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1.
Crit Care Explor ; 6(7): e1123, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39018285

RESUMEN

IMPORTANCE: The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES: To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES: We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS: We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3-11%) and 39% (95% CI, 28-49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129-1341 µg) in the KPNC cohort and 200 µg (IQR, 0-1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1-7%) and 20% (95% CI, 15-26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE: In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals' analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.


Asunto(s)
Analgésicos Opioides , Fentanilo , Pautas de la Práctica en Medicina , Respiración Artificial , Insuficiencia Respiratoria , Humanos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/efectos adversos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Fentanilo/administración & dosificación , Fentanilo/uso terapéutico , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/epidemiología , Estudios de Cohortes , California , Adulto , Unidades de Cuidados Intensivos
2.
JAMA Netw Open ; 7(6): e2417292, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38874921

RESUMEN

Importance: Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and posthospitalization opioid-related outcomes are unclear. Objective: To evaluate associations between an intravenous opioid dose received during mechanical ventilation and postdischarge opioid-related outcomes in medical (nonsurgical) patients. Design, Setting, and Participants: This retrospective cohort study evaluated adults receiving mechanical ventilation lasting 24 hours or more for acute respiratory failure and surviving hospitalization. Participants from 21 Kaiser Permanente Northern California hospitals from January 1, 2012, to December 31, 2019, were included. Data were analyzed from October 1, 2020, to October 31, 2023. Exposures: Terciles of median daily intravenous fentanyl equivalents during mechanical ventilation. Main Outcomes and Measures: The primary outcome was the first filled opioid prescription in 1 year after discharge. Secondary outcomes included persistent opioid use and opioid-associated complications. Secondary analyses tested for interaction between opioid doses during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Estimates were based on multivariable-adjusted time-to-event analyses, with death as a competing risk, and censored for hospice or palliative care referral, rehospitalization with receipt of opioid, or loss of Kaiser Permanente plan membership. Results: The study included 6746 patients across 21 hospitals (median age, 67 years [IQR, 57-76 years]; 53.0% male). Of the participants, 3114 (46.2%) filled an opioid prescription in the year prior to admission. The median daily fentanyl equivalent during mechanical ventilation was 200 µg (IQR, 40-1000 µg), with terciles of 0 to 67 µg, more than 67 to 700 µg, and more than 700 µg. Compared with patients who did not receive opioids during mechanical ventilation (n = 1013), a higher daily opioid dose was associated with opioid prescriptions in the year after discharge (n = 2942 outcomes; tercile 1: adjusted hazard ratio [AHR], 1.00 [95% CI, 0.85-1.17], tercile 2: AHR, 1.20 [95% CI, 1.03-1.40], and tercile 3: AHR, 1.25 [95% CI, 1.07-1.47]). Higher doses of opioids during mechanical ventilation were also associated with persistent opioid use after hospitalization (n = 1410 outcomes; tercile 3 vs no opioids: odds ratio, 1.44 [95% CI, 1.14-1.83]). No interaction was observed between opioid dose during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Conclusions and Relevance: In this retrospective cohort study of patients receiving mechanical ventilation, opioids administered during mechanical ventilation were associated with opioid prescriptions following hospital discharge. Additional studies to evaluate risks and benefits of strategies using lower opioid doses are warranted.


Asunto(s)
Analgésicos Opioides , Alta del Paciente , Respiración Artificial , Humanos , Masculino , Femenino , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Anciano , California , Insuficiencia Respiratoria/terapia , Administración Intravenosa
3.
BMJ Open ; 14(1): e073622, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191255

