Prehospital Naloxone Administration Patterns during the Era of Synthetic Opioids.

Background: The opioid epidemic is an ongoing public health emergency, exacerbated in recent years by the introduction and rising prevalence of synthetic opioids. The National EMS Scope of Practice Model was changed in 2017 to recommend allowing basic life support (BLS) clinicians to administer intranasal (IN) naloxone. This study examines local IN naloxone administration rates for 4 years after the new recommendation, and Glasgow Coma Scale (GCS) scores and respiratory rates before and after naloxone administration.Methods: This retrospective cohort study evaluated naloxone administrations between April 1st 2017 and March 31st 2021 in a mixed urban-suburban EMS system. Naloxone dosages, routes of administration, and frequency of administrations were captured along with demographic information. Analysis of change in the ratio of IN to intravenous (IV) naloxone administrations per patient was performed, with the intention of capturing administration patterns in the area. Analyses were performed for change over time of IN naloxone rates of administration, change in respiratory rates, and change in GCS scores after antidote administration. ALS and BLS clinician certification levels were also identified. Bootstrapping procedures were used to estimate 95% confidence intervals for correlation coefficients.Results: Two thousand and ninety patients were analyzed. There was no statistically significant change in the IN/parenteral ratio over time (p = 0.79). Repeat dosing increased over time from 1.2 ± 0.4 administrations per patient to 1.3 ± 0.5 administrations per patient (r = 0.078, 95% CI: 0.036 - 0.120; p = 0.036). Mean respiratory rates before (mean = 12.6 - 12.6, r = -0.04, 95% CI: -0.09 - 0.01; p = 0.1) and after (mean = 15.2 - 14.9, r = -0.03, 95% CI: -0.08 - 0.01; p = 0.172) naloxone administration have not changed. While initial GCS scores have become significantly lower, GCS scores after administration of naloxone have not changed (initial median GCS 10 - 6, p < 0.001; final median GCS 15 - 15, p = 0.23).Conclusions: Current dosing protocols of naloxone appear effective in the era of synthetic opioids in our region, although patients may be marginally more likely to require repeat naloxone doses.

EMS Non-Transport of Low-Risk COVID-19 Patients.

Objectives: COVID-19 infections in the community have the potential to overwhelm both prehospital and in-hospital resources. Transport of well-appearing patients, in the absence of available emergency department treatment capacity, increases strain on the hospital and EMS system. In May of 2020, the Connecticut Office of EMS issued a voluntary, EMS-initiated, non-transport protocol for selected low-risk patients with symptoms consistent with COVID-19. We evaluated the implementation of this non-transport protocol in a mixed urban/suburban EMS system.Methods: We conducted a retrospective review of contemporaneously recorded quality improvement documentation for uses of the Connecticut COVID-19 non-transport protocol by EMS clinicians within our EMS system during two implementations: from 12/14/2020 to 5/1/21, and again from 1/3/22 to 2/18/22, which coincided with large COVID-19 case surges in our region.Results: The vast majority of patients treated under the non-transport protocol were not reevaluated by EMS or in our emergency departments in the subsequent 24 hours. There was reasonable adherence to the protocol, with 83% of cases appropriate for the non-transport protocol. The most common reasons for protocol violations were age outside of protocol scope (pediatric patients), failure of documentation, or vital signs outside of the established protocol parameters. We did not find an increased 24-hour ED visit rate in patients who were inappropriately triaged to the protocol. Of patients who had ED visits within 24 hours, only two were admitted, none to higher levels of care.Conclusion: Within this small study, EMS clinicians in our system were able to safely and accurately apply a non-transport protocol for patients presenting with symptoms consistent with COVID-19. This is consistent with previous literature suggesting that EMS-initiated non-transport is a viable strategy to reduce the burden on health systems.

An Evaluation of Prehospital Adenosine Use.

