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Biomedical subjects

H Shaw

Publications and source records attributed to H Shaw.

At least 19 recordsLinked to original sources

Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial.

BACKGROUND: Cholinesterase inhibitors produce small improvements in cognitive and global assessments in Alzheimer's disease. We aimed to determine whether donepezil produces worthwhile improvements in disability, dependency, behavioural and psychological symptoms, carers' psychological wellbeing, or delay in institutionalisation. If so, which patients benefit, from what dose, and for how long? METHODS: 565 community-resident patients with mild to moderate Alzheimer's disease entered a 12-week run-in period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who completed this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged appropriate. Primary endpoints were entry to institutional care and progression of disability, defined by loss of either two of four basic, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS). Outcome assessments were sought for all patients and analysed by logrank and multilevel models. FINDINGS: Cognition averaged 0.8 MMSE (mini-mental state examination) points better (95% CI 0.5-1.2; p<0.0001) and functionality 1.0 BADLS points better (0.5-1.6; p<0.0001) with donepezil over the first 2 years. No significant benefits were seen with donepezil compared with placebo in institutionalisation (42% vs 44% at 3 years; p=0.4) or progression of disability (58% vs 59% at 3 years; p=0.4). The relative risk of entering institutional care in the donepezil group compared with placebo was 0.97 (95% CI 0.72-1.30; p=0.8); the relative risk of progression of disability or entering institutional care was 0.96 (95% CI 0.74-1.24; p=0.7). Similarly, no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms, carer psychopathology, formal care costs, unpaid caregiver time, adverse events or deaths, or between 5 mg and 10 mg donepezil. INTERPRETATION: Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than cholinesterase inhibitors are needed for Alzheimer's disease.

Activities of Daily Living↗

Dietetic guidelines: diet in secondary prevention of cardiovascular disease (first update, June 2003).

AIM: To update dietetic guidelines summarizing the systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to November 2002 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomised controlled trials relating to diet and secondary prevention of CVD. Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review. The quality and results of each review were discussed and summarized in a meeting of the whole group. RESULTS: Providing evidence-based dietary information (including increasing omega-3 fat intake) to all people who have had a myocardial infarction will save more lives than concentrating dietary advice on just those in need of weight loss or lipid lowering. The practice of prioritizing dietetic time in secondary prevention to those with raised lipids is out of date since the advent of statin therapy. However, effective dietary advice for those with angina, stroke, peripheral vascular disease or heart failure is less clear. CONCLUSION: There is good systematic review evidence that dietary advice to those with coronary heart disease can reduce mortality and morbidity as well as modify some risk factors. Dietary advice that does this most effectively should be prioritized.

Cardiovascular Diseases↗

Development of a database of functional assessment measures related to work disability.

The development of the Functional Assessment Measures Database is described. The database provides a method to organize and search for measures that are used to assess the functional abilities of people with medical impairments to determine work disability. The project identified 4,200 different measures that are used in the functional assessment of persons with disability across the life span, 812 of which are used to evaluate adults in terms of work disability. The database has 3,033 scales that are found in 633 measures. In the database, each measure is described and is linked to at least one functional assessment construct. The use of the database in the Social Security Administration Redesign Project is described. Other possible uses for the database are presented.

Databases, Factual↗

Involvement of 2p23 in pulmonary inflammatory pseudotumors.

Pulmonary inflammatory pseudotumors (IP) are rare mesenchymal proliferations that have a polymorphic histology and an unpredictable biologic behavior. The histologic spectrum of IP has led to uncertainty as to whether this tumor has a reactive or neoplastic pathogenesis. Reports of extrapulmonary IP have identified clonal chromosomal aberrations involving 2p23 in the region of the ALK gene. Using fluorescence in situ hybridization with a probe flanking the ALK gene at 2p23 and immunostaining for the ALK gene product, we studied formalin-fixed, paraffin-embedded tissues of pulmonary IP and found a subset (33%) with 2p23 aberrations. We suggest that chromosomal rearrangements and ALK immunostaining may be helpful in the diagnosis of a group of pulmonary IP and should be investigated as a potential tool for predicting their future biologic behavior. An association with anaplastic large-cell lymphoma was also observed. HUM PATHOL 32:428-433.

