This paper provides an assessment of the associations that weight loss patterns during the first year of an intensive lifestyle intervention have with four year maintenance and health outcomes. Two components described patterns of weight change during the first year of intervention: one reflected the typical pattern of weight loss over the 12 months, but distinguished those who lost larger amounts across the monthly intervals from those who lost less. The second component reflected the weight change trajectory, and distinguished a pattern of initial weight loss followed by regain versus a more sustained pattern of weight loss 2,438 individuals aged 45–76 years with type 2 diabetes mellitus, who enrolled in the weight loss intervention of a randomized clinical trial, were assigned scores according to how their weight losses reflected these patterns. Relationships these scores had with weight losses and health outcomes (glycosolated hemoglobin – HbA1c; systolic blood pressure, HDL-cholesterol, and triglycerides) over four years were described. Both individuals who had larger month-to-month weight losses in year 1 and whose weight loss was more sustained during the first year had better maintenance of weight loss over four years, independent of characteristics traditionally linked to weight loss success (p<0.001). While relationships with year 4 weight loss were stronger, the pattern of larger monthly weight loss during year 1 was also independently predictive of year 4 levels of HbA1c, HDL-cholesterol, and systolic blood pressure.
weight loss; type 2 diabetes mellitus; principal components analysis
We examined malaria cases reported to Ontario’s public health surveillance systems from 1990 through 2009 to determine how temporal scale (longitudinal, seasonal), spatial scale (provincial, health unit), and demography (gender, age) contribute to Plasmodium infection in Ontario travellers. Our retrospective study included 4,551 confirmed cases of imported malaria reported throughout Ontario, with additional analysis at the local health unit level (i.e., Ottawa, Peel, and Toronto). During the 20-year period, Plasmodium vivax accounted for 50.6% of all cases, P. falciparum (38.6%), Plasmodium sp. (6.0%), P. ovale (3.1%), and P. malariae (1.8%). During the first ten years of the study (1990–1999), P. vivax (64% of all cases) was the dominant agent, followed by P. falciparum (28%); however, during the second ten years (2000–2009) the situation reversed and P. falciparum (55%) dominated, followed by P. vivax (30%). The prevalence of P. falciparum and P. vivax cases varied spatially (e.g., P. falciparum more prevalent in Toronto, P. vivax more prevalent in Peel), temporally (e.g. P. falciparum incidence increased during the 20-year study), and demographically (e.g. preponderance of male cases). Infection rates per 100,000 international travellers were estimated: rates of infection were 2× higher in males compared to females; rates associated with travel to Africa were 37× higher compared to travel to Asia and 126× higher compared to travel to the Americas; rates of infection were 2.3–3.5× higher in June and July compared to October through March; and rates of infection were highest in those 65–69 years old. Where exposure country was reported, 71% of P. falciparum cases reported exposure in Ghana or Nigeria and 63% of P. vivax cases reported exposure in India. Our study provides insights toward improving pre-travel programs for Ontarians visiting malaria-endemic regions and underscores the changing epidemiology of imported malaria in the province.
Menopausal hormone therapy (MHT) increases risk of coronary heart disease (CHD) in older women with elevated low-density lipoprotein (LDLC) levels. The endogenous estrogen receptor antagonist 27-hydroxycholesterol (27OHC) is correlated with LDLC levels and may block beneficial effects of estrogen on the cardiovascular system.
Methods and Results
We conducted a nested case-control study in the Women’s Health Initiative trials of 350 CHD cases and 813 matched controls to explore potential mediation by 27OHC of the dependence of the CHD risk elevation with MHT on LDLC. Baseline levels of 27OHC were not associated with CHD risk when LDLC was included in the multivariable models. The odds ratio for CHD associated with increased LDLC was 1.15 (95% confidence interval 1.08, 1.23) and was unchanged at 1.14 (1.07, 1.22) when 27OHC was added to the model. Baseline 27OHC did not interact with MHT on CHD risk (p = 0.81). In contrast, LDLC levels modified the effect of MHT on CHD risk (p for interaction = 0.02), and adding 27OHC did not affect this result. Using log scales the MHT effect on CHD increased linearly with increasing level of baseline LDLC, with a transition from no risk to increased risk at approximately 3.36 mmol/L (130 mg/dl).
