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Michael J Mugavero,
Margaret May,
Heather J Ribaudo,
Roy M Gulick,
Sharon A Riddler,
Richard Haubrich,
Sonia Napravnik,
Sophie Abgrall,
Andrew Phillips, Ross Harris, [......],
Antonella D'Arminio Monforte,
Jodie L Guest,
Colette Smith,
Javier Murillas,
Juan Berenguer,
Christoph Wyen,
Pere Domingo,
Mari M Kitahata,
Jonathan A C Sterne,
Michael S Saag
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ABSTRACT: The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites.
Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/mL) at 24 and 48 weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by third drug [abacavir (ABC), efavirenz (EFV), and lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios (OR) for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death.
Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR = 0.53, 95% confidence interval: 0.36 to 0.79) and ART-CC (0.46, 0.37 to 0.57). Virologic superiority of EFV (vs. ABC) seemed comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% confidence interval: 0.54 to 1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs: 0.87, 0.45 to 1.69).
Between ART regimen virologic efficacy of third drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials seem generalizable to the routine care setting of ART-CC clinical cohorts.
JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2011; 58(3):253-60. · 4.43 Impact Factor
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ABSTRACT: We systematically reviewed and meta-analyzed literature examining associations of vitamin D (dietary intake, circulating 25-hydroxy-vitamin-D (25(OH)D), and 1,25-dihydroxy-vitamin-D (1,25(OH)(2)D) concentrations) with prostate cancer.
We searched over 24,000 papers from seven electronic databases (to October 2010) for exposures related to vitamin D. We conducted dose-response random-effects meta-analyses pooling the log odds ratio (OR) and 95% confidence intervals (CI) per change in natural units of each exposure. The I(2) statistic quantified between-study variation due to heterogeneity.
Twenty-five papers were included. In prospective studies, the OR per 1,000 IU increase in dietary intake was 1.14 (6 studies; CI: 0.99, 1.31; I (2) = 0%) for total prostate cancer and 0.93 (3 studies; 0.63, 1.39; I (2) = 25%) for aggressive prostate cancer. Five case-control studies examined dietary intake, but there was a high degree of inconsistency between studies (I (2) = 49%). The OR per 10 ng/mL increase in 25(OH)D was 1.04 (14 studies; 0.99, 1.10; I (2) = 0%) for total prostate cancer and 0.98 (6 studies; 0.84, 1.15; I (2) = 32%) for aggressive prostate cancer. The OR per 10 pg/mL increase in 1,25(OH)(2)D was 1.00 (7 studies; 0.87, 1.14; I (2) = 41%) for total prostate cancer and 0.86 (2 studies; 0.72, 1.02; I (2) = 0%) for aggressive prostate cancer.
Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression.
Cancer Causes and Control 03/2011; 22(3):319-40. · 2.88 Impact Factor
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Simon M Collin,
Chris Metcalfe,
Helga Refsum,
Sarah J Lewis,
Luisa Zuccolo,
George Davey Smith,
Lina Chen, Ross Harris,
Michael Davis,
Gemma Marsden, [......],
Kaare Harald Bønaa,
Ottar Nygård,
Per Magne Ueland,
Maria V Grau,
John A Baron,
Jenny L Donovan,
David E Neal,
Freddie C Hamdy,
A David Smith,
Richard M Martin
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ABSTRACT: Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B(12), and related metabolites were associated with prostate cancer risk.
Matched case-control study nested within the U.K. population-based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen-detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B(12) (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B(12), and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review.
In the ProtecT study, increased B(12) and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B(12) odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); P(trend) = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); P(trend) = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B(12) levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B(12); P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02].
Vitamin B(12) and (in cohort studies) folate were associated with increased prostate cancer risk.
Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations.
Cancer Epidemiology Biomarkers & Prevention 06/2010; 19(6):1632-42. · 4.12 Impact Factor
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David M Moore, Ross Harris,
Viviane Lima,
Bob Hogg,
Margaret May,
Benita Yip,
Amy Justice,
Amanda Mocroft,
Peter Reiss,
Fiona Lampe, [......],
Luigia Elzi,
Michael J Mugavero,
Antonella D'Arminio Monforte,
Caroline Sabin,
Daniel Podzamczer,
Gerd Fätkenheuer,
Schlomo Staszewski,
John Gill,
Jonathan A C Sterne,
and the Antiretroviral Therapy Cohort Collaboration (ART-CC
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ABSTRACT: Background: Achieving virologic suppression is a clear therapeutic goal for patients receiving combination antiretroviral therapy (cART). However, the effects of immunologic responses, whether measured as CD4 count changes from baseline or CD4 counts at follow-up, in patients with virologic suppression, have not been clearly established.
