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An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.
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BACKGROUND: Despite the widespread use of the phrase "harm reduction" and the proliferation of programs based on its principles during the current opioid epidemic, what it means in practice is not universally agreed upon. Harm reduction strategies have expanded from syringe and needle exchange programs that emerged in the mid-1980s primarily in response to the HIV epidemic, to include medication for opioid use disorder, supervised consumption rooms, naloxone distribution, and drug checking technologies such as fentanyl test strips. Harm reduction can often be in tension with abstinence and recovery models to address substance use, and people who use drugs may also hold competing views of what harm reduction means in practice. Street-based outreach workers are increasingly incorporated into harm reduction programs as part of efforts to engage with people more fully in various stages of drug use and nonuse. METHOD: This paper explores how peer outreach workers, called "members," in a street-based naloxone distribution program define and practice harm reduction. We interviewed 15 members of a street-based harm reduction organization in an urban center characterized by an enduring opioid epidemic. Inductive data analysis explored harm reduction as both a set of principles and a set of practices to understand how frontline providers define and enact them. RESULTS: Analysis revealed that when members talked about their work, they often conceptualized harm reduction as a collection of ways members and others can "save lives" and support people who use drugs. They also framed harm reduction as part of a "path toward recovery." This path was complicated and nonlinear but pursued a common goal of life without drug use and its residual effects. These findings suggest the need to develop harm reduction programs that incorporate both harm reduction and recovery to best meet the needs of people who use drugs and align with the value systems of implementers.
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Redução do Dano , Naloxona , Antagonistas de Entorpecentes , Grupo Associado , Humanos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Feminino , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Masculino , Adulto , Pesquisa Qualitativa , Relações Comunidade-Instituição , Programas de Troca de AgulhasRESUMO
BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.
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BACKGROUND: Viral respiratory illnesses are the most common acute illnesses experienced and generally follow a predicted pattern over time. The SARS-CoV-2 pandemic interrupted that pattern. METHODS: The HIVE (Household Influenza Vaccine Evaluation) study was established in 2010 to follow a cohort of Southeast Michigan households over time. Initially focused on influenza, surveillance was expanded to include other major respiratory pathogens, and, starting in 2015, the population was followed year-round. Symptoms of acute illness were reported, and respiratory specimens were collected and tested to identify viral infections. Based on the known population being followed, virus-specific incidence was calculated. RESULTS: From 2015 to 2022, 1755 participants were followed in HIVE for 7785 person-years with 7833 illnesses documented. Before the pandemic, rhinovirus (RV) and common cold human coronaviruses (HCoVs) were the viruses most frequently identified, and incidence decreased with increasing age. Type A influenza was next but with comparable incidence by age. Parainfluenza and respiratory syncytial viruses were less frequent overall, followed by human metapneumoviruses. Incidence was highest in young children, but infections were frequently documented in all age groups. Seasonality followed patterns established decades ago. The SARS-CoV-2 pandemic disrupted these patterns, except for RV and, to a lesser extent, HCoVs. In the first two years of the pandemic, RV incidence far exceeded that of SARS-CoV-2. CONCLUSION: Longitudinal cohort studies are important in comparing the incidence, seasonality, and characteristics of different respiratory viral infections. Studies documented the differential effect of the pandemic on the incidence of respiratory viruses in addition to SARS-CoV-2.
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From 2014-2023, infectious bronchitis virus (IBV) was detected in 6,589 samples from Canada, and partial nucleotide (nt) sequences of the IBV spike protein (S) gene were determined for 1,678 samples. Based on their S gene nt sequence identities and origin, Canadian IBVs could be classified into 4 groups: 1) 50.3% were variant viruses related to strains described in the United States; 2) 45.6% were vaccine-like viruses; 3) 2.1% were Eurasian viruses; 4) 2.0% were Canadian variants. Outbreaks with IBVs related to strains CAL1734/04, 4/91, and DMV/1639/11 were often associated with more severe disease in all chicken commodity groups. With the emergence of numerous IBV strains, the severity of infection and number of affected flocks increased. Outbreaks with various IBV strains overlapped in their emergence, peaked, and regressed, but the introduction of DMV/1639/11 has resulted in a continuous field challenge since its first detection in 2015.
