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AbstractObjective:To implement and evaluate a point-of-care (POC) molecular testing platform for respiratory viruses in congregate living settings (CLS).Design:Prospective quality improvement study.Setting:Seven CLS, including three nursing homes and four independent-living facilities.Participants:Residents of CLS.Methods:A POC platform for COVID-19, influenza A and B, and respiratory syncytial virus was implemented at participating CLS from December 1, 2022 to April 15, 2023. Residents with respiratory symptoms underwent paired testing, with respiratory specimens tested first with the POC platform and then delivered to an off-site laboratory for multiplex respiratory virus panel (MRVP) polymerase chain reaction (PCR) as per standard protocol. Turn-around time and diagnostic accuracy of the POC platform were compared against MRVP PCR. In an exploratory analysis, time to outbreak declaration among participating CLS was compared against a convenience sample of 19 CLS that did not use the POC platform.Results:A total of 290 specimens that underwent paired testing were included. Turn-around time to result was significantly shorter with the POC platform compared to MRVP PCR, with median difference of 36.2 hours (interquartile range 21.8–46.4 hours). The POC platform had excellent diagnostic accuracy compared to MRVP PCR, with area under the curve statistic of .96. Time to outbreak declaration was shorter in CLS that used the POC platform compared to CLS that did not.Conclusion:Rapid POC testing platforms for respiratory viruses can be implemented in CLS, with high diagnostic accuracy, expedited turn-around times, and shorter time to outbreak declaration.

AbstractBackground:Older adults residing in congregate living settings (CLS) such as nursing homes and independent living facilities remain at increased risk of morbidity and mortality from coronavirus disease 2019. We performed a prospective multicenter study of consecutive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) exposures to identify predictors of transmission in this setting.Methods:Consecutive resident SARS-CoV-2 exposures across 17 CLS were prospectively characterized from 1 September 2022 to 1 March 2023, including factors related to environment, source, and exposed resident. Room size, humidity, and ventilation were measured in locations where exposures occurred. Predictors were incorporated in a generalized estimating equation model adjusting for the correlation within CLS.Results:Among 670 consecutive exposures to SARS-CoV-2 across 17 CLS, transmission occurred among 328 (49.0%). Increased risk was associated with nursing homes (odds ratio (OR) = 90.8; 95% CI, 7.8–1047.4), Jack and Jill rooms (OR = 2.2; 95% CI, 1.3–3.6), from source who was pre-symptomatic (OR = 11.2; 95% CI, 4.1–30.9), symptomatic (OR = 6.5; 95% CI, 1.4–29.9), or rapid antigen test positive (OR = 35.6; 95% CI, 5.6–225.6), and in the presence of secondary exposure (OR = 6.3; 95% CI, 1.6–24.0). Exposure in dining room was associated with reduced risk (OR = 0.02; 95% CI, 0.005–0.08) as was medium room size (OR = 0.3; 95% CI, 0.2–0.6). Recent vaccination of exposed resident (OR = 0.5; 95% CI, 0.3–1.0) and increased ventilation of room (OR = 0.9; 95% CI, 0.8–1.0) were marginally associated with reduced risk.Conclusion:Prospective assessment of SARS-CoV-2 exposures in CLS suggests that source characteristics and location of exposure are most predictive of resident transmission. These findings can inform risk assessment and further opportunities to prevent transmission in CLS.

