Severity of influenza-associated hospitalisations by influenza virus type and subtype in the USA, 2010-19: a repeated cross-sectional study.

BACKGROUND: Influenza burden varies across seasons, partly due to differences in circulating influenza virus types or subtypes. Using data from the US population-based surveillance system, Influenza Hospitalization Surveillance Network (FluSurv-NET), we aimed to assess the severity of influenza-associated outcomes in individuals hospitalised with laboratory-confirmed influenza virus infections during the 2010-11 to 2018-19 influenza seasons. METHODS: To evaluate the association between influenza virus type or subtype causing the infection (influenza A H3N2, A H1N1pdm09, and B viruses) and in-hospital severity outcomes (intensive care unit [ICU] admission, use of mechanical ventilation or extracorporeal membrane oxygenation [ECMO], and death), we used FluSurv-NET to capture data for laboratory-confirmed influenza-associated hospitalisations from the 2010-11 to 2018-19 influenza seasons for individuals of all ages living in select counties in 13 US states. All individuals had to have an influenza virus test within 14 days before or during their hospital stay and an admission date between Oct 1 and April 30 of an influenza season. Exclusion criteria were individuals who did not have a complete chart review; cases from sites that contributed data for three or fewer seasons; hospital-onset cases; cases with unidentified influenza type; cases of multiple influenza virus type or subtype co-infection; or individuals younger than 6 months and ineligible for the influenza vaccine. Logistic regression models adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site compared odds of in-hospital severity by virus type or subtype. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season. FINDINGS: Data for 122 941 individuals hospitalised with influenza were captured in FluSurv-NET from the 2010-11 to 2018-19 seasons; after exclusions were applied, 107 941 individuals remained and underwent influenza A virus imputation when missing A subtype (43·4%). After imputation, data for 104 969 remained and were included in the final analytic sample. Averaging across imputed datasets, 57·7% (weighted percentage) had influenza A H3N2, 24·6% had influenza A H1N1pdm09, and 17·7% had influenza B virus infections; 16·7% required ICU admission, 6·5% received mechanical ventilation or ECMO, and 3·0% died (95% CIs had a range of less than 0·1% and are not displayed). Individuals with A H1N1pdm09 had higher odds of in-hospital severe outcomes than those with A H3N2: adjusted odds ratios (ORs) for A H1N1pdm09 versus A H3N2 were 1·42 (95% CI 1·32-1·52) for ICU admission; 1·79 (1·60-2·00) for mechanical ventilation or ECMO use; and 1·25 (1·07-1·46) for death. The adjusted ORs for individuals infected with influenza B versus influenza A H3N2 were 1·06 (95% CI 1·01-1·12) for ICU admission, 1·14 (1·05-1·24) for mechanical ventilation or ECMO use, and 1·18 (1·07-1·31) for death. INTERPRETATION: Despite a higher burden of hospitalisations with influenza A H3N2, we found an increased likelihood of in-hospital severe outcomes in individuals hospitalised with influenza A H1N1pdm09 or influenza B virus. Thus, it is important for individuals to receive an annual influenza vaccine and for health-care providers to provide early antiviral treatment for patients with suspected influenza who are at increased risk of severe outcomes, not only when there is high influenza A H3N2 virus circulation but also when influenza A H1N1pdm09 and influenza B viruses are circulating. FUNDING: The US Centers for Disease Control and Prevention.

Vaccination Status and Trends in Adult Coronavirus Disease 2019-Associated Hospitalizations by Race and Ethnicity: March 2020-August 2022.

