The influence of patient adherence on anticoagulation control with warfarin: results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study

BACKGROUND: Warfarin sodium is a highly efficacious drug, but proper levels of anticoagulation are difficult to maintain. Conflicting data exist on the influence of patient adherence on anticoagulation control. METHODS: We performed a prospective cohort study at 3 anticoagulation clinics to determine the effect of adherence on anticoagulation control. Patients treated with warfarin with a target international normalized ratio of 2.0 to 3.0 were monitored with electronic Medication Event Monitoring System (MEMS) medication bottle caps. Detailed information was collected on other factors that might alter warfarin response. RESULTS: Among 136 participants observed for a mean of 32 weeks, 92% had at least 1 missed or extra bottle opening; 36% missed more than 20% of their bottle openings; and 4% had more than 10% extra bottle openings. In multivariable analyses, there was a significant association between underadherence and underanticoagulation. For each 10% increase in missed pill bottle openings, there was a 14% increase in the odds of underanticoagulation (P<.001); participants with more than 20% missed bottle openings (1-2 missed days each week) had more than a 2-fold increase in the odds of underanticoagulation (adjusted odds ratio, 2.10; 95% confidence interval, 1.48-2.96). Participants who had extra pill bottle openings on more than 10% of days had a statistically significant increase in overanticoagulation (adjusted odds ratio, 1.73; 95% confidence interval, 1.09-2.74). CONCLUSION: Patients have substantial difficulties maintaining adequate adherence with warfarin regimens, and this poor adherence has a significant effect on anticoagulation control.     

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis

OBJECTIVES: To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. METHODS: An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence-based and expert opinion-based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. RESULTS: Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis-specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. CONCLUSIONS: On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well-designed research in non-AAV systemic vasculitides.     

Varus foot alignment and hip conditions in older adults

OBJECTIVE: Mechanical strain on the hip can result from varus malalignment of the foot. This study was undertaken to explore the cross-sectional relationship between varus foot alignment and hip conditions in a population of older adults. METHODS: The Framingham Osteoarthritis Study cohort consists of a population-based sample of older adults. Within this sample, we measured forefoot and rearfoot frontal plane alignment using photographs of a non-weight-bearing view of both feet of 385 men and women (mean age 63.1 years). Each foot segment was categorized according to the distribution of forefoot and rearfoot alignment among cases of ipsilateral hip pain, trochanter tenderness, hip pain or tenderness, and total hip replacement (THR). The relationship of foot alignment to these conditions was examined using logistic regression and generalized estimating equations, adjusting for age, body mass index, sex, and physical activity. RESULTS: The mean +/- SD rearfoot varus alignment was 0.7 +/- 5.5 degrees, and the mean +/- SD forefoot varus alignment was 9.9 +/- 9.9 degrees. Subjects in the highest category of forefoot varus alignment had 1.8 times the odds of having ipsilateral hip pain (P for trend = 0.06), 1.9 times the odds of having hip pain or tenderness (P for trend < 0.01), and 5.1 times the odds of having undergone THR (P for trend = 0.04) compared with those in the lowest category. No significant associations were found between rearfoot varus alignment and any hip conditions. CONCLUSION: Forefoot varus malalignment may be associated with ipsilateral hip pain or tenderness and THR in older adults. These findings have implications for treatment, since this risk factor is potentially modifiable with foot orthoses.     

Tc-sestamibi radio-guided surgery of loco-regional Iodine-negative recurrent thyroid cancer

Aim

We report here our experience in a larger series of differentiated thyroid cancer (DTC) patients who had been treated by ^99mTc-sestamibi radio-guided surgery (RGS) for ¹³¹Iodine (¹³¹I)-negative loco-regional recurrent disease.

