Patient Attitudinal and Behavioral Factors Associated with Warfarin Non-adherence at Outpatient Anticoagulation Clinics

Background

Warfarin is an anticoagulant effective in preventing stroke, but it has a narrow therapeutic range requiring optimal adherence to achieve the most favorable effects.

Purpose

The goal of this study was to examine specific patient factors that might help explain warfarin non-adherence at outpatient anticoagulation clinics.

Method

In a prospective cohort study of 156 adults, we utilized logistic regression analyses to examine the relationship between the five Treatment Prognostics scales from the Millon Behavioral Medicine Diagnostic (MBMD), as well as three additional MBMD scales (Depression, Future Pessimism, and Social Isolation), and daily warfarin non-adherence assessed using electronic medication event monitoring systems caps over a median of 139 days.

Results

Four of the five Treatment Prognostic scales and greater social isolation were associated with warfarin non-adherence. When controlling for pertinent demographic and medical variables, the Information Discomfort scale remained significantly associated with warfarin non-adherence over time.

Conclusion

Although several factors were related to warfarin non-adherence, patients reporting a lack of receptivity to details regarding their medical illness seemed most at risk for warfarin non-adherence. This information might aid in the development of interventions to enhance warfarin adherence and perhaps reduce adverse medical events.     

Rapid one-step carrier detection assay of mucolipidosis IV mutations in the Ashkenazi Jewish population

Two mutations in the MCOLN1 mucolipidosis IV (ML IV) gene represent approximately 95% of the mutations in Ashkenazi-Jewish patients with ML IV. The mutations, a splice site mutation (IVS3-2A>G) and an approximately 6.4-kb deletion (511del6434), account for 72% and 23% of ML IV alleles in this population, respectively. An automated high-throughput assay was developed using the 5'-nuclease (TaqMan) method for the simultaneous detection of both mutations in a single reaction. Three fluorescent probes specifically detected wild-type, IVS3-2A>G, and 511del6434 alleles in each reaction real-time. Data collected were automatically analyzed, and genotype results were uploaded into a laboratory information management system. The assay was validated using genomic controls, demonstrating high robustness and accuracy. Carrier screening of 10,527 samples revealed 77 heterozygote carriers of IVS3-2A>G, 25 heterozygote carriers of 511del6434, and two compound heterozygote of both mutant alleles. The frequency of mutated alleles was 0.73% for IVS3-2A>G and 0.24% for 511del6434. The combined carrier frequency was 1:103 with predicted disease incidence of 1:42,436 individuals in this population, slightly lower than previously described frequencies. This automated high-throughput assay is labor saving, because two mutations can be detected in a single reaction. The method has potential for use in other assays requiring simultaneous detection of two mutations.     

Estrogen-related genes and their contribution to racial differences in breast cancer risk

Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case-control study of breast cancer. Genetic variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and SNP-hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451 controls, including 949 Black women (493 cases and 456 controls), sampled from the CARE study population. No appreciable associations with breast cancer risk were detected for single SNPs or haplotypes in women overall. We detected SNP-HT interactions in women overall within CYP1B1 (rs1800440; p (het)?=?0.003) and within CYP17A1 (rs743572; p (het)?=?0.009) in which never users of HT were at a decreased risk of breast cancer, while ever users were at a non-significant increased risk. When investigated among racial groups, we detected evidence of an SNP-HT interaction with CYP1B1 in White women (p value?=?0.02) and with CYP17A1 in Black women (p value?=?0.04). This analysis suggests that HT use may modify the effect of variation in estrogen-related genes on breast cancer risk, which may affect Black and White women to a different extent.     

Radiation fibrosis: differentiation from recurrent tumor by MR imaging

Magnetic resonance (MR) images of 21 patients who had undergone radiation therapy were analyzed and compared with those of 15 patients who had untreated tumors. T2-weighted images (TR = 1,500 msec, TE = 90 msec) were most helpful in distinguishing recurrent tumor from radiation fibrosis. Radiation fibrosis, like muscle, usually remained low in signal intensity on T2-weighted images, while tumor demonstrated higher signal intensity. In no patient was the signal intensity of tumor the same or less than muscle on the T2-weighted images. However, relatively high signal intensity on T2-weighted images is not specific for tumor recurrence and may be seen in acute radiation pneumonitis, infection, hemorrhage, and even pulmonary radiation fibrosis.     

Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9

Coenzyme Q₁₀ (CoQ₁₀) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ₁₀ may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal lactic acidosis and encephalopathy, we identified a homozygous loss-of-function variant in COQ9. Functional studies in patient fibroblasts showed that the absence of the COQ9 protein was concomitant with a strong reduction of COQ7, leading to a significant accumulation of the substrate of COQ7, 6-demethoxy ubiquinone₁₀. At the same time, the total amount of CoQ₁₀ was severely reduced, which was reflected in a significant decrease of mitochondrial respiratory chain succinate-cytochrome c oxidoreductase (complex II/III) activity. Lentiviral expression of COQ9 restored all these parameters, confirming the causal role of the variant. Our report on the second COQ9 patient expands the clinical spectrum associated with COQ9 variants, indicating the importance of COQ9 already during prenatal development. Moreover, the rescue of cellular CoQ₁₀ levels and respiratory chain complex activities by CoQ₁₀ supplementation points to the importance of an early diagnosis and immediate treatment.     

Oral contraceptive use and breast cancer risk among African-American women

Recent epidemiologic studies, most of them in predominantly White populations, have suggested that long duration of oral contraceptive (OC) use may increase the risk of breast cancer at young ages. We assessed the relationship of OC use to the risk of breast cancer in African-American women aged 25 to 59 years, using interview data from a multipurpose hospital-based case-control study. Five hundred and twenty-four cases hospitalized for invasive breast cancer were compared with 1,021 controls with nonmalignant conditions unrelated to OC use. Relative risks (RR) and 95 percent confidence intervals (CI) were estimated relative to a reference category of use for less than 12 months; potential confounders were controlled by multiple logistic regression analysis. Among women under age 45, three or more years of OC use was associated with an increased risk of breast cancer: the RR estimate was 2.8 (CI=1.5–5.0) for three to four years of use, and declined to 1.5 (CI=0.8.3.0) for 10 or more years of use. Recency and timing of use did not explain the observed association. Among women aged 45 to 59, OC use was associated with little or no increase in risk: the RR estimate for three or more years of use was 1.3 (CI=0.7–2.4). The findings add to the evidence from studies of White women and a recent study of Black women which have suggested an increased risk of breast cancer at young ages for moderate or long duration use of OCs.This research was supported by the US National Cancer Institute (grants R01 CA55766 and R01 CA45762). Additional support was provided by the US Food and Drug Administration (FD-U-000082); the views expressed do not necessarily represent the views of the Food and Drug Administration. The Slone Epidemiology Unit also receives support from Hoffmann-La Roche, Inc., and Marion Merrell Dow Inc.