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1.
Clin Toxicol (Phila) ; 62(4): 256-266, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38686923

ABSTRACT

INTRODUCTION: Since the passage of the Farm Bill in 2018, the availability of synthetic tetrahydrocannabinols has increased, including delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate. The objective of this study is to investigate the characteristics of delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to United States poison centers from 2021 to 2022. METHODS: National Poison Data System data were analyzed, including year, individual demographics, substance category and type, reason for exposure, highest level of health care received, and medical outcome. United States Census Bureau data were used to calculate population-based rates. RESULTS: There were 5,022 reported cases involving delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate as the primary substance reported to United States poison centers from 1 January 2021 to 31 December 2022. The rate of exposure per 100,000 United States population increased by 89.1 percent from 0.55 in 2021 to 1.04 in 2022. Children less than 6 years old accounted for 30.1 percent of cases, with a mode at age 2 years (representing 8.9 percent of cases). Most cases involved delta-8 tetrahydrocannabinol (98.1 percent), were single-substance exposures (94.3 percent), or occurred in a residence (95.9 percent). Ingestions accounted for 94.2 percent of cases, including 95.1 percent among children less than 6 years old. The leading reason for exposure was unintentional-general (40.2 percent), followed by abuse (33.1 percent). The most common related clinical effects were mild central nervous system depression (25.0 percent), tachycardia (23.0 percent), and agitation (15.6 percent). More than one-third (38.4 percent) of cases experienced a serious medical outcome, and 10.3 percent were admitted to a noncritical care unit and 5.3 percent to a critical care unit. DISCUSSION AND LIMITATIONS: The National Poison Data System is limited by its passive surveillance design. Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate have toxic effects, and reports to United States poison centers increased from 2021 to 2022. Unintentional ingestions by young children are of particular concern. CONCLUSIONS: Opportunities exist to improve regulation, with accompanying enforcement, of these products and to educate the public about their potential toxicity.


Subject(s)
Dronabinol , Poison Control Centers , Dronabinol/poisoning , Dronabinol/analogs & derivatives , Poison Control Centers/statistics & numerical data , Humans , United States/epidemiology , Adult , Male , Adolescent , Child , Female , Young Adult , Child, Preschool , Middle Aged , Infant
2.
JAMA Netw Open ; 7(4): e245543, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38587843

ABSTRACT

Importance: Mood disorders are prevalent among adolescents and young adults, and their onset often coincides with driving eligibility. The understanding of how mood disorders are associated with youth driving outcomes is limited. Objective: To examine the association between the presence of a mood disorder and rates of licensing, crashes, violations, and suspensions among adolescents and young adults. Design, Setting, and Participants: This cohort study was conducted among New Jersey residents who were born 1987 to 2000, age eligible to acquire a driver's license from 2004 to 2017, and patients of the Children's Hospital of Philadelphia network within 2 years of licensure eligibility at age 17 years. The presence of a current (ie, ≤2 years of driving eligibility) mood disorder was identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Rates of licensure and driving outcomes among youths who were licensed were compared among 1879 youths with and 84 294 youths without a current mood disorder from 2004 to 2017. Data were analyzed from June 2022 to July 2023. Main Outcomes and Measures: Acquisition of a driver's license and first involvement as a driver in a police-reported crash and rates of other adverse driving outcomes were assessed. Survival analysis was used to estimate adjusted hazard ratios (aHRs) for licensing and driving outcomes. Adjusted rate ratios (aRRs) were estimated for driving outcomes 12 and 48 months after licensure. Results: Among 86 173 youths (median [IQR] age at the end of the study, 22.8 [19.7-26.5] years; 42 894 female [49.8%]), there were 1879 youths with and 84 294 youths without a mood disorder. A greater proportion of youths with mood disorders were female (1226 female [65.2%]) compared with those without mood disorders (41 668 female [49.4%]). At 48 months after licensure eligibility, 75.5% (95% CI, 73.3%-77.7%) and 83.8% (95% CI, 83.5%-84.1%) of youths with and without mood disorders, respectively, had acquired a license. Youths with mood disorders were 30% less likely to acquire a license than those without a mood disorder (aHR, 0.70 [95% CI, 0.66-0.74]). Licensed youths with mood disorders had higher overall crash rates than those without mood disorders over the first 48 months of driving (137.8 vs 104.8 crashes per 10 000 driver-months; aRR, 1.19 [95% CI, 1.08-1.31]); licensed youths with mood disorders also had higher rates of moving violations (aRR, 1.25 [95% CI, 1.13-1.38]) and license suspensions (aRR, 1.95 [95% CI, 1.53-2.49]). Conclusions and Relevance: This study found that youths with mood disorders were less likely to be licensed and had higher rates of adverse driving outcomes than youths without mood disorders. These findings suggest that opportunities may exist to enhance driving mobility in this population and elucidate the mechanisms by which mood disorders are associated with crash risk.


