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Background: Sudden unexpected infant death (SUID) continues to be a leading cause of death in infants in the United States (US), with significant disparities by race and socio-economic status. Infant safe sleep behaviors are associated with decreasing SUID risk, but challenges remain for families to practice these routinely. The objective of this program was to implement and evaluate a novel approach for an infant safe sleep pilot program built upon partnerships between hospitals and community-based organizations (CBOs) serving pregnant and parenting families in at-risk communities., Methods: Community Partnership Approaches to Safe Sleep (CPASS) was a prospectively implemented infant safe sleep program. CPASS included children's hospitals partnered with CBOs across five US cities: Portland, OR, Little Rock AR, Chicago, IL, Birmingham, AL, and Rochester, NY. The program consisted of (1) monthly learning community calls; (2) distribution of Safe Sleep Survival Kits; and (3) surveys of sites and families regarding program outcomes. Survey measures included (1) site participation in CPASS activities; (2) recipients' use of Safe Sleep Kits; and (3) recipients' safe sleep knowledge and behaviors., Results: CPASS learning community activities were consistently attended by at least two representatives (1 hospital-based, 1 CBO-based) from each site. Across the five sites, 1002 safe kits were distributed over 9 months, the majority (> 85%) to families with infants ≤ 1 month old. Among participating families, 45% reported no safe sleep location before receipt of the kit. Family adherence to nighttime safe sleep recommendations included: (1) no bedsharing (M 6.0, SD 1.8, range 0-7); (2) sleep on back (M 6.3, SD 1.7, range 0-7); and (3) sleep in a crib with no blankets/toys (M 6.0, SD 2.0, range 0-7). Site interviews described how participation in CPASS influenced safe sleep conversations and incorporated local data into counseling. Hospital-CBO relationships were strengthened with program participation., Conclusions: The CPASS pilot program provides a new, innovative model built on hospital-community partnerships for infant safe sleep promotion in SUID-impacted communities. CPASS reached families before their infant's peak age risk for SUID and empowered families with knowledge and resources to practice infant safe sleep. Important lessons learned included improved ways to center and communicate with families., (© 2024. The Author(s).)

Background: Injuries, the leading cause of death in children 1-17 years old, are often preventable. Injury patterns are impacted by changes in the child's environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic., Methods: This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children < 18 years old. Injury was defined by at least one International Classification of Disease-10th revision (ICD-10) code for bodily injury (S00-T78). The main study outcomes were total and proportion of PED injury-related visits compared to all visits in March through December 2020 and to the same months in 2019. Weekly injury visits as a percentage of total PED visits were calculated for all weeks between January 2019 and December 2020., Results: The study included 741,418 PED visits for injuries pre-COVID-19 pandemic (2019) and during the COVID-19 pandemic (2020). Overall PED visits from all causes decreased 27.4% in March to December 2020 compared to the same time frame in 2019; however, the proportion of injury-related PED visits in 2020 increased by 37.7%. In 2020, injured children were younger (median age 6.31 years vs 7.31 in 2019), more commonly White (54% vs 50%, p < 0.001), non-Hispanic (72% vs 69%, p < 0.001) and had private insurance (35% vs 32%, p < 0.001). Injury hospitalizations increased 2.2% (p < 0.001) and deaths increased 0.03% (p < 0.001) in 2020 compared to 2019. Mean injury severity score increased (2.2 to 2.4, p < 0.001) between 2019 and 2020. Injuries declined for struck by/against (- 4.9%) and overexertion (- 1.2%) mechanisms. Injuries proportionally increased for pedal cycles (2.8%), cut/pierce (1.5%), motor vehicle occupant (0.9%), other transportation (0.6%), fire/burn (0.5%) and firearms (0.3%) compared to all injuries in 2020 versus 2019., Conclusions: The proportion of PED injury-related visits in March through December 2020 increased compared to the same months in 2019. Racial and payor differences were noted. Mechanisms of injury seen in the PED during 2020 changed compared to 2019, and this can inform injury prevention initiatives., (© 2023. The Author(s).)

