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John Attia

Publications and source records attributed to John Attia.

17 recordsLinked to original sources
PubMed2025

Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87&#xa0;% European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20&#xa0;% of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels. RESULTS: The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint<5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint<5.0e-9 in combination with Pint<6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature. CONCLUSIONS: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.

Humans↗
PubMed2004

A clinical decision rule to prioritize polysomnography in patients with suspected sleep apnea.

STUDY OBJECTIVES: To derive and validate a clinical decision rule that can help to prioritize patients who are on waiting lists for polysomnography, DESIGN: Prospective data collection on consecutive patients referred to a sleep center. SETTING: The Newcastle Sleep Disorders Centre, University of Newcastle, NSW, Australia. PATIENTS: Consecutive adult patients who had been scheduled for initial diagnostic polysomnography. MEASUREMENTS AND RESULTS: Eight hundred and thirty-seven patients were used for derivation of the decision rule. An apnea-hypopnoea index of at least 5 was used as the cutoff point to diagnose sleep apnea. Fifteen clinical features were included in the analyses using logistic regression to construct a model from the derivation data set. Only 5 variables--age, sex, body mass index, snoring, and stopping breathing during sleep--were significantly associated with sleep apnea. A scoring scheme based on regression coefficients was developed, and the total score was trichotomized into low-, moderate-, and high-risk groups with prevalence of sleep apnea of 8%, 51%, and 82%, respectively. Color-coded tables were developed for ease of use. The clinical decision rule was validated on a separate set of 243 patients. Receiver operating characteristic analysis confirmed that the decision rule performed well, with the area under the curve being similar for both the derivation and validation sets: 0.81 and 0.79, P =.612. CONCLUSION: We conclude that this decision rule was able to accurately classify the risk of sleep apnea and will be useful for prioritizing patients with suspected sleep apnea who are on waiting lists for polysomnography.

Adult↗
PubMed2004

The number needed to vaccinate (NNV) and population extensions of the NNV: comparison of influenza and pneumococcal vaccine programmes for people aged 65 years and over.

The number needed to treat (NNT) and population extensions of the NNT describe the population outcomes of disease treatment, usually for chronic diseases. We have developed similar measures for vaccine preventable diseases based on the number needed to vaccinate. These measures quantify the number of people, or the number of vaccine doses, needed to prevent one event due to disease per year and allow the calculation of the vaccine cost to prevent one event due to disease per year. We used this method to compare influenza and pneumococcal vaccine programmes for people aged 65 years or more. We calculated the vaccine cost (dollars AUD) to prevent a case of disease, a hospitalisation or a death due to influenza or invasive pneumococcal disease each year in this age group. For influenza, the vaccine costs were dollars 598 to prevent one case per year, dollars 10787 per hospitalisation prevented and dollars 74801 per death prevented each year. We assumed all cases of invasive pneumococcal disease were hospitalised so the vaccine cost of dollars 11494 per case prevented was the same as the vaccine cost per hospitalisation prevented, while the vaccine cost per death prevented each year was dollars 49972. These results suggest the vaccine costs for the prevention of one hospitalisation or one death each year due to invasive pneumococcal disease among the elderly in Australia would be similar to the costs for the prevention of one hospitalisation or death due to influenza.

Age Factors↗
PubMed2004

Prevalence and magnitude of classical risk factors for stroke in a cohort of 5092 Chinese steelworkers over 13.5 years of follow-up.

BACKGROUND AND PURPOSE: Stroke is the most common manifestation of cardiovascular disease (CVD) among Chinese men. This study addresses the prevalence and magnitude of classic CVD risk factors associated with total, ischemic, and hemorrhagic stroke in a Chinese cohort of at-risk men, compared with white populations. We also address which blood pressure index: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP) is the best predictor of stroke. METHODS: A cohort of 5092 male steelworkers (aged 18 to 74 years) recruited between 1974 to 1980 was followed up for an average of 13.5 years. The results showed that the risk ratios (RRs) of stroke associated with classic risk factors in this Asian population were not different than in whites, except for blood pressure. The RRs of total stroke for each 10mm Hg rise in SBP and DBP in this Asian group (1.4 and 1.8, respectively) were higher than in whites (1.2 to 1.3 and 1.2 to 1.5, respectively). The population attributable risk (PAR) for hypertension (160/95 mm Hg cutoff) to stroke was higher in Asians (ie, 31% for ischemic and 42% for hemorrhagic stroke) than in whites (25% and 34%, respectively). CONCLUSIONS: Our results indicate that hypertension is a greater risk factor for stroke in Asians than whites, especially for hemorrhagic stroke. The most predictive blood pressure (BP) index for stroke is MAP. However, the prevalence or magnitude of these traditional risk factors appears unlikely to explain the differing spectrum of CVD among Asians.

