Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis

OBJECTIVE: To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin. METHODS: A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed. RESULTS: Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range. CONCLUSION: Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting.     

Assessment of Pre-Pregnancy Dietary Intake with a Food Frequency Questionnaire in Alberta Women

Purpose: Pre-pregnancy is an under-examined and potentially important time to optimize dietary intake to support fetal growth and development as well as maternal health. The purpose of the study was to determine the extent to which dietary intake reported by non-pregnant women is similar to pre-pregnancy dietary intake reported by pregnant women using the same assessment tool. Methods: The self-administered, semi-quantitative food frequency questionnaire (FFQ) was adapted from the Canadian version of the Diet History Questionnaire, originally developed by the National Cancer Institute in the United States. Pregnant women (n = 98) completed the FFQ which assessed dietary intake for the year prior to pregnancy. Non-pregnant women (n = 103) completed the same FFQ which assessed dietary intake for the previous year. Energy, macronutrients, and key micronutrients: long-chain omega-3 fatty acids, folate, vitamin B₆, vitamin B₁₂, calcium, vitamin D and iron were examined. Results: Dietary intake between groups; reported with the FFQ; was similar except for saturated fat; trans fat; calcium; and alcohol. Pregnant women reported significantly higher intakes of saturated fat; trans fat; and calcium and lower intake of alcohol in the year prior to pregnancy compared to non-pregnant women who reported intake in the previous year. Conclusions: Despite limitations; a FFQ may be used to assist with retrospective assessment of pre-pregnancy dietary intake.     

The Reliability and Validity of the Perceived Dietary Adherence Questionnaire for People with Type 2 Diabetes

Nutrition therapy is essential for diabetes treatment, and assessment of dietary intake can be time consuming. The purpose of this study was to develop a reliable and valid instrument to measure diabetic patients’ adherence to Canadian diabetes nutrition recommendations. Specific information derived from three, repeated 24-h dietary recalls of 64 type 2 diabetic patients, aged 59.2 ± 9.7 years, was correlated with a total score and individual items of the Perceived Dietary Adherence Questionnaire (PDAQ). Test-retest reliability was completed by 27 type 2 diabetic patients, aged 62.8 ± 8.4 years. The correlation coefficients for PDAQ items versus 24-h recalls ranged from 0.46 to 0.11. The intra-class correlation (0.78) was acceptable, indicating good reliability. The results suggest that PDAQ is a valid and reliable measure of diabetes nutrition recommendations. Because it is quick to administer and score, it may be useful as a screening tool in research and as a clinical tool to monitor dietary adherence.     

Identification of somatic JAK1 mutations in patients with acute myeloid leukemia

Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with wild-type JAK1, JAK1^T478S, and JAK1^V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.     

Factors predictive of the perceived osteoporosis–fracture link in fragility fracture patients

Objective

Given the asymptomatic nature of osteoporosis, a fragility fracture provides an opportunity to make the issue of osteoporosis relevant to patients. Patients who link their fragility fracture with osteoporosis are more likely to initiate osteoporosis treatment, yet to date, we know little about who is likely to make this link. This study examined whether demographic, health, and osteoporosis belief factors predicted a perceived link between a fragility fracture and osteoporosis.

Study design

This longitudinal cohort study analyzed baseline and follow up data collected as part of a provincial osteoporosis screening initiative targeting fragility fracture patients. Logistic regression analysis was used to examine the relationship between hypothesized predictors and the outcome.

Main outcome measure

Patient perception of the osteoporosis–fracture link at follow up.

Results

At baseline, 93% (1615/1735) of patients did not believe their fracture could have been caused by osteoporosis. Of these, only 8.2% changed this perception at follow up. Adjusted analyses showed that baseline characteristics associated with making the osteoporosis–fracture link at follow up were: a previous fracture (odds ratio (OR) 1.7, confidence interval (CI) 1.2–2.6), perception of osteoporosis pharmacotherapy benefits OR 1.2 (CI 1.0–1.5), diagnosis of rheumatoid arthritis OR 2.6 (CI 1.4–4.9) and the perception of bones as “thin” OR 8.2 (CI 5.1–13.1).

Conclusion

These results shed more light on patient-level barriers to osteoporosis management following an osteoporosis educational programme. They may be used to identify patients less likely to make the link between their fracture and osteoporosis and to inform interventions for this patient group.     

Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial

Recent studies indicate that mindfulness meditation training interventions reduce stress and improve stress-related health outcomes, but the neural pathways for these effects are unknown. The present research evaluates whether mindfulness meditation training alters resting state functional connectivity (rsFC) of the amygdala, a region known to coordinate stress processing and physiological stress responses. We show in an initial discovery study that higher perceived stress over the past month is associated with greater bilateral amygdala-subgenual anterior cingulate cortex (sgACC) rsFC in a sample of community adults (n = 130). A follow-up, single-blind randomized controlled trial shows that a 3-day intensive mindfulness meditation training intervention (relative to a well-matched 3-day relaxation training intervention without a mindfulness component) reduced right amygdala-sgACC rsFC in a sample of stressed unemployed community adults (n = 35). Although stress may increase amygdala-sgACC rsFC, brief training in mindfulness meditation could reverse these effects. This work provides an initial indication that mindfulness meditation training promotes functional neuroplastic changes, suggesting an amygdala-sgACC pathway for stress reduction effects.     

HIV risk and history of STDs in MCMI-III psychopathology subgroups of comorbid substance abusers

The purpose of this investigation is to investigate HIV risk-related attitudes, beliefs, expectancies, behaviors, and histories of lifetime sexually transmitted diseases in the Millon Clinical Multiaxial Inventory III (MCMI-III) defined psychopathology cluster subgroups. Hierarchical agglomerative cluster analysis, using Ward's method, was employed that led to identification of high (n = 37), medium (n = 132), and low (n = 28) MCMI-III psychopathology cluster subgroups. Members of the low psychopathology subgroup demonstrated significantly higher levels of knowledge about HIV and AIDS and less anxiety about HIV infection than high and moderate psychopathology subgroups. The high psychopathology subgroup reported greater importance of approval of condom use by partners but less sexual self-efficacy than the moderate psychopathology subgroup. This high pathology group revealed less favorable condom attitudes than did the low psychopathology subgroup and a significantly higher percentage of unprotected vaginal sex acts in the past 6 months than did members of the other two subgroups. A comparatively low rate of lifetime syphilis was reported in the low psychopathology subgroup (all ps < .05). Results are discussed in the context of a growing literature indicating distinctive treatment needs among members of high psychopathology subgroups of drug treatment participants.