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Patients and families preferring languages other than English (LOE) often experience inequitable communication with their health care providers, including the underutilization of professional interpretation. This study had 2 aims: to characterize resident-perceived communication with families preferring LOE and to evaluate the impact of language preference on frequency of resident interactions with hospitalized patients and families.This was a cross-sectional study at a quaternary care children’s hospital. We developed a questionnaire for residents regarding their interactions with patients preferring LOE. We concurrently developed a communication tracking tool to measure the frequency of resident communication events with hospitalized patients. Data were analyzed with logistic and Poisson regression models.Questionnaire results demonstrated a high level of resident comfort with interpretation, though more than 30% of residents reported “sometimes” or “usually” communicating with families preferring LOE without appropriate interpretation (response rate, 47%). The communication tracking tool was completed by 36 unique residents regarding 151 patients, with a 95% completion rate. Results demonstrated that patients and families preferring LOE were less likely to be present on rounds compared with their counterparts preferring English (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.07–0.39). Similarly, patients and families preferring LOE were less likely to receive a resident update after rounds (adjusted odds ratio, 0.29; 95% CI, 0.13–0.62) and received fewer resident updates overall (incidence rate ratio, 0.45; 95% CI, 0.30–0.69).Hospitalized patients and families preferring LOE experience significant communication-related inequities. Ongoing efforts are needed to promote equitable communication with this population and should consider the unique role of residents.

Skating produces all sorts of stories: slams, makes, spots, random street weirdos, and so on. Even the tall tales often have a nugget of truth within them. Here are some [...]

The future will see the affluent elderly receiving the best care, while less affluent elderly will need to depend on public programs that must serve a broad demographic. Conflicting demands that must be balanced will include autonomy, choice, cultural competence, access, good jobs, and reasonable cost.

AbstractBackground:Widespread testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) is necessary to curb the spread of coronavirus disease 2019 (COVID-19), but testing is undermined when the only option is a nasopharyngeal swab. Self-collected swab techniques can overcome many of the disadvantages of a nasopharyngeal swab, but they require evaluation.Methods:Three self-collected non-nasopharyngeal swab techniques (saline gargle, oral swab and combined oral-anterior nasal swab) were compared to a nasopharyngeal swab for SARS-CoV-2 detection at multiple COVID-19 assessment centers in Toronto, Canada. The performance characteristics of each test were assessed.Results:The adjusted sensitivity of the saline gargle was 0.90 (95% CI 0.86-0.94), the oral swab was 0.82 (95% CI, 0.72–0.89) and the combined oral–anterior nasal swab was 0.87 (95% CI, 0.77–0.93) compared to a nasopharyngeal swab, which demonstrated a sensitivity of ˜90% when all positive tests were the reference standard. The median cycle threshold values for the SARS-CoV-2 E-gene for concordant and discordant saline gargle specimens were 17 and 31 (P< .001), for the oral swabs these values were 17 and 28 (P< .001), and for oral–anterior nasal swabs these values were 18 and 31 (P= .007).Conclusions:Self-collected saline gargle and an oral–anterior nasal swab have a similar sensitivity to a nasopharyngeal swab for the detection of SARS-CoV-2. These alternative collection techniques are cheap and can eliminate barriers to testing, particularly in underserved populations.

There are few options available to elders who need home-based, long-term care. This article reports on the experience of a managed care model that attempts to integrate insurance funding with a point-of-service delivery system.

While deployed to the 5th Fleet AOR in support of maritime operations in the Gulf of Aden, an A/S32A-32 spotting dolly, a familiar workhorse in shipboard aviation, crunched an embarked [...]

An insider-versus-outsider concept of advocacy captures the major differences in behavior between people working in a bureaucratic institution or agency and those working outside. Inside and outside advocates need to understand their different roles in the policy process where they may cooperate at one time and contest each other at another, but they should base their interaction on mutual respect.

The KEAP1–NRF2-mediated cytoprotective response plays a key role in cellular homoeostasis. Insufficient NRF2 signaling during chronic oxidative stress may be associated with the pathophysiology of several diseases with an inflammatory component, and pathway activation through direct modulation of the KEAP1–NRF2 protein–protein interaction is being increasingly explored as a potential therapeutic strategy. Nevertheless, the physicochemical nature of the KEAP1–NRF2 interface suggests that achieving high affinity for a cell-penetrant druglike inhibitor might be challenging. We recently reported the discovery of a highly potent tool compound which was used to probe the biology associated with directly disrupting the interaction of NRF2 with the KEAP1 Kelch domain. We now present a detailed account of the medicinal chemistry campaign leading to this molecule, which included exploration and optimization of protein–ligand interactions in three energetic “hot spots” identified by fragment screening. In particular, we also discuss how consideration of ligand conformational stabilization was important to its development and present evidence for preorganization of the lead compound which may contribute to its high affinity and cellular activity.

