RESUMEN
BACKGROUND: Sudden unexpected death in children is a tragic event. Understanding the genetics of sudden death in the young (SDY) enables family counseling and cascade screening. The objective of this study was to characterize genetic variation in an SDY cohort using whole genome sequencing. METHODS: The SDY Case Registry is a National Institutes of Health/Centers for Disease Control and Prevention surveillance effort to discern the prevalence, causes, and risk factors for SDY. The SDY Case Registry prospectively collected clinical data and DNA biospecimens from SDY cases < 20 years of age. SDY cases were collected from medical examiner and coroner offices spanning 13 US jurisdictions from 2015 to 2019. The cohort included 211 children (median age 0.33 year; range 0-20 years), determined to have died suddenly and unexpectedly and from whom DNA biospecimens for DNA extractions and next-of-kin consent were ascertained. A control cohort consisted of 211 randomly sampled, sex- and ancestry-matched individuals from the 1000 Genomes Project. Genetic variation was evaluated in epilepsy, cardiomyopathy, and arrhythmia genes in the SDY and control cohorts. American College of Medical Genetics/Genomics guidelines were used to classify variants as pathogenic or likely pathogenic. Additionally, pathogenic and likely pathogenic genetic variation was identified using a Bayesian-based artificial intelligence (AI) tool. RESULTS: The SDY cohort was 43% European, 29% African, 3% Asian, 16% Hispanic, and 9% with mixed ancestries and 39% female. Six percent of the cohort was found to harbor a pathogenic or likely pathogenic genetic variant in an epilepsy, cardiomyopathy, or arrhythmia gene. The genomes of SDY cases, but not controls, were enriched for rare, potentially damaging variants in epilepsy, cardiomyopathy, and arrhythmia-related genes. A greater number of rare epilepsy genetic variants correlated with younger age at death. CONCLUSIONS: While damaging cardiomyopathy and arrhythmia genes are recognized contributors to SDY, we also observed an enrichment in epilepsy-related genes in the SDY cohort and a correlation between rare epilepsy variation and younger age at death. These findings emphasize the importance of considering epilepsy genes when evaluating SDY.
Asunto(s)
Cardiomiopatías , Epilepsia , Niño , Humanos , Femenino , Lactante , Masculino , Muerte Súbita Cardíaca/etiología , Inteligencia Artificial , Teorema de Bayes , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/genética , Cardiomiopatías/genética , Cardiomiopatías/complicaciones , Epilepsia/genética , ADN , Pruebas GenéticasRESUMEN
BACKGROUND: When there are safety concerns, healthcare professionals (HCPs) may disregard older adults' wishes to return or remain at home. A paradigm shift is needed for HCPs to move from labelling older adults as living at risk to helping them live with risk. The Living with Risk: Decision Support Tool (LwR:DST) was developed to support older adults and HCPs with difficult decision-making regarding living with risk. The study objectives were to: (1) validate, and (2) pilot-test the LwR:DST in hospital and community settings. METHODS: The study was conducted across Canada during the pandemic. The LwR:DST's content was validated with quantitative and qualitative data by: (1) 71 HCPs from hospital and community settings using the Delphi method, and (2) 17 older adults and caregivers using focus groups. HCPs provided feedback on the LwR:DST's content, format and instruction manual while older adults provided feedback on the LwR:DST's communication step. The revised LwR:DST was pilot-tested by 14 HCPs in one hospital and one community setting, and 17 older adults and caregivers described their experience of HCPs using this approach with them. Descriptive and thematic analysis were performed. RESULTS: The LwR:DST underwent two iterations incorporating qualitative and quantitative data provided by HCPs, older adults and caregivers. The quantitative Delphi method data validated the content and the process of the LwR:DST, while the qualitative data provided practical improvements. The pilot-testing results suggest that using the LwR:DST broadens HCPs' clinical thinking, structures their decision-making, improves their communication and increases their competence and comfort with risk assessment and management. Our findings also suggest that the LwR:DST improves older adults' healthcare experience by feeling heard, understood and involved. CONCLUSIONS: This revised LwR:DST should help HCPs systematically identify frail older adults' risks when they remain at or return home and find acceptable ways to mitigate these risks. The LwR:DST induces a paradigm shift by acknowledging that risks are inherent in everyday living and that risk-taking has positive and negative consequences. The challenges involved in integrating the LwR:DST into practice, i.e., when, how and with whom to use it, will be addressed in future research.
Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Humanos , Anciano , Cuidadores , Personal de Salud , Canadá , Grupos Focales , Investigación CualitativaRESUMEN
Background: Sudden unexpected death in children is a tragic event. Understanding the genetics of sudden death in the young (SDY) enables family counseling and cascade screening. The objective of this study was to characterize genetic variation in an SDY cohort using whole genome sequencing. Methods: The SDY Case Registry is a National Institutes of Health/Centers for Disease Control surveillance effort to discern the prevalence, causes, and risk factors for SDY. The SDY Case Registry prospectively collected clinical data and DNA biospecimens from SDY cases <20 years of age. SDY cases were collected from medical examiner and coroner offices spanning 13 US jurisdictions from 2015-2019. The cohort included 211 children (mean age 1 year; range 0-20 years), determined to have died suddenly and unexpectedly and in whom DNA biospecimens and next-of-kin consent were ascertained. A control cohort consisted of 211 randomly sampled, sex-and ancestry-matched individuals from the 1000 Genomes Project. Genetic variation was evaluated in epilepsy, cardiomyopathy and arrhythmia genes in the SDY and control cohorts. American College of Medical Genetics/Genomics guidelines were used to classify variants as pathogenic or likely pathogenic. Additionally, genetic variation predicted to be damaging was identified using a Bayesian-based artificial intelligence (AI) tool. Results: The SDY cohort was 42% European, 30% African, 17% Hispanic, and 11% with mixed ancestries, and 39% female. Six percent of the cohort was found to harbor a pathogenic or likely pathogenic genetic variant in an epilepsy, cardiomyopathy or arrhythmia gene. The genomes of SDY cases, but not controls, were enriched for rare, damaging variants in epilepsy, cardiomyopathy and arrhythmia-related genes. A greater number of rare epilepsy genetic variants correlated with younger age at death. Conclusions: While damaging cardiomyopathy and arrhythmia genes are recognized contributors to SDY, we also observed an enrichment in epilepsy-related genes in the SDY cohort, and a correlation between rare epilepsy variation and younger age at death. These findings emphasize the importance of considering epilepsy genes when evaluating SDY.
RESUMEN
Introduction: Postmortem genetic testing (PMGT) can provide valuable information about an individual's cause of death and potentially allow at-risk relatives to discern their risks for inherited cardiac disease. Postmortem genetic testing is most often successful with certain specimens. Methods: Investigators collected data on postmortem referrals to GeneDx, LLC for PMGT. Orders were reviewed and stratified based on provider, specimen type, and tests ordered. Discussion: This cohort included 601 deceased individuals referred for PMGT with a total of 673 genetic tests ordered from 247 different providers. The most common test categories ordered were arrhythmia (33.4%) and cardiomyopathy (29.3%). A likely pathogenic or pathogenic genetic variant was identified in approximately 15% of patients. Blood in EDTA was received for 21.6% of patients with a 95% success rate for completion of all test components. Blood samples in EDTA were most successful in completing PMGT, but sequencing was still successful in the majority of suboptimal specimens. Conclusion: The use of PMGT is increasing. Obtaining optimal samples (blood in EDTA) is important for successful completion of genetic testing. Obstacles may still exist for obtaining and storing ideal specimens. Continued efforts are needed for education and awareness around appropriate specimen types, storage and shipping of specimens, DNA banking, and overall availability of PMGT. In addition, access to resources such as supplies, proper storage conditions, DNA banking, and PMGT will allow for more opportunities to complete testing.
Asunto(s)
Abuso de Ancianos , Anciano , Abuso de Ancianos/diagnóstico , Humanos , Notificación ObligatoriaRESUMEN
Background. The Performance Assessment of Self-Care Skills (PASS) is a standardized assessment of the ability to perform daily activities. Purposes. This preliminary exploratory study aimed to 1) explore the ability of four PASS tasks to predict adverse events (readmissions and injuries) in older adults following hospitalization; 2) compare PASS's predictive validity to that of a generic tool (SMAF) and OT clinical judgement. Method.Twenty-two older patients were assessed in hospital at discharge and at home one week later. Adverse events were documented for six months post-discharge. Sensitivity and specificity analyses (ROC curves, Fisher's exact tests) were performed. Findings. Two PASS tasks (telephone, medication), the SMAF-Social and OT clinical judgement could identify individuals at risk of readmission (AUC > 0.7; p < 0.05). Implications. Using the PASS to assess more cognitively demanding tasks could be a promising way to predict adverse events after discharge, as a complement to clinical judgment.