27OHC does not independently increase risk of CHD, does not modify the increased risk of CHD due to MHT, and does not mediate the interaction of LDLC with MHT. Measuring blood lipids may aid in counseling individual women about initiating MHT and cardiovascular risk mitigation.
acute coronary syndrome; atherosclerosis; estrogen; low-density lipoprotein (LDL)-cholesterol; pathophysiology
To evaluate whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduce vasomotor symptoms (VMS, i.e., hot flashes or night sweats) in postmenopausal women.
We included 17,473 postmenopausal U.S. women, ages 50–79 at baseline who participated in the Women’s Health Initiative Dietary Modification (DM) trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations.
In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to dietary intervention vs. control arm was significantly (OR=1.14, 95%CI: 1.01–1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. Additionally, women with symptoms at baseline who lost ≥10 lbs (OR=1.23, 95%CI: 1.05–1.46) or lost ≥10% of their baseline body weight (OR=1.56, 95%CI: 1.21–2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared to women in the control arm who maintained weight, women who lost substantial weight (≥10%) as a part of the intervention (OR=1.89, 95%CI: 1.39–2.57), but not control arm (OR=1.40, 95%CI: 0.92–2.13), were significantly more likely to end VMS, though these two groups did not differ significantly from each other. Large weight loss (>22 lbs) but not dietary changes were related to elimination of moderate/severe VMS.
Weight loss as part of a healthy dietary modification may help to eliminate vasomotor symptoms among postmenopausal women.
Hot flashes; night sweats; vasomotor symptoms; weight; body mass; weight change; women
The Women’s Health Initiative Estrogen-alone Trial was stopped early after 7.1 years (mean) follow-up. Postintervention health outcomes have not been reported.
To examine health outcomes associated with randomization to conjugated equine estrogen (CEE) treatment in women with prior hysterectomy after 10.7 (mean) years follow-up through August 2009.
Design, Setting, and Participants
The intervention phase was a double-blind, placebo-controlled, randomized trial of CEE, 0.625 mg/day or placebo in 10,739 US postmenopausal women aged 50–79 years with prior hysterectomy. Follow-up continued after the planned trial completion date among 7645 (78%) surviving participants who provided written consent.
Main Outcome Measures
The primary outcomes were CHD and invasive breast cancer. A global index of risks and benefits included these 2 endpoints plus stroke, pulmonary embolism, colorectal cancer, hip fracture, and death.
Postintervention risks for women assigned to CEE vs. placebo were similar to the intervention period for CHD (annualized rates 0.64% in CEE vs. 0.67% in placebo; hazard ratio (HR)=0.97, 95% CI 0.75–1.25), breast cancer (0.26% vs. 0.34%; HR=0.75, 0.51–1.09), and total mortality (1.47% vs. 1.48%; HR=1.00, CI 0.84–1.18). Postintervention risks changed for stroke (0.36% vs. 0.41%; HR=0.89, 0.64–1.24), deep vein thrombosis (0.17% vs. 0.27%; HR=0.63, 0.41–0.98), and hip fracture (0.36% vs. 0.28%; HR=1.27, 0.88–1.82). Over the entire follow-up, lower breast cancer incidence in the CEE group persisted (0.27% vs. 0.35%; HR=0.77, 0.62–0.95). Health outcomes were more favorable for younger compared to older women for CHD (p for age-interaction=0.049), total MI (p-interaction=0.007), colorectal cancer (p-interaction=0.04), total mortality (p-interaction =0.04), and global index (p-interaction=0.009).
Among postmenopausal women with prior hysterectomy followed for 10.7 years, CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. A decreased risk of breast cancer persisted.
estrogen; coronary heart disease; breast cancer; stroke; pulmonary embolism; hip fracture; colorectal cancer; total mortality; Women’s Health Initiative
The purpose of this study was to evaluate clinical outcomes associated with the initiation of treatment for urgency-predominant incontinence in women diagnosed by a simple 3-item questionnaire.
