Efficacy of ex vivo purging for autologous bone marrow transplantation in the treatment of acute nonlymphoblastic leukemia

We used an in vitro measure of drug activity to predict the efficacy of ex vivo purging of leukemic cells from autologous bone marrow grafts. We previously found that the myeloid progenitor cell (CFU-GM) content of the marrow grafts after ex vivo purging with 4- hydroperoxycyclophosphamide (4-HC) correlates with time to hematologic recovery after autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. We observed that variable red blood cell concentration of the bone marrow incubation mixture results in differential cytotoxic activity of 4-HC. The CFU-GM content of the graft after the ex vivo treatment is a measure of this 4-HC activity. We analyzed the disease-free survival of 45 patients with acute nonlymphoblastic leukemia undergoing autologous bone marrow transplantation with 4-HC purged grafts. Patients who relapsed after transplantation had 4.2 +/- 1.1% of graft CFU-GM surviving the ex vivo purge, compared with 1.1 +/- 0.4% for patients who achieved a sustained remission (P = .06). Twenty-three patients with a CFU-GM content after 4-HC purging of greater than 1% of the pretreatment value had an actuarial disease-free survival of 12%, compared to 36% for 22 patients with a less than or equal to 1% CFU-GM content after purging (P = .006). Therefore, percent CFU-GM survival as a measure of 4-HC cytotoxicity identified a group of patients with insufficient purging. Although no randomized clinical trials have documented the need for ex vivo purging, our results suggest that effective bone marrow purging is important for the optimal application of autologous transplantation in the treatment of acute nonlymphoblastic leukemia.     

Effectiveness of individualized physiotherapy on pain and functioning compared to a standard exercise protocol in patients presenting with clinical signs of subacromial impingement syndrome. A randomized controlled trial

Background  

Shoulder impingement syndrome is a common musculoskeletal complaint leading to significant reduction of health and disability. Physiotherapy is often the first choice of treatment although its effectiveness is still under debate. Systematic reviews in this field highlight the need for more high quality trials to investigate the effectiveness of physiotherapy interventions in patients with subacromial impingement syndrome.     

Spousal bereavement in older adults: common, resilient, and chronic grief with defining characteristics

The purpose of this study was to identify empirically patterns of grief among 141 older bereaved spouses. A longitudinal hierarchical cluster procedure with the Ward agglomeration method was used to identify distinct clusters based on grief scores. Three clusters were identified: common (49%), resilient (34%), and chronic (17%) grief. Members of the common grief cluster experienced elevated levels of grief and depressive symptoms that decreased over time. Members of the resilient cluster experienced the lowest levels of grief and depression and the highest quality of life. The chronic grief cluster experienced the highest levels of grief and depression, more sudden deaths, the lowest self-esteem, and the highest marital dependency. The majority in this chronic cluster also met proposed criteria for a diagnosis of complicated grief. Five out of every six bereaved spouses adjusted well over time, and about a third of these showed considerable resilience without negative consequences. One out of six experienced a chronic grief syndrome. Early identification of this syndrome can lead to referral to newly emergent treatments specific for grief.     

Interpretation of non-invasive breath tests using 13C-labeled substrates - a preliminary report with 13C-methacetin

Non-invasive breath tests can serve as valuable diagnostic tools in medicine as they can determine particular enzymatic and metabolic functions in vivo. However, methodological pitfalls have limited the actual clinical application of those tests till today. A major challenge of non-invasive breath tests has remained the provision of individually reliable test results. To overcome these limitations, a better understanding of breath kinetics during non-invasive breaths tests is essential. This analysis compares the breath recovery of a ¹³C-methacetin breath test with the actual serum kinetics of the substrate. It is shown, that breath and serum kinetics of the same test are significantly different over a period of 60 minutes. The recovery of the tracer ¹³CO₂ in breath seems to be significantly delayed due to intermediate storage in the bicarbonate pool. This has to be taken into account for the application of non-invasive breath test protocols. Otherwise, breath tests might display bicarbonate kinetics despite the metabolic capacity of the particular target enzyme.     

