Frequency and specificity of the Trima Accel "verify WBCs" advisory: considerations for product management

BACKGROUND: The Trima Accel displays a “verify WBCs” message if the plateletpheresis product (PLT) may not be leukoreduced (LR). Most blood banks require sensitive white blood cell (WBC) testing of these PLTs by flow or Nageotte. We evaluated how often these PLTs were non‐LR by European or US Food and Drug Administration (FDA) criteria and whether sensitive WBC testing is necessary. STUDY DESIGN AND METHODS: Phase 1 reviewed the frequency of this message with various procedure types and the flow WBC results for PLTs with or without the message. Phase 2 assessed how many FDA LR failures were detectable by a hematology analyzer. In Phase 3, PLTs were managed by hematology analyzer results. RESULTS: In Phase 1, 3.8% of PLT‐only and 11.1% of PLT‐plasma collections had the “verify WBCs” message. Only 1% of “verify” PLTs contained more than 1 × 10⁶ WBCs and only 0.5% were FDA LR failures. In Phase 2, 10 of 670 “verify” PLTs and one nonflagged PLT were FDA LR failures. Six of 11 LR failures had hematology analyzer WBC concentrations of 0.4 × 10⁹/L or higher. In Phase 3, “verify” PLTs were allowed in inventory if hematology analyzer WBC concentration was below 0.4 × 10⁹/L; inventory quality control showed no FDA LR failures by flow. Trima Version 6.0 software lowered the “verify” message frequency in PLT‐plasma procedures but not in PLT‐only procedures. CONCLUSION: Four percent of Trima PLT collections have the “verify WBCs” message but almost all of these are LR by European and FDA criteria. Fifty percent of FDA LR failures were detectable by a hematology analyzer. Sensitive WBC testing of all “verify WBCs” PLTs may not be necessary to satisfy LR quality assurance requirements.     

The development and testing of an algorithm for diagnosis of active labour in primiparous women

OBJECTIVES: to describe the development and testing of an algorithm for diagnosis of active labour in primiparous women. DESIGN: qualitative and quantitative methods were used. A literature review was first conducted to identify the key cues for inclusion in the algorithm. Focus groups of midwives were then conducted to assess content validity, finally a vignette study assessed the inter-rater reliability of the algorithm. SETTING: midwives from two study sites were invited to participate. Data were collected during 2002 and 2003. PARTICIPANTS: midwives from the first site took part in the focus groups (n=13), completed vignettes (n=19), or both. Midwives from the second site then completed vignettes (n=17). FINDINGS: an algorithm, developed from the key informational cues reported in the literature, was validated in relation to content validity by the findings from the focus groups. Inter-rater reliability was tested using vignettes of admission case histories and was found to be moderate in the first test (K=0.45). However, after modifying the algorithm the kappa score was 0.86, indicating a high level of agreement. KEY CONCLUSIONS: diagnosis of labour may be straightforward on paper but is frequently problematic in practice. This may be because the diagnosis of labour is made in a high pressured environment where conflicting pressures of workload, limited resources and emotional pressures add to the complexity of the judgement. IMPLICATIONS FOR PRACTICE: we offer a valid and reliable decision-support tool as an aid for diagnosis of labour. The evaluation of the implementation of this tool is under way and will determine whether it is effective in reducing unnecessary admissions and improving clinical outcomes for women.     

A quantitative ultrastructural study of collagen fibril formation in the healing extensor digitorum longus tendon of the rat

A study was made of collagen fibril populations in healing tendon using a window lesion in rat extensor tendon. Two environments were thus created. One (the lesion area) where stress levels were reduced; the other (the non-lesion area) where stress levels were increased. In both areas a population of small diameter (less than 50nm) collagen fibrils were synthesized. Lesion area fibrils increased their diameter only slowly. Non-lesion area fibrils added to a population which increased its diameter distribution comparatively rapidly. It is suggested that in the lesion area fibrils were synthesized in response to tissue damage and low levels of stress. These may be of type III collagen. In the non-lesion area fibrils were synthesized in response to raised levels of stress. These may be of type I collagen. Implications of these events, especially as they might relate to gap formation in flexor tendon surgery are discussed.     

Protease inhibitor monotherapy is associated with a higher level of monocyte activation,bacterial translocation and inflammation

Introduction

Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation.

Methods

We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed.

Results

CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01).

Conclusions

Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.     

