High Prevalence of Abnormal General Movements in Hospitalized Very Low Birth Weight Infants.

OBJECTIVE: Abnormal general movements (GMs) are predictive of later risk of motor impairments in preterm infants. The goals of this study are to (1) describe the implementation of the GM assessment (GMA) in a neonatal intensive care unit (NICU) and (2) investigate the prevalence and evolution of abnormal GMs in very low birth weight (VLBW) infants. STUDY DESIGN: Observational study of GMs in VLBW infants (gestational age [GA] <32 weeks and/or birth weight [BW] <1,500 g) following GMA implementation in a level-IV NICU. All VLBW infants admitted between November 2017 and April 2019 were eligible for the GMA. Infants were excluded if they required high-frequency ventilation or if they could not be unbundled for video acquisition. GMAs were scored weekly by at least 2 GMA-certified providers. RESULTS: The GMA was performed in 121 VLBW infants with a mean (standard deviation [SD]) GA of 28.3 (2.6) and BW of 1,113 (400 g). Only 28% of infants had normal GMs on initial assessment (32.9 ± 2.7 weeks' GA), while 61 and 11% had poor repertoire and cramped-synchronized GMs, respectively. At NICU discharge (37.6 ± 3.4 weeks corrected GA), 45 and 21% of infants were classified as having poor repertoire and cramped-synchronized GMs, respectively. Most infants with cramped-synchronized GMs on initial assessment had persistent abnormal GMs at discharge. In contrast, only one infant with normal GMs on first assessment developed cramped-synchronized GMs. CONCLUSION: Abnormal GMs are common in VLBW infants, including a high prevalence of the more concerning cramped-synchronized movement pattern. The GMA can be successfully performed in VLBW infants. The GMA may be helpful in identifying infants at increased risk of later motor impairments, as well as assisting clinicians, in the stratification of infants who may benefit from additional brain imaging and/or an intensive hospital-based interventions. KEY POINTS: · Abnormal GMs are common in VLBW infants.. · Poor repertoire in the most prevalent pattern observed.. · Infants at risk for abnormal motor outcomes can be identified in the NICU..

A Maternal-Administered Multimodal Neonatal Bundle in Hospitalized Very Preterm Infants: A Pilot Study.

BACKGROUND: Premature infants are at an increased risk for developing cerebral palsy (CP). Evidence-based strategies designed to promote healthy brain development and facilitate adaptation after brain injury in infants still admitted to the neonatal intensive care unit (NICU) represent a novel approach that may lead to improved long-term outcomes. PURPOSE: To investigate the feasibility of a maternal-administered early intervention bundle in very preterm infants prior to NICU discharge. METHODS: A pilot trial evaluating a maternal-administered NICU-based bundle of interventions in preterm infants (≤32 weeks' gestational age and/or ≤1500 g birth weight). The impact of the bundle on short-term developmental outcomes of infants, as well as maternal stress, anxiety, and depression, is evaluated. RESULTS: The intervention bundle was implemented in 11 mother-infant dyads (including 1 set of twins) for a median of 8 weeks and was overall well received. Vocal soothing, scent exchange, and comforting touch were feasible, performed at or above the predetermined goal of 71% of the time (5/7 days), while kangaroo care and infant massage were not. Maternal stress, anxiety, and depression were decreased during the study time. IMPLICATIONS TO PRACTICE: A neonatal multimodal intervention bundle provided by mothers is feasible. IMPLICATIONS TO RESEARCH: Additional randomized controlled studies are needed to determine whether this type of bundled interventions can (1) improve the neurodevelopmental outcomes of participating infants and (2) improve long-term parental outcomes, including decreased burden of anxiety and depression, as well as improved attachment and optimal patterns of social interaction.

Identification of Pediatric Sepsis for Epidemiologic Surveillance Using Electronic Clinical Data.

