Prediction of intra-abdominal injury using natural language processing of electronic medical record data.

BACKGROUND: This study aimed to use natural language processing to predict the presence of intra-abdominal injury using unstructured data from electronic medical records. METHODS: This was a random-sample retrospective observational cohort study leveraging unstructured data from injured patients taken to one of 9 acute care hospitals in an integrated health system between 2015 and 2021. Patients with International Classification of Diseases External Cause of Morbidity codes were identified. History and physical, consult, progress, and radiology report text from the first 8 hours of care were abstracted. Annotator dyads independently annotated encounters' text files to establish ground truth regarding whether intra-abdominal injury occurred. Features were extracted from text using natural language processing techniques, bag of words, and principal component analysis. We tested logistic regression, random forests, and gradient boosting machine to determine accuracy, recall, and precision of natural language processing to predict intra-abdominal injury. RESULTS: A random sample of 7,000 patient encounters of 177,127 was annotated. Only 2,951 had sufficient information to determine whether an intra-abdominal injury was present. Among those, 84 (2.9%) had an intra-abdominal injury. The concordance between annotators was 0.989. Logistic regression of features identified with bag of words and principal component analysis had the best predictive ability, with an area under the receiver operating characteristic curve of 0.9, recall of 0.73, and precision of 0.17. Text features with greatest importance included "abdomen," "pelvis," "spleen," and "hematoma." CONCLUSION: Natural language processing could be a screening decision support tool, which, if paired with human clinical assessment, can maximize precision of intra-abdominal injury identification.

Prediction of Time to Hemodynamic Stabilization of Unstable Injured Patient Encounters Using Electronic Medical Record Data.

BACKGROUND: This study sought to predict time to patient hemodynamic stabilization during trauma resuscitations of hypotensive patient encounters using electronic medical records (EMR) data. METHODS: This observational cohort study leveraged EMR data from a nine-hospital academic system composed of Level I, Level II and non-trauma centers. Injured, hemodynamically unstable (initial systolic blood pressure < 90 mmHg) emergency encounters from 2015-2020 were identified. Stabilization was defined as documented subsequent systolic blood pressure > 90 mmHg. We predicted time to stabilization testing random forests, gradient boosting and ensembles using patient, injury, treatment, EPIC Trauma Narrator and hospital features from the first four hours of care. RESULTS: Of 177,127 encounters, 1347 (0.8%) arrived hemodynamically unstable; 168 (12.5%) presented to Level I trauma centers, 853 (63.3%) to Level II, and 326 (24.2%) to non-trauma centers. Of those, 747 (55.5%) were stabilized with a median of 50 minutes (IQR 21-101 min). Stabilization was documented in 94.6% of unstable patient encounters at Level I, 57.6% at Level II and 29.8% at non-trauma centers (p < 0.001). Time to stabilization was predicted with a C-index of 0.80. The most predictive features were EPIC Trauma Narrator measures; documented patient arrival, provider exam, and disposition decision. In-hospital mortality was highest at Level I, 3.0% vs. 1.2% at Level II, and 0.3% at non-trauma centers (p < 0.001). Importantly, non-trauma centers had the highest re-triage rate to another acute care hospital (12.0%) compared to Level II centers (4.0%, p < 0.001). CONCLUSION: Time to stabilization of unstable injured patients can be predicted with EMR data.

Sub-Saharan Africa Surveillance Metrics and History of the COVID-19 Pandemic: Updated Epidemiological Assessment.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in Sub-Saharan Africa (SSA) we first conducted in 2020 by providing two additional years of data for the region. OBJECTIVE: First, we aim to measure whether there was an expansion or contraction in the pandemic in SSA when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in SSA. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study by Post et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional weekly speed was greater than an outbreak threshold of ten. We ran the test iteratively with a rolling, six month-window of data across the sample period. RESULTS: Speed for the region remained well below the outbreak threshold before and after the WHO declaration. Acceleration and jerk were also low and stable. The 7-day persistence coefficient remained somewhat large (1.11) and statistically significant. However, both shift parameters for the weeks around the WHO declaration were negative, meaning the clustering effect of new COVID-19 cases had become recently smaller. From November 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to ten was insignificant for the entire sample period. CONCLUSIONS: While COVID-19 continues to circulate in SSA, the region never reached outbreak status, and the weekly transmission rate had remained below one case per 100,000 population for well over one year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of a pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had ended in SSA by the time of the WHO declaration.

