but only in the context of those tumors with
NF1
inactivation lacking additional oncogenic alterations. Together, these findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.
Rationale
Epidemiological data indicate that drivers testing positive for an opioid drug are twice as likely to cause a fatal car crash; however, there are limited controlled data available.
...Objectives
The primary aim of this study was to assess the effects of a therapeutic dose range of oxycodone alone and in combination with alcohol on simulated driving performance.
Methods
Healthy participants (
n
= 10) completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Six 7-h sessions were completed during which oxycodone (0, 5, 10 mg, p.o.) was administered 30 min before alcohol (0, 0.8 g/kg (15% less for women), p.o.) for a total of 6 test conditions. Driving assessments and participant-, observer-rated, psychomotor and physiological measures were collected in regular intervals before and after drug administration.
Results
Oxycodone alone (5, 10 mg) did not produce any changes in driving outcomes or psychomotor task performance, relative to placebo (
p
> 0.05); however, 10 mg oxycodone produced increases in an array of subjective ratings, including sedation and impairment (
p
< 0.05). Alcohol alone produced driving impairment (e.g., decreased lateral control) (
p
< 0.05); however, oxycodone did not potentiate alcohol-related driving or subjective effects.
Conclusions
These preliminary data suggest that acute doses of oxycodone (5, 10 mg) do not significantly impair acuity on laboratory-based simulated driving models; however, 10 mg oxycodone produced increases in self-reported outcomes that are not compatible with safe driving behavior (e.g., sedation, impairment). Additional controlled research is needed to determine how opioid misuse (higher doses; parenteral routes of administration) impacts driving risk.
The ENCODE project is an international consortium with a goal of cataloguing all the functional elements in the human genome. The ENCODE Data Coordination Center (DCC) at the University of ...California, Santa Cruz serves as the central repository for ENCODE data. In this role, the DCC offers a collection of high-throughput, genome-wide data generated with technologies such as ChIP-Seq, RNA-Seq, DNA digestion and others. This data helps illuminate transcription factor-binding sites, histone marks, chromatin accessibility, DNA methylation, RNA expression, RNA binding and other cell-state indicators. It includes sequences with quality scores, alignments, signals calculated from the alignments, and in most cases, element or peak calls calculated from the signal data. Each data set is available for visualization and download via the UCSC Genome Browser (http://genome.ucsc.edu/). ENCODE data can also be retrieved using a metadata system that captures the experimental parameters of each assay. The ENCODE web portal at UCSC (http://encodeproject.org/) provides information about the ENCODE data and links for access.
To examine the relationship between prior physician malpractice experience and patients' satisfaction with care.
Women were interviewed using a questionnaire that contained structured and open-ended ...questions.
Mothers of all stillborn infants, infant deaths, and a random sampling of viable infants drawn from 1987 Florida Vital Statistics were sorted into four groups based on the malpractice claims experience of their obstetricians between 1983 and 1986. Interviews were completed with 963 of 1536 women, most by telephone, 53 by in-person interview.
Mothers' responses to closed-ended and open-ended questions about their perceptions of the care they received during their pregnancy, labor, and delivery.
Even though none of the women actually filed a claim, a consistent pattern of differences emerged when comparing women's perceptions of care received. Patients seeing physicians with the most frequent numbers of claims but without high payments were significantly more likely to complain that they felt rushed, never received explanations for tests, and were ignored. In response to the open-ended question, "What part of your care were you least satisfied with?" women seeing physicians in the High Frequency malpractice risk group offered twice as many complaints as those seeing physicians who had never been sued. Problems with physician-patient communication were the most commonly offered complaints.
Physicians who have been sued frequently are more often the objects of complaints about the interpersonal care they provide even by their patients who do not sue.
Conventional disaster preparedness messaging focuses largely on promoting survival actions and communications planning for the immediate post-disaster period. While such preparedness is vital, we ...have long-observed a gap in preventive medicine and disaster planning for building personal resilience--preventatively--to persevere through prolonged recovery timeframes. There are many helpful attitudes and behaviors that people can develop to increase their readiness and capacity for drastic life changes, encompassing not only health-protective preparedness actions but health-promoting attitudes for "minding the risk" and "practicing resilience" as well. For instance, quality of life assessments and well-being interventions are widely-known for the clinically significant improvements they can produce in patient-reported outcomes. Similarly, health promotion interventions are implemented preventatively when a risk is identified yet a disease is not present, and can provide health benefits throughout people's lives, regardless of the type of adversities they eventually encounter (medical, environmental, or other).
We argue there is an overlooked opportunity to leverage well-being theories and methods from clinical settings and public health practice for the purpose of preventatively boosting disaster readiness and bolstering capacity for long-term resilience. We also highlight our previously-published research indicating a role for integrating personal meaning into preparedness messages. This is an opportune time for applying well-being concepts and practices as tools for developing disaster readiness, as risk awareness grows through real-time tracking of hazardous events via social media. For example, two sudden-onset disasters occurred within ten days of each other in 2014 and caught worldwide attention for their extreme hazards, despite dramatic differences in scale. The 22 March 2014 landslide tragedy in Washington State, USA, and the 1 April 2014 Chilean earthquake and Pacific-wide tsunami alerts brought home how persistently vulnerable we all are, and how developing intrinsic personal readiness for scientifically-known risks before disaster unfolds is essential policy. Gap programming that addresses personal readiness challenges in prevention timeframes could save lives and costs. We contend that bridging this readiness gap will prevent situations where people, communities, and systems survive the initial impact, but their resilience trajectories are vulnerable to the challenges of long-haul recovery.
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