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STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim was to investigate the clinical relevance of preoperative caudal adjacent segment degeneration (ASD) in patients undergoing isolated L4-5 fusion to determine a threshold of degeneration at which a primary L4-S1 fusion would be warranted. SUMMARY OF BACKGROUND DATA: Increased motion and biomechanical forces across the adjacent caudal segment in isolated L4-L5 fusion leads to concerns regarding the increased incidence of revision surgery because of the development of ASD. METHODS: Patients who underwent isolated L4-L5 fusion between 2014 and 2019 were reviewed. Pfirrmann grading and the disc heights of the caudal level relative to the rostral level were used to quantify preoperative adjacent degenerative disc disease. To assess the influence of preoperative caudal degenerative disc disease, preoperative disc height ratios (DHRs) were compared for patients who reported minimal, moderate, and severe Oswestry disability index (ODI) sores on postoperative assessment. For each patient-reported outcome measure (PROM), adjacent DDD was compared for those who did and did not meet MCID. An area under curve analysis was used to identify a threshold of degeneration impacting outcomes from the preoperative DHR. RESULTS: A total of 123 patients were studied with an average follow-up of 2.11 years. All patients demonstrated a significant improvement in all PROMs after surgery. When categorizing patients based on the severity of postoperative ODI scores, there were no preoperative differences in the L5-S1 Pfirrmann grading or DHRs. There was a significant association between greater preoperative anterior DHR and an increased number patients who met MCID for visual analog scale back. There were no radiographic differences in preoperative L5-S1 Pfirrmann grade or DHR for ODI, visual analog scale leg, MCS-12, or PCS-12. area under curve analysis was not able to identify a preoperative DHR threshold that reflected worse MCID for any PROM. CONCLUSION: No preoperative radiographic indicators of caudal ASD were predictive of worse clinical outcomes after isolated L4-5 fusion. LEVEL OF EVIDENCE: Level III.
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Degeneração do Disco Intervertebral , Fusão Vertebral , Humanos , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do TratamentoRESUMO
STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to determine the effect of a statewide, government-mandated prescription drug monitoring program (PDMP) on patient-initiated phone calls after lumbar and cervical spinal surgery. SUMMARY OF BACKGROUND DATA: Prior studies have examined the most common reasons for a postoperative phone calls, most of which pertain to pain or prescription medications. However, no studies have investigated the effects of mandatory opioid prescription reporting on these calls. METHODS: Patients who underwent lumbar decompression, lumbar fusion, or posterior cervical fusion were retrospectively identified. Patients were sorted into 1 of 2 cohorts based on their procedure date's relation to the initiation of the state's PDMP: "pre-PDMP" and "post-PDMP." All clinical and demographic data were obtained from electronic health records. Telephone communications from or on behalf of patients were retrospectively reviewed. Multivariable logistic regression was performed to determine independent factors associated with a postoperative phone call. RESULTS: Five hundred and twenty-five patients (2689 phone calls) were included in the study. Average number of phone calls per patient increased significantly after PDMP implementation among lumbar (3.27 vs. 5.18, P<0.001), cervical (5.08 vs. 11.67, P<0.001), and all (3.59 vs. 6.30, P<0.001) procedures. Age [odds ratio (OR): 1.05 (1.01, 1.09), P=0.02], cervical procedure [OR: 4.65 (1.93, 11.21), P=0.001], and a post-PDMP date of surgery [OR: 6.35 (3.55, 11.35), P<0.001] were independently associated with an increased likelihood of a postoperative phone call. A higher percentage of calls were in reference to postoperative care (4.6% vs. 2.4%, P=0.01) and wound care (4.3% vs. 1.4%, P<0.001) in the post-PDMP cohort compared with the pre-PDMP cohort. CONCLUSIONS: Patient-initiated telephone calls increased significantly after implementation of a mandatory statewide PDMP. Increasing age, operation involving the cervical spine, and surgery occurring after implementation of the state's PDMP were independently associated with an increased likelihood of postoperative phone call to health care providers.