OBJECTIVES: A method to identify pediatric sepsis episodes that is not affected by changing diagnosis and claims-based coding practices does not exist. We derived and validated a surveillance algorithm to identify pediatric sepsis using routine clinical data and applied the algorithm to study longitudinal trends in sepsis epidemiology. DESIGN: Retrospective observational study. SETTING: Single academic children's hospital. PATIENTS: All emergency and hospital encounters from January 2011 to January 2019, excluding neonatal ICU and cardiac center. EXPOSURE: Sepsis episodes identified by a surveillance algorithm using clinical data to identify infection and concurrent organ dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A surveillance algorithm was derived and validated in separate cohorts with suspected sepsis after clinician-adjudication of final sepsis diagnosis. We then applied the surveillance algorithm to determine longitudinal trends in incidence and mortality of pediatric sepsis over 8 years. Among 93,987 hospital encounters and 1,065 episodes of suspected sepsis in the derivation period, the surveillance algorithm yielded sensitivity 78% (95% CI, 72-84%), specificity 76% (95% CI, 74-79%), positive predictive value 41% (95% CI, 36-46%), and negative predictive value 94% (95% CI, 92-96%). In the validation period, the surveillance algorithm yielded sensitivity 84% (95% CI, 77-92%), specificity of 65% (95% CI, 59-70%), positive predictive value 43% (95% CI, 35-50%), and negative predictive value 93% (95% CI, 90-97%). Notably, most "false-positives" were deemed clinically relevant sepsis cases after manual review. The hospital-wide incidence of sepsis was 0.69% (95% CI, 0.67-0.71%), and the inpatient incidence was 2.8% (95% CI, 2.7-2.9%). Risk-adjusted sepsis incidence, without bias from changing diagnosis or coding practices, increased over time (adjusted incidence rate ratio per year 1.07; 95% CI, 1.06-1.08; p < 0.001). Mortality was 6.7% and did not change over time (adjusted odds ratio per year 0.98; 95% CI, 0.93-1.03; p = 0.38). CONCLUSIONS: An algorithm using routine clinical data provided an objective, efficient, and reliable method for pediatric sepsis surveillance. An increased sepsis incidence and stable mortality, free from influence of changes in diagnosis or billing practices, were evident.

Volunteering Internationally: Why, Where and How.

Oral health volunteers have an important role in addressing oral health care shortages around the world, but to be effective they need to understand and prepare for the challenges of working overseas.

Brief report #3: building a rural community caregiver network: student learning in small town America.

The Rural Caregiver Network Project in Eastern Maine is a prime example of indigenous coalition-building in a region struggling to ensure that vulnerable older adults can age-in-place and manage with scarce resources. Through this innovative initiative, a range of elder caregiver interventions were mobilized, coordinated, and sustained in a rural two-county region in Maine, including navigator services, adult day care, information and referral, caregiver support groups, a caregiver resource center, and caregiver skills-building workshops. The endorsement of participatory research, evaluation, and programming principles enabled undergraduate and graduate social work students to assume major roles in all aspects of project planning, implementation, and assessment while remaining grounded in the realities of rural life. Competence in such a generalist gerontological social work practice perspective is critical in small towns and nonmetropolitan communities.

Inhibition of spleen tyrosine kinase attenuates allergen-mediated airway constriction.

Spleen tyrosine kinase (SYK) is a key activator of signaling pathways downstream of multiple surface receptors implicated in asthma. SYK function has been extensively studied in mast cells downstream of the high-affinity IgE receptor, FcεR1. Preclinical studies have demonstrated a role for SYK in models of allergic inflammation, but a role in airway constriction has not been demonstrated. Here, we have used a potent and selective pharmacological inhibitor of SYK to determine the role of SYK in allergen-mediated inflammation and airway constriction in preclinical models. Attenuation of allergic airway responses was evaluated in a rat passive anaphylaxis model and rat and sheep inhaled allergen challenge models, as well as an ex vivo model of allergen-mediated airway constriction in rats and cynomolgus monkeys. Pharmacological inhibition of SYK dose-dependently blocked IgE-mediated tracheal plasma extravasation in rats. In a rat ovalbumin-sensitized airway challenge model, oral dosing with an SYK inhibitor led to a dose-dependent reduction in lung inflammatory cells. Ex vivo analysis of allergen-induced airway constriction in ovalbumin-sensitized brown Norway rats showed a complete attenuation with treatment of a SYK inhibitor, as well as a complete block of allergen-induced serotonin release. Similarly, allergen-mediated airway constriction was attenuated in ex vivo studies from nonhuman primate lungs. Intravenous administration of an SYK inhibitor attenuated both early- and late-phase allergen-induced increases in airway resistance in an Ascaris-sensitive sheep allergen challenge model. These data support a key role for SYK signaling in mediating allergic airway responses.