In the beginning, there was no skate stoke. It is a powerful gift (and some say curse) bestowed to Earth after escaping to our planet from a higher dimension. In [...]

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SURRENDERING THE HELM IN STYLE Philip Caldwell, who has just retired as chairman after a 31-year-career at Ford Motor Company and who has been named Automotive Industries' 1985 Man of [...]

I'm writing in response to your article about bi-fuel CNG (compressed natural gas) vehicles, especially with regard to the issues of cargo space, refueling, and towing. I began writing to [...]

Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.

Intranasal medication administration in the emergency care of children has been reported for at least 20 years and is gaining popularity because of ease of administration, rapid onset of action, and relatively little pain to the patient. The ability to avoid a needle stick is often attractive to practitioners, in addition to children and their parents. In time-critical situations for which emergent administration of medication is needed, the intranasal route may be associated with more rapid medication administration. This article reviews the use of intranasal medications in the emergency care of children. Particular attention will be paid to anatomy and its impact on drug delivery, pharmacodynamics, medications currently administered by this route, delivery devices available, tips for use, and future directions.

AbstractBackgroundAwareness of the primary literature is important for clinicians. Lack of time, poor access to information, and lack of personal initiative may be barriers for some trainees. Really Simple Syndication (RSS) readers aggregate web content, such as journal abstracts, in a single location for easy viewing.ObjectiveWe assessed whether use of an RSS reader would increase resident reading frequency, familiarity, and understanding of the primary literature.MethodsWe conducted a single-center, prospective, randomized, nonblinded, controlled trial of the effect of RSS reader use on knowledge of recent literature among pediatrics residents. Residents were randomly assigned to the RSS group (education in RSS use and receipt of the PediatricsRSS feed) or a control group that followed standard reading practices. Outcome measures were differences on baseline and monthly surveys of reading frequency, familiarity with recent publications, and knowledge of recent articles (familiarity validation).ResultsOf 144 eligible residents, 79 (55) were enrolled in the survey, with 81 (64 of 79) of participants completing all surveys. The RSS reader use was correlated with greater familiarity with selected articles, but not with improved understanding (as measured by ability to answer multiple-choice questions about content). Participants reported satisfaction with the RSS reader based on its ease of use, accessibility, and as an aid in supplementing reading.ConclusionsThe RSS reader use was accepted by residents and associated with increased familiarity with the primary literature but not with increased understanding.

Children evaluated in emergency departments for blunt head trauma (BHT) frequently undergo computed tomography (CT), with some requiring pharmacological sedation. Cranial CT sedation complications are understudied. The objective of this study was to document the frequency, type, and complications of pharmacological sedation for cranial CT in children.

Pediatric head trauma is a common occurrence. There is mounting evidence that even patients with minor head injury require limits on school activities andor removal from sports and play to help speed recovery and limit morbidity. The objective of this study was to determine whether discharge instructions given to children who had sustained head injuries included information regarding activity restrictions, activity time constraints, andor specifics of follow-up care.

In the United States accredited residency programs in addiction exist only for psychiatrists specializing in addiction psychiatry (ADP); nonpsychiatrists seeking training in addiction medicine (ADM) can train in nonaccredited “fellowships,” or can receive training in some ADP programs, only to not be granted a certificate of completion of accredited training. Information about ADP residency programs has been tabulated, but it is not available for ADM fellowships. The authors conducted a national survey to compile information about the location, structure, curriculum, and other characteristics of active ADM fellowships. Of the 40 accredited ADP residency programs, 7 offered training in addiction to nonpsychiatrists. The authors identified 14 nonaccredited ADM fellowships. In 2009 and 2010, there were approximately 15 nonpsychiatrists in ADP programs and 25 in ADM fellowships. Clinical experiences included inpatient services, outpatient treatment services such as methadone maintenance or buprenorphine maintenance, and providing addiction consult services. The most common academic activities included weekly lectures and the teaching of medical students.