Subject(s)
Eligibility Determination , Mood Disorders , Child , Young Adult , Humans , Adolescent , Female , Child, Preschool , Adult , Male , Cohort Studies , Mood Disorders/epidemiology , Hospitals, Pediatric , International Classification of Diseases
3.
J Med Toxicol ; 20(2): 193-204, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38421490

ABSTRACT

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications for management of diabetes and obesity. The objective of this study is to characterize the epidemiology of GLP-1RA cases reported to US poison centers. METHODS: We analyzed cases involving a GLP-1RA reported to the National Poison Data System during 2017-2022. RESULTS: There were 5,713 single-substance exposure cases reported to US poison centers involving a GLP-1RA. Most cases were among females (71.3%) and attributable to therapeutic errors (79.9%). More than one-fifth (22.4%) of cases were evaluated in a healthcare facility, including 0.9% admitted to a critical care unit and 4.1% admitted to a non-critical care unit. Serious medical outcomes were described in 6.2% of cases, including one fatality. The rate of cases per one million US population increased from 1.16 in 2017 to 3.49 in 2021, followed by a rapid increase of 80.9% to 6.32 in 2022. Trends for rates of serious medical outcomes and admissions to a healthcare facility showed similar patterns with 129.9% and 95.8% increases, respectively, from 2021 to 2022. CONCLUSIONS: Most GLP-1RA cases reported to US poison centers were associated with no or minimal effects and did not require referral for medical treatment; however, a notable minority of individuals experienced a serious medical outcome or healthcare facility admission. The rate of reported cases increased during the study period, including an 80.9% increase from 2021 to 2022. Opportunities exist to improve provider and patient awareness of the adverse effects of these medications.


Subject(s)
Diabetes Mellitus, Type 2 , Poisons , Female , Humans , United States/epidemiology , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Liraglutide/toxicity , Liraglutide/therapeutic use , Glucagon-Like Peptide-1 Receptor Agonists , Poisons/therapeutic use
4.
Clin Toxicol (Phila) ; 61(11): 990-998, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38112310

ABSTRACT

BACKGROUND: Liquid laundry detergent packet exposures modestly declined in the mid-2010s among children less than 6 years of age due to public awareness and voluntary product safety standards. We aimed to assess longitudinal trends in the number and rate of liquid laundry detergent packet exposures in the United States by age. METHODS: Data from the National Poison Data System were analyzed to characterize liquid laundry detergent packet exposures between January 2014 and December 2022. RESULTS: From 2014-2022, there were 114,826 single and polysubstance exposures to liquid laundry detergent packets. Children less than 6 years of age (86.8 percent) were most commonly exposed. When evaluating multi-year trends, we found that the annual exposure rate per 1 million children less than 6 years old increased by 16.8 percent from 392.6 in 2018 to 458.7 in 2020. Subsequently, the annual exposure rate in children less than 6 years of age declined by 6.8 percent from 2020 to 2022 (427.4 exposures per 1 million). The annual rate of adolescent exposures increased by 85.4 percent from 2014 (4.1 exposures per 1 million) to 2017 (7.6 exposures per 1 million), with a subsequent increase of 155.3 percent from 2017 to 2018 (19.4 exposures per 1 million). Among adults, the annual exposure rate increased by 147.1 percent from 2014 (1.7 exposures per 1 million) to 2022 (4.2 exposures per 1 million). The number of more serious medical outcomes and hospital admissions among children less than 6 years of age declined by 44.3 percent and 68.6 percent, respectively, between 2014 and 2018. CONCLUSIONS: Despite declines in the number, rate, and severity of liquid laundry detergent packet exposures among children less than 6 years old, the exposure burden remains high. Additionally, exposures have increased among older children, adolescents, and adults. Renewed safety efforts are warranted to protect prior public health gains and further reduce exposures.