Background: Expert consensus recommends prescription opioid safety counseling be provided when prescribing an opioid. This may be especially important for youth with preexistent alcohol and other drug (AOD) use who are at higher risk of developing opioid use disorder. This study examined the frequency that adolescent trauma patients prescribed opioids at hospital discharge received counseling and if this differed by adolescents' AOD use., Method: This study was embedded within a larger prospective stepped-wedge type III hybrid implementation study of AOD screening across a national cohort of pediatric trauma centers. Data were collected during 2018-2021 from admitted adolescent trauma patients (12-17 yo) at seven centers. Patient data were extracted from the electronic health record (EHR) on any prescribed discharged opioids, documentation of counseling delivered on prescribed opioid, who delivered counseling, and patients' AOD screening results. Additionally, adolescents received an online survey within 30 days of hospital discharge that included asking about hospital discussions on safe use of prescription pain medication., Results: Of the 247 adolescent trauma patients enrolled, 158 completed the 30-day survey. AOD screening results were documented in the EHR for 139 patients (88%), with 69 (44.1%) screening AOD-positive. Opioids at discharge were prescribed to 86 (54.4%) adolescent patients, with no significant difference between those screened AOD-positive and AOD-negative (42.4% vs. 46.3%, p = 0.89). Counseling was documented in the EHR for 30 (34.9%) of those prescribed an opioid and was not significantly different by sex, age, race, ethnicity or between adolescent patients with documentation of AOD use (29.3%) versus those who did not (33.3%, p = 0.71). According to the adolescent survey, among those prescribed an opioid, 61.2% reported someone had talked with them about safe use of newly prescribed pain medications with again no difference between AOD-positive and AOD-negative screening results (p = 0.34)., Conclusions: Although adolescent trauma patients recalled discussions on safe use of prescribed pain medication more often than was documented in the EHR, these discussions were not universal and did not differ if adolescents had screened positive or negative for AOD use as documented in the EHR., Trial Registry: clinicaltrials.gov NCT03297060., (© 2023. The Author(s).)

Background: Multiple sclerosis (MS) is prevalent among working age individuals (20-60 years), leading to high burden on work productivity. Few data are available about the absenteeism and presenteeism in employed individuals with MS in comparison to non-MS personnel. This study aimed to quantify the burden of illness of employed US adults with relapsing-remitting multiple sclerosis (RRMS) and examine burden by levels of work impairment., Methods: A retrospective cross-sectional analysis was conducted using patient-reported responses from the US National Health and Wellness Survey (NHWS). Data from NHWS 2015-2016 were analyzed from 196 employed RRMS respondents who were matched 1:4 to employed respondents without MS based on demographic and general health characteristics. Demographic and general health characteristics for employed RRMS individuals were analyzed by levels of work impairment (none, 1-30%; 31-68%; 69-100%). Work productivity (absenteeism, presenteeism, and work impairment), decrements in health-related quality of life (HRQoL) (short form-36, EQ-5D), and healthcare resource utilization (HCRU) were compared to determine the burden of RRMS., Results: After propensity score matching, the levels of absenteeism and presenteeism were 2 and 1.8 times higher in the employed RRMS population than the employed non-MS population, respectively (P < 0.001 for both). HRQoL was significantly lower in employed respondents with RRMS than those without MS (P < 0.001 for all). Employed respondents with RRMS had significantly more HCRU over 6 months compared to those without MS (P < 0.001). Furthermore, among employed RRMS respondents, greater levels of impairment were associated with increasing disease severity, greater healthcare resource use, fatigue, and cognitive impairment and inversely associated with mental and physical HRQoL (P < 0.0001 for all)., Conclusions: Among employed individuals, respondents with RRMS had lower, work productivity, HRQoL, and higher HCRU as compared with those without MS. Given the large impact RRMS has on work impairment, a need exists to manage individuals on therapies that improve HRQoL, reduce symptoms, and improve their ability to perform in the workforce.

Background: Pediatric head trauma management varies between emergency departments globally. Here we aim to compare the pediatric minor head trauma management between a US and Italian hospital., Methods: We conducted a retrospective chart review of children 0-18 years old presenting after minor head trauma (Glasgow Coma Scale 14-15) from two emergency departments, in Boston, Massachusetts, United States and Trieste, Italy, between January and December 2013. Frequencies of demographic, clinical, and management characteristic were calculated. We compared rate ratios for characteristics of patients receiving cranial computed tomography (CT) scans between the two populations., Results: There were 1783 patients in Boston, Massachusetts and 183 patients in Trieste, Italy. Patients in Boston had more reported neurologic symptoms (61.2%) than in Trieste (6%) (p < 0.001). More CT scans were ordered on the patients in Boston (17.3% vs. 6.6%) (p < 0.001), while more children were hospitalized in Trieste (55.7% vs. 8.6%) (p < 0.001). Patients with neurological symptoms more commonly had a CT scan in Trieste (45.5%) than in Boston (23.5%) (RR 0.52, 95% CI 0.27, 1.00), while more patients without neurological symptoms had CTs in Boston (7.5%) than in Trieste (4.1%) (RR 1.85, 95% CI 0.86, 4.00). Assignment of triage levels and definitions of head injury severity varied considerably between the two hospitals, resulting in dissimilar populations presenting to the two hospitals, and thus, differences in the management of these children., Conclusion: The population of head trauma patients and the management of pediatric minor head trauma differs between Boston and Trieste, with a preference for CT scans in Boston and a preference for hospitalization in Trieste. Clinical guidelines used at each institution likely lead to this variation in care influenced by the different patient populations and institutional resources.