Traumatic brain injury is common in children. Fortunately, most patients suffer mild traumatic brain injury (MTBI). Appropriate guidelines for follow-up care are not well established. We sought to determine practice experience and preferences of general pediatricians related to follow-up care of MTBI.

A previously healthy adolescent girl presented to the emergency department with new onset chest and right upper quadrant abdominal pain. Laboratory studies and imaging were consistent with myocarditis. She developed heart block after admission and required stabilization in the cardiac intensive care unit. Lyme serology returned positive, and her condition was diagnosed as Lyme disease-associated myocarditis.

CT imaging of head-injured children has risks of radiation-induced malignancy. Our aim was to identify children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary.

The IB kinases (IKKs) are essential components of the signaling pathway by which the NF-B p50/RelA transcription factor is activated in response to pro-inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor (TNF). NF-B signaling results in the expression of numerous genes involved in innate and adaptive immune responses. The pathway is also implicated in chronic inflammatory disorders including rheumatoid arthritis (RA), chronic obstructive pulmonary disorder (COPD), and asthma. Inhibition of the kinase activity of the IKKs is therefore a promising mechanism for intervention in these diseases. Here, we will review the literature describing small molecule inhibitors of IKK (IKK2), the most widely studied of the IKKs.

ABSTRACTBackground:Neither professional consensus nor evidence exists to guide the choice of essential hospital disaster interventions. The objective of our study was to demonstrate a method for developing consensus on hospital disaster interventions that should be regarded as essential, quantitatively balancing needs and resources.Methods:A panel of pediatric acute care practitioners developed consensus using a modified Delphi process. Interventions were chosen such that workload per staff member would not exceed the previously validated maximum according to the Therapeutic Intervention Scoring System. Based on published models, it was assumed that the usual numbers of staff would care for a disaster surge of 4 times the usual number of intensive care and non–intensive care hospital patients.Results:Using a single set of assumptions on constrained resources and overwhelming needs, the panel ranked and agreed on essential interventions. A number of standard interventions would exceed crisis workload constraints, including detailed recording of vital signs and fluid balance, administration of vasoactive agents, invasive monitoring of pressures (central venous, intraarterial, intracranial), dialysis, and tube feedings.Conclusions:The quantitative methodology and consensus development process described in the present report may have utility in future planning. Groups with appropriate expertise must develop action plans according to authority within each jurisdiction, addressing likely disaster scenarios, according to the needs in each medical service region, using available regional resources, and accounting for the capabilities of each institution. (Disaster Med Public Health Preparedness. 2009;3:27–32)

Demonstration that IkappaB kinase 2 (IKK-2) plays a pivotal role in the nuclear factor-kappaB-regulated production of proinflammatory molecules by stimuli such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 suggests that inhibition of IKK-2 may be beneficial in the treatment of rheumatoid arthritis. In the present study, we demonstrate that a novel, potent (IC(50) = 17.9 nM), and selective inhibitor of human IKK-2, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), inhibits lipopolysaccharide-induced human monocyte production of TNF-alpha, IL-6, and IL-8 with an IC(50) = 170 to 320 nM. Prophylactic administration of TPCA-1 at 3, 10, or 20 mg/kg, i.p., b.i.d., resulted in a dose-dependent reduction in the severity of murine collagen-induced arthritis (CIA). The significantly reduced disease severity and delay of disease onset resulting from administration of TPCA-1 at 10 mg/kg, i.p., b.i.d. were comparable to the effects of the antirheumatic drug, etanercept, when administered prophylactically at 4 mg/kg, i.p., every other day. Nuclear localization of p65, as well as levels of IL-1beta, IL-6, TNF-alpha, and interferon-gamma, were significantly reduced in the paw tissue of TPCA-1- and etanercept-treated mice. In addition, administration of TPCA-1 in vivo resulted in significantly decreased collagen-induced T cell proliferation ex vivo. Therapeutic administration of TPCA-1 at 20 mg/kg, but not at 3 or 10 mg/kg, i.p., b.i.d., significantly reduced the severity of CIA, as did etanercept administration at 12.5 mg/kg, i.p., every other day. These results suggest that reduction of proinflammatory mediators and inhibition of antigen-induced T cell proliferation are mechanisms underlying the attenuation of CIA by the IKK-2 inhibitor, TPCA-1.

