Biomedical subjects

M Pearson

Publications and source records attributed to M Pearson.

At least 19 recordsLinked to original sources

PubMed2025

Reproducibility of genetic risk factors identified for long COVID using combinatorial analysis across US and UK patient cohorts with diverse ancestries.

BACKGROUND: Long COVID is a major public health burden causing a diverse array of debilitating symptoms in tens of millions of patients globally. In spite of this overwhelming disease prevalence, staggering cost, severe impact on patients' lives and intense global research efforts, study of the disease has proved challenging due to its complexity. Genome-wide association studies (GWAS) have identified only four loci potentially associated with the disease, although these results did not statistically replicate between studies. A previous combinatorial analysis study identified a total of 73 genes that were highly associated with two long COVID cohorts in the predominantly (> 91%) white European ancestry Sano GOLD population, and we sought to reproduce these findings in the independent and ancestrally more diverse All of Us (AoU) population. METHODS: We assessed the reproducibility of the 5343 long COVID disease signatures from the original study in the AoU population. Because the very small population sizes provide very limited power to replicate findings, we initially tested whether we observed a statistically significant enrichment of the Sano GOLD disease signatures that are also positively correlated with long COVID in the AoU cohort after controlling for population substructure. RESULTS: For the Sano GOLD disease signatures that have a case frequency greater than 5% in AoU, we consistently observed a significant enrichment (77-83%, p < 0.01) of signatures that are also positively associated with long COVID in the AoU cohort. These encompassed 92% of the genes identified in the original study. At least five of the disease signatures found in Sano GOLD were also shown to be individually significantly associated with increased long COVID prevalence in the AoU population. Rates of signature reproducibility are strongest among self-identified white patients, but we also observe significant enrichment of reproducing disease associations in self-identified black/African-American and Hispanic/Latino cohorts. Signatures associated with 11 out of the 13 drug repurposing candidates identified in the original Sano GOLD study were reproduced in this study. CONCLUSION: These results demonstrate the reproducibility of long COVID disease signal found by combinatorial analysis, broadly validating the results of the original analysis. They provide compelling evidence for a much broader array of genetic associations with long COVID than previously identified through traditional GWAS studies. This strongly supports the hypothesis that genetic factors play a critical role in determining an individual's susceptibility to long COVID following recovery from acute SARS-CoV-2 infection. It also lends weight to the drug repurposing candidates identified in the original analysis. Together these results may help to stimulate much needed new precision medicine approaches to more effectively diagnose and treat the disease. This is also the first reproduction of long COVID genetic associations across multiple populations with substantially different ancestry distributions. Given the high reproducibility rate across diverse populations, these findings may have broader clinical application and promote better health equity. We hope that this will provide confidence to explore some of these mechanisms and drug targets and help advance research into novel ways to diagnose the disease and accelerate the discovery and selection of better therapeutic options, both in the form of newly discovered drugs and/or the immediate prioritization of coordinated investigations into the efficacy of repurposed drug candidates.

Humans↗

PubMed2006

A multistate cluster of red blood cell transfusion reactions associated with use of a leucocyte reduction filter.

In 2000, the American Red Cross (ARC) received reports of unusual transfusion reactions of unknown aetiology among patients receiving leucocyte-reduced (LR) red blood cell (RBC) units in multiple distribution regions. We evaluated potential risk factors of reactions among patients who received LR-RBC transfusions. A case-patient was defined as any patient with onset of back pain while receiving an LR-RBC transfusion from 1 January to 25 May 2000. Controls were chosen randomly and selected in a 1:3 case : control ratio from healthcare facilities in which case-patients were transfused. Product-specific risk factors of reactions were further determined through nested case-control study, procedural review of blood collection facility and quality-control-testing record review of product processing. Reaction incidence rates were determined through ARC blood product distribution data by region of blood collection and processing. There were 29 reactions detected in patients who received transfusions in 13 healthcare facilities in five states. Eighteen case-patients and 78 controls were included in the case-control study. In univariate analysis, case-patients were more likely than controls to have a haematologic malignancy, to have received the transfusion as an outpatient, to have received an RBC transfusion within the previous 3 months, to have received medication used to prevent reactions or to diminish their intensity upon transfusion (i.e. premedication) or to have received LR-RBC units prepared with the HemaSure r\LS System(HS) rather than two other filters used. In multivariate analysis limited to recipients of HS-filtered RBC units, transfusion premedication [adjusted odds ratio (AOR) = 7; 95% confidence interval (CI) 1.4-37; P = 0.02] and transfusion as an outpatient (AOR = 5; 95% CI 1.1-20; P = 0.03) were independently associated with reactions. The rate of reported transfusion reactions was 2.0 reactions per 10 000 RBC units distributed. A multistate cluster of transfusion reactions was significantly associated with leucocyte filtration of RBC units prepared with a specific product, the HS filter. The reactions also were independently associated with premedication and transfusion as an outpatient; these may be surrogates for an increased risk of reaction or for greater likelihood of detection. The mechanism for these reactions has not been elucidated. This cluster of reactions underscores the importance of surveillance efforts to detect adverse events after transfusion, particularly when new methods to modify blood products are introduced.