BACKGROUND: Adenosine has been safely used by paramedics for the treatment of stable supraventricular tachycardia since the mid-1990s. However, there continues to be variability in paramedics' ability to identify appropriate indications for adenosine administration. As the first of a planned series of studies aimed at improving the accuracy of SVT diagnosis and successful administration of adenosine by paramedics, this study details the current usage patterns of adenosine by paramedics. METHODS: This cross-sectional retrospective study investigated adenosine use within a large northeast EMS region from January 1, 2019, through September 30, 2021. Excluding pediatric and duplicate case reports, we created a dataset containing patient age, sex, and vital signs before, during, and after adenosine administration; intravenous line location; and coded medical history from paramedic narrative documentation, including a history of atrial fibrillation, suspected arrhythmia diagnosis, and effect of adenosine. In cases with available prehospital electrocardiograms (EKGs) for review, two physicians independently coded the arrhythmia diagnosis and outcome of adenosine administration. Statistical analysis included interrater reliability with Cohen's kappa statistic. RESULTS: One hundred eighty-three cases were included for final analysis, 84 did not have a documented EKG for review. Categorization of presenting rhythms in these cases occurred by a physician reviewing EMS narrative and documentation. Forty of these 84 cases (48%) were adjudicated as SVT likely, 32 (38%) as SVT unlikely and 12 (14%) as uncategorized due to lack of supporting documentation. Of the 99 cases with EKGs available to review, there was substantial agreement of arrhythmia diagnosis interpretation between physician reviewers (Cohen's kappa 0.77-1.0); 54 cases were adjudicated as SVT by two physician reviewers. Other identified cardiac rhythms included atrial fibrillation (16), sinus tachycardia (11), and ventricular tachycardia (2). Adenosine cardioversion occurred in 47 of the 99 cases with EKGs available for physician review (47.5%). Adenosine cardioversion was also deemed to occur in 87% (47/54) of cases when the EKG rhythm was physician adjudicated SVT. CONCLUSIONS: This study supports the use of adenosine as a prehospital treatment for SVT while highlighting the need for continued efforts to improve paramedics' identification and management of tachyarrhythmias.

Early Changes in Patient Access Interval during the COVID-19 Pandemic.

Background: COVID-19 was first reported in the United States in January 2020. Its spread throughout the country required EMS systems to rapidly adapt to patient needs while protecting EMS personnel. EMS agencies developed protocols requiring personnel to don enhanced personal protective equipment prior to patient contact. We hypothesized that the Patient Access Interval (PAI), defined as the time from wheels stopped on scene to initial patient contact, had increased during the COVID pandemic. This had the potential to affect patient outcomes, particularly in time-sensitive emergencies such as cardiac arrest or respiratory distress. Methods: This retrospective cohort study used commercial ambulance data from the four largest cities in Connecticut at two different time points: (Pre-COVID) March-May 2019, and (COVID) March-May 2020. PAI was calculated from contemporaneously reported scene times. Total cases were analyzed, and sub-analyses performed for calls located at extended care facilities (ECFs), for all emergent (Echo/Delta) calls, and for medical cardiac arrest calls. Results: 92,846 total cases were evaluated: 50,083 from 2019, and 42,763 from 2020. Cases that did not include necessary time data for PAI were removed, yielding 75,796 total cases (41,852 from 2019, 33,944 from 2020). The average PAI increased from 1 minute 55 seconds (1 m:55s) Pre-COVID to 2 m:18s COVID. ECF PAI increased from 2 m:39s to 3 m:42s. Echo/Delta PAI increased from 1 m:42s to 2 m:07s. Medical cardiac arrest PAI increased from 1 m:27s to 2 m:04s, and ECF cardiac arrest PAI increased from 2 m:18s to 4 m:35s (all comparisons p < 0.01). Conclusions: There were statistically significant increases in all studied PAIs during COVID. The 23 second increase in PAI for all calls may not have been clinically significant in most cases; however, for life-threatening patient presentations, the increase may have been particularly relevant. The increased PAI was compounded in the ECF environment, possibly due to state-mandated screening and temperature checks of EMS personnel before entering facilities. This was highlighted in the ECF cardiac arrest data, which demonstrated a clinically significant increase in PAI of 2m:17s. While this study was limited by the accuracy of contemporaneous time reports by EMS, the results support our hypothesis that PAI had increased during the COVID pandemic.

STEMI Equivalents and Their Incidence during EMS Transport.

