Predictors of Varenicline Adherence Among Cancer Patients Treated for Tobacco Dependence and its Association With Smoking Cessation.

INTRODUCTION: The degree to which smokers adhere to pharmacotherapy predicts treatment success. The development of interventions to increase adherence requires identification of predictors of treatment adherence, particularly among specific clinical populations. METHODS: Using data from a 12-week open-label phase of a clinical trial of varenicline for tobacco dependence among cancer patients (N = 207), we examined: (1) the relationship between self-reported varenicline adherence and verified smoking cessation and (2) demographic and disease-related variables, and early changes in cognition, affect, withdrawal, the reinforcing effects of smoking, and medication side effects, as correlates of varenicline adherence. RESULTS: At the end of 12 weeks, 35% of the sample had quit smoking and 52% reported taking ≥80% of varenicline. Varenicline adherence was associated with cessation (p < .001): 58% of participants who were adherent had quit smoking versus 11% of those who were not. Participants who experienced early reductions in depressed mood and satisfaction from smoking and experienced an increase in the toxic effects of smoking, showed greater varenicline adherence (p < .05); the relationship between greater adherence and improved cognition, reduced craving, and reduced sleep problems and vomiting approached significance (p < .10). CONCLUSIONS: Among cancer patients treated for tobacco dependence with varenicline, adherence is associated with smoking cessation. Initial changes in depressed mood and the reinforcing effects of smoking are predictive of adherence. IMPLICATIONS: The benefits of varenicline for treating tobacco dependence among cancer patients may depend upon boosting adherence by addressing early signs of depression and reducing the reinforcing dimensions of cigarettes.

An atypical presentation of endometrial cancer as angina secondary to critically low hemoglobin and iron deficiency associated pancytopenia: A case report.

Endometrial cancer is the most common type of gynaecological cancer in high-income countries. Abnormal uterine bleeding (AUB) is the most common symptom of endometrial cancer; however, patients can often present in an atypical fashion. This case is an example of an atypical presentation of endometrial cancer, with angina secondary to severe iron deficiency anemia, and a rare example of pancytopenia secondary to iron deficiency. A 46-year-old nulliparous woman with no past medical history presented to the emergency department with acute chest pain. All her vitals were normal. The ECG showed T-wave inversion with a negative serum troponin. She had obvious pallor but appeared well. She had a critical hemoglobin of 1.9 g/dL and severe iron deficiency with a plasma iron level of <2 µg/L. In the 6 months leading up to her presentation, she had heavy and prolonged menstruation of up to 10 days. She received a total of 6 units of packed red blood cells and an iron infusion. Her chest pain resolved, and her pancytopenia corrected following replenishment of iron stores. She underwent a laparoscopic total hysterectomy, bilateral salpingo-oophorectomy for stage 1b, grade 2 endometroid adenocarcinoma. This is one of the lowest hemoglobin levels recorded in a hemodynamically stable patient with endometrial cancer, and the only case report of iron deficiency induced pancytopenia secondary to abnormal uterine bleeding. This case is a reminder that female patients with angina should have their hemoglobin checked, and patients with anemia should have a thorough review of their gynaecological history.

A randomized clinical trial testing two implementation strategies to promote the treatment of tobacco dependence in community mental healthcare.

INTRODUCTION: People with serious mental illness (SMI) are more likely to smoke and less likely to receive tobacco treatment. Implementation strategies may address clinician and organizational barriers to treating tobacco in mental healthcare. METHODS: A cluster-randomized trial (Clinic N=13, Client N=610, Staff N=222) tested two models to promote tobacco treatment in community mental healthcare: standard didactic training vs. Addressing Tobacco Through Organizational Change (ATTOC), an organizational model that provides clinician and leadership training and addresses system barriers to tobacco treatment. Primary outcomes were changes in tobacco treatment from clients, staff, and medical records. Secondary outcomes were changes in smoking, mental health, and quality of life (QOL), and staff skills and barriers to treat tobacco. RESULTS: Clients at ATTOC sites reported a significant increase in receiving tobacco treatment from clinician at weeks 12 and 24 (ps<0.05) and tobacco treatments and policies from clinics at weeks 12, 24, 36, and 52 (ps<0.05), vs. standard sites. ATTOC staff reported a significant increase in skills to treat tobacco at week 36 (p=0.05), vs. standard sites. For both models, tobacco use medications, from clients (week 52) and medical records (week 36), increased (ps<0.05), while perceived barriers decreased at weeks 24 and 52 (ps<0.05); 4.3% of clients quit smoking which was not associated with model. QOL and mental health improved over 24 weeks for both models (ps<0.05). CONCLUSIONS: Standard training and ATTOC improve use of evidence-based tobacco treatments in community mental healthcare without worsening mental health, but ATTOC may more effectively address this practice gap.