Health status of migrant farmworkers in the Shenandoah Valley.

The purpose of this study is to describe the characteristics and health status of a sample of migrant farmworkers in the Shenandoah Valley. The methodology for this study is a retrospective record review and analysis of data on 390 male migrant farmworkers. The group included men from Mexico (57. 2%), Jamaica (26. 9%), and Haiti (13. 0%) with a mean age of 38.5 years. The most common health problems reported were work-related and included musculoskeletal pain, irritated eyes, and respiratory symptoms. This study identifies areas for community and public health nurses to target interventions to address health promotion/disease prevention efforts.

Implementation of a Follow-Up System for Pediatric Sepsis Survivors in a Large Academic Pediatric Intensive Care Unit.

Background: Survivors of pediatric sepsis often develop new morbidities and deterioration in quality of life after sepsis, leading to a need for improved follow-up for children who survive sepsis. Objective: To implement a follow-up system for pediatric sepsis survivors in a pediatric health system. Methods: We performed a retrospective case series of patients treated for sepsis from October 2018 through October 2019 in a pediatric intensive care unit in a quaternary children's hospital, and describe implementation of a follow-up system for sepsis survivors. Program planning started in 2017 with multidisciplinary meetings including physical, occupational, and speech therapists, teachers, neuropsychologists, and coordinators from other survivorship programs (neonatology, stroke, and oncology). In 2018, a workshop was held to consult with local and national experts. The Pediatric Sepsis Survivorship Program launched in October 2018 led by a nurse coordinator who met with families to educate about sepsis and offer post-discharge follow-up. Patients with high pre-existing medical complexity or established subspecialty care were referred for follow-up through existing care coordination or subspecialty services plus guidance to monitor for post-sepsis morbidity. For patients with low-moderate medical complexity, the nurse coordinator administered a telephone-based health-assessment 2-3 months after discharge to screen for new physical or psychosocial morbidity. Patients flagged with concerns were referred to their primary physician and/or to expedited neuropsychological evaluation to utilize existing medical services. Results: Of 80 sepsis patients, 10 died, 20 were referred to care coordination by the program, and 13 had subspecialty follow-up. Five patients were followed in different health systems, four were adults not appropriate for existing follow-up programs, four remained hospitalized, and four were missed due to short stay or unavailable caregivers. The remaining 20 patients were scheduled for follow-up with the Pediatric Sepsis Program. Nine patients completed the telephone assessment. Four patients were receiving new physical or occupational therapy, and one patient was referred for neuropsychology evaluation due to new difficulties with attention, behavior, and completion of school tasks. Conclusions: Implementation of an efficient, low-cost pediatric sepsis survivorship program was successful by utilizing existing systems of care, when available, and filling a follow-up gap in screening for select patients.

COVID-19 and Orthopaedic International Humanitarianism.

As the world continues to adjust to life with COVID-19, one topic that requires further thought and discussion is whether elective international medical volunteerism can continue, and, if so, what challenges will need to be addressed. During a pandemic, the medical community is attentive to controlling the disease outbreak, and most of the literature regarding physician involvement during a pandemic focuses primarily on physicians traveling to areas of need to help treat the disease. As a result, little has been written about medical volunteerism that focuses on medical treatment unrelated to the disease outbreak. In a world-wide pandemic, many factors are to be considered in determining whether, and when, a physician should travel to another region to provide care and training for medical issues not directly related to the pandemic. Leaders of humanitarian committees of orthopaedic surgery subspecialties engaged with one another and host orthopaedic surgeons and a sponsoring organization to provide thoughtful insight and expert opinion on the challenges faced and possible pathways to provide continued orthopaedic support around the globe. Although this discussion focuses on international orthopaedic care, these suggestions may have a much broader application to the international medical community as a whole.