Methods: Treatment-naive individuals aged ≥16 years, who initiated cART between 1998 and 2005 in participating cohorts of the ART Cohort Collaboration and achieved viral load ≤400 copies per milliliter 6 months after cART initiation, were included. We used Cox models to examine associations of CD4 change from baseline to 6 months, and absolute CD4 counts at 6 months, with subsequent rates of mortality and AIDS. Analyses were stratified by baseline CD4 count.
Results: Among 23,679 eligible participants, the median increase in CD4 count at 6 months, and the implications of these increases for subsequent mortality and AIDS, varied with baseline CD4 count. Mortality hazard ratios for increases of 0-50 cells per microliter, compared with >100 cells per microliter, were 1.87 (95% confidence interval: 1.28 to 2.73), 1.60 (1.13 to 2.28), 0.98 (0.58 to 1.65) and 1.24 (0.70 to 2.18) in participants with baseline CD4 cell count <50, 50-199, 200-349 and ≥350 cells per microliter, respectively. In contrast, hazard ratios for mortality or AIDS associated with absolute CD4 cell counts at 6 months were similar across all but the highest baseline CD4 cell count strata.
Conclusion: It is not possible to derive thresholds for change in CD4 count that define an adequate immunologic response in individuals receiving cART. Absolute CD4 counts at 6 months are a more useful measure of immunologic response and subsequent prognosis.
JAIDS Journal of Acquired Immune Deficiency Syndromes 10/2009; 52(3):357-363. · 4.43 Impact Factor
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Amanda Mocroft,
Jonathan A C Sterne,
Matthias Egger,
Margaret May,
Sophie Grabar,
Hansjakob Furrer,
Caroline Sabin,
Gerd Fatkenheuer,
Amy Justice,
Peter Reiss,
Antonella d'Arminio Monforte,
John Gill,
Robert Hogg,
Fabrice Bonnet,
Mari Kitahata,
Schlomo Staszewski,
Jordi Casabona, Ross Harris,
Michael Saag
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ABSTRACT: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy.
We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a "rare ADEs" category.
During a median follow-up period of 43 months (interquartile range, 19-70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin's lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55-9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76-3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08-2.00]).
In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.
Clinical Infectious Diseases 04/2009; 48(8):1138-51. · 9.15 Impact Factor
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ABSTRACT: To estimate and compare associations of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) with incident diabetes.
ALT and GGT were studied as determinants of diabetes in the British Women's Heart and Health Study, a cohort of 4,286 women 60-79 years old (median follow-up 7.3 years). A systematic review and a meta-analysis of 21 prospective, population-based studies of ultrasonography, which diagnosed nonalcoholic fatty liver disease (NAFLD), ALT, and GGT as determinants of diabetes, were conducted, and associations of ALT and GGT with diabetes were compared.
Ultrasonography-diagnosed NAFLD was associated with more than a doubling in the risk of incident diabetes (three studies). ALT and GGT both predicted diabetes. The fully adjusted hazard ratio (HR) for diabetes per increase in one unit of logged ALT was 1.83 (95% CI 1.57-2.14, I(2) = 8%) and for GGT was 1.92 (1.66-2.21, I(2) = 55%). To directly compare ALT and GGT as determinants of diabetes, the fully adjusted risk of diabetes in the top versus bottom fourth of the ALT and GGT distributions was estimated using data from studies that included results for both markers. For ALT, the HR was 2.02 (1.59-2.58, I(2) = 27%), and for GGT the HR was 2.94 (1.98-3.88, I(2) = 20%), suggesting that GGT may be a better predictor (P = 0.05).
Findings are consistent with the role of liver fat in diabetes pathogenesis. GGT may be a better diabetes predictor than ALT, but additional studies with directly determined liver fat content, ALT, and GGT are needed to confirm this finding.
Diabetes care 02/2009; 32(4):741-50. · 8.09 Impact Factor
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ABSTRACT: Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1–6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta-analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) IGF-I; 10 (923) IGF-II; 3 (485) IGFBP-1; 5 (577) IGFBP-2; 29 (6,541) IGFBP-3 and 11 (3,545) IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide were: IGF-I, OR = 1.21 (1.07, 1.36); IGF-II, OR = 1.17 (0.93, 1.47); IGFBP-1, OR = 1.21 (0.62, 2.33); IGFBP-2, OR = 1.18 (0.90, 1.54); IGFBP-3, OR = 0.88 (0.79, 0.98); IGFI:IGFBP-3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I2 > 75%), partly explained by study design: the magnitude of associations was smaller in prospective vs. retrospective studies, and for IGFBP-3, the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease. Our meta-analysis confirms that raised circulating lGF-I is positively associated with prostate cancer risk. Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer risk. © 2008 Wiley-Liss, Inc.