The association between self-reported varenicline adherence and varenicline blood levels in a sample of cancer patients receiving treatment for tobacco dependence.

INTRODUCTION: The degree to which smokers quit successfully with varenicline is strongly associated with their adherence to the medication regimen. Thus, measuring varenicline adherence to identify smokers needing additional intervention is a priority. Few studies, however, have examined the validity of self-reported varenicline adherence, using a biological assessment of adherence as a reference. No study has examined this issue among cancer patients trying to quit smoking, who may show unique patterns of adherence given their medical comorbidity. METHODS: This study used data from 76 cancer patients who received varenicline and provided self-reported varenicline adherence data (pill count) and a blood sample to determine varenicline metabolites 4 weeks after initiating varenicline. RESULTS: Receiver operating characteristic (ROC) curve analyses of plasma varenicline levels showed that 4 ng/ml was the optimal cut-point for differentiating adherence with significant (p's < 0.04) area under the curve values, ranging from 0.73-0.80 for 3-day, 7-day, and 4-week self-reported pill count; specificity values ranged from 0.63-0.78 and sensitivity values ranged from 0.82-0.94. Using this cut-point, adherence was high (88%). However, plasma varenicline levels were weakly correlated with 3-day and 4-week pill count and total pill count (12 weeks) was not correlated with plasma varenicline levels. Patients with head and neck cancer, gastrointestinal cancer, and more advanced disease showed lower varenicline adherence and lower plasma varenicline. CONCLUSIONS: Using the 4 ng/ml cut-point, this study suggests validity of short-term self-reported varenicline adherence among cancer patients undergoing tobacco dependence treatment in contrast to studies in the general population, which supported 12-week pill count.

Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C deficiency.

UNLABELLED: Using a mouse mutant that fractures spontaneously and dies at a very young age, we identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures. INTRODUCTION: A major public health problem worldwide, osteoporosis is a disease characterized by inadequate bone mass necessary for mechanical support, resulting in bone fracture. To identify the genetic basis for osteoporotic fractures, we used a mouse model that develops spontaneous fractures (sfx) at a very early age. MATERIALS AND METHODS: Skeletal phenotype of the sfx phenotype was evaluated by DXA using PIXImus instrumentation and by dynamic histomorphometry. The sfx gene was identified using various molecular genetic approaches, including fine mapping and sequencing of candidate genes, whole genome microarray, and PCR amplification of candidate genes using cDNA and genomic DNA as templates. Gene expression of selected candidate genes was performed using real-time PCR analysis. Osteoblast differentiation was measured by bone marrow stromal cell nodule assay. RESULTS: Femur and tibial BMD were reduced by 27% and 36%, respectively, in sfx mice at 5 weeks of age. Histomorphometric analyses of bones from sfx mice revealed that bone formation rate is reduced by >90% and is caused by impairment of differentiated functions of osteoblasts. The sfx gene was fine mapped to a 2 MB region containing approximately 30 genes in chromosome 14. By using various molecular genetic approaches, we identified that deletion of the gulonolactone oxidase (GULO) gene, which is involved in the synthesis of ascorbic acid, is responsible for the sfx phenotype. We established that ascorbic acid deficiency caused by deletion of the GULO gene (38,146-bp region) contributes to fractures and premature death because the sfx phenotype can be corrected in vivo by treating sfx mice with ascorbic acid and because osteoblasts derived from sfx mice are only able to form mineralized nodules when treated with ascorbic acid. Treatment of bone marrow stromal cells derived from sfx/sfx mice in vitro with ascorbic acid increased expression levels of type I collagen, alkaline phosphatase, and osteocalcin several-fold. CONCLUSION: The sfx is a mutation of the GULO gene, which leads to ascorbic acid deficiency, impaired osteoblast cell function, and fractures in affected mice. Based on these and other findings, we propose that ascorbic acid is essential for the maintenance of differentiated functions of osteoblasts and other cell types.