Determine prevalence of participation and underimmunization rate in a regional immunization registry (IR) among patients presenting to a university pediatric emergency department (PED). Rate of agreement between parental report and documented immunization status was also measured.

AbstractThis study examined the differential predictive bias of CBM in reading across African American and Caucasian students in Grades 2 through 5. Participants included 136 students who were administered CBM oral reading fluency passages and the Reading Comprehension subtest of the Woodcock-Johnson Psychoeducational Battery—Revised. A series of hierarchical multiple regression analyses indicated that CBM neither over-or underpredicted reading comprehension skills controlling for age, sex, and socioeconomic status. Results of this study suggest that CBM continues to appear to be a sensitive form of direct reading assessment in the local curriculum for both African American and Caucasian elementary-age students.

Small molecule inhibitors have proven extremely useful for investigating signal transduction pathways and have the potential for development into therapeutics for inhibiting signal transduction pathways whose activities contribute to human diseases. Transforming growth factor β (TGF-β) is a member of a large family of pleiotropic cytokines that are involved in many biological processes, including growth control, differentiation, migration, cell survival, adhesion, and specification of developmental fate, in both normal and diseased states. TGF-β superfamily members signal through a receptor complex comprising a type II and type I receptor, both serine/threonine kinases. Here, we characterize a small molecule inhibitor (SB-431542) that was identified as an inhibitor of activin receptor-like kinase (ALK)5 (the TGF-β type I receptor). We demonstrate that it inhibits ALK5 and also the activin type I receptor ALK4 and the nodal type I receptor ALK7, which are very highly related to ALK5 in their kinase domains. It has no effect on the other, more divergent ALK family members that recognize bone morphogenetic proteins (BMPs). Consistent with this, we demonstrate that SB-431542 is a selective inhibitor of endogenous activin and TGF-β signaling but has no effect on BMP signaling. To demonstrate the specificity of SB-431542, we tested its effect on several other signal transduction pathways whose activities depend on the concerted activation of multiple kinases. SB-431542 has no effect on components of the ERK, JNK, or p38 MAP kinase pathways or on components of the signaling pathways activated in response to serum.

Small molecule inhibitors have proven extremely useful for investigating signal transduction pathways and have the potential for development into therapeutics for inhibiting signal transduction pathways whose activities contribute to human diseases. Transforming growth factor beta (TGF-beta) is a member of a large family of pleiotropic cytokines that are involved in many biological processes, including growth control, differentiation, migration, cell survival, adhesion, and specification of developmental fate, in both normal and diseased states. TGF-beta superfamily members signal through a receptor complex comprising a type II and type I receptor, both serine/threonine kinases. Here, we characterize a small molecule inhibitor (SB-431542) that was identified as an inhibitor of activin receptor-like kinase (ALK)5 (the TGF-beta type I receptor). We demonstrate that it inhibits ALK5 and also the activin type I receptor ALK4 and the nodal type I receptor ALK7, which are very highly related to ALK5 in their kinase domains. It has no effect on the other, more divergent ALK family members that recognize bone morphogenetic proteins (BMPs). Consistent with this, we demonstrate that SB-431542 is a selective inhibitor of endogenous activin and TGF-beta signaling but has no effect on BMP signaling. To demonstrate the specificity of SB-431542, we tested its effect on several other signal transduction pathways whose activities depend on the concerted activation of multiple kinases. SB-431542 has no effect on components of the ERK, JNK, or p38 MAP kinase pathways or on components of the signaling pathways activated in response to serum.

