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Catheter-associated urinary tract infections in 592 hospitals immediately declined after federal value-based incentive program implementation, but this was fully attributable to a concurrent surveillance case definition revision. Post revision, more hospitals had favorable standardized infection ratios, likely leading to artificial inflation of their performance scores unrelated to changes in patient safety.
Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
The primary aim of the Michigan State University Twin Registry (MSUTR) is to examine developmental differences in genetic, environmental, neural, epigenetic, and neurobiological influences on psychopathology and resilience, particularly during childhood and adolescence. The MSUTR has two broad components: a large-scale, population-based registry of child, adolescent, and adult twins and their families (current N ~30,000) and a series of more focused and in-depth studies drawn from the registry (projected N ~7200). Participants in the population-based registry complete a family health and demographic questionnaire via mail. Families can then be recruited for one or more of the intensive, in-person studies from the population-based registry, using any one of several recruitment strategies (e.g., population-based, based on their answers to the registry questionnaire). These latter studies target a variety of biological, genetic, and environmental phenotypes, including multi-informant measures of psychiatric and behavioral phenotypes, functional and structural neuroimaging, comprehensive measures of the twin family environment (e.g., census and neighborhood informant reports of twin neighborhood characteristics, videotaped interactions of child twin families), buccal swab and salivary DNA samples, and/or assays of adolescent and adult steroid hormone levels. This article provides an overview of the MSUTR and describes current and future research directions.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
The study examined (a) whether alcohol use subgroups could be identified among African Americans assessed from adolescence through early adulthood, and (b) whether subgroup membership was associated with the interaction between internalizing symptoms and antisocial behavior polygenic risk scores (PRSs) and environmental characteristics (i.e., parental monitoring, community disadvantage). Participants (N = 436) were initially recruited for an elementary school-based prevention trial in a Mid-Atlantic city. Youths reported on the frequency of their past year alcohol use from ages 14–26. DNA was obtained from participants at age 21. Internalizing symptoms and antisocial behavior PRSs were created based on a genome-wide association study (GWAS) conducted by Benke et al. (2014) and Tielbeek et al. (2017), respectively. Parental monitoring and community disadvantage were assessed at age 12. Four classes of past year alcohol use were identified: (a) early-onset, increasing; (b) late-onset, moderate use; (c) low steady; and (d) early-onset, decreasing. In high community disadvantaged settings, participants with a higher internalizing symptoms PRS were more likely to be in the early-onset, decreasing class than the low steady class. When exposed to elevated community disadvantage, participants with a higher antisocial behavior PRS were more likely to be in the early-onset, increasing class than the early-onset, decreasing and late-onset, moderate use classes.
Prior work has robustly suggested that social processes in the neighborhood (i.e. informal social control, social cohesion, norms) influence child conduct problems (CP) and related outcomes, but has yet to consider how these community-level influences interact with individual-level genetic risk for CP. The current study sought to do just this, evaluating neighborhood-level social processes as etiologic moderators of child CP for the first time.
We made use of two nested samples of child and adolescent twins within the Michigan State University Twin Registry (MSUTR): 5649 families who participated in in the Michigan Twins Project (MTP) and 1013 families who participated in the Twin Study of Behavioral and Emotional Development (TBED-C). The neighborhood social processes of informal social control, social cohesion, and norms were assessed using neighborhood sampling techniques, in which residents of each twin family's neighborhood reported on the social processes in their neighborhood. Standard biometric GxE analyses evaluated the extent to which they moderated the etiology of CP.
The ‘no moderation’ model provided the best fit to the data in nearly all cases, arguing against neighborhood social processes as etiologic moderators of youth CP.
