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1.
J Am Board Fam Med ; 33(2): 252-261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32179608

RESUMO

PURPOSE: Clinical evidence shows minimal benefit to vitamin D screening and subsequent treatment in the general population. This study aims to assess the effectiveness of 2 light-touch interventions on reducing vitamin D test orders. METHODS: The outcomes were weekly average vitamin D rates, computed from adult primary care encounters (preventive or nonpreventive) with a family medicine (FM) or internal medicine (IM) provider from June 14, 2018 through December 12, 2018. We conducted an interrupted time series analysis and estimated the cost impact of the interventions. The interventions consisted of an educational memo (August 9, 2018) distributed to providers and removal of the vitamin D test (FM: August 15, 2018; IM: October 17, 2018) from the providers' quick order screen in the electronic health record. Change in order rates were analyzed among physicians (MDs and DOs), physician assistants (PAs), and nurse practitioners (NPs). RESULTS: There were 587,506 primary care encounters (FM = 367,947; IM = 219,559). Vitamin D order rates decreased from 6.9% (FM = 5.1%; IM = 9.9%) to 5.2% (FM = 4% [P < .01], IM = 7.9% [P < .01]). For FM, the vitamin D test order rate continued to fall at a 0.08% per week rate after the interventions (end of study: 2.73%). The education intervention showed a relative decrease in each provider type (FM-physician = 16% [P < .01], FM-PA = 47% [P < .01], FM-NP = 20% [P = .01], IM-physician = 14% [P = .02], IM-PA = 52% [P < .01], IM-NP = 34% [P = .04]). Annualized savings was approximately 1 million dollars. CONCLUSIONS: Emailed evidence-based provider education may be an effective tool for modifying providers' vitamin D test ordering behavior. The lack of the effectiveness of the vitamin D test removal from the quick order screen found for IM highlights the challenges facing simple electronic health record interventions when multiple alternate ordering pathways exist.

2.
Sci Rep ; 10(1): 4683, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170117

RESUMO

Large litter sizes have resulted in more piglets being exposed to intrauterine growth restriction (IUGR). Growth restriction during fetal life is linked with lower growth efficiency and increased susceptibility to infections in postnatal life and IUGR may associate with an altered innate immune system. We investigated the haematological, thromboelastography and plasma biochemical profiles of IUGR and normal piglets as well as cytokine responses in peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS) at 24 days of age. Piglets were classified at birth based on their head morphology as either IUGR or normal. The present study showed a modulation of the immune function of IUGR pigs, characterized by an increase in neutrophil percentage and fibrinogen levels but a decrease in CD4+ T-cells. A lower level of LPS-induced IL-1ß production was evident in IUGR pigs, suggesting immunological hypo-responsiveness. Furthermore, higher levels of reticulocytes, MCV and MCH and lower levels of erythrocytes in IUGR pigs suggest altered bone marrow hematopoiesis. All together, the results suggest a moderate suppression of the immune response of IUGR piglets, which may have implications for resistance to pathogen challenges in the post-weaning period. Serum metabolites and blood clotting profile did not differ between IUGR and normal piglets.

3.
Mol Immunol ; 121: 127-135, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32200170

RESUMO

Consumption of fermentable dietary fibres, such as inulin, or administration of helminth products (e.g. Trichuris suis ova) have independently been shown to alleviate inflammation in vivo. We recently found that dietary inulin and T. suis infection in pigs co-operatively suppressed type-1 inflammatory responses in the gut, suggesting the potential of dietary components to augment anti-inflammatory responses induced by certain helminths. Here, we explored whether T. suis antigens and inulin could directly suppress inflammatory responses in vitro in a cooperative manner. T. suis soluble products (TsSP) strongly suppressed lipopolysaccharide (LPS)-induced IL-6 and TNF-α secretion from murine macrophages and induced an anti-inflammatory phenotype as evidenced by transcriptomic and gene pathway analyses. Inulin regulated the expression of a small number of genes and transcriptional pathways in macrophages after exposure to LPS, but did not enhance the suppressive activity of TsSP, either directly or in co-culture experiments with intestinal epithelial cells. Culture of macrophages with short-chain fatty acids, the products of microbial fermentation of inulin, did however appear to enhance TsSP-mediated inhibition of TNF-α production. Our results confirm a direct role for helminth products in suppressing inflammatory responses in macrophages. In contrast, inulin had little capacity to directly modulate LPS-induced responses. Our results suggest distinct mode-of-actions of T. suis and inulin in regulating inflammatory responses, and that the role of inulin in modulating the response to helminth infection may be dependent on other factors such as production of metabolites by the gut microbiota.