Adolescent↗

PubMed2005

Improving clinical practice in stroke through audit: results of three rounds of National Stroke Audit.

BACKGROUND: The results of three rounds of National Stroke Audit in England, Wales and Northern Ireland are compared. METHODS: Audit of the organization of stroke services and retrospective case-note audit of up to 40 consecutive cases admitted per hospital over a 3-month period was conducted in each of 1998, 1999 and 2001/02. The changes in the organizational, case-mix and process results of the hospitals that had participated in all three rounds were analysed. RESULTS: 60% of all eligible trusts from England, Wales and Northern Ireland took part in all three audits in 1998, 1999 and 2001/02. Total numbers of cases were 4996, 4841 and 5152, respectively. Case-mix variables were similar over the three rounds. Mortality at 7 and 30 days fell by 3% and 5%, respectively. The proportion of hospitals with a stroke unit rose from 48% to 77%. The proportion of patients spending most of their stay in a stroke unit rose from 17% in 1998 to 26% in 1999 and 29% in 2001/02. Improvements achieved in process standards of care between 1998 and 1999 (median change was a gain of 9%) failed to improve further by 2001/02 (median change was 0%). In all three rounds process standards of care tended to be better in stroke units. CONCLUSIONS: Three rounds of national audit of stroke care have shown standards of care on stroke units were notably higher than on general wards. Slowing in the rise of the proportion managed on stroke units mirrors the slow down in improvement to overall national standards of care. To further improve outcomes and national standards of stroke care a much higher proportion of patients needs to be managed in stroke units.

Aged↗

PubMed2005

Lessons from the management of acute myocardial infarction.

The National Service Framework for coronary heart disease set a number of challenging targets for the care of patients following an acute myocardial infarction. The Myocardial Infarction National Audit Project (MINAP) was devised to monitor progress and has been notably successful in winning professional support and participation and helping trusts to meet these targets. The new challenge is in translating this success to other areas of medicine. Heart failure is one such area, although it poses a number of difficulties relating primarily to disease definition and the definition of a successful outcome. MINAP was overseen by a multidisciplinary group of stakeholders, including patient organisations, and was project managed by a professionally led team at the Royal College of Physicians. Successful projects must retain confidence of all stakeholders and in part this depends on ensuring that timelines are met. Central monitoring of returns and anticipation of problems has been an important component of data completeness and quality. Next day updates to those collecting the data and more detailed quarterly reports for clinicians and chief executives within days of quarter end have been vital. Change depends on clinicians and managers working together. But most importantly, the attention to detail outlined above means the data have been believed and the resulting change for patients has been remarkable.

Costs and Cost Analysis↗

PubMed2005

Stroke units: research and reality. Results from the National Sentinel Audit of Stroke.

OBJECTIVES: To use data from the 2001-2 National Stroke Audit to describe the organisation of stroke units in England, Wales and Northern Ireland, and to see if key characteristics deemed effective from the research literature were present. DESIGN: Data were collected as part of the National Sentinel Audit of Stroke in 2001, both on the organisation and structure of inpatient stroke care and the process of care to hospitals managing stroke patients. SETTING: 240 hospitals from England, Wales and Northern Ireland took part in the 2001-2 National Stroke Audit, a response rate of over 95%. These sites audited a total of 8200 patients. AUDIT TOOL: Royal College of Physicians Intercollegiate Working Party Stroke Audit Tool. RESULTS: 73% of hospitals participating in the audit had a stroke unit but only 36% of stroke admissions spent any time on one. Only 46% of all units describing themselves as stroke units had all five organisational characteristics that previous research literature had identified as being key features, while 26% had four and 28% had three or less. Better organisation was associated with better process of care for patients, with patients managed on stroke units receiving better care than those managed in other settings. CONCLUSION: The National Service Framework for Older People set a target for all hospitals treating stroke patients to have a stroke unit by April 2004. This study suggests that in many hospitals this is being achieved without adequate resource and expertise.

