An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized CYP2C8 inhibitors that may cause other clinically important drug-drug interactions. Cases of rhabdomyolysis using cerivastatin (n=72) were compared with controls using atorvastatin (n=287) between 1998–2001. The use of clopidogrel (OR 29.6; 95% CI, 6.1–143) was strongly associated with rhabdomyolysis. In a replication effort that used the FDA Adverse Event Reporting System (AERS), clopidogrel was used more commonly by rhabdomyolysis cases using cerivastatin (17%) than by rhabdomyolysis cases using atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in-vitro findings suggest that clopidogrel may cause clinically important, dose dependent, drug-drug interactions with other medications metabolized by CYP2C8.
rhabdomyolysis; statins; clopidogrel; adverse drug reaction; drug-drug interaction prediction; 2-oxo-clopidogrel; acyl glucuronide
To test whether angiotensin-converting enzyme inhibitor use is associated with decreased risk of community-acquired pneumonia in older adults.
We analyzed data from a nested case-control study of community-dwelling, immunocompetent adults aged 65–94 within an integrated healthcare delivery system. Cases of ambulatory and hospitalized pneumonia from 2000–2003 were identified from International Classification of Disease, version 9, codes and validated using medical record review. Controls were matched to cases by age, sex and calendar year. Using health plan pharmacy data, we defined current use as filling ≥ 2 prescriptions during the 180 days prior to the case's diagnosis date. We calculated standardized doses per day using World Health Organization defined daily doses. Multivariable conditional logistic regression estimated adjusted odds ratios (ORs) for pneumonia in relation to angiotensin-converting enzyme inhibitor use, adjusting for comorbidity, functional and cognitive status, and other covariates from medical record review and pharmacy data.
Current use of angiotensin-converting enzyme inhibitors was seen in 23% (242/1039) of cases and 21% (433/2022) of controls. Lisinopril accounted for 95% of prescriptions. The OR for pneumonia comparing current use to no current use was 0.99 (95% confidence interval [CI] 0.83–1.19). The OR for use of more than 2 standardized daily doses per day was 1.39 (95% CI 0.93–2.06) compared to no current use.
Angiotensin-converting enzyme inhibitor use is not associated with reduced pneumonia risk in community-dwelling older adults.
pneumonia; angiotensin-converting enzyme inhibitors; case-control studies; antihypertensive agents
Detection of meningococcal carriers is key to understanding the epidemiology of Neisseria meningitidis, yet no gold standard has been established. Here, we directly compare two methods for collecting pharyngeal swabs to identify meningococcal carriers.
We conducted cross-sectional surveys of schoolchildren at multiple sites in Africa to compare swabbing the posterior pharynx behind the uvula (U) to swabbing the posterior pharynx behind the uvula plus one tonsil (T). Swabs were cultured immediately and analyzed using molecular methods.
One thousand and six paired swab samples collected from schoolchildren in four countries were analyzed. Prevalence of meningococcal carriage was 6.9% (95% CI: 5.4-8.6%) based on the results from both swabs, but the observed prevalence was lower based on one swab type alone. Prevalence based on the T swab or the U swab alone was similar (5.2% (95% CI: 3.8-6.7%) versus 4.9% (95% CI: 3.6-6.4%) respectively (p=0.6)). The concordance between the two methods was 96.3% and the kappa was 0.61 (95% CI: 0.50-0.73), indicating good agreement.
These two commonly used methods for collecting pharyngeal swabs provide consistent estimates of the prevalence of carriage, but both methods misclassified carriers to some degree, leading to underestimates of the prevalence.
