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Rationale/Objective@#Neoadjuvant chemotherapy (NAC) is recommended for locally-advanced breast cancer (LABC) to improve resectability and provide in-vivo tumor response assessment. This study aimed to describe the clinical and pathologic tumor response of LABC patients after response-guided NAC.@*Methods@#This is a retrospective cohort analysis of 128 LABC patients who underwent NAC using sequential doxorubicin/cyclophosphamide (AC) – docetaxel (T) regimen at the Philippine General Hospital Breast Care Center. Clinical and pathologic response rates were analyzed according to clinicopathologic variables including tumor intrinsic subtype.@*Results@#Objective clinical response (complete and partial) was observed in 88% (111/128) of patients with 11% (14/128) achieving pathologic complete response (pCR). The hormone receptor-negative/ Her2-enriched (HR-/Her2+) subtype had the highest pCR rate (23.5%) followed by triple negative subtype (HR-/Her2-) at 19%. The hormone receptor-positive/Her2-positive (HR+/Her2+) subtype had the lowest pCR (4.7%). Two patients with initial poor response to AC but had good response upon shifting to T achieved pCR. Twelve patients (9.4%) had poor response to AC and T chemotherapy. Patients who were pre-menopausal (p=0.04), had ductal histology (p=0.03), with a HR-/Her2- (p=0.002) or HR+/Her2+ subtype (p=0.03) had good response to AC. Intrinsic subtype was not significantly associated with treatment response in those who received docetaxel. There was strong association between the pathologic and clinical responses (Spearman’s Rho score 0.69, p-value <0.0001).@*Conclusion@#Clinical and pathologic response to NAC was highly dependent on tumor subtype. Clinical response was predictive of pathologic response. Response-guided NAC allowed direct and early evaluation of tumor treatment response that allowed for treatment modifications.
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Neoplasias da Mama , Terapia Neoadjuvante , Tratamento FarmacológicoRESUMO
BACKGROUND: Human immunodeficiency virus (HIV) risky behaviours including multiple sexual partnership (MSP) and non-condom use (nCU) are known to be drivers of the spread of HIV; cognitive factors including perceived susceptibility of HIV, self-efficacy and attitudes play a significant role in influencing risky sexual behaviours. OBJECTIVES: We sought to investigate personal beliefs, perceptions, thoughts and actions that are associated with MSP and nCU in South Africa. METHODS: We analysed nationally representative data from the 2012 National HIV Communication Survey (NCS) that included about 10 000 participants aged 16-55 years. Five constructs were created to measure psychosocial and cognitive determinants. Cronbach's alpha coefficient for internal consistency reliability was calculated. Multivariable logistic regression was used to determine factors associated with MSP and nCU. RESULTS: Of the 6061 sexually active respondents, 13% (95% CI: 11.47-13.12) reported MSP and 52.7% (n = 3158 of 6039) (95% CI: 51.0-53.55) nCU at last sex. Factors associated with MSP included perceived benefits, adjusted odds ratio (aOR) = 2.16 (95% CI: 1.80-2.58), perceived susceptibility to HIV, aOR = 2.22 (95% CI: 1.83-2.69) and engaging in intergenerational sex, aOR = 2.14 (95% CI: 1.78-2.56). Predictors of nCU were perceived benefits, aOR = 1.25 (95% CI: 1.09-1.43); perceived susceptibility to HIV, aOR = 1.6 (95% CI: 1.39-1.83); and personal beliefs, aOR = 1.35 (95% CI: 1.13-1.62). CONCLUSION: Cognitive and behavioural factors were found to be predictors of risky sexual behaviours for HIV. This highlights the importance of considering personal perception and reasoning when attempting to understand and influence an individual's sexual behaviour. This could be done through enhancing awareness of HIV risk in the general population and by influencing cognitive behaviour change through community mobilisation, advocacy and creating activities to improve self-esteem.