Central Asian Surveillance Metrics and History of the COVID-19 Pandemic: Longitudinal Analyses.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in Central Asia we first conducted in 2020 by providing two additional years of data for the region. The historical context provided through additional data can inform regional preparedness and early responses to infectious outbreaks of either the SARS-CoV-2 virus or future pathogens in Central Asia. OBJECTIVE: First, we aim to measure whether there was an expansion or contraction in the pandemic in Central Asia when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in Central Asia. METHODS: Traditional surveillance metrics, including counts and rates of COVID-19 transmissions and deaths, and enhanced surveillance indicators, including speed, acceleration, jerk, and persistence, were used to measure shifts in the pandemic. To identify the appearance and duration of variants of concern, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional speed was greater than an outbreak threshold of ten. We ran the test iteratively with six months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for seven months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1- and 7-day persistence coefficients remained statistically significant, the coefficients were relatively small in magnitude (0.125 and 0.347, respectively). Furthermore, the shift parameters for either of the two most recent weeks around May 5, 2023, were both significant and negative, meaning the clustering effect of new COVID-19 cases became even smaller in the two weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to ten became entirely insignificant for the first time in March of 2023. CONCLUSIONS: While COVID-19 continues to circulate in Central Asia, the rate of transmission remained well below the threshold of an outbreak for seven months ahead of the WHO declaration. COVID-19 appeared to be endemic in the region and no longer reached the threshold of pandemic. Both standard and enhanced surveillance metrics suggest the pandemic had ended by the time of the WHO declaration.

South Asia's COVID-19 History and Surveillance: Updated Epidemiological Assessment.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in South Asia we first conducted in 2020 with two additional years of data for the region. We assess whether COVID-19 had transitioned from pandemic to endemic at the point the World Health Organization (WHO) ended the publication health emergency status for COVID-19 on May 5, 2023. OBJECTIVE: First, we aim to measure whether there was an expansion or contraction in the pandemic in South Asia around the WHO declaration. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in South Asia. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study Welch et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional weekly speed or transmission rate per 100,000 population was greater than an outbreak threshold of ten. We ran the test iteratively with six months of data across the sample period. RESULTS: Speed for the region remained below the outbreak threshold for over a year by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day persistence coefficients remained statistically significant and positive (1.168), the 7-day persistence coefficient was negative (-0.185), suggesting limited cluster effects in which cases on a given day predict cases seven days forward. Furthermore, the shift parameters for either of the two most recent weeks around May 5, 2023, did not indicate any overall change in the persistence measure around the time of WHO declaration. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to ten was statistically insignificant across the entire pandemic. CONCLUSIONS: While COVID-19 continues to circulate in South Asia, the rate of transmission had remained below the outbreak threshold for well over a year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had ended by the time of the WHO declaration. Prevention policies should be a focus ahead of future pandemics. On that point, policy should emphasize an epidemiological task force with widespread testing and a contact-tracing system.

Substitution of Methods in Suicide Deaths - Firearm Injury and Hanging.

Background: Prevention strategies for suicide emphasize restrictions on firearm access. These restrictions may lose efficacy if individuals substitute other lethal suicide methods. Aims: The objective of this study is to determine the extent to which individuals who die by suicide in the United States substitute hanging for firearm injury. Methods: This study is a repeated cross-sectional analysis of suicide deaths in the United States from 2003 to 2021. Multiple regression was used to estimate the effect of firearm access proxies on individual suicide methods (hanging vs. firearm injury). Results: The probability of death by hanging was significantly and negatively associated with proxies of firearm access. Limitations: This study does not compare crude rates of suicide by state, which rise on average with rates of firearm ownership. The National Violent Death Reporting System expanded over the sample period, so early years have incomplete ascertainment. Rates of gun ownership and gun safety law scales are measured as proxies. Conclusions: Although means restriction around firearm access is a critical tool for suicide prevention, complementary strategies for prevention around hanging merit further study.

Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023) in Latin America and the Caribbean: Longitudinal Trend Analysis.