BACKGROUND: We sought to determine whether race/ethnicity disparities in severe coronavirus disease 2019 (COVID-19) outcomes persist in the era of vaccination. METHODS: Population-based age-adjusted monthly rate ratios (RRs) of laboratory-confirmed COVID-19-associated hospitalizations were calculated among adult patients from the COVID-19-Associated Hospitalization Surveillance Network, March 2020 - August 2022 by race/ethnicity. Among randomly sampled patients July 2021 - August 2022, RRs for hospitalization, intensive care unit (ICU) admission, and in-hospital mortality were calculated for Hispanic, Black, American Indian/Alaskan Native (AI/AN), and Asian/Pacific Islander (API) persons vs White persons. RESULTS: Based on data from 353 807 patients, hospitalization rates were higher among Hispanic, Black, and AI/AN vs White persons March 2020 - August 2022, yet the magnitude declined over time (for Hispanic persons, RR = 6.7; 95% confidence interval [CI], 6.5-7.1 in June 2020 vs RR < 2.0 after July 2021; for AI/AN persons, RR = 8.4; 95% CI, 8.2-8.7 in May 2020 vs RR < 2.0 after March 2022; and for Black persons RR = 5.3; 95% CI, 4.6-4.9 in July 2020 vs RR < 2.0 after February 2022; all P ≤ .001). Among 8706 sampled patients July 2021 - August 2022, hospitalization and ICU admission RRs were higher for Hispanic, Black, and AI/AN patients (range for both, 1.4-2.4) and lower for API (range for both, 0.6-0.9) vs White patients. All other race and ethnicity groups had higher in-hospital mortality rates vs White persons (RR range, 1.4-2.9). CONCLUSIONS: Race/ethnicity disparities in COVID-19-associated hospitalizations declined but persist in the era of vaccination. Developing strategies to ensure equitable access to vaccination and treatment remains important.

Structural plasticity of GABAergic and glutamatergic networks in the motor thalamus of parkinsonian monkeys.

In the primate thalamus, the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM) receive GABAergic projections from the internal globus pallidus (GPi) and glutamatergic inputs from motor cortices. In this study, we used electron microscopy to assess potential structural changes in GABAergic and glutamatergic microcircuits in the VApc and CM of MPTP-treated parkinsonian monkeys. The intensity of immunostaining for GABAergic markers in VApc and CM did not differ between control and parkinsonian monkeys. In the electron microscope, three major types of terminals were identified in both nuclei: (a) vesicular glutamate transporter 1 (vGluT1)-positive terminals forming asymmetric synapses (type As), which originate from the cerebral cortex, (b) GABAergic terminals forming single symmetric synapses (type S1), which likely arise from the reticular nucleus and GABAergic interneurons, and (c) GABAergic terminals forming multiple symmetric synapses (type S2), which originate from GPi. The density of As terminals outnumbered that of S1 and S2 terminals in VApc and CM of control and parkinsonian animals. No significant change was found in the abundance and synaptic connectivity of S1 and S2 terminals in VApc or CM of MPTP-treated monkeys, while the prevalence of "As" terminals in VApc of parkinsonian monkeys was 51.4% lower than in controls. The cross-sectional area of vGluT1-positive boutons in both VApc and CM of parkinsonian monkeys was significantly larger than in controls, but their pattern of innervation of thalamic cells was not altered. Our findings suggest that the corticothalamic system undergoes significant synaptic remodeling in the parkinsonian state.

Are Meaningful Use Stage 2 certified EHRs ready for interoperability? Findings from the SMART C-CDA Collaborative.

BACKGROUND AND OBJECTIVE: Upgrades to electronic health record (EHR) systems scheduled to be introduced in the USA in 2014 will advance document interoperability between care providers. Specifically, the second stage of the federal incentive program for EHR adoption, known as Meaningful Use, requires use of the Consolidated Clinical Document Architecture (C-CDA) for document exchange. In an effort to examine and improve C-CDA based exchange, the SMART (Substitutable Medical Applications and Reusable Technology) C-CDA Collaborative brought together a group of certified EHR and other health information technology vendors. MATERIALS AND METHODS: We examined the machine-readable content of collected samples for semantic correctness and consistency. This included parsing with the open-source BlueButton.js tool, testing with a validator used in EHR certification, scoring with an automated open-source tool, and manual inspection. We also conducted group and individual review sessions with participating vendors to understand their interpretation of C-CDA specifications and requirements. RESULTS: We contacted 107 health information technology organizations and collected 91 C-CDA sample documents from 21 distinct technologies. Manual and automated document inspection led to 615 observations of errors and data expression variation across represented technologies. Based upon our analysis and vendor discussions, we identified 11 specific areas that represent relevant barriers to the interoperability of C-CDA documents. CONCLUSIONS: We identified errors and permissible heterogeneity in C-CDA documents that will limit semantic interoperability. Our findings also point to several practical opportunities to improve C-CDA document quality and exchange in the coming years.

