Reaching adults who smoke cigarettes in rural Appalachia: Rationale, design & analysis plan for a mixed-methods study disseminating pharmacy-delivered cessation treatment.

INTRODUCTION: Unlike other U.S. geographical regions, cigarette smoking prevalence remains stagnant in rural Appalachia. One avenue for reaching rural residents with evidence-based smoking cessation treatments could be utilizing community pharmacists. This paper describes the design, rationale, and analysis plan for a mixed-method study that will determine combinations of cessation treatment components that can be integrated within community pharmacies in rural Appalachia. The aim is to quantify the individual and synergistic effects of five highly disseminable and sustainable cessation components in a factorial experiment. METHODS: This sequential, mixed-method research design, based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, will use a randomized controlled trial with a 25 fully crossed factorial design (32 treatment combinations) to test, alone and in combination, the most effective evidence-based cessation components: (1) QuitAid (yes vs. no) (2) tobacco quit line (yes vs. no) (3) SmokefreeTXT (yes vs. no) (4) combination NRT lozenge + NRT patch (vs. NRT patch alone), and (5) eight weeks of NRT (vs. standard four weeks). RESULTS: Logistic regression will model abstinence at six-months, including indicators for the five treatment factors and all two-way interactions between the treatment factors. Demographic and smoking history variables will be considered to assess potential effect modification. Poisson regression will model quit attempts and percent of adherence to treatment components as secondary outcomes. CONCLUSION: This study will provide foundational evidence on how community pharmacies in medically underserved, rural regions can be leveraged to increase utilization of existing evidence-based tobacco cessation resources for treating tobacco dependence. CLINICAL TRIALS: NCT05660525.

Impact of comorbidities and treatment burden on general well-being among women's cancer survivors.

BACKGROUND: Gains in cancer detection and treatment have meant that more patients are now living with both cancer and other chronic health conditions, which may become burdensome. We used the Patient Experience with Treatment and Self-Management (PETS) framework to study challenges in self-management and its impact on health among survivors of women's cancers who are caring for other chronic health conditions. METHODS: Applicability of the PETS domains among survivors of women's cancers with comorbidities was assessed in focus groups to create the study survey. Women surviving primary breast, cervical, ovarian, or endometrial/uterine cancer treated between 6 months and 3 years prior at two large healthcare systems in Virginia were mailed study invitation letters to complete a telephone-based survey. The survey included questions on cancer treatment history, comorbid conditions prior to cancer, treatment and self-management experiences, health literacy, financial security, and items on self-management activities, self-management difficulties and self-management impact (i.e., role/social activity limitations and physical/mental exhaustion). Additionally, general health was assessed with items from the Patient-Reported Outcomes Measurement Information System (PROMIS). Hierarchical regression models and path analysis were used to examine correlates of self-management impact on general physical health (GPH) and mental health (GMH). RESULTS: Of 1448 patients contacted by mail, 274 (26%) returned an interest form providing their consent to be contacted. Of these, 183 completed the survey. Reasons for non-completion included ineligibility (42), unable to be reached (33) and refusal (6). The majority were survivors of breast (58%) or endometrial/uterine cancer (28%), and 45% resided in non-urban locations. After adjusting for age, race, and cancer type, survivors with higher self-management difficulty reported higher self-management impact, which was associated with lower perceived general health. Reports of higher self-management impact was associated with being single or unmarried, white race, fulltime employed, higher financial insecurity, lower health literacy and more comorbidities. In path analysis, self-management impact was a significant mediator in the association of comorbidity and financial insecurity on GPH and GMH. CONCLUSIONS: Among survivors of women's cancer, pre-diagnosis comorbidity, health literacy, and financial security are associated with psychosocial impact of self-management and general physical and mental health in the 6 month to 3-year period after cancer treatment has ended. The impact of self-management on psychosocial functioning is an important factor among cancer survivors caring for multiple chronic health conditions. This study provides evidence on the importance of assessing cancer survivors' self-management difficulties such as in future interventions to promote health and wellness.

Negative feedback regulation of thyrotropin subunits and pituitary deiodinases in red drum, Sciaenops ocellatus.