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Programas de Monitoramento de Prescrição de Medicamentos , Analgésicos Opioides/uso terapêutico , Humanos , Cuidados Pós-Operatórios , Período Pós-Operatório , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the association between cleavage stage development, embryonic competence, and euploidy in patients undergoing in vitro fertilization (IVF) with subsequent next generation sequencing. METHODS: The retrospective cohort study included patients at an academic fertility center who underwent IVF with at least one cleavage stage embryo from 2016 to 2019. Embryos were analyzed as slow (<6 cells), intermediate (6-8 cells), or fast (>8 cells); day 3 cell count was also analyzed as a continuous variable. Primary outcomes were blastulation rate, biopsied blastocyst rate, and euploid rate. Odds of blastulation, biopsy, and euploidy were also calculated. Additionally, we modeled the predicted probability of an embryo reaching blastulation, biopsy, and euploidy based on cleavage stage development. RESULTS: When compared with intermediate and slow cohorts, fast cleaving embryos had significantly higher rates of blastulation (82.70% vs. 75.13 vs. 42.48%), biopsy (55.04% vs. 44.00% vs. 14.98%), and euploidy (50.65% vs. 47.93% vs. 48.05%). After adjustment for covariates, there was a significant association between cleavage stage development and odds of blastulation (OR 1.38, 95% CI 1.29-1.48), biopsy (OR 1.42, 95% CI 1.34-1.51), and euploidy (OR 1.08, 95% CI 1.01-1.17). Finally, we observed significant associations between cleavage stage development and predicted probability of reaching blastulation (OR 1.29, 95% CI 1.27-1.32), biopsy (OR 1.24, 95% CI 1.22-1.26), and euploidy (OR 1.02, 95% CI 1.01-1.04). CONCLUSIONS: Cleavage stage embryos with greater mitotic activity perform as well as or better than intermediate or slower cleaving embryos. Rapidly cleaving embryos have high rates of euploidy and significant clinical potential.
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Diagnóstico Pré-Implantação , Blastocisto , Implantação do Embrião , Feminino , Fertilização , Fertilização in vitro , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: This study evaluates the patient-reported Health Related Quality of Life outcomes and radiographic parameters of patients who underwent a single level transforaminal lumbar interbody fusion with either a polyetheretherketone (PEEK) or titanium interbody cage. SUMMARY OF BACKGROUND DATA: Spinal stenosis with instability is a common diagnosis that is often treated with interbody fusion, in particular transforaminal lumbar interbody fusion. Titanium and PEEK interbody cage properties have been extensively studied to understand their effect on fusion rates and subsidence. MATERIALS AND METHODS: A retrospective cohort study was conducted from a single, high volume, academic hospital. Health Related Quality of Life outcomes were obtained from Outcomes Based Electronic Research Database and electronic medical record chart review. Subsidence was defined as a loss of 2 mm or more in the anterior or posterior disk height. Spinopelvic alignment parameters measured were sacral slope, pelvic tilt, pelvic incidence, lumbar lordosis, segmental lordosis, and pelvic incidence-lumbar lordosis mismatch. Fusion rates were assessed by the Brantigan-Steffee criteria. RESULTS: The study included a total of 137 patients (108 PEEK, 29 titanium). Overall, no significant changes were noted between the 2 groups at 3 month or 1-year follow-up. Perioperatively, patients did report improvement in all outcome parameters within the PEEK and titanium groups. No significant difference was noted in subsidence rate between the 2 groups. Segmental lordosis significantly increased within the PEEK (+4.8 degrees; P<0.001) and titanium (+4.6 degrees; P=0.003) cage groups, however no difference was noted between groups. No significant difference was noted in fusion between the PEEK and titanium cage cohorts (92.6% vs. 86.2%; P=0.36). CONCLUSION: Overall, while PEEK and titanium cages exhibit unique biomaterial properties, our study shows that there were no significant differences with respect to patient-reported outcomes or radiographic outcomes between the 2 groups at the 1-year follow-up time point. LEVEL OF EVIDENCE: Level III.
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Fusão Vertebral , Titânio , Benzofenonas , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Polímeros , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Although chromosomal heteromorphisms are commonly found in the general population, some researchers have suggested a correlation with higher rates of embryo aneuploidy. This study aimed to assess the rates of embryo aneuploidy in couples who carry a chromosome heteromorphism. METHODS: The study included couples who had G-banding karyotype testing and underwent an IVF/PGT-A cycle between January 2012 and March 2018. The participants were classified by couple karyotype: Group A: ≥1 patient reported to be a heterochromatic variant carrier; Group B: both partners reported to be "normal". We assessed the rates of aneuploidy among the groups. We ran a multivariate regression analysis to assess the relationship between heterochromatic variants and the rates of embryo aneuploidy. RESULTS: Of the 946 couples analyzed, 48 (5.0%) reported being a carrier of ≥1 heterochromatic variant. We had 869 IVF/PGT-A cycles included in the analysis (Group A: n=48; Group B: n=82). There were no significant differences in embryo ploidy rates among the groups. The heterochromatic chromosome variant was not associated with increased likelihoods of aneuploidy (OR=1.04, CI:95% 0.85- 1.07; p=0.46). Finally, the gender of the heterochromatic variant carrier had no association with increased likelihood of aneuploidy (OR 1.02, CI 95% 0.81-1.28, p=0.82). CONCLUSIONS: Our study showed no association between parental heterochromatic chromosome variants and subsequent embryo aneuploidy rates. Ploidy rates do not appear to be negatively associated with couples when at least one patient is reported to be a carrier of a heterochromatic variant on the karyotype.