A Role for Short-term Volunteers in Global Health.

 Properly trained volunteers with interests and motivations that match the needs of settings with limited resources help meet the global shortage of well-trained healthcare workers. Health Volunteers Overseas (HVO) paves the way for successful volunteering experiences that help improve healthcare outcomes and enrich volunteers' lives.

Design, power, and interpretation of studies in the standard murine model of ALS.

Identification of SOD1 as the mutated protein in a significant subset of familial amyotrophic lateral sclerosis (FALS) cases has led to the generation of transgenic rodent models of autosomal dominant SOD1 FALS. Mice carrying 23 copies of the human SOD1(G93A) transgene are considered the standard model for FALS and ALS therapeutic studies. To date, there have been at least 50 publications describing therapeutic agents that extend the lifespan of this mouse. However, no therapeutic agent besides riluzole has shown corresponding clinical efficacy. We used computer modeling and statistical analysis of 5429 SOD1(G93A) mice from our efficacy studies to quantify the impact of several critical confounding biological variables that must be appreciated and should be controlled for when designing and interpreting efficacy studies. Having identified the most critical of these biological variables, we subsequently instituted parameters for optimal study design in the SOD1(G93A) mouse model. We retested several compounds reported in major animal studies (minocycline, creatine, celecoxib, sodium phenylbutyrate, ceftriaxone, WHI-P131, thalidomide, and riluzole) using this optimal study design and found no survival benefit in the SOD1(G93A) mouse for any compounds (including riluzole) administered by their previously reported routes and doses. The presence of these uncontrolled confounding variables in the screening system, and the failure of these several drugs to demonstrate efficacy in adequately designed and powered repeat studies, leads us to conclude that the majority of published effects are most likely measurements of noise in the distribution of survival means as opposed to actual drug effect. We recommend a minimum study design for this mouse model to best address and manage this inherent noise and to facilitate more significant and reproducible results among all laboratories employing the SOD1(G93A) mouse.

Nongovernmental organizations in musculoskeletal care: Orthopaedics Overseas.

Injuries are a major worldwide contributor to morbidity and mortality. The negative impact caused by such injuries is disproportionately heavy in developing countries. Such disparities are caused by a complex array of problems, including a lack of physical resources, poor infrastructure, and a shortage of trained health professionals. Overcoming such deficits in care will require the involvement of organizations that can offer broad-based solutions. These organizations must bridge the gap between private and public institutions to establish a systems-based approach to program development and institution-building. They must provide not just an adequate level of care, but a transfer of knowledge that leads to sustainable and cost-effective intervention. Orthopedics Overseas is an example of such an organization. We examine the development of Orthopedics Overseas and describe their interventions in Uganda as a case-study to show the unique position they have to affect change.

Child Fatalities Due to Heroin/Fentanyl Exposure: What the Case History Missed.

This case report presents three unrelated children found to have heroin and/or fentanyl in their systems after general unknown systematic toxicological analysis (STA). The first case involves an 11-month-old male found unresponsive at their residence. The scene response suggested a potentially unsafe sleeping condition or a sudden unexplained infant death. The second case is a 14-month-old female found unresponsive after eating soft candies, suggesting that a choking related death may have occurred. The third case is a 12-year-old male found unresponsive in bed and foaming from the mouth. Gum was removed from the child's airway, suggesting another choking related death. The STA included a 14-drug category enzyme linked immunosorbant assay (ELISA) screening in whole blood. Cases 1 and 3 were presumptively positive for fentanyl, while Case 2 was presumptively positive for opiates and fentanyl. Reflex confirmation was performed in blood, urine and gastric contents, by solid-phase extraction (SPE) for 12 opiates including morphine and 6-monoacetylmorphine (6MAM) by gas chromatography-mass spectrometry (GC-MS) and for fentanyl, norfentanyl, and novel analogs, by liquid chromatography tandem mass spectrometry (LC-MS-MS). High concentrations of fentanyl and 6MAM in the gastric contents of Case 1, along with the presence of diacetylmorphine, suggested probable enteral ingestion of heroin and fentanyl, separately or in a combined formulation. Interpretation of the toxicology results could not determine a probable route of exposure to heroin/fentanyl in Case 2, however, the cause of death was clearly related to this drug mixture. In Case 3, the presence of acetylfentanyl suggested an illicit fentanyl exposure. The intention of this case report is to demonstrate the need for a STA approach for all non-trauma postmortem cases regardless of case circumstances, age or suspicion of drug use.