Adolescent↗

Reexamining the prevalence of Chlamydia trachomatis infection among gay men with urethritis: implications for STD policy and HIV prevention activities.

BACKGROUND: Evidence of an STD-HIV interaction and the availability of noninvasive urine-based screening tests have resulted in an increased focus on chlamydial infections in men. GOAL: To evaluate the prevalence of chlamydial infections among men with urethritis at the San Francisco City Clinic (SFCC). STUDY DESIGN: In 1997, male SFCC patients diagnosed with urethritis were tested for chlamydia using urine-based ligase chain reaction and for gonorrhea using urethral culture. RESULTS: Gonorrhea was identified in 45% of men who have sex with men (MSM) versus 26% of men who have sex with women (MSW). Among men with gonorrhea, chlamydia coinfection was found among 15.2% of MSM and 8.4% of MSW. Among men with nongonococcal urethritis, 18% and 20% of MSM and MSW had chlamydial infection, respectively. Young age was associated with chlamydial infection in MSM. CONCLUSION: After a period of low chlamydial infection rates in MSM during the pre-AIDS era, infection rates are increasing among this population. SFCC's revised clinical practice guidelines include chlamydia testing of MSM with urethritis.

Adolescent↗

Pig and goat blood as substitutes for sheep blood in blood-supplemented agar media.

In many developing countries sheep and horse blood, the recommended blood supplements in bacteriological media, are not readily available, whereas pig and goat blood are. Therefore, this study examined the use of pig and goat blood as potential substitutes for sheep blood in blood-supplemented bacteriologic media commonly used in clinical microbiology laboratories. In general, the growth characteristics and colony morphologies of a wide range of aerobic and anaerobic bacteria and Candida albicans were similar on media containing pig, goat, and sheep blood, although differences were found. Enterococcus sp. uniformly produced alpha-hemolysis when incubated in CO(2), but in anaerobic conditions the hemolysis varied. In contrast, beta-hemolytic streptococci produced identical hemolytic reactions on all three media. Synergistic hemolysis was not observed on pig blood agar in the CAMP test nor on goat blood agar in the reverse CAMP test. The preparation of chocolate agar (heated) with pig blood required heating to a higher temperature than with sheep or goat blood to yield suitable growth of Haemophilus species. In general, we conclude that pig and goat blood are suitable alternatives to sheep blood for use in bacteriological media in settings where sheep and horse blood are not readily available.

Agar↗

Malignant meningioma with extension into the neck.

One per cent of all brain tumours and twenty per cent of meningiomas eventually develop an extracranial extension. The least common site is the neck. We report a case of malignant meningioma with extension into the neck of a 39-year-old male.

Adult↗

Duration of intravenous therapy and hospital stay according to choice of empirical antimicrobial treatment for community-acquired respiratory infection.

A review of patients admitted to medical wards with respiratory infection was undertaken to look for differences in duration of intravenous (IV) therapy and length of patient stay based on the class of IV antimicrobial used in treatment. Data was analysed from 231 patients with community-acquired respiratory infection who were treated empirically for at least 24 h with either an IV cephalosporin (146 patients) or an IV penicillin or macrolide (85 patients). The severity of illness and indication for IV treatment was similar in each group. Those treated with a cephalosporin received IV therapy for a significantly longer period (mean = 4.44 days, SD = 2.6) than those given a penicillin or macrolide (mean = 3.3 days, SD = 1.8): P < 0.001. Patient stay was significantly longer in the cephalosporin group (mean = 11.6 days, SD = 10.4) than the penicillin/macrolide group (mean = 9.4 days, SD = 6.3): P = 0.04. These differences are most readily accounted for by the absence from the hospital formulary of a third generation oral cephalosporin, a drug that might be regarded as an obvious form of follow-on therapy in patients treated empirically with an injectable cephalosporin.

Anti-Bacterial Agents↗

Factors contributing to dehydration in nursing homes: inadequate staffing and lack of professional supervision.