Background: Although patent ductus arteriosus (PDA) ligations in the Neonatal Intensive Care Unit (NICU) have been an accepted practice, many are still performed in the Operating Room (OR). Whether avoiding transport leads to improved perioperative outcomes is unclear. Here we aimed to determine whether PDA ligations in the NICU corresponded to higher risk of surgical site infection or mortality and if transport was associated with worsened perioperative outcomes., Methods: We performed a retrospective cohort study of NICU patients, ≤37 weeks post-menstrual age, undergoing surgical PDA ligation in the NICU or OR. We excluded any infants undergoing device PDA closure. We measured the incidence of perioperative hypothermia, cardiac arrest, decreases in SpO2, hemodynamic instability and postoperative surgical site infection, sepsis and mortality., Results: Data was collected on 189 infants (100 OR, 89 NICU). After controlling for number of preoperative comorbidities, weight at time of procedure, procedure location and hospital in the mixed-effect model, no significant difference in mortality or sepsis was found (odds ratio 0.31, 95%CI 0.07, 1.30; p = 0.107, and odds ratio 0.40; 95%CI 0.14, 1.09; p = 0.072, respectively). There was an increased incidence of hemodynamic instability on transport postoperatively in the OR group (12.4% vs 2%, odds ratio 6.93; 95% CI 1.48, 35.52; p = 0.014)., Conclusion: PDA ligations in the NICU were not associated with higher incidences of surgical site infection or mortality. There was an increased incidence of hemodynamic instability in the OR group on transport back to the NICU. Larger multicenter studies following long-term outcomes are needed to evaluate the safety of performing all PDA ligations in the NICU.

Background: The real-world experience of women receiving extended-cycle combined oral contraception (COC) versus monthly-cycle COC has not been reported., Methods: Data were from the United States 2013 National Health and Wellness Survey. Eligible women (18-50 years old, premenopausal, without hysterectomy) currently using extended-cycle COC (3 months between periods) were compared with women using monthly-cycle COC. Treatment satisfaction (1 "extremely dissatisfied" to 7 "extremely satisfied"), adherence (8-item Morisky Medication Adherence Scale © ), menstrual cycle-related symptoms, health-related quality of life (HRQOL) and health state utilities (Medical Outcomes Short Form Survey-36v2®), depression (9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and Activity Impairment-General Health, and healthcare resource use were assessed using one-way analyses of variance, chi-square tests, and generalized linear models (adjusted for covariates)., Results: Participants included 260 (6.7%) women using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using extended-cycle COC reported significantly higher treatment satisfaction (P = 0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029). A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using extended-cycle versus monthly-cycle COC. Significantly more women using extended-cycle COC reported health-related diagnoses, indicating preferential prescription for extended-cycle COC among women reporting more health problems. Consistent with this poorer health, more women using extended-cycle COC reported fatigue, headache, and activity impairment (P values < 0.05). There were no other significant differences between groups., Conclusions: This real-world observational study supports extended-cycle COC as a valuable treatment option with high satisfaction, high adherence, and reduced heavy menstrual bleeding.