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INTRODUCTION: South Africa is among countries with the highest burden of drug resistant tuberculosis (DR-TB). The Eastern Cape Province reported the highest MDR-TB mortality rates in South Africa for the 2010 treatment cohorts. This study aimed to determine risk factors for mortality among adult patients registered for DR-TB treatment in the province. METHODS: We conducted a retrospective cohort study of adult patients treated for laboratory confirmed DR-TB between January 2011 and December 2013. Demographic and clinical characteristics of the patients were obtained from a web-based electronic database of patients treated for DR-TB. We applied modified Poisson regression with robust standard errors to identify risk factors for DR-TB mortality. We also stratified the analyses into multi-drug resistant TB (MDR-TB) and extensively drug resistant (XDR-TB). RESULTS: Among 3,729 patients that met the inclusion criteria, 39% (n = 1,445) died. Of the patients that died, 53% (n = 766) were male, 68% (n = 982) had MDR-TB, 72% (n = 1,038) were HIV co-infected, and median age was 37 years (Interquartile Range [IQR] 30-46). Patients were at higher risk of mortality during DR-TB treatment if they were HIV co-infected not on antiretroviral treatment (ART) (adjusted incidence risk ratio [aIRR] 3.3, 95% confidence interval [CI] 2.9-3.8), were 60 years or older (aIRR 1.7, 95%CI 1.5-2.0), had a diagnosis of XDR-TB (aIRR 1.6, 95%CI 1.5-1.7), or had been hospitalised at treatment start (aIRR 1.7, 95%CI 1.5-1.8). Among MDR-TB patients, risk of mortality was higher if patients were HIV co-infected not on ART (aIRR 3.9, 95%CI 3.3-4.6), were 60 years or older (aIRR 1.9, 95%CI 1.6-2.3), or had been hospitalised at start of MDR-TB treatment (aIRR 1.7, 95%CI 1.5-1.9). Among XDR-TB patients, risk of mortality was higher in patients who were HIV co-infected not on ART (aIRR 1.8, 95%CI 1.5-2.2), or had been hospitalised at the start of XDR-TB treatment (aIRR 1.5, 95%CI 1.3-1.8). CONCLUSION: HIV co-infected not on ART, older age, XDR-TB and hospital admission for DR-TB treatment were independent risk factors for DR-TB mortality. Integration of TB and HIV services, with focus on voluntary HIV testing and counselling of DR-TB patients with unknown HIV status, and provision of ART for all co-infected patients may reduce DR-TB mortality in the Eastern Cape.
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Coinfecção/mortalidade , Bases de Dados Factuais , Infecções por HIV/mortalidade , Sistema de Registros , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Adulto , Antirretrovirais/administração & dosagem , Coinfecção/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , África do Sul/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
Strengthening current surveillance systems for syphilis is important to track and monitor disease burden. We used routinely collected laboratory information to generate surveillance estimates for syphilis trends among women of reproductive age (12-49 years) in the Northern Cape Province, a high syphilis burden region (2003 [8.6%] to 2011 [3.8%]) in South Africa. We extracted records meeting inclusion criteria from the National Health Laboratory Service electronic database for the period 2003-2012. A total of 286,024 women were included in the analysis. Syphilis seropositivity decreased between 2003 (5.7%) and 2012 (1.8%); p trend = 0.001, which was largely consistent with findings reported in the annual national syphilis and HIV survey from 2003 (8.6%) to 2011 (3.8%). Annually for the period from 2003 to 2012 there was an approximate 14% reduction in the prevalence ratio of syphilis seroprevalence (PR = 0.86, 95% CI = 0.85-0.87, p < 0.001). Three of five districts had significant decreases in syphilis seropositivity over this period. There were also declines in prevalence ratios for syphilis seropositivity for the various age groups for the period. This study shows that the national laboratory database in South Africa can be used as a complimentary surveillance tool to describe and understand trends in syphilis seroprevalence in South Africa.