The neighborhood social processes evaluated here do not appear to exert their effects on child CP via etiologic moderation. The documented links between neighborhood social processes and child CP are thus likely to reflect a different etiologic process. Possibilities include environmental main effects of neighborhood social processes on child CP, or genotype-environment correlations.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Background: While recent clinical trials have demonstrated immense efficacy of mechanical thrombectomy (MT) in the setting of acute stroke, there remains debate over the safety in performing this procedure under general anesthesia (GA). In the Saskatchewan Acute Stroke Pathway, all patients presenting with LVO have endovascular thrombectomy performed under GA. Methods: Data was retrospectively reviewed on 108 consecutive LVO in 2016-2017. All MT were done under GA. Anatomical location of LVO, pre-MT ASPECTS score, post-MT TICI scores and 90-day NIHSS and mRS were recorded. Results: Of 108 LVO, 103 went on to have MT. 44 were right anterior circulation, 50 were left anterior circulation and 9 were posterior circulation. Of 94 anterior circulation strokes, 47 (50.0%), 43 (45.7%) and 4 (4.3%) had good, moderate and poor collateral circulation respectively, and the average pre-MT ASPECTS was 8.6. The average pre-MT NIHSS was 14.7. 81/90 (90.0%) achieved thrombolysis in cerebral infarction (TICI) perfusion scale grade of 2b/3 after recanalization. Average documented 90-day NIHSS was 2.4 and mRS was 2.5. Overall mortality was 21/103 (20.4%). Conclusions: In the Saskatchewan acute stroke pathway, general anesthesia is a safe modality for MT. This adds to the body of evidence supporting GA as a viable option for sedation in MT.
Background: Older adults in the emergency department (ED) take an increasingly larger portion of resources, have increased length of stay and a higher likelihood of adverse outcomes. In many cases bad planning, multiple vague handovers, and lack of coordinated care exacerbate this problem. With the impending onset of our aging population this is a situation that can be expected to compound in complexity in the years to come. Aim Statement: We describe daily interdisciplinary review of ED patients over the age of 75 years (or otherwise identified as a challenging discharge) to discuss barriers and facilitators to discharge/disposition. We will use data to identify the impact of this particular population to ED flow. Measures & Design: This initiative developed from our participation in the Acute Care of the Elderly (ACE) Collaborative and applies Plan/Do/Study/Act (PDSA) cycles and run reports to compare: length of stay; Identification of Seniors at Risk (ISAR) screening tool; ED census, admission/discharge rates, bounce back rates, consulting services, and interdisciplinary participation. Evaluation/Results: The average daily census of our ED between the months of July-October of 2018 was over 211 patients/day, of which over 12% were patients 75 years and older. We conducted over 70 huddles, reviewing an average of 11 patients per day. The average length of stay for patients at the time of the huddle was 19 hours, significantly higher than the general emergency population. Next day admission and discharge rates were comparable, 44.8% and 43.1% respectively with the additional patients remaining in the ED with no disposition. Internal medicine was consulted on 30% of all huddle patients and 38.4% subsequently admitted. Thirty day bounce back rates for huddle patients discharged home was 29.3%. Around 60% of patients 75 and older were screened with the ISAR and 55.7% of these were positive (2 or more questions). Discussion/Impact: Older patients consume a disproportionate amount of ED resources. Daily interdisciplinary ‘geriatric huddles’ improved communication between members of the ED team and with consulting services. The huddles enhanced awareness of the unique demands that older adults place on the flow of the ED, and identified opportunities to enhance patient flow.
Introduction: While boarding of patients in the emergency department (ED) has been well documented and is carefully monitored, the time spent in emergency beds by patients waiting for Adult Protection (AP) placement is often relatively unnoticed, as they are not flagged as ‘admitted’. These patients have no emergency needs, yet consume considerable ED resources, often in excess of patients requiring emergency care. Staff familiarity with this issue may also bias them to premature diagnostic closure of patients as ‘placement problems’, risking misdiagnosis of active medical conditions. An observational study to retrospectively quantify the time spent in the ED by patients referred to AP services for urgent placement from the ED. Methods: A three-year audit of ED social work records of patients referred for AP. Results: For the period of October 1 2015-September 30, 2018, the ED social work service kept records of patients referred for AP from the ED. During this period, a total of 142 patients were referred to AP (40, 50, and 52 in each year respectively). There was an increase of 10 patients between 2015/16 and 2016/17 and two patients from 2016/17 to 2017/18. The overall length of stay for this subset of ED patients during this three-year period was alarmingly high, with an average length of stay of four days per patient (range 2.7 hours-18.5 days) compared to an average of all patients of 4.9 hours and admitted patients of 13.6 hours. Conclusion: Patients in the ED who are referred to AP services consume considerable ED resources, often requiring complete medical work-up, capacity assessments and close monitoring by multiple emergency personnel. This has been reported to cause considerable stress and friction between staff and consulting services. Furthermore, these patients are poorly served in a hectic, brightly lit, and noisy environment. The impact is often not fully appreciated due to ineffective capture by patient tracking systems.
