Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.     

Reviewing emergency care systems 2: measuring patient preferences using a discrete choice experiment

Objective: To investigate patients' strength of preferences for attributes associated with modernising delivery of out of hours emergency care services in Nottingham.

Methods: A discrete choice experiment was applied to quantify preferences for key attributes of out of hours emergency care. The attributes reflected the findings of previous research, current policy initiatives, and discussions with local key stakeholders. A self complete questionnaire was administered to NHS Direct callers and adults attending accident and emergency, GP services and NHS walk-in centre. Regression analysis was used to estimate the relative importance of the different attributes.

Results: Response was 74% (n = 457) although 61% (n = 378) were useable. All attributes were statistically significant. Being consulted by a doctor was the most important attribute. This was followed by being consulted by a nurse, being kept informed about waiting time, and quality of the consultation. Respondents were prepared to wait an extra 2 hours 20 minutes to be consulted by a doctor. There were no measurable preference differences between patients surveyed at different NHS entry points. Younger respondents preferred single telephone call access to health care out of hours. Although having services provided close to home and making contact in person were generally preferred, they were less important than others, suggesting that a range of service locations may be acceptable to patients.

Conclusions: This study showed that local solutions for reforming emergency out of hours care should take account of the strength of patient preferences. The method was acceptable and the results have directly informed the development of a local service framework for emergency care.

     

Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia

Reported here are studies of Fanconi anemia fetal cells that led to the first use of umbilical cord blood for hematopoietic reconstitution in a clinical trial. Prenatal diagnosis and HLA typing were performed in fetuses at risk for Fanconi anemia (FA) to identify, prior to birth, those that were unaffected with the syndrome and were HLA-identical to affected siblings. Umbilical cord blood was harvested at the delivery of these infants; assays of progenitor cells indicated the presence of colony-forming units-granulocyte-macrophage (CFU-GM) in numbers similar to those of bone marrow CFU-GM that are associated with successful engraftment in HLA-matched allogeneic bone marrow transplantation. The possibility that umbilical cord blood from a single individual can be used as an alternative to bone marrow for hematopoietic reconstitution has now been demonstrated by the successful engraftment of two patients with FA. Progenitor cell assays of umbilical cord blood collected at the birth of a child affected with FA, who had been misdiagnosed on the basis of chorionic villus sampling (CVS) studies, indicated a profound deficiency in colony formation, consistent with previously reported abnormalities in the growth of FA cells in vitro. These results suggest that the hematopoietic disorder in FA is related to an underlying problem with cell proliferation.     

Retrospective drug detection in cases of drug-facilitated sexual assault: challenges and perspectives for the forensic toxicologist

Reported incidences of drug-facilitated sexual assault (DFSA) are on the increase worldwide. These cases represent a particular challenge for the forensic toxicologist due to the difficulty in obtaining adequate evidence of drug administration. Primarily, this is due to the nature and diversity of the drugs involved, their pharmacology and sampling timescales. Evaluating whether a drug has been administered to a victim for the purpose of sexual assault can often be difficult, if not impossible. This review draws attention to this burgeoning crime and focuses on the unique challenges DFSA cases present in terms of evidential analysis. Current analytical methodologies for investigating DFSA are highlighted and discussed along with developments in improving analytical procedures. In particular, enlarging detection windows by adopting emerging LC-MS techniques is also discussed. This review also highlights the use of cutting-edge technologies such as ultra-HPLC and the use of alternative matrices for addressing the problem of improved retrospective drug detection.     