Objective: The management of patients with ST-elevation myocardial infarction (STEMI) is time-critical, with a focus on early reperfusion to decrease morbidity and mortality. It is imperative that prehospital clinicians recognize STEMI early and initiate transport to hospitals capable of percutaneous coronary intervention (PCI) with a door-to-balloon time of ≤90 minutes. Three patterns have been identified as STEMI equivalents that also likely warrant prompt attention and potentially PCI: Wellens syndrome, De Winter T waves, and aVR ST elevation. The goal of our study was to assess the incidence of these findings in prehospital patients presenting with chest pain. Methods: We conducted a retrospective chart review from a large urban tertiary care emergency department. We reviewed the prehospital ECG, or ECG upon arrival, of 861 patients who were hospitalized and required cardiac catheterization between 4/10/18 and 5/7/19. Patients who had field catheterization lab activation by EMS for STEMI were excluded. If a prehospital ECG was not available for review, the first ECG obtained in the hospital was used as a proxy. Each ECG was screened for aVR elevation, De Winter T waves, and Wellens syndrome. Results: Of 278 charts with prehospital ECGs available, 12 met our criteria for STEMI equivalency (4.4%): 6 Wellens syndrome and 6 aVR STEMI. There were no cases of De Winters T waves. Of 573 charts with no prehospital ECG available, 27 had initial hospital ECGs that met our STEMI equivalent criteria (4.7%): 7 Wellens syndrome and 20 aVR STEMI. Again, there were no cases of De Winters T waves. Conclusions: These preliminary data suggest that there are significant numbers of patients whose prehospital ECG findings do not currently meet criteria for field activation of the cardiac catheterization lab, but who may require prompt catheterization. Further studies are needed to look at outcomes, but these results could support the need for further education of prehospital clinicians regarding recognition of these STEMI equivalents, as well as quality initiatives aimed at decreasing door-to-balloon time for patients with STEMI equivalents.

RETINAL DETACHMENT WITH INFERIOR RETINAL BREAKS: Primary Vitrectomy Versus Vitrectomy With Scleral Buckle (PRO Study Report No. 9).

INTRODUCTION: Rhegmatogenous retinal detachments with inferior retinal breaks are believed to have a higher risk of recurrent rhegmatogenous retinal detachment. This study compared anatomic and visual outcomes between primary pars plana vitrectomy (PPV) and combination PPV with scleral buckle (PPV/SB) for rhegmatogenous retinal detachments with inferior retinal breaks. METHODS: This is an analysis of the Primary Retinal Detachment Outcomes study, a multi-institutional cohort study of consecutive primary rhegmatogenous retinal detachment surgeries from January 1, 2015, through December 31, 2015. The primary outcome was single-surgery success rate. Only eyes with inferior retinal breaks (one break in the detached retina between five and seven o'clock) were included. RESULTS: There were 238 eyes that met the inclusion criteria, 95 (40%) of which underwent primary PPV and 163 (60%) that underwent combined PPV/SB. The single-surgery success rate was 76.8% for PPV and 87.4% for PPV/SB (P = 0.0355). This remained significant on multivariate analysis (P = 0.01). Subgroup analysis showed that a superior single-surgery success rate of PPV/SB was especially noted in phakic eyes (85.2% vs. 68.6%; P = 0.0464). CONCLUSION: Retinal detachment with inferior retinal breaks had a higher single-surgery success rate if treated with PPV/SB compared with PPV alone, particularly in phakic eyes.

CHARACTERISTICS AND SURGICAL OUTCOMES OF RHEGMATOGENOUS RETINAL DETACHMENT IN OLDER ADULTS: A Multicenter Comparative Cohort Study.