Thyroxine (T4) undergoes dynamic daily cycles in the perciform fish the red drum, Sciaenops ocellatus, that are inversely timed to cycles of thyrotropin (TSH) subunit mRNA expression in the pituitary gland. We have proposed that these daily cycles are regulated by negative feedback of circulating T4 on expression of pituitary thyroid hormone deiodinase type 3 (Dio3), such that elevated circulating T4 results in diminished pituitary thyroid hormone catabolism and consequent increased negative feedback on expression of TSH subunits during the day. To determine whether thyroid hormones function to modulate expression of pituitary deiodinase enzymes we developed an immersion technique to administer physiological doses of T3 and T4in vivo. Immersion in T4 or T3 significantly inhibited the mRNA expression of the TSH α and ß subunits from 4 to 66h of immersion. Pituitary Dio3 expression was significantly diminished by T3 and T4 at 22h. These results indicate that both T4 and T3 are capable of negative feedback regulation of TSH subunit expression in red drum at physiological concentrations and on a time scale consistent with the T4 daily cycle. Furthermore, thyroid hormones negatively regulate Dio3 expression in the pituitary in a manner suggesting that negative thyroxine feedback on Dio3 promotes the release of TSH subunits from TH inhibition and may be an important mechanism for generating daily thyroid hormone cycles. These results highlight a potentially important role for D3 in mediating thyroid hormone feedback on TSH expression, not previously described in other species.

Cyclic mRNA expression of thyrotropin subunits and deiodinases in red drum, Sciaenops ocellatus.

The role of thyrotropin (thyroid-stimulating hormone, TSH) in driving peripheral thyroid function in non-mammalian species is still poorly understood. Thyroxine (T4), the principal hormone released from the thyroid gland in response to TSH stimulation, circulates with a robust daily rhythm in the teleost fish the red drum. Previous research suggests that the red drum T4 cycle is circadian in nature, driven by TSH secretion in the early photophase and inhibited by T4 feedback in the early scotophase. To determine whether TSH is produced in a pattern consistent with feedback inhibition by this T4 cycle, we used quantitative real time PCR (qPCR) to quantify the daily cycle of expression of the pituitary TSH subunits GSUα, and TSHß. We found that TSH expression cycled inversely to, and 6-12 h out of phase with, the T4 cycle, consistent with the hypothesis that TSH secretion drives the T4 cycle. To examine the potential role of deiodinases in negative feedback regulation of this TSH cycle, we also utilized qPCR to assess the pituitary expression patterns of the TH activating enzyme outer-ring deiodinase (Dio2) and the TH deactivating enzyme inner-ring deiodinase (Dio3). Dio2 was not expressed with an obvious daily cycle, whereas Dio3 expression mirrored the expression of TSH. These results are consistent with circulating T4 providing the negative feedback signal controlling both TSH production and Dio3 expression in the pituitary, and suggest that TH inactivation by inner ring deiodination is an important component of TSH negative feedback control.

Health Heritage© a web-based tool for the collection and assessment of family health history: initial user experience and analytic validity.

A detailed family health history is currently the most potentially useful tool for diagnosis and risk assessment in clinical genetics. We developed and evaluated the usability and analytic validity of a patient-driven web-based family health history collection and analysis tool. Health Heritage(©) guides users through the collection of their family health history by relative, generates a pedigree, completes risk assessment, stratification, and recommendations for 89 conditions. We compared the performance of Health Heritage to that of Usual Care using a nonrandomized cohort trial of 109 volunteers. We contrasted the completeness and sensitivity of family health history collection and risk assessments derived from Health Heritage and Usual Care to those obtained by genetic counselors and genetic assessment teams. Nearly half (42%) of the Health Heritage participants reported discovery of health risks; 63% found the information easy to understand and 56% indicated it would change their health behavior. Health Heritage consistently outperformed Usual Care in the completeness and accuracy of family health history collection, identifying 60% of the elevated risk conditions specified by the genetic team versus 24% identified by Usual Care. Health Heritage also had greater sensitivity than Usual Care when comparing the identification of risks. These results suggest a strong role for automated family health history collection and risk assessment and underscore the potential of these data to serve as the foundation for comprehensive, cost-effective personalized genomic medicine.

In-hospital outcomes of off-pump versus on-pump coronary artery bypass procedures: a multicenter experience.

