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Background: Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder characterized by progressive muscle weakness and eventual paralysis, for which there is currently no curative treatment. Mainstream medical interventions primarily focus on providing supportive care. However, acupuncture offers promising avenues for alleviating symptoms and enhancing quality of life. Specific acupuncture points are targeted to address bulbar paralysis as well as paralysis affecting the upper and lower extremities. Objective: To investigate the efficacy of electroacupuncture combined with Chinese herbal medicine in delaying disease progression and alleviating symptoms of bulbar paralysis in patients with ALS. Case Presentation: A 51-year-old male presented with a 4-year and 8-month history of weakness in his left arm and both legs, accompanied by muscle cramps and diminished coordination, which had rapidly worsened over the past year. ALS was diagnosed, and the patient was initiated on oral Riluzole (50 mg) and Qidong Huoluo granule, a Chinese herbal compound, administered twice daily. Concurrently, he underwent acupuncture treatment sessions twice weekly for over 8 months. Results: Following acupuncture therapy, the patient experienced gradual stabilization of symptoms, notably improvement in swallowing function. The combination of electroacupuncture and Qidong Huoluo granule resulted in sustained clinical enhancements post-treatment, including improvements in speech, coughing, articulation, and breathing. Conclusion: Electroacupuncture therapy demonstrates the potential to slow disease progression and ameliorate symptoms of bulbar paralysis in ALS patients. However, further robust clinical research is imperative to explain the precise therapeutic role of electroacupuncture in managing this debilitating condition. Continued investigation into the efficacy and safety profile of electroacupuncture holds promise for advancing treatment modalities for ALS.
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Touch perception is enabled by mechanically activated ion channels, the opening of which excites cutaneous sensory endings to initiate sensation. In this study, we identify ELKIN1 as an ion channel likely gated by mechanical force, necessary for normal touch sensitivity in mice. Touch insensitivity in Elkin1-/- mice was caused by a loss of mechanically activated currents (MA currents) in around half of all sensory neurons activated by light touch (low-threshold mechanoreceptors). Reintroduction of Elkin1 into sensory neurons from Elkin1-/- mice restored MA currents. Additionally, small interfering RNA-mediated knockdown of ELKIN1 from induced human sensory neurons substantially reduced indentation-induced MA currents, supporting a conserved role for ELKIN1 in human touch. Our data identify ELKIN1 as a core component of touch transduction in mice and potentially in humans.
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Canais Iônicos , Mecanorreceptores , Mecanotransdução Celular , Proteínas de Membrana , Células Receptoras Sensoriais , Percepção do Tato , Animais , Humanos , Camundongos , Células HEK293 , Canais Iônicos/genética , Canais Iônicos/fisiologia , Mecanorreceptores/fisiologia , Mecanotransdução Celular/genética , Mecanotransdução Celular/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , RNA Interferente Pequeno , Tato , Camundongos Mutantes , Masculino , FemininoRESUMO
Tixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre-exposure prophylaxis against COVID-19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID-19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID-19 infection, severity of COVID-19 infection, graft function, and rejection. Safety outcomes included cardiovascular (CV) and hypersensitivity events post tix/cil administration. A total of 410 transplant patients were included in the analysis: 20 heart, 92 liver, 243 kidney, 25 simultaneous pancreas/kidney, 23 simultaneous liver/kidney, and seven simultaneous heart/kidney. Twenty-seven (6.5%) patients tested positive for COVID-19 via PCR or antigen test post tix/cil. No apparent difference was observed in patients testing positive for COVID-19 by type of organ transplant (p = .122). Twenty-five of the 27 patients testing positive for COVID-19 reported symptomatic infection, only nine of whom were hospitalized. No patients were mechanically ventilated and no deaths due to COVID-19 occurred. No significant changes in graft function were observed. Clinically significant rejection was diagnosed and treated in four patients. COVID-19 breakthrough infection rates remained low in immunocompromised solid organ transplant recipients who received tix/cil. No significant immunologic risks were observed.