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Monitoramento Epidemiológico , Sífilis/diagnóstico , Sífilis/epidemiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Laboratórios , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , África do Sul/epidemiologia , Adulto JovemRESUMO
Locally manufactured sodium hypochlorite (chlorine) solution has been sold in Zimbabwe since 2010. During October 1, 2011-April 30, 2012, 4,181 suspected and 52 confirmed cases of typhoid fever were identified in Harare. In response to this outbreak, chlorine tablets were distributed. To evaluate household water treatment uptake, we conducted a survey and water quality testing in 458 randomly selected households in two suburbs most affected by the outbreak. Although 75% of households were aware of chlorine solution and 85% received chlorine tablets, only 18% had reportedly treated stored water and had the recommended protective level of free chlorine residuals. Water treatment was more common among households that reported water treatment before the outbreak, and those that received free tablets during the outbreak (P < 0.01), but was not associated with chlorine solution awareness or use before the outbreak (P > 0.05). Outbreak response did not build on pre-existing prevention programs.
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Surtos de Doenças/prevenção & controle , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Purificação da Água/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cloro/farmacologia , Estudos Transversais , Água Potável , Características da Família , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Saúde Pública , Inquéritos e Questionários , Abastecimento de Água , Adulto Jovem , Zimbábue/epidemiologiaRESUMO
Reversibility of airway obstruction in response to ß2-agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) to inhaled albuterol, 534 290 single-nucleotide polymorphisms (SNPs) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations. The primary replication phase included 1397 polymorphisms in three asthma trials (pooled n=764). The second replication phase tested 13 SNPs in three additional asthma populations (n=241, n=215 and n=592). An intergenic SNP on chromosome 10, rs11252394, proximal to several excellent biological candidates, significantly replicated (P=1.98 × 10(-7)) in the primary replication trials. An intronic SNP (rs6988229) in the collagen (COL22A1) locus also provided strong replication signals (P=8.51 × 10(-6)). This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics.
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Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Adolescente , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/genética , Broncodilatadores/administração & dosagem , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: South Africa has targeted to eliminate malaria by the year 2018. Constant monitoring of malaria morbidity and mortality trends in affected subpopulations is therefore crucial in guiding and refining control interventions. Mutale Municipality in Limpopo Province is one of the areas with the highest risk of malaria in the country. This paper describes trends in malaria incidence, case fatality and household indoor residual spraying (IRS) coverage in Mutale Municipality, during the period 2005 to 2010. METHODS: A retrospective descriptive analysis was conducted on malaria data routinely collected through the Limpopo provincial malaria information system between July 2005 and June 2010. Five malaria seasons were defined. Annualized malaria incidence rates, case fatality rates (CFR) and IRS coverage rates were calculated. RESULTS: Cumulatively, 4,663 malaria cases and 21 malaria deaths were reported in Mutale between July 2005 and June 2010. Investigation of likely origin of the malaria in 3,517 patients revealed that 6.6% were imported cases, mostly from neighbouring Zimbabwe (222/231). Malaria incidence rates fell from 13.6 cases per 1,000 person-years in the 2005-2006 season to 2.7 cases per 1,000 person-years in the 2009-2010 season. The mean malaria CFR was stable between 0.3 and 0.6% during the first four seasons, and increased sharply to 2.1% in the 2009-2010 season. The median age of the 21 malaria deaths was 34 years (range: 16 to 60 years). CFRs were 0% in children below 15 years and above 0.5% in patients more than 24 years old. Regular IRS achieved coverage above 80% in all five seasons. CONCLUSION: Malaria control interventions implemented in Mutale significantly reduced the incidence of malaria in the population. In order to accurately monitor progress towards the elimination goal, the malaria control programme should strengthen the reporting and capturing of the data in the provincial malaria information system; all patients diagnosed with malaria should be investigated to determine the likely source of the malaria, and malaria related deaths should be audited to improve case detection and management. Furthermore, the country should strengthen cross border malaria control collaborations in order to minimize malaria importation.