International Journal of Cancer 12/2008; 124(10):2416 - 2429. · 5.44 Impact Factor
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Michael J Mugavero,
Margaret May, Ross Harris,
Michael S Saag,
Dominique Costagliola,
Matthias Egger,
Andrew Phillips,
Huldrych F Günthard,
Francois Dabis,
Robert Hogg,
Frank de Wolf,
Gerd Fatkenheuer,
M John Gill,
Amy Justice,
Antonella D'Arminio Monforte,
Fiona Lampe,
Jose M Miró,
Schlomo Staszewski,
Jonathan A C Sterne
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ABSTRACT: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART.
Observational cohort study of patients initiating ART between January 2000 and December 2005.
The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States.
A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone.
Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes).
Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48).
Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.
AIDS (London, England) 12/2008; 22(18):2481-92. · 4.91 Impact Factor
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ABSTRACT: Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta-analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) IGF-I; 10 (923) IGF-II; 3 (485) IGFBP-1; 5 (577) IGFBP-2; 29 (6,541) IGFBP-3 and 11 (3,545) IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide were: IGF-I, OR = 1.21 (1.07, 1.36); IGF-II, OR = 1.17 (0.93, 1.47); IGFBP-1, OR = 1.21 (0.62, 2.33); IGFBP-2, OR = 1.18 (0.90, 1.54); IGFBP-3, OR = 0.88 (0.79, 0.98); IGFI:IGFBP-3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I(2) > 75%), partly explained by study design: the magnitude of associations was smaller in prospective vs. retrospective studies, and for IGFBP-3, the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease. Our meta-analysis confirms that raised circulating lGF-I is positively associated with prostate cancer risk. Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer risk.
International Journal of Cancer 12/2008; 124(10):2416-29. · 5.44 Impact Factor
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ABSTRACT: Leukoplakia is an asymptomatic, potentially malignant change in the oral mucosa. Previous studies have reported that smoking and betel quid chewing are associated with increased risk of leukoplakia; few studies have reported on these associations in populations where betel quid does not contain tobacco. We conducted a case-control study nested in a cross-sectional study in Papua New Guinea and a systematic review of studies that included chewers of betel quid without tobacco. Our study recruited 1,670 adults. We recorded betel quid chewing and smoking. The prevalence of leukoplakia was 11.7%. In the nested case-control study of 197 cases and 1,282 controls, current betel chewing was associated with increased risk of leukoplakia with an adjusted odds ratio for current chewers of 3.8 (95% CI 1.7, 8.4) and in the heaviest chewers of 4.1 (95% CI 1.8, 9.1) compared to non-chewers. Current smoking was associated with an increased risk of leukoplakia with an adjusted odds ratio for current smokers of 6.4 (95% CI 4.1, 9.9) and amongst heaviest smokers of 9.8 (95% CI 5.9, 16.4) compared to non-smokers. The systematic review identified 5 studies examining risk of leukoplakia associated with betel quid chewing in populations where betel quid did not contain tobacco and that controlled for smoking. In studies that adjusted for smoking, the combined random effect odds ratio was 7.9 (95% CI 4.3, 14.6) in betel quid chewers. The results of this study and systematic review of similar studies provide evidence of the role of betel quid not containing tobacco and leukoplakia.
International Journal of Cancer 11/2008; 123(8):1871-6. · 5.44 Impact Factor
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Luisa Zuccolo, Ross Harris,
David Gunnell,
Steven Oliver,
Jane Athene Lane,
Michael Davis,
Jenny Donovan,
David Neal,
Freddie Hamdy,
Rebecca Beynon,
Jelena Savovic,
Richard Michael Martin
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ABSTRACT: Height, a marker of childhood environmental exposures, is positively associated with prostate cancer risk, perhaps through the insulin-like growth factor system. We investigated the relationship of prostate cancer with height and its components (leg and trunk length) in a nested case-control study and with height in a dose-response meta-analysis.
We nested a case-control study within a population-based randomized controlled trial evaluating treatments for localized prostate cancer in British men ages 50 to 69 years, including 1,357 cases detected through prostate-specific antigen testing and 7,990 controls (matched on age, general practice, assessment date). Nine bibliographic databases were searched systematically for studies on the height-prostate cancer association that were pooled in a meta-analysis.
