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1.
Trauma Surg Acute Care Open ; 9(1): e001503, 2024.
Article in English | MEDLINE | ID: mdl-39005706

ABSTRACT

Background: Restorative justice interventions can help address the harm created by gun violence, although few restorative justice programs focus solely on survivors or loved ones of victims of gun violence. Our aim was to assess how gun violence impacts those injured by firearms through qualitative analysis of their lived experiences. Methods: From August 2022 to October 2023, we operated a program entitled Prescriptions for Repair in Durham, North Carolina, USA, which was supported by community groups, public government, and academia. Through a series of structured listening sessions using a restorative justice framework, trained community-based facilitators helped 30 participants (11 survivors of gun violence and 19 loved ones of victims of gun violence) tell their stories through a non-judgmental narrative process. We conducted a qualitative thematic analysis of the listening sessions from 19 participants to define the major lessons learned from survivors of gun violence. We summarized participant responses into individual-level and community-level views on how to 'make things as right as possible'. Results: The lived experiences of gun violence survivors and their loved ones confirmed the inherent value of structured listening programs, how poverty, race and racism impact gun violence, and the need to focus resources on children and youth. Conclusions: Listening to the survivors of gun violence through restorative justice programs can help address the personal and community harm resulting from gun violence. Level of evidence: Level IV, prospective observational study.

2.
JAMA Netw Open ; 7(7): e2419274, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38967927

ABSTRACT

Importance: While widely measured, the time-varying association between exhaled end-tidal carbon dioxide (EtCO2) and out-of-hospital cardiac arrest (OHCA) outcomes is unclear. Objective: To evaluate temporal associations between EtCO2 and return of spontaneous circulation (ROSC) in the Pragmatic Airway Resuscitation Trial (PART). Design, Setting, and Participants: This study was a secondary analysis of a cluster randomized trial performed at multicenter emergency medical services agencies from the Resuscitation Outcomes Consortium. PART enrolled 3004 adults (aged ≥18 years) with nontraumatic OHCA from December 1, 2015, to November 4, 2017. EtCO2 was available in 1172 cases for this analysis performed in June 2023. Interventions: PART evaluated the effect of laryngeal tube vs endotracheal intubation on 72-hour survival. Emergency medical services agencies collected continuous EtCO2 recordings using standard monitors, and this secondary analysis identified maximal EtCO2 values per ventilation and determined mean EtCO2 in 1-minute epochs using previously validated automated signal processing. All advanced airway cases with greater than 50% interpretable EtCO2 signal were included, and the slope of EtCO2 change over resuscitation was calculated. Main Outcomes and Measures: The primary outcome was ROSC determined by prehospital or emergency department palpable pulses. EtCO2 values were compared at discrete time points using Mann-Whitney test, and temporal trends in EtCO2 were compared using Cochran-Armitage test of trend. Multivariable logistic regression was performed, adjusting for Utstein criteria and EtCO2 slope. Results: Among 1113 patients included in the study, 694 (62.4%) were male; 285 (25.6%) were Black or African American, 592 (53.2%) were White, and 236 (21.2%) were another race; and the median (IQR) age was 64 (52-75) years. Cardiac arrest was most commonly unwitnessed (n = 579 [52.0%]), nonshockable (n = 941 [84.6%]), and nonpublic (n = 999 [89.8%]). There were 198 patients (17.8%) with ROSC and 915 (82.2%) without ROSC. Median EtCO2 values between ROSC and non-ROSC cases were significantly different at 10 minutes (39.8 [IQR, 27.1-56.4] mm Hg vs 26.1 [IQR, 14.9-39.0] mm Hg; P < .001) and 5 minutes (43.0 [IQR, 28.1-55.8] mm Hg vs 25.0 [IQR, 13.3-37.4] mm Hg; P < .001) prior to end of resuscitation. In ROSC cases, median EtCO2 increased from 30.5 (IQR, 22.4-54.2) mm HG to 43.0 (IQR, 28.1-55.8) mm Hg (P for trend < .001). In non-ROSC cases, EtCO2 declined from 30.8 (IQR, 18.2-43.8) mm Hg to 22.5 (IQR, 12.8-35.4) mm Hg (P for trend < .001). Using adjusted multivariable logistic regression with slope of EtCO2, the temporal change in EtCO2 was associated with ROSC (odds ratio, 1.45 [95% CI, 1.31-1.61]). Conclusions and Relevance: In this secondary analysis of the PART trial, temporal increases in EtCO2 were associated with increased odds of ROSC. These results suggest value in leveraging continuous waveform capnography during OHCA resuscitation. Trial Registration: ClinicalTrials.gov Identifier: NCT02419573.