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Diagnóstico Pré-Implantação , Aneuploidia , Blastocisto , Cromossomos , Feminino , Fertilização in vitro , Testes Genéticos , Humanos , Pais , Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: Venezuela is in the throes of a complex humanitarian crisis that is one of the worst in decades to impact any country outside of wartime. This case analysis describes the challenges faced by the ongoing Maracaibo Aging Study (MAS) during the deteriorating conditions in Venezuela. When the MAS began in 1997, it focused on memory-related disorders. Since then, strategic planning and proactive community participation allowed us to anticipate and address logistical, funding, and ethical challenges, and facilitated the enrollment and retention of more than 2500 subjects over 55 years of age. All participants, who are residents of the city of Maracaibo, Venezuela, underwent various assessments on several occasions. Here, we discuss how our approach to implementing a longitudinal, population-based study of age-related conditions has allowed our research program to continue throughout this period of political, economic, and social upheaval. DISCUSSION: As the social context in Venezuela became more complicated, new challenges emerged, and strategies to sustain the study and participation were refined. We identified five main mechanisms through which the evolving humanitarian crisis has affected implementation of the MAS: 1) community dynamics; 2) morale of researchers, staff, and participants; 3) financial feasibility; 4) components of the research process; and 5) impact on the health of staff, participants, and their families. Strategies to compensate for the impact on these components were implemented, based on inputs from community members and staff. Improved communication, greater involvement of stakeholders, broadening the scope of the project, and strengthening international collaboration have been the most useful strategies. Particular demands emerged, related to the increased mortality and comorbidities of participants and staff, and deterioration of basic services and safety. CONCLUSION: Although the MAS has faced numerous obstacles, it has been possible to continue a longitudinal research project throughout the humanitarian crisis, because our research team has engaged the community deeply and developed a sense of mutual commitment, and also because our project has provided funding to help keep researchers employed, somewhat attenuating the brain drain.
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Participação da Comunidade , Hispânico ou Latino , Envelhecimento , Humanos , Pesquisadores , VenezuelaRESUMO
BACKGROUND: Very few studies have investigated the association between total plasma homocysteine (tHcy) and depressive symptoms in older Hispanics. OBJECTIVE: To test the hypothesis that high tHcy associates with depressive symptoms in older Hispanics. METHODS: A total of 1,418 participants .55 years old from the Maracaibo Aging Study (MAS) underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. The Neuropsychiatric Inventory Depression Subscale (NPId) was used to assess the burden of depressive symptoms. The tHcy levels and other biochemical parameters in blood samples were measured. Univariate and multivariate logistic regression models were applied. RESULTS: Participants with depressive symptoms had higher levels of tHcy than those without (15.1 versus 13.9 µmol/L; p = 0.009). Elevated tHcy levels were associated with depressive symptoms after adjusting for age, sex, education, smoking, diabetes, hypertension, alcohol intake, stroke, and dementia (OR = 1.58; 95% CI, 1.18-2.12). CONCLUSION: Elevated levels of tHcy were associated with depressive symptoms in older Hispanics living under the nutritional and environmental conditions of a developing country.
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Envelhecimento/metabolismo , Envelhecimento/psicologia , Depressão/sangue , Depressão/psicologia , Hispânico ou Latino/psicologia , Homocisteína/sangue , Idoso , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Venezuela/epidemiologiaRESUMO
BACKGROUND: Dementia of the Alzheimer's type (DAT) impacts Hispanics disproportionately, with almost a twofold elevated risk of developing DAT, as well as earlier onset of the disease, than in non-Hispanic Whites. However, the role of main risk factors for DAT, such as APOE-É4 and blood pressure (BP) levels, remains uncertain among Hispanics. OBJECTIVE: To investigate the association of APOE-É4 and BP levels, measures with 24-h ambulatory BP monitoring, with incidence of DAT in an elderly cohort of Hispanics. METHODS: 1,320 participants from the Maracaibo Aging Study, free of dementia at the baseline, and with ambulatory BP measurements and APOE genotype available were included. Adjusted Cox proportional models were performed to examine 1) the incidence of DAT and 2) the relationship between BP levels and DAT according to APOE genotypes. Models were adjusted by competing risk of death before the onset of DAT. Model performance was assessed by likelihood test. RESULTS: The average follow-up time was 5.3 years. DAT incidence was 5.8 per 1000 person-year. APOE-É4 carriers had a higher risk of DAT. In unadjusted analyses, conventional, 24-h, and nighttime systolic BP levels were significantly higher in participants who developed DAT and of APOE-É4 carriers (p < 0.05). After adjustment for competing risks, only higher nighttime systolic BP was associated with DAT incidence, but only among subjects carrying APOE-É4. CONCLUSION: In this Hispanic population, both APOE-É4 genotype and assessment of nocturnal systolic BP (rather than diurnal or office BP) were necessary to estimate DAT risk.