BACKGROUND: In May 2020, the World Health Organization (WHO) declared Latin America and the Caribbean (LAC) the epicenter of the COVID-19 pandemic, with over 40% of worldwide COVID-19-related deaths at the time. This high disease burden was a result of the unique circumstances in LAC. OBJECTIVE: This study aimed to (1) measure whether the pandemic was expanding or contracting in LAC when the WHO declared the end of COVID-19 as a public health emergency of international concern on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history; and (3) provide, with a focus on prevention policies, a historical context for the course of the pandemic in the region. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern (VOCs). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Additionally, we conducted a 1-sided t test for whether the regional weekly speed (rate of novel COVID-19 transmission) was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the period from August 2020 to May 2023. RESULTS: The speed of pandemic spread for the region had remained below the outbreak threshold for 6 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant for the 120-day period ending on the week of May 5, 2023, the coefficients were relatively modest in magnitude (0.457 and 0.491, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any change in this clustering effect of cases on future cases. From December 2021 onward, Omicron was the predominant VOC in sequenced viral samples. The rolling t test of speed=10 became entirely insignificant from January 2023 onward. CONCLUSIONS: Although COVID-19 continues to circulate in LAC, surveillance data suggest COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. However, the region experienced a high COVID-19 burden in the early stages of the pandemic, and prevention policies should be an immediate focus in future pandemics. Ahead of vaccination development, these policies can include widespread testing of individuals and an epidemiological task force with a contact-tracing system.

Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023) in Europe: Longitudinal Trend Analysis.

BACKGROUND: In this study, we built upon our initial research published in 2020 by incorporating an additional 2 years of data for Europe. We assessed whether COVID-19 had shifted from the pandemic to endemic phase in the region when the World Health Organization (WHO) declared the end of the public health emergency of international concern on May 5, 2023. OBJECTIVE: We first aimed to measure whether there was an expansion or contraction in the pandemic in Europe at the time of the WHO declaration. Second, we used dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we provided the historical context for the course of the pandemic in Europe in terms of policy and disease burden at the country and region levels. METHODS: In addition to the updates of traditional surveillance data and dynamic panel estimates from the original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-tailed t test for whether regional weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for 4 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day and 7-day persistence coefficients remained statistically significant, the coefficients were moderate in magnitude (0.404 and 0.547, respectively; P<.001 for both). The shift parameters for the 2 weeks around the WHO declaration were small and insignificant, suggesting little change in the clustering effect of cases on future cases at the time. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 became insignificant for the first time in April 2023. CONCLUSIONS: While COVID-19 continues to circulate in Europe, the rate of transmission remained below the threshold of an outbreak for 4 months ahead of the WHO declaration. The region had previously been in a nearly continuous state of outbreak. The more recent trend suggested that COVID-19 was endemic in the region and no longer reached the threshold of the pandemic definition. However, several countries remained in a state of outbreak, and the conclusion that COVID-19 was no longer a pandemic in Europe at the time is unclear.

Appendicitis Hospitalization Care Costs Among Patients With Delayed Diagnosis of Appendicitis.

Importance: Delayed appendicitis diagnosis is associated with worse outcomes. Appendicitis hospital care costs associated with delayed diagnosis are unknown. Objective: To determine whether delayed appendicitis diagnosis was associated with increased appendicitis hospital care costs. Design, Setting, and Participants: This cohort study used data from patients receiving an appendectomy aged 18 to 64 years in 5 states (Florida, Maryland, Massachusetts, New York, Wisconsin) that were captured in the Healthcare Cost and Utilization Project State Inpatient and Emergency Department databases for the years 2016 and 2017 with no additional follow-up. Data were analyzed January through April 2023. Exposures: Delayed diagnosis was defined as a previous emergency department or inpatient hospital encounter with an abdominal diagnosis other than appendicitis, and no intervention 7 days prior to appendectomy encounter. Main Outcomes and Measures: The main outcome was appendicitis hospital care costs. This was calculated from aggregated charges of encounters 7 days prior to appendectomy, the appendectomy encounter, and 30 days postoperatively. Cost-to-charge ratios were applied to charges to obtain costs, which were then adjusted for wage index, inflation to 2022 US dollar, and with extreme outliers winsorized. A multivariable Poisson regression estimated appendicitis hospital care costs associated with a delayed diagnosis while controlling for age, sex, race and ethnicity, insurance status, care discontinuity, income quartile, hospital size, teaching status, medical school affiliation, percentage of Black and Hispanic patient discharges, core-based statistical area, and state. Results: There were 76 183 patients (38 939 female [51.1%]; 2192 Asian or Pacific Islander [2.9%], 14 132 Hispanic [18.5%], 8195 non-Hispanic Black [10.8%], 46 949 non-Hispanic White [61.6%]) underwent appendectomy, and 2045 (2.7%) had a delayed diagnosis. Delayed diagnosis patients had median (IQR) unadjusted cost of $11 099 ($6752-$17 740) compared with $9177 ($5575-$14 481) for nondelayed (P < .001). Patients with delayed diagnosis had 1.23 times (95% CI, 1.16-1.28 times) adjusted increased appendicitis hospital care costs. The mean marginal cost of delayed diagnosis was $2712 (95% CI, $2083-$3342). Even controlling for delayed diagnosis, non-Hispanic Black patients had 1.22 times (95% CI, 1.17-1.28 times) the adjusted increased appendicitis hospital care costs compared with non-Hispanic White patients. Conclusions and Relevance: In this cohort study, delayed diagnosis of appendicitis was associated with increased hospital care costs.

Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023) in the Middle East and North Africa: Longitudinal Trend Analysis.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in the Middle East and North Africa (MENA) we first conducted in 2020 with 2 additional years of data for the region. OBJECTIVE: The objective of this study is to determine whether the MENA region meets the criteria for moving from a pandemic to endemic. In doing so, this study considers pandemic trends, dynamic and genomic surveillance methods, and region-specific historical context for the pandemic. These considerations continue through the World Health Organization (WHO) declaration of the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. METHODS: In addition to updates to traditional surveillance data and dynamic panel estimates from the original study by Post et al, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed of COVID-19 spread was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data from September 4, 2020, to May 12, 2023. RESULTS: The speed of COVID-19 spread for the region had remained below the outbreak threshold for 7 continuous months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant and positive, the weekly shift parameters suggested the coefficients had most recently turned negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of the speed of spread equal to 10 became entirely insignificant from October 2022 onward. CONCLUSIONS: The COVID-19 pandemic had far-reaching effects on MENA, impacting health care systems, economies, and social well-being. Although COVID-19 continues to circulate in the MENA region, the rate of transmission remained well below the threshold of an outbreak for over 1 year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had transitioned to endemic by the time of the WHO declaration.

Older adult drug overdose: an application of latent class analysis to identify prevention opportunities.

BACKGROUND: Older adult overdose death rates have increased significantly in recent years. However, research for prevention of drug overdose death specific to older adults is limited. Our objective is to identify profiles based on missed intervention points (touchpoints) to inform prevention of future older adult unintentional overdose deaths. METHODS: We used latent class analysis methods to identify profiles of decedents aged 55 + years in the Illinois Statewide Unintentional Drug Overdose Reporting System. This system collects data on 92.6% of all unintentional overdose deaths in Illinois and includes data from death certificates, coroner/medical examiner, toxicology, and autopsy reports. Data include decedent demographics, circumstances leading up to and surrounding the fatal overdose and details regarding the overdose. Variables in the latent class analysis model included sex, race, alcohol test result, social isolation, recent emergency department (ED) visit, chronic pain, and pain treatment. RESULTS: We identified three distinct decent profiles. Class 1 (13% of decedents) included female decedents who were in pain treatment, had physical health problems, and had greater likelihood of a recent ED visit before their death. Class 2 (35% of decedents) decedents were most likely to be socially connected (live with others, employed, had social or family relationships) but less likely to have recent healthcare visits. Class 3 (52% of decedents) decedents had higher social isolation (lived alone, unemployed, unpartnered), were mostly male, had fewer known physical health conditions, and more alcohol positivity at time of death. White decedents are clustered in class 1 while Black decedents are predominant in classes 2 and 3. CONCLUSIONS: These profiles link to potential touchpoint opportunities for substance use disorder screening harm reduction and treatment. Class 1 members were most likely to be reachable in healthcare settings. However, most decedents were members of Classes 2 and 3 with less engagement in the healthcare system, suggesting a need for screening and intervention in different contexts. For Class 2, intervention touchpoints might include education and screening in work or social settings such as senior centers given the higher degree of social connectivity. For Class 3, the most isolated group, touchpoints may occur in the context of harm reduction outreach and social service delivery.

Overlapping Delta and Omicron Outbreaks During the COVID-19 Pandemic: Dynamic Panel Data Estimates.