We conducted a multicenter, double-blinded, 12-week randomized trial of pharmacologic therapy for urgency-predominant incontinence in ambulatory women diagnosed by the simple 3-item questionnaire. Participants (N = 645) were assigned randomly to fesoterodine therapy (4-8 mg daily) or placebo. Urinary incontinence was assessed with the use of voiding diaries; postvoid residual volume was measured after treatment.
After 12 weeks, women who had been assigned randomly to fesoterodine therapy reported 0.9 fewer urgency and 1.0 fewer total incontinence episodes/day, compared with placebo (P ≤ .001). Four serious adverse events occurred in each group, none of which was related to treatment. No participant had postvoid residual volume of ≥250 mL after treatment.
Among ambulatory women with urgency-predominant incontinence diagnosed with a simple 3-item questionnaire, pharmacologic therapy resulted in a moderate decrease in incontinence frequency without increasing significant urinary retention or serious adverse events, which provides support for a streamlined algorithm for diagnosis and treatment of female urgency-predominant incontinence.
antimuscarinic therapy; diagnostic algorithm; fesoterodine; urgency incontinence
High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels are influenced by both genes and the environment. Genome-wide association studies (GWAS) have identified ~100 common genetic variants associated with HDL-C, LDL-C, and/or TG levels, mostly in populations of European descent, but little is known about the modifiers of these associations. Here, we investigated whether GWAS-identified SNPs for lipid traits exhibited heterogeneity by sex in the Population Architecture using Genomics and Epidemiology (PAGE) study.
A sex-stratified meta-analysis was performed for 49 GWAS-identified SNPs for fasting HDL-C, LDL-C, and ln(TG) levels among adults self-identified as European American (25,013). Heterogeneity by sex was established when phet < 0.001. There was evidence for heterogeneity by sex for two SNPs for ln(TG) in the APOA1/C3/A4/A5/BUD13 gene cluster: rs28927680 (phet = 7.4x10-7) and rs3135506 (phet = 4.3x10-4), one SNP in PLTP for HDL levels (rs7679; phet = 9.9x10-4), and one in HMGCR for LDL levels (rs12654264; phet = 3.1x10-5). We replicated heterogeneity by sex in five of seventeen loci previously reported by genome-wide studies (binomial p = 0.0009). We also present results for other racial/ethnic groups in the supplementary materials, to provide a resource for future meta-analyses.
We provide further evidence for sex-specific effects of SNPs in the APOA1/C3/A4/A5/BUD13 gene cluster, PLTP, and HMGCR on fasting triglyceride levels in European Americans from the PAGE study. Our findings emphasize the need for considering context-specific effects when interpreting genetic associations emerging from GWAS, and also highlight the difficulties in replicating interaction effects across studies and across racial/ethnic groups.
Lipids; Genetics; Cardiovascular disease; Heterogeneity; Sex-specific effect; Association study
Background and Purpose
To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized APC resistance ratio, nAPCsr) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy (PHT).
Nested case-control study of 455 cases of ischemic stroke and 565 matched controls in the Women’s Health Initiative trials of PHT.
Baseline free TFPI was associated with ischemic stroke risk, OR (95% CI) per SD increase = 1.17 (1.01, 1.37, p=0.039, but baseline nAPCsr was not, OR per SD increase = 0.89 (0.75, 1.05), p=0.15. Baseline TFPI levels and nAPCsr did not modify the effect of PHT on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction p = 0.452 and 0.971 respectively). In subgroup analyses baseline nAPCsr was inversely associated with lacunar strokes, OR per SD increase = 0.74 (0.57, 0.96), p=0.025, and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes, p=0.008.
Pro-coagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to PHT.
