No impact of atrial fibrillation on mortality risk in optimally treated heart failure patients

Background:

Several studies have shown that atrial fibrillation (AF) is associated with increased risk of death in heart failure (HF) patients. However, it is not clear whether this increased risk is independent of other risk factors.

Hypothesis:

We hypothesized that AF would be an independent risk factor for death in a large cohort of HF patients.

Methods:

Patients referred to Norwegian HF outpatient clinics were enrolled between October 2000 and February 2008. Patients with heart rhythm other than AF or sinus rhythm were excluded. Mortality data were obtained from the National Statistics Bureau, Statistics Norway with the last update February 2008.

Results:

There were 4048 patients included in the analysis, with a median follow‐up of 28 months. Adherence to guidelines regarding medical treatment was high. In univariate analysis, AF patients (n = 1391) had a higher risk of death than patients in sinus rhythm (n = 2657) (hazard ratio [HR] 1.181; 95% confidence interval (CI), 1.044–1.336; P = 0.008). However, after adjusting for confounding factors (age, New York Heart Association class, coronary artery disease as the main cause of HF, use of any loop diuretic, hemoglobin level, and serum creatinine), AF was no longer associated with increased risk of death (HR 1.037; 95% CI, 0.901–1.193; P = 0.619).

Conclusions:

In this cohort of heart failure patients receiving optimal medical treatment at specialized HF clinics, AF was not associated with increased risk of death after adjusting for confounding factors. © 2011 Wiley Periodicals, Inc. AstraZeneca Norway provided secretarial assistance in maintaining the Norwegian heart failure registry by financing an independent IT consultant. The authors have received research grants, consultancy fees, and/or honoraria for lectures from several pharmaceutical companies. The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

Mental health and sleep in permanent atrial fibrillation patients from the general population

Background:

Anxiety and depression has been found in atrial fibrillation (AF) patients referred to secondary care. Little is known about the level of such distress in AF patients from the general population.

Hypothesis:

Permanent AF patients from the general population might have more anxiety, depression, and sleep impairment than subjects in sinus rhythm.

Methods:

Patients with permanent AF and controls in sinus rhythm were recruited from a 75‐year‐old cohort from 2 Norwegian municipalities. The main outcome variables were anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS) and sleep quality measured by Pittsburgh Sleep Quality Index (PSQI) score. Short Form 36 (SF‐36) was also completed.

Results:

Twenty‐seven patients with permanent AF and 71 subjects in sinus rhythm participated. No significant score differences were found between AF patients and controls for HADS anxiety (median, inter quartile range, 3 [1, 5] vs 4 [1, 6]; HADS depression, 3 [1,6] vs 2 [1,4]; and PSQI 6 [3, 11] vs 5 [4, 8]). AF patients had significantly poorer scores for SF‐36 physical functioning, physical role, general health, vitality, and social functioning compared to subjects in sinus rhythm.

Conclusions:

Elderly permanent AF patients from the general population had similar levels of anxiety, depression, and sleep quality, despite poorer physical health‐related quality of life compared to controls in sinus rhythm. Copyright © 2011 Wiley Periodicals, Inc. This work was supported by unrestricted grants from the governmental Health Region South‐East, Norway, and from the Stein Erik Hagen Foundation for Clinical Heart Research, Norway. The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

Caries assessment and restorative treatment thresholds reported by Swedish dentists.

The aim was to study any variability in approximal and occlusal caries diagnoses and restorative treatment decisions among Swedish dentists. The material consisted of a pre-coded questionnaire sent to a random sample of 923 dentists with 4 items concerning approximal and occlusal caries diagnosis and restorative treatment decisions. Responses were received from 651 (70.5%) dentists. In an adolescent with low caries activity and good oral hygiene, more than 90% of the dentists stated that they would not automatically restore a primary approximal caries lesion if its radiographic appearance did not show obvious progression in the outer 1/3 to 1/2 of the dentin. Moreover, 67% of the dentists would only consider immediate restorative treatment of an occlusal surface if obvious cavitation and/or radiographic signs of dentin caries could be observed. When diagnosing questionable occlusal caries, the dentists largely relied on the radiographic appearance. Concerning both approximal and occlusal caries, the threshold for restorative treatment differed between the metropolitan regions in Sweden, and younger more often than older dentists would postpone restorative treatment of approximal caries until the lesion had reached a relatively advanced stage of progression. The responses also showed that dentists in private practice would restore approximal caries at an earlier stage of progression than the dentists in the Public Dental Health Service.     

Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation screening

Screening for mutations in the breast and ovarian cancer susceptibility gene, BRCA1, is complicated by the wide spectrum of mutations found in this large gene. In the present study a constant denaturant gel electrophoresis (CDGE) mutation screening strategy was established for ˜80% of the genomic coding sequence (exons 2, 11, 13–16, 20, 24). This strategy was applied to screen genomic DNA from 50 familial breast and/or ovarian cancer patients who had previously been examined for BRCA1 mutations by SSCP. A total of 14 carriers of 12 distinct disease-associated mutations and 7 carriers of 6 distinct rare substitutions leading to amino acid substitutions were identified. The SSCP failed to detect 40% of the different deletions/insertions (4/10) and 75% (6/8) of the different base substitutions leading to terminating codons or rare amino acid changes. SSCP did, however, identify one rare base substitution that could not be detected in the CDGE screening. To evaluate the CDGE mutation screening strategy further, 25 unrelated patients from Norwegian breast and/or ovarian cancer families were examined for BRCA1 mutations using a combined genomic DNA/cDNA approach covering the entire coding sequence of the gene. A total of six mutation carriers were detected, all of whom had cases of ovarian cancer in their families. Three patients from independent families carried an 1135insA mutation in exon 11, two others had a Gly484ter and an 1675delA mutation, respectively, and the sixth carried a splice mutation (5194-2 a→c) causing deletion of exon 18. CDGE may become an efficient tool in diagnostic and population based screening for BRCA1 mutations. Hum Mutat 11:166–174, 1998. © 1998 Wiley-Liss, Inc.     

Survey of Croatian dentists' restorative treatment decisions on approximal caries lesions

Aim

To assess Croatian dentists’ restorative treatment decisions on approximal caries lesions, including treatment threshold and restorative methods and materials.

Methods

Croatian translation of the questionnaire assessing restorative treatment decisions on approximal caries, previously validated and used in Norway and Sweden, was distributed to a random sample (n = 800) of Croatian dentists. A total of 307 (38%) dentists answered the questionnaire. The assessed variables were treatment threshold for hypothetical approximal caries lesion and the most favored types of restorative techniques and materials.

Results

A third of the respondents (39%, 95% confidence interval [CI], 34-44%) would intervene for an approximal caries lesion at the dentin-enamel junction, but a larger proportion (42%; 95% CI, 36-48%) would treat a caries lesion confined to the enamel. For restoration of approximal caries, the majority (66%; 95% CI, 61-71%) would use composite resin.