RESUMEN

OBJECTIVES: In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients' referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Adult members before COVID-19 vaccine availability (1 February 2020-31 January 2021) with positive SARS-CoV-2 tests. INTERVENTION: Virtual programme to track and treat patients with 'CHCT programme'. OUTCOMES: The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral. MEASURES: We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting. RESULTS: There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p<0.001) and more comorbid with COmorbidity Point Score, V.2, score ≥65 (1.7% vs 1.1%, p<0.001). Unadjusted analyses showed more COVID-19-related emergency department visits (9.5% vs 8.5%, p<0.001) and hospitalisations (3.9% vs 3.2%, p<0.001) in patients followed by CHCT but lower inpatient death or 30-day hospice referral (0.3% vs 0.5%, p<0.001). After weighting, there were higher rates of COVID-19-related emergency department visits (estimated intervention effect -0.8%, 95% CI -1.4% to -0.3%) and hospitalisation (-0.5%, 95% CI -0.9% to -0.1%) but lower inpatient mortality or 30-day hospice referral (-0.5%, 95% CI -0.7% to -0.3%) in patients followed by CHCT. CONCLUSIONS: Despite CHCT following older patients with higher comorbidity burden, there appeared to be a protective effect. Patients followed by CHCT were more likely to present to acute care and less likely to die inpatient.


Asunto(s)
COVID-19 , Prestación Integrada de Atención de Salud , Hospitales para Enfermos Terminales , Adulto , Humanos , Estudios Retrospectivos , Vacunas contra la COVID-19 , Pandemias , COVID-19/terapia , SARS-CoV-2 , Pacientes Internos
4.
JAMA Netw Open ; 6(1): e2253269, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-36701159

RESUMEN

This cohort study of patients at a single integrated health system examines trends in COVID-19­related treatment location and mortality.


Asunto(s)
COVID-19 , Humanos , Adulto , COVID-19/epidemiología , Pacientes Ambulatorios , Atención a la Salud , Hospitales , Unidades de Cuidados Intensivos
5.
Microbiol Resour Announc ; 11(10): e0053822, 2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36066250

RESUMEN

Arthrobacter phage Iter was isolated in North Georgia. Its genome is 43,963 bp with 70 open reading frames (ORFs) and a GC content of 67.4%. It shares 89.11% nucleotide identity with Arthrobacter phage Phives. Actinobacteriophages that share over 50% nucleotide identity are sorted into clusters, with Iter in cluster AZ.

6.
J Med Genet ; 58(7): 442-452, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-32709676

RESUMEN

BACKGROUND: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility. METHODS: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues. RESULTS: A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma. CONCLUSION: SPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.


Asunto(s)
Microbiota , Otitis Media/genética , Otitis Media/microbiología , Inhibidor de Serinpeptidasas Tipo Kazal-5/genética , Adulto , Animales , Bacterias/clasificación , Bacterias/genética , Niño , Susceptibilidad a Enfermedades/microbiología , Oído Externo/microbiología , Oído Medio/microbiología , Exoma , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Ratones , Boca/microbiología , Nasofaringe/microbiología , Linaje , Análisis de Secuencia de ADN , Análisis de Secuencia de ARN
7.
Sci Rep ; 10(1): 15035, 2020 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-32929111

RESUMEN

Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.


Asunto(s)
Mutación Missense , Otitis Media/genética , Plasminógeno/genética , Animales , Oído Medio/metabolismo , Oído Medio/microbiología , Femenino , Genómica/métodos , Humanos , Masculino , Ratones , Microbiota , Otitis Media/microbiología , Otitis Media/patología , Linaje , Plasminógeno/metabolismo , Polimorfismo de Nucleótido Simple , Saliva/metabolismo
8.
Am J Hum Genet ; 103(5): 679-690, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30401457

RESUMEN

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10-5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10-7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.


Asunto(s)
Fucosiltransferasas/genética , Variación Genética/genética , Otitis Media/genética , Animales , Células COS , Línea Celular , Chlorocebus aethiops , Oído Medio/microbiología , Exoma/genética , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Microbiota/fisiología , Otitis Media/microbiología , Linaje , Galactósido 2-alfa-L-Fucosiltransferasa
9.
Nat Genet ; 47(8): 917-20, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26121085

RESUMEN

A duplication variant within the middle ear-specific gene A2ML1 cosegregates with otitis media in an indigenous Filipino pedigree (LOD score = 7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by 3 otitis-prone European-American and Hispanic-American children but is absent in non-otitis-prone children and >62,000 next-generation sequences. We identified seven additional A2ML1 variants in six otitis-prone children. Collectively, our studies support a role for A2ML1 in the pathophysiology of otitis media.