Dietary phosphorus consumption has risen steadily in the United States. Oral phosphorus loading alters key regulatory hormones and impairs vascular endothelial function which may lead to an increase in left ventricular mass (LVM). We investigated the association of dietary phosphorus with LVM in 4,494 participants from the Multi-Ethnic Study of Atherosclerosis, a community-based study of individuals free of known cardiovascular disease. The intake of dietary phosphorus was estimated using a 120-item food frequency questionnaire and the LVM was measured using magnetic resonance imaging. Regression models were used to determine associations of estimated dietary phosphorus with LVM and left ventricular hypertrophy (LVH). Mean estimated dietary phosphorus intake was 1,167 mg/day in men and 1,017 mg/day in women. After adjustment for demographics, dietary sodium, total calories, lifestyle factors, comorbidities, and established LVH risk factors, each quintile increase in the estimated dietary phosphate intake was associated with an estimated 1.1 gram greater LVM. The highest gender-specific dietary phosphorus quintile was associated with an estimated 6.1 gram greater LVM compared to the lowest quintile. Higher dietary phosphorus intake was associated with greater odds of LVH among women, but not men. These associations require confirmation in other studies.
Phosphorus; phosphate; diet; consumption; left ventricular mass; left ventricular hypertrophy
The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancers.
Examine the association between screening colonoscopy and incident late-stage colorectal cancer (CRC) risk.
Nested case-control study.
Four U.S. health plans
Average-risk adults with ≥5 years of enrollment in one of the health plans (n=1,039). Cases were 55–85 years old on their diagnosis date (reference date) of stage ≥IIB (late-stage) CRC during 2006–2008. We selected 1–2 controls for each case, matched on birth year, gender, health plan, and prior enrollment duration.
Receipt of CRC screening between 3 months and up to 10 years before the reference date, ascertained through medical record audits. We compared cases and controls on receipt of screening colonoscopy or sigmoidoscopy using conditional logistic regressions that accounted for health history, socioeconomic status and other screening exposures.
In analyses restricted to 471 eligible cases and their matched controls (n=509), 13 cases (2.8%) and 46 controls (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.30 (95% confidence interval [CI]: 0.15–0.59) for any late-stage CRC, 0.37 (CI: 0.16–0.82) for right colon cancers, and 0.26 (CI: 0.06–1.11) for left-sided colon/rectum cancers. Ninety-two cases (19.5%) and 173 controls (34.0%) underwent screening sigmoidoscopy, corresponding to an AOR of 0.51 (CI: 0.36–0.71) overall, 0.80 (CI: 0.52–1.25) for right colon late-stage cancers, and 0.26 (CI: 0.14–0.49) for left colon/rectum cancers.
The small number of screening colonoscopies affected the precision of our estimates.
Screening with colonoscopy in average-risk persons was associated with reduced risk of diagnosis with incident late-stage CRC in both the right colon and left colon/rectum. For sigmoidoscopy, this association was observed for left-sided CRC, but the association for right colon late-stage cancer was not statistically significant.
Primary Funding Source
National Cancer Institute of the National Institutes of Health.
Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (Ptrend < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years.
endometrial neoplasms; parity; reproductive history
Diabetes is the leading cause of kidney disease in the developed world. Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies.
To define temporal changes in DKD prevalence in the United States.
Design, Setting, and Participants
Cross-sectional analyses of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988–1994 (N = 15 073), NHANES 1999–2004 (N = 13 045), and NHANES 2005–2008 (N=9588). Participants with diabetes were defined by levels of hemoglobin A1c of 6.5% or greater, use of glucose-lowering medications, or both (n = 1431 in NHANES III; n = 1443 in NHANES 1999–2004; n = 1280 in NHANES 2005–2008).
Main Outcome Measures
Diabetic kidney disease was defined as diabetes with albuminuria (ratio of urine albumin to creatinine >30 mg/g), impaired glomerular filtration rate (<60 mL/min/1.73 m2 estimated using the Chronic Kidney Disease Epidemiology Collaboration formula), or both. Prevalence of albuminuria was adjusted to estimate persistent albuminuria.
