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Biomedical subjects

P Cleary

Publications and source records attributed to P Cleary.

At least 19 recordsLinked to original sources

Quality collaboratives: lessons from research.

Quality improvement collaboratives are increasingly being used in many countries to achieve rapid improvements in health care. However, there is little independent evidence that they are more cost effective than other methods, and little knowledge about how they could be made more effective. A number of systematic evaluations are being performed by researchers in North America, the UK, and Sweden. This paper presents the shared ideas from two meetings of these researchers. The evidence to date is that some collaboratives have stimulated improvements in patient care and organisational performance, but there are significant differences between collaboratives and teams. The researchers agreed on the possible reasons why some were less successful than others, and identified 10 challenges which organisers and teams need to address to achieve improvement. In the absence of more conclusive evidence, these guidelines are likely to be useful for collaborative organisers, teams and their managers and may also contribute to further research into collaboratives and the spread of innovations in health care.

Cooperative Behavior↗

Antibody against surface-bound C5a peptidase is opsonic and initiates macrophage killing of group B streptococci.

The capsular polysaccharides of group B streptococci (GBS) are a primary focus of vaccine development. Immunogenicity and long-lasting protection are best achieved by conjugating polysaccharides to a T-cell-dependent protein antigen. Streptococcal C5a peptidase (SCPB) is a conserved surface protein that is expressed by all streptococcal serotypes tested to date, and it is a possible carrier protein that could itself induce a protective immune response. Clearance of GBS from lungs, mucosal surfaces, or blood probably depends on the opsonophagocytic response of tissue-specific macrophages and polymorphonuclear leukocytes (PMNs). In this study, we examined the potential of antibody directed against SCPB from a serotype II strain to enhance the capacity of mouse bone marrow macrophages (from primary cultures) and human PMNs in whole blood to kill GBS in vitro. Our experiments demonstrated that Streptococcus serotypes Ia, Ib, II, III, and V, preopsonized with anti-SCPB antibody, were killed more rapidly by cultured macrophages and PMNs in whole blood than were nonopsonized GBS. The increased rate of killing was accompanied by an increased macrophage oxidative burst. Furthermore, opsonization was serotype transparent. Immunization with SCPB conjugated to capsular polysaccharide type III produced polysaccharide-specific antibodies. It is interesting that this antiserum promoted serotype-independent killing of streptococci. These data support the use of SCPB in a GBS polysaccharide conjugate vaccine. SCPB not only enhanced the immunogenicity of polysaccharide components of the vaccine, but it might also induce additional serotype-independent protective antibodies.

Adhesins, Bacterial↗

Helping children with communication difficulties in the classroom.

As we move towards a more inclusive education system teachers are becoming more aware of children with speech and language difficulties and the implications for their future learning and literacy development. In order to address this and promote collaborative working practice between teachers and speech and language therapists two advisory speech and language therapy posts were created for a two-year pilot project.

Child↗

Maximal exercise systolic pressure, exercise training, and mortality in myocardial infarction patients.

The relation of maximal exercise systolic pressure to physical conditioning and to mortality was determined in 641 men with > or =1 myocardial infarctions. Each performed a standardized multistage exercise test before randomized assignment either to an exercise group or a control group and at scheduled periodic intervals over 3 years. This study compares 123 men with maximal exercise systolic pressures (MESP) of < or =140 mm Hg with 518 men whose maximal exercise systolic pressure was > or =140 mm Hg. At baseline, the 2 groups were comparable for age, entry time since the occurrence of the qualifying cardiac event, and reported use of antihypertensive medications. Men with low MESP used more beta blockers, had lower systolic pressure measurements at rest and by definition at maximal exercise, and lower work capacity than men with higher levels of MESP. Men with low MESP experienced: (1) no reduction in mortality with exercise conditioning (p<0.86), and (2) a significantly higher mortality rate over 3 years (p<0.003) compared with men with higher levels of MESP. The relation of a low MESP to mortality persisted: (1) whether MESP or work capacity increased from the baseline exercise test to the last performed exercise test, and (2) whether it was measured at low (<6 METs) or high (> or =6 METs) levels of work capacity. We conclude that low maximal exercise systolic blood pressure is a predictor of mortality and is associated with an ineffective training response in men with myocardial infarction.