PURPOSE: To describe characteristics and outcomes of primary rhegmatogenous retinal detachment in older adults (age ≥ 80). METHODS: Consecutive patients with rhegmatogenous retinal detachment undergoing pars plana vitrectomy (PPV), scleral buckling (SB), or PPV/SB in the Primary Retinal Detachment Outcomes Study were evaluated. Outcome measures included single surgery anatomic success and visual acuity. RESULTS: Of 2,144 patients included, 125 (6%) were 80 years or older. Compared with younger patients (age 40-79), older adults were more likely to be pseudophakic (P < 0.001), have macula-off detachments (P < 0.001), and have preoperative proliferative vitreoretinopathy (P = 0.02). In older adults, initial surgery was PPV in 73%, PPV/SB in 27%, and primary SB in 0%. Single surgery anatomic success was 78% in older adults compared with 84% in younger patients (P = 0.03). In older adults, single surgery anatomic success was 74% for PPV and 91% for PPV/SB (P = 0.03). The final mean logMAR was lower for older adults (0.79 [20/125] vs. 0.40 [20/40], [P < 0.001]). In older adults, the final mean logMAR for eyes that underwent PPV was 0.88 (20/160) compared with 0.50 (20/63) for PPV/SB (P = 0.03). CONCLUSION: Octogenarians and nonagenarians presented with relatively complex pseudophakic rhegmatogenous retinal detachments. Single surgery anatomic success and visual outcomes were worse compared with younger patients, and PPV/SB had better outcomes compared with PPV alone.

Primary Retinal Detachment Outcomes Study: Pseudophakic Retinal Detachment Outcomes: Primary Retinal Detachment Outcomes Study Report Number 3.

PURPOSE: This study evaluates outcomes of comparable pseudophakic rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy (PPV) or PPV with scleral buckle (PPV-SB). DESIGN: Multicenter, retrospective, interventional cohort study. PARTICIPANTS: Data were gathered from patients from multiple retina practices in the United States with RRD in 2015. METHODS: A large detailed database was generated. Pseudophakic patients with RRD managed with PPV or PPV-SB were analyzed for anatomic and visual outcomes. Eyes with proliferative vitreoretinopathy, giant retinal tears, previous invasive glaucoma surgery, and ≤90 days of follow-up were excluded from outcomes analysis. Single surgery anatomic success (SSAS) was defined as retinal attachment without ongoing tamponade and with no other RRD surgery within 90 days. MAIN OUTCOME MEASURES: Single surgery anatomic success and final Snellen visual acuity (VA). RESULTS: A total of 1158 of 2620 eyes (44%) with primary RRD were pseudophakic. A total of 1018 eyes had greater than 90 days of follow-up. Eyes with proliferative vitreoretinopathy, previous glaucoma surgery, and giant retinal tears were excluded, leaving 893 pseudophakic eyes eligible for outcome analysis. A total of 461 (52%) were right eyes. A total of 606 patients (67%) were male, with a mean age of 65±11 years. Pars plana vitrectomy and PPV-SB as the first procedure were performed on 684 eyes (77%) and 209 eyes (23%), respectively. The mean follow-up was 388±161 days, and overall SSAS was achieved in 770 eyes (86%). Single surgery anatomic success was 84% (577/684) for PPV and 92% (193/209) for PPV-SB. The difference in SSAS between types of treatment was significant (P = 0.009). In eyes with macula-on RRD, SSAS was 88% in eyes treated with PPV and 100% in eyes treated with PPV-SB (P = 0.0088). In eyes with macula-off RRD, SSAS was 81% in eyes treated with PPV and 89% in eyes treated with PPV-SB (P = 0.029). Single surgery anatomic success was greater for PPV-SB than PPV for inferior (96% vs. 82%) and superior (90% vs. 82%) detachments. Mean final VA was similar for PPV (20/47) and PPV-SB (20/46; P = 0.805). CONCLUSIONS: In pseudophakic RRDs, SSAS was better in patients treated with PPV-SB compared with PPV alone, whereas visual outcomes were similar for both groups.

Primary Retinal Detachment Outcomes Study Report Number 2: Phakic Retinal Detachment Outcomes.