Subject(s)
Detergents , Hospitalization , Child , Adult , Adolescent , Humans , United States/epidemiology , Public Health , Reference Standards , Poison Control Centers
5.
Pediatrics ; 151(4)2023 04 01.
Article in English | MEDLINE | ID: mdl-36897244

ABSTRACT

BACKGROUND AND OBJECTIVES: Fatal poisoning is a preventable cause of death among young children. Understanding factors surrounding these deaths will inform future prevention efforts. Our objective was to describe the characteristics of fatal pediatric poisonings using child death review data. METHODS: We acquired data from 40 states participating in the National Fatality Review-Case Reporting System on deaths attributed to poisonings among children aged ≤5 years from 2005 to 2018. We analyzed select demographic, supervisor, death investigation, and substance-related variables using descriptive statistics. RESULTS: During the study period, 731 poisoning-related fatalities were reported by child death reviews to the National Fatality Review-Case Reporting System. Over two-fifths (42.1%, 308 of 731) occurred among infants aged <1 year, and most fatalities (65.1%, 444 of 682) occurred in the child's home. One-sixth of children (97 of 581) had an open child protective services case at time of death. Nearly one-third (32.2%, 203 of 631) of children were supervised by an individual other than the biological parent. Opioids (47.3%, 346 of 731) were the most common substance contributing to death, followed by over-the-counter pain, cold, and allergy medications (14.8%, 108 of 731). Opioids accounted for 24.1% (7 of 29) of the substances contributing to deaths in 2005 compared with 52.2% (24 of 46) in 2018. CONCLUSIONS: Opioids were the most common substances contributing to fatal poisonings among young children. Over-the-counter medications continue to account for pediatric fatalities even after regulatory changes. These data highlight the importance of tailored prevention measures to further reduce fatal child poisonings.


Subject(s)
Analgesics, Opioid , Poisoning , Child , Humans , Infant , United States/epidemiology , Child, Preschool , Poisoning/epidemiology
6.
J Emerg Med ; 63(3): 339-347, 2022 09.
Article in English | MEDLINE | ID: mdl-36210284

ABSTRACT

BACKGROUND: Pyogenic granulomas are acquired, benign growths of capillary blood vessels that are commonly seen in the pediatric population. Patients with these lesions often present to emergency departments and urgent care centers with persistent bleeding after minor trauma. Much of the published literature describing the management of pyogenic granulomas, however, is focused on outpatient or definitive therapies, and there is limited information on the management of acute bleeding. OBJECTIVE: We conducted a narrative review to present and evaluate strategies and therapies available to emergency physicians for managing actively bleeding pyogenic granulomas in acute care settings. DISCUSSION: Multiple options are available to emergency physicians to achieve hemostasis. Direct pressure with a nonadherent dressing remains first-line treatment. Additional therapeutic options, such as dressings impregnated with topical vasoconstrictors or hemostatic dressings or agents, can be used if bleeding persists. Certain approaches-silver nitrate, suture ligation, or electrocautery-may be available to some emergency physicians. These therapies, however, can compromise future histologic analysis of tissue for definitive diagnosis and have potential risks. CONCLUSION: Although there are multiple options to achieve hemostasis in cases of bleeding, some treatments may lead to suboptimal cosmesis or interfere with future management. Many bleeding pyogenic granulomas will become hemostatic with treatments available to emergency physicians. Surgical consultation may be warranted for pyogenic granulomas that are unresponsive to the therapies described in this review.