4.
BMJ Open ; 10(2): e026168, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32086347

RESUMO

OBJECTIVE: To examine the association between high maternal weight status and complications during pregnancy and delivery. SETTING: Scotland. PARTICIPANTS: Data from 132 899 first-time singleton deliveries in Scotland between 2008 and 2015 were used. Women with overweight and obesity were compared with women with normal weight. Associations between maternal body mass index and complications during pregnancy and delivery were evaluated. OUTCOME MEASURES: Gestational diabetes, gestational hypertension, pre-eclampsia, placenta praevia, placental abruption, induction of labour, elective and emergency caesarean sections, pre-term delivery, post-term delivery, low Apgar score, small for gestational age and large for gestational age. RESULTS: In the multivariable models controlling for potential confounders, we found that, compared with women with normal weight, the odds of the following outcomes were significantly increased for women with overweight and obesity (overweight adjusted ORs; 95% CI, followed by the same for women with obesity): gestational hypertension (1.61; 1.49 to 1.74), (2.48; 2.30 to 2.68); gestational diabetes (2.14; 1.86 to 2.46), (8.25; 7.33 to 9.30); pre-eclampsia (1.46; 1.32 to 1.63) (2.07; 1.87 to 2.29); labour induction (1.28; 1.23 to 1.33), (1.69; 1.62 to 1.76) and emergency caesarean section (1.82; 1.74 to 1.91), (3.14; 3.00 to 3.29). CONCLUSIONS: Women with overweight and obesity in Scotland are at greater odds of adverse pregnancy and delivery outcomes. The odds of these conditions increases with increasing body mass index. Health professionals should be empowered and trained to deliver promising dietary and lifestyle interventions to women at risk of overweight and obesity prior to conception, and control excessive weight gain in pregnancy.

5.
Pediatr Blood Cancer ; 67(5): e28153, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32072730

RESUMO

BACKGROUND: Image-guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma. PROCEDURE: A multi-institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3-year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children's Oncology Group for risk stratification. RESULTS: A total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P < .05; and 58.0% vs. 88.5%, P < .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy. CONCLUSIONS: PCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real-time pathology assessment of specimen quality.

8.
J Pediatr Surg ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32067810

RESUMO

PURPOSE: Rapid sequence intubation (RSI) drugs, such as propofol, affect clinical outcomes, but this has not been examined in the pediatric population. This descriptive study compares the outcomes associated with intubation drugs used in pediatric traumatic brain injury (TBI) patients. METHODS: A retrospective chart review and descriptive analysis of intubated TBI patients, ages 0-17, admitted to Children's Hospital London Health Sciences Centre (LHSC) from January 2006-December 2016 was performed. RESULTS: Out of 259 patients intubated, complete data was available for 107 cases. Average injury severity score was 28; 46 were intubated at LHSC, 55 at primary care site, and 6 on scene. Intubation attempts were recorded in 87 of 107 paper charts. First-pass intubation success rate was 88.5%. Propofol (n = 21), midazolam (n = 31), etomidate (n = 13), and ketamine (n = 7) were the most commonly used intubation drugs. Paralytics were used in 50% of patients. Following use of propofol, Pediatric Adjusted Shock Index was increased as a result of worsening hypotension. Mean total hospital length of stay was 21 days with 7.5 days in ICU. Survival was 87%. CONCLUSION: Great variability exists in the use of induction agents and paralytics for RSI. Propofol was commonly used and is potentially associated with poorer clinical outcomes. TYPE OF STUDY: Retrospective. LEVEL OF EVIDENCE: IV.