Methods

Fifty-eight patients with loco-regional ¹³¹I-negative recurrent disease from DTC were studied with ^99mTc-sestamibi directed RGS using a hand-held 11-mm gamma probe as an intra-operative detector. Patients were selected for RGS on the basis of (a) progressive increase of serum thyroglobulin (Tg) levels after first treatment during follow-up, (b) negative high dose (100 mCi, 3.7 GBq) ¹³¹I whole-body scan, and (c) positive pre-operative ^99mTc-sestamibi scintigraphy for the presence of loco-regional recurrent disease. There were 41 papillary (1 “tall” cell variant), 13 follicular and 4 Hürthle cells tumours. In 14 patients thyroid cancer recurred in the thyroid bed while cervical lymph node metastases were found in 37 patients, and 7 patients had recurrent disease both in the thyroid bed and in cervical lymph nodes.

Results

At bilateral neck exploration, 147 metastastic foci ranging from 4 mm to 51 mm in largest diameter (mean tumour diameter = 17.3 ± 9.5 mm) were removed. Eighty-five of them (58%) had been pre-operatively identified at ^99mTc-sestamibi scintigraphy. After RGS, serum Tg levels normalised in 43 of 58 patients (serum Tg < 2 ng/ml – they were considered disease-free), serum Tg remained slightly increased in 12 patients without evidence of metastatic disease at scintigraphic and radiologic imaging (serum Tg < 10 ng/mg – they were considered living with microscopic disease), while serum Tg significantly increased up to values > 900 ng/ml in 3 patients who developed lung metastases. The mean lesion to background ^99mTc-sestamibi uptake ratios decreased in all 58 patients (p < 0.0001). Post-surgical follow-up ranged 6–72 months (mean ± SD = 29.6 ± 13.5 months). The operating surgeon assessed RGS as very useful in 14 patients in whom metastatic foci were embedded in fibrotic tissues or located behind blood vessels, useful in 22 patients, moderately useful 17 patients and not useful in 5 patients.

Conclusion

Our data suggest that a ^99mTc-sestamibi intra-operative gamma probe can be used to identify and guide resection of recurrent loco-regional tumour in DTC patients with ¹³¹I-negative loco-regional metastatic foci.     

Report on the workshop "workflow rectal cancer II" in Burghausen

The task force "workflow rectal cancer II" defined operative techniques in lower rectal cancer, especially the total mesorectal excision and an improved technique of abdominalperineal resection. New aspects for treatment of rectal cancer with primary distant metastases are described. Due to newer publications a concept of bidirectional procedure with surgery and radiochemotherapy is recommended, where the operation must not be inevitably the first step. In anastomoses below 6 cm of the anocutaneous verge a reservoir should be performed on principle due to better functional results. The colon-j-pouch with a maximal loop length of 6 cm is best investigated under these conditions, the other procedures should be further evaluated.     

Multiple cutaneous granular cell tumors: a case report and review of the literature

Granular cell tumors are benign neoplasms derived from Schwann cells. Their clinical presentation ranges from large verrucose nodules, as in our patient, to small, nonspecific, subcutaneous papules. Approximately half of granular cell tumors develop in the head-and-neck region, most commonly on the tongue. Multiple granular cell tumors are not a sign of malignancy and may be more common than generally reported.     

DNA microarray technology and its applications in dermatology

The use of DNA microarray technology in biomedical research has dramatically increased during the past years. In the present report, we provide an overview on the basic DNA microarray technology and biostatistical methods for gene expression analysis. A focus is then put on its applications in dermatological research. In recent years, a series of gene expression studies have been performed for various dermatological diseases, such as malignant melanoma, psoriasis and lupus erythematosus. These analyses have identified interesting target genes as well as putative disease susceptibility loci. However, further functional studies will be needed for a more complete understanding of the pathogenesis of these diseases. This may be performed by means of the recently developed RNA interference technology. Besides its role in large-scale gene expression studies, DNA microarray technology has proved to be a valuable tool for genomic screens of genetic alterations, e.g. single nucleotide polymorphisms. These play a role in tumour development and progression, and also function as genetic markers for disease susceptibility. Taken together, DNA microarray technology opens enormous perspectives for dermatologists. It may help us understand the complex pathogenesis of a wide variety of dermatologic diseases and identify their genetic background.