Subject(s)
Granuloma, Pyogenic , Hemostatics , Child , Humans , Granuloma, Pyogenic/complications , Granuloma, Pyogenic/therapy , Granuloma, Pyogenic/diagnosis , Hemorrhage/etiology , Hemorrhage/therapy , Vasoconstrictor Agents/therapeutic use , Hemostatics/therapeutic use , Critical Care
7.
Pediatrics ; 148(5)2021 11.
Article in English | MEDLINE | ID: mdl-34610947

ABSTRACT

A previously healthy, term, 5-week-old girl initially presented to her primary care physician with a solitary, enlarging scalp nodule. The infant was otherwise well without additional signs or symptoms of illness. Over the next several weeks, the nodule continued to grow, and additional lesions appeared on her scalp. An ultrasound of the primary nodule revealed a hypoechoic structure favored to represent a serosanguinous fluid collection. After evaluation by general surgery and dermatology, she underwent a scalp biopsy of the largest lesion. While biopsy specimen results were pending, her parents noted that she was developing increased irritability, difficulty closing her right eye, and facial weakness. She was referred to the emergency department where a right-sided facial droop involving the brow and forehead was noted. The skin biopsy specimen results, along with subsequent laboratory studies and imaging, led to the final diagnosis.


Subject(s)
Bell Palsy/etiology , Head and Neck Neoplasms/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Scalp , Skin Neoplasms/diagnosis , Facial Nerve/pathology , Female , Gene Rearrangement , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/genetics , Histone-Lysine N-Methyltransferase/genetics , Humans , Infant , Leukemic Infiltration/complications , Myeloid-Lymphoid Leukemia Protein/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Skin Neoplasms/complications , Skin Neoplasms/genetics
8.
Clin Toxicol (Phila) ; 59(7): 619-627, 2021 07.
Article in English | MEDLINE | ID: mdl-33164588

ABSTRACT

BACKGROUND: Case studies and small series have demonstrated that beverage ethanol may pose a serious poisoning hazard to infants. Intoxicated infants may not present with the classic signs or symptoms of ethanol poisoning. The objective of this study was to describe the epidemiology of beverage ethanol exposures among infants reported to the United States poison control centers. METHODS: Data from the National Poison Data System were retrospectively analyzed for infants <12 months of age who were exposed to beverage ethanol from 2009-2018. RESULTS: Over the 10-year study period, 1,818 infant exposures to beverage ethanol were reported. Most exposures were single substance (95.2%), and the most common route of exposure was ingestion (n = 1,738). Infants 9-11 months were the most commonly exposed age group subset (45.3%). The annual number and rate of alcoholic beverage exposure increased by 37.5% and 42.9%, respectively, from 2009 to 2018. Of the 563 infants evaluated at a healthcare facility, 38% of exposures were hospitalized. Infants 0-5 months of age had higher odds of being admitted to a non-critical (OR: 2.35, 95% CI: 1.41-3.92) or critical care unit (OR: 2.39; 95% CI: 1.50-3.79) compared to infants 6-11 months of age. Infants 0-5 months of age were more likely to (OR: 4.65; 95% CI: 3.18-6.79) experience a serious outcome compared to infants ages 6-11 months. Five fatalities in infants <6 months old were documented. An in-depth case review identified improper storage and subsequent formula preparation with beverage ethanol as a common exposure mechanism. CONCLUSIONS: Beverage ethanol exposures among infants are associated with hospitalization, serious clinical effects, and mortality. Infants may present with atypical signs and symptoms of intoxication, requiring a high index of suspicion. Opportunities exist to reduce exposures by addressing improper storage of beverage alcohols.


