Generic Health-Related Quality of Life Utility Measure for Preschool Children (Health Utilities Preschool): Design, Development, and Properties.

OBJECTIVES: Health Utilities Preschool (HuPS) was developed to fill the need for a generic preference-based measure (GPM) applicable in early childhood. A GPM has all the properties for higher-order summary measures, such as quality-adjusted life-years, required to inform important policy decisions regarding health and healthcare services. METHODS: Development was in accordance with published standards for a GPM, statistical procedures, and modeling. HuPS incorporates key components of 2 existing measurement systems: Health Status Classification System for Preschool Children and Health Utilities Index Mark 3 (HUI3). The study included a series of 4 measurement surveys: definitional, adaptational, quantificational, and evaluational health-related quality of life (HRQL). HuPS measurements were evaluated for reliability, validity, interpretability, and acceptability. RESULTS: Definitional measurements identified 8 Health Status Classification System for Preschool Children attributes in common with HUI3 (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain and discomfort), making the HUI3 scoring equation commensurate with HuPS health states. Adaptational measurements informed the content of attribute-level descriptions (n = 35). Quantificational measurements determined level scoring coefficients. HRQL scoring inter-rater reliability (intraclass correlation coefficient = 0.79) was excellent. Continuity of HRQL scoring with HUI3 was reliable (intraclass correlation coefficient = 0.80, P < .001) and valid (mean absolute difference = 0.016, P = .396). CONCLUSIONS: HuPS is an acceptable, reliable, and valid GPM. HRQL scoring is continuous with HUI3. Continuity expands the applicability of GPM (HUI3) scoring to include subjects as young as 2 years of age. Widespread applications of HuPS would inform important health policy and management decisions as HUI3 does for older subjects.

Nursing Bedside Dysphagia Screen: Is it Valid?

Screening for dysphagia on stroke patient admissions in a timely manner, with early risk identification, and implementation of appropriate oral intake measures is a priority to reduce negative patient outcomes. Containing patient and facility costs, along with reducing length of stay, is a priority for all healthcare institutions. To ensure the provision of care at our facility was consistent with these priorities, we reviewed our processes and looked for opportunities for improvement. Assuring we had a reliable and valid nursing bedside screening tool for dysphagia was identified as a priority. We designed a study to answer the questions of validity and reliability. The findings suggest that our facility-developed Nursing Bedside Dysphagia Screen is a valid and reliable tool to help identify patients with stroke who are at risk for aspiration pneumonia.

Communication regarding breathing support options for youth with Duchenne muscular dystrophy.

BACKGROUND: Ventilators for home use, manual and mechanically assisted coughing techniques, and the services of in-home respiratory therapists are options for youth with Duchenne muscular dystrophy (DMD). Evidence supports the use of these modalities, but there seems to be few youth who are receiving these therapies. Is there a knowledge transfer issue? Is there a lack of resources? What is the best way to discuss the issues? What do youth and parents want? OBJECTIVE: To determine practices, attitudes and beliefs regarding the timing and content of client/family communication related to ventilatory support decisions for individuals with DMD. METHODS: A questionnaire was sent to all 19 children's treatment centres in Ontario. The lead clinician responded on behalf of his or her centre. Another questionnaire was given to 11 families who attended a parent support meeting. RESULTS: Respondents from the treatment centres who provide services for youth with DMD indicated that there are resources in terms of personnel and an obligation to provide information about ventilatory support, but provision of information is often late and/or inconsistent. The family respondents wanted more information and they wanted it earlier than they are currently receiving it. CONCLUSIONS: Parents and youth dealing with DMD have many resources at their disposal in Ontario. The evidence is clear that there are long-term health benefits to providing ventilatory support as well as instruction in coughing assistance. Due to the classical nature of disease progression in DMD, information should be provided within reasonable timelines.

Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies.

BACKGROUND: Monoclonal antibodies (MAbs) can target therapy to tumours while minimising normal tissue exposure. Efficacy of immunoconjugates containing peptide 101, designed around the first 22 amino acids of bee venom, melittin, to maintain the amphipathic helix, to enhance water solubility, and to increase hemolytic activity, was assessed in nude mice bearing subcutaneous human prostate cancer xenografts. METHODS: Mouse MAbs, J591 and BLCA-38, which recognise human prostate cancer cells, were cross-linked to peptide 101 using SPDP. Tumour-bearing mice were used to compare biodistributions of radiolabeled immunoconjugates and MAb, or received multiple sequential injections of immunoconjugates. Therapeutic efficacy was assessed by delay in tumour growth and increased mouse survival. RESULTS: Radiolabeled immunoconjugates and antibodies showed similar xenograft tropism. Systemic or intratumoural injection of immunoconjugates inhibited tumour growth in mice relative to carrier alone, unconjugated antibody and nonspecific antibody-peptide conjugates and improved survival for treated mice. CONCLUSIONS: Immunoconjugates deliver beneficial effects; further peptide modifications may increase cytotoxicity.

Biodistributions of intact monoclonal antibodies and fragments of BLCA-38, a new prostate cancer directed antibody.

BACKGROUND: Monoclonal antibodies (MAbs) are used for targeting agents to tumours while minimizing normal tissue exposure. METHODS: A new anti-prostate cancer MAb, BLCA-38, was radioiodinated (I125) and assessed for its ability to target subcutaneous human prostate cancer (DU-145) xenografts after systemic intraperitoneal administration. For comparison, the profile of J591 MAb (now in clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles were obtained at various times, by assessing injected dose/gram (%ID/g) and xenograft to blood (X/B) ratios. Microautoradiography of xenografts was performed. After conjugation with a melittin peptide toxin, the profiles of BLCA-38 and J591 were compared with that of an irrelevant antibody, DS-1. RESULTS: Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant antigen-positive tumors was comparable, and there was no unusual localization in nontumour tissues. F(ab')2 and Fab fragments gave improved X/B ratios, but the %ID/g xenograft was decreased and they accumulated in kidneys, bladder and stomach. In contrast, the conjugates of irrelevant antibody showed no tumour targeting. Microautoradiography showed more tumour accumulation of MAbs than F(ab')2s or Fabs. CONCLUSIONS: BLCA-38 can target prostate cancer in vivo almost as effectively as J591. Given that J591 is used clinically, BLCA-38, which targets a different antigen, has potential for radioimmunoscintigraphy and for therapeutic targeting of prostate cancer.