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Anticorpos Monoclonais , Infecções Irruptivas , COVID-19 , Transplante de Órgãos , Humanos , COVID-19/epidemiologia , Estudos Retrospectivos , Transplantados , Transplante de Órgãos/efeitos adversosRESUMO
INTRODUCTION: COVID-19 underscored the importance of field epidemiology training programmes (FETPs) as countries struggled with overwhelming demands. Experts are calling for more field epidemiologists with better training. Since 1951, FETPs have been building public health capacities across the globe, yet explorations of learning in these programmes are lacking. This qualitative study will (1) describe approaches to training field epidemiologists in FETP; (2) describe strategies for learning field epidemiology among FETP trainees and (3) explain the principles and practices aligning training approaches with learning strategies in FETP. METHODS AND ANALYSIS: The research design, implementation and interpretation are collaborative efforts with FETP trainers. Data collection will include interviews with FETP trainers and trainees and participant observations of FETP training and learning events in four FETP in the Western Pacific Region. Data analysis will occur in three phases: (1) we will use the constant comparison method of Charmaz's grounded theory during open coding to identify and prioritise categories and properties in the data; (2) during focused coding, we will use constant comparison and Polkinghorne's analysis of narratives, comparing stories of prioritised categories, to fill out properties of those categories and (3) we will use Polkinghorne's narrative analysis to construct narratives that reflect domains of interest, identifying correspondence among Carr and Kemmis's practices, understandings and situations to explain principles and processes of learning in FETP. ETHICS AND DISSEMINATION: We have obtained the required ethics approvals to conduct this research at The Australian National University (2021/771) and Taiwan's Ministry of Health and Welfare (112206). Data will not be available publicly, but anonymised findings will be shared with FETP for collaborative interpretation. Ultimately, findings and interpretations will appear in peer-reviewed journals and conferences.
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Epidemiologistas , Vigilância da População , Humanos , Austrália , Saúde Pública/educação , Pesquisa QualitativaRESUMO
Taiwan learned from its 2003 SARS experience and established multiple surveillance systems to be able to detect and respond to COVID-19. With the find, test, trace, isolate, and support (FTTIS) strategy, Taiwan was successful in containing SARS-CoV-2 from spreading for two years. During the surge of the Omicron variant in the community, COVID-19 control strategy shifted from containment to mitigation in April 2022, to reduce morbidity and mortality. Lessons learned from COVID-19 response re-emphasizes the importance of having sensitive public health surveillance and linking surveillance with public health actions.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Vigilância em Saúde Pública , Taiwan/epidemiologia , Surtos de Doenças , Saúde PúblicaRESUMO
The canonical role of platelets as central players in cardiovascular disease by way of their fundamental role in mediating thrombosis and haemostasis is well appreciated. However, there is now a large body of experimental evidence demonstrating that platelets are also pivotal in various physiological and pathophysiological processes other than maintaining haemostasis. Foremost amongst these is the emerging data highlighting the key role of platelets in driving cancer growth, metastasis and modulating the tumour microenvironment. As such, there is significant interest in targeting platelets therapeutically for the treatment of cancer. Therefore, the purpose of this review is to provide an overview of how platelets contribute to the cancer landscape and why platelets present as valuable targets for the development of novel cancer diagnosis tools and therapeutics.