Asunto(s)
Terapia Ocupacional , Alta del Paciente , Actividades Cotidianas , Cuidados Posteriores , Anciano , Humanos , AutocuidadoRESUMEN
In a US population-based registry of sudden death in the young, this study performed familial evaluation of surviving relatives.
Asunto(s)
Muerte Súbita Cardíaca , Investigación , Niño , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Familia , Pruebas Genéticas , Humanos , Estudios RetrospectivosRESUMEN
This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.
RESUMEN
BACKGROUND: Thorough investigation of sudden cardiac death (SCD) in those aged 1-40 years commonly reveals a heritable cause, yet access to postmortem genetic testing is variable. OBJECTIVE: The purpose of this study was to explore practices of postmortem genetic testing and attitudes of health care professionals worldwide. METHODS: A survey was administered among health care professionals recruited through professional associations, social media, and networks of researchers. Topics included practices around postmortem genetic testing, level of confidence in health care professionals' ability, and attitudes toward postmortem genetic testing practices. RESULTS: There were 112 respondents, with 93% from North America, Europe, and Australia/New Zealand, and 7% from South America, Asia and Africa. Only 30% reported autopsy as mandatory, and overall practices were largely case by case and not standardized. North American respondents (87%) more often perceived practices as ineffective compared to those from Europe (58%) and Australia/New Zealand (48%; P = .002). Where a heritable cause is suspected, 69% considered postmortem genetic testing and 61% offered genetic counseling to surviving family members. Financial resources varied widely. Half of participants believed practices in their countries perpetuated health inequalities. CONCLUSION: Postmortem genetic testing is not consistently available in the investigation of young SCD despite being a recommendation in international guidelines. Access to postmortem genetic testing, which is critical in ascertaining a cause of death in many cases, must be guided by well-resourced, multidisciplinary teams.
Asunto(s)
Actitud del Personal de Salud , Autopsia/métodos , Muerte Súbita Cardíaca/patología , Personal de Salud/psicología , Patólogos/psicología , Encuestas y Cuestionarios , Estudios Transversales , Muerte Súbita Cardíaca/epidemiología , Asesoramiento Genético , Pruebas Genéticas , Salud Global , Humanos , IncidenciaRESUMEN
This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.
Asunto(s)
Arritmias Cardíacas/complicaciones , Consenso , Muerte Súbita Cardíaca/prevención & control , Familia , Muerte Súbita Cardíaca/epidemiología , Salud Global , Humanos , Morbilidad , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To describe epidemiologic data from the Sudden Death in the Young (SDY) Case Registry. Understanding the scope of SDY may optimize prevention efforts. STUDY DESIGN: We analyzed sudden, unexpected deaths of infants (<365 days) and children (1-17 years) from a population-based registry of 8 states/jurisdictions in 2015 and 9 in 2016. Natural deaths and injury deaths from drowning, motor vehicle accident drivers, and infant suffocation were included; other injury deaths, homicide, suicide, intentional overdose, and terminal illness were excluded. Cases were categorized using a standardized algorithm. Descriptive statistics were used to characterize deaths, and mortality rates were calculated. RESULTS: Of 1319 cases identified, 92% had an autopsy. We removed incomplete cases, leaving 1132 analyzable deaths (889 infants, 243 children). The SDY rate for infants was 120/100 000 live births and for children was 1.9/100 000 children. Explained Cardiac rates were greater for infants (2.7/100 000 live births) than children (0.3/100 000 children). The pediatric Sudden Unexpected Death in Epilepsy (SUDEP) mortality rate was 0.2/100 000 live births and children. Blacks comprised 42% of infant and 43% of child deaths but only 23% of the population. In all ages, myocarditis/endocarditis was the most common Explained Cardiac cause; respiratory illness was the most common Explained Other cause. SDY occurred during activity in 13% of childhood cases. CONCLUSIONS: Prevention strategies include optimizing identification and treatment of respiratory and cardiac diseases.