BACKGROUND: Concern about the possible adverse effects of the cardiopulmonary bypass (CPB) pump and advances in retractors and operative techniques to access all coronary segments have resulted in increased interest in off-pump coronary artery bypass (OPCAB) procedures. Four of the Northern New England Cardiovascular Disease Study Group centers initiated OPCAB programs in 1998. We compared the preoperative risk profiles and in-hospital outcomes of patients done off-pump with those done by conventional coronary artery bypass (CCAB) with CPB. METHODS: Between 1998 and 2000, 1,741 OPCAB and 6,126 CCAB procedures were performed at these four medical centers. Minimally invasive direct coronary artery bypass grafting procedures were excluded. Data were available for patient and disease risk factors, extent of coronary disease and adverse in-hospital outcomes. RESULTS: The OPCAB and CCAB groups were somewhat different in their preoperative patient and disease characteristics. The OPCAB patients were more likely to be female and to have peripheral vascular disease. The CCAB patients were more likely to have an ejection fraction less than 0.40 and be urgent or emergent at operation. However, overall predicted risk of in-hospital mortality, based on preoperative factors, was similar in the OPCAB and CCAB groups; the mean predicted risk was 2.6% (p = 0.567). Crude rates of mortality (2.54% OPCAB versus 2.57%, CCAB), intraoperative or postoperative stroke (1.33% versus 1.82%), mediastinitis (1.10% versus 1.37%), and return to the operating room for bleeding (3.46% versus 2.93%) did not differ significantly. The OPCAB patients did have a statistically significant reduction in the need for intraoperative or postoperative intraaortic balloon pump support (2.31% versus 3.41%; p = 0.023) and in the incidence of postoperative atrial fibrillation (21.21% versus 26.31%; p < 0.001). Adjustment for preoperative risk factors and extent of coronary disease did not substantially change the crude results. Median postoperative length of stay was significantly shorter (5 days versus 6 days, p < 0.001) for OPCAB patients than for CCAB patients. CONCLUSIONS: This multicenter study showed that patients having OPCAB are not exposed to a greater risk of short-term adverse outcomes. These data also provided evidence that patients having OPCAB have significantly lower need for intraoperative or postoperative intraaortic balloon pump, lower rates of postoperative atrial fibrillation, and a shorter length of stay.

Factors predictive of difficult colonoscopy.

BACKGROUND: Prediction of a technically difficult colonoscopy may influence patient selection and procedure scheduling. Identification of predictive factors may be difficult because a common endpoint used to evaluate the success of colonoscopy is intubation of the cecum, which is usually achieved. The goal of this study was to examine the feasibility of using an alternative measure, time required for cecal intubation, to identify factors that can impact performance of colonoscopy. METHODS: The time required for cecal intubation was prospectively recorded for 802 consecutive outpatient colonoscopies performed by 7 experienced gastroenterologists. Patient data collected included height, weight, age, bowel habits, surgical history, and findings at colonoscopy. Forty-seven examinations that were stopped because of disease or unacceptable bowel preparation were excluded. The impact of the patient characteristics of the remaining sample of 755 patients on the median time required for cecal intubation for men and women was examined. RESULTS: Older age and female gender, body mass index < or =25.0 (regardless of gender), diverticular disease in women, and a history of constipation or reported laxative use in men were predictors of difficult colonoscopy. CONCLUSIONS: By using median time required for cecal intubation, several patient characteristics were identified that may predict technical difficulty at colonoscopy. These findings have implications for practice and teaching.

Corynebacterium jeikeium native valve endocarditis following femoral access for coronary angiography.

We present a unique case of rapidly fatal native aortic-valve endocarditis due to Corynebacterium jeikeium, with inoculation as a complication of repeated femoral vascular access for coronary angiography.

Knowledge about breast cancer risk factors and hereditary breast cancer among early-onset breast cancer survivors.