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BackgroundHealthcare personnel (HCP) are at high risk for respiratory infections through occupational exposure to respiratory viruses.AimWe used data from a prospective influenza vaccine effectiveness study in HCP to quantify the incidence of acute respiratory infections (ARI) and their associated presenteeism and absenteeism.MethodsAt the start and end of each season, HCP at two Israeli hospitals provided serum to screen for antibodies to influenza virus using the haemagglutination inhibition assay. During the season, active monitoring for the development of ARI symptoms was conducted twice a week by RT-PCR testing of nasal swabs for influenza and respiratory syncytial virus (RSV). Workplace presenteeism and absenteeism were documented. We calculated incidences of influenza- and RSV-associated ARI and applied sampling weights to make estimates representative of the source population.ResultsThe median age of 2,505 participating HCP was 41 years, and 70% were female. Incidence was 9.1 per 100 person-seasons (95%â¯CI:â¯5.8-14.2) for RT-PCR-confirmed influenza and 2.5 per 100 person-seasons (95%â¯CI:â¯0.9-7.1) for RSV illness. Each season, 18-23% of unvaccinated and influenza-negative HCP seroconverted. The incidence of seroconversion or RT-PCR-confirmed influenza was 27.5 per 100 person-seasons (95%â¯CI:â¯17.8-42.5). Work during illness occurred in 92% (95%â¯CI:â¯91-93) of ARI episodes, absence from work in 38% (95%â¯CI:â¯36-40).ConclusionInfluenza virus and RSV infections and associated presenteeism and absenteeism were common among HCP. Improving vaccination uptake among HCP, infection control, and encouraging sick HCP to stay home are important strategies to reduce ARI incidence and decrease the risk of in-hospital transmission.
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Absenteísmo , Pessoal de Saúde , Influenza Humana , Presenteísmo , Infecções por Vírus Respiratório Sincicial , Estações do Ano , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Humana/diagnóstico , Influenza Humana/prevenção & controle , Feminino , Incidência , Masculino , Pessoal de Saúde/estatística & dados numéricos , Israel/epidemiologia , Adulto , Presenteísmo/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Vírus Sincicial Respiratório Humano/isolamento & purificação , Vírus Sincicial Respiratório Humano/genética , Exposição Ocupacional/estatística & dados numéricos , Testes de Inibição da HemaglutinaçãoRESUMO
Saturn's mid-sized icy moons have complex relationships with Saturn's interior, the rings, and with each other, which can be expressed in their shapes, interiors, and geology. Observations of their physical states can, thus, provide important constraints on the ages and formation mechanism(s) of the moons, which in turn informs our understanding of the formation and evolution of Saturn and its rings. Here, we describe the cratering records of the mid-sized moons and the value and limitations of their use for constraining the histories of the moons. We also discuss observational constraints on the interior structures of the moons and geologically-derived inferences on their thermal budgets through time. Overall, the geologic records of the moons (with the exception of Mimas) include evidence of epochs of high heat flows, short- and long-lived subsurface oceans, extensional tectonics, and considerable cratering. Curiously, Mimas presents no clear evidence of an ocean within its surface geology, but its rotation and orbit indicate a present-day ocean. While the moons need not be primordial to produce the observed levels of interior evolution and geologic activity, there is likely a minimum age associated with their development that has yet to be determined. Uncertainties in the populations impacting the moons makes it challenging to further constrain their formation timeframes using craters, whereas the characteristics of their cores and other geologic inferences of their thermal evolutions may help narrow down their potential histories. Disruptive collisions may have also played an important role in the formation and evolution of Saturn's mid-sized moons, and even the rings of Saturn, although more sophisticated modeling is needed to determine the collision conditions that produce rings and moons that fit the observational constraints. Overall, the existence and physical characteristics of Saturn's mid-sized moons provide critical benchmarks for the development of formation theories.