Adolescent↗
PubMed2004

Haplotype analysis of VDR gene polymorphisms: a meta-analysis.

INTRODUCTION: Although many studies have addressed the relationship between multiple individual polymorphisms in the vitamin D receptor (VDR) gene and bone health, few have analyzed this data in terms of haplotypes. We performed a meta-analysis of studies with data on the BsmI, ApaI, and TaqI polymorphisms in order to (a) estimate haplotype frequencies, (b) determine linkage disequilibrium (LD), and (c) estimate the magnitude of the association between haplotypes and osteoporosis/bone mineral density (BMD). METHODS: Haplotypes were inferred using the expectation-maximization algorithm (EM); log-linear models were used to determine association with osteoporosis; and regression analysis with variance components was used to determine association with BMD. RESULTS: Our results indicate that the most common haplotype for the VDR gene, regardless of ethnicity, is baT, followed by BAt and bAT in Caucasians, and bAT and BaT in Asians. This indicates strong LD between the BsmI and TaqI polymorphisms. We demonstrate a gain in power when considering the haplotypes rather than the individual polymorphisms separately, i.e., although BsmI, ApaI, and TaqI were not significantly associated with osteoporosis on their own, the haplotypes Bat and BAt were significantly associated, with an OR of approximately 4. CONCLUSION: We have applied haplotype analysis to the VDR polymorphisms and bone measures. We also highlight a number of methodologic issues, including linkage disequilibrium, the robustness of the EM algorithm in this context, and the potential for exploring effect modification.

Bone Density↗
PubMed2004

Does dietary calcium have a protective effect on bone fractures in women? A meta-analysis of observational studies.

It is generally accepted that supplemental Ca and/or vitamin D is effective in reducing the incidence of bone fractures; this is supported by numerous randomised controlled trials and meta-analyses. However, a question that has received much less attention is whether dietary Ca, i.e. Ca in physiological doses in normal food intake, also affects bone fracture risk. The present study aims to review the effect of dietary Ca on bone fractures at the hip, spine and radius in women >35 years old, and to compare these results with previous meta-analyses. MEDLINE (1966-1999) and reference lists in papers were searched for observational dietary Ca studies. Data were extracted in duplicate and separately. Heterogeneity and publication bias were tested. Observational studies failed to show any association between dietary Ca intake and risk of hip fracture (risk ratio 1.01, 95 % CI 0.96, 1.07 for each increment of 300 mg dietary Ca intake/d). There is a suggestion that either extremely low Ca intake may increase fracture risk, or that East Asian women may respond differently to increasing Ca intake.

Adult↗
PubMed2004

Prevalence and magnitude of classical risk factors for coronary heart disease in a cohort of 4400 Chinese steelworkers over 13.5 years follow-up.

BACKGROUND: The incidence and mortality of cardiovascular disease among Orientals are very different than among Caucasians. This study addresses the prevalence and magnitude of classic cardiovascular disease risk factors associated with coronary heart disease (CHD) in an Oriental cohort of at-risk men (blood pressure, total cholesterol, Body Mass Index [BMI] and smoking), compared to Caucasian populations. We also address which blood pressure index (SBP, DBP, mean arterial pressure [MAP] and pulse pressure [PP]) is the best predictor of CHD. METHODS AND RESULTS: A cohort of 5092 male steelworkers (18-74 years old) recruited between 1974-1980 was followed up for an average of 13.5 years. The prevalence of risk factors was lower in Orientals than in Caucasians, except for smoking. The relative risks (RRs) of CHD associated with classic risk factors in this Oriental population were similar to Caucasians, except for blood pressure. The RRs of CHD associated with both SBP and DBP in this Oriental group were higher than in Caucasians; RR of CHD was approximately 3 for each 40 mmHg rise of SBP versus approximately 2 in Caucasians. SBP was the single best predictor for CHD, followed by MAP, and DBP. The population attributable risk (PAR%) for hypertension (140/90 mmHg) was 42.4. CONCLUSION: Our results would indicate that the lower incidence of CHD in Orientals is at least partly due to the lower prevalence of hypertension, hypercholesterolemia, and obesity. The magnitude of the risk associated with these factors is similar to that in Caucasians, except perhaps for a greater risk associated with hypertension. The most predictive BP index for CHD is SBP. These results are based on indirect comparisons only and should be studied further in prospective multi-ethnic cohorts.

Adult↗
PubMed2004

The association between adverse pregnancy outcomes and maternal factor V Leiden genotype: a meta-analysis.