Blood Pressure↗

The Consumer Assessment of Health Plan Study (CAHPS) survey of children's health care.

BACKGROUND: Little is known about the experience of children and families with pediatric care. Asking parents about their experiences and the treatment of their children in health care plans can yield important information about selected aspects of medical care quality. Such data can be used to motivate, focus, and evaluate quality improvement efforts. METHODS: Development of the Child Core Survey followed the survey development principles of the Consumer Assessment of Health Plan Study (CAHPS) project, starting with assembly of existing instruments, consultation with experts, focus groups, and cognitive testing. A field test of the survey was conducted by mail among members enrolled in 1 of 25 plans originally identified as providing health care services to the public employees of the state of Washington (response rate, 52%). RESULTS: The 3,083 respondents rated personal doctors most highly, with overall care and specialty care rated nearly as well, and plan administration rated lowest. Parent-clinician and child-clinician communication, as well as spending sufficient time with the child were the strongest correlates of assessments of overall care and of personal doctors. Plans differed significantly in their performance along all the dimensions of child health care assessed in the survey except for aspects of access ("getting the care you need"). IMPLICATIONS: The Child Core Survey from the CAHPS provides a readily accessible method to assess the interpersonal care of children. Such data could be used to make plans accountable to the needs of children, to focus specific improvement initiatives, or both.

Adolescent↗

Impact of M49, Mrp, Enn, and C5a peptidase proteins on colonization of the mouse oral mucosa by Streptococcus pyogenes.

Resistance to phagocytosis is a hallmark of virulent Streptococcus pyogenes (group A streptococcus). Surface-bound C5a peptidase reduces recruitment of phagocytes to the site of infection, and hyaluronic acid capsules and/or the M protein limit the uptake of streptococci. In this study the relative impact of M and M-like proteins and the C5a peptidase on the virulence of a serotype M49 strain was assessed. The capacities of isogenic strains with an insertion mutation in emm49; with a deletion mutation in scpA49 (C5a peptidase gene); and with a deletion that removes all three M-like genes, mrp49, emm49, and enn49, to colonize mice and resist phagocytosis were compared. Experiments confirmed results obtained in an earlier study, which showed that the M49 protein was not required for in vitro resistance to phagocytosis, and also showed that the M protein was not required for colonization of mice. Failure to produce all three M-like proteins, M49, Mrp, and Enn49, significantly reduced the ability of these streptococci to resist phagocytosis in vitro but did not significantly alter the persistence of streptococci on the oral mucosa. In vitro experiments indicate that M+ streptococci are phagocytized by polymorphonuclear leukocytes that have been activated with phorbol-12-myristate 13-acetate or recombinant human C5a. This observation may explain the finding that expression of M49 protein is not essential for short-term colonization of the mouse oral mucosa.

Adhesins, Bacterial↗

Group A streptococcal immunoglobulin-binding proteins: adhesins, molecular mimicry or sensory proteins?

Pathogenic streptococci express multiple immunoglobulin-binding proteins (IGPs) on their surface that are similar in sequence and structure to the antiphagocytic M proteins. Both are evolutionary products of a duplicated ancestral gene and are components of the Vir gene cluster. Except for M proteins, there is little direct experimental evidence to implicate IGPs in pathogenesis. Several functions of IGPs are postulated and discussed.

Animals↗

ASA Physical Status and age predict morbidity after three surgical procedures.