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Doença de Alzheimer/genética , Apolipoproteína E4/genética , Pressão Sanguínea/genética , Ritmo Circadiano/genética , Demência/genética , Genótipo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etnologia , Demência/diagnóstico , Demência/etnologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Venezuela/etnologiaRESUMO
OBJECTIVE: Genetic carrier screening has the potential to identify couples at risk of having a child affected with an autosomal recessive or X-linked disorder. However, the current prevalence of carrier status for these conditions in developing countries is not well defined. This study assesses the prevalence of carrier status of selected genetic conditions utilizing an expanded, pan-ethnic genetic carrier screening panel (ECS) in a large population of Mexican patients. METHODS: Retrospective chart review of all patients tested with a single ECS panel at an international infertility center from 2012 to 2018 were included, and the prevalence of positive carrier status in a Mexican population was evaluated. RESULTS: Eight hundred five individuals were analyzed with ECS testing for 283 genetic conditions. Three hundred fifty-two carriers (43.7%) were identified with 503 pathogenic variants in 145 different genes. Seventeen of the 391 participating couples (4.34%) were identified as being at-risk couples. The most prevalent alleles found were associated with alpha thalassemia, cystic fibrosis, GJB2 nonsyndromic hearing loss, biotinidase deficiency, and familial Mediterranean fever. CONCLUSION: Based on the prevalence and severity of Mendelian disorders, we recommend that couples who wish to conceive regardless of their ethnicity background explore carrier screening and genetic counseling prior to reproductive medical treatment.
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Triagem de Portadores Genéticos , Doenças Genéticas Inatas/epidemiologia , Cuidado Pré-Concepcional , Adulto , Biotinidase/genética , Deficiência de Biotinidase/epidemiologia , Deficiência de Biotinidase/genética , Conexina 26/genética , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Feminino , Aconselhamento Genético , Doenças Genéticas Inatas/genética , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/genética , Hemoglobina A/genética , Heterozigoto , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Pirina/genética , Estudos Retrospectivos , Medição de Risco , Talassemia alfa/epidemiologia , Talassemia alfa/genéticaRESUMO
The incidence and prevalence of Alzheimer's disease (AD) dementia are higher among Caribbean Hispanics than among non-Hispanic Whites. The causes of this health disparity remain elusive, partially because of the relative limited capacity for biomedical research in the developing countries that comprise Caribbean Latin America. To begin to address this issue, we were awarded a Development Research Award from the US NIH and Fogarty International Center in order to establish the local capacity to integrate magnetic resonance imaging (MRI) into studies of cognitive aging and dementia in Dominican Republic, establish collaborations with Dominican investigators, and conduct a pilot study on the role of cerebrovascular markers in the clinical expression of AD. Ninety older adult participants with and without AD dementia and with and without a strong family history of AD dementia received MRI scans and clinical evaluation. We quantified markers of cerebrovascular disease (white matter hyperintensities [WMH], presence of infarct, and presence of microbleed) and neurodegeneration (entorhinal cortex volume) and compared them across groups. Patients with AD dementia had smaller entorhinal cortex and greater WMH volumes compared with controls, regardless of family history status. This study provides evidence for the capacity to conduct MRI studies of cognitive aging and dementia in Dominican Republic. The results are consistent with the hypothesis that small vessel cerebrovascular disease represents a core feature of AD dementia, as affected participants had elevated WMH volumes irrespective of family history status.
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Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , Doenças Neurodegenerativas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Atrofia/diagnóstico por imagem , República Dominicana , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
[This corrects the article DOI: 10.1099/jmmcr.0.005145.].
