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Biomedical subjects

Michael Pearson

Publications and source records attributed to Michael Pearson.

11 recordsLinked to original sources

Variability in the organisation and management of hospital care for COPD exacerbations in the UK.

Previous smaller UK audits have demonstrated wide variation in organisation, resources, and process of care for acute chronic obstructive pulmonary disease (COPD) admissions. Smallest units appeared to do less well. UK acute hospitals supplied information on (1) resources and organisation of care, (2) clinical data on process of care and outcomes for up to 40 consecutive COPD admissions. Comparisons were made against national recommendations. Eight thousand and thirteen admissions involved 7529 patients from 233 units (93% of UK acute Trusts). Twenty-six percent of units had at most one whole-time equivalent respiratory consultant while 12% had at least four. Thirty percent patients were admitted under a respiratory specialist and 48% discharged under their care whilst 28% had no specialist input at all. Variation in care provision was wide across all hospitals but patients in smaller hospitals had less access to specialist respiratory or admission wards, pulmonary rehabilitation programs, specialty triage or an early discharge scheme. Six percent of units did not have access to NIV and 18% to invasive ventilatory support. There remains wide variation in all aspects of acute hospital COPD care in the UK, with smaller hospitals offering fewest services. Those receiving specialist input are more likely to be offered interventions of proven effect. Management guidelines alone are insufficient to address inequalities of care and a clear statement of minimum national standards for resource provision and organisation of COPD care are required. This study provides a unique insight into the current state of care for patients admitted with COPD exacerbations in the UK.

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Method for detection and identification of multiple chromosomal integration sites in transgenic animals created with lentivirus.

Transgene delivery systems, particularly those involving retroviruses, often result in the integration of multiple copies of the transgene throughout the host genome. Since site-specific silencing of trangenes can occur; it becomes important to identify the number and chromosomal location of the multiple copies of the transgenes in order to correlate inheritance of the transgene at a particular chromosomal site with a specific and robust phenotype. Using a technique that combines restriction endonuclease digest and several rounds of PCR amplification followed by nucleotide sequencing, it is possible to identify multiple chromosomal integration sites in transgenic founder animals. By designing genotyping assays to detect each individual integration site in the offspring of these founders, the inheritance of transgenes integrated at specific chromosomal locations can be followed efficiently as the transgenes randomly segregate in subsequent generations. Phenotypic characteristics can then be correlated with inheritance of a transgene integrated at a particular chromosomal location to allow rational selection of breeding animals in order to establish the transgenic line.

Animals↗

The complete set of tRNA species in Nanoarchaeum equitans.

The archaeal parasite Nanoarchaeum equitans was found to generate five tRNA species via a unique process requiring the assembly of seperate 5' and 3' tRNA halves [Randau, L., Munch, R., Hohn, M.J., Jahn, D. and Soll, D. (2005) Nanoarchaeum equitans creates functional tRNAs from separate genes for their 5'- and 3'-halves. Nature 433, 537-541]. Biochemical evidence was missing for one of the computationally-predicted, joined tRNAs designated as tRNA(Trp). Our RT-PCR and sequencing results identify this tRNA as tRNA(Lys) (CUU) joined at the alternative position between bases 30 and 31. We show that the intron-containing tRNA(Trp) was misidentified in the initial Nanoarchaeum equitans genome annotation [E. Waters et al. (2003) The genome of Nanoarchaeum equitans: insights into early archaeal evolution and derived parasitism. Proc. Natl. Acad. Sci. USA 100, 12984-12988]. Along with a previously unidentified joined tRNA(Gln) (UUG), Nanoarchaeum equitans exhibits 44 tRNAs and is enabled to read all 61 sense codons. Features unique to this set of tRNA molecules are discussed.

Base Sequence↗

National audit of continence care for older people: results of a pilot study*.