The prevalence of DKD in the US population was 2.2% (95% confidence interval [CI], 1.8%–2.6%) in NHANES III, 2.8% (95% CI, 2.4%–3.1%) in NHANES 1999–2004, and 3.3% (95% CI, 2.8%–3.7%) in NHANES 2005–2008 (P<.001 for trend). The prevalence of DKD increased in direct proportion to the prevalence of diabetes, without a change in the prevalence of DKD among those with diabetes. Among persons with diabetes, use of glucose-lowering medications increased from 56.2% (95% CI, 52.1%–60.4%) in NHANES III to 74.2% (95% CI, 70.4%–78.0%) in NHANES 2005–2008 (P<.001); use of renin-angiotensin-aldosterone system inhibitors increased from 11.2% (95% CI, 9.0%–13.4%) to 40.6% (95% CI, 37.2%–43.9%), respectively (P<.001); the prevalence of impaired glomerular filtration rate increased from 14.9% (95% CI, 12.1%–17.8%) to 17.7% (95% CI, 15.2%–20.2%), respectively (P=.03); and the prevalence of albuminuria decreased from 27.3% (95% CI, 22.0%–32.7%) to 23.7% (95% CI, 19.3%–28.0%), respectively, but this was not statistically significant (P=.07).
Prevalence of DKD in the United States increased from 1988 to 2008 in proportion to the prevalence of diabetes. Among persons with diabetes, prevalence of DKD was stable despite increased use of glucose-lowering medications and renin-angiotensin-aldosterone system inhibitors.
MF59-adjuvanted trivalent influenza vaccine (Novartis Vaccines and Diagnostics, Siena, Italy) has been shown to be more effective than nonadjuvanted vaccine in the elderly population. Here we present results from a large-scale, observational, noninterventional, prospective postlicensure study that evaluated the safety of MF59-adjuvanted vaccine in elderly subjects aged 65 years or more. The study was performed in 5 northern Italian health districts during the 2006–2007, 2007–2008, and 2008–2009 influenza seasons. The choice of vaccine—either adjuvanted vaccine or a nonadjuvanted influenza vaccine—was determined by individual providers on the basis of local influenza vaccination policy. Hospitalizations for potential adverse events of special interest (AESIs) were identified from hospital databases and then reviewed against recognized case definitions to identify confirmed cases of AESI. Cumulative incidences were calculated for AESIs in predefined biologically plausible time windows, as well as in a 6-month window following vaccination. During the 3-year study period, 170,988 vaccine doses were administered to a total of 107,661 persons. Despite the large study size, cases of AESI resulting in hospitalization were rare, and risks of AESI were similar in both the MF59-adjuvanted and nonadjuvanted vaccination groups. In conclusion, similar safety profiles were observed for both nonadjuvanted and MF59-adjuvanted seasonal influenza vaccines in elderly recipients.
adjuvants; elderly; influenza; influenza vaccine; MF59; vaccines; vaccine safety
Many carcinogens in tobacco smoke cause DNA damage, and some of that damage can be mitigated by the actions of DNA repair enzymes. In a case-control study nested within the Beta-Carotene and Retinol Efficacy Trial, a randomized chemoprevention trial in current and former heavy smokers, we examined whether lung cancer risk was associated with variation in 26 base excision repair, mismatch repair, and homologous recombination repair genes. Analyses were limited to Caucasians (744 cases, 1477 controls), and logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for individual SNPs and common haplotypes, with adjustment for matching factors. Lung cancer associations were observed (p<0.05) with SNPs in MSH5 (rs3131379, rs707938), MSH2 (rs2303428), UNG (rs246079), and PCNA (rs25406). MSH5 rs3131379 is a documented lung cancer susceptibility locus in complete linkage disequilibrium with rs3117582 in BAT3, and we observed associations similar in magnitude to those in prior studies (per A allele OR 1.37, 95% CI 1.13-1.65). UNG was associated with lung cancer risk at the gene level (p=0.02), and the A allele of rs246079 was associated with an increased risk (per A allele OR 1.15, 95% CI1.01-1.31). We observed stronger associations with UNG rs246079 among individuals who carried the risk genotypes (AG/AA) for MSH5 rs3131379 (pinteraction= 0.038). Our results provide additional evidence to suggest that the MSH5/BAT3 locus is associated with increased lung cancer risk among smokers, and that associations with other SNPs may vary depending upon MSH5/BAT3 genotype. Future studies to examine this possibility are warranted.