Subject(s)
Ethanol/poisoning , Beverages , Female , Humans , Infant , Male , Poison Control Centers , Poisoning/epidemiology , Retrospective Studies , United States/epidemiology
9.
Pediatrics ; 146(6)2020 12.
Article in English | MEDLINE | ID: mdl-33154153

ABSTRACT

A primary goal of our medical education system is to produce physicians qualified to promote health, prevent and treat disease, and relieve suffering. Although some aspects of the practice of medicine can be learned in classrooms, from textbooks, or with simulators, other aspects can only be learned through the direct provision of patient care. Residency programs therefore offer essential educational experiences that support residents' acquisition of knowledge, skills, and professional judgment through the assumption of progressive responsibility under an appropriate level of supervision. Yet, ethical questions can arise when medical education is integrated with patient care. How should we balance the educational needs of residents and the social benefits of medical education against obligations to patients and families? In this article, we present the case of a child whose family requests that residents not be allowed to perform any procedures on their child and then ask experts (a pediatric residency program director, a pediatrics resident, and an ethicist) to comment.


Subject(s)
Child Care/ethics , Family/psychology , Internship and Residency/ethics , Pyelonephritis/therapy , Students, Medical/psychology , Child Care/psychology , Child, Preschool , Female , Humans
10.
Clin Pediatr (Phila) ; 59(13): 1150-1160, 2020 11.
Article in English | MEDLINE | ID: mdl-32668957

ABSTRACT

The objective of this study was to characterize how pediatric primary care and emergency medicine health care providers and trainees engage in injury prevention counseling and assess perceptions toward injury prevention resources. We surveyed physicians, advanced practice providers, and trainees in the Emergency Department, Primary Care Network, and Pediatric Residency Program at Children's Hospital of Philadelphia from September to November 2019. Of the 578 eligible participants, 208 (36.0%) completed the survey. When asked to rank the suitability of alternative personnel for providing counseling, 63.0% of the participants selected an injury prevention specialist as best suited. Seventy-six percent of the providers considered a tablet or mobile device used before a patient encounter to be a helpful resource. Variability existed in provider comfort, knowledge, and frequency of counseling by injury topic. Free-text responses cited time as a barrier to counseling. Opportunities exist to improve the provision of injury education through the utilization of novel resources and personnel.


Subject(s)
Counseling/methods , Emergency Medical Services/statistics & numerical data , Health Personnel/statistics & numerical data , Patient Education as Topic/methods , Pediatrics/methods , Primary Health Care/methods , Adult , Computers, Handheld , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pediatricians , Philadelphia
11.
Am J Emerg Med ; 38(6): 1062-1068, 2020 06.
Article in English | MEDLINE | ID: mdl-31402233

ABSTRACT

BACKGROUND: Horse-related injuries can cause severe morbidity and mortality. The objective of this study is to investigate the epidemiological features of horse-related injuries treated in emergency departments (EDs) in the United States. METHODS: A retrospective analysis of horse-related injuries from 1990 through 2017 was conducted utilizing the National Electronic Injury Surveillance System (NEISS). Cases were identified using the NEISS code 1239 (Horseback Riding: Activity, Apparel, or Equipment). Analyses performed included calculation of national injury estimates, relative risks (RRs) with 95% confidence intervals (CIs), and linear regression. RESULTS: From 1990 through 2017, an estimated 1,836,536 (95% CI: 1,494,788-2,178,284) individuals presented to United States EDs with horse-related injuries. The annual injury rate decreased by 30.8% from 1990 to 1996, increased by 33.0% from 1996 to 2000, and then decreased by 46.0% from 2000 to 2017. Among older adults >60 years of age, the annual injury rate increased by 139.6% during the study period. The number of concussion and closed head injury diagnoses increased by 337.2% from 1990 to 2009. The most common mounted mechanism of injury was a fall or being thrown (73.9%), while the most common unmounted mechanism was being kicked (42.1%). Mounted injuries were more likely to lead to hospitalization than unmounted injuries (RR, 2.10, 95% CI: 1.59-2.77). CONCLUSIONS: Despite the recent decline in horse-related injuries, these injuries are still common. Clinicians should be aware of the spectrum of ED presentations of horse-related injuries. Prevention efforts focused on older adults and concussions and closed head injuries warrant special attention.