PURPOSE: Anatomically similar rhegmatogenous retinal detachments (RRDs) can be treated with scleral buckle (SB), pars plana vitrectomy (PPV), or SB combined with PPV (PPV/SB). This study compares moderately complex phakic primary RRD treated with SB, PPV, or PPV/SB to review anatomic and visual outcomes. DESIGN: Multicenter, retrospective, interventional cohort study. PARTICIPANTS: Data were gathered on all patients from multiple retina practices in the United States with RRD in 2015 and >90 days of follow-up. The cohort of phakic patients with moderately complex RRD was analyzed. METHODS: A large and detailed database was generated. Eyes with findings that would bias toward PPV (vitreous hemorrhage, dense cataract, proliferative vitreoretinopathy, giant retinal tear, among others) were excluded. Age <40 years (bias toward SB) was excluded. Comparable cases of moderately complex RRD were then chosen naive to surgeon, surgery, and outcome for subgroup analysis. MAIN OUTCOME MEASURES: Single surgery anatomic success (SSAS), defined as retinal attachment with no other RRD surgery within 90 days, is the main outcome measure. Final visual acuity is the secondary outcome measure. Pearson's chi-square and analysis of variance were used to test treatment effect of surgery type on SSAS and vision. RESULTS: Single surgery anatomic success was noted in 155 of 169 SB cases (91.7%), 207 of 249 PPV cases (83.1%), and 271 of 297 PPV/SB cases (91.2%). Scleral buckle and PPV/SB were superior to PPV for SSAS (P = 0.0041). For macula-on or split cases, SB had significantly better visual outcomes than PPV or PPV/SB even after controlling for cataract (cases with minimal cataract at final follow-up or after cataract surgery) (P < 0.001). CONCLUSIONS: For phakic moderately complex primary RRDs in this study of PPV versus SB versus PPV/SB, SB had the best visual outcomes, and PPV had the worst SSAS outcomes.

FACTORS ASSOCIATED WITH THE USE OF 360-DEGREE LASER RETINOPEXY DURING PRIMARY VITRECTOMY WITH OR WITHOUT SCLERAL BUCKLE FOR RHEGMATOGENOUS RETINAL DETACHMENT AND IMPACT ON SURGICAL OUTCOMES (PRO STUDY REPORT NUMBER 4).

PURPOSE: To determine factors associated with 360-degree laser retinopexy (360LR) during primary pars plana vitrectomy ± scleral buckle for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. METHODS: This is a multicenter, retrospective, interventional study. Patients undergoing primary pars plana vitrectomy or primary pars plana vitrectomy + scleral buckle for noncomplex primary RRD in 2015 were evaluated. Primary outcomes were single surgery anatomical success (SSAS) and final anatomical success. Secondary outcomes included final logarithm of the minimum angle of resolution visual acuity, epiretinal membrane formation, cystoid macular edema development, and number of subsequent vitrectomies. Multivariate regressions were performed. RESULTS: Two thousand two hundred and forty-eight surgeries by 61 surgeons were included; of which, 516 underwent 360LR. Younger age (P = 0.01), more retinal breaks (P = 0.01), more extensive RRD (P < 0.001), and surgeon ID (P < 0.001) were significantly associated with 360LR. No significant associations between 360LR and single surgery anatomical success (P = 0.44), epiretinal membrane formation (P = 0.14), cystoid macular edema development (P = 0.28), or number of subsequent vitrectomies (P = 0.41) were found. Controlling for case complexity, 360LR was significantly associated with lower final anatomical success (P < 0.001) and worse final logarithm of the minimum angle of resolution visual acuity (P < 0.001). CONCLUSION: Multiple factors influenced whether 360LR was performed during primary pars plana vitrectomy ± scleral buckle for RRD. However, 360LR was not associated with improved surgical outcomes, and in fact, it may be associated with poorer outcomes.

Effects of Real-time EMS Direction on Optimizing EMS Turnaround and Load-balancing Between Neighboring Hospital Campuses.

Background: Implemented in September 2017, the "nurse navigator program" identified the preferred emergency department (ED) destination within a single healthcare system using real-time assessment of hospital and ED capacity and crowding metrics. Objective: The primary objective of the navigator program was to improve load-balancing between two closely situated emergency departments, both of which feed into the same inpatient facilities of a single healthcare system. A registered nurse in the hospital command center made real-time recommendations to emergency medical services (EMS) providers via radio, identifying the preferred destination for each transported patient based on such factors as chief complaint, ED volume, and waiting room census. The destination decision was made via the utilization of various real-time measures of health system capacity in conjunction with existing protocols dictating campus-specific clinical service availability. The objective of this study was to evaluate the efficacy of this real-time ambulance destination direction program as reflected in changes to emergency medical services (EMS) turnaround time and the incidence of intercampus transports. Methods: A before-and-after time series was performed to determine if program implementation resulted in a change in EMS turnaround time or incidence of intercampus transfers. Results: Implementation of the nurse navigator program was associated with a statistically significant decrease in EMS turnaround times for all levels of dispatch and transport at both hospital campuses. Intercampus transfers also showed significant improvement following implementation of the intervention, although this effect lagged behind implementation by several months. Conclusion: A proactive approach to EMS destination control using a nurse navigator with access to real-time hospital and ED capacity metrics appears to be an effective method of decreasing EMS turnaround time.