Asunto(s)
Duplicación de Gen , Predisposición Genética a la Enfermedad/genética , Otitis Media/genética , alfa-Macroglobulinas/genética , Animales , Secuencia de Bases , Niño , Cóclea/metabolismo , Cóclea/patología , Exoma/genética , Salud de la Familia , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Ratones Endogámicos C57BL , Modelos Moleculares , Otitis Media/patología , Linaje , Análisis de Componente Principal , Conformación Proteica , Análisis de Secuencia de ADN , alfa-Macroglobulinas/química
10.
Vaccine ; 32(51): 6948-6955, 2014 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-25444821

RESUMEN

A randomized trial of an investigational 9-valent pneumococcal conjugate vaccine (PCV-9) or placebo given to pregnant women during the last trimester to prevent early infant otitis media (OM) was conducted. All infants received Prevnar(®) at 2, 4, 6, and 12 months. Clinic and adverse event records were reviewed to identify OM. Variables significantly related to acute OM by age 6 months (p<0.05) were: vaccine group (9 valent or placebo), sibling history of tympanostomy tubes, upper respiratory infection, and number of clinic visits by 6 months. Infant OM rates were similar between 6 and 12 months (58% and 56%). Results suggested that immunizing pregnant women with PCV-9 increased infants' risk of acute OM in the first 6 months of life, and this correlated with decreased infant antibody responses to their infant Streptococcus pneumoniae vaccine serotypes, but did not influence antibody responses to 3 other serotypes two of which were in maternal vaccine (types 1 and 5) and one was a control (type 7F). Explanations for these results include dampening of infant antibody production by high levels of passively acquired maternal pneumococcal antibodies and/or altered B lymphocyte immune responses in infants exposed to these specific polysaccharide antigens in utero.


Asunto(s)
Inmunidad Materno-Adquirida , Inmunización/métodos , Otitis Media/epidemiología , Otitis Media/prevención & control , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Adulto , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Placebos/administración & dosificación , Vacunas Neumococicas/administración & dosificación , Embarazo , Resultado del Tratamiento , Vacunas Conjugadas
11.
PLoS One ; 9(8): e104212, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25089819

RESUMEN

The first Genome Wide Association Study (GWAS) of otitis media (OM) found evidence of association in the Western Australian Pregnancy Cohort (Raine) study, but lacked replication in an independent OM population. The aim of this study was to investigate association at these loci in our family-based sample of chronic otitis media with effusion and recurrent otitis media (COME/ROM). Autosomal SNPs were selected from the Raine OM GWAS results. SNPs from the Raine cohort GWAS genotyped in our GWAS of COME/ROM had P-values ranging from P = 0.06-0.80. After removal of SNPs previously genotyped in our GWAS of COME/ROM (N = 21) and those that failed Fluidigm assay design (N = 1), 26 SNPs were successfully genotyped in 716 individuals from our COME/ROM family population. None of the SNP associations replicated in our family-based population (unadjusted P = 0.03-0.93). Replication in an independent sample would confirm that these represent novel OM loci, and that further investigation is warranted.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Otitis Media/genética , Australia , Femenino , Genotipo , Humanos , Otitis Media/patología , Polimorfismo de Nucleótido Simple , Embarazo , Factores de Riesgo
13.
J Assoc Res Otolaryngol ; 14(6): 791-800, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23974705

RESUMEN

Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with P < 10(-4) and 12 imputed SNPs with P < 10(-4) on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P = 1.30 × 10(-5)) on chromosome 2 in the independent otitis media population (P = 4.7 × 10(-5); meta-analysis P = 1.52 × 10(-8)). Three additional SNPs had replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P = 3.4 ×10(-7)) in KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2 (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P = 0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.