Health Services Research↗

PubMed2005

Institutionalization after stroke.

BACKGROUND AND PURPOSE: There are widespread regional variations in the institutionalization rate after stroke. This study sought to identify the factors that predict institutionalization after a primary diagnosis of stroke and determine whether institutionalization rate could be used to assess the quality of hospital care. METHODS: A retrospective case note audit of 2778 consecutive admissions with stroke, between 1 September and 31 October 2000 from a randomly selected sample of 79 hospitals in England, Wales and Northern Ireland. Data were collected on demographics, case-mix, clinical outcome, organization of discharge, and place of residence at discharge and at three and six months. The figures from this audit were validated using data from the 1998 National Sentinel Audit of Stroke. RESULTS: Overall 14% of patients previously living at home were discharged to nursing or residential homes. Using logistic regression, Barthel Index score at discharge accounted for 40% of variation. Two-thirds of patients with a discharge Barthel score of < 5 were institutionalized. Age alone explained 14% and when taken together with discharge Barthel and length of stay it accounted for 54% of variation. On admission 22% of the variation in institutionalization rate could be accounted for by total Glasgow Coma Score (15, < 15), age and ability to walk unaided. Regional variations in institutionalization rates are evident and may in part be explained by differences in ease of access to the institutions. CONCLUSIONS: Discharge disability and older age were the dominant factors determining admission to nursing and residential homes. It is not possible to predict sufficiently reliably for an individual patient the likelihood of institutionalization at admission or at 72 h after admission, to justify early resource allocation decisions.

Age Distribution↗

PubMed2005

Design as a research development tool.

The design and development process is due for some innovation. Current practices use design as a downstream activity. This article explores how to use it during research and development and the benefits this offers companies.

Equipment Design↗

PubMed2004

Secondary prevention for stroke in the United Kingdom: results from the National Sentinel Audit of Stroke.

STUDY OBJECTIVES: To measure the quality of secondary prevention of stroke provided to patients in England, Wales and Northern Ireland. DESIGN: Retrospective case note analysis. SETTING: 235 hospitals (95% of all such hospitals), providing care for acute stroke patients in England, Wales and Northern Ireland and primary health care for follow-up data. PATIENTS: 8,200 patients admitted with stroke between 1(st) April and 30(th) June 2001. Data on up to 40 consecutive cases submitted by each hospital. AUDIT TOOL: Royal College of Physicians Intercollegiate Stroke Working Party Stroke Audit. RESULTS: 24% of patients with previous cerebrovascular disease were not on anti-thrombotic medication at the time of admission. Nine percent of appropriate patients were not taking anti-thrombotic medication at discharge. Patients left with moderate to very severe disability (Barthel scores 14 or less) compared with those independent with mild disability (Barthel score 15-20) were more likely not to have anti-thrombotic treatment (18% versus 8%). Fifty-four percent of patients with known hyperlipidaemia and 21% of those with previous ischaemic heart disease were on lipid lowering therapy on admission. Sixty-four percent of patients had lipids measured during their hospital stay and of those with high total cholesterol or LDL the rate of non-treatment was 36%. Older patients (75+ years) were less likely to be treated (54%) than those <65 years (71%). Seventy-nine percent of known patients with hypertension were on treatment at admission, with 78% being treated by discharge from hospital. At 6 months after stroke a systolic blood pressure of 140 mmHg or less, and a diastolic of 85 mmHg or less, was achieved in 41% of known pre-stroke hypertensives on treatment, 31% of previously untreated hyper-tensives but on treatment at follow-up and 40% of patients not previously labelled as hypertensive. CONCLUSIONS: Major deficiencies in delivery of secondary prevention after stroke have been demonstrated. Services need reorganisation to prevent unnecessary mortality and morbidity in this group of patients.

Aged↗

PubMed2004

Trends in childhood and parental asthma prevalence in Merseyside, 1991-1998.