9.
JAMA Netw Open ; 3(1): e1919954, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31995214

RESUMO

Importance: The number of patients presenting to emergency departments (EDs) for psychiatric care continues to increase. Psychiatrists often make a conservative recommendation to admit patients because robust outpatient services for close follow-up are lacking. Objective: To assess whether the availability of a 45-day behavioral health-virtual patient navigation program decreases hospitalization among patients presenting to the ED with a behavioral health crisis or need. Design, Setting, and Participants: This randomized clinical trial enrolled 637 patients who presented to 6 EDs spanning urban and suburban locations within a large integrated health care system in North Carolina from June 12, 2017, through February 14, 2018; patients were followed up for up to 45 days. Eligible patients were aged 18 years or older, with a behavioral health crisis and a completed telepsychiatric ED consultation. The availability of the behavioral health-virtual patient navigation intervention was randomly allocated to specific days (Monday through Friday from 7 am to 7 pm) so that, in a 2-week block, there were 5 intervention days and 5 usual care days; 323 patients presented on days when the program was offered, and 314 presented on usual care days. Data analysis was performed from March 7 through June 13, 2018, using an intention-to-treat approach. Interventions: The behavioral health-virtual patient navigation program included video contact with a patient while in the ED and telephonic outreach 24 to 72 hours after discharge and then at least weekly for up to 45 days. Main Outcomes and Measures: The primary outcome was the conversion of an ED encounter to hospital admission. Secondary outcomes included 45-day follow-up encounters with a self-harm diagnosis and postdischarge acute care use. Results: Among 637 participants, 358 (56.2%) were men, and the mean (SD) age was 39.7 (16.6) years. The conversion rates were 55.1% (178 of 323) in the intervention group vs 63.1% (198 of 314) in the usual care group (odds ratio, 0.74; 95% CI, 0.54-1.02; P = .06). The percentage of patient encounters with follow-up encounters having a self-harm diagnosis was significantly lower in the intervention group compared with the usual care group (36.8% [119 of 323] vs 45.5% [143 of 314]; P = .03). Conclusions and Relevance: Although the primary result did not reach statistical significance, there is a strong signal of potential positive benefit in an area that lacks evidence, suggesting that there should be additional investment and inquiry into virtual behavioral health programs. Trial Registration: ClinicalTrials.gov identifier: NCT03204643.


Assuntos
Terapia Comportamental/métodos , Serviço Hospitalar de Emergência , Transtornos Mentais/terapia , Admissão do Paciente/estatística & dados numéricos , Telemedicina/organização & administração , Adulto , Medicina do Comportamento/métodos , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , North Carolina , Autogestão/educação , Resultado do Tratamento , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-31958106

RESUMO

PURPOSE: To characterize evolution of macular injury from a high-powered blue handheld laser using multimodal imaging and describe successful surgical treatment. METHODS: Observational clinical case report. RESULTS: A 17-year-old boy presented with unilateral acute loss of vision with discrete white macular lesions, full-thickness disruption of retinal layers, and hyperreflective material at the fovea on optical coherence tomography caused by exposure to a 445 nm blue-light handheld laser with power up to 2,000 mW characterized as a Class IV laser. The injury evolved into an approximately 950-µm full-thickness macular hole 3 weeks later with visual acuity of 20/400. Vitrectomy and internal limiting membrane peel resulted in anatomic success and final vision at 4 months of 20/25. CONCLUSION: High-powered lasers can induce significant disruption of retinal layers, inflammatory debris, and full-thickness macular holes with momentary exposure that, despite poor anatomic prognostic factors, can have successful surgical outcomes.

11.
PLoS One ; 15(1): e0226718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910437

RESUMO

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) after cerebral infarction is a complex and multifactorial phenomenon in the acute stage of ischemic stroke, and often results in a poor prognosis. Thus, identifying risk factors and making an early prediction of HT in acute cerebral infarction contributes not only to the selections of therapeutic regimen but also, more importantly, to the improvement of prognosis of acute cerebral infarction. The purpose of this study was to develop and validate a model to predict a patient's risk of HT within 30 days of initial ischemic stroke. METHODS: We utilized a retrospective multicenter observational cohort study design to develop a Lasso Logistic Regression prediction model with a large, US Electronic Health Record dataset which structured to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). To examine clinical transportability, the model was externally validated across 10 additional real-world healthcare datasets include EHR records for patients from America, Europe and Asia. RESULTS: In the database the model was developed, the target population cohort contained 621,178 patients with ischemic stroke, of which 5,624 patients had HT within 30 days following initial ischemic stroke. 612 risk predictors, including the distance a patient travels in an ambulance to get to care for a HT, were identified. An area under the receiver operating characteristic curve (AUC) of 0.75 was achieved in the internal validation of the risk model. External validation was performed across 10 databases totaling 5,515,508 patients with ischemic stroke, of which 86,401 patients had HT within 30 days following initial ischemic stroke. The mean external AUC was 0.71 and ranged between 0.60-0.78. CONCLUSIONS: A HT prognostic predict model was developed with Lasso Logistic Regression based on routinely collected EMR data. This model can identify patients who have a higher risk of HT than the population average with an AUC of 0.78. It shows the OMOP CDM is an appropriate data standard for EMR secondary use in clinical multicenter research for prognostic prediction model development and validation. In the future, combining this model with clinical information systems will assist clinicians to make the right therapy decision for patients with acute ischemic stroke.