Subject(s)
Athletic Injuries/epidemiology , Craniocerebral Trauma/epidemiology , Disease Management , Emergency Service, Hospital/statistics & numerical data , Horses , Adolescent , Adult , Animals , Athletic Injuries/therapy , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Retrospective Studies , United States/epidemiology , Young Adult
12.
Pediatr Emerg Care ; 35(10): 722-730, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31593052

ABSTRACT

Ethanol intoxication of infants and young children can be a challenging diagnosis in the pediatric emergency department, and features of the poisoning may differ in comparison with adolescents. The sources of ethanol exposures in this age are varied and include unintentional, malicious, and iatrogenic etiologies. Young children exposed to ethanol often present with mixed clinical signs and symptoms that may not fit the traditional ethanol or sedative-hypnotic toxidrome. Pediatric ethanol intoxications are often managed supportively, and recovery is usually rapid. The purpose of this review is to describe the sources of ethanol poisoning among children 6 years and younger, highlight presenting symptoms and pharmacokinetic considerations unique to this age group, and review management strategies. In addition, published cases of ethanol poisoning due to ingestion among young infants are compiled for presentation.


Subject(s)
Alcoholic Intoxication/diagnosis , Consciousness Disorders/diagnosis , Ethanol/poisoning , Poisoning/psychology , Alcoholic Intoxication/epidemiology , Alcoholic Intoxication/pathology , Alcoholic Intoxication/psychology , Child , Child, Preschool , Consciousness Disorders/etiology , Diagnosis, Differential , Eating/physiology , Emergency Service, Hospital , Ethanol/blood , Ethanol/pharmacokinetics , Female , Humans , Iatrogenic Disease/epidemiology , Infant , Infant, Newborn , Male , Poisoning/epidemiology
14.
Pediatrics ; 144(1)2019 07.
Article in English | MEDLINE | ID: mdl-31160344

ABSTRACT

OBJECTIVES: To investigate exposures to liquid laundry detergent packets among children <6 years old in the United States and to evaluate the impact of the American Society for Testing and Materials voluntary product safety standard. METHODS: Data from the National Poison Data System involving exposures to liquid laundry detergent packets from 2012 to 2017 were analyzed. RESULTS: From January 2012 to December 2017, there were 72 947 single and polysubstance exposures to liquid laundry detergent packets. Most exposures (91.7%) were documented among children <6 years old. The annual number and rate of exposures for children <6 years old increased by 110.4% and 111.9%, respectively, from 2012 to 2015. From 2015 to 2017, the number and rate of exposures in this age group decreased by 18.0%. Among individuals ≥6 years old, the annual number and rate of exposures increased by 292.7% and 276.7%, respectively, from 2012 to 2017. Annual hospital admissions among children <6 years old increased by 63.4% from 2012 to 2015 and declined by 55.5% from 2015 to 2017. Serious outcomes among children <6 years old increased by 78.5% from 2012 to 2015 and declined by 32.9% from 2015 to 2017. CONCLUSIONS: The number, rate, and severity of liquid laundry detergent packet exposures have decreased modestly in recent years among children <6 years old, likely attributable, in part, to the voluntary product safety standard and public awareness efforts. Exposures among older children and adults are increasing. Opportunities exist to strengthen the current product safety standard to further reduce exposures.