Subject(s)
Capnography , Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Humans , Out-of-Hospital Cardiac Arrest/therapy , Male , Capnography/methods , Female , Middle Aged , Aged , Cardiopulmonary Resuscitation/methods , Return of Spontaneous Circulation , Emergency Medical Services/methods , Carbon Dioxide/analysis , Carbon Dioxide/metabolism , Time Factors
3.
Ophthalmology ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38849055

ABSTRACT

PURPOSE: To report the efficacy of the oral hypoxia-inducible factor 2α inhibitor belzutifan in participants with von Hippel-Lindau disease-associated retinal hemangioblastomas in the LITESPARK-004 study. DESIGN: Subgroup analysis of the phase 2, single-arm, open-label LITESPARK-004 study. PARTICIPANTS: Adults with 1 or more von Hippel-Lindau disease-associated measurable renal cell carcinoma tumors not requiring immediate surgical intervention were eligible. METHODS: Participants received oral belzutifan 120 mg once daily until disease progression or unacceptable treatment-related toxicity. MAIN OUTCOME MEASURES: Efficacy of belzutifan in retinal hemangioblastomas was a secondary end point, measured as response (improved, stable, or progressed) by independent reading center-certified graders based on color fundus imaging performed every 12 weeks using the investigator's preferred imaging standards. Additional assessments, where available, included OCT and ultra-widefield fluorescein angiography. RESULTS: Among 61 participants in LITESPARK-004, 12 had 1 or more evaluable active retinal hemangioblastomas in 16 eyes at baseline per independent reading center. As of April 1, 2022, the median follow-up for participants with ocular von Hippel-Lindau disease at baseline was 37.3 months. All 16 eyes were graded as improved, with a response rate of 100.0% (95% confidence interval, 79.4%-100%). No new retinal hemangioblastomas or ocular disease progression were reported as of data cutoff date. Eight participants underwent additional multimodal eye assessments performed at the National Institutes of Health study site. Among this subgroup, 10 of 24 hemangioblastomas in 8 eyes of 6 participants measured 500 µm or more in greatest linear dimension at baseline and were analyzed further. All 10 hemangioblastomas had a mean area reduction of 15% or more by month 12 and of 30% or more by month 24. CONCLUSIONS: Belzutifan showed promising activity against ocular von Hippel-Lindau disease, including capacity to control retinal hemangioblastomas, with effects sustained for more than 2 years while treatment is ongoing. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