Synthetic biology has a huge potential to produce the next generation of advanced materials by accessing previously unreachable (bio)chemical space. In this prospective review, we take a snapshot of current activity in this rapidly developing area, focusing on prominent examples for high-performance applications such as those required for protective materials and the aerospace sector. The continued growth of this emerging field will be facilitated by the convergence of expertise from a range of diverse disciplines, including molecular biology, polymer chemistry, materials science, and process engineering. This review highlights the most significant recent advances and addresses the cross-disciplinary challenges currently being faced.
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
Available twin-family data on sex differences in antisocial behavior (ASB) simultaneously suggest that ASB is far more prevalent in males than in females, and that its etiology (i.e. the effects of genes, environments, hormones, culture) does not differ across sex. This duality presents a conundrum: How do we make sense of mean sex differences in ASB if not via differences in genes, environments, hormones, and/or cultures? The current selective review and critique explores possible contributions to these seemingly incompatible sets of findings. We asked whether the presence of sex differences in behavior could be smaller than is typically assumed, or confined to a specific set of behaviors. We also asked whether there might be undetected differences in etiology across sex in twin-family studies. We found little evidence that bias or measurement invariance across sex account for phenotypic sex differences in ASB, but we did identify some key limitations to current twin-family approaches. These included the questionable ability of qualitative sex difference analyses to detect gender norms and prenatal exposure to testosterone, and concerns regarding specific analytic components of quantitative sex difference analyses. We conclude that the male preponderance in ASB is likely to reflect a true sex difference in observed behavior. It was less clear, however, that the genetic and environmental contributions to ASB are indeed identical across sex, as argued by prior twin-family studies. It is our hope that this review will inspire the development of new, genetically-informed methods for studying sex differences in etiology.
Official counts of deaths attributed to disasters are often under-reported, thus adversely affecting public health messaging designed to prevent further mortality. During the Oklahoma (USA) May 2013 tornadoes, Oklahoma State Health Department Division of Vital Records (VR; Oklahoma City, Oklahoma USA) piloted a flagging procedure to track tornado-attributed deaths within its Electronic Death Registration System (EDRS). To determine if the EDRS was capturing all tornado-attributed deaths, the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) evaluated three event fatality markers (EFM), which are used to collate information about deaths for immediate response and retrospective research efforts.
Oklahoma identified 48 tornado-attributed deaths through a retrospective review of hospital morbidity and mortality records. The Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) analyzed the sensitivity, timeliness, and validity for three EFMs, which included: (1) a tornado-specific flag on the death record; (2) a tornado-related term in the death certificate; and (3) X37, the International Classification of Diseases, 10th Revision (ICD-10) code in the death record for Victim of a Cataclysmic Storm, which includes tornadoes.
The flag was the most sensitive EFM (89.6%; 43/48), followed by the tornado term (75.0%; 36/48), and the X37 code (56.2%; 27/48). The most-timely EFM was the flag, which took 2.0 median days to report (range 0-10 days), followed by the tornado term (median 3.5 days; range 1-21), and the X37 code (median >10 days; range 2-122). Over one-half (52.1%; 25/48) of the tornado-attributed deaths were missing at least one EFM. Twenty-six percent (11/43) of flagged records had no tornado term, and 44.1% (19/43) had no X37 code. Eleven percent (4/36) of records with a tornado term did not have a flag.
The tornado-specific flag was the most sensitive and timely EFM. Using the flag to collate death records and identify additional deaths without the tornado term and X37 code may improve immediate response and retrospective investigations. Moreover, each of the EFMs can serve as quality controls for the others to maximize capture of all disaster-attributed deaths from vital statistics records in the EDRS.
Issa AN, Baker K, Pate D, Law R, Bayleyegn T, Noe RS. Evaluation of Oklahoma’s Electronic Death Registration System and event fatality markers for disaster-related mortality surveillance – Oklahoma USA, May 2013. Prehosp Disaster Med. 2019;34(2):125–131
To investigate the relative importance of 10 attributes identified in prior studies as essential for effective disaster medical responders and leaders.
Emergency and disaster medical response personnel (N=220) ranked 10 categories of disaster worker attributes in order of their importance in contributing to the effectiveness of disaster responders and leaders.
Attributes of disaster medical leaders and responders were rank ordered, and the rankings differed for leaders and responders. For leaders, problem-solving/decision-making and communication skills were the highest ranked, whereas teamwork/interpersonal skills and calm/cool were the highest ranked for responders.