Lung cancer; base excision repair; mismatch repair; homologous recombination repair; DNA repair; genetic polymorphism
We review uses of electronic healthcare data algorithms, measures of their accuracy, and reasons for prioritizing one measure of accuracy over another.
Study design and setting
We use real studies to illustrate the variety of uses of automated healthcare data in epidemiologic and health services research. Hypothetical examples show the impact of different types of misclassification when algorithms are used to ascertain exposure and outcome.
High algorithm sensitivity is important for reducing the costs and burdens associated with the use of a more accurate measurement tool, for enhancing study inclusiveness, and for ascertaining common exposures. High specificity is important for classifying outcomes. High positive predictive value is important for identifying a cohort of persons with a condition of interest but that need not be representative of or include everyone with that condition. Finally, a high negative predictive value is important for reducing the likelihood that study subjects have an exclusionary condition.
Epidemiologists must often prioritize one measure of accuracy over another when generating an algorithm for use in their study. We recommend researchers publish all tested algorithms—including those without acceptable accuracy levels—to help future studies refine and apply algorithms that are well-suited to their objectives.
algorithms; bias; databases; factual; epidemiology; medical records systems; computerized; misclassification
The duration of protection conferred by prophylactic human papillomavirus (HPV) L1 virus-like particle vaccines is a critical determinant of their public health impact. A feature of vaccines that confer long-term immunity is their ability to induce immune memory.
We evaluated antibody responses against HPV types 6, 11, 16 and 18 following administration of the quadrivalent HPV-6/11/16/18 vaccine to women who had previously received a monovalent HPV-16 vaccine.
As part of an extended follow-up study conducted between 2006 and 2009 in Seattle, Washington, we administered the quadrivalent HPV-6/11/16/18 vaccine to 52 women (19 vaccine and 33 placebo recipients) who had participated in a monovalent HPV-16 vaccine trial 8.5 years earlier. Serum samples were tested for anti-HPV antibodies using competitive Luminex immunoassay.
Following administration of the first dose of the quadrivalent HPV-6/11/16/18 vaccine, the anti-HPV-16 geometric mean titer among monovalent HPV-16 vaccine recipients (GMT = 5024.0 milli-Merck units per milliliter [mMU/mL]; 95% confidence interval [CI]: 2710.1, 9313.6 mMU/mL) substantially exceeded that among the placebo recipients (GMT = 136.1; 95% CI: 78.5, 235.8 mMU/mL; p < 0.01) and their own highest anti-HPV-16 response observed during the original trial (GMT at month 7 of the original trial = 1552.7 mMU/mL; 95% CI: 1072.6, 2247.7 mMU/mL; p < 0.01).
The findings suggest that the administration of the three-dose regimen of the monovalent HPV-16 vaccine had produced memory lymphocytes, characterized by a heightened immune response following administration of the quadrivalent HPV-6/11/16/18 vaccine that effectively served as an antigen challenge.
Human papillomavirus type 16; Vaccines; Immune memory
Bacterial vaginosis (BV) recurs frequently after metronidazole treatment. This randomized, single-blinded clinical trial (RCT) evaluated the efficacy of topical application of 62% ethyl alcohol in emollient gel (gel) to the penis by male partners of women diagnosed with BV for preventing post-treatment BV recurrence.
