ALT-946 and aminoguanidine,inhibitors of advanced glycation,improve severe nephropathy in the diabetic transgenic (mREN-2)27 rat

The severe diabetic nephropathy that develops in the hypertensive transgenic (mRen-2)27 rat with streptozotocin (STZ) diabetes has previously been considered angiotensin II-dependent. Because metabolic pathways are also activated in the diabetic kidney, the present study aimed to determine whether renoprotection could be afforded with inhibitors of advanced glycation end products (AGEs), ALT-946, and aminoguanidine (AG). At 6 weeks of age, nondiabetic control and STZ diabetic Ren-2 rats were randomized to receive vehicle, ALT-946 (1 g/l), or AG (1 g/l) and were studied for 12 weeks. Systolic blood pressure was unchanged with diabetes, ALT-946, or AG. Both kidney weight and glomerular filtration rate were increased with diabetes and unchanged with ALT-946 or AG. ALT-946 and AG equally ameliorated glomerulosclerosis and medullary pathology; however, ALT-946 did reduce cortical tubular degeneration to a greater extent than AG. Albumin excretion rate, which was elevated with diabetes, was reduced with ALT-946 but not AG. AGE immunolabeling was increased in glomeruli and reduced with ALT-946 and AG. These findings indicate that even in the context of renal injury presumed to be primarily blood pressure- and/or angiotensin II-dependent, approaches that interfere with metabolic pathways such as inhibitors of AGE formation can confer renal protection in experimental diabetes.     

Development and validation of CF-Medication Beliefs Questionnaire: A mixed-methods approach

Background

Beliefs about medication have been associated with adherence in other diseases but there are no existing disease-specific medication beliefs questionnaires for CF. This mixed-methods validated the Cystic Fibrosis Medication Belief Questionnaire (CF-MBQ), based on social cognitive theory.

Uso de terapia con presión negativa en heridas con fístulas entéricas

Objective

Negative pressure therapy (VAC, vacuum assisted closure) is a method used still in our country. It consists of a system of aspirating a wound by means of a piece of foam and a few adhesive films. It allows the treatment of complex wounds, included (although this is still controversial) those with intestinal fistulas. We present 3 cases of treatment with VAC in this situation and a review of the published literature.

Patients and method

We have treated 10 patients, since VAC therapy was introduced into our centre of which 3 of whom had a fistula in the bed of the surgical wound. We describe the clinical information of the patients and the therapy that followed in each of the cases.

Results

Significant local clinical improvement of the disease, with control of the symptoms, was achieved in all 3 cases. We were able to re-operate to close the fistula in one of the patients, with subsequent good progression of the wound. In the other two cases it gave them a better quality of life although both died due to the overall complexity of their situation.

Conclusions

VAC therapy, although controversial in the treatment of intestinal fistulas, can help to improve the local situation of the wounds, the comfort of the patients and their general situation.     

Predictors of in-hospital mortality and 6-month functional outcomes in older adults after moderate to severe traumatic brain injury

Introduction

Traumatic brain injury (TBI) is the single largest cause of death and disability following injury worldwide. While TBI in older adults is less common, it still contributes to significant morbidity and mortality in this group. Understanding the patient characteristics that result in good and poor outcome after TBI is important in the clinical management and prognosis of older adult TBI patients. This population-based study investigated predictors of mortality and longer term functional outcomes following serious TBI in older adults.

Methods

All older adults (aged > 64 years), isolated moderate to severe TBI cases from the population-based Victorian State Trauma Registry for the period July 2005 to June 2007 (inclusive) were extracted for analysis. Demographic, injury event, injury diagnosis, management and comorbid status information were obtained and the outcomes of interest were in-hospital mortality, and the Glasgow Outcome Scale-Extended (GOS-E) score at 6 months post-injury. Multivariate logistic regression analyses were used to identify independent predictors of in-hospital mortality and independent living (GOS-E > 4) status at 6 months.

Results

Of the 428 isolated, older adult TBI cases, the majority were the result of a fall (88%), male (55%), and aged > 74 years (76%). The in-hospital death rate was 28% and increasing age (p = 0.009), decreasing GCS (p < 0.001) and injury type (p = 0.002) were significant independent predictors of in-hospital mortality. Of the 310 patients who survived to discharge, 65% were successfully followed-up 6 months following injury. There was no difference between patients lost to follow-up and those successfully followed-up with respect to the key population indicators of age, gender, or head injury severity. Younger (<75 years) patients, and those with an SBP on arrival at hospital of 131-150 mmHg, were at increased odds of living independently at follow-up. No patients with a GCS < 9 had a good 6-month outcome, and most of them died. The survival rate for brainstem injury was also low (21%).

Conclusion

In this population-based study, we found that age, GCS, brainstem injury, and systolic blood pressure were the most important factors in predicting outcome in older adults with an isolated moderate to severe TBI.     

Does the presence of an upper extremity injury affect outcomes after major trauma?

BACKGROUND: There is a paucity of information about the impact of upper extremity (UE) injuries on patient outcomes, particularly after major trauma. METHODS: Data were obtained from a statewide trauma registry. Cases were defined as major trauma cases (Injury Severity Score > 15) with (UE group) and without (no-UE group) an associated upper extremity injury. Multivariate analysis was performed to identify independent predictors of outcome. RESULTS: Major trauma patients with UE injury were 1.5 times (p = 0.011) more likely than the no-UE group to have a length of stay greater than 7 days. After adjusting for age, mechanism of injury, and Injury Severity Score, UE injury was not an independent predictor of discharge destination. CONCLUSION: In major trauma patients, the presence of an upper extremity injury is a significant predictor of length of stay, indicating a greater complexity and cost of care associated with this group of major trauma patients.     