Ethical and legal issues in the use of related donors for therapeutic insemination

Donor insemination involving family members can be complex. Although it may offer some advantages to the requesting individuals, to the donor, or to the family, related donation does raise a significant number of concerns. The specific circumstances of these requests should be considered carefully--in most cases more carefully than with anonymous sperm donation. Still, in the United States the freedom of couples or individuals to decide whether, when, and how to reproduce is highly valued. Respect for the autonomy of the involved family members would favor serious consideration of proposals for intrafamilial sperm donation, when all parties have freely consented to participate. Without exception, standards governing anonymous sperm donation should be followed in evaluating the proposed sperm donor for infectious and genetic diseases. The semen specimens should be frozen and quarantined for 180 days. In many cases, the 6-month delay that results from this quarantine will discourage a couple from pursuing intrafamilial sperm donation. Adequate time is essential to assess these relationships when requested. Multiple visits to physicians, nurses, counselors, and lawyers may be necessary for a thorough assessment. Programs should require prospective participants, including recipients, donors, and partners of donors, to undergo psychologic counseling by a professional knowledgeable about gamete donation. Counselors should address issues such as emotional risks, potential impact on family relationships, the donor-recipient relationship, the future role of the donor in the offspring's life, and what information will be disclosed to the offspring. The process of obtaining informed consent from the requesting individuals, the donor, and, possibly, the donor's wife should involve a thorough discussion of potential risks to all parties. Clinicians should assure that the decision to be a sperm donor has been voulntary and free from manipulative and coercive influences. Financial incentives, including direct and indirect payment and inheritance, should not be so substantial that they become inducements that may lead the prospective donor to discount the emotional risk associated with the procedure. Legal counsel should be strongly encouraged to clarify issues of disclosure, rights, and duties, as well as the donor's relationship to the resulting offspring. Any possible changes in these issues in the event of divorce or death of requesting individuals should be addressed. In certain cases, requests should be immediately denied. Gametes from consanguineous relationships should never be used to initiate a pregnancy. Because of potential parental conflicts of interest, programs should not allow minors under the age of 18 years to donate sperm. The use of a family member may not be appropriate when sperm donation is chosen to prevent genetic diseases. Careful genetic counseling should be done before intrafamilial sperm donation is allowed in this situation. If, after careful consideration of the proposed arrangement, the physician chooses to facilitate the relationship, then all precautions should be taken to prevent medical, psychologic, and legal harm to the requesting couple or individual, the potential donor, and the prospective child. Programs that offer these arrangements should make every effort to obtain long-term follow up on the outcomes of these relationships, so that programs can provide more accurate information to families considering these relationships in the future. The physician or program should not feel obligated to agree to every request for intrafamilial sperm donation. When the assessment reveals consistent concerns about coercion of the prospective donor or about unhealthy family dynamics, the physician should feel free to deny these procedures. The physician should advise the requesting couple or individual to seek alternative methods, such as anonymous sperm donation, to conceive.     

Phase I escalation of gemcitabine combined with protracted oral etoposide in gynecologic malignancies: A Gynecologic Oncology Group study

Objective: Although improvementshave been made in the management ofpatients with advanced ovarian cancer,long-term survivors are still uncommon. Gemcitabine and prolonged oral etoposidehave shown reproducible single-agentactivity in patients withplatinum/paclitaxel-resistant ovariancancer. This, combined with preclinicalsynergism, prompted the GynecologicOncology Group to determine the maximumtolerated dose (MTD) of this combination. Methods: Eligible patients hadrecurrent epithelial ovarian cancer,primary papillary peritoneal, or fallopiantube carcinoma. All had received priorplatinum/paclitaxel-based chemotherapy andhad adequate hepatic, renal and bone marrowfunction. Oral etoposide was administeredat 50 mg/m² for ten days, with threeproposed dose levels for gemcitabine ondays 1 and 8: 400, 550 and 700 mg/m². Cycles were to be repeated every 28 days. Three patients were to enter at each doselevel. Results: Patients were enrolled onlyto dose level 1 as this dose exceeded MTD. Of six patients initially enrolled, one wasremoved after three days with fever,ascites and decreased albumin believed notto be treatment related. Five patientswere evaluable for toxicity and response. One of the first three patients developeddose limiting toxicity (DLT) manifested asgrade 4 neutropenia. A second DLT(neutropenic fever and thrombocytopeniaassociated with bleeding) occurred amongthe next three patients; therefore, MTD wasreached at dose level 1. Grade 4toxicities included episodes of neutropenia(4) and thrombocytopenia (3). No objectiveresponse was observed. Conclusions: Oral etoposide andgemcitabine at this dose and schedule wasassociated with substantial toxicity inthis population. Patients who are previously treated withplatinum/paclitaxel-based chemotherapy maybe at particular risk for toxicity.