Among 587 Kenyan women presenting with vulvovaginal symptoms, 236 had BV (vaginal Gram stain Nugent score ≥ 7), of whom 223 (94.3%) agreed, along with their partners, to be randomized: 115 to the intervention and 108 to the control arm. In the intervention arm, male partners agreed to apply gel each morning, and before and after sexual intercourse. All couples received counseling, condoms, and syndromic treatment of STI symptoms. Follow-up visits were scheduled 1 week, 1 month, and 2 months post-enrollment, with vaginal Gram stains at every visit and culture for H2O2-producing lactobacilli at the 2 month visit. The primary outcome was time to diagnosis of BV during follow-up.
In the primary intent-to-treat analysis, diagnosis of BV was significantly more frequent in the intervention arm (Hazard ratio 1.44, 95% CI 1.01-2.04). After adjustment for baseline covariates, the hazard ratio was 1.39 (95% CI 0.98-1.99). At the 2 month visit, prevalences of any vaginal lactobacilli or of H2O2-producing lactobacilli did not differ appreciably in the two study arms (p=0.81, and 0.32 respectively).
Daily use of the 62% ethyl alcohol gel by men before and after sex significantly increased persistence or early recurrence of BV in their partners through two months after metronidazole treatment. However, no difference was observed in prevalences of vaginal lactobacilli within this same period.
Bacterial vaginosis; recurrence; male factor; Kenya; microbicide
While laboratory data suggest that antidepressants may promote mammary tumor growth, there has been little research investigating whether antidepressant use after breast cancer diagnosis is associated with the risk of breast cancer recurrence.
We conducted a retrospective cohort study within Group Health, an integrated healthcare delivery system in Washington state. Women diagnosed with a first primary invasive, stage I, IIA, or IIB, unilateral breast carcinoma between 1990–1994 (aged ≥65 years) and 1996–1999 (aged ≥18 years) were eligible for the study (N=1306). Recurrence within 5-years of diagnosis was ascertained by medical chart review. We used the pharmacy database to identify antidepressant dispensings from Group Health pharmacies. We used multiple Cox regression to estimate the hazard ratio for recurrence and breast cancer mortality, comparing users and non-users antidepressant medications. Results for recurrence were examined separately in users and non-users of tamoxifen.
We did not observe an association between antidepressant use after breast cancer diagnosis and the risk of recurrence either in general (hazard ratio for any antidepressant use: 0.8; 95% confidence interval: 0.5 to 1.4) or for specific types of antidepressant medication. Risk of death from breast cancer did not differ between non-users and users of antidepressants.
The results of this study suggest that women who use antidepressants after breast cancer diagnosis do not have an increased risk of recurrence or mortality.
antidepressant medications; breast cancer; cancer epidemiology; pharmacoepidemiology; recurrence
The daily administered dose of progestin in continuous-combined estrogen-progestin therapy is provided to counteract the proliferative effect of estrogen on the postmenopausal endometrium. However, there remains some uncertainty as to whether use of such a combined regimen, over the long-term, is associated with an altered risk of endometrial cancer. We pooled data from four population-based case-control studies of endometrial cancer in western Washington State. Cases, ages 45–74, were diagnosed between 1985 and 2005. Using logistic regression with adjustment for confounding factors, women who had exclusively used continuous-combined estrogen-progestin therapy (90 endometrial cancer cases, 227 controls) were compared to women who had never used any type of hormone therapy (774 cases, 1116 controls). Associations with duration and recency of use were evaluated overall and within strata defined by body mass index. Long-term use of continuous-combined estrogen-progestin therapy (≥10 years) was associated with a reduced risk of endometrial cancer (OR=0.37, 95% CI: 0.21–0.66). This association was most pronounced in women with a body mass index ≥30 kg/m2 (OR=0.19, 95% CI: 0.05–0.68). Associations did not differ according to recency of use. These results suggest that long duration of use of continuous-combined estrogen-progestin therapy is associated with a reduced risk of endometrial cancer risk.
endometrial cancer; hormone therapy; estrogen; progestin; body mass index
The value of neoadjuvant chemotherapy (NAC) for the treatment of advanced ovarian cancer has yet to be determined. While NAC may facilitate and simplify complete cytoreduction and reduce the risk of surgery, the delay of surgery related to NAC needs to be balanced against any potential benefit.
