Pharmacokinetic properties of esomeprazole in adolescent patients aged 12 to 17 years with symptoms of gastroesophageal reflux disease: A randomized, open-label study

OBJECTIVE: The aim of this study was to assess the pharmacokinetic (PK) properties and tolerability of esomeprazole 20 and 40 mg after single and repeated oral doses in adolescents with symptoms of gastroesophageal reflux disease (GERD). RESULTS: The study included 15 boys and 13 girls (mean age, 14.3 years). Geometric mean AUC(0-infinity) values (overall drug exposure) were 1.58 and 5.57 micromol . h/L (0.027 and 0.083 pmol x h x L(-1)/kg) after single-dose administration of esomeprazole 20 and 40 mg, respectively, on day 1. Corresponding values with repeated doses (day 8) were 3.65 and 13.86 micromol x h/L (0.064 and 0.207 micromol x h x L(-1)/kg). Geometric mean Cmax values were 0.67 and 2.78 micromol/L (0.012 and 0.041 micromol/L x kg(-1)) with single-dose administration of esomeprazole 20 and 40 mg, respectively, and 1.45 and 5.13 micromol/L (0.026 and 0.075 micromol/L x kg(-1)), respectively, with repeated doses (day 8). These mean AUC(0-infinity) and CmaX values were >2-fold with the 40 mg dose compared with the 20-mg dose with single- and repeated-dose administration. The most common adverse event was headache (2 [7.1%] patients). CONCLUSIONS: The results of this study suggest that the PK parameters of esomeprazole were both dose- and time-dependent in these adolescents with GERD. Both doses of esomeprazole were well tolerated in this study population.     

Focal spasticity therapy with botulinum toxin: effects on function, activities of daily living and pain in 100 adult patients.

OBJECTIVE: Analysis of the effects of a comprehensive focal spasticity program in adult patients. DESIGN: Retrospective study of an out-patient cohort. PATIENTS: One hundred patients were enrolled in the study (54 men and 46 women, mean age 41 years (SD 14). Cerebral palsy and stroke were equally common (80% in total). The remaining patients had miscellaneous diagnoses, including traumatic brain injury. METHODS: On average 230 units (SD 101) of botulinum toxin A Botox was given for 227 principal therapy targets chosen by the patient or the caregiver. One patient could have several targets for therapy. Administration of botulinum toxin was combined with 260 additional therapeutic interventions, most of which were forms of physical therapy. The effects were assessed after 6 weeks and compared with baseline functional abilities 1-2 weeks prior to therapy. RESULTS: Improvement was observed for 211 (93%) therapy targets, no change in 15 (7%), and impairment in 1, corresponding to an overall improvement in 90 patients (90%), 9 unchanged (9%) and worsening in 1. Spasticity assessment (Ashworth scale 0-4; 30 patients) showed a statistically significant improvement (median at baseline was 3 vs 2 after therapy, mean difference 1.2, p<0.001). CONCLUSION: Improvement was observed in >or=90% of patients and in their principal therapeutic targets in a cohort receiving their first focal spasticity treatment with botulinum toxin A and additional therapy. A strict strategy for patient selection and comprehensive management was followed.     

Experiences of a low-intensity anticoagulation regimen for extended secondary prevention of venous thromboembolism

Extended treatment with vitamin K antagonists for more than 6 months is often used for secondary prevention of venous thromboembolism (VTE) in patients at high or moderate risk for recurrent events. The intensity of anticoagulant therapy is usually maintained at an International Normalized Ratio (INR) of 2-3. An INR of 1.5-2 might also prevent thromboembolic events with less complications of bleeding, but results from randomized trials are not yet available. In a non-prospective, uncontrolled study 40 patients with a history of VTE and an estimated high risk for recurrent events due to several previous events and/or thrombophilic defects were, after a median of 11.5 months on regular intensity anticoagulation (INR 2-3), switched to a low intensity regimen (INR 1.5-2). In six of the patients an estimated high risk for complications of bleeding contributed to this decision. After a median follow-up of 36 months (140 patient-years) recurrent events, complications of bleeding and some basic quality of life measurements regarding the new treatment were registered. No recurrent events, four minor bleedings and no major bleedings were registered. Twenty-six patients preferred an INR of 1.5-2 compared to 2-3. The main reasons for that preference were a lower risk for bleeding (13 patients) and less frequent monitoring of the INR (18 patients). No patient preferred full-dose anticoagulation at INR 2-3. In patients at a high risk for recurrence of VTE an initial period of regular intensity anticoagulation, followed by a low-intensity regimen, may provide effective and safe secondary prophylaxis.     