Asunto(s)
Cromosomas Humanos Par 2 , Predisposición Genética a la Enfermedad , Otitis Media con Derrame/genética , Otitis Media/genética , Polimorfismo de Nucleótido Simple , Enfermedad Crónica , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Desequilibrio de Ligamiento , Masculino , Sitios de Carácter Cuantitativo , Recurrencia
14.
Psychiatr Serv ; 64(7): 672-9, 2013 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-23545784

RESUMEN

OBJECTIVE: Community integration is recognized as a crucial component of recovery from serious mental illness. Although the construct of community integration can be measured with structured instruments, little is known about the subjective and experiential meaning of community and community involvement for persons with serious mental illness. METHODS: In 2010, 30 individuals with serious mental illness treated in two public mental health clinics completed semistructured interviews that elicited the places and people that they associate with the experience of community and the larger meaning of community in their lives. RESULTS: Participants described four experiences as integral to their concepts of community: receiving help, minimizing risk, avoiding stigma, and giving back. Participants looked for communities that provide reliable support, and they described the need to manage community contact in order to protect themselves and others from their symptoms and from discrimination. Most participants experienced communities centered on mental health treatment or mentally ill peers as providing opportunities for positive engagement. CONCLUSIONS: The experience of having a serious mental illness shapes preferences for and perceptions of community in pervasive ways. Participants described community involvement not as a means to move away from illness experiences and identities but as a process that is substantially influenced by them. Mental health communities may help individuals with serious mental illness to both manage their illness and recognize and enjoy a sense of community. The findings indicate the need for further research on the relationship between community integration and outcome in serious mental illness.


Asunto(s)
Actitud Frente a la Salud , Integración a la Comunidad/psicología , Trastornos Mentales/rehabilitación , Participación Social/psicología , Apoyo Social , Estereotipo , Adaptación Psicológica , Adulto , Femenino , Humanos , Relaciones Interpersonales , Estudios Longitudinales , Masculino , Trastornos Mentales/psicología , Persona de Mediana Edad , Grupo Paritario , Investigación Cualitativa , Discriminación Social/prevención & control , Discriminación Social/psicología
15.
Otolaryngol Head Neck Surg ; 148(4 Suppl): E1-E25, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23536527

RESUMEN

BACKGROUND: The First International Symposium on Recent Advances in Otitis Media (OM) with Effusion was held in Columbus, Ohio, in 1975. The symposium has been organized in the United States every 4 years since, followed by a research conference to (a) assess major research accomplishments, (b) identify important research questions and opportunities, (c) develop consensus on definitions and terminology, and (d) establish priorities with short- and long-term research goals. One of the principal areas reviewed quadrennially is Epidemiology, Natural History, and Risk Factors. OBJECTIVE: To provide a review of recent literature on the epidemiology, natural history, and risk factors for OM. DATA SOURCES AND REVIEW METHODS: A search of OM articles in English published July 2007 to June 2011 was conducted using PubMed and related databases. Those with findings judged of importance for epidemiology, public health, and/or statistical methods were reviewed. RESULTS: The literature has continued to expand, increasing understanding of the worldwide burden of OM in childhood, complications from treatment failures, and comorbidities. Novel risk factors, including genetic factors, have been examined for OM susceptibility. Population-based studies in Canada, the United States, and other countries confirmed reductions in OM prevalence. Although most studies concentrated on acute OM (AOM) or OM with effusion (OME), a few examined severe chronic suppurative OM (CSOM), a major public health problem in developing countries and for certain indigenous populations around the world. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Recent publications have reinforced earlier epidemiological findings, while extending our knowledge in human population groups with high burden of OM.