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Neoplasias , Trombose , Humanos , Plaquetas/fisiologia , Hemostasia , Neoplasias/tratamento farmacológico , Trombose/etiologia , Microambiente TumoralRESUMO
OBJECTIVES: To determine the impact of higher bilirubin thresholds on testing and treatment of healthy infants during the neonatal period. METHODS: This quality improvement study included infants born at ≥35 weeks gestation and admitted to the well-baby nursery between July 2018 and December 2020. We assessed the transition from infants treated according to the 2004 AAP guidelines (pregroup) with those following the Northern California Neonatal Consortium guidelines (postgroup). We examined the proportion of infants receiving phototherapy and total serum bilirubin (TSB) assessments as outcome measures. We examined critical hyperbilirubinemia (TSB above 25 mg/dL or TSB within 2 mg/dL of threshold for exchange transfusion), exchange transfusion, and readmission for jaundice as balancing measures. We compared the differences in outcomes over time using Statistical Process Control p charts. Balancing measures between the pre and postgroups were compared using χ square tests and t-tests. RESULTS: In our population of 6173 babies, there was a significant shift in the proportion receiving phototherapy from 6.4% to 4%. There were no significant changes in incidences of bilirubin >25 mg/dL (0 of 1472 vs 7 of 4709, P = .37), bilirubin within 2 mg/dL of exchange transfusion thresholds (4 of 1472 vs 5 of 4709, P = .15), exchange transfusion (0 of 1472 vs 1 of 4709, P = .70) or readmission for phototherapy (2.9% versus 2.4%, P = .30), between the 2 groups. CONCLUSIONS: Higher thresholds for phototherapy treatment of neonatal hyperbilirubinemia can decrease the need for phototherapy without increasing critical hyperbilirubinemia or readmission rate.
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Hiperbilirrubinemia Neonatal , Icterícia , Recém-Nascido , Lactente , Humanos , Fototerapia , Bilirrubina , Hospitalização , Hiperbilirrubinemia Neonatal/terapiaRESUMO
Background: Prenatal and perinatal care of pregnant mothers has been adversely affected during the COVID-19 pandemic. Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal death and long-term neurological disabilities. Therapeutic hypothermia is effective for neonatal HIE. This study evaluated the effect of the pandemic on neonatal HIE. Methods: This retrospective single-center study compared neonatal HIE evaluation and hypothermia treatment between pre-COVID-19 pandemic (1 January 2018-31 December 2019) and COVID-19 pandemic (1 January 2020-31 December 2021) periods. Infants with abnormal neurological examination and or significant metabolic acidosis were admitted to NICU for evaluation of HIE and therapeutic hypothermia. Demographics, NICU admission and interventions, and neonatal outcomes were compared between infants born during the two periods using χ2, t-test, and Wilcoxon rank-sum test as appropriate. Statistical Process Control charts show the yearly proportion of infants evaluated for HIE and those treated with therapeutic hypothermia. Results: From the pre-pandemic to the pandemic period, the proportion of infants that met HIE screening criteria increased from 13% to 16% (p < 0.0001), the proportion of infants admitted to NICU for HIE evaluation increased from 1% to 1.4% (p = 0.02), and the maternal hypertension rates of the admitted infants increased from 30% to 55% (p = 0.006). There was no difference in the proportions of the infants diagnosed with HIE (0.7% vs. 0.9%, p = 0.3) or treated with therapeutic hypothermia (0.2% vs. 0.3%, p = 0.3) between the two periods. There were no differences in the HIE severity and outcomes of the infants treated with therapeutic hypothermia between the two periods. Conclusion: During the COVID-19 pandemic, we observed a significant increase in NICU admission for HIE evaluation. While we did not find significant increases in neonatal HIE and the need for therapeutic hypothermia, larger studies are needed for a comprehensive assessment of the impact of the COVID-19 pandemic on neonatal HIE.