Based on the nested case-control, the odds ratio (OR) of prostate-specific antigen-detected prostate cancer per 10 cm increase in height was 1.06 [95% confidence interval (95% CI): 0.97-1.16; p(trend) = 0.2]. There was stronger evidence of an association of height with high-grade prostate cancer (OR: 1.23; 95% CI: 1.06-1.43), mainly due to the leg component, but not with low-grade disease (OR: 0.99; 95% CI: 0.90-1.10). In general, associations with leg or trunk length were similar. A meta-analysis of 58 studies found evidence that height is positively associated with prostate cancer (random-effects OR per 10 cm: 1.06; 95% CI: 1.03-1.09), with a stronger effect for prospective studies of more advanced/aggressive cancers (random-effects OR: 1.12; 95% CI: 1.05-1.19).
These data indicate a limited role for childhood environmental exposures-as indexed by adult height-on prostate cancer incidence, while suggesting a greater role for progression, through mechanisms requiring further investigation.
Cancer Epidemiology Biomarkers & Prevention 10/2008; 17(9):2325-36. · 4.12 Impact Factor
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ABSTRACT: metacum provides cumulative pooled estimates and confidence limits obtained from fixed or random effects meta-analysis and plots the cumulative pooled estimates in the style of Lau et al. (1992).
09/2008;
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Annals of internal medicine 09/2008; 149(3):219. · 16.73 Impact Factor
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ABSTRACT: We investigated the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) with cancer risk.
We examined the associations of CRP and IL-6 with incident cancer in two prospective cohorts, the British Women's Heart and Health Study (4,286 women aged 60-80) and the Caerphilly Cohort (2,398 men aged 45-59) using Cox regression and pooled our findings with previous prospective studies' in fixed and random effects meta-analyses.
CRP and IL-6 were associated with some incident cancers in our cohorts, but the numbers of cancer cases were small. In our meta-analyses elevated CRP was associated with an increased overall risk of cancer (random effects estimate (RE): 1.10, 95% CI: 1.02, 1.18) and lung cancer (RE: 1.32, 95% CI: 1.08, 1.61). Its associations with colorectal (RE: 1.09, 95% CI: 0.98, 1.21) and breast cancer risks (RE: 1.10, 95% CI: 0.97, 1.26) were weaker. CRP appeared unrelated to prostate cancer risk (RE: 1.00 0.88, 1.13). IL-6 was associated with increased lung and breast cancer risks and decreased prostate cancer risk, and was unrelated to colorectal cancer risk.
Our findings suggest an etiological role for CRP and IL-6 in some cancers. Further large prospective and genetic studies would help to better understand this role.
Cancer Causes and Control 09/2008; 20(1):15-26. · 2.88 Impact Factor
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ABSTRACT: To investigate the association of gamma-glutamyltransferase (GGT) with incident CHD and stroke [corrected] GGT [corrected] is a marker of alcohol intake but may also reflect oxidative stress and nonalcoholic fatty liver disease. Alanine aminotransferase (ALT) is the enzyme most closely associated with liver fat content.
Associations of GGT and ALT with incident CHD, stroke, and a combined outcome of CHD or stroke were examined in the British Women's Heart and Health study (n=2961), and a meta-analysis of population based studies examining these associations was performed. In pooled analyses of fully adjusted results of 10 prospective studies, a change of 1 U/L of GGT was associated with a HR=1.20 (95% CI: 1.02, 1.40) for CHD; a HR=1.54 (95% CI: 1.20, 2.00) for stroke; and HR=1.34 (95% CI: 1.22, 1.48) for CHD or stroke. Heterogeneity was substantially decreased when 2 studies in Asian populations were excluded. In a subgroup of nondrinkers results were similar to the main analysis. Meta analyses of the only 2 studies that examined the association of ALT with incident cardiovascular events found a HR=1.18, 95% CI: 0.99, 1.41) for CHD and a HR=1.10 (95% CI: 0.89, 1.36) for CHD or stroke (combined).
GGT is associated with incident vascular events independently of alcohol intake. The mechanisms underlying this association remain unclear and require future study.
Arteriosclerosis Thrombosis and Vascular Biology 01/2008; 27(12):2729-35. · 6.37 Impact Factor
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ABSTRACT: Article is available online at http://www.stata-journal.com/sjpdf.html?articlenum=sbe24_2
These routines provide facilities to conduct meta-analyses of data from more than one study and to graph the results. Either binary (event) or continuous data from two groups may be combined using the metan command. Additionally, intervention effect estimates with corresponding standard errors or confidence intervals may be meta-analysed. Recently added facilities include by() processing and an update to Stata 9 graphics. This is an updated version of metan as published in STB-44, authored by Michael J Bradburn, Jonathan J Deeks, Douglas G Altman. The package includes a command to produce funnel plots to assess small study effects, and L'Abbe plots to examine whether the assumption of a common odds ratio, risk ratio or risk difference is reasonable. Also included is the metannt program for binary data, which displays estimated intervention effects in terms of the absolute reduction in risk and number needed to treat. A description of available Stata meta-analysis commands may be found at http://www.stata.com/support/faqs/stat/meta.html.
