Nicotine dependence and biochemical exposure measures in the second trimester of pregnancy

Introduction: The Heaviness of Smoking Index (HSI) is validated to measure nicotine dependence in nonpregnant smokers, and in these smokers, mean salivary and serum cotinine levels are related by a ratio of 1.25. However, as nicotine metabolism increases during gestation, these findings may differ in pregnancy. We investigated the validity of HSI in pregnancy by comparing this with 3 biochemical measures; and in a search for a less-invasive cotinine measure in pregnancy, we also explored the relationship between mean blood and salivary cotinine levels. Methods: Cross-sectional analyses using baseline data from the Smoking, Nicotine, and Pregnancy Trial. Participants were 16–46 years old, 12–24 weeks gestation, smoked more than 5 cigarettes per day and had exhaled carbon monoxide (CO) readings of at least 8 ppm. Linear regression was used to examine correlations between HSI and blood cotinine, and salivary cotinine and exhaled CO. Correlation between blood and salivary cotinine was investigated using linear regression through the origin. Results: HSI scores were associated with blood cotinine (R2 = 0.20, n = 662, p < .001), salivary cotinine (R2 = 0.11, n = 967, p < .001), and exhaled CO (R2 = 0.13, n = 1,050, p < .001). Salivary and blood cotinine levels, taken simultaneously, were highly correlated (R2 = 0.91, n = 628, p < .001) and the saliva:blood level ratio was 1.01 (95% CI 0.99–1.04). Conclusions: Correlations between HSI and biochemical measures in pregnancy were comparable with those obtained outside pregnancy, suggesting that HSI has similar validity in pregnant smokers. Salivary and blood cotinine levels are roughly equivalent in pregnant smokers

A before-after implementation trial of smoking cessation guidelines in hospitalized veterans

Abstract Background Although most hospitalized smokers receive some form of cessation counseling during hospitalization, few receive outpatient cessation counseling and/or pharmacotherapy following discharge, which are key factors associated with long-term cessation. US Department of Veterans Affairs (VA) hospitals are challenged to find resources to implement and maintain the kind of high intensity cessation programs that have been shown to be effective in research studies. Few studies have applied the Chronic Care Model (CCM) to improve inpatient smoking cessation. Specific objectives The primary objective of this protocol is to determine the effect of a nurse-initiated intervention, which couples low-intensity inpatient counseling with sustained proactive telephone counseling, on smoking abstinence in hospitalized patients. Key secondary aims are to determine the impact of the intervention on staff nurses' attitudes toward providing smoking cessation counseling; to identify barriers and facilitators to implementation of smoking cessation guidelines in VA hospitals; and to determine the short-term cost-effectiveness of implementing the intervention. Design Pre-post study design in four VA hospitals Participants Hospitalized patients, aged 18 or older, who smoke at least one cigarette per day. Intervention The intervention will include: nurse training in delivery of bedside cessation counseling, electronic medical record tools (to streamline nursing assessment and documentation, to facilitate prescription of pharmacotherapy), computerized referral of motivated inpatients for proactive telephone counseling, and use of internal nursing facilitators to provide coaching to staff nurses practicing in non-critical care inpatient units. Outcomes The primary endpoint is seven-day point prevalence abstinence at six months following hospital admission and prolonged abstinence after a one-month grace period. To compare abstinence rates during the intervention and baseline periods, we will use random effects logistic regression models, which take the clustered nature of the data within nurses and hospitals into account. We will assess attitudes of staff nurses toward cessation counseling by questionnaire and will identify barriers and facilitators to implementation by using clinician focus groups. To determine the short-term incremental cost per quitter from the perspective of the VA health care system, we will calculate cessation-related costs incurred during the initial hospitalization and six-month follow-up period. Trial number NCT00816036http://deepblue.lib.umich.edu/bitstream/2027.42/112349/1/13012_2009_Article_190.pd

Transmission of X-linked Ovarian Cancer: Characterization and Implications

We recently reported evidence that a strong, BRCA-independent locus on the X-chromosome may contribute to ovarian cancer predisposition in families ascertained from the Familial Ovarian Cancer Registry (Buffalo, NY, USA). While it has been estimated that approximately 20% of all ovarian cancer cases are hereditary, it is possible that a significant proportion of cases previously believed to be sporadic may, in fact, be X-linked. Such X-linked disease has a distinct pattern; it implies that a father will necessarily pass a risk allele to each of his daughters, increasing the prevalence of cancers clustered within a family. X-chromosome inactivation further influences the expression of X-linked alleles and may represent a novel target for screening and therapy. Herein, we review the current literature regarding X-linked ovarian cancer and interpret allele transmission-based models to characterize X-linked ovarian cancer and develop a framework for clinical and epidemiological familial ascertainment to inform the design of future studies

Prognostic impact of adjuvant chemotherapy treatment intensity for ovarian cancer.

OBJECTIVE:We aimed to investigate the prognostic impact of duration of first-line chemotherapy administration in patients with epithelial ovarian cancer (EOC). METHODS:Chemotherapy records were abstracted from the electronic medical record. Patients with on-time completion (105 days) were compared to patients finishing early (4 weeks. For 222 women with stage IIIC/IV, stage-stratified estimates of progression-free survival (PFS) and overall survival (OS) were compared. A delay sub-study was performed with outliers removed. Each week of delay was correlated with the change in PFS and OS to identify time points associated with change in outcome. RESULTS:Most women had on-time completion of chemotherapy (23.6%) or a treatment delay of ≤4 weeks (21.8%); 21.6% of women experienced a delay longer than 4 weeks. R0 resection at initial debulking (OR = 1.99, 95%CI: 1.18-3.36, p = 0.010) and RECIST complete response (OR = 4.88, 95%CI: 2.47-10.63, p1 month delay had decreased median survival of 18.1 months (14.7-24.9 months), while women with short intervals survived 35.0 months (95%CI: 21.8-49.8 months). Short-term delays lead to progressively decreasing OS. This was significantly different from the on-schedule survival estimate after 6 weeks of delay. CONCLUSIONS:On-time completion of chemotherapy correlates with increased survival and higher complete response rates. Increasing delays in chemotherapy completion were associated with decreased survival

Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study

<div><p>Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89) and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001). Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12–2.25) independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034). Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005). We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in <i>MAGEC3</i>) reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75–4.65) advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families.</p></div

Age-of-onset by genotype and familial pattern.

<p>Age-of-onset by genotype and familial pattern.</p

Representative registry pedigrees.

<p>Ovarian cancers are represented by teal circles, breast cancers by pink circles, prostate cancers by blue squares and prophylactic oophorectomies by grey circles. The earliest of age of onset, prophylaxis, death or last follow up is indiciated below individuals as well as oophorectomies (ooph.) and one heterozygous variant carrier (A/G).</p