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Background: Increasing evidence has shown that the COVID-19 pandemic has had a profound negative impact on vulnerable populations and a significant effect on maternal and neonatal health. We observed an increase in the percentage of infants admitted to NICU from 8% to 10% in the first year of the pandemic. This study aimed to compare the delivery room outcomes, NICU admissions and interventions, and neonatal outcomes two years before and during the pandemic. Methods: This was a retrospective study in a public hospital between pre-COVID-19 (April 2018-December 2019) and COVID-19 (April 2020-December 2021). Data were obtained from all live births at ≥35 weeks gestation (GA). Maternal and neonatal demographics, delivery room (DR), and NICU neonatal outcomes were compared between the study periods using simple bivariable generalized estimating equations (GEE) regression. Multivariable GEE logistic regression analysis was performed to adjust for the effects of baseline differences in demographics on the outcomes. Results: A total of 9,632 infants were born ≥35 weeks gestation during the study period (pre-COVID-19 n = 4,967, COVID-19 n = 4,665). During the COVID-19 period, there was a small but significant decrease in birth weight (33â g); increases in maternal diabetes (3.3%), hypertension (4.1%), and Hispanic ethnicity (4.7%). There was a decrease in infants who received three minutes (78.1% vs. 70.3%, p < 0.001) of delayed cord clamping and increases in the exclusive breastfeeding rate (65.9% vs. 70.1%, p < 0.001), metabolic acidosis (0.7% vs. 1.2%, p = 0.02), NICU admission (5.1% vs. 6.4%, p = 0.009), antibiotic (0.7% vs. 1.7%, p < 0.001), and nasal CPAP (1.2% vs. 1.8%, p = 0.02) use. NICU admissions and nasal CPAP were not significantly increased after adjusting for GA, maternal diabetes, and hypertension; however, other differences remained significant. Maternal hypertension was an independent risk factor for all these outcomes. Conclusion: During the COVID-19 pandemic period, we observed a significant increase in maternal morbidities, exclusive breastfeeding, and NICU admissions in infants born at ≥35 weeks gestation. The increase in NICU admission during the COVID-19 pandemic was explained by maternal hypertension, but other adverse neonatal outcomes were only partly explained by maternal hypertension. Socio-economic factors and other social determinants of health need to be further explored to understand the full impact on neonatal outcomes.
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Bioadhesives are an important class of biomaterials for wound healing, hemostasis, and tissue repair. To develop the next generation of bioadhesives, there is a societal need to teach trainees about their design, engineering, and testing. This study designed, implemented, and evaluated a hands-on, inquiry-based learning (IBL) module to teach bioadhesives to undergraduate, master's, and PhD/postdoctoral trainees. Approximately 30 trainees across three international institutions participated in this IBL bioadhesives module, which was designed to last approximately 3 h. This IBL module was designed to teach trainees about how bioadhesives are used for tissue repair, how to engineer bioadhesives for different biomedical applications, and how to assess the efficacy of bioadhesives. The IBL bioadhesives module resulted in significant learning gains for all cohorts; whereby, trainees scored an average of 45.5% on the pre-test assessment and 69.0% on the post-test assessment. The undergraduate cohort experienced the greatest learning gains of 34.2 points, which was expected since they had the least theoretical and applied knowledge about bioadhesives. Validated pre/post-survey assessments showed that trainees also experienced significant improvements in scientific literacy from completing this module. Similar to the pre/post-test, improvements in scientific literacy were most significant for the undergraduate cohort since they had the least amount of experience with scientific inquiry. Instructors can use this module, as described, to introduce undergraduate, master's, and PhD/postdoctoral trainees to principles of bioadhesives.
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STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: To determine how historical management of thoracolumbar spine injuries compares to the recently proposed AO Spine Thoracolumbar Injury Classification System treatment algorithm. SUMMARY OF BACKGROUND DATA: Classifications of the thoracolumbar spine are not uncommon. The frequent advent of new classifications is typically due to previous classifications being primarily descriptive or unreliable. Thus, AO Spine created a classification with an associated treatment algorithm to guide injury classification and management. METHODS: Thoracolumbar spine injuries were retrospectively identified from a prospectively collected spine trauma database at a single, urban, academic medical center during the years 2006 to 2021. Each injury was classified and assigned points based on the AO Spine Thoracolumbar Injury Classification System injury severity score. Patients were grouped into scores of 3 or less (preferred initial conservative treatment) and greater than 6 (preferred initial surgical intervention). Either operative or non-operative treatment was considered appropriate for injury severity scores of 4 or 5. RESULTS: A total of 815 patients (TL AOSIS 0-3: 486, TL AOSIS 4-5: 150, TL AOSIS 6+: 179) met inclusion status. Injury severity scores of 0-3 were more likely to undergo non-operative management compared to scores of 4-5 or 6+ (99.0% vs. 74.7% vs. 13.4%, P <0.001). Thus, guideline congruent treatment was 99.0%, 100%, and 86.6%, respectively ( P <0.001). Most injuries determined to be a 4 or 5 were treated non-operatively (74.7%). Based on the treatment algorithm, 97.5% of patients who received operative treatment and 96.1% who received non-operative treatment were managed in accordance with the algorithm. Of the 29 patients who did not receive algorithm congruent treatment, 5 (17.2%) were treated surgically. CONCLUSIONS: A retrospective review of thoracolumbar spine injuries at our urban academic medical center identified that patients are historically treated in accordance with the proposed AO Spine Thoracolumbar Injury Classification System treatment algorithm.