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Malária/epidemiologia , Malária/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , África do Sul/epidemiologia , Análise de Sobrevida , Adulto JovemRESUMO
The Uthungulu District in KwaZulu-Natal province is the area that is most affected by rabies in South Africa. Usually; the transmission of rabies to humans occurs through the bites of infected dogs. In 2008; Uthungulu commenced a programme to eliminate human rabies in the district. This paper describes the epidemiology of dog bites and human rabies in the UThungulu District from 2008-2010; and the extent of adherence to rabies post-exposure prophylaxis (PEP). The method was a retrospective analysis of dog-bite and human rabies surveillance data that were collected in Uthungulu from January 2008-December 2010. Dog-bite injuries in Uthungulu increased from 1 176 in 2008 to 2 365 in 2009; and decreased to 1 598 in 2010. Of 2 601 patients who were offered rabies PEP in 2009 and 2010; 83.7 [95 confidence interval (CI): 82.4-85.2] completed the treatment. Logistic regression analysis found that investigation of the report by an environmental healthcare practitioner [odds ratio (OR) = 3.95; 95 CI: 2.43-6.43; p-value = 0 .0001]; the availability of patient telephone contact details in the healthcare facility's records (OR = 1.76; 95 CI: 1.02-3.03; p-value = 0.041); and bite wounds that were classified as Category 3 exposure injuries (OR = 2.96; 95 CI: 1.39-6.29; p-value = 0.004); were independently associated with completion of rabies PEP. Seven human rabies cases were reported (four in 2008; two in 2009 and one in 2010). Annualised human rabies incidence rates decreased from four cases per million in 2008 to one case per million in 2010. The findings suggest that the rabies elimination initiative is having an impact on the reduction of the incidence of human rabies in Uthungulu. The district should strengthen the follow-up of people who are exposed to rabies to ensure PEP completion
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Mordeduras e Picadas , Pacientes , Profilaxia Pós-Exposição , Raiva , VacinaçãoRESUMO
PURPOSE: Tuberculosis (TB) is endemic in India and the burden of multi-drug-resistant tuberculosis (MDR-TB) is high. Early detection of MDR-TB is of primary importance in controlling the spread of TB. The microscopic observational drug susceptibility (MODS) assay has been described as a cost-effective and rapid method by which mycobacterial culture and the drug susceptibility test (DST) can be done at the same time. MATERIALS AND METHODS: A total of 302 consecutive sputum samples that were received in an accredited mycobacteriology laboratory for conventional culture and DST were evaluated by the MODS assay. RESULTS: In comparison with conventional culture on Lowenstein Jensen (LJ) media, the MODS assay showed a sensitivity of 94.12% and a specificity of 89.39% and its concordance with the DST by the proportion method on LJ media to isoniazid and rifampicin was 90.8% and 91.5%, respectively. The turnaround time for results by MODS was 9 days compared to 21 days by culture on LJ media and an additional 42 days for DST by the 1% proportion method. The cost of performing a single MODS assay was Rs. 250/-, compared to Rs. 950/- for culture and 1st line DST on LJ. CONCLUSION: MODS was found to be a sensitive and rapid alternative method for performing culture and DST to identify MDR-TB in resource poor settings.
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Antituberculosos/farmacologia , Microscopia/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Índia , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Rifampina/farmacologia , Sensibilidade e Especificidade , Escarro/microbiologia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The Prevention of Mother to Child Transmission of HIV (PMTCT) programme was introduced at Bindura Hospital in 2003. Seven additional satellite PMTCT clinics were set up in the district to increase service coverage but uptake of PMTCT interventions remained unsatisfactory. In this study we determined the prevalence of and factors associated with non-adherence to the single dose nevirapine (SD-NVP) regimen for PMTCT in Bindura town. METHODS: An analytic cross-sectional study was conducted in four health institutions in Bindura town. Participants were mother-baby pairs on the PMTCT programme attending routine six weeks post natal visits in the participating health institutions from March to July 2008. We interviewed 212 mothers using a structured questionnaire. RESULTS: The non-adherence rate to the maternal nevirapine dose was 30.7%, while non-adherence to the newborn nevirapine dose was 26.9%. The combined mother-baby pair nevirapine non-adherence was 42.9%. Non-adherence to the maternal dose of nevirapine was associated with lack of maternal secondary education (POR = 2.38; 95%CI: 1.05-3.39) and multi-parity (POR = 2.66; 95%CI: 1.05-6.72), while previous maternal exposure to the PMTCT programme (POR = 0.22; 95%CI: 0.08-0.57) and giving the mother a NVP tablet to take home during antenatal care (POR = 0.03; 95%CI: 0.01-0.09) were associated with improved maternal adherence to nevirapine. Non-adherence to the infant dose of nevirapine was associated with maternal non-disclosure of HIV results to sexual partner (POR = 2.75; 95%CI: 1.04-7.32) and home deliveries (POR = 48.76; 95%CI: 17.51-135.82). CONCLUSIONS: Non-adherence to nevirapine prophylaxis for PMTCT was high in Bindura. Ensuring institutional deliveries, encouraging self-disclosure of HIV results by the mothers to their partners and giving HIV positive mothers nevirapine doses to take home early in pregnancy all play significant roles in improving adherence to PMTCT prophylaxis.