Cerebrovascular Accident; Estrogen; Hemostasis; Menopause; Randomized Controlled Trials
The authors’ objective was to discern whether lifestyle or health-related factors were confounders, effect modifiers, or irrelevant with regard to understanding observational associations of serum 25-hydroxyvitamin D (25(OH)D) with colorectal and breast cancer. The authors conducted nested case-control studies of colorectal cancer (310 cases, 310 controls) and breast cancer (1,080 cases, 1,080 controls) in the Women’s Health Initiative Calcium and Vitamin D Clinical Trial (1994–2005). Case-control matching factors included age, latitude, race/ethnicity, and blood collection date. Serum 25(OH)D was assayed in baseline fasting blood. Conditional logistic regression was used to estimate odds ratios for each cancer by serum 25(OH)D concentration, comparing the relative effects of successively adding body mass index, physical activity, and other health and lifestyle characteristics particular to each cancer. In models with matching factors only, low (vs. high) serum 25(OH)D was associated with a colorectal cancer odds ratio of 2.72 (95% confidence interval (CI): 1.55, 4.77) and a breast cancer odds ratio of 1.33 (95% CI: 1.02, 1.72). In multivariate-adjusted models for colorectal cancer, the association strengthened (OR = 4.45, 95% CI: 1.96, 10.10). However, in multivariate-adjusted breast cancer models, associations were no longer significant (OR = 1.06, 95% CI: 0.78, 1.43). Adjusting for health and lifestyle characteristics has differential effects depending on the cancer site; when modeling such relations, investigators should take these factors into account.
breast neoplasms; colorectal neoplasms; 25-hydroxyvitamin D; postmenopausal women; randomized controlled trials
Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in bone mineral density (BMD) over 12 months. Overweight and obese adults with type 2 diabetes were randomly assigned to ILI or DSE. In a sub-study of BMD conducted at 5 of 16 clinical centers, hip, spine and whole body dual x-ray absorptiometry scans were obtained at baseline and one year later on 642 of 739 ILI and 632 of 740 DSE participants. At baseline, mean age was 58.4 years, and average body mass index was 35.2 kg/m2. Total hip BMD T-score was <−2.5 in 1% and <−1.0 in 8%. At one year, weight loss was greater in ILI than DSE (−8.6% versus −0.7%), and glycemic control and fitness were also improved. Bone loss over one year was greater in ILI at the total hip (−1.4% versus −0.4%; p<0.001) and femoral neck (−1.5% versus −0.8%; p=0.009), but change in BMD for the lumbar spine and whole body did not differ between groups. In ILI, bone loss at the total hip was independently associated with weight loss in men and women and with poorer glycemic control in men, but was not associated with changes in fitness. One year of an intensive lifestyle intervention in adults with type 2 diabetes, resulting in weight loss, was associated with a modest increase in hip bone loss despite improved fitness and glycemic control.
bone mineral density; weight loss; type 2 diabetes; obesity; glycemic control; physical fitness
Calcium and vitamin D may be inversely related to breast cancer risk, in part by affecting mammographic density. However, results from previous, mostly cross-sectional studies have been mixed, and there have been few randomized clinical trials of the effect of calcium and vitamin D supplementation on change in mammographic density.
We assessed the effect of one year of supplementation on mammographic density in 330 postmenopausal women enrolled in the Women’s Health Initiative Hormone Therapy (HT) and Calcium and Vitamin D (CaD) trials. Women were randomized to receive 1000 mg/day of elemental calcium carbonate plus 400 IU/day of vitamin D3 or placebo.
After approximately one year, mammographic density decreased 2% in the CaD supplementation group and increased 1% in the placebo group (ratio of means = 0.97; 95% confidence interval (CI) = 0.81–1.17). Results suggested potential interaction by HT use (P = 0.08). Among women randomized to HT placebo, the ratio of mean density comparing CaD supplementation and placebo groups was 0.82 (95%CI = 0.61–1.11) vs. 1.16 (95%CI = 0.92–1.45) in women randomized to active HT. In sensitivity analyses limited to women taking ≥80% of study supplements, ratios were 0.67 (95%CI = 0.41–1.07) in women not assigned to HT and 1.07 (95%CI = 0.79–1.47) women assigned to HT.
We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year.
Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study.
breast; calcium; clinical trial; mammography; vitamin D
The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes. A prospective cross-sectional study of 1000 households was implemented in 2005 to evaluate characteristics of the owned and unowned population of dogs and cats in Santa Clara County, California. The same population was previously studied 12 years earlier. During this time period, the county instituted in 1994 and then subsequently disestablished a municipal spay/neuter voucher program for cats. Dog intakes declined from 1992–2005, as they similarly did for an adjacent county (San Mateo). However, cat intakes declined significantly more in Santa Clara County than San Mateo, with an average annual decline of approximately 700 cats for the 12 year period. Time series analysis showed a greater than expected decline in the number of cats surrendered to shelters in Santa Clara County during the years the voucher program was in effect (1994–2005). The net savings to the county by reducing the number of cat shelter intakes was estimated at approximately $1.5 million. The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes.
Animal euthanasia; Epidemiology; Animal population groups; Population control; Population policy
Because arctic plant communities are highly vulnerable to climate change, shifts in their composition require rapid, accurate identifications, often for specimens that lack diagnostic floral characters. The present study examines the role that DNA barcoding can play in aiding floristic evaluations in the arctic by testing the effectiveness of the core plant barcode regions (rbcL, matK) and a supplemental ribosomal DNA (ITS2) marker for a well-studied flora near Churchill, Manitoba.
This investigation examined 900 specimens representing 312 of the 354 species of vascular plants known from Churchill. Sequencing success was high for rbcL: 95% for fresh specimens and 85% for herbarium samples (mean age 20 years). ITS2 worked equally well for the fresh and herbarium material (89% and 88%). However, sequencing success was lower for matK, despite two rounds of PCR amplification, which reflected less effective primer binding and sensitivity to the DNA degradation (76% of fresh, 45% of herbaria samples). A species was considered as taxonomically resolved if its members showed at least one diagnostic difference from any other taxon in the study and formed a monophyletic clade. The highest species resolution (69%) was obtained by combining information from all three genes. The joint sequence information for rbcL and matK distinguished 54% of 286 species, while rbcL and ITS2 distinguished 63% of 285 species. Discrimination of species within Salix, which constituted 8% of the flora, was particularly problematic. Despite incomplete resolution, the barcode results revealed 22 misidentified herbarium specimens, and enabled the identification of field specimens which were otherwise too immature to identify. Although seven cases of ITS2 paralogy were noted in the families Cyperaceae, Juncaceae and Juncaginaceae, this intergenic spacer played an important role in resolving congeneric plant species at Churchill.
Our results provided fast and cost-effective solution to create a comprehensive, effective DNA barcode reference library for a local flora.
Arctic; DNA barcoding; rbcL; matK; ITS2; Species resolution; Climate change; Biomonitoring
Gastrointestinal illnesses (GI) continue to pose a substantial burden in terms of morbidity and economic impact in Canada. We describe the epidemiology of reportable GI in Ontario by characterizing the incidence of each reportable GI, as well as associated demographics, clinical outcomes, seasonality, risk settings, and likely sources of infection.
Reports on laboratory confirmed cases of amebiasis, botulism, campylobacteriosis, cryptosporidiosis, cyclosporiasis, giardiasis, hepatitis A, listeriosis, paratyphoid fever, salmonellosis, shigellosis, typhoid fever, illness due to verotoxin-producing Escherichia coli (VTEC-illness), and yersiniosis, from January 1, 2007 to December 31, 2009 were obtained from Ontario’s passive reportable disease surveillance system. Cases were classified by history of relevant travel, association with outbreaks, and likely source of infection, obtained through follow-up of reported cases by local health authorities.
There were 29,897 GI reported by health authorities in Ontario from 2007 to 2009. The most frequently reported diseases were campylobacteriosis (10,916 cases or 36.5% of all GI illnesses) and salmonellosis (7,514 cases, 25.1%). Overall, 26.9% of GI cases reported travel outside of Ontario during the relevant incubation period. Children four years of age and younger had the highest incidence rate for most GI, and significantly more (54.8%, p<0.001) cases occurred among males than females. The most commonly reported sources of infections were food (54.2%), animals (19.8%), and contact with ill persons (16.9%). Private homes (45.5%) and food premises (29.7%) were the most commonly reported exposure settings. Domestic cases of campylobacteriosis, cryptosporidiosis, giardiasis, salmonellosis, and VTEC-illness showed seasonal patterns with incidence peaking in the summer months.