OBJECTIVE: To investigate the factors that influenced fluid intake among nursing home residents who were not eating well. DESIGN: A prospective, descriptive, anthropological study. SETTING: Two proprietary nursing homes with 105 and 138 beds, respectively. PARTICIPANTS: Forty nursing home residents. MEASUREMENTS: Participant observation, event analysis, bedside dysphagia screening, mental and functional status evaluation, assessment of level of family/advocate involvement, and chart review were used to collect data. Data were gathered on the amount of liquid served and consumed over a 3- day period. Daily fluid intake was compared with three established standards: Standard 1 (30 mL/kg body weight), Standard 2 (1 mL/kcal/energy consumed), and Standard 3 (100 mL/kg for the first 10 kg, 50 mL/kg for the next 10 kg, 15 mL/kg for the remaining kg). RESULTS: The residents' mean fluid intake was inadequate; 39 of the 40 residents consumed less than 1500 mL/day. Using three established standards, we found that the fluid intake was inadequate for nearly all of the residents. The amount of fluid consumed with and between meals was low. Some residents took no fluids for extended periods of time, which resulted in their fluid intake being erratic and inadequate even when it was resumed. Clinical (undiagnosed dysphagia, cognitive and functional impairment, lack of pain management), sociocultural (lack of social support, inability to speak English, and lack of attention to individual beverage preferences), and institutional factors (an inadequate number of knowledgeable staff and lack of supervision of certified nursing assistants by professional staff) contributed to low fluid intake. During the data collection, 25 of the 40 residents had illnesses/conditions that may have been related to dehydration. CONCLUSIONS: When staffing is inadequate and supervision is poor, residents with moderate to severe dysphagia, severe cognitive and functional impairment, aphasia or inability to speak English, and a lack of family or friends to assist them at mealtime are at great risk for dehydration. Adequate fluid intake can be achieved by simple interventions such as offering residents preferred liquids systematically and by having an adequate number of supervised staff help them to drink while properly positioned.

Activities of Daily Living↗

Commissioning health services research: an iterative method.

The standard linear method of commissioning research involves many stages, some lengthy. While assessment criteria are usually explicit, their weighting and interaction are not. Output is assessed on completion. This method is suitable where the research question is clear-cut. However, it has drawbacks when the research question and the form and scope of the research are not clear at the outset, as is often the case with research on the delivery and organisation of services. Also, it does not encourage potential users of the research to develop a sense of ownership. An alternative method is proposed by which the scope, form and content of research are not specified in advance but are developed iteratively. A programme director, advised by a group of potential users and research commissioners, has devolved authority to commit funding for the stages of the work as it unfolds, predicated on evolving need. There are foreseeable but avoidable risks of the group over-identifying with the researchers, of research management becoming cumbersome, and of unproductive friction between research groups when they are required to work together. The iterative method, being new and untried, is itself an organisational change requiring evaluation. However, from our local experience, it provides for productive dialogue between research commissioners, researchers and potential users.

Health Services Research↗

Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.

Mutation and deletion of the PTEN tumor suppressor gene occurs in about 40% of endometrial carcinomas. The purpose of this study was to determine whether PTEN mutations also are present in endometrial hyperplasias, which are premalignant precursors of invasive endometrial adenocarcinomas. Genomic DNA from 51 endometrial hyperplasias was extracted from paraffin blocks, and PCR was used to amplify the nine exons of the PTEN gene. These products were screened using single-strand conformation analysis, and variant bands were sequenced. Somatic mutations in the PTEN gene were seen in 10 of 51 cases (20%), and two mutations were found in one case. An identical 4-bp deletion in exon 8 was seen in three cases, and 8 of 11 PTEN mutations predicted truncated protein products. There was no higher frequency of PTEN mutations in endometrial hyperplasias with atypia (6 of 32; 19%) relative to those without atypia (4 of 19; 21%). These data suggest that inactivation of the PTEN tumor suppressor gene is an early event in the development of some endometrial cancers.

Endometrial Hyperplasia↗

Mutation of the PTEN tumor suppressor gene is not a feature of ovarian cancers.