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Background: Respiratory syncytial virus (RSV)-associated lower respiratory tract infection contributes significantly to morbidity/mortality worldwide in low birthweight (LBW) infants (<2500 g). Studies have demonstrated decreased maternal immunoglobulin G (IgG) transfer of various antibodies to LBW infants. We aimed to evaluate naturally acquired RSV anti-prefusion F protein (anti-preF) antibody transfer in pregnancies with LBW versus normal birthweight (NBW) infants. Methods: In this cohort study conducted among pregnant individuals and their infants, we tested paired maternal and singleton infant cord samples for RSV anti-preF IgG via an electrochemiluminescence immunoassay, using linear regression to evaluate associations between LBW and anti-preF IgG. Covariates included seasonality, insurance, small-for-gestational-age birthweight, and gestational age at delivery. Results: We tested maternal/cord RSV anti-preF IgG from 54 and 110 pregnancies with LBW and NBW infants, respectively. Of LBW infants, 22 (40.7%) were born both preterm and with small-for-gestational-age birthweight. The median (interquartile range) gestational age at delivery and birthweight were 34.0 (31.7-37.1) weeks and 1902 (1393-2276) g for LBW infants versus 39.1 (38.3-39.9) weeks and 3323 (3109-3565) g for NBW infants (both P < .001). In unadjusted comparisons, preterm infants had significantly lower cord anti-preF IgG levels and cord-maternal IgG ratios compared with full-term infants, while LBW infants had significantly lower cord-maternal IgG ratios than NBW infants (all P < .01). After adjustment for covariates, there was no difference in cord-maternal IgG ratios (ß =-0.29 [95% confidence interval, -.63 to .05]) between LBW and NBW infants. Conclusions: We documented robust transfer of maternal RSV anti-preF IgG in pregnancies with both LBW and NBW infants. Further studies are needed to assess immune protection in at-risk infants.
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We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection.
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Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologia , Idoso , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Adulto Jovem , Imunidade Humoral , Formação de AnticorposRESUMO
OBJECTIVE: People who use opioids are vulnerable to sleep disturbances due to a range of factors, including the substances they use and the various structural vulnerabilities they face. We aimed to understand the burden of sleep-related impairment and problems pertaining to sleep context and schedule among people who use opioids. METHODS: We explored sleep quality and problems among a suburban sample of people who use opioids experiencing extensive structural vulnerabilities (N = 170). Participants reported their most urgent concern in the past week (e.g., sleep, drug use, housing), their sleep context, sleep problems, sleep schedules, and scores on the PROMIS Sleep-Related Impairment measure. We then quantified associations between Sleep-Related Impairment scores and sociodemographics and substance use. RESULTS: Participants were primarily men (66%) and non-Hispanic Black (67%) with a mean age of 42 (SD: 12.1). Many experienced hunger (44%) and literal homelessness (40%). One-quarter (28%) reported that sleep was their most urgent concern in the past week. The most common problems when falling or staying asleep were mental health-related symptoms (81%) and pain/discomfort (32%). Literal homelessness (ß = 2.2, 95% CI: 0.6, 3.7), hunger (ß = 2.3, 95% CI: 1.0, 3.6), and frequent alcohol use (ß = 1.5, 95% CI: 0.2, 2.7) were significantly associated with Sleep-Related Impairment scores. CONCLUSIONS: Homelessness and hunger are associated with sleep-related impairment in people who use opioids. Poor sleep quality, substance use, structural vulnerability, and mental health problems are all interrelated sources of functional impairment in this population. Interventions that address poverty as an underlying cause of sleep-related impairment and provide safe sleeping environments are needed.
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BACKGROUND: We assessed associations between binding antibody (bAb) concentration <5 days from symptom onset and testing positive for COVID-19 among patients in a test-negative study. METHODS: From October 2021 to June 2022, study sites in 7 states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain (RBD) and nucleocapsid antigens from the ancestral strain in standardized bAb units (BAU). Percentage change in odds of COVID-19 by increasing anti-RBD bAb was estimated via logistic regression as (1 - adjusted odds ratio of COVID-19) × 100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. RESULTS: Out of 2018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb levels were lower among COVID-19 cases than SARS-CoV-2 test-negative controls during the Delta-predominant period (112 vs 498 BAU/mL) and Omicron-predominant period (823 vs 1189 BAU/mL). Acute-phase ancestral spike RBD bAb levels associated with 50% lower odds of COVID-19 were 1968 BAU/mL against Delta and 3375 BAU/mL against Omicron; thresholds may differ in other laboratories. CONCLUSIONS: During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.