Asunto(s)
Otitis Media/epidemiología , Otitis Media/etiología , Canadá/epidemiología , Congresos como Asunto , Países en Desarrollo , Medicina Basada en la Evidencia , Humanos , Otitis Media/fisiopatología , Otitis Media con Derrame/epidemiología , Otitis Media con Derrame/etiología , Otitis Media Supurativa/epidemiología , Otitis Media Supurativa/etiología , Prevalencia , Factores de Riesgo , Estados Unidos/epidemiología
16.
Genet Med ; 13(12): 1006-10, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21912263

RESUMEN

PURPOSE: : Bedside newborn hearing screening is highly successful in identifying deaf or hard-of-hearing infants. However, newborn hearing screening protocols have high loss to follow-up rates. We propose that bloodspot-based genetic testing for GJB2 alleles can provide a means for rapid confirmation in a subset of infants who fail bedside newborn hearing screening. METHODS: : We performed a case-control study comparing the prevalence of common GJB2 mutations from deidentified bloodspots designated as "refer" by newborn hearing screening and contemporaneously selected randomly chosen controls designated as "pass." Between March 2006 and December 2007, 2354 spots were analyzed for common alleles, c.35delG, c.167delT, c.235delC, and p.V37I in GJB2 with a subset reanalyzed by conventional Sanger sequencing to search for additional alleles. RESULTS: : The prevalence of biallelic GJB2 mutations in bloodspots from infants who referred by newborn hearing screening is approximately 1 in 50 (23/1177). In contrast, one bloodspot from an infant who passed newborn hearing screening was identified to harbor biallelic GJB2 mutations. CONCLUSIONS: : These findings show that when a newborn refers by newborn hearing screening, there is a significant chance that GJB2-related hearing loss is present. Bloodspot-based genetic testing for common GJB2 alleles should be considered as second tier testing for bedside newborn hearing screening.


Asunto(s)
Biomarcadores de Tumor/genética , Conexinas/genética , Pruebas Genéticas/métodos , Pérdida Auditiva/diagnóstico , Audición/fisiología , Tamizaje Neonatal/métodos , Alelos , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Conexina 26 , Conexinas/sangre , Análisis Mutacional de ADN , Estudios de Seguimiento , Genotipo , Pérdida Auditiva/sangre , Pérdida Auditiva/epidemiología , Pérdida Auditiva/genética , Humanos , Recién Nacido , Mutación , Prevalencia , Estados Unidos/epidemiología
17.
BMC Med Genet ; 12: 124, 2011 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-21943191

RESUMEN

BACKGROUND: In previous analyses, we identified a region of chromosome 19 as harboring a susceptibility locus for chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). Our aim was to further localize the linkage signal and ultimately identify the causative variant or variants. We followed up our previous linkage scan with dense SNP genotyping across in a 5 Mb region. A total of 607 individuals from 139 families, including 159 affected sib pairs and 62 second-degree affected relative pairs, were genotyped at 1,091 SNPs. We carried out a nonparametric linkage analysis, modeling marker-to-marker linkage disequilibrium. RESULTS: The maximum log of the odds (LOD) score increased to 3.75 (P = 1.6 × 10(-5)) at position 63.4 Mb, with a LOD-1 support interval between 61.6 Mb and 63.8 Mb, providing significant evidence of linkage between this region and COME/ROM. The support interval contains over 90 known genes, including several genes involved in the inflammasome protein complex, a key regulator of the innate immune response to harmful exogenous or endogenous stimuli. Parametric linkage analysis suggests that for a sib of an affected individual, the recurrence risk of COME/ROM due to this linkage region is twice the recurrence risk in the population. We examined potential associations between the SNPs genotyped in this region and COME/ROM, however none provided evidence for association. CONCLUSION: This study has refined the 19q region of linkage with COME/ROM, and association results suggest that the linkage signal may be due to rare variants.


Asunto(s)
Cromosomas Humanos Par 19 , Ligamiento Genético , Otitis Media con Derrame/genética , Genotipo , Humanos , Desequilibrio de Ligamiento , Escala de Lod , Polimorfismo de Nucleótido Simple , Recurrencia
18.
PLoS One ; 6(8): e22297, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21857919