RESUMEN
Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Manejo de la Enfermedad , Epitelio Pigmentado de la Retina/patología , Agudeza Visual , Degeneración Macular Húmeda/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Tomografía de Coherencia Óptica , Degeneración Macular Húmeda/diagnósticoRESUMEN
The Sudden Death in the Young (SDY) Case Registry, a prospective, population-based registry active in ten states, has developed tools to aid pathologists and death investigators in the evaluation and autopsy of unexplained, natural sudden deaths in the pediatric population. The tools were developed by a team of experts representing forensic pathology; pediatric-, cardiac-, and neuropathology; cardiology; neurology/epileptology; pediatrics; genetic counseling; and public health. These tools focus on collecting data relevant to determination of cause of death with a focus on dissection of the cardiovascular system. The tools provide an objective checklist format for ease of use and data extraction. By sharing the tools here and highlighting the examination of the cardiovascular system, the SDY Case Registry encourages a standardized approach to death investigation, autopsy, and data collection for sudden, unexpected deaths in the young towards a goal of informing prevention efforts. Acad Forensic Pathol. 2018 8(2): 347-391.
RESUMEN
A significant portion of sudden death cases result from an underlying genetic etiology, which may be determined through postmortem genetic testing. The National Association of Medical Examiners (NAME) recommends that an appropriate postmortem sample is saved on all sudden death cases under the age of 40. Genetic counselors (GCs) play an important role in this process by working with medical examiners and coroners (ME/Cs) to recommend and interpret specific testing and to guide family members. A survey sent to the National Society of Genetic Counselors was designed and implemented to learn more about the experiences of genetic counselors who had considered or ordered postmortem genetic testing. Results showed that cardiovascular GCs were significantly more willing to recommend genetic testing in younger age decedents (ages 10, 18, 30, 40, and 50) compared to other specialty GCs (p<0.05, Chi-square). Thirty-seven percent (7 of 19) of GCs reported insurance covering some portion of genetic testing. Participants also reported highest success for DNA extractions with fresh and frozen blood, reinforcing NAME recommendations for appropriate sample collection for postmortem genetic testing. Overall, participating GCs demonstrated a very good understanding for the appropriate use of postmortem genetic testing and did identify suspected barriers of cost and lack of insurance coverage as deterrents. With the rapid decrease in costs for diagnostic genetic testing, ME/C awareness of NAME recommendations for sample collection and storage remain important to facilitate postmortem genetic testing.
RESUMEN
Knowledge gaps persist about the incidence of and risk factors for sudden death in the young (SDY). The SDY Case Registry is a collaborative effort between the National Institutes of Health, the Centers for Disease Control and Prevention, and the Michigan Public Health Institute. Its goals are to: (1) describe the incidence of SDY in the United States by using population-based surveillance; (2) compile data from SDY cases to create a resource of information and DNA samples for research; (3) encourage standardized approaches to investigation, autopsy, and categorization of SDY cases; (4) develop partnerships between local, state, and federal stakeholders toward a common goal of understanding and preventing SDY; and (5) support families who have lost loved ones to SDY by providing resources on bereavement and medical evaluation of surviving family members. Built on existing Child Death Review programs and as an expansion of the Sudden Unexpected Infant Death Case Registry, the SDY Case Registry achieves its goals by identifying SDY cases, providing guidance to medical examiners/coroners in conducting comprehensive autopsies, evaluating cases through child death review and an advanced review by clinical specialists, and classifying cases according to a standardized algorithm. The SDY Case Registry also includes a process to obtain informed consent from next-of-kin to save DNA for research, banking, and, in some cases, diagnostic genetic testing. The SDY Case Registry will provide valuable incidence data and will enhance understanding of the characteristics of SDY cases to inform the development of targeted prevention efforts.
Asunto(s)
Muerte Súbita/epidemiología , Sistema de Registros , Autopsia , Médicos Forenses , ADN/genética , Bases de Datos de Ácidos Nucleicos , Muerte Súbita/etiología , Pruebas Genéticas , Humanos , Consentimiento Informado , Estados Unidos/epidemiologíaRESUMEN
Vaccines play a vital role in modern medicine. The development of novel vaccines for emerging and resistant pathogens has been aided in recent years by the use of novel adjuvants in subunit vaccines. A deeper understanding of the molecular pathways behind adjuvanticity is required to better select immunostimulatory molecules for use in individual vaccines. To this end, we have undertaken a study of the essential signaling pathways involved in the innate and adaptive immune responses to the Neisseria meningitidis outer membrane protein Porin B (PorB). We have previously demonstrated that PorB is an agonist of Toll-Like Receptor 2 (TLR2) and acts as an adjuvant in vaccines for protein, carbohydrate and lipopolysaccharide antigens using murine models. Here we demonstrate NFκB translocation following stimulation with PorB only occurs in the presence of TLR2. IL-6 and TNF-α secretion was shown to be MAPK dependent. Surface expression of activation markers on macrophages, including CD40, CD69, and CD86, was increased following PorB stimulation in vitro. Interestingly, some upregulation of CD54 and CD69 was still observed in macrophages obtained from TLR2 KO mice, indicating a possible non-TLR2 mediated activation pathway induced by PorB. In a murine vaccination model, using ovalbumin as the antigen and PorB as the adjuvant, a decreased antigen-specific IgG production was observed in TLR2 KO mice; adjuvant-dependent increased IgG production was entirely ablated in MyD88 KO mice. These observations demonstrate the importance of the above pathways to the adjuvant activity of PorB. The potential TLR2 independent effect is currently being explored.