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Introduction: Although the current Zika virus (ZIKV) epidemic is a major public health concern, most reports have focused on congenital ZIKV syndrome, its most devastating manifestation. Severe ocular complications associated with ZIKV infections and possible pathogenetic factors are rarely described. Here, we describe three Venezuelan patients who developed severe ocular manifestations following ZIKV infections. We also analyse their serological response to ZIKV and dengue virus (DENV). Case presentation: One adult with bilateral optic neuritis, a child of 4 years of age with retrobulbar neuritis [corrected]. and a newborn with bilateral congenital glaucoma had a recent history of an acute exanthematous infection consistent with ZIKV infection. The results of ELISA tests indicated that all patients were seropositive for ZIKV and four DENV serotypes. Conclusion: Patients with ZIKV infection can develop severe ocular complications. Anti-DENV antibodies from previous infections could play a role in the pathogenesis of these complications. Well-designed epidemiological studies are urgently needed to measure the risk of ZIKV ocular complications and confirm whether they are associated with the presence of anti-flaviviral antibodies.
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BACKGROUND: Orthostatic hypotension (OH) occurs when mechanisms regulating blood pressure (BP) levels after standing-up are altered. It is unclear how prevalence and risk factors for OH are different between sexes. We aimed to investigate sex differences in prevalence and risk factors for OH elderly individuals. METHODS: We included 882 participants from Maracaibo Aging Study. OH was a sustained reduction of ≥20 mm Hg in systolic BP, ≥10 mm Hg in diastolic BP, or both, after 3 minutes of changing positions from supine to standing. Multivariable logistic regression models were used to examine the relationships among risk factors for OH in men and women considering interaction sex-term and stratified by sex. RESULTS: The mean age was 66.7 ± 8.5 years, being similar by sex. Women and men 55-74 years had similar prevalence of OH+ (18.5% vs. 20.9%, respectively). After 75 years, the proportion of women with OH+ was lower than men (11% vs. 30%, respectively). Hypertension, specifically systolic BP ≥140 mm Hg, and high pulse pressure (PP) were related with OH+ accounted by interaction sex-term, while diastolic BP ≥90 mm Hg, antihypertensive treatment, body mass index (BMI), diabetes mellitus and age were not. Systolic BP ≥140 mm Hg increases the risk of OH only among women, while BMI showed an inverse association in both sexes. CONCLUSIONS: Although the prevalence of OH is similar in both sexes, there are different risk factors associated by sex. Systolic BP ≥140 mm Hg was associated with increased risk of OH only with women while BMI was a protective factor for OH in men and women.
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Pressão Sanguínea , Hipotensão Ortostática/epidemiologia , Postura , Distribuição por Idade , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Hipotensão Ortostática/diagnóstico , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Proteção , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Venezuela/epidemiologiaRESUMO
PURPOSE: To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. DESIGN: Observational cross-sectional study. PARTICIPANTS: A subset (n = 93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants, who were at least 40 years of age, had measurements for optical tomography coherence, visual field (VF) tests, 24-hour BP, office BP, and intraocular pressure <22 mmHg. METHODS: Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to decreases in nocturnal BP. MAIN OUTCOME MEASURES: Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and VF defects. RESULTS: The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 19 (26.5%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme decreases in nighttime systolic and diastolic BP (>20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio, 19.78 and 5.55, respectively). CONCLUSIONS: In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme decreases in nocturnal BP in individuals at high risk of glaucoma are warranted.
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Envelhecimento/fisiologia , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Hipotensão/fisiopatologia , Doenças do Nervo Óptico/fisiopatologia , Idoso , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Gonioscopia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Tonometria Ocular , Venezuela , Campos Visuais/fisiologiaRESUMO
INTRODUCTION: We performed linkage analyses in Caribbean Hispanic families with multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may contain disease causative variants. METHODS: We selected 67 LOAD families to perform genome-wide linkage scan. Analysis of the linked regions was repeated using the entire sample of 282 families. Validated chromosomal regions were analyzed using joint linkage and association. RESULTS: We identified 26 regions linked to LOAD (HLOD ≥3.6). We validated 13 of the regions (HLOD ≥2.5) using the entire family sample. The strongest signal was at 11q12.3 (rs2232932: HLODmax = 4.7, Pjoint = 6.6 × 10(-6)), a locus located â¼2 Mb upstream of the membrane-spanning 4A gene cluster. We additionally identified a locus at 7p14.3 (rs10255835: HLODmax = 4.9, Pjoint = 1.2 × 10(-5)), a region harboring genes associated with the nervous system (GARS, GHRHR, and NEUROD6). DISCUSSION: Future sequencing efforts should focus on these regions because they may harbor familial LOAD causative mutations.