Conclusion

Croatian dentists tend to restore approximal caries lesions when the lesions are confined to the enamel and their development can still be arrested.Caries diagnosis remains a major challenge in dentistry. Since clinical pattern of caries in industrialized countries is changing and a growing proportion of caries shows slow progression and late cavitation (1), there is an increased risk of hidden approximal caries, ie, the caries that can progress beneath sound enamel surface. In this type of caries, visual examination alone is often insufficient (2) and the use of bitewing radiographs is required (3,4,5). Besides clinical and radiographic findings, the dentist''s decision on restorative threshold and restorative techniques and materials is influenced by patient’s characteristics such as age (6), dental hygiene, dietary habits, and fluoride uptake. Better understanding of demineralization and remineralization of caries lesions and availability of products for mineralization of caries lesions confined to the enamel have resulted in new minimally invasive approaches in restorative dentistry. These approaches can preserve healthy hard dental tissues and therefore should be used in preference to operative treatments indicated when the caries lesion has reached the dentin-enamel junction or cavitation stage (7). However, it is unclear to what extent these approaches have been adopted in Croatia. In addition to variations in materials and techniques, dentists in different countries differ in how well they detect approximal caries lesions (8) and how they plan treatment (9-19). Since dentists'' preferences for restorative treatment are often difficult to be directly inferred from patient files, anonymous questionnaire is used. For example, studies from Norway and Sweden (9,15) that used an anonymous questionnaire showed a relationship between dentists'' preferences for restorative treatment and their age and type of practice.To assess variations among Croatian dentists in the treatment threshold and restorative methods and materials, a pilot study using the survey from Sweden (15) was conducted among Croatian dentists in Split-Dalmatia county (20). The study found that dentists tended to restore caries lesions when the approximal lesion had reached the dentin-enamel junction or had just penetrated the dentin, and that they preferred to use tunnel preparation and composite resin material (20). The present study was designed as an extension of the pilot study and included more dentists, from all parts of Croatia.     

Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer

Background:

The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC).

Methods:

Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses.

Results:

Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis.

Conclusion:

Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer.     

Swedish dentists' decisions on preparation techniques and restorative materials

This study aimed at mapping the preparation techniques and restorative materials that Swedish dentists are using for primary approximal and occlusal carious lesions. It involved sending a pre-coded questionnaire to a random sample of 923 dentists, with eight items concerning approximal and occlusal restorative preparation techniques and dental materials. Responses were received from 651 (70.5%) dentists. To restore a primary approximal carious lesion in an adolescent with low caries activity and good oral hygiene, the tunnel preparation was chosen by 48% of the dentists, the saucer-shaped preparation by 32%, and the traditional Class II preparation by 20%. The most common preparation technique for restoring an occlusal carious lesion was removal of the carious part only, which was chosen by 74% of the dentists. For a lower second molar with a minor occlusal caries lesion combined with a suspected dentin lesion as judged radiographically, about half of the dentists chose to restore the carious part only and 27% would seal the rest of the fissure system in addition. For a similar lesion with no obvious radiolucency in the dentin, about 1/3 chose the 'no treatment' alternative, 1/3 fluoride treatment, and the rest fissure sealing or other techniques. Composite was used most often and amalgam least often for both approximal and occlusal carious lesions.     

Biochemical signs of impaired cobalamin status during and after radiotherapy for rectal cancer

PURPOSE: The aim of the study was to investigate whether pelvic radiotherapy for rectal cancer had a negative impact on cobalamin status. METHODS AND MATERIALS: Consecutive patients receiving pelvic radiotherapy (50 Gy) for rectal cancer were evaluated prospectively (n = 54). Serum cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) were measured at start and end of radiotherapy, at follow-up 4-6 weeks and 1 year (n = 23) after radiotherapy. RESULTS: Mean serum cobalamin decreased from 306 pmol/L before treatment to 267 pmol/L at the end of radiotherapy (p < 0.001), 247 pmol/L 4-6 weeks after radiotherapy (p < 0.001), and 249 pmol/L 1 year after radiotherapy (p = 0.02). Mean serum MMA was 0.16 micromol/L pretreatment, 0.17 micromol/L at the end of radiotherapy (n.s.), and increased to 0.19 micromol/L after 4-6 weeks (p = 0.007), and to 0.21 micromol/L after 1 year (p < 0.001). There was no change in serum tHcy. Mean serum holoTC was reduced from 111 pmol/L pretreatment to 93 pmol/L 4-6 weeks after radiotherapy (p = 0.002). CONCLUSIONS: The data suggest rapid and persistent decrease in cobalamin status after radiotherapy for rectal cancer, as reflected by reduced serum cobalamin combined with increased serum MMA. This observation, though modest, may motivate routine monitoring of cobalamin status at follow-up after radiotherapy.