Asunto(s)
Inmunidad/efectos de los fármacos , Porinas/farmacología , Inmunidad Adaptativa/efectos de los fármacos , Adenosina Trifosfato/farmacología , Animales , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Citocinas/metabolismo , Femenino , Inmunoglobulina G/metabolismo , Inflamasomas/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-1beta/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 2/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: The 2009 H1N1 pandemic strained healthcare systems. There was a need for supportive services, rapid antiviral access, and minimization of unnecessary healthcare contacts particularly face-to-face interactions. In response, the Minnesota Department of Health (MDH) launched a telephone-based nurse triage line (NTL) called the Minnesota FluLine coordinating all major MN healthcare systems with NTLs to form a single toll-free number triage service. Callers were evaluated for symptoms of influenza-like illness (ILI) and were prescribed an antiviral if indicated, using nurse administered protocols. METHODS: To determine caller outcomes, associated healthcare seeking, and satisfaction a telephone survey of Minnesota FluLine callers was conducted using a 5% random sample of those who completed the protocol and those who did not. RESULTS: Of 6,122 callers with ILI who began the nurse protocol administered by the contract NTL, 1,221 people were contacted for the survey and 325 agreed to participate; response rate was 26%. Of those who completed the nurse protocol 73% said they would have sought healthcare without the Minnesota FluLine, 89% reported the service was moderately or very helpful, and 91% reported being satisfied or very satisfied. Of those not completing the protocol, 50% reported the service was moderately or very helpful and 50% reported being satisfied or very satisfied. 72% of qualitative responses to open-ended questions were positive regarding the MN FluLine. Cost to MDH for operating the Minnesota FluLine service was $331,226 to service 27,391 callers ($12.09/call). DISCUSSION: The Minnesota FluLine diverted patients with mild ILI symptoms away from acute care visits at low cost and had a high rate of satisfaction among callers. Early intervention likely prevented morbidity and possibly additional cases. NTLs are powerful and flexible tools for pandemic response and should be considered as an important tool for future emergency responses.
Asunto(s)
Costos de la Atención en Salud , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/economía , Satisfacción del Paciente , Salud Pública/economía , Triaje/economía , Adolescente , Adulto , Anciano , Servicios de Contestadora , Niño , Preescolar , Estudios de Evaluación como Asunto , Femenino , Encuestas Epidemiológicas , Líneas Directas , Humanos , Lactante , Recién Nacido , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Enfermeras y Enfermeros , Pandemias , Encuestas y Cuestionarios , Adulto JovenAsunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/terapia , Pandemias , Triaje/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Líneas Directas/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Gripe Humana/tratamiento farmacológico , Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Minnesota , Enfermeras y Enfermeros , Triaje/estadística & datos numéricos , Adulto JovenRESUMEN
Development of long-term humoral immunity, characterized by the formation of long-lived plasma cells (PCs) in the bone marrow and memory B cells, is a critical component of protective immunity to pathogens, and as such it is the major goal of vaccination. However, the mechanisms involved in the generation of long-term humoral immunity remain poorly understood. In this study, we used IL-21R-deficient (IL-21R.KO) mice to examine the role of the IL-21 pathway in the development of the B cell memory response. Primary IgG serum Ab responses to the T cell-dependent Ag 4-hydroxy-3-nitrophenylacetyl (NP) hapten conjugated to chicken γ globulin were delayed in IL-21R.KO mice, but reached normal titers within 3 to 4 wk of immunization. IL-21R.KO mice formed germinal centers and generated normal numbers of PCs in their bone marrow. Additionally, memory B cell formation was similar in wild-type and IL-21R.KO mice. However, NP-specific memory B cells and PCs failed to expand following secondary immunization of IL-21R.KO mice, and consequently, secondary IgG Ab responses to NP hapten conjugated to chicken γ globulin were significantly impaired. These results identify the IL-21 pathway as a critical component of the memory B cell response.