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Fraturas Ósseas , Traumatismos da Coluna Vertebral , Humanos , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Traumatismos da Coluna Vertebral/diagnóstico , Traumatismos da Coluna Vertebral/terapia , AlgoritmosRESUMO
BACKGROUND: Current clinical imaging of thromboembolic diseases often relies on indirect detection of thrombi, which may delay diagnosis and ultimately the institution of beneficial, potentially lifesaving treatment. Therefore, the development of targeting tools that facilitate the rapid, specific, and direct imaging of thrombi using molecular imaging is highly sought after. One potential molecular target is FXIIa (factor XIIa), which initiates the intrinsic coagulation pathway but also activates the kallikrein-kinin system, thereby initiating coagulation and inflammatory/immune responses. As FXII (factor XII) is dispensable for normal hemostasis, its activated form (FXIIa) represents an ideal molecular target for diagnostic and therapeutic approaches, the latter combining diagnosis/identification of thrombi and effective antithrombotic therapy. METHODS: We conjugated an FXIIa-specific antibody, 3F7, to a near-infrared (NIR) fluorophore and demonstrated binding to FeCl3-induced carotid thrombosis with 3-dimensional fluorescence emission computed tomography/computed tomography and 2-dimensional fluorescence imaging. We further demonstrated ex vivo imaging of thromboplastin-induced pulmonary embolism and detection of FXIIa in human thrombi produced in vitro. RESULTS: We demonstrated imaging of carotid thrombosis by fluorescence emission computed tomography/computed tomography and measured a significant fold increase in signal between healthy and control vessels from mice injected with 3F7-NIR compared with mice injected with nontargeted probe (P=0.002) ex vivo. In a model of pulmonary embolism, we measured increased NIR signal in lungs from mice injected with 3F7-NIR compared with mice injected with nontargeted probe (P=0.0008) and healthy lungs from mice injected with 3F7-NIR (P=0.021). CONCLUSIONS: Overall, we demonstrate that FXIIa targeting is highly suitable for the specific detection of venous and arterial thrombi. This approach will allow direct, specific, and early imaging of thrombosis in preclinical imaging modalities and may facilitate monitoring of antithrombotic treatment in vivo.