OBJECTIVE: American Society of Anesthesiologists-Physical Status scores (ASA-PS) and age were used to adjust for case-mix differences when evaluating surgical morbidity and resource use after total hip replacement (THR), transurethral prostatectomy (TURP), or cholecystectomy. SUMMARY BACKGROUND DATA: Variations in complication rates or resource use among patients treated for a particular primary condition should be adjusted for coexistent disease. Age and ASA-PS scores are readily available and can be useful to stratify surgical patients for risk. METHODS: One thousand ninety patients at five academic medical centers in California and Massachusetts who underwent THR, TURP, or cholecystectomy between 1985 and 1987 were studied. Data were obtained from medical records and a self-administered questionnaire to measure length of stay (LOS), postoperative complication rates, and follow-up physician visits. Data were analyzed with one- and two-way analysis of variance with the Bonferroni correction. RESULTS: Increasing age and ASA-PS scores were associated significantly with increased LOS, complication rates, and frequency of post-discharge physician office visits. No interaction effect between age and ASA-PS scores was observed. CONCLUSIONS: Age and ASA-PS scores can predict postoperative morbidity, specific for each operation studied. Assessment of co-morbidity in surgical patients can be accomplished easily and with minimal expense. While remaining budget neutral, the distribution of reimbursements should be based on those preoperative risk factors that predict longer LOS and higher complication rates.

Adult↗

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

BACKGROUND: Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. METHODS: A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. RESULTS: In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. CONCLUSIONS: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

Adolescent↗

Surface protein-CAT reporter fusions demonstrate differential gene expression in the vir regulon of Streptococcus pyogenes.

Streptococcus pyogenes expresses at least two virulence factors, the anti-phagocytic M protein and an inhibitor of chemotaxis, the C5a peptidase (ScpA), under control of the virR locus. To facilitate studies of this regulatory unit, we constructed a new shuttle vector with a staphylococcal chloramphenicol acetyl transferase (CAT) reporter box which replicates in S. pyogenes. We cloned polymerase chain reaction (PCR)-derived potential promoter regions of the virR, M protein (emm12), and ScpA (scpA) genes from an M type 12 S. pyogenes, strain CS24. Promoter activity was assessed by measurements of specific mRNAs, transacetylase activity, and minimum inhibitory concentrations (MICs) for chloramphenicol resistance. We demonstrated that VirR is a necessary but not always sufficient positive trans-acting regulator of emm12 and scpA expression; however, virR is not autoregulated. A potential virR-binding consensus sequence is postulated for emm12, scpA and other M-like protein genes. Promoter activity of the structural genes was found to be dramatically influenced by growth conditions such as anaerobiosis. Levels of control, over and above the requirement for virR, are realized. The virR and scpA promoters were mapped for the first time using primer extension analysis. The observed mRNA start sites did not completely agree within the sequence predicted start sites. Data suggest that scpA could be subject to transcription attenuation.

Antigens, Bacterial↗

Epidemiology of delirium: an overview of research issues and findings.

This paper provides a review of research issues and findings on the epidemiology of delirium. Despite the fact that research on this important geriatric syndrome has been conducted for many decades, several methodological issues make it difficult to compare findings across studies. In this paper we first discuss broadly methodological issues related to diagnosis, case-finding, and populations studied. We next review data on the occurrence and consequences of the syndrome. A discussion of the design and preliminary results of the Commonwealth-Harvard Study of Delirium in Elderly Hospitalized Patients documents both how we responded to the methodological issues outlined and how these choices influenced our findings. We conclude with a discussion of the needs for further research on the epidemiology of delirium.

Aged↗

Review of research instruments and techniques used to detect delirium.

Over the past several decades, numerous investigators have studied the syndrome of delirium. Researchers have relied on a number of different case finding methods to detect the syndrome. This paper provides an overview of instruments used in studies of delirium. We assess the validity and reliability of these instruments and compare the advantages and disadvantages of the different methods. We then present the rationale for the development of the Delirium Symptom Interview, an instrument constructed for use in the Commonwealth-Harvard Study of delirium in elderly hospitalized patients.

Aged↗

Comparison of the leader sequences of four group A streptococcal M protein genes.