Surveillance, Epidemiology and End-Results (SEER) data linked to Medicare claims were used to identify 6844 women with treated stage III/IV epithelial ovarian cancer (1995–2005). Patients were classified by primary treatment (surgery (PDS) or chemotherapy), and the primary chemotherapy group was characterized as having NAC or palliative chemotherapy (PC) based on whether there was documentation that surgery was recommended. We compared surgical complications and survival between the groups.
4827 (71%) of women were treated with PDS, 958 received NAC (14%) and 1059 (15%) had PC. Only 577 (60%) of women with NAC underwent surgery and they had fewer ostomies (8.5% vs. 19.2%, p<0.001) and fewer infections, gastrointestinal and pulmonary complications than PDS (all p<0.01). Comparing NAC to PDS there was a 16% increase in the risk of death at 2 years (RR 1.16, 95%CI 1.01–1.34) for women with stage III disease and a 15% reduction in the risk for women with stage IV disease (RR 0.85, 95%CI 0.73–0.99).
NAC followed by surgery was associated with fewer surgical complications than PDS. The direction and magnitude of the difference in survival between women receiving NAC and those receiving PDS differed according to the stage of disease and follow up time.
rhabdomyolysis; statins; adverse drug reaction; natural language processing
To examine whether use of opioids or benzodiazepines is associated with increased risk of community-acquired pneumonia in older adults.
Population-based case-control study.
An integrated healthcare delivery system.
Community-dwelling, immunocompetent adults aged 65–94 from 2000–2003. Presumptive pneumonia cases were identified from health plan automated data and validated through medical record review. Two matched controls were selected for each case with pneumonia, matched on age, sex and calendar year.
Information about opioid and benzodiazepine use came from computerized pharmacy data. Information on covariates including comorbid illnesses and functional and cognitive status came from medical record review and electronic health data.
1039 validated cases of pneumonia and 2022 matched controls were identified. 13.9% (144/1039) of cases and 8.0% (161/2022) of controls used prescription opioids (adjusted OR 1.38, 95% CI 1.08 to 1.76, vs. nonuse). Risk was highest for opioids categorized as immunosuppressive based on immunologic studies (OR 1.88 [95% CI, 1.26 to 1.79] vs. nonuse), while for non-immunosuppressive opioids the OR was 1.23 (95% CI, 0.89 to 1.69). Risk was highest in the first 14 days of use (OR 3.24 [95% CI, 1.64 to 6.39] vs. nonuse). For long-acting opioids, the OR was 3.43 [95% CI, 1.44 to 8.21] vs. nonuse, while for short-acting opioids it was 1.27 [95% CI, 0.98 to 1.64]. No increased risk was seen for current benzodiazepine use (OR 1.08, 95% CI 0.80 to 1.47, compared to nonuse).
Use of opioids but not benzodiazepines was associated with increased pneumonia risk. The differences in risk seen for different opioid regimens warrant further study.
pneumonia; epidemiology; opioids; adverse drug effects; benzodiazepines
Patients and physicians strongly endorse the importance of preventive or periodic health examinations (PHEs). However, the extent to which PHEs contribute to the delivery of cancer screening is uncertain.
In a retrospective cohort study, we determined the association between receipt of a PHE and cancer testing in a population-based sample of enrollees in a Washington State health plan who were aged 52 to 78 years and eligible for colorectal, breast, or prostate cancer screening in 2002–2003 (N = 64 288). Outcomes included completion of any colorectal cancer testing (fecal occult blood testing, sigmoidoscopy, colonoscopy, or barium enema), screening mammography, and prostate-specific antigen testing.
