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"Kelly, Timothy D"
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Peripartum Cardiac Arrest with Terminal QRS Distortion: A Case Report
Introduction: Peripartum cardiac arrest is increasing in incidence. While pulmonary embolism (PE) remains an important cause of peripartum morbidity and mortality, other cardiovascular emergencies such as myocardial infarction (MI) are now the leading cause of pregnancy-related death. Emergency physicians (EP) need to be well versed in subtle electrocardiographic (ECG) signs of coronary ischemia to better care for peripartum patients in cardiac arrest.Case Report: A 38-year-old gravida 2 parity1 female three days post-partum presented in cardiac arrest. After approximately 12 minutes of Advanced Cardiac Life Support including electric defibrillation, the patient experienced sustained return of spontaneous circulation. The physician team was primarily concerned for PE based on an initial ECG demonstrating terminal QRS distortion in V2 but no ST-segment elevation myocardial infarction (STEMI). Computed tomography angiography (CTA) of the chest did not reveal PE. Repeat ECG after CTA demonstrated STEMI criteria, and the patient was emergently taken to the cardiac catheterization laboratory where she was found to have 99% occlusion of the left anterior descending artery.Conclusion: Emergency physicians should have a high index of suspicion for MI when managing peripartum patients in cardiac arrest. The ECG findings specific for coronary-occlusive acute MI but not included in the classic STEMI criteria increase accuracy and prevent delays in diagnosis; however, the clinical uptake of this paradigm has been slow. Early recognition of terminal QRS distortion can help EPs more rapidly diagnose the etiology of cardiac arrest.
Journal Article
Improving Uptake of Emergency Department-initiated Buprenorphine: Barriers and Solutions
Emergency departments (ED) are increasingly providing buprenorphine to persons with opioid use disorder. Buprenorphine programs in the ED have strong support from public health leaders and emergency medicine specialty societies and have proven to be clinically effective, cost effective, and feasible. Even so, few ED buprenorphine programs currently exist. Given this imbalance between evidence-based practice and current practice, proven behavior change approaches can be used to guide local efforts to expand ED buprenorphine capacity. In this paper, we use the theory of planned behavior to identify and address the 1) clinician factors, 2) institutional factors, and 3) external factors surrounding ED buprenorphine implementation. By doing so, we seek to provide actionable and pragmatic recommendations to increase ED buprenorphine availability across different practice settings.
Journal Article
Peripheral Nerve Stimulation in Chronic Knee Pain: A Case Series
Introduction Chronic knee pain is increasing in prevalence and is associated with substantial limitations in functional mobility. Peripheral nerve stimulation (PNS) has been increasingly used to treat various chronic pain conditions. However, there is a paucity of research exploring the potential therapeutic benefit of PNS for chronic knee pain. Methods This research is a retrospective case series of all patients who received PNS for the treatment of chronic knee pain performed at a single-center academic medical institution between March 2021 and June 2022. The primary outcome was percent pain reduction six months after implantation. Outcome data was obtained via chart review and phone calls to patients. Secondary outcomes included percent pain reduction two weeks and two months after implantation and adverse medical events related to the procedure and nerve stimulation. Results Fourteen individual patients received PNS for chronic knee pain during the study period. Three of these patients received bilateral PNS for a total of 17 cases. The mean percent pain reduction six months after implantation was 52% (SD=28.2) (N=12). A total of 75.0% of participants (9/12) reported
50% reductions in pain six months after implantation. No adverse events were reported relating to the implantation procedure and/or nerve stimulation. Conclusion PNS is a safe and efficacious treatment modality for chronic knee pain with demonstrated long-term benefit. Further research should clarify patient factors associated with improved treatment response.
Journal Article
Targeted Drug Delivery for the Treatment of Abdominal Pain in Chronic Pancreatitis: A Retrospective Case Series
Abdominal pain secondary to chronic pancreatitis (CP) is difficult to manage and often requires chronic oral opioid therapy (OOT). Targeted drug delivery (TDD) allows for a diminished dose of opioid intake and improved pain levels. TDD has been used in different pain syndromes with only limited reports in CP.
The objective of this article is to perform a retrospective review of CP patients treated with TDD versus OOT to compare chronic pain control and consumed morphine-equivalent doses.
Patients receiving TDD between September 2011 and August 2018 were included. All patients were weaned off oral opioids one week before intrathecal trial and pump implantation. Patients with intrathecal trials providing at least 50% pain relief underwent pump implantation. Data were collected while on OOT and at two weeks, three months, and nine months post-implant. Data were analyzed with Microsoft Excel 365 MSO using means and standard deviations. P-values were calculated using a two-tailed student's t-test with paired two-sample means.