Little is known about knowledge levels regarding hereditary breast cancer among breast cancer survivors. This study explored, among women with early-onset breast cancer (<50 years): 1) knowledge regarding breast cancer risk factors and hereditary breast cancer; and 2) differences in knowledge based on risk for hereditary disease. Participants recruited from 34 Virginia hospitals responded to two questionnaires. The Family History Questionnaire assessed risk for hereditary breast cancer. The Knowledge, Attitudes, and Beliefs Questionnaire evaluated knowledge of general breast cancer risk factors and hereditary breast cancer. Of 314 respondents, 273 (87%) returned both questionnaires. A total of 137 (52%) participants met the study's criteria for hereditary breast cancer risk. Most participants knew common breast cancer-associated risk factors, including family history of breast cancer. Only 35% recognized family history of non-breast malignancies as a risk factor for breast cancer. Most participants recognized that prophylactic mastectomy does not eliminate breast cancer risk (63%), that not all women carrying a mutation develop disease (73%), and that men can develop breast cancer (96%). The majority selected 'I don't know' for knowledge of several characteristics of hereditary breast cancer, including: early-onset disease (54%); multifocal or bilateral disease (62%); risk transmission through fathers (58%); association with other cancer types (61%); and male breast cancer (70%). Knowledge regarding hereditary breast cancer did not vary between women with suspected hereditary disease and those with presumed sporadic disease. These data highlight the need for information regarding hereditary breast cancer for early-onset breast cancer survivors.

Factors influencing patients' decisions to decline cancer genetic counseling services.

Little is known about the factors influencing patients' decisions about whether to utilize cancer genetic counseling services. The purpose of this study is to identify potential barriers to broad utilization of such services. Of a total of 136 decliners of cancer genetic counseling services at our institution, 117 were deemed eligible to participate. Of these, 73 were randomly selected for study. A total of 37/73 (51%) agreed to participate in a semistructured telephone survey designed to assess the factors that impacted their decisions to decline cancer genetic counseling. An interview script, composed of both closed- and open-ended questions was used to direct the survey. Interviews were audiotaped. Responses to open-ended questions were content analyzed. Of the participants, 34 were female and 36 were Caucasian. Seventy-two percent of the participants were between ages 36 and 55 years. Participants cited the following reasons for choosing not to proceed with cancer genetic counseling: concern over health insurability for self or family (n=15); cost (n=12); emotional impact on self or family (n=11); no perceived benefit (n=11); and time commitment (n=9). These data provide an understanding of patient's attitudes and concern impacting their decisions to decline cancer genetic counseling. This information provides guidance for the development of interventions designed to limit barriers among patients referred for such services.

Informed consent for BRCA1 and BRCA2 testing: what clinicians should know about the process and content.

The exploration and understanding of the human genome has begun to alter the nature of health care. Scientific advances have provided tools to predict susceptibility to a number of adult-onset diseases, including cancer. Some of the most powerful lessons learned about both the promise and the threat of hereditary cancer risk assessment have come from the study of the genetic testing process among women and families at risk for breast and ovarian cancer. The complexity of the issues associated with genetic testing for these cancers has raised concerns about the informed consent process. This paper reviews the issues associated with informed consent for genetic testing for breast and ovarian cancer risk. The paper also addresses the risks, benefits, and limitations of genetic testing, as well as confidentiality issues that should be addressed in this process. Included is a discussion of the alternatives available to women and families considering genetic testing.

Postoperative atrial tachyarrhythmias in patients undergoing coronary artery bypass graft surgery without cardiopulmonary bypass: a role for intraoperative magnesium supplementation.

OBJECTIVE: To determine if intraoperative magnesium supplementation would be associated with a reduction in postoperative atrial tachyarrhythmias (POAT) in patients undergoing coronary artery bypass grafting (CABG) surgery without cardiopulmonary bypass (off-pump CABG surgery). DESIGN: Retrospective study. SETTING: University Medical Center. PARTICIPANTS: Patients who had undergone off-pump CABG surgery (n = 124). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The charts of 124 patients who had undergone off-pump CABG surgery (64 by anterior thoracotomy and 60 by median sternotomy) were retrospectively reviewed. Demographic data and perioperative care were recorded and compared among patients who did and did not experience POAT and among patients who did and did not receive intraoperative magnesium supplementation. Logistic regression analysis was used to assess the association between magnesium supplementation and incidence of POAT, controlling for other covariables. Of the 124 patients, 16 had a prior history of atrial or ventricular arrhythmias and/or were receiving antiarrhythmic medications. Medical records of the remaining 108 patients were reviewed. Twenty-four patients (22%) had POAT. Forty-two patients (39%) received intraoperative magnesium. In patients receiving intraoperative magnesium, the incidence of POAT was significantly decreased (12% v 29%; p = 0.03). In these patients, initial postoperative serum magnesium was significantly higher (2.37 mEq/L v 1.86 mEq/L; p < 0.01). In patients not receiving intraoperative magnesium, 35% had hypomagnesemia (serum magnesium < 1.8 mEq/L) compared with 9% of patients receiving magnesium (p < 0.01). Patients who received intraoperative magnesium and beta-adrenergic blockers had a lower incidence of POAT (5%) than patients who received only one (19%) or neither (33%) (p < 0.05). CONCLUSIONS: Intraoperative magnesium supplementation is associated with a decrease in POAT after off-pump CABG surgery. The combination of a beta-blocker and magnesium may reduce POAT further. It is recommended that intraoperative magnesium supplementation be part of the care of patients undergoing off-pump CABG surgery.