Background: Understanding the interaction between Aedes vectors and dengue viruses (DENV) has significant implications in determining the transmission dynamics of dengue. The absence of an animal model and ethical concerns regarding direct feeding of mosquitoes on patients has resulted in most infection studies using blood meals spiked with laboratory-cultured DENV. Data obtained from such studies may not reflect the natural human-mosquito transmission scenario. This study explored the potential of using membrane feeding of dengue patient's blood as a substitute for direct skin feeding., Methods: Four to six-day old female Ae. aegypti were provided the opportunity to feed via direct exposure to a patient's forearm for 15 min or via exposure to EDTA-treated blood from the same patient through an artificial membrane for 30 min. Mosquitoes from both feeding methods were incubated inside environmental chambers. Mosquitoes were sampled at day 13 post-feeding. Midgut and salivary glands of each mosquito were dissected to determine DENV infection by RT-qPCR and viral titration, respectively., Results: Feeding rates: Direct skin feeding assay (DSFA) consistently showed higher mosquito feeding rates (93.3-100%) when compared with the membrane feeding assay (MFA) (48-98.2%). Midgut infection: Pair-wise comparison between methods showed no significant difference in midgut infection rates between mosquitoes exposed via each method and a strong correlation was observed in midgut infection rates for both feeding methods (r = 0.89, P < 0.0001). Overall midgut viral titers (n = 20) obtained by both methods were comparable (P ≥ 0.06). Salivary gland infection: Pair-wise comparison between both methods revealed no significant difference in salivary gland infection rate. Strong correlation in salivary gland infection was observed between DSFA and MFA (r = 0.81, P < 0.0001). In general, mosquitoes fed directly on dengue patients and those on patients' blood (n = 11) had comparable virus titer (P ≥ 0.09)., Conclusion: DENV midgut and salivary gland infection rates showed good concordance between DSFA and MFA blood meal exposure methods. Freshly-obtained venous blood in EDTA from dengue patients for MFA can be used as a substitute to DSFA, especially in circumstances where bioethics approval or patient recruitment is difficult to obtain for vector competence studies. Nevertheless, mosquito numbers will need to be increased to compensate for lower feeding rate in MFA.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) poses an increasingly large disease and economic burden worldwide. The effectiveness of screening programs in the tropics is poorly understood. The aims of this study are: (i) to analyze the factors affecting MRSA colonization at admission and acquisition during hospitalization and (ii) to evaluate the cost-effectiveness of a screening program which aims to control MRSA incidence during hospitalization., Methods: We conducted a retrospective case-control study of patients admitted to the Communicable Disease Centre (CDC) in Singapore between Jan 2009 and Dec 2010 when there was an ongoing selective screening and isolation program. Risk factors contributing to MRSA colonization on admission and acquisition during hospital stay were evaluated using a logistic regression model. In addition, a cost-effectiveness analysis was conducted to determine the cost per disability-adjusted life year (DALY) averted due to implementing the screening and isolation program., Results: The average prevalence rate of screened patients at admission and the average acquisition rate at discharge during the study period were 12.1 and 4.8 % respectively. Logistic regression models showed that older age (adjusted odds ratio (OR) 1.03, 95 % CI 1.02-1.04, p < 0.001) and dermatological conditions (adjusted OR 1.49, 95 % CI 1.11-1.20, p = 0.008) were independently associated with an increased risk of MRSA colonization at admission. Age (adjusted OR 1.02, 95 % CI 1.01-1.03, p = 0.002) and length of stay in hospital (adjusted OR 1.04, 95 % CI 1.03-1.06, p < 0.001) were independent factors associated with MRSA acquisition during hospitalization. The screening and isolation program reduced the acquisition rate by 1.6 % and was found to be cost saving. For the whole study period, the program cost US$129,916, while it offset hospitalization costs of US$103,869 and loss of productivity costs of US$50,453 with -400 $/DALY averted., Discussion: This study is the first to our knowledge that evaluates the cost-effectiveness of screening and isolation of MRSA patients in a tropical country. Another unique feature of the analysis is the evaluation of acquisition rates among specific types of patients (dermatological, HIV and infectious disease patients)and the comparison of the cost-effectiveness of screening and isolation between them., Conclusions: Overall our results indicate high MRSA prevalence that can be cost effectively reduced by selective screening and isolation programs in Singapore.

Background: Helical membrane proteins are vital for the interaction of cells with their environment. Predicting the location of membrane helices in protein amino acid sequences provides substantial understanding of their structure and function and identifies membrane proteins in sequenced genomes. Currently there is no comprehensive benchmark tool for evaluating prediction methods, and there is no publication comparing all available prediction tools. Current benchmark literature is outdated, as recently determined membrane protein structures are not included. Current literature is also limited to global assessments, as specialised benchmarks for predicting specific classes of membrane proteins were not previously carried out., Description: We present a benchmark server at http://sydney.edu.au/pharmacy/sbio/software/TMH&#95;benchmark.shtml that uses recent high resolution protein structural data to provide a comprehensive assessment of the accuracy of existing membrane helix prediction methods. The server further allows a user to compare uploaded predictions generated by novel methods, permitting the comparison of these novel methods against all existing methods compared by the server. Benchmark metrics include sensitivity and specificity of predictions for membrane helix location and orientation, and many others. The server allows for customised evaluations such as assessing prediction method performances for specific helical membrane protein subtypes.We report results for custom benchmarks which illustrate how the server may be used for specialised benchmarks. Which prediction method is the best performing method depends on which measure is being benchmarked. The OCTOPUS membrane helix prediction method is consistently one of the highest performing methods across all measures in the benchmarks that we performed., Conclusions: The benchmark server allows general and specialised assessment of existing and novel membrane helix prediction methods. Users can employ this benchmark server to determine the most suitable method for the type of prediction the user needs to perform, be it general whole-genome annotation or the prediction of specific types of helical membrane protein. Creators of novel prediction methods can use this benchmark server to evaluate the performance of their new methods. The benchmark server will be a valuable tool for researchers seeking to extract more sophisticated information from the large and growing protein sequence databases.