Twenty-three patients were analyzed. Pre-trial average pain score was 6.5/10 with a mean improvement with trials greater than 71%. The mean chronic baseline oral morphine milligram equivalents (MME) was 188. The mean MME on TDD at two weeks (0.36), three months (1.39), and nine months (2.47) were significantly lower than OOT. Mean pain scores were 6, 4.9, and 5.6 at two weeks, three months, and nine months, respectively, compared to 6.5 on OOT.
The results of this study indicate that TDD provides improved pain control with significantly lower opioid doses.
Journal Article
Evolutionary genomic dynamics of Peruvians before, during, and after the Inca Empire
Native Americans from the Amazon, Andes, and coastal geographic regions of South America have a rich cultural heritage but are genetically understudied, therefore leading to gaps in our knowledge of their genomic architecture and demographic history. In this study, we sequence 150 genomes to high coverage combined with an additional 130 genotype array samples from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date. Demographic modeling reveals that the peopling of Peru began ∼12,000 y ago, consistent with the hypothesis of the rapid peopling of the Americas and Peruvian archeological data. We find that the Native American populations possess distinct ancestral divisions, whereas the mestizo groups were admixtures of multiple Native American communities that occurred before and during the Inca Empire and Spanish rule. In addition, the mestizo communities also show Spanish introgression largely following Peruvian Independence, nearly 300 y after Spain conquered Peru. Further, we estimate migration events between Peruvian populations from all three geographic regions with the majority of between-region migration moving from the high Andes to the low-altitude Amazon and coast. As such, we present a detailed model of the evolutionary dynamics which impacted the genomes of modern-day Peruvians and a Native American ancestry dataset that will serve as a beneficial resource to addressing the underrepresentation of Native American ancestry in sequencing studies.
Journal Article
Late Miocene global cooling and the rise of modern ecosystems
During the late Miocene epoch, about seven million years ago, large areas of the continents experienced drying, enhanced seasonality, and a restructuring of terrestrial plant and animal communities. These changes are seen throughout the subtropics, but have typically been attributed to regional tectonic forcing. Here we present a set of globally distributed sea surface temperature records spanning the past 12 million years based on the alkenone unsaturation method. We find that a sustained late Miocene cooling occurred synchronously in both hemispheres, and culminated with ocean temperatures dipping to near-modern values between about 7 and 5.4 million years ago. The period of maximum cooling coincides with evidence for transient glaciations in the Northern Hemisphere and with a steepening of the pole-to-equator temperature gradient, as well. We thus infer that late Miocene aridity and terrestrial ecosystem changes occurred in a global context of increasing meridional temperature gradients. We conclude that a global forcing mechanism, such as the previously hypothesized decline in atmospheric CO
2
levels between eight and six million years ago, is required to explain the late Miocene changes in temperature, climate and ecosystems.
A period of continental aridification and ecosystem change occurred about seven million years ago. A global sea surface temperature reconstruction identifies cooling temperatures and a strengthened meridional temperature gradient at this time.
Journal Article
Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection
Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ~2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (~six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.
Journal Article
Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model
Down syndrome (DS), the genetic condition caused by trisomy 21, is characterized by variable cognitive impairment, immune dysregulation, dysmorphogenesis and increased prevalence of diverse co-occurring conditions. The mechanisms by which trisomy 21 causes these effects remain largely unknown. We demonstrate that triplication of the interferon receptor (
IFNR
) gene cluster on chromosome 21 is necessary for multiple phenotypes in a mouse model of DS. Whole-blood transcriptome analysis demonstrated that
IFNR
overexpression associates with chronic interferon hyperactivity and inflammation in people with DS. To define the contribution of this locus to DS phenotypes, we used genome editing to correct its copy number in a mouse model of DS, which normalized antiviral responses, prevented heart malformations, ameliorated developmental delays, improved cognition and attenuated craniofacial anomalies. Triplication of the
Ifnr
locus modulates hallmarks of DS in mice, suggesting that trisomy 21 elicits an interferonopathy potentially amenable to therapeutic intervention.
A mouse model of Down syndrome (DS) highlights the importance of triplication of the
IFNR
gene cluster for a variety of DS-associated traits. Copy number correction resulted in amelioration of multiple phenotypes associated with the condition.
Journal Article