Stata Journal 01/2007; 8(1):3-28. · 2.22 Impact Factor
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ABSTRACT: Evidence from case-control studies suggests that increasing dietary folate intake is associated with a reduced risk of breast cancer. However, large cohort studies have found no such association, and animal studies suggest that folate supplementation may promote tumorigenesis. We conducted a meta-analysis to summarize the available evidence from observational studies on this issue and a meta-analysis of the association between a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate metabolism, and breast cancer risk.
We searched Medline and ISI Web of Knowledge databases for relevant studies that were published through May 31, 2006. We used random-effects analysis to calculate odds ratios (ORs) for case-control studies or relative risks (RRs) for cohort studies for a 100-microg/d increase in folate intake. Unadjusted odds ratios were calculated for the studies of MTHFR genotype based on published genotype frequencies.
A total of 13 case-control studies and nine cohort studies were included in the meta-analysis of folate intake and breast cancer risk. We found a summary OR of 0.91 (95% confidence interval [CI] = 0.87 to 0.96) from the case-control studies and a summary RR of 0.99 (95% CI = 0.98 to 1.01) from the cohort studies for a 100-microg/d increase in folate intake. We found evidence that the case-control studies may have suffered from substantial publication bias. The case-control and cohort studies may have been subject to measurement error, confounding, and possibly spurious associations arising from subgroup analyses; in addition, the case-control studies were potentially subject to recall bias and publication bias. Seventeen studies were included in the meta-analysis of MTHFR C677T genotype and breast cancer risk. We found no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes (OR = 1.05, 95% CI = 0.88 to 1.25), and there was no evidence of an interaction between folate intake and MTHFR genotype on breast cancer risk.
A lack of dietary folate intake is not associated with the risk of breast cancer.
CancerSpectrum Knowledge Environment 12/2006; 98(22):1607-22. · 14.07 Impact Factor
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Michael Mugavero,
Margaret May, Ross Harris,
Michael Saag,
Dominique Costagliola,
Matthias Egger,
Andrew Phillips,
Huldrych Günthard,
Francois Dabis,
Robert Hogg,
Frank de Wolf,
Gerd Fatkenheuer,
M John Gill,
Amy Justice,
Antonella d'Arminio Monforte,
Fiona Lampe,
Jose Miró,
Schlomo Staszewski,
Jonathan Sterne
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ABSTRACT: OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-na? patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between January 2000 and December 2005. SETTING: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. STUDY PARTICIPANTS: A total of 13 546 antiretroviral-na? HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). RESULTS: Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). CONCLUSION: Among antiretroviral-na? patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.
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Jonathan Sterne,
Margaret May,
Dominique Costagliola,
Frank de Wolf,
Andrew Phillips, Ross Harris,
Michele Jönsson Funk,
Ronald Geskus,
John Gill,
François Dabis, [......],
Amy Justice,
Bruno Ledergerber,
Gerd Fätkenheuer,
Robert Hogg,
Antonella d'Arminio Monforte,
Michael Saag,
Colette Smith,
Schlomo Staszewski,
Matthias Egger,
Stephen Cole
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ABSTRACT: BACKGROUND: The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies. METHODS: We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for inclusion if they had started combination antiretroviral therapy (while AIDS-free, with a CD4 cell count less than 550 cells per microL, and with no history of injecting drug use) on or after Jan 1, 1998. We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989-95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups. We compared the effect of deferred initiation of combination therapy with immediate initiation on rates of AIDS and death, and on death alone, in adjacent CD4 cell count ranges of width 100 cells per microL. FINDINGS: Data were obtained for 21 247 patients who were followed up during the era before the introduction of combination therapy and 24 444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251-350 cells per microL was associated with higher rates of AIDS and death than starting therapy in the range 351-450 cells per microL (hazard ratio [HR] 1.28, 95% CI 1.04-1.57). The adverse effect of deferring treatment increased with decreasing CD4 cell count threshold. Deferred initiation of combination therapy was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR 1.13, 0.80-1.60, for deferred initiation of treatment at CD4 cell count 251-350 cells per microL compared with initiation at 351-450 cells per microL). INTERPRETATION: Our results suggest that 350 cells per microL should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.