OBJECTIVE: To determine changes in childhood and parental asthma prevalence in Merseyside between 1991 and 1998. METHODS: Three standardized cross-sectional respiratory health surveys using a parent-completed questionnaire were completed in 1991 (n = 1171), 1993 (n = 2368) and 1998 (n = 1964) amongst primary school children (5-11 years) attending the same 10 schools. The main outcome measures were prevalence of reported doctor diagnosed asthma, the symptom triad of cough, wheeze and breathlessness (C+W+B+) and parental asthma. RESULTS: Significant changes in prevalence for all respiratory variables occurred between 1991 and 1998, except for the symptom triad C+W+B+. Between 1991 and 1998 the prevalence of reported doctor diagnosed asthma increased from 17.7 to 29.8 per cent (p < 0.001), history of wheezing increased from 22.5 to 29.4 per cent (p < 0.001). The symptom triad of C+W+B+ changed from 9.6 to 9.9 per cent (p = 0.78). Childhood reported hospital admissions for respiratory illness increased from 5.5 to 10.7 per cent (p < 0.001). Paternal asthma increased from 6.5 per cent in 1991, to 8.6 per cent in 1998 (p = 0.031), and maternal asthma almost doubled in the same period from 6.6 to 11.2 per cent (p < 0.001). Children living in poorer areas (Townsend score 8-11) were more likely to have doctor diagnosed asthma (OR = 2.99, 95 per cent CI, 2.06 to 4.33) and C+W+B+ (OR = 2.17, CI 1.13 to 4.18). Childhood obesity was significantly associated with increased risk of both doctor diagnosed asthma (OR = 1.74, 95 per cent CI, 1.29 to 2.37) and C+W+B+ (OR = 1.88, 95 per cent CI, 1.21 to 2.90). CONCLUSION: A rising prevalence of reported doctor diagnosed asthma, but not C+W+B+ was observed during the 1990s in a low socio-economic area of Liverpool. Asthma prevalence was related to socio-economic deprivation and was associated with obesity. The rising prevalence of reported doctor diagnosed asthma is likely to be attributable to several factors, including changes in diagnostic labelling and the distribution of factors related to socio-economic status.

Adult↗

PubMed2004

Improving care for patients with acute coronary syndromes: initial results from the National Audit of Myocardial Infarction Project (MINAP).

OBJECTIVE: To describe the improvements in care that have followed the introduction of an electronic data entry and analysis system providing contemporary feedback on the management of acute coronary syndromes in 230 hospitals in England and Wales. DESIGN: Observational study METHODS: A secure electronic system was used to transfer encrypted data on patients with acute coronary syndromes from collaborating hospitals to central servers for analysis. Immediate online data entry to the central servers by hospitals allowed contemporary analyses of performance and immediate comparison with the national aggregate performance. RESULTS: The records of 156 902 patients receiving a final diagnosis of acute coronary syndrome during three years between October 2000 and September 2003 were analysed. Of 69 113 patients with ST segment elevation infarction, 75.4% received thrombolytic treatment. Between the first and last years of the study the median interval from hospital arrival to treatment fell for eligible patients from 38 (interquartile range 22-58) to 20 (interquartile range 14-28) minutes. By mid 2003 77.6% were receiving thrombolytic treatment within 30 minutes of arrival. The proportion treated within two hours of onset of symptoms increased from 32.5% to 40.3% (a difference of 7.8 percentage points, p < 0.0001). The use of secondary prevention medication for acute coronary syndromes increased over this period: angiotensin converting enzyme inhibitors, 62.4% to 72.4%; beta blockers, 76.3% to 82.6%; statins, 69.6% to 83.8%; and aspirin, 89.3% to 90.2%. CONCLUSION: The provision of contemporary online performance analyses has underpinned substantial improvement in the care of patients with acute coronary syndromes.

Adrenergic beta-Antagonists↗

PubMed2004

Scintigraphic measurement of tracheal mucus velocity in vivo.