4.
Resuscitation ; 201: 110266, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38857847

ABSTRACT

BACKGROUND: Early administration of adrenaline is associated with improved survival after out-of-hospital cardiac arrest (OHCA). Delays in vascular access may impact the timely delivery of adrenaline. Novel methods for administering adrenaline before vascular access may enhance survival. The objective of this study was to determine whether an initial intramuscular (IM) adrenaline dose followed by standard IV/IO adrenaline is associated with improved survival after OHCA. METHODS STUDY DESIGN: We conducted a before-and-after study of the implementation of an early, first-dose IM adrenaline EMS protocol for adult OHCAs. The pre-intervention period took place between January 2010 and October 2019. The post-intervention period was between November 2019 and May 2024. SETTING: Single-center urban, two-tiered EMS agency. PARTICIPANTS: Adult, nontraumatic OHCA meeting criteria for adrenaline use. INTERVENTION: Single dose (5 mg) IM adrenaline. All other care, including subsequent IV or IO adrenaline, followed international guidelines. MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. Secondary outcomes were time from EMS arrival to the first dose of adrenaline, survival to hospital admission, and favorable neurologic function at discharge. RESULTS: Among 1450 OHCAs, 372 (29.9%) received IM adrenaline and 985 (70.1%) received usual care. Fifty-two patients received the first dose of adrenaline through the IV or IO route within the post-intervention period and were included in the standard care group analysis. Age was younger and bystander CPR was higher in the IM adrenaline group. All other characteristics were similar between IM and standard care cohorts. Time to adrenaline administration was faster for the IM cohort [(median 4.3 min (IQR 3.0-6.0) vs. 7.8 min (IQR 5.8-10.4)]. Compared with standard care, IM adrenaline was associated with improved survival to hospital admission (37.1% vs. 31.6%; aOR 1.37, 95% CI 1.06-1.77), hospital survival (11.0% vs 7.0%; aOR 1.73, 95% CI 1.10-2.71) and favorable neurologic status at hospital discharge (9.8% vs 6.2%; aOR 1.72, 95% CI 1.07-2.76). CONCLUSION: In this single-center before-and-after implementation study, an initial IM dose of adrenaline as an adjunct to standard care was associated with improved survival to hospital admission, survival to hospital discharge, and functional survival. A randomized controlled trial is needed to fully assess the potential benefit of IM adrenaline delivery in OHCA.

5.
PLoS One ; 19(6): e0304165, 2024.
Article in English | MEDLINE | ID: mdl-38913675

ABSTRACT

BACKGROUND: There is limited understanding of how social determinants of health (SDOH) impact family decision-making when seeking surgical care for children. Our objectives of this study are to identify key family experiences that contribute to decision-making when accessing surgical care for children, to confirm if family experiences impact delays in care, and to describe differences in family experiences across populations (race, ethnicity, socioeconomic status, rurality). METHODS: We will use a prospective, cross-sectional, mixed methods design to examine family experiences during access to care for children with appendicitis. Participants will include 242 parents of consecutive children (0-17 years) with acute appendicitis over a 15-month period at two academic health systems in North Carolina and Virginia. We will collect demographic and clinical data. Parents will be administered the Adult Responses to Children's Symptoms survey (ARCS), the child and parental forms of the Adverse Childhood Experiences (ACE) survey, the Accountable Health Communities Health-Related Social Needs Screening Tool, and Single Item Literacy Screener. Parallel ARCS data will be collected from child participants (8-17 years). We will use nested concurrent, purposive sampling to select a subset of families for semi-structured interviews. Qualitative data will be analyzed using thematic analysis and integrated with quantitative data to identify emerging themes that inform a conceptual model of family-level decision-making during access to surgical care. Multivariate linear regression will be used to determine association between the appendicitis perforation rate and ARCS responses (primary outcome). Secondary outcomes include comparison of health literacy, ACEs, and SDOH, clinical outcomes, and family experiences across populations. DISCUSSION: We expect to identify key family experiences when accessing care for appendicitis which may impact outcomes and differ across populations. Increased understanding of how SDOH and family experiences influence family decision-making may inform novel strategies to mitigate surgical disparities in children.


Subject(s)
Appendicitis , Decision Making , Health Services Accessibility , Humans , Child , Cross-Sectional Studies , Adolescent , Child, Preschool , Male , Female , Appendicitis/surgery , Infant , Prospective Studies , Parents/psychology , Infant, Newborn , Family/psychology , North Carolina , Virginia
7.
medRxiv ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38883717