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Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adesão à Medicação/psicologia , Nevirapina/administração & dosagem , Adulto , Estudos Transversais , Parto Obstétrico , Escolaridade , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estado Civil , Adesão à Medicação/estatística & dados numéricos , Gravidez , Estudos de Amostragem , Autorrevelação , Inquéritos e Questionários , Zimbábue/epidemiologiaRESUMO
Little is known about how HIV-positive mothers experience and react to knowing the HIV status of their baby as diagnosed by the polymerase chain reaction (PCR) test at 4-6 weeks. This qualitative study drew on interviews with 20 mothers of HIV-negative and 18 mothers of HIV-positive babies after receiving their baby's PCR results. Thematic analysis combined exploration of themes that appeared significant to the participants and those relevant to health care. Amongst the themes identified were the following: The period before getting the results involved active mental preparation and was emotionally stressful. Most women accepted the results, but some had doubts about their reliability. Mothers of HIV-negative babies were relieved, but mothers of HIV-positive babies were generally very distressed and expressed a sense of responsibility and guilt. Both groups of mothers had similar hopes for the future of their babies, but the timelines of mothers of HIV-positive babies tended to be shorter. Most women experienced significant levels of stress, but were able to call on support networks and use various individual coping mechanisms to manage their stress. Most women were formula feeding their babies, but regretted not being able to breastfeed. Many women had not planned their current baby and most did not intend to have more children, but many of the latter had not taken active steps to prevent further pregnancy. The findings provide pointers to shortcomings in health worker communication and suggest that more effective communication should take account of normative community views and be more closely attuned to the changing needs and experiences of HIV-positive mothers.
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Anticoncepção/psicologia , Infecções por HIV/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Transmissão Vertical de Doenças Infecciosas , Mães/psicologia , Adaptação Psicológica , Adulto , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Fórmulas Infantis , Reação em Cadeia da Polimerase , Estresse Psicológico , Adulto JovemRESUMO
Asthma affects approximately 300 million individuals worldwide. Medications comprise a substantial portion of asthma expenditures. Despite the availability of three primary therapeutic classes of medications, there are a significant number of nonresponders to therapy. Available data, as well as previous pharmacogenetic studies, suggest that genetics may contribute as much as 60-80% to the interindividual variability in treatment response. In this methodologic review, after providing a broad overview of the asthma pharmacogenetics literature to date, we describe the application of a novel family-based screening algorithm to the analysis of pharmacogenetic data and highlight our approach to identifying and verifying loci influencing asthma treatment response. This approach seeks to address issues related to multiple comparisons, statistical power, population stratification, and failure to replicate from which previous population-based or case-control pharmacogenetic association studies may suffer. Identification of such replicable loci is the next step towards the goal of 'individualized therapy' for asthma.