More than half (52.4%) of the enrollees received a PHE during the study period. After adjusting for demographics, comorbidity, number of outpatient visits, and historical preventive service use before January 1, 2002, receipt of a PHE was significantly associated with completion of colorectal cancer testing (incidence difference, 40.4% [95% confidence interval (CI), 39.4%–41.3%]; relative incidence, 3.47 [95% CI, 3.34–3.59]), screening mammography [incidence difference, 14.2% [95% CI, 12.7%–15.7%]; relative incidence, 1.23 [95% CI, 1.20–1.25]), and prostate-specific antigen testing (incidence difference, 39.4% [95% CI, 38.3%–40.5%]; relative incidence, 3.06 [95% CI, 2.95–3.18]).
Among managed care enrollees eligible for cancer screening, PHE receipt is associated with completion of colorectal, breast, and prostate cancer testing. In similar populations, the PHE may serve as a clinically important forum for the promotion of evidence-based colorectal cancer and breast cancer screening and of screening with relatively less empirical support, such as prostate cancer screening.
Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk.
We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of four population-based endometrial cancer case-control studies of women 45–74 years of age (1,712 cases and 2,134 controls) during 1985–2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews.
Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14–0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree.
In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.
Exposure to estrogens increases the risk of endometrial cancer. Certain estrogen metabolites can form bulky DNA adducts, which are removed via nucleotide excision repair (NER), and the ability to perform this repair might be related to endometrial cancer risk.
We examined 64 tag- and functional SNPs in the NER genes ERCC1, ERCC2 (XPD), ERCC3 (XPB), ERCC4 (XPF), ERCC5 (XPG), LIG1, XPA, and XPC in a population-based case-control study in Washington State, with 783 endometrial cancer cases and 795 controls.
The presence of ERCC5 rs4150386 C, LIG1 rs3730865 C, XPA rs2808667 T, or XPC rs3731127 T alleles was associated with risk of endometrial cancer, with respective age-, county- and reference year-adjusted per-allele odds ratios (ORs) and 95% confidence intervals (CIs) of 0.68 (0.53–0.87, p=0.002), 1.46 (1.02–2.10, p=0.04), 0.71 (0.52–0.97, p=0.03) and 1.57 (1.13–2.17, p=0.007).
Certain ERCC5, LIG1, XPA and XPC genotypes might influence endometrial cancer risk.
Because of multiple redundancies in DNA repair pathways (and therefore a low prior probability), and the large number of associations examined, false positive findings are likely. Further characterization of the relation between variation in NER genes and endometrial cancer risk is warranted.
Endometrial cancer; nucleotide excision repair; ERCC5; LIG1; XPC
Although vaccination against influenza is recommended for elderly and high-risk patients in many countries, efficacy in the elderly has been suboptimal. The MF59 adjuvanted trivalent inactivated vaccine (ATIV) was developed to increase the immune response of elderly subjects to influenza vaccination, but its effectiveness has not yet been well documented. This prospective, observational study evaluated the relative effectiveness of ATIV versus nonadjuvanted trivalent inactivated vaccine (TIV) in individuals at least 65 years of age in Lombardy, northern Italy. Hospitalizations for influenza or pneumonia (International Classification of Diseases, Ninth Revision, Clinical Modification, codes 480–487) during the 2006–2007, 2007–2008, and 2008–2009 influenza seasons were identified from administrative databases. Stratified and regression analyses, including the propensity score to adjust for confounding, as well as generalized estimating equations to account for repeated vaccination, were used. Overall, 107,661 records were evaluated, contributing 170,988 person-seasons of observation. Since ATIV is preferentially recommended for more frail individuals, subjects vaccinated with ATIV were older and had more functional impairment and comorbidities. In the primary analysis, risk of hospitalization for influenza or pneumonia was 25% lower for ATIV relative to TIV (relative risk = 0.75, 95% confidence interval: 0.57, 0.98). To the extent that there is residual bias, ATIV is likely to be even more protective than this result suggests.