The conclusions of studies to date which evaluate a possible association between factor V Leiden and adverse pregnancy outcome have been conflicting. This study was undertaken to further investigate this association. Our objective was to evaluate the association between adverse pregnancy outcomes and maternal factor V Leiden genotype by meta-analysis. Inclusion criteria were: (a) cohort or case control design; (b) outcomes clearly defined as one of the following: first or second/ third trimester miscarriage or intrauterine death, preeclampsia, fetal growth retardation, or placental abruption; (c) both the case and control mothers tested for the factor V Leiden mutation; (d) sufficient data for calculation of an odds ratio. Both fixed and random effect models were used to pool results and heterogeneity and publication bias were checked. For first trimester fetal loss, the pooled odds ratio was heterogeneous (p=0.06) and no dose-response curve could be found. For second/third trimester fetal loss, there was a consistent and graded increase in risk: the odds ratio was 2.4 (95% CI 1.1-5.2) for isolated (non-recurrent) third trimester fetal loss, rising to 10.7 (95% CI 4.0-28.5) for those with 2 or more second/third trimester fetal losses. Factor V Leiden is associated with a 2.9 fold (95% CI 2.0-4.3) increased risk of severe preeclampsia, and a 4.8 fold (95% CI 2.4-9.4) increased risk of fetal growth retardation. These results support factor V Leiden testing for women with recurrent fetal loss in the second/third trimester. Women with only 1 event may also warrant testing if the fetal loss occurred in the third trimester. Conversely, in those women known to have the factor V Leiden mutation, monitoring for adverse pregnancy outcomes is warranted; whether this means increased vigilance or anti-coagulant prophylaxis is still contentious.

Abruptio Placentae↗
PubMed2004

Which test to detect microalbuminuria in diabetic patients? A systematic review.

BACKGROUND: Current guidelines suggest general practitioners should screen their diabetic patients for microalbuminuria. There is a range of possible tests. We looked for studies that compared a timed urine sample (the gold standard) with a random spot sample. METHOD: Systematic review and meta analysis of studies comparing albumin to creatinine ratio (ACR) on a random specimen to albumin excretion rate from an overnight or 24 hour timed sample. Studies were identified using Medline and EMBASE to June 2003. Studies were pooled using diagnostic odds ratios and were checked for heterogeneity. RESULTS: Ten studies covering 1470 patients were included. Use of the ACR in screening 100 diabetic patients would miss only two out of the 20 patients who would be expected to have microalbuminuria, while there would be 13 false positives. A timed specimen would be required to clarify the diagnosis for 31 patients. DISCUSSION: The marginal benefit of using a timed urine collection over a spot ACR to detect microalbuminuria in the screening of diabetic patients is small, and not worth the cost and inconvenience of collecting a timed sample.

Albuminuria↗
PubMed2003

Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study.

UNLABELLED: With the rise of molecular and genetic epidemiology, molecular association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the association of the vitamin D receptor (VDR) gene polymorphisms and BMD. We also highlight methodological issues that need to be resolved. INTRODUCTION: With the rise of molecular and genetic epidemiology, molecular association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the association of vitamin D receptor (VDR) gene polymorphisms and BMD/osteoporosis and highlights methodological issues. MATERIALS AND METHODS: Studies published from 1994 to 2001 were identified through Medline using PubMed software. The reference lists of the articles retrieved were also reviewed. Where eligible papers had insufficient information, we contacted authors by mail (up to three mailings) for additional information. Any observational study, which tested the association between VDR BsmI genotypes and either BMD or osteoporosis at the femoral neck or spine in adult women, was included in the review. Data were extracted independently by two reviewers (AT and JA) using a standardized data extraction form. RESULTS: The B allele was significantly associated with BMD at the spine; it seemed to follow a recessive model, with the BB genotype having lower BMD than Bb/bb genotypes at baseline, which led to greater bone mineral loss over time. Highlighted methodological lessons included the need to check Hardy-Weinberg equilibrium and the importance of exploring heterogeneity, pooling data in a manner that is sensitive to genetic models, and avoiding multiple comparisons. CONCLUSION: With the proliferation of molecular association studies, there will be an increased need to quantify the magnitude of the risk associated with genetic polymorphisms. This will likely entail meta-analytic methods, and this meta-analysis highlights some of the methodological issues that will need to be resolved.

Adult↗
PubMed2003

Does this patient have pulmonary embolism?