ABSTRACT

Objective: To describe the distribution of alcohol and drug involvement in injurious falls by location and subtype of fall. Methods: Using the 2019 National Emergency Medical Services Information System (NEMSIS) dataset we identified 1,854,909 patients injured from falls requiring an Emergency Medical Services (EMS) response and determined the fall location (e.g. indoors or on street/sidewalk) and the EMS clinician's notation of alcohol or drug involvement. We analyzed substance involvement by fall subtype, location of fall and patient demographics. Results: Overall, for 7.4% of injurious falls there was a notation of substance use: 6.5% for alcohol alone, 0.6% for drugs and 0.3% for alcohol and drugs. 21.2% of falls that occurred on a street or sidewalk had a notation of substance use; alcohol use alone for 18.5% of falls, drugs alone for 1.7% of falls and alcohol and drugs for 0.9% of falls. Substance use prevalence was highest, at 30.3%, in the age group 21 to 64 years, for falls occurring on streets and sidewalks, without syncope or heat illness as contributing factors; alcohol use alone for 26.3%, drugs alone for 2.6%, and alcohol and drugs for 1.4%. Reported substance use involvement was more frequent for men compared to women for each location type. Conclusions: Overall, 1-in-5 injurious falls on streets and sidewalks and requiring EMS attention involved substance use, and these numbers likely underestimate the true burden. As cities seek to expand nightlife districts, design strategies to protect pedestrians from falls should be enacted.

8.
Res Sq ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38766041

ABSTRACT

Background: Injurious falls represent a significant public health burden. Research and polices have primarily focused on falls occurring indoors despite evidence that outdoor falls account for 47-58% of all falls requiring some medical attention. This study compared the clinical trauma severity of indoor versus outdoor injurious falls requiring Emergency Medical Services (EMS) response. Methods: Using the 2019 National Emergency Medical Services Information System (NEMSIS) dataset, we identified the location of patients injured from falls that required EMS response. We classified injury severity using 1) the Revised Trauma Score for Triage (T-RTS): ≤ 11 indicated the need for transport to a Trauma Center; 2) Glasgow Coma Scale (GCS): ≤8 and 9-12 indicated moderate and severe neurologic injury; and 3) patient clinical acuity by EMS: Dead, Critical, Emergent, Low. Results: Of 1,854,909 encounters for patients with injurious falls, the vast majority occurred indoors (n=1,596,860) compared to outdoors (n=152,994). The proportions of patients with moderate or severe GCS scores, were comparable between those with indoor falls (3.0%) and with outdoor falls on streets or sidewalks (3.8%), T-RTS scores indicating need for transport to a Trauma Center (5.2% vs 5.9%) and EMS acuity rated as Emergent or Critical (27.7% vs 27.1%).Injurious falls were more severe among male patients compared to females: and males injured by falling on streets or sidewalks had higher percentages for moderate or severe GCS scores (4.8% vs 3.6%) and T-RTS scores indicating the need for transport to a Trauma Center (7.3% vs 6.5%) compared to indoor falls. Young and middle-aged patients whose injurious falls occurred on streets or sidewalks were more likely to have a T-RTS score indicating the need for Trauma Center care compared to indoor falls among this subgroup. Yet older patients injured by falling indoors were more likely to have a T-RTS score indicating the need for Trauma Center than older patients who fell on streets or sidewalks. Conclusions: There was a similar proportion of patients with severe injurious falls that occurred indoors and on streets or sidewalks. These findings suggest the need to determine outdoor environmental risks for outdoor falls to support location-specific interventions.

9.
Sci Adv ; 10(21): eadj4452, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38781344

ABSTRACT

Most genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to construct a comprehensive atlas of candidate brain cis-regulatory elements. Using deep learning, we model these elements' sequence syntax and predict how binding sites for lineage-specific transcription factors contribute to cell type-specific gene regulation in various types of glia and neurons. The elements' evolutionary history suggests that new regulatory information in the brain emerges primarily via smaller sequence mutations within conserved mammalian elements rather than entirely new human- or primate-specific sequences. However, primate-specific candidate elements, particularly those active during fetal brain development and in excitatory neurons and astrocytes, are implicated in the heritability of brain-related human traits. Additionally, we introduce PsychSCREEN, a web-based platform offering interactive visualization of PsychENCODE-generated genetic and epigenetic data from diverse brain cell types in individuals with psychiatric disorders and healthy controls.