Small to modest impact of social group on the gut microbiome of wild Costa Rican capuchins in a seasonal forest.

The horizontal transmission of pathogenic and beneficial microbes has implications for health and development of socially living animals. Social group is repeatedly implicated as an important predictor of gut microbiome structure among primates, with individuals in neighboring social groups exhibiting distinct microbiomes. Here we examine whether group membership is a predictor of gut microbiome structure and diversity across three groups of white-faced capuchins (Cebus capucinus imitator) inhabiting a seasonal Costa Rican forest. We collected 62 fecal samples from 18 adult females during four sampling bouts. Sampling bouts spanned the dry-to-wet-to-dry seasonal transitions. To investigate gut microbial composition, we sequenced the V4 region of the 16S rRNA gene. We used the DADA2 pipeline to assign amplicon sequence variants and the RDP database to classify taxa. Our findings are: 1) gut microbiomes of capuchins clustered by social group in the late dry season, but this pattern was less evident in other sampling bouts; 2) social group was a significant variable in a PERMANOVA test of beta diversity, but it accounted for less variation than season; 3) social group was not an important predictor of abundance for the ten most abundant microbial taxa in capuchins; 4) when examining log2-fold abundances of microbes between social groups, there were significant differences in some pairwise comparisons. While this is suggestive of group-wide differences, individual variation may have a strong impact and should be assessed in future studies. Overall, we found a minor impact of social group membership on the gut microbiota of wild white-faced capuchins. Future research including home range overlap and resource use, as well as fine-scale investigation of individual variation, will further elucidate patterns of socially structured microbes.

Alcohol as a Factor in 911 Calls in Denver.

BACKGROUND: Excessive alcohol consumption is associated with a substantial number of emergency department visits annually and is responsible for a significant number of lives lost each year in the United States. However, a minimal amount is known about the impact of alcohol on the EMS system. OBJECTIVES: The primary objective was to determine the proportion of 9-1-1 calls in Denver, Colorado in which (1) alcohol was a contributing factor or (2) the individual receiving EMS services had recently ingested alcohol. The secondary objectives were to compare the characteristics of EMS calls and to estimate the associated costs. METHODS: This was a prospective observational cohort study of EMS calls for adults from July 1, 2012, to June 30, 2014. Primary outcomes for the study were alcohol as a contributing factor to the EMS call and recent alcohol consumption by the patient receiving EMS services. Logistic regression was utilized to determine the associations between EMS call characteristics and the outcomes. Cost was estimated using historic data. RESULTS: During the study period, 169,642 EMS calls were completed by the Denver Health Paramedic Division. Of these 71% were medical and 29% were trauma-related. The median age was 45 (interquartile range [IQR] 29-59) years, and 55% were male. 50,383 calls (30%) had alcohol consumption, and 49,165 (29%) had alcohol as a contributing factor. Alcohol related calls were associated with male sex, traumatic injuries including head trauma, emergent response, use of airway adjuncts, cardiac monitoring, glucose measurement, use of restraints, use of spinal precautions, and administration of medications for sedation. Estimated costs to the EMS system due to alcohol intoxication exceeded $14 million dollars over the study period and required in excess of 37 thousand hours of paramedic time. CONCLUSIONS: Compared to 9-1-1 calls that do not involve alcohol, alcohol-related calls are more likely to involve male patients, emergent response, traumatic injuries, advanced monitoring, airway adjuncts, and medications for sedation. This represents a significant burden on the emergency system and society. Further studies are needed to evaluate whether additional interventions such as social services could be used to lessen this burden.

Down syndrome in diverse populations.