Reportable GI continues to be a burden in Ontario. Since more than one in four GI cases experienced in Ontario were acquired outside of the province, international travel is an important risk factor for most GI. Because private homes are the most commonly reported risk settings and the main suspect sources of infection are food, animal contact and ill persons, these findings support the continued need for public health food safety programs, public education on safe handling of food and animals, and proper hand hygiene practices.
Three clinical research projects are described that are relevant to pediatric hearing loss. The three projects fall into two distinct areas. The first area emphasizes clinical studies that track developmental outcomes in children with hearing loss; one project is specific to cochlear implants and the other to hearing aids. The second area addresses speech perception test development for very young children with hearing loss. Although these two lines of research are treated as separate areas, they begin to merge as new behavioral tests become useful in developing protocols for contemporary studies that address longitudinal follow-up of children with hearing loss.
Adaptive behavior; cochlear implants; development; hearing aids; pediatric hearing loss; speech perception
The food frequency questionnaire approach to dietary assessment is ubiquitous in nutritional epidemiology research. Food records and recalls provide approaches that may also be adaptable for use in large epidemiologic cohorts, if warranted by better measurement properties. The authors collected (2007–2009) a 4-day food record, three 24-hour dietary recalls, and a food frequency questionnaire from 450 postmenopausal women in the Women’s Health Initiative prospective cohort study (enrollment, 1994–1998), along with biomarkers of energy and protein consumption. Through comparison with biomarkers, the food record is shown to provide a stronger estimate of energy and protein than does the food frequency questionnaire, with 24-hour recalls mostly intermediate. Differences were smaller and nonsignificant for protein density. Food frequencies, records, and recalls were, respectively, able to “explain” 3.8%, 7.8%, and 2.8% of biomarker variation for energy; 8.4%, 22.6%, and 16.2% of biomarker variation for protein; and 6.5%, 11.0%, and 7.0% of biomarker variation for protein density. However, calibration equations that include body mass index, age, and ethnicity substantially improve these numbers to 41.7%, 44.7%, and 42.1% for energy; 20.3%, 32.7%, and 28.4% for protein; and 8.7%, 14.4%, and 10.4% for protein density. Calibration equations using any of the assessment procedures may yield suitable consumption estimates for epidemiologic study purposes.
bias (epidemiology); biological markers; diet; energy intake; epidemiologic methods; measurement error; nutrition assessment
Invasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada.
We retrieved information on confirmed IMD cases reported to Ontario’s reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70% and 80%, and assuming only direct protection (no herd effects).
A total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4% occurred in infants, of which 72.7% were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7% overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease.
Although rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone.
Invasive meningococcal disease; Neisseria meningitidis; Serogroup B; Epidemiology; Surveillance; Ontario; Canada
The safe lower limit of hematocrit or hemoglobin that should trigger a red blood cell (RBC) transfusion has not been defined. The objective of this study was to examine the physiological effects of anemia and compare the acute responses to transfusion in preterm infants who were transfused at higher or lower hematocrit thresholds.
We studied 41 preterm infants with birth weights 500-1300 g, who were enrolled in a clinical trial comparing high (“liberal”) and low (“restrictive”) hematocrit thresholds for transfusion. Measurements were performed before and after a packed RBC transfusion of 15 ml/kg, which was administered because the infant's hematocrit had fallen below the threshold defined by study protocol. Hemoglobin, hematocrit, red blood cell count, reticulocyte count, lactic acid, and erythropoietin were measured before and after transfusion using standard methods. Cardiac output was measured by echocardiography. Oxygen consumption was determined using indirect calorimetry. Systemic oxygen transport and fractional oxygen extraction were calculated.
Systemic oxygen transport rose in both groups following transfusion. Lactic acid was lower after transfusion in both groups. Oxygen consumption did not change significantly in either group. Cardiac output and fractional oxygen extraction fell after transfusion in the low hematocrit group only.