The 5' portions and flanking sequences of genes encoding types 1, 12, 24, and 6 M proteins were compared. Although the DNA sequences encoding the amino-termini of the mature M proteins had no obvious similarity, upstream sequences, and those encoding the signal peptides (leader sequences) of the four M protein genes had considerable similarity. In general, the 5' ends of all the leader sequences were more conserved than the 3' ends, although the M6 and M24 leader sequences had identical 3' ends. Sequence similarity among the deduced amino acid sequences of the four signal peptides was more extensive than the corresponding DNA sequences. We found that strict DNA similarity among all four sequences extended only to the ends of the hydrophilic amino-terminal regions of the signal peptides, but that amino acid sequence conservation continued to the ends of the respective hydrophobic cores. With the exception of the M6 and M24 sequences, the regions adjacent to the signal peptidase cleavage sites were highly variable.

Amino Acid Sequence↗

The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex.

Infection with human immunodeficiency virus type 1 (HIV-1) is frequently complicated in its late stages by the AIDS dementia complex, a neurological syndrome characterized by abnormalities in cognition, motor performance, and behavior. This dementia is due partially or wholly to a direct effect of the virus on the brain rather than to opportunistic infection, but its pathogenesis is not well understood. Productive HIV-1 brain infection is detected only in a subset of patients and is confined largely or exclusively to macrophages, microglia, and derivative multinucleated cells that are formed by virus-induced cell fusion. Absence of cytolytic infection of neurons, oligodentrocytes, and astrocytes has focused attention on the possible role of indirect mechanisms of brain dysfunction related to either virus or cell-coded toxins. Delayed development of the AIDS dementia complex, despite both early exposure of the nervous system to HIV-1 and chronic leptomeningeal infection, indicates that although this virus is "neurotropic," it is relatively nonpathogenic for the brain in the absence of immunosuppression. Within the context of the permissive effect of immunosuppression, genetic changes in HIV-1 may underlie the neuropathological heterogeneity of the AIDS dementia complex and its relatively independent course in relation to the systemic manifestations of AIDS noted in some patients.

Acquired Immunodeficiency Syndrome↗

Screening for alcohol abuse using the CAGE questionnaire.

A prospective study of 518 patients admitted to the orthopedic and medical services of a community-based teaching hospital during a six-month period was performed to test the hypothesis that a short, easily administered questionnaire would improve the detection rate by physicians of alcohol abuse. The CAGE questionnaire--a mnemonic for attempts to cut back on drinking, being annoyed at criticisms about drinking, feeling guilty about drinking, and using alcohol as an eye opener--was utilized as a screening instrument. The mean corpuscular volume of red blood cells, liver transaminase levels, and the gamma-glutamyl transpeptidase level were also evaluated as screening tests. The presence or absence of alcoholism and alcohol abuse for a consecutive sample of CAGE-negative patients and all patients answering "yes" to one or more of the CAGE questions was established through the administration of the Michigan Alcoholism Screening Test, a detailed chart review, and analysis of quantity of alcohol consumed. Diagnostic criteria were those described in the Diagnostic and Statistical Manual III. The prevalence of alcohol abuse was 20 percent. The mean corpuscular volume, gamma-glutamyl transpeptidase value, and liver transaminase levels were very insensitive as screening tests. In contrast, the CAGE questionnaire had a sensitivity of 85 percent and a specificity of 89 percent. Only 63 percent of the alcoholic subjects and alcohol abusers were detected by their physicians, and in only 24 percent of these cases did a physician address the problem with the patient. The CAGE questionnaire is a simple, sensitive, and specific screening test for alcohol abusers.

Alcoholism↗

A five-year survey of ocular shotgun injuries in Ireland.

Between November 1980 and September 1985 20 patients in Ireland sustained accidental ocular shotgun injuries severe enough to necessitate hospital admission. Eight patients had contusion injuries and 12 perforating injuries. Contusion damage was disproportionate to the size of the pellet. Through and through perforation of the globe occurred in eight patients; the remaining four patients in this group had retained intraocular pellets. Twelve patients sustained perforating eye injuries. Those that were treated by primary closure alone lost the sight in that eye. Those treated by vitreoretinal surgery recovered vision directly related to where the pellet had its exit from the eye. It was possible to contact 15 of the patients. All 15 were shooting pheasant. It was not possible to relate the distance of the patient from the gun to the severity of the ocular injury.

Adolescent↗