12.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999321

RESUMO

The composition of dietary macronutrients (proteins, carbohydrates, and fibers) and micronutrients (vitamins, phytochemicals) can markedly influence the development of immune responses to enteric infection. This has important implications for livestock production, where a significant challenge exists to ensure healthy and productive animals in an era of increasing drug resistance and concerns about the sector's environmental footprint. Nutritional intervention may ultimately be a sustainable method to prevent disease and improve efficiency of livestock enterprises, and it is now well established that certain phytonutrients can significantly improve animal performance during challenge with infectious pathogens. However, many questions remain unanswered concerning the complex interplay between diet, immunity, and infection. In this review, we examine the role of phytonutrients in regulating immune and inflammatory responses during enteric bacterial and parasitic infections in livestock, with a specific focus on some increasingly well-studied phytochemical classes-polyphenols (especially proanthocyanidins), essential oil components (cinnamaldehyde, eugenol, and carvacrol), and curcumin. Despite the contrasting chemical structures of these molecules, they appear to induce a number of similar immunological responses. These include promotion of mucosal antibody and antimicrobial peptide production, coupled with a strong suppression of inflammatory cytokines and reactive oxygen species. Although there have been some recent advances in our understanding of the mechanisms underlying their bioactivity, how these phytonutrients modulate immune responses in the intestine remains mostly unknown. We discuss the complex inter-relationships between metabolism of dietary phytonutrients, the gut microbiota, and the mucosal immune system, and propose that an increased understanding of the basic immunological mechanisms involved will allow the rational development of novel dietary additives to promote intestinal health in farmed animals.

13.
Ann Am Thorac Soc ; 17(1): 89-97, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31644304

RESUMO

Rationale: Postsepsis care recommendations target specific deficits experienced by sepsis survivors in elements such as optimization of medications, screening for functional impairments, monitoring for common and preventable causes of health deterioration, and consideration of palliative care. However, few data are available regarding the application of these elements in clinical practice.Objectives: To quantify the delivery of postsepsis care for patients discharged after hospital admission for sepsis and evaluate the association between receipt of postsepsis care elements and reduced mortality and hospital readmission within 90 days.Methods: We conducted a retrospective chart review of a random sample of patients who were discharged alive after an admission for sepsis (identified from International Classification of Diseases, 10th Revision discharge codes) at 10 hospitals during 2017. We used a structured chart abstraction to determine whether four elements of postsepsis care were provided within 90 days of hospital discharge, per expert recommendations. We used multivariable logistic regression to evaluate the association between receipt of care elements and 90-day hospital readmission and mortality, adjusted for age, comorbidity, length of stay, and discharge disposition.Results: Among 189 sepsis survivors, 117 (62%) had medications optimized, 123 (65%) had screening for functional or mental health impairments, 86 (46%) were monitored for common and preventable causes of health deterioration, and 110 (58%) had care alignment processes documented (i.e., assessed for palliative care or goals of care). Only 20 (11%) received all four care elements within 90 days. Within 90 days of discharge, 66 (35%) patients were readmitted and 33 (17%) died (total patients readmitted or died, n = 82). Receipt of two (odds ratio [OR], 0.26; 95% confidence interval [95% CI], 0.10-0.69) or more (three OR, 0.28; 95% CI, 0.11-0.72; four OR, 0.12; 95% CI, 0.03-0.50) care elements was associated with lower odds of 90-day readmission or 90-day mortality compared with zero or one element documented. Optimization of medications (no medication errors vs. one or more errors; OR, 0.44; 95% CI, 0.21-0.92), documented functional or mental health assessments (physical function plus swallowing/mental health assessments vs. no assessments; OR, 0.14; 95% CI, 0.05-0.40), and documented goals of care or palliative care screening (OR, 0.52; 95% CI, 0.25-1.05; not statistically significant) were associated with lower odds of 90-day readmission or 90-day mortality.Conclusions: In this retrospective cohort study of data from a single health system, we found variable delivery of recommended postsepsis care elements that were associated with reduced morbidity and mortality after hospitalization for sepsis. Implementation strategies to efficiently overcome barriers to adopting recommended postsepsis care may help improve outcomes for sepsis survivors.