Subject(s)
Consumer Product Safety , Detergents/poisoning , Laundering , Accidents, Home/prevention & control , Child , Child, Preschool , Female , Hospitalization/statistics & numerical data , Humans , Male , Poisoning/epidemiology , Poisoning/prevention & control , Product Labeling , Product Packaging , United States/epidemiology
15.
Nat Commun ; 9(1): 3431, 2018 08 24.
Article in English | MEDLINE | ID: mdl-30143619

ABSTRACT

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder causing progressive muscle degeneration. Although cardiomyopathy is a leading mortality cause in DMD patients, the mechanisms underlying heart failure are not well understood. Previously, we showed that NF-κB exacerbates DMD skeletal muscle pathology by promoting inflammation and impairing new muscle growth. Here, we show that NF-κB is activated in murine dystrophic (mdx) hearts, and that cardiomyocyte ablation of NF-κB rescues cardiac function. This physiological improvement is associated with a signature of upregulated calcium genes, coinciding with global enrichment of permissive H3K27 acetylation chromatin marks and depletion of the transcriptional repressors CCCTC-binding factor, SIN3 transcription regulator family member A, and histone deacetylase 1. In this respect, in DMD hearts, NF-κB acts differently from its established role as a transcriptional activator, instead promoting global changes in the chromatin landscape to regulate calcium genes and cardiac function.


Subject(s)
Muscular Dystrophy, Duchenne/metabolism , Myocytes, Cardiac/metabolism , NF-kappa B/metabolism , Animals , CCCTC-Binding Factor/metabolism , Calcium/metabolism , Cells, Cultured , Chromatin Assembly and Disassembly/genetics , Chromatin Assembly and Disassembly/physiology , Histone Deacetylase 1/genetics , Histone Deacetylase 1/metabolism , Male , Mice , Mice, Inbred mdx , Muscular Dystrophy, Duchenne/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism , Signal Transduction/physiology , Sin3 Histone Deacetylase and Corepressor Complex , Sodium-Calcium Exchanger/genetics , Sodium-Calcium Exchanger/metabolism
16.
Infect Control Hosp Epidemiol ; 39(4): 383-390, 2018 04.
Article in English | MEDLINE | ID: mdl-29428002

ABSTRACT

BACKGROUND The decision to utilize antimicrobials in end-of-life situations is complex. Understanding the reasons why physicians prescribe antimicrobials in this patient population is important for informing the design of antimicrobial stewardship interventions. METHODS A 51-item survey containing both closed and open-ended questions on end-of-life antimicrobial use was administered to physicians affiliated with the University of Pennsylvania and Children's Hospital of Philadelphia from January through April 2017. A mixed-methods approach was used to analyze responses. RESULTS Of 637 physicians surveyed, 283 responses (44.4%) were received. Most (86.2%) physicians believed that respecting a patient's wish to continue antimicrobials was important. Approximately half of physicians (49.8%) believed that antimicrobial use at the end of life contributes to resistance. A higher proportion of pediatricians would often or always continue antimicrobial treatment for active infections and for hospice patients whose death was imminent compared to adult physicians (P<.001). Analysis of free-text responses revealed additional reasons why physicians may continue antimicrobials at end of life, including meeting family expectations, wanting to avoid the perception of "giving up," uncertainty about prognosis, and reducing patient pain or discomfort. CONCLUSIONS Physician decision making concerning antimicrobial use in patients at the end of life is multifactorial. Clinicians may overweigh the benefits of antimicrobial therapy in end-of-life situations and view the importance of adhering to stewardship policies differently. Pediatric and adult clinicians have different approaches to this patient population. Better understanding of the complex decision making that occurs in the end-of-life patient population can help guide antimicrobial stewardship policies and improve patient care. Infect Control Hosp Epidemiol 2018;39:383-390.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Infection Control/standards , Practice Patterns, Physicians' , Terminal Care , Attitude of Health Personnel , Clinical Decision-Making , Humans , Pediatrics/methods , Pennsylvania , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/statistics & numerical data , Quality Improvement , Terminal Care/methods , Terminal Care/psychology
17.
Clin Toxicol (Phila) ; 56(2): 113-119, 2018 02.
Article in English | MEDLINE | ID: mdl-28705022