Down syndrome is the most common cause of cognitive impairment and presents clinically with universally recognizable signs and symptoms. In this study, we focus on exam findings and digital facial analysis technology in individuals with Down syndrome in diverse populations. Photos and clinical information were collected on 65 individuals from 13 countries, 56.9% were male and the average age was 6.6 years (range 1 month to 26 years; SD = 6.6 years). Subjective findings showed that clinical features were different across ethnicities (Africans, Asians, and Latin Americans), including brachycephaly, ear anomalies, clinodactyly, sandal gap, and abundant neck skin, which were all significantly less frequent in Africans (P < 0.001, P < 0.001, P < 0.001, P < 0.05, and P < 0.05, respectively). Evaluation using a digital facial analysis technology of a larger diverse cohort of newborns to adults (n = 129 cases; n = 132 controls) was able to diagnose Down syndrome with a sensitivity of 0.961, specificity of 0.924, and accuracy of 0.943. Only the angles at medial canthus and ala of the nose were common significant findings amongst different ethnicities (Caucasians, Africans, and Asians) when compared to ethnically matched controls. The Asian group had the least number of significant digital facial biometrics at 4, compared to Caucasians at 8 and Africans at 7. In conclusion, this study displays the wide variety of findings across different geographic populations in Down syndrome and demonstrates the accuracy and promise of digital facial analysis technology in the diagnosis of Down syndrome internationally. © 2016 Wiley Periodicals, Inc.

Structures of intermediate transport states of ZneA, a Zn(II)/proton antiporter.

Efflux pumps belonging to the ubiquitous resistance-nodulation-cell division (RND) superfamily transport substrates out of cells by coupling proton conduction across the membrane to a conformationally driven pumping cycle. The heavy metal-resistant bacteria Cupriavidus metallidurans CH34 relies notably on as many as 12 heavy metal efflux pumps of the RND superfamily. Here we show that C. metallidurans CH34 ZneA is a proton driven efflux pump specific for Zn(II), and that transport of substrates through the transmembrane domain may be electrogenic. We report two X-ray crystal structures of ZneA in intermediate transport conformations, at 3.0 and 3.7 Å resolution. The trimeric ZneA structures capture protomer conformations that differ in the spatial arrangement and Zn(II) occupancies at a proximal and a distal substrate binding site. Structural comparison shows that transport of substrates through a tunnel that links the two binding sites, toward an exit portal, is mediated by the conformation of a short 14-aa loop. Taken together, the ZneA structures presented here provide mechanistic insights into the conformational changes required for substrate efflux by RND superfamily transporters.

Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats.

Genetic modifier loci influence the inheritance of diseases and lead to variability in phenotype progression. We report the influence of modifier loci in female Wistar Kyoto (WKY) rats on cellular pathogenesis of nephronophthisis inherited from Lewis polycystic kidney (LPK) rats. The loci modified cellular expression and progression of nephronophthisis in the backcross 1 (BC1) progeny. Mating experiments to produce BC1 progeny were carried out between three male LPK and seven female WKY rats. Fifteen female rats from the F1 generation were mated with the male LPK rats to produce the BC1 progeny. The rats with cystic kidney disease were identified and histology of the kidneys was carried out. Mapping studies and linkage analysis were carried out to identify the modifier loci. The BC1 progeny were less affected than the LPK strain with respect to disease severity and progression of the kidneys to end stage renal disease. It was found that the mean values of all the disease phenotypes of the mutant BC1 progeny were significantly different from those of the LPK rats, and these segregated with the genotypes of the markers located on chromosomes 5q34-q36 and 7q11-q34, giving maximum LOD scores greater than 3 (p < 0.001).

Factors and clinical prediction score for complication development after cellulitis diagnosis in adult patients.