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Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Glicoproteína da Espícula de Coronavírus/imunologia , Adolescente , Adulto Jovem , Criança , Estados Unidos/epidemiologia , Pré-Escolar , Vacinas contra COVID-19/imunologia , Pacientes Ambulatoriais , Lactente , Idoso de 80 Anos ou mais , Eficácia de Vacinas , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagemRESUMO
Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.
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INTRODUCTION: Despite a longstanding Israel Ministry of Health recommendation that all healthcare personnel (HCP) receive a seasonal influenza vaccine, vaccine uptake among HCP remains below the country's target of 60% coverage. To understand factors related to vaccine hesitancy, we used data from a prospective three-year (2016-2019) influenza vaccine effectiveness study among Israeli HCP to examine knowledge, attitudes, and practices (KAP) about influenza vaccination and their association with vaccine uptake. METHODS: At the start of each influenza season, all participating HCP completed a questionnaire that included questions about socio-demographic and occupational characteristics, health status, and KAP related to seasonal influenza vaccination. We extracted vaccination history from electronic medical records and employee vaccination registries. We used logistic regression models to identify demographic and occupational factors, and KAP about influenza vaccination, associated with receipt of vaccination. RESULT: A total of 2,126 HCP were enrolled and had available data on vaccination history. Their median age was 42 years [IQR 35-52], and 73 % self-identified as female. Influenza vaccine uptake in 2016, 2017 and 2018 was 46 %, 48 % and 47 %, respectively. Overall, 36 % of HCP had received an influenza vaccine in ≥ 4 of the eight years prior. HCP aged 35-49 years were less likely to receive influenza vaccine compared to HCP aged ≥ 50 years (OR: 0.81 [95 % CI: 0.67-0.98]). Nurses and allied personnel were less likely to receive influenza vaccine compared to physicians (OR: 0.63 [95 % CI: 0.50-0.78] and OR: 0.53 [95 % CI: 0.40-0.70], respectively). The emotional benefit of vaccination (e.g., anticipating regret if not vaccinated) and the perception of vaccine safety were factors associated with vaccine uptake (OR: 7.60 [95 % CI: 6.27-9.22] and OR: 3.43 [95 % CI:2.91-4.03], respectively). CONCLUSION: Among HCP at two hospitals in Israel, less than half received an annual influenza vaccine. Older HCP, physicians, and those who reported the emotional benefit of vaccination or agreed that influenza vaccines are safe were more likely to be vaccinated. Future influenza vaccination campaigns could focus on these demographic groups and tailor messages emphasizing the emotional benefits of vaccination and vaccine safety to increase seasonal influenza vaccine uptake among HCP in Israel.
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Significance: Widefield microscopy of the entire dorsal part of mouse cerebral cortex enables large-scale ("mesoscopic") imaging of different aspects of neuronal activity with spectrally compatible fluorescent indicators as well as hemodynamics via oxy- and deoxyhemoglobin absorption. Versatile and cost-effective imaging systems are needed for large-scale, color-multiplexed imaging of multiple fluorescent and intrinsic contrasts. Aim: We aim to develop a system for mesoscopic imaging of two fluorescent and two reflectance channels. Approach: Excitation of red and green fluorescence is achieved through epi-illumination. Hemoglobin absorption imaging is achieved using 525- and 625-nm light-emitting diodes positioned around the objective lens. An aluminum hemisphere placed between objective and cranial window provides diffuse illumination of the brain. Signals are recorded sequentially by a single sCMOS detector. Results: We demonstrate the performance of our imaging system by recording large-scale spontaneous and stimulus-evoked neuronal, cholinergic, and hemodynamic activity in awake, head-fixed mice with a curved "crystal skull" window expressing the red calcium indicator jRGECO1a and the green acetylcholine sensor GRAB ACh 3.0 . Shielding of illumination light through the aluminum hemisphere enables concurrent recording of pupil diameter changes. Conclusions: Our widefield microscope design with a single camera can be used to acquire multiple aspects of brain physiology and is compatible with behavioral readouts of pupil diameter.