ABSTRACT

BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) exposures among children younger than 6 years of age are generally well tolerated. Vilazodone is an SSRI with partial agonism at the 5-HT1A receptor with demonstrated clinical efficacy for depression whose off-label usage is likely to increase. Recent evidence suggests that unintentional ingestion of vilazodone in children under 6 years old is associated with more severe clinical effects than other SSRIs. We chose to evaluate dose and outcomes for pediatric vilazodone ingestions. METHODS: A retrospective analysis of single-substance exposures associated with vilazodone among children younger than 6 years of age from 2011 through 2016 was conducted using data from the National Poison Data System. RESULTS: During 2011-2016, 753 vilazodone ingestions among children <6 years old were reported to US poison control centers. A near majority (49.0%, n = 369) experienced one or more clinical effects. The dose ingested was reported for 596 children (79%). The median dose associated with major effects was 50.0mg (Mean: 106.0) compared with 40.0mg (Mean 81.1) for moderate effects. Half (50.0%) of children with a major effect and 54.0% with a moderate effect ingested ≤40 mg of vilazodone. As the dose of vilazodone ingested increased, the proportions of exposures admitted to a healthcare facility (HCF) (p < .001) and with serious outcomes (p < .001) both increased. Children ≤2 years had higher proportions of HCF admission (33.8% vs 23.1%) and serious outcomes (27.0% vs 17.7%) than children 3-5 years of age. Clinical effects, such as coma, seizures, ataxia, and hallucinations/delusions, were observed among children ingesting doses of vilazodone as low as 10 mg. CONCLUSIONS: Exposure to vilazodone poses a unique and potentially serious threat to children <6 years of age. Children in this age group who are exposed to vilazodone should be evaluated promptly in a clinical setting. Off-label use of vilazodone in children under 6 years should be discouraged until further research is conducted regarding its safety in this population.


Subject(s)
Selective Serotonin Reuptake Inhibitors/poisoning , Vilazodone Hydrochloride/poisoning , Adolescent , Age Factors , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Infant , Male , Patient Admission/statistics & numerical data , Poison Control Centers , Retrospective Studies , Selective Serotonin Reuptake Inhibitors/administration & dosage , Treatment Outcome , United States/epidemiology , Vilazodone Hydrochloride/administration & dosage
19.
Acad Pediatr ; 17(8): 893-901, 2017.
Article in English | MEDLINE | ID: mdl-28723589

ABSTRACT

OBJECTIVE: To investigate the circumstances of death and types and roles of objects present in the sleep environment at the time of death for infants who died from suffocation or strangulation during sleep. METHODS: This study analyzed 1736 reported incidents of accidental suffocation and strangulation in bed (ASSB) of infants younger than 1 year of age. These fatalities occurred from 2000 through 2012 and were reported to the United States Consumer Product Safety Commission. RESULTS: The mean age of ASSB death was 3.76 months (SD, 2.51). Infants younger than 5 months accounted for 67.3% (1168 of 1736) of all reported fatalities and 58.3% (1009 of 1731) were male. Deceased infants were often found in a crib or bassinet (30.6%; 383 of 1253) or in the prone orientation (84.9%; 595 of 701). The most common objects associated with infant ASSB were pillows (24.5%; 425 of 1736), mattresses (21.0%; 364 of 1736), blankets (13.1%; 228 of 1736), and walls (11.5%; 199 of 1736). Wedged (43.3%; 616 of 1424) or positioned on top of an object (25.9%; 369 of 1424) were the most common positions associated with death. Infants were often found wedged between a mattress and wall (30.2%; 181 of 599) or oriented face-down or prone on top of a pillow (52.2%; 187 of 358). Sleep surface sharing was associated with 6.5% (112 of 1736) of ASSB deaths. CONCLUSIONS: Pillows and blankets are objects in sleep environments frequently associated with unintentional suffocation and strangulation of infants. Increased efforts should be made to remove these and other objects from sleep environments of infants.


Subject(s)
Asphyxia/epidemiology , Bedding and Linens , Beds , Infant Equipment , Sudden Infant Death/epidemiology , Consumer Product Safety , Female , Humans , Infant , Infant, Newborn , Male , Prone Position , Sleep , United States/epidemiology
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