Aspirin in Alzheimer's disease (AD2000): a randomised open-label trial

BACKGROUND: Cardiovascular risk factors and a history of vascular disease can increase the risk of Alzheimer's disease (AD). AD is less common in aspirin users than non-users, and there are plausible biological mechanisms whereby aspirin might slow the progression of either vascular or Alzheimer-type pathology. We assessed the benefits of aspirin in patients with AD. METHODS: 310 community-resident patients who had AD and who had no potential indication or definite contraindication for aspirin were randomly assigned to receive open-label aspirin (n=156; one 75-mg enteric-coated tablet per day, to continue indefinitely) or to avoid aspirin (n=154). Primary outcome measures were cognition (assessed with the mini-mental state examination [MMSE]) and functional ability (assessed with the Bristol activities of daily living scale [BADLS]). Secondary outcomes were time to formal domiciliary or institutional care, progress of disability, behavioural symptoms, caregiver wellbeing, and care time. Patients were assessed at 12-week intervals in the first year and once each year thereafter. Analysis of the primary outcome measures was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN96337233. FINDINGS: Patients had a median age of 75 years; 156 patients had mild AD, 154 had moderate AD, and 18 had concomitant vascular dementia. Over the 3 years after randomisation, in patients who took aspirin, mean MMSE score was 0.10 points higher (95% CI -0.37 to 0.57; p=0.7) and mean BADLS score was 0.62 points lower (-1.37 to 0.13; p=0.11) than in patients assigned to aspirin avoidance. There were no obvious differences between the groups in any other outcome measurements. 13 (8%) patients on aspirin and two (1%) patients in the control group had bleeds that led to admission to hospital (relative risk=4.4, 95% CI 1.5-12.8; p=0.007); three (2%) patients in the aspirin group had fatal cerebral bleeds. INTERPRETATION: Although aspirin is commonly used in dementia, in patients with typical AD 2 years of treatment with low-dose aspirin has no worthwhile benefit and increases the risk of serious bleeds.     

A study on the association with hepatitis B and hepatitis C in 1557 patients with lichen planus

Background Previous reports have demonstrated contradicting results on the association between lichen planus and hepatitis. Objectives The aim of this study was to investigate the association between lichen planus and viral hepatitis. Methods Patients with lichen planus were compared with controls regarding the prevalence of viral hepatitis in a case‐control study using logistic multivariate regression models. The study was performed utilizing the medical database of Clalit Health Services. Results The study included 1557 lichen planus patients over the age of 20 years and 3115 age‐ and gender‐matched controls. The prevalence of hepatitis C in patients with lichen planus was higher than that in the control group (1.9%, 0.4% respectively, P < 0.001). In a multivariate analysis, lichen planus was associated with hepatitis C (OR 4.19, 95% CI 2.21; 7.93). The prevalence of hepatitis B in patients with lichen planus was similar to that in the control group (0.9%, 0.5% respectively, P = 0.12). A multivariate analysis revealed that lichen planus was not associated with hepatitis B (OR 1.69, 95% CI 0.82; 3.47). Conclusion Lichen planus is associated with hepatitis C but not with hepatitis B. Physicians who care for patients with lichen planus should consider screening patients with lichen planus for hepatitis C.     

Relationship between oral hygiene practices and oral status in dentate elderly people living in residential homes

OBJECTIVES: To investigate the relationship between the oral hygiene practices of dentate elderly people living in residential homes, their requests for assistance and their oral health status. METHODS: 164 people (81.2+/-7.4 years) participated in an interview and oral examination, and provided a stimulated saliva sample. RESULTS: The mean number of coronal decayed surfaces (CDS) was 2.4+/-5.9, stimulated salivary levels (log(10)cfu/ml) of mutans streptococci, lactobacilli and yeasts were 1.6+/-2.1, 3.0+/-2.2, 2.1+/-1.7, respectively, and 53% had root decayed surfaces (RDS). Plaque (PI) and gingival (GI) Indices were 2.3+/-0.7 and 1.6+/-0.4 and denture debris scores (DDS) were high. 31% of the population cleaned their mouths twice daily without requesting help and they had significantly fewer yeasts, RDS, restorations on root surfaces, lower PI, GI (P<0.005) and DDS (P<0.0001) than the 69% who cleaned less often. 50% of those who cleaned less frequently requested assistance with oral hygiene but only 5% said that their carers supported them. Those residents who requested help had significantly higher levels of yeasts, lactobacilli (P<0.001), retained roots, DDS, RDS (P<0.005), PI and GI (P<0.0001). CONCLUSION: The elderly residents' perceived need for assistance with oral hygiene was related directly to oral hygiene status and to clinical indicators of mucosal and dental diseases.