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BACKGROUND: Despite electroconvulsive therapy being one of the most effective treatments in psychiatry, few studies report trends in the provision of electroconvulsive therapy over time. This study aims to investigate the use of electroconvulsive therapy between 2009 and 2020 in an Australian public tertiary mental health facility, and to describe the electroconvulsive therapy patient population and change in courses of treatment. METHODS: Routinely collected data for 677 patients who received 1669 electroconvulsive therapy courses of treatment at an Australian public tertiary mental health facility between 2009 and 2020 were examined. RESULTS: The provision of acute electroconvulsive therapy was stable across the study period; however, the number of maintenance electroconvulsive therapy courses commenced declined over the study. Schizophrenia was the most common indication for index treatment (37.4%). The majority of patients (85.7%) received acute electroconvulsive therapy only. Voluntary provision of electroconvulsive therapy declined over the study period, reducing from 44.9% in 2009 to 16.3% in 2020. CONCLUSION: Over the study period, there was a significant reduction in the number of maintenance electroconvulsive therapy courses commenced, and a large increase in involuntary treatment. The provision of electroconvulsive therapy was more likely to occur in males with a diagnosis of schizophrenia. Further studies are needed to generate a greater understanding of the factors influencing the provision of electroconvulsive therapy within differing geographical, social and healthcare landscapes.
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Eletroconvulsoterapia , Centros de Atenção Terciária , Humanos , Eletroconvulsoterapia/estatística & dados numéricos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Austrália , Centros de Atenção Terciária/estatística & dados numéricos , Esquizofrenia/terapia , Idoso , Hospitais Psiquiátricos/estatística & dados numéricos , Transtornos Mentais/terapiaRESUMO
BACKGROUND: The 2022-23 US influenza season peaked early in fall 2022. METHODS: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design. RESULTS: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval -9%, 54%); low late-season activity precluded estimation for most subgroups. CONCLUSIONS: 2022-23 late-season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza , Influenza Humana , Pacientes Ambulatoriais , Estações do Ano , Eficácia de Vacinas , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Adulto , Masculino , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Criança , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Pré-Escolar , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/genética , Pacientes Ambulatoriais/estatística & dados numéricos , Lactente , Vacinação/estatística & dados numéricos , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: To determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects. STUDY DESIGN: Experimental study; randomized, crossover design. ANIMALS: Six healthy adult horses. METHODS: Each horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with ≥1 week washout period between. Plasma was analyzed by UPLC-MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored. RESULTS: Tmax (h) for SC bolus was 0.583 ± 0.204 versus 17.3 ± 6.41 for IV CRI, while Cmax (ng/mL) was 27.7 ± 6.38 versus 43.6 ± 9.97, respectively. AUC (h × ng/mL) was calculated as 902 ± 189 for 24 h IV CRI versus 244 ± 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 ± 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted. CONCLUSION: Repeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and Tmax than IV CRI administration but would be highly bioavailable. CLINICAL SIGNIFICANCE: Higher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted.
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Antieméticos , Estudos Cross-Over , Metoclopramida , Metoclopramida/farmacocinética , Metoclopramida/administração & dosagem , Animais , Cavalos/sangue , Masculino , Infusões Intravenosas/veterinária , Feminino , Injeções Subcutâneas/veterinária , Antieméticos/farmacocinética , Antieméticos/administração & dosagem , Antieméticos/sangue , Área Sob a Curva , Motilidade Gastrointestinal/efeitos dos fármacosRESUMO
BACKGROUND: Data on the true prevalence of RSV among medically-attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over three seasons, which is informative in light of the recommendations for shared decision-making for vaccination in older adults. METHODS: Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated Multimorbidity-Weighted Index (MWI) were collected by in-person survey and electronic medical record review. RESULTS: Over three surveillance seasons (fall 2017 to spring 2020), 9.9% (n=441) of 4,442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months-4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). CONCLUSIONS: RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision-making for vaccination.