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Trombose das Artérias Carótidas , Embolia Pulmonar , Trombose , Camundongos , Humanos , Animais , Coagulação Sanguínea , Trombose/diagnóstico por imagem , Fator XII/metabolismo , Fator XIIa/metabolismo , Imagem MolecularRESUMO
BACKGROUND: There is a lack of consensus regarding the definition and treatment threshold for neonatal hypoglycaemia. The American Academy of Pediatrics (AAP) has a published clinical report making recommendations on practice guidelines. There is limited literature discussing the impact of these guidelines. In this study, we evaluated the screening and diagnosis of neonatal hypoglycaemia following the AAP guidelines. METHODS: Infants born ≥35 weeks gestational age and admitted to the well-baby nursery between January and December 2017 were included in this study. Our hypoglycaemia policy was based on the AAP clinical report for hypoglycaemia management in newborns. Chart review was done to obtain infant hypoglycaemia risk factors and blood glucose values in the first 24 hours. Data analysis was conducted using Stata V.14.2 (StataCorp). RESULTS: Of 2873 infants born and admitted to the well-baby nursery, 32% had at least one hypoglycaemia risk factor and 96% of them were screened for hypoglycaemia. Screened infants were more likely to be born at a lower gestational age, via C-section, and to a multiparous older mother. Screened infants and hypoglycaemic infants had lower exclusive breastfeeding rates compared with those who were not screened or not hypoglycaemic, respectively. Sixteen per cent of screened infants were diagnosed with hypoglycaemia; 0.8% of at-risk screened infants and 5% of hypoglycaemic infants were admitted to the NICU for treatment of hypoglycaemia. Thirty-one per cent of preterm infants, 15% of large for gestational age infants, 13% of small for gestational age infants and 15% of infants of diabetic mothers were hypoglycaemic. Hypoglycaemic infants were more likely to be born preterm and via C-section. CONCLUSION: Using the AAP time-based definitional blood glucose cut-off values, our incidence of hypoglycaemia found in those who were screened for risk factors was lower compared with other studies. Future long-term follow-up studies will be important.
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Hipoglicemia , Doenças do Recém-Nascido , Feminino , Recém-Nascido , Humanos , Lactente , Estados Unidos , Criança , Glicemia , Recém-Nascido Prematuro , Estudos Retrospectivos , Hipoglicemia/diagnóstico , Hipoglicemia/epidemiologia , HipoglicemiantesRESUMO
STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To (1) investigate the effect of marijuana use on surgical outcomes following lumbar fusion, (2) determine how marijuana use affects patient-reported outcomes measures (PROMs), and (3) determine if marijuana use impacts the quantity of opioids prescribed. METHODS: Patients > 18 years of age who underwent primary one- or two-level lumbar fusion with preoperative marijuana use at our institution were identified. A 3:1 propensity match incorporating patient demographics and procedure type was conducted to compare preoperative marijuana users to non-marijuana users. Patient demographics, surgical characteristics, surgical outcomes (90-day all-cause and 90-day surgical readmissions, reoperations, and revision surgeries), pre- and postoperative narcotic usage, and PROMs were compared between groups. Multivariate regression models were created to determine the effect of marijuana on surgical reoperations patient-reported outcomes (PROMs) 1-year postoperatively. RESULTS: Of the 259 included patients, 65 used marijuana preoperatively. Multivariate logistic regression analysis demonstrated that marijuana use (OR = 2.28, P = .041) significantly increased the likelihood of having a spine reoperation. No other surgical outcome was found to be significantly different between groups. Multivariate linear regression analysis showed that marijuana use was not significantly associated with changes in 1-year postoperative PROMs (all, P > .05). The quantity of pre- and postoperative opioids prescriptions was not significantly different between groups (all, P > .05). CONCLUSIONS: Preoperative marijuana use increased the likelihood of a spine reoperation for any indication following lumbar fusion, but it was not associated with 90-day all cause readmission, surgical readmission, the magnitude of improvement in PROMs, or differences in opioid consumption. LEVEL OF EVIDENCE: III.
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OBJECTIVE: To describe factors impacting receipt of mother's own milk (MOM) at discharge among California infants diagnosed with neonatal abstinence syndrome (NAS). STUDY DESIGN: Cohort study of the California Perinatal Quality Care Collaborative's Maternal Substance Exposure Database for infants with NAS and gestational age ≥ 34 weeks from 2019 to 2020. RESULT: 245 infants with NAS were identified. Variables with an increased likelihood of being discharged on MOM included maternal medication assisted treatment (p = 0.001), use of maternal addiction services (p < 0.001), receiving donor human milk (p = 0.001), being treated in the well baby unit (p < 0.001), rooming-in (p < 0.001), and kangaroo care (p < 0.001). Among infants with NAS for whom MOM was recommended (n = 84), rooming-in was the only factor associated with being discharged on MOM (p = 0.002); receiving formula was the only inversely associated factor (p < 0.001). CONCLUSION: Results suggest supporting the mother-infant dyad and using non-pharmacologic treatment methods, such as rooming-in, increase receipt of MOM at discharge.