BACKGROUND: Cellulitis is defined as a bacterial infection of the skin and subcutaneous tissue that can cause multiple complications, such as sepsis and necrotizing fasciitis. In extreme cases, it may lead to multiorgan failure and death. We sought to analyze the clinical factors that contribute to the development of complicated disease, including demographics, clinical presentation, initial vital signs, and laboratory studies. METHODS: Our study is a retrospective cohort study carried out in a university-based tertiary care hospital in Bangkok, Thailand. Adult patients who presented with cellulitis from January 1, 2018, to December 31, 2022, were evaluated for eligibility and inclusion in this study. All related variables for both outcomes, bacteremia and necrotizing fasciitis, were gathered from electronic medical records and analyzed using multivariable logistic regression analysis. RESULTS: Of the 1,560 visits to this hospital, 47 cases reported at least one complication, with bacteremia noted in 27 visits (1.73%) and necrotizing fasciitis in 20 visits (1.27%). From the multivariable logistic regression analysis, six variables emerge as predictors of cellulitis complications. These are: Age ≥ 65 years, Body Mass Index ≥ 30 kg/m2, diabetes mellitus, body temperature ≥ 38 °C, systolic blood pressure ≤ 100 mmHg, and involvement of lower extremities. The predictive score was developed from these factors and was named the Ramathibodi Necrotizing Fasciitis/Bacteremia (RAMA-NFB) Prediction Score. Our predictive score has an accuracy of 82.93% (95% CI, 0.77-0.89). Patients in the high-risk group (RAMA NFB score > 6) have a likelihood ratio of 8.75 (95% CI, 4.41-18.12; p < 0.001) times to develop complications of cellulitis. CONCLUSION: In our study, the RAMA-NFB Prediction Score predicts complications of necrotizing fasciitis and bacteremia in adult patients who present with cellulitis. External validation of this predictive score is still needed for further practical application.

Very-low-density lipoprotein triglyceride and free fatty acid plasma kinetics in women with high or low brown adipose tissue volume and overweight/obesity.

Although a high amount of brown adipose tissue (BAT) is associated with low plasma triglyceride concentration, the mechanism responsible for this relationship in people is not clear. Here, we evaluate the interrelationships among BAT, very-low-density lipoprotein triglyceride (VLDL-TG), and free fatty acid (FFA) plasma kinetics during thermoneutrality in women with overweight/obesity who had a low (<20 mL) or high (≥20 mL) volume of cold-activated BAT (assessed by using positron emission tomography in conjunction with 2-deoxy-2-[18F]-fluoro-glucose). We find that plasma TG and FFA concentrations are lower and VLDL-TG and FFA plasma clearance rates are faster in women with high BAT than low BAT volume, whereas VLDL-TG and FFA appearance rates in plasma are not different between the two groups. These findings demonstrate that women with high BAT volume have lower plasma TG and FFA concentrations than women with low BAT volumes because of increased VLDL-TG and FFA clearance rates. This study was registered at ClinicalTrials.gov (NCT02786251).

Estimating averted illnesses from influenza vaccination for children and pregnant women - El Salvador, Panama, and Peru, 2011-2018.

BACKGROUND: Estimating the burden of disease averted by vaccination can assist policymakers to implement, adjust, and communicate the value of vaccination programs. Demonstrating the use of a newly available modeling tool, we estimated the burden of influenza illnesses averted by seasonal influenza vaccination in El Salvador, Panama, and Peru during 2011-2017 among two influenza vaccine target populations: children aged 6-23 months and pregnant women. METHODS: We derived model inputs, including incidence, vaccine coverage, vaccine effectiveness, and multipliers from publicly available country-level influenza surveillance data and cohort studies. We also estimated changes in illnesses averted when countries' vaccine coverage was achieved using four different vaccine deployment strategies. RESULTS: Among children aged 6-23 months, influenza vaccination averted an estimated cumulative 2,161 hospitalizations, 81,907 medically-attended illnesses, and 126,987 overall illnesses during the study period, with a prevented fraction ranging from 0.3 % to 12.5 %. Among pregnant women, influenza vaccination averted an estimated cumulative 173 hospitalizations, 6,122 medically attended illnesses, and 16,412 overall illnesses, with a prevented fraction ranging from 0.2 % to 10.9 %. Compared to an influenza vaccine campaign with equal vaccine distribution during March-June, scenarios in which total cumulative coverage was achieved in March and April consistently resulted in the greatest increase in averted illness (23 %-3,129 % increase among young children and 22 %-3,260 % increase among pregnant women). DISCUSSION: Influenza vaccination campaigns in El Salvador, Panama, and Peru conducted between 2011 and 2018 prevented hundreds to thousands of influenza-associated hospitalizations and illnesses in young children and pregnant women. Existing vaccination programs could prevent additional illnesses, using the same number of vaccines, by achieving the highest possible coverage within the first two months of an influenza vaccine campaign.