Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort

Objectives

Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women.

Study design

We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13–55 who delivered 1964–1976, with Israel’s National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1–4 (n = 19,703), adjusting for reproductive and demographic variables.

Results

Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HR_adj) = 0.62, 95 % confidence interval (CI) 0.54–0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HR_adj = 1.69, CI 1.39–2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HR_adj = 2.48, CI 1.22–5.03).

Conclusion

Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.

     

Candidate Molecular Pathway Genes Related to Appetite Regulatory Neural Network,Adipocyte Homeostasis and Obesity: Results from the CARDIA Study

Appetite regulatory neural network and adipocyte homeostasis molecular pathways are critical to long‐term weight maintenance. Associations between obesity‐related phenotypes and four genes in these pathways – leptin (LEP), leptin receptor (LEPR), neuropeptide Y2 receptor (NPY2R) and peptide YY (PYY) were examined in CARDIA Study participants (aged 18–30 at recruitment in 1985–6). Weight, BMI and waist circumference were measured at baseline and at years 2, 5, 7, 10, 15, and 20. Genotyping was conducted using tag SNPs characterising common genetic variations in these genes. Generalized estimating equation (GEE) models estimated associations between SNPs and repeated anthropometric measurements, controlling for sex and age. False discovery rate was used to adjust for multiple testing. In African‐Americans, SNPs across the LEP gene demonstrated significant overall associations with all obesity‐related phenotypes. The associations between LEP rs17151919 with weight tended to strengthen with time – the difference in weight associated with each additional minor allele increased from 2.6 kg at baseline to 4.8 kg at year 20 (SNP*time interaction p = 0.0193). NPY2R gene SNPs were associated with waist circumference among African‐American men (p = 0.0462). In Caucasians, LEP SNPs also tended to be associated with weight (p = 0.0471), and PYY rs11684664 was associated with obesity‐related phenotypes in women only (p = 0.010–0.026). Several LEP, and NPY2R and PYY SNPs were associated with obesity‐related phenotypes in young adults, particularly among African‐Americans.     

Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma

BACKGROUND: Despite their potential for increased morbidity, 75% to 90% of asthmatic children do not receive influenza vaccination. Live attenuated influenza vaccine (LAIV), a cold-adapted, temperature-sensitive, trivalent influenza vaccine, is approved for prevention of influenza in healthy children 5 to 19 years of age. LAIV has been studied in only a small number of children with asthma. METHODS: Children 6 to 17 years of age, with a clinical diagnosis of asthma, received a single dose of either intranasal CAIV-T (an investigational refrigerator-stable formulation of LAIV; n = 1114) or injectable trivalent inactivated influenza vaccine (TIV; n = 1115) in this randomized, open-label study during the 2002-2003 influenza season. Participants were followed up for culture-confirmed influenza illness, respiratory outcome, and safety. RESULTS: The incidence of community-acquired culture-confirmed influenza illness was 4.1% (CAIV-T) versus 6.2% (TIV), demonstrating a significantly greater relative efficacy of CAIV-T versus TIV of 34.7% (90% confidence interval [CI] 9.4%-53.2%; 95% CI = 3.9%-56.0%). There were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate findings, asthma symptom scores, or nighttime awakening scores. The incidence of runny nose/nasal congestion was higher for CAIV-T (66.2%) than TIV (52.5%) recipients. Approximately 70% of TIV recipients reported injection site reactions. CONCLUSIONS: CAIV-T was well tolerated in children and adolescents with asthma. There was no evidence of a significant increase in adverse pulmonary outcomes for CAIV-T compared with TIV. CAIV-T had a significantly greater relative efficacy of 35% compared with TIV in this high-risk population.     

Family history as a risk factor for stroke in young women

BACKGROUND: Family history of stroke (FHS) is associated with risk of stroke in middle-aged to elderly populations. However, few studies have examined this association in younger women or by stroke type. A population-based, case-control study was conducted to examine the association of FHS and risk of stroke in young women, and to determine whether the association is independent of other stroke risk factors. METHODS: Cases were women aged 18 to 44 years, with first, nonfatal ischemic (n =49) and hemorrhagic (n = 63) strokes in western Washington State in 1991 to 1995. Demographically similar community controls (n = 446) were identified through random-digit telephone dialing. Information on FHS in first-degree relatives (parents and siblings) and other risk factors was obtained through an interview. Person-years (P-Y) at risk of stroke for relatives of each subject were included in polytomous logistic regression models to adjust for family size. The analysis was conducted between 1999 and 2000. RESULTS: After adjustment for age and P-Y, FHS in first-degree relatives was significantly associated with an increased risk of hemorrhagic (odds ratio [OR]=2.6, 95% confidence interval [CI]=1.5-4.3) and ischemic stroke (OR=2.1, 95% CI=1.2-3.9). FHS remained associated with risk of hemorrhagic stroke (OR=2.4, 95% CI=1.4-4.1) and ischemic stroke (OR=1.8, 95%CI=0.9-3.5) after further adjustment for diabetes, hypertension, hypercholesterolemia, body mass index, physical activity, smoking, alcohol, and family history of myocardial infarction. Findings were similar when associations with parental and sibling FHS were examined separately. CONCLUSIONS: Family history of stroke is a risk factor for both hemorrhagic and ischemic strokes among young women.     

Local recurrence after low anterior resection using the EEATM stapling device

Fifty-five patients underwent curative stapled low anterior resection for rectal adenocarcinomas located 5 to 15 cm from the anal verge. Two patients (3.7 percent) died postoperatively. The mean follow-up for the remaining 53 patients was 40 months. Local recurrence was diagnosed in 17 patients (32 percent), in most (88 percent) within the first two years after surgery. Most local recurrences appeared in patients classified as Dukes' C1 and C2 but, surprisingly, no significant difference was found between rectal tumors of high and low location as regards recurrence. The high rate of recurrence in this series may be attributable to the large number of patients with advanced tumors, and poorly differentiated carcinoma, or both.     

The role of procalcitonin as a predictor of nosocomial sepsis in preterm infants

AIM: To assess the role of procalcitonin in detecting nosocomial sepsis in preterm infants, after the onset of clinical symptoms. SUBJECTS: 100 preterm infants, 24-36 wk of gestation, were followed from the age of 3 d until discharge. Procalcitonin and C-reactive protein (CRP) levels were measured within 3 d of sepsis workup events. RESULTS: 141 blood samples were drawn from 36 infants during 85 episodes of sepsis workup performed between 4 and 66 d of life. Of these episodes, 51 (60%) were not a result of documented sepsis and thereby served as the negative comparison group. Median procalcitonin levels were higher in the septic group compared with the non-septic group at the time of the sepsis workup (2.7 vs 0.5 ng/ml, p=0.003), at 1-24 h after the sepsis workup (4.6 vs 0.6 ng/ml, p=0.003), and at 25-48 h (6.9 vs 2.0 ng/ml, p=0.016). Using high cutoff levels, both procalcitonin (2.3 ng/ml) and CRP (30 mg/l) had high specificity and positive predictive value (97%, 91% and 96%, 87%, respectively) but low sensitivity (48% and 41%, respectively) to detect sepsis. Areas under the ROC curve for procalcitonin and CRP were 0.74 and 0.73, respectively. CONCLUSION: Procalcitonin >2.3 ng/ml or CRP >30 mg/l indicates a high likelihood for neonatal sepsis, and antibiotic therapy should be continued even in the presence of sterile cultures.