INTRODUCTION AND AIM: Bladder and bowel problems are common in the elderly and are associated with a considerable morbidity and impact on quality of life. Inequalities in service provision and access to services have been recognized but there has been no systematic approach to measuring the quality of continence care for older people. This study aimed to develop quality standards, to assess the reliability and utility of the resulting audit package and to report on the standards of care provided in primary care, secondary care and care home setting. METHOD: Fifteen sites in secondary care, primary care and in long-term care settings were randomly selected to pilot the audit package. Data collectors completed audit questionnaires relating to the structure [organization] of care, the outcomes of care, and the process of care for 20 subjects with urinary incontinence and 10 subjects with faecal or double incontinence. RESULTS: The audit tool was reliable (median kappa score of 0.7). Access to integrated continence services, as defined by Good Practice in Continence Services was inadequate. Eighty-five per cent of hospitals had no written policy for continence care. There were deficiencies in obtaining information, in carrying out basic and specialist examinations and investigations and in determining the cause of incontinence. There was a high prevalence of catheter use in secondary care settings. CONCLUSION: The pilot has indicated significant inadequacies in continence care and demonstrates that in many sites the National Service Framework milestone for integrated continence services has not been met. A national audit of continence care is required to determine the extent of inadequate continence care.

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National audit of continence care: laying the foundation.

INTRODUCTION: National audit provides a basis for establishing performance against national standards, benchmarking against other service providers and improving standards of care. For effective audit, clinical indicators are required that are valid, feasible to apply and reliable. This study describes the methods used to develop clinical indicators of continence care in preparation for a national audit. AIM: To describe the methods used to develop and test clinical indicators of continence care with regard to validity, feasibility and reliability. METHOD: A multidisciplinary working group developed clinical indicators that measured the structure, process and outcome of care as well as case-mix variables. Literature searching, consensus workshops and a Delphi process were used to develop the indicators. The indicators were tested in 15 secondary care sites, 15 primary care sites and 15 long-term care settings. RESULTS: The process of development produced indicators that received a high degree of consensus within the Delphi process. Testing of the indicators demonstrated an internal reliability of 0.7 and an external reliability of 0.6. Data collection required significant investment in terms of staff time and training. CONCLUSION: The method used produced indicators that achieved a high degree of acceptance from health care professionals. The reliability of data collection was high for this audit and was similar to the level seen in other successful national audits. Data collection for the indicators was feasible to collect, however, issues of time and staffing were identified as limitations to such data collection. The study has described a systematic method for developing clinical indicators for national audit. The indicators proved robust and reliable in primary and secondary care as well as long-term care settings.

Delphi Technique↗

Apoptotic-regulatory and complement-protecting protein expression in chronic lymphocytic leukemia: relationship to in vivo rituximab resistance.

PURPOSE: Rituximab has clinical activity in patients with chronic lymphocytic leukemia (CLL) and has a variety of proposed mechanisms, including apoptosis, complement-dependent cell lysis (CDC), and antibody-dependent cellular cytotoxicity (ADCC). Here we examine pretreatment biologic features that promote resistance to apoptosis and CDC in CLL patients and correlate it with clinical outcome to rituximab-based therapy. PATIENTS AND METHODS: Pretreatment samples from 21 CLL patients treated on a prospective, single-agent rituximab trial were examined for quantitative expression of apoptotic and CDC regulatory proteins, and the level of expression of these proteins was correlated with clinical outcome. RESULTS: Of the 21 patents for whom samples were available, 10 attained a partial response and 11 failed to respond to rituximab therapy. The mean pretreatment expression of Bcl-2, Mcl-1, XIAP, and the ratio of Bcl-2/Bax were higher but not statistically increased in nonresponding patients versus those responding to treatment. In contrast, the pretreatment Mcl-1/Bax ratio was significantly elevated (0.82 +/- 0.28 v 0.39 +/- 0.29, P <.016) in nonresponding patients compared with patients responding to rituximab therapy. Although pretreatment expression of CD55 and CD59 was not associated with response to rituximab therapy, significantly higher levels of CD59 were observed in the CLL cells that were not cleared from the blood at completion of therapy than the level observed at baseline levels (P =.02). CONCLUSION: These data indicate that baseline expression of the Mcl-1/Bax ratio, but not CD55 and CD59, predict for clinical response to rituximab therapy in CLL patients. Further study of disrupted apoptosis in CLL as a potential mechanism of resistance to rituximab appears warranted.