BACKGROUND: The Omicron variant of SARS-CoV-2 is more transmissible than prior variants of concern (VOCs). It has caused the largest outbreaks in the pandemic, with increases in mortality and hospitalizations. Early data on the spread of Omicron were captured in countries with relatively low case counts, so it was unclear how the arrival of Omicron would impact the trajectory of the pandemic in countries already experiencing high levels of community transmission of Delta. OBJECTIVE: The objective of this study is to quantify and explain the impact of Omicron on pandemic trajectories and how they differ between countries that were or were not in a Delta outbreak at the time Omicron occurred. METHODS: We used SARS-CoV-2 surveillance and genetic sequence data to classify countries into 2 groups: those that were in a Delta outbreak (defined by at least 10 novel daily transmissions per 100,000 population) when Omicron was first sequenced in the country and those that were not. We used trend analysis, survival curves, and dynamic panel regression models to compare outbreaks in the 2 groups over the period from November 1, 2021, to February 11, 2022. We summarized the outbreaks in terms of their peak rate of SARS-CoV-2 infections and the duration of time the outbreaks took to reach the peak rate. RESULTS: Countries that were already in an outbreak with predominantly Delta lineages when Omicron arrived took longer to reach their peak rate and saw greater than a twofold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in an outbreak. CONCLUSIONS: These results suggest that high community transmission of Delta at the time of the first detection of Omicron was not protective, but rather preluded larger outbreaks in those countries. Outbreak status may reflect a generally susceptible population, due to overlapping factors, including climate, policy, and individual behavior. In the absence of strong mitigation measures, arrival of a new, more transmissible variant in these countries is therefore more likely to lead to larger outbreaks. Alternately, countries with enhanced surveillance programs and incentives may be more likely to both exist in an outbreak status and detect more cases during an outbreak, resulting in a spurious relationship. Either way, these data argue against herd immunity mitigating future outbreaks with variants that have undergone significant antigenic shifts.

Has Omicron Changed the Evolution of the Pandemic?

BACKGROUND: Variants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy. OBJECTIVE: The aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak. METHODS: We analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections. RESULTS: The observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread. CONCLUSIONS: The transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.

The Adult Murine Intestine is Dependent on Constitutive Laminin-γ1 Synthesis.

Laminin-γ1 is required for early embryonic development; however, the need for laminin-γ1 synthesis in adulthood is unknown. A global and inducible mouse model of laminin-γ1 deficiency was generated to address this question. Genetic ablation of the Lamc1 gene in adult mice was rapidly lethal. Despite global Lamc1 gene deletion in tamoxifen-induced mutant mice, there was minimal change in total cardiac, pulmonary, hepatic or renal laminin protein. In contrast, laminin-γ1 was significantly depleted in the small intestines, which showed crypt hyperplasia and dissociation of villous epithelium from adjacent mesenchyme. We conclude that the physiologic requirement for laminin-γ1 synthesis in adult mice is dependent on a tissue-specific basal rate of laminin-γ1 turnover that results in rapid depletion of laminin-γ1 in the intestine.

Refinement of embolic stroke model in rats: Effect of post-embolization anesthesia duration on arterial blood pressure, cerebral edema and mortality.

BACKGROUND: Injection of a clot into the internal carotid artery is an experimental model of ischemic stroke that is considered to closely mimic embolic stroke in humans. In this model, the common carotid artery typically remains temporarily occluded to permit time for stabilization of the clot in the middle cerebral artery. However, the associated lengthening of the anesthesia duration could affect arterial blood pressure and stroke outcome. NEW METHOD: We refined the model by examining how increasing isoflurane anesthesia duration from 30 to 60 min after clot embolization affects mortality, infarct volume, edema, blood-brain barrier permeability, and the 8-h post-ischemic time course of blood pressure, which has not been reported previously in this model. RESULTS: We found that arterial pressure increased after discontinuing anesthesia in both embolized groups and that the increase was greater than in the corresponding non-embolized sham-operated rats. At 24 h, the group with 60-min post-ischemia anesthesia exhibited greater brain water content and a greater ipsilateral-to-contralateral ratio of extravasated Evans blue dye. Mortality was greater in the 60-min group, but infarct volume among survivors was not different from that in the 30-min anesthesia group. COMPARISON WITH EXISTING METHODS: This study refines the embolic stroke model by demonstrating the importance of minimizing the duration of anesthesia after embolization. CONCLUSIONS: These data indicate that early discontinuation of isoflurane anesthesia after clot embolization permits an earlier hypertensive response that limits edema formation and mortality without significantly affecting infarct volume in survivors, thereby decreasing the required number of animals.