14.
Immunology ; 159(3): 322-334, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31705653

RESUMO

Dendritic cells (DCs) are essential for generating T-cell-based immune responses through sensing of potential inflammatory and metabolic cues in the local environment. However, there is still limited insight into the processes defining the resultant DC phenotype, including the type of early transcriptional changes in pro-inflammatory cues towards regulatory or type 2 immune-based cues induced by a variety of exogenous and endogenous molecules. Here we compared the ability of a selected number of molecules to modulate the pro-inflammatory phenotype of lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-stimulated human monocyte-derived DCs towards an anti-inflammatory or regulatory phenotype, including Ascaris suum body fluid [helminth pseudocoelomic fluid (PCF)], the metabolites succinate and butyrate, and the type 2 cytokines thymic stromal lymphopoietin and interleukin-25. Our data show that helminth PCF and butyrate treatment suppress the T helper type 1 (Th1)-inducing pro-inflammatory DC phenotype through induction of different transcriptional programs in DCs. RNA sequencing indicated that helminth PCF treatment strongly inhibited the Th1 and Th17 polarizing ability of LPS + IFN-γ-matured DCs by down-regulating myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways in Toll-like receptor 4 signaling. By contrast, butyrate treatment had a strong Th1-inhibiting action, and transcripts encoding important gut barrier defending factors such as IL18, IL1B and CXCL8 were up-regulated. Collectively, our results further understanding of how compounds from parasites and gut microbiota-derived butyrate may exert immunomodulatory effects on the host immune system.

15.
Arch Dis Child ; 105(2): 197-198, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30381289
16.
Public Health Rep ; 135(1): 47-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31725345

RESUMO

OBJECTIVE: Cardiometabolic disease is the leading cause of mortality in the United States. Cardiometabolic function during adolescence predicts future cardiometabolic disease, yet few studies have examined early determinants of cardiometabolic function. Informed by evidence of sex differences in the prevalence and severity of cardiometabolic disorders and evidence of sexual dimorphism in the stress response, we examined sex differences in the association between living in poverty and cardiometabolic function during adolescence, a precursor of later cardiometabolic disorders. METHODS: We linked data from 10 415 adolescents aged 12-19 in the National Health and Nutrition Examination Survey (1999-2012) with US Census-tract data on area-level poverty (percentage of the population living in poverty, grouped into quartiles). We parameterized cardiometabolic dysfunction by summing the z scores of 6 cardiometabolic biomarkers, grouped into quintiles. Hierarchical ordinal models estimated associations. RESULTS: Compared with residents in low-poverty areas, residents in high-poverty areas had elevated odds of cardiometabolic dysfunction (highest quartile of poverty odds ratio [OR] = 1.27; 95% confidence interval [CI], 1.08-1.50). This association was more pronounced among boys than girls (highest quartile of poverty for boys: OR = 1.36; 95% CI, 1.10-1.70; highest quartile of poverty for girls: OR = 1.17; 95% CI, 0.94-1.47). CONCLUSION: Our study supports the existence of sex-specific associations. These results highlight the potential for community-based programs, such as housing assistance, to improve population health.

17.
Sci Rep ; 9(1): 18226, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796879

RESUMO

Anticipation is the ability to accurately predict future actions or events ahead of the act itself. When attempting to anticipate, researchers have identified that at least two broad sources of information are used: contextual information relating to the situation in question; and biological motion from postural cues. However, the neural correlates associated with the processing of these different sources of information across groups varying in expertise has yet to be examined empirically. We compared anticipation performance and electrophysiological activity in groups of expert (n = 12) and novice (n = 15) performers using a video-based task. Participants made anticipation judgements after being presented information under three conditions: contextual information only; kinematic information only; and both sources of information combined. The experts responded more accurately across all three conditions. Stronger alpha event-related desynchronization over occipital and frontocentral sites occurred in experts compared to the novices when anticipating. The experts relied on stronger preparatory attentional mechanisms when they processed contextual information. When kinematic information was available, the domain specific motor representations built up over many years of practice likely underpinned expertise. Our findings have implications for those interested in identifying and subsequently, enhancing the neural mechanisms involved in anticipation.