Mucociliary clearance (MCC) is an important mechanism for removing inhaled particles, secretions and cellular debris from the respiratory tract. Here, a direct measurement of tracheal mucus velocity (TMV) for assessment of MCC, suitable for clinical and research use, is reported, and a comparison is made of TMV in normal subjects and patients with chronic obstructive pulmonary disease (COPD). A 0.1-mL bolus of radiolabelled (2-5 MBq), technetium-labelled macroaggregated human albumin (99mTc MAA) was injected through the cricothyroid membrane into the trachea of 20 young (< 50 yrs) and 12 older (> 50 yrs) normal subjects and 34 patients with COPD. Repeat studies were carried out in 13 normal subjects and 16 COPD patients. Movement of the bolus in the trachea was recorded (15 min) using a gamma camera interfaced to a computer. Data were analysed using specifically designed software. The test was well tolerated by subjects and patients, and no significant adverse events were reported. No significant differences were observed between data recorded from different regions of the bolus (leading edge, peak, trailing edge) by analysis of variance (ANOVA). Bland-Altman plots of the repeat studies indicated that data were more variable in normal subjects (coefficient of repeatability (COR) 10.3 mm.min-1) than in COPD patients (COR 5.5 mm.min-1). TMV (mean +/- SD) in young normal subjects (n = 20) was 10.7 +/- 3.5 mm.min-1. TMV was reduced in older normal subjects (n = 12; 6.5 +/- 2.6 mm.min-1) and further reduced in COPD (n = 34; 2.1 +/- 2.7 mm.min-1). In conclusion, this technique can be used to measure tracheal mucus velocity rapidly and safely in healthy subjects and patients with respiratory tract disease. This study has confirmed that tracheal mucus velocity declines with age and is further impaired in patients with chronic obstructive pulmonary disease.

Adult↗

PubMed2003

Investigation of media formulations promoting differential antigen expression by Photobacterium damsela ssp. piscicida and recognition by sea bass, Dicentrarchus labrax (L.), immune sera.

Photobacterium damsela ssp. piscicida (Phdp) isolates were grown in various bacteriological media, in eukaryotic cell culture media and in the presence of fish cells (resembling some aspects of in vivo growth environments). Bacterial cells, extracellular products (ECPs) and crude capsular polysaccharide were isolated and analysed by electrophoresis and Western blot using sea bass sera. Growth in bacteriological media conserved the synthesis of cell and extracellular components when these were compared with those prepared under near-in vivo growth conditions. In fact, synthesis of a larger range of cell components was induced after growth in bacteriological media. Certain media based on yeast extract and peptones from various sources and a specific salt formulation induced the synthesis of novel cell components at approximately 21.3 and 14 kDa. These antigens were recognized by sea bass sera collected after natural pasteurellosis outbreaks and other sea bass sera raised against live or inactivated Phdp cells. The ECPs of the pathogen were not good immunogens in their soluble form despite various treatments prior to immunization. The results are discussed with respect to vaccine development.

Animals↗

PubMed2002

Raising the profile of chronic obstructive pulmonary disease with healthcare decision-makers.

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Attitude of Health Personnel↗

PubMed2002

Obtaining evidence for use by healthcare payers on the success of chronic obstructive pulmonary disease management.

Healthcare payers make decisions on funding for treatments for diseases, such as chronic obstructive pulmonary disease (COPD), on a population level, so require evidence of treatment success in appropriate populations, using usual routine care as the comparison for alternative management approaches. Such health outcomes evidence can be obtained from a number of sources. The 'gold standard' method for obtaining evidence of treatment success is usually taken as the randomized controlled prospective clinical trial. Yet the value of such studies in providing evidence for decision-makers can be questioned due to the restricted entry criteria limiting the ability to generalize to real life populations, narrow focus on individual parameters, use of placebo for comparison rather than usual therapy and unrealistic intense monitoring of patients. Evidence obtained from retrospective and observational studies can supplement that from randomized clinical trials, providing that care is taken to guard against bias and confounders. However, very large numbers of patients must be investigated if small differences between drugs and treatment approaches are to be detected. Administrative databases from healthcare systems provide an opportunity to obtain observational data on large numbers of patients. Such databases have shown that high healthcare costs in patients with COPD are associated with co-morbid conditions and current smoking status. Analysis of an administrative database has also shown that elderly patients with COPD who received inhaled corticosteroids within 90 days of discharge from hospital had 24% fewer repeat hospitalizations for COPD and were 29% less likely to die during the 1-year follow-up period. In conclusion, there are a number of sources of meaningful evidence of the health outcomes arising from different therapeutic approaches that should be of value to healthcare payers making decisions on resource allocation.