The validity and reliability of scales for the evaluation of end-of-life care in advanced dementia

The lack of valid and reliable instruments designed to measure the experiences of older persons with advanced dementia and those of their health care proxies has limited palliative care research for this condition. This study evaluated the reliability and validity of 3 End-of-Life in Dementia (EOLD) scales that measure the following outcomes: (1) satisfaction with the terminal care (SWC-EOLD), (2) symptom management (SM-EOLD), and (3) comfort during the last 7 days of life (CAD-EOLD). Data were derived from interviews with the health care proxies (SWC-EOLD) and primary care nurses (SM-EOLD, CAD-EOLD) for 189 nursing home residents with advanced dementia living in 15 Boston-area facilities. The scales demonstrated satisfactory to good reliability: SM-EOLD (alpha=0.68), SWC-EOLD (alpha=0.83), and CAD-EOLD (alpha=0.82). The convergent validity of these scales, as measured against other established instruments assessing similar constructs, was good (correlation coefficients ranged from 0.50 to 0.81). The results of this study demonstrate that the 3 EOLD scales demonstrate "internal consistency" reliability and demonstrate convergent validity, and further establish their utility in palliative care dementia research.     

Gender differences in the effects of bereavement-related psychological distress in health outcomes

BACKGROUND: This study examined whether traumatic grief, depressive and anxiety symptoms formed three distinct factors for widows and widowers. In addition, we examined whether high symptom levels of traumatic grief, depression and anxiety predicted different mental and physical health outcomes for widows and widowers. METHOD: Ninety-two future widows and 58 future widowers were interviewed at the time of their spouse's hospital admission and then at 6 weeks, 6, 13 and 25 month follow-ups. Principal axis factor analyses tested the distinctiveness of traumatic grief, depressive and anxiety symptoms, by gender. Repeated measures ANOVA tested for gender differences and changes over time in mean symptom levels of traumatic grief, depression and anxiety. Linear and logistic regression models estimated the effects of high symptom levels of traumatic grief, depression and anxiety at 6 months on health outcomes at 13 and 25 months post-intake by gender. RESULTS: Three distinct symptom clusters (i.e. traumatic grief, depressive and anxiety symptoms) were found to emerge for both widows and widowers. Widows had higher mean levels of traumatic grief, depressive and anxiety symptoms. High symptom levels of traumatic grief measured at 6 months predicted a physical health event (e.g. cancer, heart attack) at 25 months post-intake for widows. High symptom levels of anxiety measured at 6 months predicted suicidal ideation at 25 months for widowers. CONCLUSIONS: The results suggest that there are gender differences in the levels of psychological symptoms resulting from bereavement and in their effects on subsequent mental and physical health for widows and widowers.     

Treatment of pregnancy-related pelvic girdle and/or low back pain after delivery design of a randomized clinical trial within a comprehensive prognostic cohort study [ISRCTN08477490]

Background  

Pregnancy-related pelvic girdle and/or low back pain is a controversial syndrome because insight in etiology and prognosis is lacking. The controversy relates to factors eliciting pain and some prognostic factors such as the interpretation of pain at the symphysis. Recent research about treatment strategies also reflects those various opinions, in fact suggesting there is professional uncertainty about the optimal approach. Currently, physiotherapists often prescribe a pain-contingent treatment regime of relative rest and avoiding several day-to-day activities. Additionally, treatment more often includes an exercise program to guide rectification of the muscle imbalance and alignment of the pelvic girdle. Effectiveness of those interventions is not proven and the majority of the studies are methodologically flawed. Investigators draw particular attention to biomedical factors but there is growing evidence that important prognostic issues such as biopsychosocial factors appear to be even more important as point of action in a treatment program.