Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission.

PURPOSE: The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. PATIENTS AND METHODS: The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen-identical related (n = 103), or matched unrelated (n = 118) donor. RESULTS: Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P =.014) or who relapsed (P <.001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P =.052), and Philadelphia chromosome-positive patients had no poorer outcome than Philadelphia chromosome-negative patients. Total-body irradiation-based conditioning improved DFS in comparison with busulfan (P =.041). CONCLUSION: Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.     

Estimating numbers of injecting drug users in metropolitan areas for structural analyses of community vulnerability and for assessing relative degrees of service provision for injecting drug users

This article estimates the population prevalence of current injection drug users (IDUs) in 96 large US metropolitan areas to facilitate structural analyses of its predictors and sequelae and assesses the extent to which drug abuse treatment and human immunodeficiency virus (HIV) counseling and testing are made available to drug injectors in each metropolitan area. We estimated the total number of current IDUs in the United States and then allocated the large metropolitan area total among large metropolitan areas using four different multiplier methods. Mean values were used as best estimates, and their validity and limitations were assessed. Prevalence of drug injectors per 10,000 population varied from 19 to 173 (median 60; interquartile range 42–87). Proportions of drug injectors in treatment varied from 1.0% to 39.3% (median 8.6%); and the ratio of HIV counseling and testing events to the estimated number of IDUs varied from 0.013 to 0.285 (median 0.082). Despite limitations in the accuracy of these estimates, they can be used for structural analyses of the correlates and predictors of the population density of drug injectors in metropolitan areas and for assessing the extent of service delivery to drug injectors. Although service provision levels varied considerably, few if any metropolitan areas seemed to be providing adequate levels of services.     

Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines form performing HSCT in MS. This conference was organized in order to : (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution. Received: 14 May 1999, Received in revised form: 4 January 2000, Accepted: 19 January 2000     

Pharmacist involvement in antimicrobial use at rural community hospitals in four Western states.

PURPOSE: Pharmacist involvement in antimicrobial use at small rural hospitals in four Western states was studied. METHODS: Surveys were mailed in July 2000 to hospitals with a daily patient census of <150 in Idaho, Nevada, Utah, and eastern Washington. RESULTS: Seventy-seven (77%) of 100 hospitals returned completed surveys. Only 5% of the hospitals had onsite pharmacists 24 hours per day. An onsite pharmacist was present for a median of 26 hours per week in hospitals without 24-hour pharmacist coverage (range, 0-116 hr/wk). Many hospitals (71%) had policies for monitoring or controlling antimicrobial use, but only 28% had a system capable of monitoring compliance with such policies. Few hospitals had systems for recommending changes in antimicrobial selection on the basis of susceptibility test results (27%) or for monitoring physician compliance with dosage recommendations by pharmacists (21%). Onsite pharmacist hours were significantly associated with pharmacists being involved in the initial ordering of antibiotics and providing active oversight of antimicrobial use. There was a negative correlation between onsite pharmacist hours and use of third-generation cephalosporins and carbapenems. CONCLUSION: A survey showed that rural hospital pharmacists in four Western states spent relatively little time monitoring and influencing antimicrobial prescribing.     

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES‐bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine‐1‐phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.     

Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics,Interaction with Food,and Influence on Liver Function

Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ≥ 25 kg/m²) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different CBD formulations were ingested (one per visit). On two additional occasions, CBD or placebo was ingested following a meal. CBD servings were standardized to 30 mg. Considerable pharmacokinetic variability existed between formulations; this pharmacokinetic variability transferred to several of the metabolites. CBD did not influence food induced thermogenesis but did favorably modify early insulin and triglyceride responses. Food appreciably altered the pharmacokinetics of CBD. Finally, CBD did not evoke physiologically relevant changes in markers of liver function. Collectively, these data suggest that consumers should be aware of the appreciable pharmacokinetic differences between commercial CBD formulations, CBD is unlikely to influence the caloric cost of eating but may prove to be of some benefit to initial metabolic responses, consuming CBD with food alters the dynamics of CBD metabolism and increases systemic availability, and low-dose CBD probably does not represent a risk to normal liver function.     

Framing Concerns about Body Image during Pre- and Post-Surgical Consultations for Head and Neck Cancer: A Qualitative Study of Patient–Physician Interactions

Patients with head and neck cancer report high unmet psychosocial needs as they undergo lifesaving treatments that can significantly alter their appearance and cause functional impairments. This qualitative analysis of recordings of 88 pre- and post-surgical consultations involving 20 patients respond to the need for empirical studies of patient–provider conversations about body image concerns. It indicates that the emphasis on concerns about survival, cure, and physical recovery during clinical consultations may leave concerns about the impacts of surgery on appearance and function unexplored and even silenced. The interviews with patients and medical team members that complement the analysis of the recordings suggest that an emphasis on survival, cure, and physical recovery can respond to the need for reassurance in the context of serious illness. However, it can also be problematic as it contributes to the silencing of patients’ concerns and to a potential lack of preparedness for the consequences of surgery. The results of this study can contribute to raising surgeons’ awareness of the interactional dynamics during clinical consultations. Moreover, the results highlight the unique role that surgeons can play in validating patients’ psychosocial concerns to support patients’ rehabilitation in both physical and psychosocial domains.     

Dietary Fibre and Organic Acids in Kiwifruit Suppress Glycaemic Response Equally by Delaying Absorption—A Randomised Crossover Human Trial with Parallel Analysis of 13C-Acetate Uptake

Non-sugar components of kiwifruit reduce the amplitude of the glycaemic response to co-consumed cereal starch. We determined the relative contribution of different non-sugar kiwifruit components to this anti-glycaemic effect. Healthy participants (n = 9) ingested equal carbohydrate meals containing 20 g starch as wheat biscuit (WB, 30 g), and the sugar equivalent of two kiwifruit (KFsug, 20.4 g), either intrinsic or added as glucose, fructose and sucrose (2:2:1). The meals were WB+KFsug (control, no non-sugar kiwifruit components), WB + whole kiwifruit pulp (WB+KF), WB + neutralised kiwifruit pulp (WB+KFneut), WB + low-fibre kiwifruit juice (WB+KFjuice) and WB+KFsug + kiwifruit organic acids (WB+KFsug+OA). All meals were spiked with 100 mg sodium [1-¹³C] acetate to measure intestinal absorption. Each participant ingested all meals in random order. Blood glucose and breath ¹³CO₂ were measured at ingestion and at 15 min intervals up to 180 min. Compared with WB+KFsug, whole kiwifruit pulp (WB+KF) almost halved glycaemic response amplitude (p < 0.001), reduced incremental area under the blood glucose response curve (iAUC) at 30 min (peak) by 50% (p < 0.001), and averted late postprandial hypoglycaemia. All other treatments suppressed response amplitude half as much as whole kiwifruit and averted acute hypoglycaemia, with little effect on iAUC. Effects on ¹³CO₂ exhalation paralleled effects on blood glucose (R² = 0.97). Dietary fibre and organic acids contributed equally to the anti-glycaemic effect of kiwifruit by reducing intestinal absorption rate. Kiwifruit flesh effectively attenuates glycaemic response in carbohydrate exchange, as it contains fructose, dietary fibre and organic acids.