Prosthesis use in adult acquired major upper-limb amputees: patterns of wear, prosthetic skills and the actual use of prostheses in activities of daily life

Purpose: To describe patterns of prosthesis wear and perceived prosthetic usefulness in adult acquired upper-limb amputees (ULAs). To describe prosthetic skills in activities of daily life (ADL) and the actual use of prostheses in the performance of ADL tasks. To estimate the influence of prosthetic skills on actual prosthesis use and the influence of background factors on prosthetic skills and actual prosthesis use. Method: Cross-sectional study analysing population-based questionnaire data (n?=?224) and data from interviews and clinical testing in a referred/convenience sample of prosthesis-wearing ULAs (n?=?50). Effects were analysed using linear regression. Results: 80.8% wore prostheses. 90.3% reported their most worn prosthesis as useful. Prosthetic usefulness profiles varied with prosthetic type. Despite demonstrating good prosthetic skills, the amputees reported actual prosthesis use in only about half of the ADL tasks performed in everyday life. In unilateral amputees, increased actual use was associated with sufficient prosthetic training and with the use of myoelectric vs cosmetic prostheses, regardless of amputation level. Prosthetic skills did not affect actual prosthesis use. No background factors showed significant effect on prosthetic skills. Conclusions: Most major ULAs wear prostheses. Individualised prosthetic training and fitting of myoelectric rather than passive prostheses may increase actual prosthesis use in ADL. [Box: see text].     

A randomized controlled trial of a support group intervention on the quality of life and fatigue in women after primary treatment for early breast cancer

Background

When diagnosed with breast cancer, most women’s lives change as well as their perspectives on and appreciation of life. The aim of the present study was to evaluate whether psychosocial support intervention could influence health-related quality of life (HRQOL) and fatigue during the first year after diagnosis.

Material and methods

Of 382 patients with newly diagnosed breast cancer, 191 patients were randomized to an intervention group and 191 patients were randomized to a routine control group. The intervention group received support intervention that lasted 1?week on a residential basis, followed by 4?days of follow-up 2?months later. The support intervention included informative educational parts, relaxation training, mental visualization, and nonverbal communication. HRQOL was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-BR23 questionnaires and fatigue with the Norwegian version of the fatigue scale at baseline and at 2, 6, and 12?months after intervention.

Result

There was a time-dependent improvement in both functional and symptom scales between baseline and 12?months as measured by the EORTC QLQ-C30 and BR23 questionnaires and there was a decrease in fatigue between baseline and after 2?months with further improvement up to 12?months in both groups, but there were no differences between the intervention and control groups at any point in time.

Conclusion

HRQOL improves and symptoms of fatigue decrease over time, but we could not see any additional effect from the rehabilitation program in this setting.     

Low-frequency oscillations of the laser Doppler perfusion signal in human skin

Spectral analysis of the laser Doppler flow (LDF) signal in the frequency interval from 0.0095-2.0 Hz reveals blood flow oscillations with frequencies around 1.0, 0.3, 0.1, 0.04 and 0.01 Hz. The heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, the neurogenic activity of the vessel wall and the vascular endothelium influence these oscillations, respectively. The first aim of this study was to investigate if a slow oscillatory component could be detected in the frequency area below 0.0095 Hz of the human cutaneous blood perfusion signal. Unstimulated basal blood skin perfusion and enhanced perfusion during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were measured in healthy male volunteers and the wavelet transform was computed. A low-frequency oscillation between 0.005 and 0.0095 Hz was found both during basal conditions and during iontophoresis with ACh and SNP. Iontophoresis with ACh increased the normalized amplitude to a greater extent than SNP (P = 0.001) indicating modulation by the vascular endothelium. To gain further insight into the mechanisms for this endothelium dependency, we inhibited nitric oxide (NO) synthesis with N(G)-monomethyl-L-arginine (L-NMMA) and prostaglandin (PG) synthesis by aspirin. L-NMMA did not affect the increased response to ACh vs. SNP iontophoresis in the 0.005-0.0095-Hz interval (P = 0.006) but abolished the difference in the 0.0095-0.021-Hz interval (P = 0.97). Aspirin did not affect the difference in response to ACh and SNP in either of the two frequency intervals. Thus, other endothelial mechanisms, such as endothelium-derived hyperpolarizing factor (EDHF), might be involved in the regulation of this sixth frequency interval (0.005-0.0095 Hz).     