Men's attitudes regarding genetic testing for hereditary prostate cancer risk.

OBJECTIVES: Little is known about the attitudes of men unselected for a family history for prostate cancer concerning genetic testing for prostate cancer risk or genetic testing for inherited cancer predisposition. To explore this, we examined the interest in molecular testing for hereditary prostate cancer (HPC) predisposition among a self-selected cohort of 342 men presenting for prostate cancer screening. METHODS: Participants were surveyed concerning their attitudes about DNA testing for HPC predisposition and knowledge of prostate cancer-associated risk factors, including heredity. RESULTS: Of the participants completing the survey, 92% expressed interest in learning about DNA testing, and 89% stated that they would undergo DNA analysis for HPC predisposition, if available. Twenty-eight percent of respondents failed to demonstrate an adequate understanding of the concept of "inherited tendency." The demonstrated level of understanding of this concept did not differ by the respondent's family history, although it varied by race. An interest in learning about or undergoing testing did not vary by race, family history, or demonstrated understanding of the concept of inherited risk. CONCLUSIONS: Among men presenting for routine prostate cancer screening, interest in learning about testing for HPC predisposition and in having such testing performed may be high. The data also provide evidence that, in a population of men unselected for family history, interest in molecular testing for this common, male-specific cancer may parallel the high interest level demonstrated among women in DNA testing for inherited breast and ovarian cancer risk.

Surgical ICU recidivism after cardiac operations.

BACKGROUND: Decreasing the ICU length of stay (LOS) after cardiac operations may increase ICU recidivism, obviating the benefit of early discharge. METHODS: From January 1, 1994 to January 1, 1998, there were 2,388 consecutive cardiac operations, from which 2,228 patients were discharged alive from the ICU and had sufficient information to determine their incidence of ICU return, the reasons for their return, their ICU LOS (initial and secondary LOS), and mortality. RESULTS: A decrease occurred in the initial ICU LOS from 1994 through 1997 (medians for 1994, 1995, 1996, and 1997, respectively: 31 h, 26.4 h, 24.5 h, and 24 h; and means, respectively: 69.4 +/- 139.8, 62.8 +/- 114.1, 52.5 +/- 104.0, and 56.2 +/- 103.4 h; p = 0.048). In association with this, however, ICU recidivism increased (as percentage of discharges, respectively: 3.9%, 4.2%, 6.1%, and 8.4%; p = 0.005). Inclusive of secondary ICU LOS, the total ICU LOS hours still decreased over the 4-year period. Most notably, the incidence of readmission increased with longer initial LOS (initial LOS quartiles from shortest to longest: 3.9%, 5.2%, 4.7%, and 9.2%; p = 0.0008). Predictors of ICU recidivism included preoperatively, a history of congestive heart failure, and a lower mean left ventricular ejection fraction (52.7 +/- 19.3% vs 49.8 +/- 21.5%; p = 0.0080); and, postoperatively, an increased mean weight gain (8.5 +/- 5.6 kg vs 10.3 +/- 4.7 kg; p = 0.040) and longer mean initial ventilator time (157 +/- 299 h vs 35 +/- 107 h; p = 0.038). The most common reason for readmission was pulmonary problems. CONCLUSIONS: Over the years studied, the initial ICU LOS after cardiac operations has decreased in association with a significant increase in ICU recidivism. Importantly, however, patients readmitted to the ICU are those with longer initial LOSs. Decreased initial stay does not account for our increased ICU recidivism, and efforts to decrease ICU recidivism can focus on the patients with poor preoperative cardiac function and longer initial ICU stays.