Subject(s)
Brain , Epigenesis, Genetic , Regulatory Sequences, Nucleic Acid , Humans , Brain/metabolism , Regulatory Sequences, Nucleic Acid/genetics , Animals , Evolution, Molecular , Mental Disorders/genetics , Regulatory Elements, Transcriptional/genetics , Neurons/metabolism , Gene Expression Regulation , Transcription Factors/genetics , Transcription Factors/metabolism
10.
Essays Biochem ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813783

ABSTRACT

Malate dehydrogenase (MDH) is a ubiquitous enzyme involved in cellular respiration across all domains of life. MDH's ubiquity allows it to act as an excellent model for considering the history of life and how the rise of aerobic respiration and eukaryogenesis influenced this evolutionary process. Here, we present the diversity of the MDH family of enzymes across bacteria, archaea, and eukarya, the relationship between MDH and lactate dehydrogenase (LDH) in the formation of a protein superfamily, and the connections between MDH and endosymbiosis in the formation of mitochondria and chloroplasts. The development of novel and powerful DNA sequencing techniques has challenged some of the conventional wisdom underlying MDH evolution and suggests a history dominated by gene duplication, horizontal gene transfer, and cryptic endosymbiosis events and adaptation to a diverse range of environments across all domains of life over evolutionary time. The data also suggest a superfamily of proteins that do not share high levels of sequential similarity but yet retain strong conservation of core function via key amino acid residues and secondary structural components. As DNA sequencing and 'big data' analysis techniques continue to improve in the life sciences, it is likely that the story of MDH will continue to refine as more examples of superfamily diversity are recovered from nature and analyzed.

11.
J Am Coll Emerg Physicians Open ; 5(3): e13167, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38721037

ABSTRACT

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

12.
BMC Cancer ; 24(1): 457, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609910

ABSTRACT

INTRODUCTION: The SARS-CoV-2 (COVID-19) pandemic has strained healthcare systems and presented unique challenges for children requiring cancer care, particularly in low- and middle-income countries. This study aimed to assess the impact of the COVID-19 pandemic on access to cancer care for children and adolescents in Northern Tanzania. METHODS: In this cross-sectional study, we assessed the demographic and clinical characteristics of 547 pediatric and adolescent cancer patients (ages 0-19 years old) between 2016 and 2022 using the population-based Kilimanjaro Cancer Registry (KCR). We categorized data into pre-COVID-19 (2016-2019) and COVID-19 (2020-2022) eras, and performed descriptive analyses of diagnostic, treatment, and demographic information. A secondary analysis was conducted on a subset of 167 patients with stage of diagnosis at presentation. RESULTS: Overall admissions nearly doubled during the pandemic (n = 190 versus 357). The variety of diagnoses attended at KCMC increased during the pandemic, with only five groups of diseases reported in 2016 to twelve groups of diseases in 2021. Most patients were diagnosed at a late stage (stage III or IV) across eras, with the proportion of under-five years old patients increasing late-diagnoses from 29.4% (before the pandemic), 52.8% (during the pandemic), when compared to the overall cohort. Around 95% of children in this age category reported late-stage diagnosis during the pandemic. Six out of the twelve cancer site groups also reported an increase in late-stage diagnosis. During the pandemic, the proportion of children receiving surgery increased from 15.8 to 30.8% (p < 0.001). CONCLUSION: Childhood and adolescent cancer care changed in Northern Tanzania during the COVID-19 pandemic, with increased late-stage diagnoses presentations among younger patients and the increased use of surgical therapies in the context of a growing practice. Understanding the impact of the COVID-19 pandemic on pediatric and adolescent cancer care can help us better adapt healthcare systems and interventions to the emerging needs of children and adolescents with cancer in the midst of a health crisis.