Is syrup of ipecac still for sale? Comparison of pharmacies in a large urban area--2003 versus 2005.

There has been considerable publicity about the lack of benefit and potential dangers of syrup of ipecac. In November 2003, the American Academy of Pediatrics recommended against its use. Pharmacies in Houston, Texas were surveyed by telephone before (survey 1) and after (survey 2) the American Academy of Pediatrics' recommendation to determine whether ipecac availability changed. There were 126 pharmacies interviewed at survey 1, and 128 interviewed at survey 2. Pharmacies in survey 1 were more likely than those in survey 2 to sell ipecac (79% versus 64%, P < .01) and to have it in stock (75% versus 48%, P < .001). Pharmacies mostly stored ipecac on the shelves (67%, survey 1; 59%, survey 2, P = .27). Although syrup of ipecac availability has declined significantly, it is still available in more than 50% of pharmacies. Health care providers should advise against its use and advocate that pharmacies remove it.

Transportation barriers to accessing health care for urban children.

The Texas Children's Hospital Residents' Primary Care Group Clinic provides primary care to urban low-income children. The objective of this cross-sectional study was to investigate the impact of transportation problems on a family's ability to keep an appointment. One hundred eighty-three caregivers of children with an appointment were interviewed. Caregivers who kept their appointment were compared with those who did not with respect to demographic and transportation-related characteristics. Logistic regression modeling predicted caregivers with the following characteristics were more likely not to keep an appointment: not using a car to the last kept appointment, not keeping an appointment in the past due to transportation problems, having more than two people in the household, and not keeping an appointment in the past due to reasons other than transportation problems. Future research should focus on developing interventions to help low-income urban families overcome non-financial access barriers, including transportation problems.

Overcoming mutagenicity and ion channel activity: optimization of selective spleen tyrosine kinase inhibitors.

Development of a series of highly kinome-selective spleen tyrosine kinase (Syk) inhibitors with favorable druglike properties is described. Early leads were discovered through X-ray crystallographic analysis, and a systematic survey of cores within a selected chemical space focused on ligand binding efficiency. Attenuation of hERG ion channel activity inherent within the initial chemotype was guided through modulation of physicochemical properties including log D, PSA, and pKa. PSA proved most effective for prospective compound design. Further profiling of an advanced compound revealed bacterial mutagenicity in the Ames test using TA97a Salmonella strain, and subsequent study demonstrated that this mutagenicity was pervasive throughout the series. Identification of intercalation as a likely mechanism for the mutagenicity-enabled modification of the core scaffold. Implementation of a DNA binding assay as a prescreen and models in DNA allowed resolution of the mutagenicity risk, affording molecules with favorable potency, selectivity, pharmacokinetic, and off-target profiles.

The domain management model: a tool to help organize care of stroke survivors in skilled nursing facilities.

More rehabilitative care takes place in nursing homes than in any other setting. Skilled nursing facilities (SNFs) face increasing challenges in delivering stroke rehabilitation care. The Domain Management Model (DMM) organizes care of stroke survivors by identifying four critical domains that include all problems patients and families may face. Problems identified through the Minimum Data Set and Resident Assessment Protocols can be organized by the domains as well. In the SNF setting, the DMM can help organize rehabilitation care by assisting in the identification of all relevant clinical problems and by serving as a structured format for team meetings, problem management, and discharge summaries.