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Leite Humano , Síndrome de Abstinência Neonatal , Aleitamento Materno/métodos , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Mães , Síndrome de Abstinência Neonatal/terapia , Alta do Paciente , GravidezRESUMO
Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare, but serious, syndrome characterised by thrombocytopenia, thrombosis, a markedly raised D-dimer and the presence of anti-platelet factor-4 (PF4) antibodies following COVID-19 adenovirus vector vaccination. VITT occurs at a rate of approximately 2 per 100 000 first-dose vaccinations and appears exceedingly rare following second doses. Our current understanding of VITT pathogenesis is based on the observations that patients with VITT have antibodies that bind to PF4 and have the ability to form immune complexes that induce potent platelet activation. However, the precise mechanisms that lead to pathogenic VITT antibody development remain a source of active investigation. Thrombosis in VITT can manifest in any vascular bed and affect multiple sites simultaneously. While there is a predilection for splanchnic and cerebral venous sinus thrombosis, VITT also commonly presents with deep vein thrombosis and pulmonary embolism. Pillars of management include anticoagulation with a non-heparin anticoagulant, intravenous immunoglobulin and 'rescue' therapies, such as plasma exchange for severe cases. VITT can be associated with a high mortality rate and significant morbidity, but awareness and optimal therapy have significantly improved outcomes in Australia. A number of questions remain unanswered, including why VITT is so rare, reasons for the predilection for thrombosis in unusual sites, how long pathological antibodies persist, and the optimal duration of anticoagulation. This review will provide an overview of the presentation, diagnostic workup and management strategies for patients with VITT.
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COVID-19 , Trombocitopenia , Trombose , Vacinas , Anticoagulantes/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , Humanos , Fator Plaquetário 4/efeitos adversos , SARS-CoV-2 , Trombocitopenia/induzido quimicamente , Trombose/induzido quimicamente , Trombose/complicações , Vacinas/efeitos adversosRESUMO
The coronavirus disease (COVID-19) pandemic has highlighted the link between individual behavior and public health, along with the importance of evidence-based efforts to promote prosocial individual behavior. Insights from behavioral science can inform the design of effective behavior change techniques, or nudges, to influence individual behavior. The MINDSPACE framework organizes 9 behavioral science principles that can be used to guide policy design: Messenger, Incentives, Norms, Defaults, Salience, Priming, Affect, Commitments, and Ego. Using MINDSPACE as an organizing framework, this article provides a review of the literature on nudges to influence prosocial behaviors relevant during a pandemic: handwashing, avoidance of social gatherings, self-isolation and social distancing, and sharing public health messages. Additionally, empirical evidence on the use of nudges during the first several months of the COVID-19 pandemic in 2020 is summarized. Recommendations regarding the use of nudges to achieve public health policy goals during pandemics are provided. Organizational leaders, policymakers, and practitioners can use nudges to promote public health when mandates are not politically feasible or enforceable.
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COVID-19 , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Promoção da Saúde , Humanos , Pandemias/prevenção & controle , Distanciamento Físico , Saúde PúblicaRESUMO
Objective: We evaluated the prevalence of preterm birth (PTB) and very low birth weight (VLBW) during Jan-Dec 2,020 (early COVID era) at 5 hospitals (2 in West Virginia, 3 in California) compared to Jan 2017-Dec 2019 (pre-COVID) inclusive of 2 regional perinatal centers (1 in Huntington, WV and 1 in San Jose, CA) and 3 community hospitals (1 each in Cabell, Los Angeles and Santa Clara counties). Design/methods: We examined PTB and VLBW rates of live births at 5 US hospitals from Jan 2017-Dec 2020. We compared PTB and VLBW rates in 2020 to 2017-2019 using Poisson regression and rate ratio with a 95% confidence interval. We stratified live births by gestational age (GA) (<37, 33-36, and <33 weeks) and birth weight (≤1,500â g, >1,001â g to ≤1,500â g, ≤1,000â g). We examined PTB rates at 4 of the hospitals during Jan-Dec 2020 and compared them to the prior period of Jan 2017-Dec 2019 using Statistical Process Control (SPC) for quarterly data. Results: We examined PTB and VLBW rates in 34,599 consecutive live births born Jan 2017-Dec 2019 to rates of 9,691 consecutive live births in 2020. There was no significant change in PTB (<37 weeks GA) rate, 10.6% in 2017-2019 vs. 11.0% in 2020 (p = 0.222). Additionally, there was no significant change when comparing VLBW rates in 2017-2019 to 2020, 1.4% in 2017-2019 vs. 1.5% in 2020 (p = 0.832). Conclusion: We found no significant change in the rates of PTB or VLBW when combining the live birth data of 5 US hospitals in 3 different counties.