Attitude of Health Personnel↗

PubMed2002

Design of an intervention addressing multiple levels of influence on dietary and activity patterns of low-income, postpartum women.

Low-income, multi-ethnic women are at elevated risk for obesity and chronic diseases, yet influences at different levels may act as barriers to changing risk behaviors. Following the birth of a child, childrearing and social isolation can exacerbate these influences. The social ecological framework integrates behavior-change strategies at different levels, providing a strong theoretical base for developing interventions in this high-risk population. The primary purpose of this randomized controlled trial is to test the efficacy of an educational model delivered by community-based paraprofessionals in improving diet, activity and weight loss among new mothers over a 12-month postpartum period and a 6-month maintenance period. This model fosters institutional change to support behavior changes influenced at intrapersonal and interpersonal levels, through collaboration with federal programs for low-income families: the Special Supplemental Food Program for Women, Infants and Children (WIC), and the Expanded Food and Nutrition Education Program (EFNEP). Participants are randomized to the Usual Care, e.g. WIC nutrition and breastfeeding education, or Enhanced EFNEP intervention arm, consisting of Usual WIC Care plus a sustained, multi-component intervention including home visits, group classes and monthly telephone counseling. If shown to be efficacious, this program will be readily sustainable through existing federal agencies.

Adult↗

PubMed2002

Measuring consultation skills in primary care in England: evaluation and development of content of the MAAS scale.

BACKGROUND: Consultation skills are essential for general practice. Tools for measuring consultation skills in everyday practice are not well developed AIM: To examine and develop the content validity of the MAAS History-taking and Advice Checklist GP (MAAS-GP) tool which is used in The Netherlands for testing consultation skills, with simulated patients in United Kingdom general practice from the perspectives of both general practitioners and patients. DESIGN OF STUDY: Qualitative research using semi-structured interviews. SETTING: Alternate patients attending seven general practices in the north west of England. METHOD: Thematic analysis of the contents of patient and GP interviews, and of focus groups, mapping key themes to the MAAS-GP. RESULTS: There was strong agreement between patients and GPs on issues mapping to 46 out of 68 items of the MAAS-GP. Eight further MAAS-GP items were linked to issues only raised by patients and four to issues raised only by GPs. The remaining 10 items could not be related to issues raised by either. All of the issues raised by GPs could be mapped but 27 patient items could not. These were included in a revised checklist, the Liverpool MAAS (LIV-MAAS). CONCLUSION: the revised tool seems to have content validity in measuring consultation skills. Measurement of its relability is now required.

Adult↗

PubMed2001

PML interaction with p53 and its role in apoptosis and replicative senescence.

A network of control pathways has been characterized that arrest growth or induce apoptosis in response to potentially tumorogenic events such as genotoxic stress or oncogene expression. Ablation, or functional disruption, of these pathways is frequently observed during multistep carcinogenesis. Analysis of those genes most commonly compromized in tumours has led to the identification of the transcription factor p53 and the E2F binding protein Retinoblastoma (Rb), as key regulators of these processes. This review discusses recent data, demonstrating that the Promyelocytic Leukemia (PML) protein can physically and functionally interact with both p53 and Rb, suggesting that PML may be a novel regulator of these pathways.

Acetyltransferases↗

PubMed2001

Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity.

PURPOSE: Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with significant infusion-related toxicity. This study sought to decrease the initial toxicity and optimize the pharmacokinetics with an alternative treatment schedule. PATIENTS AND METHODS: Thirty three patients with SLL/CLL received dose 1 of rituximab (100 mg) over 4 hours. In cohort I (n = 3; 250 mg/m(2)) and cohort II (n = 7; 375 mg/m(2)) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a standard administration schedule. Cohort III (n = 23; 375 mg/m(2)) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter. RESULTS: A total of 33 CLL/SLL patients were enrolled; only one patient discontinued therapy because of infusion-related toxicity. Thirteen patients developed transient hypoxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleukin-8, tumor necrosis factor alpha, and interferon gamma compared with those not experiencing such reactions. Infusion-related toxicity occurred more commonly in older (median age 73 v 62 years; P =.02) patients with no other pretreatment clinical or laboratory features predicting occurrence of these events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%). Median response duration for these 15 patients was 10 months (95% CI, 6.8-13.2; range, 3 to 17+). CONCLUSION: Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted.

Aged↗