adjuvanted influenza vaccine; elderly; influenza; pneumonia
We sought to determine whether oral fluid can be used to assess serum human papillomavirus (HPV) antibody status by enrolling women who had received a prophylactic HPV-16 vaccine in a new follow-up study. After the prophylactic HPV-6/11/16/18 vaccine was licensed in the United States, we administered it to consenting participants. The sensitivity of oral fluid, treating serology as the gold standard, before and after administration of the quadrivalent vaccine was 49.6% (95% confidence interval [CI]: 42.0%–57.3%) and 100% (95% CI: 92.0%–100%), respectively. Oral fluid may have the potential to be used for monitoring of prophylactic HPV vaccines in the future.
Human papillomavirus; Prophylactic vaccines; Antibodies; Oral fluid
Optimal care for most patients with advanced ovarian cancer generally includes both surgery and chemotherapy. Little is known about the proportion of women in the US who receive combination care or the sequence in which this care is delivered. This study evaluated patterns of care, frequency of completion of recommended therapy and factors associated with sequencing of therapy.
Using the Surveillance, Epidemiology and End-Results data we identified a cohort of 8211 women aged 65 and above with stage III/IV epithelial ovarian cancer diagnosed between 1995–2005. Receipt of chemotherapy or surgery was identified using Medicare claims. Logistic regression was used to evaluate factors associated with sequencing of treatment and the receipt of surgery.
3241 (39.1%) had surgery and at least 6 cycles of chemotherapy in either order. Surgery was performed initially in 4827 (58.8%) women and 3658/4827 (75.8%) had subsequent chemotherapy. 2017 (24.6%) had primary chemotherapy and 649/2017 (32.2%) of these women had subsequent surgery. Advanced age, African American race, stage IV disease, non-married status and increasing medical comorbidity were all associated with the failure to receive both surgery and at least 6 cycles of chemotherapy (all p<0.01).
The majority of women with advanced ovarian cancer in the Medicare population do not receive both combination therapy with surgery and at least 6 cycles of chemotherapy. A large proportion of women are receiving chemotherapy as primary treatment for advanced ovarian cancer, and the majority of these patients do not have cancer-directed surgery.
Ovarian Neoplasms; Aged; Guideline Adherence; Chemotherapy; Surgery
Administration of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), omega-3 fatty acids in fish oil, has been associated with improved patient outcomes in acute lung injury (ALI) when studied in a commercial enteral formula. However, fish oil has not been tested independently in ALI. We therefore sought to determine if enteral fish oil alone would reduce pulmonary and systemic inflammation in patients with ALI.
Phase II randomized controlled trial.
Four North American medical centers.
Mechanically ventilated patients with ALI ≥ 18 years of age.
Subjects were randomized to receive enteral fish oil (9.75g EPA and 6.75g DHA daily) or saline placebo for up to 14 days.
Measurements and Main Results
Bronchoalveolar lavage fluid (BALF) and blood were collected at baseline (day 0), day 4±1, and day 8±1. The primary endpoint was BALF interleukin (IL)-8 levels. Forty-one participants received fish oil and 49 received placebo. Enteral fish oil administration was associated with increased serum EPA concentration (p<0.0001). However, there was no significant difference in the change in BALF IL-8 from baseline to day 4 (p=0.37) or day 8 (p=0.55) between treatment arms. There were no appreciable improvements in other BALF or plasma biomarkers in the fish oil group compared to the control group. Similarly, organ failure score, ventilator-free days, ICU-free days, and 60-day mortality did not differ between the groups.
Fish oil did not reduce biomarkers of pulmonary or systemic inflammation in patients with ALI, and the results do not support the conduct of a larger clinical trial in this population with this agent. This experimental approach is feasible for proof of concept studies evaluating new treatments for ALI.
Acute lung injury; randomized controlled trial; eicosapentaenoic acid; docosahexaenoic acid; acute respiratory distress syndrome; fish oils