RESUMEN

DNA sequence variants in genes involved in the innate immune response and secondary response to infection may confer susceptibility to chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). We evaluated single nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99 SNPs were successfully genotyped on the Sequenom platform in 142 families (618 subjects) from the Minnesota COME/ROM Family Study. Data were analyzed for association with COME/ROM using the Generalized Disequilibrium Test (GDT). Sex and age at exam were adjusted as covariates, relatedness was accounted for, and genotype differences from all phenotypically discordant relative pairs were utilized to measure the evidence of association between COME/ROM and each SNP. SNP rs2735733 in the region of the mucin 5, subtypes A/C gene (MUC5AC) exhibited nominal evidence for association with COME/ROM (P = 0.002). Two additional SNPs from this region had P values<0.05. Other variants exhibiting associations with COME/ROM at P<0.05 included the SCN1B SNP rs8100085 (P = 0.013), SFTPD SNP rs1051246 (P = 0.039) and TLR4 SNP rs2770146 (P = 0.038). However, none of these associations replicated in an independent sample of COME/ROM families. The candidate gene variants examined do not appear to make a major contribution to COME/ROM susceptibility, despite a priori evidence from functional or animal model studies for a role in COME/ROM pathology.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Otitis Media con Derrame/genética , Otitis Media/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Alelos , Niño , Enfermedad Crónica , Salud de la Familia , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Mucina 5AC/genética , Otitis Media/patología , Otitis Media con Derrame/patología , Recurrencia , Canales de Sodio/genética , Receptor Toll-Like 4/genética , Subunidad beta-1 de Canal de Sodio Activado por Voltaje , Adulto Joven
19.
Int J Pediatr Otorhinolaryngol ; 74(3): 231-40, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19836843

RESUMEN

The 2007 Recent Advances in Otitis Media Research Conference Panel Report provides an update on otitis media (OM) research published from 2003 to 2007. This report summarizes important trends in disease incidence and prevalence, describes established and newly identified risk factors for acute and chronic OM and OM with effusion, and conveys information on newly discovered genetic factors. In this report, researchers have described declining rates of OM diagnosis, antibiotic prescriptions, offices visits for OM, and middle ear surgery since the licensure and routine use of pneumococcal conjugate vaccine in infants. The panel report also recommends short and long term goals for current and future OM research.


Asunto(s)
Cooperación Internacional , Otitis Media/epidemiología , Otitis Media/etiología , Lactancia Materna , Niño , Preescolar , Congresos como Asunto , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Otitis Media/terapia , Prevalencia , Estudios Prospectivos , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/microbiología , Factores de Riesgo , Medio Social
20.
Matern Child Health J ; 12 Suppl 1: 46-54, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18266094

RESUMEN

OBJECTIVES: We examined the breastfeeding attitudes and practices in an American Indian population in Minnesota. METHODS: We interviewed women prenatally (n = 380), at 2-weeks (n = 342) and at 6-months postpartum (n = 256). We conducted multivariable analyses to examine the demographic, behavioral, and attitudinal correlates of breastfeeding initiation and duration. RESULTS: Factors positively associated with breastfeeding initiation included positive breastfeeding attitudes and social support for breastfeeding from the woman's husband/boyfriend and her mother. Factors positively associated with breastfeeding at 2-weeks postpartum were support from the woman's mother and positive attitudes about breastfeeding. The prenatal use of traditional American Indian medicines and cigarette smoking were both significantly associated with breastfeeding at 6-months postpartum. CONCLUSIONS: Programs to encourage breastfeeding in American Indian communities may be strengthened with protocols to encourage social support, recognition of the perceived health, developmental, and practical benefits of breastfeeding, and a focus on traditional American Indian health practices.


Asunto(s)
Lactancia Materna/etnología , Conocimientos, Actitudes y Práctica en Salud , Indígenas Norteamericanos/estadística & datos numéricos , Medicina Tradicional , Periodo Posparto , Adolescente , Adulto , Lactancia Materna/psicología , Lactancia Materna/estadística & datos numéricos , Intervalos de Confianza , Recolección de Datos , Análisis Factorial , Femenino , Humanos , Lactante , Recién Nacido , Entrevistas como Asunto , Estudios Longitudinales , Minnesota/epidemiología , Análisis Multivariante , Investigación en Enfermería/estadística & datos numéricos , Oportunidad Relativa , Embarazo , Adulto Joven
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