Our results demonstrate no acute physiological benefit of transfusion in the high hematocrit group. The fall in cardiac output with transfusion in the low hematocrit group shows that these infants had increased their cardiac output to maintain adequate tissue oxygen delivery in response to anemia and, therefore, may have benefitted from transfusion.
Neonatology; haematology; circulatory; physiology; clinical procedures
Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS).
We compared the risk of incident CVD events and all-cause mortality between four groups of women (total N=60,027): (1) No VMS at menopause onset and no VMS at WHI-OS enrollment (no VMS [referent group]); (2) VMS at menopause onset, but not at WHI-OS enrollment (early VMS); (3) VMS at both menopause onset and WHI-OS enrollment (persistent VMS [early and late]); and (4) VMS at WHI-OS enrollment, but not at menopause onset (late VMS).
For women with early VMS (N=24,753), compared to no VMS (N=18,799), hazard ratios (HRs) and 95% confidence intervals (CIs) in fully-adjusted models were: major CHD, 0.94 (0.84, 1.06); stroke, 0.83 (0.72, 0.96); total CVD, 0.89 (0.81, 0.97); and all-cause mortality, 0.92 (0.85, 0.99). For women with persistent VMS (N=15,084), there was no significant association with clinical events. For women with late VMS (N=1,391) compared to no VMS, HRs and 95% CIs were: major CHD, 1.32 (1.01, 1.71); stroke, 1.14 (0.82, 1.59); total CVD, 1.23 (1.00, 1.52); and all-cause mortality, 1.29 (1.08, 1.54).
Early VMS were not associated with increased CVD risk. Rather, early VMS were associated with decreased risk of stroke, total CVD events, and all-cause mortality. Late VMS were associated with increased CHD risk and all-cause mortality. The predictive value of VMS for clinical CVD events may vary with onset of VMS at different stages of menopause. Further research examining the mechanisms underlying these associations is needed. Future studies will also be necessary to investigate whether VMS that develop for the first time in the later postmenopausal years represent a pathophysiologic process distinct from classical perimenopausal VMS.
Vasomotor symptoms; Hot flashes; Cardiovascular disease; Women's health
In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 produced a large number of false-positive tests. We examined relationships between histopathologic diagnoses, false-positive test group, and participant and screening test characteristics.
The PLCO ovarian cancer screening arm included 39,105 women aged 55-74 years assigned to annual CA-125 and TVU. Histopathologic diagnoses from women with false-positive tests and subsequent surgery were reviewed in this analysis: all CA125+ (n=121); all CA125+/TVU+ (n=46); and a random sample of TVU+ (n=373). Demographic and ovarian cancer risk factor data were self-reported. Pathologic diagnoses were abstracted from surgical pathology reports. We compared participant characteristics and pathologic diagnoses by category of false-positive using Pearson χ2, Fisher's exact, or Wilcoxon-Mann-Whitney tests.
Women with a false-positive TVU were younger (P < 0.001), heavier (P < 0.001), and reported a higher frequency of prior hysterectomy (P < 0.001). Serous cystadenoma, the most common benign ovarian diagnosis, was more frequent among women with TVU+ compared to CA-125+ and CA-125+/TVU+ (P < 0.001). Benign non-ovarian findings were commonly associated with all false-positives, although more frequently with CA-125+ than TVU+ or CA-125+/TVU+ groups (P=0.019). Non-ovarian cancers were diagnosed most frequently among CA-125+ (P < 0.001).
False-positive ovarian cancer screening tests were associated with a range of histopathologic diagnoses, some of which may be related to patient and screening test characteristics. Further research into the predictors of false-positive ovarian cancer screening tests may aid efforts to reduce false-positive results.
Nutritional epidemiology cohort studies primarily use food frequency questionnaires (FFQs). In part because FFQs are more reliable for nutrient densities than for absolute nutrient consumption, reports from association studies typically present only nutrient density measures in relation to disease risk.
We used objective biomarkers to correct FFQ assessments for measurement error, and examined absolute energy and protein consumption in relation to cardiovascular disease incidence. FFQs and subsequent physician-adjudicated cardiovascular disease incidence were assessed for 80,370 postmenopausal women in the age range 50–79 years at enrollment in the comparison group of the Dietary Modification Trial or the prospective Observational Study in the Women’s Health Initiative. Urinary recovery biomarkers of energy and protein were obtained from a subsample of 544 women, with concurrent FFQ information.