Antibodies, Monoclonal↗

The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction.

Rituximab is a chimeric monoclonal antibody directed at CD20 with significant activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). A variety of pathways of tumor cytotoxicity different from cytotoxic chemotherapy have been proposed for this therapeutic antibody including antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. This report describes that a proportion of patients with CLL receiving rituximab treatment have in vivo activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage in blood leukemia cells immediately following infusion of rituximab. This suggests that apoptosis using a pathway similar to fludarabine and other chemotherapeutic agents is intricately involved in the blood elimination of tumor cells after rituximab treatment. Patients having caspase-3 activation and PARP cleavage in vivo had a significantly lower blood leukemia cell count after treatment as compared to those without caspase activation. Significant down-modulation of the antiapoptotic proteins XIAP and Mcl-1 was also noted, possibly explaining in part how rituximab sensitizes CLL cells to the cytotoxic effect of chemotherapy in vivo. These findings suggest that the therapeutic benefit of antibody-based therapy in vivo for patients with CLL depends in part on induction of apoptosis and provides another area of focus for studying mechanisms of antibody-resistance in neoplastic cells.

Antibodies, Monoclonal↗

The role of health informatics in clinical audit: part of the problem or key to the solution?

The concepts of quality assurance (for which clinical audit is an essential part), evaluation and clinical governance each depend on the ability to derive and record measurements that describe clinical performance. Rapid IT developments have raised many new possibilities for managing health care. They have allowed for easier collection and processing of data in greater quantities. These developments have encouraged the growth of quality assurance as a key feature of health care delivery. In the past most of the emphasis has been on hospital information systems designed predominantly for the administration of patients and the management of financial performance. Large, hi-tech information system capacity does not guarantee quality information. The task of producing information that can be confidently used to monitor the quality of clinical care requires attention to key aspects of the design and operation of the audit. The Myocardial Infarction National Audit Project (MINAP) utilizes an IT-based system to collect and process data on large numbers of patients and make them readily available to contributing hospitals. The project shows that IT systems that employ rigorous health informatics methodologies can do much to improve the monitoring and provision of health care.

Data Collection↗

Measuring outcomes with tools of proven feasibility and utility: the example of a patient-focused asthma measure.

Best quality care is clearly desirable and instituting quality assurance should be logical and simple. However, the practicality of setting standards for a product or service, and designing systems to measure against the standards, is more difficult. In the health service it is only likely to be feasible if data can be generated from efficient and reliable information systems. The ideal measure of quality is an outcome measure that evaluates whether or not the quality of care has achieved the desired standard of outcome. Direct measures of outcome are not easy to construct and the information systems required to provide data are not widely available. The National Centre for Health Outcomes Development (NCHOD) has produced a series of indicators in 10 areas of health care, where an indicator is a pointer to, rather than a direct measure of, a desired outcome. Feasibility studies measuring their sensitivity and reliability have drawn attention to their possible utility within different health care settings. This paper reports on an investigation into a patient-focused outcome indicator for asthma. There is broad agreement about the need to measure the outcome of disease. However, when outcome indicators are defined there are major obstacles to their successful uptake. A key challenge for outcomes measurement is to ensure that the cost of collecting the data and ensuring completeness, accuracy and standardization are justified by the benefits derived. Health outcome indicators should not be treated as a panacea, but as a part of the clinical and health care tool kit.

Algorithms↗