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Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/genética , Farmacogenética , Agonistas Adrenérgicos beta/farmacologia , Agonistas Adrenérgicos beta/uso terapêutico , Algoritmos , Animais , Antiasmáticos/farmacologia , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/metabolismo , Asma/metabolismo , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/uso terapêutico , Fenótipo , Polimorfismo de Nucleotídeo Único , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Adrenérgicos beta/efeitos dos fármacos , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Receptores de Hormônio Liberador da Corticotropina/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Resultado do TratamentoRESUMO
C-reactive protein (CRP) is a well-documented marker of atherosclerotic cardiovascular disease risk. We resequenced CRP to identify a comprehensive set of common SNP variants, then studied and replicated their association with baseline CRP level among apparently healthy subjects in the Women's Health Study (WHS; n = 717), Pravastatin Inflammation/CRP Evaluation trial (PRINCE; n = 1,110) and Physicians' Health Study (PHS; n = 509) cohorts. The minor alleles of four SNPs were consistently associated in all three cohorts with higher CRP, while the minor alleles of two SNPs were associated with lower CRP (p < 0.05 for each). Single marker and haplotype analysis in all three cohorts were consistent with functional roles for the 5'-flanking triallelic SNP -286C>T>A and the 3'-UTR SNP 1846G>A. None of the SNPs associated with higher CRP were associated with risk of incident myocardial infarction (MI) or ischemic stroke in a prospective, nested case-control study design from the PHS cohort (610 case-control pairs). One SNP, -717A>G, was unrelated to CRP levels but associated with decreased risk of MI (p = 0.001). Taken together, these data imply significant interactions between both genetic and environmental contributions to the increased CRP levels that predict a greater risk of future atherothrombotic events in epidemiological studies.
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Aterosclerose/genética , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Saúde da MulherRESUMO
BACKGROUND: The association between white matter lesions on magnetic resonance imaging (MRI) and the presence of vascular risk factors has been investigated in different populations, and results have varied widely. However, this relationship has not been adequately addressed in memory clinic attenders who have relatively early cognitive impairment. OBJECTIVES: This study was undertaken to determine the relationship between the severity of white matter lesions and vascular risk factors in elderly subjects referred to a Memory Clinic, irrespective of their diagnoses. Patients attending the Memory Clinic had relatively early, mild cognitive impairment and differed, in this respect, from typical unselected community-based samples and from patients with established dementia. The study also investigated whether periventricular and deep white matter lesions differed in their relationship with vascular risk factors. METHODS: All patients assessed in the Memory Clinic at Leicester General Hospital between April 1998 and October 2000 who had undergone an MRI scan were included in the study. They received a comprehensive clinical and cognitive assessment, a standard dementia laboratory screen and evaluation of vascular risk factors. MRI scans were reviewed by two independent raters and semi-quantitative ratings of the severity of white matter lesions were made using standardised protocols. The relationship between cerebral white matter lesions and vascular risk factor variables was examined by multiple linear regression. RESULTS: One hundred and seventy-seven subjects were included in the study. The mean age was 69.8 and the mean MMSE score was 23.2. Of the risk factors investigated, only age and prior cerebrovascular disease were significantly associated with severe periventricular white matter lesions; age, hypertension and diabetes were significantly associated with severe deep white matter lesions. CONCLUSIONS: Periventricular and deep white matter lesions are differentially influenced by vascular risk factors.
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Encéfalo/patologia , Transtornos Cognitivos/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/patologia , Ventrículos Cerebrais/patologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/patologia , Transtornos Cognitivos/complicações , Complicações do Diabetes/patologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Fatores de RiscoRESUMO
Interleukin17F (IL17F) is a regulatory cytokine for T-cell-mediated immune responses. The gene coding for IL17F (IL17F) is located on chromosome 6p, a genomic region linked to asthma and asthma-related phenotypes in multiple genome scans. IL17F is expressed in lung tissue, in bronchoalveolar lavage fluid from asthmatic subjects, and in activated CD4+ cells. We were thus interested in testing for association between single-nucleotide polymorphisms (SNPs) and haplotypes in IL17F and asthma. To characterize polymorphisms in IL17F, we sequenced this gene in a group of African Americans and a group of European Americans. A total of 50 SNPs (30 not previously reported in a public database (dbSNP build 118)) and two insertions/deletions were detected in IL17F; five of these polymorphisms were genotyped in participants of the Nurses' Health Study. We then tested for association between SNPs and haplotypes in IL17F and physician-diagnosed asthma in subjects with (cases) and without (control subjects) physician-diagnosed asthma. None of the SNPs or haplotypes tested in IL17F were associated with asthma. The polymorphisms identified in this study may be used in future studies of association between IL17F and phenotypes related to immune responses.