Gemcitabine and cisplatin treatment over a 3-week versus a 4-week dosing schedule: a randomized trial coducted in Chinese patients with nonsmall cell lung cancer

Background Gemcitabine plus cisplatin is a standard treatment for stages IIIB and IV nonsmall cell lung cancer （NSCLC）. This randomized phase Ⅱ study evaluated a 3-week versus a 4-week schedule of gemcitabine-cisplatin as first line treatment for Chinese patients with advanced NSCLC.
Methods Patients were randomized to receive cisplatin 75 mg/m^2 on day 1 plus either gemcitabine 1250 mg/m^2 on days 1 and 8 of a 21-day cycle （3-week group） or gemcitabine 1000 mg/m2 on days 1,8 and 15 of a 28-day cycle （4-week group）.
Results One hundred patients were enrolled in this study. The response rate was 24% （12/51 patients） in the 3-week group and 27% （13/49 patients） in the 4-week group. There were no statistically significant differences between the two treatment groups in survival （hazard ratio： 1.19; 95% CI： 0.68-2.09） with a median survival of 12.1 months and 13.8 months in the 3-week group and the 4-week group respectively. The rate of grade 3/4 toxicity in the 3-week group was 55% compared with 86% in the 4-week group （P=0.001）. The difference in the incidence of grade 3/4 haematological toxicities did not reach statistical significance （3-week： 37%, 4-week： 57%）, however grade 3/4 drug related neutropenia （3-week： 27%, 4-week： 51%） and thrombocytopenia （3-week： 8%, 4-week： 31%） were significantly lower in the 3-week group. Grade 3/4 nonhaematological toxicities were less in the 3-week group （33% cf 63%; P=0.005）.
Conclusions The differences in the efficacy endpoints were all in favour of the 4-week schedule of gemcitabine plus cisplatin, however these differences did not reach statistical significance. Fewer grade 3/4 toxicities were observed in the 3-week group compared with the 4-week group.     

Prevalence of sleep disturbance and the association between poor disease control in people with ankylosing spondylitis within the Australian clinical setting (ASLEEP study): a real-world observational study using the OPAL dataset

Clinical Rheumatology - Sleep disturbance and fatigue are commonly reported in ankylosing spondylitis (AS) but specific prevalence and the relationship to disease control are unknown. This...     

Getting comfortable with “comfort feeding”: An exploration of legal and ethical aspects of the Australian speech-language pathologist’s role in palliative dysphagia care

Purpose: With an ageing population, speech-language pathologists (SLPs) can expect to encounter legal and ethical challenges associated with palliative and end-of-life care more frequently. An awareness of the medico-legal and ethical framework for palliative dysphagia management will better equip SLPs to work effectively in this area.

Method: This narrative review examines a range of legislation, legal, ethical and SLP literature that is currently available to orient SLPs to legal and ethical palliative dysphagia management in the Australian context.

Result: Relevant legal and ethical considerations in palliative and end-of-life care are described.

Conclusion: SLPs have a role in palliative dysphagia management, however, this can involve unique legal and ethical challenges. The legal position on provision and cessation of nutrition and hydration differs between Australian States and Territories. Decisions by the courts have established a body of relevant case law. This article introduces SLPs to some of the important considerations for legal and ethical palliative care, but is not intended to be directive. SLPs are encouraged to explore their local options for ethical and medico-legal guidance. It is hoped that increasing SLPs awareness of many of the concepts discussed in this article enhances the provision of high-quality patient-centred care.     

A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome

OBJECTIVES: Psychological treatments are considered to be useful in the irritable bowel syndrome (IBS), although the evidence is based on small, often flawed trials. Although cognitive behavior therapy (CBT) and relaxation therapy have both been promising, we hypothesized that CBT would be superior to relaxation and standard care alone in IBS patients. The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS. METHODS: Patients (n = 105) with Rome I criteria for IBS were recruited from advertisement (n = 51) and outpatient clinics (n = 54); those patients with resistant IBS were not included. A randomized controlled trial with three arms (standard care for all groups plus either CBT or relaxation) for 8 wk was conducted, which applied blinded outcome assessments using validated measures with 1 yr of follow-up. The primary outcome for this study was bowel symptom severity. RESULTS: Of 105 patients at the commencement of treatment, the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1; this persisted at the 52-wk follow-up, with a significant linear trend for scores to change over time (F = 39.57 p < 0.001). However, there were no significant differences among the three treatment conditions. Significant changes over time were found for physical functioning (F = 4.37, p < 0.001), pain (F = 3.12, p < 0.05), general health (F = 2.71, p < 0.05), vitality (F = 2.94, p < 0.05), and the social functioning scales on the Medical Outcomes Study Short Form 36 (F = 4.08, p < 0.05); however, all three arms showed similar improvement. There were significant reductions in anxiety, depression, and locus of control scales, but no significant differences among the treatment groups were detected. CONCLUSION: Cognitive behavior and relaxation therapy seem not to be superior to standard care alone in IBS.