The 10 previously identified attributes of effective disaster medical responders and leaders include personal characteristics and general skills in addition to knowledge of incident command and disaster medicine. The differences in rank orders of attributes for leaders and responders suggest that when applying these attributes in personnel recruitment, selection, and training, the proper emphasis and priority given to each attribute may vary by role. (Disaster Med Public Health Preparedness. 2019;13:700–703)
Callous-unemotional (CU) traits are critical to developmental, diagnostic, and clinical models of antisocial behaviors (AB). However, assessments of CU traits within large-scale longitudinal and neurobiologically focused investigations remain remarkably sparse. We sought to develop a brief measure of CU traits using items from widely administered instruments that could be linked to neuroimaging, genetic, and environmental data within already existing datasets and future studies.
Data came from a large and diverse sample (n = 4525) of youth (ages~9–11) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study. Moderated nonlinear factor analysis was used to assess measurement invariance across sex, race, and age. We explored whether CU traits were distinct from other indicators of AB, investigated unique links with theoretically-relevant outcomes, and replicated findings in an independent sample.
The brief CU traits measure demonstrated strong psychometric properties and evidence of measurement invariance across sex, race, and age. On average, boys endorsed higher levels of CU traits than girls and CU traits were related to, yet distinguishable from other indicators of AB. The CU traits construct also exhibited expected associations with theoretically important outcomes. Study findings were also replicated across an independent sample of youth.
In a large, multi-site study, a brief measure of CU traits can be measured distinctly from other dimensions of AB. This measure provides the scientific community with a method to assess CU traits in the ABCD sample, as well as in other studies that may benefit from a brief assessment of CU.
For more than four decades after the introduction of cv. Italia (Vitis vinifera L.) in Brazil, several somatic mutations in the genome of cv. Italia and its somatic mutants gave rise to phenotypes which generated at least five new cultivars of fine table grapes. Since no molecular marker proved to be effective in discriminating cv. Italia (V. vinifera L.) and its coloured mutants (Rubi, Benitaka, Brasil, Black Star), primers for the long terminal repeat (LTR) sequences were developed to analyse Inter Retrotransposon Amplified Polymorphism (IRAP) and Retrotransposon-Microsatellite Amplified Polymorphism (REMAP), and investigate how the coloured cultivars derived from clonal propagations of somatic mutations are genetically structured. Primers for LTR sequences of IRAP and REMAP markers were edited from grape sequence databases available at a GenBank. Twenty-four primers, denominated DKS001–DKS024, were edited. Three hundred and forty-nine DNA segments were amplified by individual DKS primers and DKS/ISSR (Inter Simple Sequence Repeats) primer combinations, at an average of 13.96 amplicons per primer pair. High genetic divergence between the five cultivars was inferred from polymorphism in retrotransposons IRAP and REMAP. The analysis of polymorphism of IRAP and REMAP retrotransposons was crucial to show that clonal propagation of somatic mutations may lead towards the formation of genetically divergent cultivars by the formation of genetically structured vineyards and show the mixture of genomes within each cultivar.
Understanding which characteristics of persons with dementia (PWD) and their caregivers are associated with unmet needs can inform strategies to address those needs. Our purpose was to determine the percentage of PWD having unmet needs and significant correlates of unmet needs in PWD.
Cross-sectional data were analyzed using bivariate and hierarchical multiple linear regression analyses.
Participants lived in the greater Baltimore, Maryland and Washington DC suburban area.
A sample of 646 community-living PWD and their informal caregivers participated in an in-home assessment of dementia-related needs.
Unmet needs were identified using the Johns Hopkins Dementia Care Needs Assessment. Correlates of unmet needs were determined using demographic, socioeconomic, clinical, functional and quality of life characteristics of the PWD and their caregivers.
PWD had a mean of 10.6 (±4.8) unmet needs out of 43 items (24.8%). Unmet needs were most common in Home/Personal Safety (97.4%), General Health Care (83.1%), and Daily Activities (73.2%) domains. Higher unmet needs were significantly related to non-white race, lower education, higher cognitive function, more neuropsychiatric symptoms, lower quality of life in PWD, and having caregivers with lower education or who spent fewer hours/week with the PWD.
Unmet needs are common in community-living PWD, and most are non-medical. Home-based dementia care can identify and address PWD’s unmet needs by focusing on care recipients and caregivers to enable PWD to remain safely at home.