Background: Whilst there have been studies on the risks and outcomes of MRSA colonization and infections in HIV-positive patients, local data is limited on the risk factors for MRSA colonization among these patients. We undertook this study in a tertiary HIV care centre to document the risk factors for colonization and to determine the prevalence of MRSA colonization among HIV-positive outpatients in Singapore., Methods: This was a cross-sectional study in which factors associated with MRSA positivity among patients with HIV infection were evaluated. A set of standardized questionnaire and data collection forms were available to interview all recruited patients. Following the interview, trained nurses collected swabs from the anterior nares/axilla/groin (NAG), throat and peri-anal regions. Information on demographics, clinical history, laboratory results and hospitalization history were retrieved from medical records., Results: MRSA was detected in swab cultures from at least 1 site in 15 patients (5.1%). Inclusion of throat and/or peri-anal swabs increased the sensitivity of NAG screening by 20%. Predictors for MRSA colonization among HIV-positive patients were age, history of pneumonia, lymphoma, presence of a percutaneous device within the past 12 months, history of household members hospitalized more than two times within the past 12 months, and a most recent CD4 count less than 200., Conclusions: This study highlights that a proportion of MRSA carriers would have been undetected without multiple-site screening cultures. This study could shed insight into identifying patients at risk of MRSA colonization upon hospital visit and this may suggest that a risk factor-based approach for MRSA surveillance focusing on high risk populations could be considered.

Background: One of the earliest steps in synaptogenesis at the neuromuscular junction is the aggregation of nicotinic acetylcholine receptors at the postsynaptic membrane. This study presents quantitative analyses of receptor and alpha-Dystroglycan aggregation in response to agrin and laminin-1, alone or in combination., Results: Both laminin and agrin increased overall expression of receptors on the plasma membrane. Following a 24 hour exposure, agrin increased the number of receptor aggregates but did not affect the number of alpha-Dystroglycan aggregates, while the reverse was true of laminin-1. Laminin also increased receptor concentration within aggregates, while agrin had no such effect. Finally, the spatial distribution of aggregates was indistinguishable from random in the case of laminin, while agrin induced aggregates were closer together than predicted by a random model., Conclusions: Agrin and laminin-1 both increase acetylcholine receptor aggregate size after 24 hours, but several lines of evidence indicate that this is achieved via different mechanisms. Agrin and laminin had different effects on the number and density of receptor and alpha-Dystroglycan aggregates. Moreover the random distribution of laminin induced (as opposed to agrin induced) receptor aggregates suggests that the former may influence aggregate size by simple mass action effects due to increased receptor expression.

Background: Acetylcholine receptors become aggregated at the developing neuromuscular synapse shortly after contact by a motorneuron in one of the earliest manifestations of synaptic development. While a major physiological signal for receptor aggregation (agrin) is known, the mechanism(s) by which muscle cells respond to this and other stimuli have yet to be worked out in detail. The question of mechanism is addressed in the present study via a quantitative examination of ultrastructural receptor arrangement within aggregates., Results: In receptor rich cell membranes resulting from stimulation by agrin or laminin, or in control membrane showing spontaneous receptor aggregation, receptors were found to be closer to neighboring receptors than would be expected at random. This indicates that aggregation proceeds heterogeneously: nanoaggregates, too small for detection in the light microscope, underlie developing microaggregates of receptors in all three cases. In contrast, the structural arrangement of receptors within nanoaggregates was found to depend on the aggregation stimulus. In laminin induced nanoaggregates receptors were found to be arranged in an unstructured manner, in contrast to the hexagonal array of about 10 nm spacing found for agrin induced nanoaggregates. Spontaneous aggregates displayed an intermediate amount of order, and this was found to be due to two distinct population of nanoaggregates., Conclusions: The observations support earlier studies indicating that mechanisms by which agrin and laminin-1 induced receptor aggregates form are distinct and, for the first time, relate mechanisms underlying spontaneous aggregate formation to aggregate structure.