Subject(s)
COVID-19 , Neoplasms , Adolescent , Humans , Child , Infant, Newborn , Infant , Child, Preschool , Young Adult , Adult , COVID-19/epidemiology , Cross-Sectional Studies , Pandemics , SARS-CoV-2 , Tanzania/epidemiology , Neoplasms/diagnosis , Neoplasms/epidemiology , Neoplasms/therapy
14.
World J Surg ; 48(4): 967-977, 2024 04.
Article in English | MEDLINE | ID: mdl-38491818

ABSTRACT

BACKGROUND: Choledochal cysts are rare congenital anomalies of the biliary tree that may lead to obstruction, chronic inflammation, infection, and malignancy. There is wide variation in the timing of resection, operative approach, and reconstructive techniques. Outcomes have rarely been compared on a national level. METHODS: We queried the Pediatric National Surgical Quality Improvement Program (NSQIP) to identify patients who underwent choledochal cyst excision from 2015 to 2020. Patients were stratified by hepaticoduodenostomy (HD) versus Roux-en-Y hepaticojejunostomy (RNYHJ), use of minimally invasive surgery (MIS), and age at surgery. We collected several outcomes, including length of stay (LOS), reoperation, complications, blood transfusions, and readmission rate. We compared outcomes between cohorts using nonparametric tests and multivariate regression. RESULTS: Altogether, 407 patients met the study criteria, 150 (36.8%) underwent RNYHJ reconstruction, 100 (24.6%) underwent MIS only, and 111 (27.3%) were less than one year old. Patients who underwent open surgery were younger (median age 2.31 vs. 4.25 years, p = 0.002) and more likely underwent RNYHJ reconstruction (42.7% vs. 19%, p = 0.001). On adjusted analysis, the outcomes of LOS, reoperation, transfusion, and complications were similar between the type of reconstruction, operative approach, and age. Patients undergoing RNYHJ had lower rates of readmission than patients undergoing HD (4.0% vs. 10.5%, OR 0.34, CI [0.12, 0.79], p = 0.02). CONCLUSIONS: In children with choledochal cysts, most short-term outcomes were similar between reconstructive techniques, operative approach, and age at resection, although HD reconstruction was associated with a higher readmission rate in this study. Clinical decision-making should be driven by long-term and biliary-specific outcomes.


Subject(s)
Choledochal Cyst , Laparoscopy , Child , Humans , Child, Preschool , Infant , Choledochal Cyst/surgery , Quality Improvement , Anastomosis, Roux-en-Y/methods , Laparoscopy/methods , Treatment Outcome , Retrospective Studies
15.
JAMA Ophthalmol ; 142(4): 345-355, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38483382

ABSTRACT

Importance: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable. Objective: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD. Design, Setting, and Participants: This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023. Intervention: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years. Main Outcomes and Measures: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase. Results: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 µm per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants). Conclusions and Relevance: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.


Subject(s)
Geographic Atrophy , Wet Macular Degeneration , Humans , Female , Aged , Geographic Atrophy/drug therapy , Minocycline/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Prospective Studies , Vascular Endothelial Growth Factor A , Visual Acuity , Wet Macular Degeneration/drug therapy , Fluorescein Angiography
16.
Trop Med Health ; 52(1): 24, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38486241

ABSTRACT

BACKGROUND: The COVID-19 pandemic had a profound impact on healthcare and ophthalmology services globally. Numerous studies amongst various medical and surgical specialties showed a reduction in patient attendance and surgical procedures performed. Prior published ophthalmic literature focused on specific types of procedures and were usually single centre. The current study attempts to quantify the impact on a larger scale, namely that of sub-Saharan Africa, and to include all ophthalmic subspecialties. METHODS: This is a retrospective analysis of the surgical records from 17 ophthalmology centres in seven countries located in East, Central, West and Southern Africa. The date of declaration of the first lockdown was used as the beginning of the pandemic and the pivot point to compare theatre records one year prior to the pandemic and the first year of the pandemic. We examined the total number of surgical procedures over the two year period and categorized them according to ophthalmic subspecialty and type of procedure performed. We then compared the pre-pandemic and pandemic surgical numbers over the two year period. RESULTS: There were 26,357 ophthalmic surgical procedures performed with a significant decrease in the first year of the pandemic (n = 8942) compared to the year prior to the pandemic (n = 17,415). The number of surgical procedures performed was lower in the first year of the pandemic compared to the year prior to the pandemic by 49% [Incidence rate ratio (IRR) 0.51, 95% CI 0.41-0.64), 27% (0.73, 0.55-0.99), 46% (0.54, 0.30-0.99), 40% (0.60, 0.39-0.92) and 59% (0.41, 0.29-0.57) in sub-Saharan Africa (4 regions combined), West, Central, East and Southern Africa, respectively]. The number of surgical procedures in the different sub-specialty categories in sub-Saharan Africa (4 regions combined) was significantly lower in the first year of the pandemic compared to the year prior to the pandemic, except for glaucoma (IRR 0.72, 95% CI 0.52-1.01), oncology (0.71, 0.48-1.05), trauma (0.90, 0.63-1.28) and vitreoretinal (0.67, 0.42-1.08) categories. CONCLUSION: This study provides insight into the impact of the COVID-19 pandemic in multiple regions and countries on the African continent. The identification of which surgical subspecialty was most affected by the COVID-19 pandemic in each region allows for better planning and resource allocation to address these backlogs.