CONTEXT: Experienced clinicians' gestalt is useful in estimating the pretest probability for pulmonary embolism and is complementary to diagnostic testing, such as lung scanning. However, it is unclear whether recently developed clinical prediction rules, using explicit features of clinical examination, are comparable with clinicians' gestalt. If so, clinical prediction rules would be powerful tools because they could be used by less-experienced health care professionals to simplify the diagnosis of pulmonary embolism. Recent studies have shown that the combination of a low pretest probability (using a clinical prediction rule) and a normal result of a D-dimer test reliably excludes pulmonary embolism without the need for further testing. OBJECTIVE: To evaluate and demonstrate the accuracy of pretest probability assessment for pulmonary embolism using clinical gestalt vs clinical prediction rules. DATA SOURCES: The MEDLINE database was searched for relevant articles published between 1966 and March 2003. Bibliographies of pertinent articles also were scanned for suitable articles. STUDY SELECTION: To be included in the analysis, studies were required to have consecutive, unselected patients enrolled; participating physicians in the studies, blinded to the results of diagnostic testing, had to estimate pretest probability of pulmonary embolism; and validated diagnostic methods had to be used to confirm or exclude pulmonary embolism. DATA EXTRACTION: Three reviewers independently scanned titles and abstracts for inclusion of studies. An initial MEDLINE search identified 1709 studies, of which 16 involving 8306 patients were included in the final analysis. DATA SYNTHESIS: A clinical gestalt strategy was used in 7 studies, and in the low, moderate, and high pretest categories, the rates of pulmonary embolism ranged from 8% to 19%, 26% to 47%, and 46% to 91%, respectively. Clinical prediction rules were used in 10 studies, and 3% to 28%, 16% to 46%, and 38% to 98% in the low, moderate, and high pretest probability groups, respectively, had pulmonary embolism. CONCLUSIONS: The clinical gestalt of experienced clinicians and the clinical prediction rules used by physicians of varying experience have shown similar accuracy in discriminating among patients who have a low, moderate, or high pretest probability of pulmonary embolism. We advocate the use of a clinical prediction rule because it has shown to be accurate and can be used by less-experienced clinicians.

Adult↗
PubMed2003

Case-control study of cleft lip or palate after maternal use of topical corticosteroids during pregnancy.

A case-control survey of 48 children with nonsyndromic cleft lip or palate showed a significant increase in prevalence of maternal use of topical corticosteroid preparations in the first trimester of pregnancy, compared to 58 controls born in the same hospital; the odds ratio was 13.154, 95% confidence interval 1.67-586, P = 0.0049 on Fisher's exact two-tail test. The results were statistically significant although the wide confidence interval reflected the small sample size. Although older epidemiological studies have not detected any association between systemic corticosteroid treatment and the combined incidence of all congenital malformations, experimental studies over several decades have shown that maternal corticosteroid exposure in several species of animals is specifically associated with oral clefts. This association has been confirmed by more specific case-control surveys where the cases were children with cleft lip or palate and the exposure was maternal systemic corticosteroid treatment in the first trimester. Only one previous survey also analyzed topical corticosteroids, and it demonstrated an increased odds ratio for cleft lip or palate. A national survey of children with cleft palate will be necessary to evaluate the results of this pilot study.

Administration, Topical↗
PubMed2003

Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology.

Meta-analyses of population-based molecular association studies have become increasingly common over the last 10 years, but little attention has been paid to methodology. In addition to the traditional considerations pertinent to any meta-analysis, there are genetic issues particular to molecular association studies: checking Hardy-Weinberg equilibrium, handling data from more than two groups while avoiding multiple comparisons, and pooling data in a way that is sensitive to genetic models. We systematically reviewed all meta-analyses of molecular association studies identified via MEDLINE. Of a total of 37 studies, eight (22%) described the search terms. Nineteen (51%) did not state inclusion or exclusion criteria. Heterogeneity was assessed in 28 (76%), but only 7 of 37 (19%) studies checked for publication bias. Nine (24%) studies assessed the goodness-of-fit of Hardy-Weinberg equilibrium, and eight (22%) gave any biological rationale to justify the choice of genetic model used for pooling. There is a need for greater communication between epidemiologists and geneticists to develop methods appropriate to this area.

Data Interpretation, Statistical↗
PubMed2002

Estimating the contribution of individual risk factors to disease in a person with more than one risk factor.

Various measures have been proposed to express the excess risk of an outcome attributable to one particular risk factor, such as attributable risk and risk fraction. However, there is sometimes a need, both in epidemiological studies and in awarding compensation in legal cases, to simultaneously consider the contribution of several risk factors to a disease outcome, when a biological model is not available. We propose a method that allocates the proportional contribution of several risk factors to a disease outcome, based on the weighted contribution of the risk fraction for each risk factor. We demonstrate the use of this method using figures for renal cell carcinoma, and discuss the caveats in using this method for epidemiologic studies, and in awarding compensation in legal cases.

Asbestos↗