Surgical treatment of endocrine pancreatic tumours

Endocrine pancreatic tumours (EPTs) are uncommon, with a major challenge to alert physicians to their recognition and requirements of treatment. Functioning EPTs cause well-known clinical syndromes of hormone excess. Insulinomas, gastrinomas and glucagonomas are most common; vipomas and somatostatinomas are rare. EPTs also occur as non-functioning lesions without symptoms of hormone excess occasionally with ectopic hormone, such as ACTH and Cushing syndrome as a late complication. The majority of EPTs are sporadic, but they may also be part of a multiple endocrine neoplasia type 1 syndrome or rarely the von Hippel-Lindau syndrome. EPTs have been of great interest to endocrine surgeons and we have, during recent years, witnessed continuing advances in diagnosis, imaging and treatment of the different tumour entities. It has become obvious that surgical treatment of these tumours is of increased concern and can have a marked impact on symptoms and survival.     

The proinflammatory CXC-chemokines GRO-α/CXCL1 and MIG/CXCL9 are concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids

Background Ulcerative colitis is characterized by relapsing mucosal inflammation where the lesions include tissue-damaging granulocytes. In addition, T cells and natural killer (NK) cells play important pathophysiologic roles. Chemokines are a large family of peptides that play key roles in the regulation of inflammation. The CXC-chemokines, growth-related oncogene (GRO)-α/CXCL1 and interleukin (IL)-8/CXCL8, both recruit neutrophils and possess mitogenic properties, whereas the interferon-dependent CXC-chemokines monokine induced by gamma-interferon (MIG)/CXCL9, interferon-γ inducible protein of 10 kD/CXCL10, and IFN-inducible T cell alpha chemoattractant/CXCL11 recruit and activate T cells and NK cells. Materials and methods The expression of CXC-chemokines was studied in eight controls and in 11 patients suffering from ulcerative colitis in the distal part of the colon, before and during topical treatment with corticosteroids. Perfusates (obtained before, after 7 days, and after 28 days of treatment) and pinch biopsies (obtained before and after 28 days of treatment) were collected by colonoscopy. The rectal release of GRO-α and MIG was determined by enzyme-linked immunosorbent assay (ELISA), and tissue expression of the chemokines was detected in colonic tissue by immunohistochemistry. Results In perfusates, high levels of GRO-α, IL-8, and MIG were detected compared with controls (p = 0.02, 0.005, and p = 0.03, respectively). During treatment with corticosteroids, both GRO-α and MIG decreased. In clinical nonresponders, characterized by sustained inflammation, the levels of GRO-α and MIG remained elevated. Both epithelial cells and granulocytes, present in the submucosa, expressed GRO-α and MIG as detected by immunohistochemistry. Conclusions CXC-chemokines are likely to be important in the pathophysiology of ulcerative colitis and may become targets for novel treatment strategies. In addition, GRO-α may serve as a marker of disease activity.     

Surgery for ventricular tachycardia in patients undergoing surgical ventricular restoration: The Karolinska approach

This article presents a review on the efficacy of surgical ventricular restoration and direct surgery for ventricular tachycardia in patients with left ventricular aneurysm or dilated ischemic cardiomyopathy. The procedure includes a non-electrophysiologically guided subtotal endocardiectomy and cryoablation in addition to endoventricular patch plasty of the left ventricle. Coronary artery bypass surgery and mitral valve repair are performed concomitantly as needed. In our experience, this procedure yielded a 90% success rate in terms of freedom from spontaneous ventricular tachycardia, with an early mortality rate of 3.8%. A practical guide to the pre- and postoperative management of these patients is provided. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.