Following biomarker correction, energy consumption was positively associated with coronary heart disease incidence (hazard ratio = 1.18 [95% confidence interval = 1.04–1.33], for 20% consumption increment) and protein density was inversely associated (0.85 [0.75–0.97]). The positive energy association appeared to be mediated by body fat accumulation. Ischemic stroke incidence was inversely associated with energy and protein consumption, but not with protein density.
A positive association between energy and coronary heart disease risk can be attributed to body mass accumulation. Ischemic stroke risk is inversely associated with energy and protein consumption, possibly due to correlations between consumption and physical activity.
To examine whether lower serum levels of serum 25-hydroxyvitamin (OH) D [25(OH)D] are associated with increased risk of developing type 2 diabetes.
RESEARCH DESIGN AND METHODS
A post hoc analysis of three nested case-control studies of fractures, colon cancer, and breast cancer that measured serum 25(OH)D levels in women participating in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline. Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication. We used inverse probability weighting to make the study population representative of the WHI population as a whole. Weighted logistic regression models compared 25(OH)D levels (divided into quartiles, clinical cut points [<50, 50–<75, ≥75 nmol/L], or as a continuous variable) using the distribution of control subjects and adjusted for multiple confounding factors.
Of 5,140 women (mean age 66 years) followed for an average of 7.3 years, 317 (6.2%) developed diabetes. Regardless of the cut points used or as a continuous variable, 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models. Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI, race/ethnicity, or randomization status in the Calcium Vitamin D trial.
Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women.
In the United States cancer as a whole is the second leading cause of death and a major burden to health care, thus the medical progress against cancer is a major public health goal. There are many individual studies to suggest that cancer treatment breakthroughs and early diagnosis have significantly improved the prognosis of cancer patients. To better understand the relationship between medical improvements and the survival experience for the patient population at large, it is useful to evaluate cancer survival trends on the population level, e.g., to find out when and how much the cancer survival rates changed. In this paper, we analyze the population-based grouped cancer survival data by incorporating joinpoints into the survival models. A joinpoint survival model facilitates the identification of trends with significant change points in cancer survival, when related to cancer treatments or interventions. The Bayesian Information Criterion is used to select the number of joinpoints. The performance of the joinpoint survival models is evaluated with respect to cancer prognosis, joinpoint locations, annual percent changes in death rates by year of diagnosis, and sample sizes through intensive simulation studies. The model is then applied to the grouped relative survival data for several major cancer sites from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute. The change points in the survival trends for several major cancer sites are identified and the potential driving forces behind such change points are discussed.
Annual percentage change; BIC; relative survival; joinpoint model; proportional hazards; SEER
Multiple-day diet records can be unsuitable for cohort studies because of high administrative and analytical costs. Costs could be reduced if a subsample of participants were analyzed in a nested case-control study. However, completed records are usually reviewed (“documented”) with participants to correct errors and omissions before analysis. The authors evaluated the suitability of using undocumented 3-day food records in 2 samples of women in a Northern California cohort study of breast cancer survivorship (2006–2009). One group of participants (n = 130) received an introduction to the food record at enrollment, while another (n = 70) received more comprehensive instruction. Food records were mailed to participants 6 months later for follow-up and were analyzed as received and after phone documentation. Error rates for adequate completion were high in the first group but substantially lower among persons receiving instruction; prevalences of missing data on serving size and incomplete food descriptions changed from 30% to 4% and from 32% to 6%, respectively (P < 0.0001). Correlations between nutrient intakes calculated from undocumented and documented records were 0.72–0.93 in the first group and were significantly stronger (0.84–0.99) among persons receiving instruction. Documentation had little effect on intraclass correlation coefficients across days, but training increased the coefficients for many nutrients. When participants receive proper instruction, undocumented food records can be satisfactory for large epidemiologic studies.
breast neoplasms; cohort studies; data collection; diet records; reproducibility of results