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Asma/metabolismo , Predisposição Genética para Doença , Interleucina-17/genética , Negro ou Afro-Americano , Humanos , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , População BrancaRESUMO
Toll-like receptor 6 (TLR6) is one of a series of highly conserved innate immune receptors. We resequenced TLR6 in DNA samples from 24 African Americans, 23 European Americans, and 24 Hispanic Americans, identifying 53 SNPs, 22 with an allele frequency >5%. Significant differences in SNP frequencies among the three populations were noted. In all, 11 SNPs caused amino-acid changes, including one with a frequency >5% in all three populations. Utilizing this SNP (Ser249Pro), we performed exploratory nested case-control disease-association studies, including one involving 56 African Americans with asthma and 93 African American controls. The minor allele of this SNP was associated with decreased risk for asthma (odds ratio 0.38, 95% CI 0.16-0.87, P=0.01), an effect consistent with the known biology of the toll-like receptors. Although replication of this finding in other, larger samples is needed, variation in TLR6 may have relevance to the pathogenesis of immunologically mediated diseases.
Assuntos
Asma/diagnóstico , Asma/genética , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Receptores de Superfície Celular/genética , Asma/etnologia , Feminino , Frequência do Gene , Humanos , Masculino , Receptor 6 Toll-LikeRESUMO
The National Bioterrorism Syndromic Surveillance Demonstration Program identifies new cases of illness from electronic ambulatory patient records. Its goals are to use data from health plans and practice groups to detect localized outbreaks and to facilitate rapid public health follow-up. Data are extracted nightly on patient encounters occurring during the previous 24 hours. Visits or calls with diagnostic codes corresponding to syndromes of interest are counted; repeat encounters are excluded. Daily counts of syndromes by zip code are sent to a central data repository, where they are statistically analyzed for unusual clustering by using a model-adjusted SaTScan approach. The results and raw data are displayed on a restricted website. Patient-level information stays at the originating health-care organization unless required by public health authorities. If a cluster surpasses a threshold of statistical aberration chosen by the corresponding public health department, an electronic alert can be sent to that department. The health department might then call a clinical responder, who has electronic access to records of cases contributing to clusters. The system is flexible, allowing for changes in participating organizations, syndrome definitions, and alert thresholds. It is transparent to clinicians and has been accepted by the health-care organizations that provide the data. The system's data are usable by local and national health agencies. Its software is compatible with commonly used systems and software and is mostly open-source. Ongoing activities include evaluating the system's ability to detect naturally occurring outbreaks and simulated terrorism events, automating and testing alerts and response capability, and evaluating alternative data sources.
Assuntos
Bioterrorismo/prevenção & controle , Surtos de Doenças/prevenção & controle , Sistemas Computadorizados de Registros Médicos , Vigilância da População/métodos , Informática em Saúde Pública , Assistência Ambulatorial , Análise por Conglomerados , Humanos , Estados UnidosAssuntos
Fibrose Cística/genética , Testes Genéticos/psicologia , Estudantes/psicologia , Doença de Tay-Sachs/genética , Adolescente , Austrália , Feminino , Triagem de Portadores Genéticos , Testes Genéticos/métodos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Judeus/genética , Masculino , Educação de Pacientes como Assunto/métodos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Latex allergy has emerged as an important cause of allergic reactions particularly in health workers. Due to the lack of a standardized extract for objective skin testing a screening questionnaire was developed. METHODS: At the 1995 Australian Dental Association Conference, all attendees were invited to complete a questionnaire and undergo skin testing to assess the level of latex allergy in this population and to assess the performance of the questionnaire as a screening test for latex allergy. RESULTS: The questionnaire had high specificity but poor sensitivity compared to skin testing with latex extract. CONCLUSION: This study compares at risk individuals identified by a screening questionnaire with those identified by objective skin testing. A questionnaire designed to screen for latex allergy was reliable for identifying those with low risk while overestimating those at risk of true latex allergy, demonstrating the need for objective testing with reliable allergens.