18.
Trials ; 20(1): 660, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783900

RESUMO

BACKGROUND: Hospital mortality for patients with sepsis has recently declined, but sepsis survivors still suffer from significant long-term mortality and morbidity. There are limited data that support effective strategies to address post-discharge management of patients hospitalized with sepsis. METHODS: The Improving Morbidity during Post-Acute Care Transitions for Sepsis (IMPACTS) study is a pragmatic, randomized controlled trial at three hospitals within a single healthcare delivery system comparing clinical outcomes between sepsis survivors who receive usual care versus care delivered through the Sepsis Transition and Recovery (STAR) program. The STAR program includes a centrally located nurse navigator using telephone counseling and electronic health record-based support to facilitate best-practice post-sepsis care strategies for patients during hospitalization and the 30 days after hospital discharge, including post-discharge review of medications, evaluation for new impairments or symptoms, monitoring existing comorbidities, and palliative care referral when appropriate. Adults admitted through the Emergency Department with suspected infection (i.e., antibiotics initiated, bacterial cultures drawn) and deemed, by previously developed risk-stratification models, high risk for readmission or death are included. Eligible patients are randomly allocated 1:1 to either Arm 1, usual care or Arm 2, STAR. Planned enrollment is 708 patients during a 6-month period. The primary outcome is the composite of all-cause hospital readmissions and mortality assessed 30 days post discharge. Secondary outcomes include 30- and 90-day hospital readmissions, mortality, emergency department visits, acute care-free days alive, and acute care and total costs. DISCUSSION: This pragmatic evaluation provides the most comprehensive assessment to date of a strategy to improve delivery of recommended post-sepsis care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03865602. Registered retrospectively on 6 March 2019.

19.
Mutat Res ; 847: 403035, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31699340

RESUMO

The working group reached complete or majority agreement on many issues. Results from TGR and in vivo comet assays for 91 chemicals showed they have similar ability to detect in vivo genotoxicity per se with bacterial mutagens and Ames-positive carcinogens. TGR and comet assay results were not significantly different when compared with IARC Group 1, 2 A, and unclassified carcinogens. There were significantly more comet assay positive responses for Group 2B chemicals, and for IARC classified and unclassified carcinogens combined, which may be expected since mutation is a sub-set of genotoxicity. A liver comet assay combined with the bone marrow/blood micronucleus (MNviv) test would detect in vivo genotoxins that do not exhibit tissue-specific or site-of-contact effects, and is appropriate for routine in vivo genotoxicity testing. Generally for orally administered substances, a comet assay at only one site-of-contact GI tract tissue (stomach or duodenum/jejunum) is required. In MNviv tests, evidence of target tissue exposure can be obtained in a number of different ways, as recommended by ICH S2(R1) and EFSA (Hardy et al., 2017). Except for special cases the i.p. route is inappropriate for in vivo testing; for risk evaluations more weight should be given to data from a physiologically relevant administration route. The liver MN test is sufficiently validated for the development of an OECD guideline. However, the impact of dosing animals >6 weeks of age needs to be evaluated. The GI tract MN test shows promise but needs more validation for an OECD guideline. The Pig-a assay detects systemically available mutagens and is a valuable follow-up to in vitro positive results. A new freeze-thaw protocol provides more flexibility. Mutant reticulocyte and erythrocyte frequencies should both be determined. Preliminary data are available for the Pig-a assay in male rat germ cells which require validation including germ cell DNA mutation origin.

20.
Seizure ; 73: 51-55, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31743826

RESUMO

PURPOSE: Non-epileptic seizures are paroxysmal events which to an observer resemble epileptic seizures. Proposed risk factors incorporate biopsychosocial aspects including factors in the affected individual. Unexpectedly high rates of autism spectrum disorder (ASD) occurred in the clinical population reported here. Although elevated levels of psychiatric co-morbidity are known to be present in patients with NES, ASD has only been previously described in a single case report. METHODS: This case series captures rates of ASD in 59 children and young people who were referred to a specialist paediatric mental health service at Great Ormond Street Hospital, London, UK for assessment and treatment of non-epileptic seizures between 2012 and 2016. RESULTS: 10/59 (16.9%) of the children and young people with non-epileptic seizures also had ASD, with 5/10 (50%) of these undiagnosed with ASD before referral. Children and young people with ASD were significantly more likely to have tics or attention-deficit hyperactivity disorder than those without ASD. CONCLUSION: ASD may be a common co-morbidity in non-epileptic seizures. Careful clinical assessment with consideration of ASD traits is therefore important in the non-epileptic seizures population. It is beneficial to diagnose ASD early as its presence is likely to require a modified approach to assessment and treatment of non-epileptic seizures. Study of the development of non-epileptic seizures in ASD may suggest hypotheses for the pathogenesis of non-epileptic seizures in the wider population.

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