Minimally invasive direct coronary artery bypass grafting: changes in anesthetic management and surgical procedure.

OBJECTIVE: The authors hypothesized that changes in surgical procedures for minimally invasive direct coronary artery bypass grafting (MIDCAB) have led to changes in anesthetic management with a resultant decrease in the complexity of care. DESIGN: Retrospective observational study. SETTING: University teaching hospital. PARTICIPANTS: Review of the records of 60 patients who underwent MIDCAB surgery. MEASUREMENTS AND MAIN RESULTS: Data included preoperative demographics, perioperative anesthetic management, and postoperative cardiac and noncardiac issues and complications. Two groups were formed: in group I, a coronary stabilizer (CS) was not used, and in group II, it was. With the exception of a greater incidence of those with no preoperative comorbidities in group II (CS), there were no differences between the two groups with respect to demographics or preoperative variables. A surgical design called H-graft was used in a greater number of group II (CS) patients, whereas a direct anastomosis was performed in the majority of group I patients. Use of pharmacologically induced bradycardia/asystole has not been performed after the introduction of the CS. The use of central venous catheters (instead of pulmonary artery catheters) and single-lumen (v double-lumen) endotracheal tubes was greater in group II (CS) patients. Despite changes in intraoperative management, there was no significant change in the incidence of postoperative complications, intensive care unit stay, and hospital stay between groups I and II. New-onset atrial fibrillation was the most common postoperative complication (13 of 56 patients; 23%). Three of 24 patients (12.5%) who received intraoperative magnesium experienced atrial fibrillation compared with 10 of 32 patients (31%) who did not receive magnesium. CONCLUSIONS: The complexity of anesthetic technique has decreased since the onset of MIDCAB surgery. The decrease in complexity may be related to changes in surgical design and technology.

Videoscopic harvest of the inferior epigastric artery.

The inferior epigastric artery has been found to be a useful conduit for performing arterial coronary revascularization. The present report describes a minimally invasive port access technique for harvesting the inferior epigastric artery.

Atrial fibrillation after minimally invasive coronary artery bypass grafting: A retrospective, matched study.

BACKGROUND: Atrial fibrillation after cardiac operations is a source of morbidity and resource consumption. Various factors common to cardiac operations have been cited as causal. Comparison of the incidences of atrial fibrillation after conventional cardiac operations and minimally invasive cardiac operations may provide some insight into the mechanisms of this complication. METHODS: All patients undergoing minimally invasive direct coronary artery bypass grafting from January 26, 1996, through September 17, 1997, were evaluated for the occurrence of in-hospital postoperative atrial fibrillation. Data from these 55 patients were compared with data from a control cohort of patients undergoing conventional, solitary coronary artery bypass grafting. Each patient undergoing minimally invasive direct coronary artery bypass grafting was matched by age (+/- 3 years) and date of operation (+/- 7 days) with a patient undergoing conventional coronary artery bypass grafting. RESULTS: During the period since the advent of minimally invasive direct coronary artery bypass grafting at our institution, the incidence of postoperative atrial fibrillation has been slightly lower among the patients undergoing this form of coronary artery bypass grafting (26%) than among the total population of patients undergoing conventional coronary artery bypass grafting (34%). Comparison of the age-matched groups, however, showed the incidence to be slightly but not significantly greater in the minimally invasive direct coronary artery bypass grafting cohort (13/55, 24%) than in the conventional coronary artery bypass grafting cohort (11/55, 20%; P =. 6). The minimally invasive direct coronary artery bypass grafting group was less likely to be discharged with antiarrhythmic therapy than was the conventional coronary artery bypass grafting group (6 versus 10; P =.006). CONCLUSIONS: According to these data, mechanisms traditionally implicated in atrial fibrillation after coronary artery bypass grafting, such as the use of cardiopulmonary bypass, mechanical manipulation of the atrium, and atrial ischemia, are not causal but may be related to the duration of the arrhythmic complication. Strategies directed toward management and reduction of the incidence of postoperative atrial fibrillation should be focused accordingly.