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BACKGROUND: 3F7 is a monoclonal antibody targeting the enzymatic pocket of activated factor XII (FXIIa), thereby inhibiting its catalytic activity. Given the emerging role of FXIIa in promoting thromboinflammation, along with its apparent redundancy for hemostasis, the selective inhibition of FXIIa represents a novel and highly attractive approach targeting pathogenic processes that cause thromboinflammation-driven cardiovascular diseases. METHODS: The effects of FXIIa inhibition were investigated using three distinct mouse models of cardiovascular disease-angiotensin II-induced abdominal aortic aneurysm (AAA), an ApoE-/- model of atherosclerosis, and a tandem stenosis model of atherosclerotic plaque instability. 3F7 or its isotype control, BM4, was administered to mice (10 mg/kg) on alternate days for 4 to 8 weeks, depending on the experimental model. Mice were examined for the development and size of AAAs, or the burden and instability of atherosclerosis and associated markers of inflammation. RESULTS: Inhibition of FXIIa resulted in a reduced incidence of larger AAAs, with less acute aortic ruptures and an associated fibro-protective phenotype. FXIIa inhibition also decreased stable atherosclerotic plaque burden and achieved plaque stabilization associated with increased deposition of fibrous structures, a >2-fold thicker fibrous cap, increased cap-to-core ratio, and reduction in localized and systemic inflammatory markers. CONCLUSION: Inhibition of FXIIa attenuates disease severity across three mouse models of thromboinflammation-driven cardiovascular diseases. Specifically, the FXIIa-inhibiting monoclonal antibody 3F7 reduces AAA severity, inhibits the development of atherosclerosis, and stabilizes vulnerable plaques. Ultimately, clinical trials in patients with cardiovascular diseases such as AAA and atherosclerosis are warranted to demonstrate the therapeutic potential of FXIIa inhibition.
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Anticorpos Monoclonais/administração & dosagem , Aneurisma da Aorta Abdominal/prevenção & controle , Aterosclerose/prevenção & controle , Fator XIIa/antagonistas & inibidores , Placa Aterosclerótica/metabolismo , Animais , Aneurisma da Aorta Abdominal/epidemiologia , Apolipoproteínas E , Modelos Animais de Doenças , Inflamação , Masculino , CamundongosRESUMO
There is minimal data on the optimal treatment of lower inoculum infections such as urinary tract infections (UTIs) caused by SPICE organisms which encode the betalactamase enzyme, AmpC. This single-center, retrospective review of adult hospitalized patients with UTIs caused by a SPICE organism compared outcomes amongst patients treated with drugs susceptible to AmpC hydrolysis versus drugs stable against AmpC. Of 156 patients, similar rates of clinical response, 30-day infection related readmission, 30-day infection recurrence, 30-day mortality rates, and median length of hospital stay were found between the two groups. Notably, 44% of patients with ceftriaxone resistance reported had recent ß-lactam exposure versus only 11% of patients without ceftriaxone resistance (P = 0.002). Based on our data, there does not appear to be a difference in clinical response or any of the secondary outcomes in patients with UTIs treated with AmpC stable and AmpC susceptible agents.