The activity of a novel series of peptidomimetic hematoregulatory compounds, designed based on a pharmacophore model inferred from the structure–activity relationships of a peptide SK&F 107647 (1Figure 1Structure of SK&F 107647 (1).), is reported. These compounds induce a hematopoietic synergistic factor (HSF) which in turn modulates host defense. The compounds may represent novel therapeutic agents in the area of hematoregulation.

No abstract available for this article.

Immunologic effects of our previously reported treatment protocol were determined in eight systemic sclerosis (SSc) patients treated with plasmapheresis, cyclophosphamide, and prednisone as tolerated. Prior to treatment total serum IgG and circulating lymphocytes including the percentage of B, T, and NK cells were normal. Peripheral blood lymphocytes showed evidence of activation by increased spontaneous proliferation and expression of CD25 on T cells. In addition, CD4⁺ T cells showed increased expression of both activation (HLA-DR) and maturation (CD29) markers. The percentage of CD8⁺ T cells was low, resulting in a high CD4:CD8 T cell ratio. During treatment all patients showed clinical improvement. Laboratory testing showed that their NK cells had declined by 81%, B cells declined by 96%, and serum IgG declined by 49%; high titer ANA were abrogated. Total T cells declined by 52%, and the CD4:CD8 ratio fell to normal, due to an almost twofold increase in the percentage of CD8⁺ T cells. Spontaneous lymphocyte proliferation increased further and was accompanied by increased maturation and activation of both CD4⁺ and CD8⁺ T cells, as well as a reduction of immature CD4⁺ T cells. Among CD8⁺ T cells the percentage of cytotoxic cells increased as shown by an increase in the CD11b^-, CD38⁺, and CD29⁺ phenotypes, a finding confirmed on follow-up three-color flow cytometry which showed an increase in activated CD8 cells bearing the cytotoxic CD28 marker. Three-color cytometry also showed that cells with the CD4⁺CD45RA⁺CD31⁺ suppressor inducer phenotype were low and those with the CD4⁺CD45RO⁺CD31^- helper inducer phenotype were high in treated SSc patients. Deficient CD4⁺CD45RA⁺CD31⁺ and CD8⁺ T cell populations suggest an immune regulatory imbalance in SSc which could have led to CD4⁺ T cell activation and autoimmunity. Depletion of B cells, in conjunction with augmentation of cytotoxic CD8⁺ T cells through combined therapy, may have diminished the autoimmune response. Copyright 1994, 1999 Academic Press

This investigation evaluates how successfully the Massachusetts model of home care targets services to vulnerable elders. It compares data from a random sample of home care recipients with a probability sample of non-institutionalized elders in Massachusetts. The data indicate that the Massachusetts statewide system developed under minimum regulation and decentralized management has successfully reached the vulnerable elders, particularly those living alone and the widowed. The demand for home services exists but is neither excessive nor uncontrollable. These findings support the continued use of a social model of home care delivery instead of a more restrictive medical model.

Abstract:Massachusetts was the first state to introduce a statewide specialty mental health managed care plan for its Medicaid program. This study assesses the impact of this program on expenditures, access, and relative quality. Over a one-year period, expenditures were reduced by 22 percent below predicted levels without managed care, without any overall reduction in access or relative quality. Reduced lengths-of-stay, lower prices, and fewer inpatient admissions were the major factors. However, for one population segment—children and adolescents—readmission rates increased slightly, and providers for this group were less satisfied than they were before managed care was adopted. Less costly types of twenty-four-hour care were substituted for inpatient hospital care. This experience supports the usefulness of a managed care program for mental health and substance abuse services, and the applicability of such a program to high-risk populations.