17.
J Am Coll Emerg Physicians Open ; 5(2): e13107, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38486833

ABSTRACT

Objectives: Traumatic brain injury (TBI) is an important public health problem resulting in significant death and disability. Emergency medical services (EMS) personnel often provide initial treatment for TBI, but only limited data describe the long-term course and outcomes of this care. We sought to characterize changes in neurologic status among adults with TBI patients enrolled in the Resuscitation Outcomes Consortium Hypertonic Saline (ROC-HS) trial. Methods: We used data from the TBI cohort of the ROC-HS trial. The trial included adults with TBI, with Glasgow Coma Scale (GCS) ≤8, and excluded those with shock (systolic blood pressure [SBP] ≤70 or SBP 71-90 with a heart rate [HR] ≥108). The primary outcome was Glasgow Outcome Scale-Extended (GOS-E; 1 = dead, 8 = no disability) determined at (a) hospital discharge and (b) 6-month follow-up. We assessed changes in GOS-E between hospital discharge and 6-month follow-up using descriptive statistics and Sankey graphs. Results: Among 1279 TBI included in the analysis, GOS-E categories at hospital discharge were as follows: favorable (GOS-E 5-8) 220 (17.2%), unfavorable (GOS-E 2-4) 664 (51.9%), dead (GOS-E 1) 321 (25.1%), and missing 74 (5.8%). GOS-E categories at 6-month follow-up were as follows: favorable 459 (35.9%), unfavorable 279 (21.8%), dead 346 (27.1%), and missing 195 (15.2%). Among initial TBI survivors with complete GOS-E, >96% followed one of three neurologic recovery patterns: (1) favorable to favorable (20.0%), (2) unfavorable to favorable (40.3%), and (3) unfavorable to unfavorable (36.0%). Few patients deteriorated from favorable to unfavorable neurologic status, and there were few additional deaths. Conclusions: Among TBI receiving initial prehospital care in the ROC-HS trial, changes in 6-month neurologic status followed distinct patterns. Among TBI with unfavorable neurologic status at hospital discharge, almost half improved to favorable neurologic status at 6 months. Among those with favorable neurologic status at discharge, very few worsened or died at 6 months. These findings have important implications for TBI clinical care, research, and trial design.

18.
J Am Coll Emerg Physicians Open ; 5(2): e13118, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38464331

ABSTRACT

Acute respiratory failure is a common reason for emergency department visits and hospital admissions. Diverse underlying physiologic abnormalities lead to unique aspects about the most common causes of acute respiratory failure: acute decompensated heart failure, acute exacerbation of chronic obstructive pulmonary disease, and acute de novo hypoxemic respiratory failure. Noninvasive respiratory support strategies are increasingly used methods to support work of breathing and improve gas exchange abnormalities to improve outcomes relative to conventional oxygen therapy or invasive mechanical ventilation. Noninvasive respiratory support includes noninvasive positive pressure ventilation and nasal high flow, each with unique physiologic mechanisms. This paper will review the physiology of respiratory failure and noninvasive respiratory support modalities and offer data and guideline-driven recommendations in the context of key clinical controversies.

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