Mitigating error vulnerability at the transition of care through the use of health IT applications.

Adverse drug events are largely considered to be errors in which the severity of effects could be lessened or even prevented through more effective medication reconciliation practices. Transitions of care, particularly at the time of discharge from the hospital, represent a time of heightened error vulnerability that contributes to medication discrepancy occurrences. The observed vulnerability can be attributed to communication and care continuity gaps across health care settings and can often lead to preventable errors. Health IT tools developed through research can identify factors which increase the risk of medication discrepancies. Additionally, the implementations of optimized clinical workflow processes to form effective transitions of care are approaches to decreasing medication discrepancies which may lead to adverse drug events. While federal policies and certifying organizations have implemented quality initiatives to increase focus on medication reconciliation practices in the hospital and primary care settings, the same practices must be implemented after a patient is discharged to their homes or another health care facility in order to mitigate error vulnerabilities that occur at the transition of care. This paper provides an overview of health IT system capabilities and their applications within and across health care delivery settings to facilitate care coordination to ensure continuity of care.

Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea.

Cytochrome P450 2D6 (CYP2D6), an important CYP isoform with regard to drug-drug interactions, accounts for the metabolism of approximately 30% of all medications. To date, few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo. Six botanical extracts were evaluated in three separate studies (two extracts per study), each incorporating 16 healthy volunteers (eight females). Subjects were randomized to receive a standardized botanical extract for 14 days on separate occasions. A 30-day washout period was interposed between each supplementation phase. In study 1, subjects received milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa). In study 2, kava kava (Piper methysticum) and goldenseal (Hydrastis canadensis) extracts were administered, and in study 3 subjects received St. John's wort (Hypericum perforatum) and Echinacea (Echinacea purpurea). The CYP2D6 substrate, debrisoquine (5 mg), was administered before and at the end of supplementation. Pre- and post-supplementation phenotypic trait measurements were determined for CYP2D6 using 8-h debrisoquine urinary recovery ratios (DURR). Comparisons of pre- and post-supplementation DURR revealed significant inhibition (approximately 50%) of CYP2D6 activity for goldenseal, but not for the other extracts. Accordingly, adverse herb-drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates.

Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics.

Concomitant administration of botanical supplements with drugs that are P-glycoprotein (P-gp) substrates may produce clinically significant herb-drug interactions. This study evaluated the effects of St. John's wort and Echinacea on the pharmacokinetics of digoxin, a recognized P-gp substrate. Eighteen healthy volunteers were randomly assigned to receive a standardized St. John's wort (300 mg three times daily) or Echinacea (267 mg three times daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (300 mg twice daily, 7 days) and clarithromycin (500 mg twice daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin 0.25 mg) was administered orally before and after each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), elimination half-life, and maximum serum concentration were used to assess the effects of St. John's wort, Echinacea, rifampin, and clarithromycin on digoxin disposition. St. John's wort and rifampin both produced significant reductions (p < 0.05) in AUC((0-3)), AUC((0-24)), and C(max), while clarithromycin increased these parameters significantly (p < 0.05). Echinacea supplementation did not affect digoxin pharmacokinetics. Clinically significant P-gp-mediated herb-drug interactions are more likely to occur with St. John's wort than with Echinacea.

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.