OBJECTIVE: The PTEN tumor suppressor gene on chromosome 10q23 undergoes inactivating mutations in several types of malignancies including glioblastomas and prostate and endometrial carcinomas. The aim of this study was to determine if mutation of the PTEN tumor suppressor gene is a feature of sporadic or BRCA1-associated ovarian carcinomas. METHODS: Genomic deoxyribonucleic acid was extracted from 11 ovarian cancer cell lines and 50 frozen ovarian cancers, including 4 cases that developed in women with germline mutations in the BRCA1 breast/ovarian cancer susceptibility gene. The polymerase chain reaction was used to amplify each of the nine exons and intronic splice sites of the PTEN gene. These products were then screened for mutations using single strand conformation polymorphism analysis. Variant bands were further evaluated using automated DNA sequencing. RESULTS: A previously unreported silent polymorphism at codon 240 (TAT to TAC) in exon 7 was noted in one of the primary ovarian carcinomas. Mutations in the PTEN gene were not found in any of the 50 primary ovarian cancers or 11 immortalized ovarian cancer cell lines. CONCLUSION: Alteration of the PTEN tumor suppressor gene does not appear to be a feature of sporadic or BRCA1-associated ovarian cancers.

Exons↗

The effect of intravenous-to-oral switch guidelines on the use of parenteral antimicrobials in medical wards.

The effect of an intravenous (i.v.)-to-oral switch policy on antibiotic prescribing in general medical wards was examined. Three audits, each of 2 months' duration, were carried out to examine the duration of i.v. therapy and length of patient stay. The first audit (S1) was performed before the introduction of switch guidelines, the second (S2) after guidelines had been placed in patient case-notes and the third (S3) after the guidelines had been introduced into the drug charts. The duration of i.v. therapy was significantly shorter in the S3 group (mean = 3.7 days) than in the S2 or S1 groups (mean 4.4 and 4.35 days, respectively) (P < 0.05). There was no significant difference in the length of patient stay between the three audit periods but the stay was significantly shorter in 81 switched patients (mean duration = 8.9 days) than in matched controls (mean duration = 12.6 days) (P = 0.01). Fewer patients with respiratory infection were treated for > 24 h with i.v. antimicrobials in the S3 audit period (75/549) than in the S2 (85/372) and S1 audits (83/326) (P < 0.01). The introduction of switch guidelines to drug charts reduces the length of i.v. therapy. Switched patients spend less time in hospital than their matched controls.

Administration, Oral↗

Comparison of virus culture and the polymerase chain reaction for diagnosis of mucocutaneous herpes simplex virus infection.

BACKGROUND AND OBJECTIVES: The diagnosis of mucocutaneous herpes simplex virus (HSV) is hampered by suboptimal sensitivity of virus culture and atypical clinical morphology. GOALS: To compare the diagnostic usefulness of the polymerase chain reaction (PCR) and virus culture. STUDY DESIGN: Consecutive samples from 246 patients at an urban sexually transmitted diseases clinic were tested for HSV by both PCR and virus culture. RESULTS: Only 59% of HSV-positive samples were correctly diagnosed by the clinician; 11% had an atypical appearance. HSV-positive lesions were more often vesiculoulcerative or crusted than HSV-negative lesions, and of shorter median duration. Thirty-one samples were PCR positive and virus culture negative; these were often from crusted or older lesions. However, PCR was negative in 27 instances in which HSV was diagnosed clinically, of which 2 were vesicular and 15 ulcerative. CONCLUSIONS: HSV PCR is more rapid and sensitive than virus culture for diagnosis of mucocutaneous lesions. The data suggesting that PCR may be suboptimally sensitive need to be further investigated.

Female↗

Is urine leukocyte esterase test a useful screening method to predict Chlamydia trachomatis infection in women?

We evaluated the use of the leukocyte esterase test (LET) on first-catch urine specimens from women as a screening test to predict infection with Chlamydia trachomatis. For diagnosis, we used Abbott's ligase chain reaction (LCR) on urine specimens and isolation by tissue culture (TC) on cervical brushes. Of 4,053 women attending sexually transmitted disease and family planning clinics, 4.3% (n = 174) were positive by TC and 5.9% (n = 239) were positive by LCR. When LET was compared to TC, the sensitivity, specificity, positive predictive value, and negative predictive value were 54.0, 67.0, 6.8, and 97.0%, respectively. The corresponding performance of LET versus LCR was 53.1, 67.3, 10.1, and 95.8%. Almost half of the laboratory-confirmed chlamydial infections were negative by LET. The low specificity probably reflects multiple causes of pyuria in women and results in a low positive predictive value. LET is neither sensitive nor specific as a predictor of chlamydial infection and cannot be recommended for use as a screening test for C. trachomatis with first-catch urine samples from females from low- or moderate-prevalence populations.

Chlamydia Infections↗