Doxazosin for the management of hypertension: implications of the findings of the ALLHAT trial.
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Adrenergic alpha-Antagonists↗
Biomedical subjects
B Williams
Publications and source records attributed to B Williams.
Does neonatal ocular misalignment predict later abnormality?
PURPOSE: A longitudinal prospective study was carried out to ascertain the significance of neonatal ocular misalignments. METHODS: Pre-school vision screening and hospital records were examined to determine the visual outcome of 1150 infants classified into 'often' (> 15% of waking hours), 'occasionally' (< 15%) or 'never' having an ocular misalignment (neonatal squint) in the first 8 weeks of life. Chi2 and Fisher's exact tests and ANOVA were used to analyse the data. RESULTS: When compared with infants who had squinted occasionally or never, frequent squinting in the neonatal period (which occurred in 7.7% of the subjects) was significantly associated with having been prescribed spectacles (p = 0.04), both for hypermetropia (p = 0.04) and for myopia (p = 0.05). Frequent squinters also had a higher incidence of significant esodeviation (p = 0.04) and were more likely to be > 21 days premature (p = 0.05). Small numbers of abnormalities made statistical analysis limited, but there were weak trends towards more myopic and oblique astigmatism in the 'never' group. The esotropias in the 'often' group were more frequently intermittent than those found in the other groups. CONCLUSIONS: Occasional squinting in the first 8 weeks of life appears to be normal neonatal behaviour. Frequent squinting trebles the chances of developing a significant esodeviation or refractive error severe enough to require spectacles before 5 years of age but incidence of abnormality still does not exceed 9%.
Analysis of Variance↗
Opioid analgesic prescribing and use - an audit of analgesic prescribing by general practitioners and The Multidisciplinary Pain Centre at Royal Brisbane Hospital.
AIMS: This study evaluated the use of and need for opioids in patients attending the Multidisciplinary Pain Centre at the Royal Brisbane Hospital (RBH). METHODS: All consecutive in-patient admissions in 1998 were reviewed. A 10-point scoring system based on the World Health Organization (WHO) analgesic ladder was devised to facilitate comparison of analgesic prescribing on admission and at the time of discharge. A conversion table was used to standardize opioid analgesic doses to an oral morphine equivalent. RESULTS: Of the 370 patients reviewed, 233 (81%) were by their general practitioners. Records of 288 (78%) were available for full review and 270 (94%) of these had noncancer pain. On admission, 239 (83%) were taking an opioid analgesic, with 135 (47%) taking strong opioids (e.g. morphine, oxycodone, methadone). There was a significant decrease in the mean total daily oral morphine equivalent prescribed on discharge 36.9 mg (95% CI: 33.4, 40.4) compared with that on admission 88.7 mg (95% CI: 77.6, 99.8) (P < 0.001). There was a significant decrease (P < 0.05) in the proportion of patients taking a primary opioid on discharge 153 (58%) compared with admission 239 (83%), although the proportion of patients taking a strong opioid on discharge 150 (52%) compared with admission 135 (47%) was not significantly different (P > 0.05). The proportion of patients taking a laxative showed a significant increase on discharge 110 (73%) compared with admission 38 (28%) (P < 0.05). CONCLUSIONS: Our analgesic prescribing scoring system and opioid conversion table have the potential to be developed further as tools for assessing opioid analgesic prescribing. The significant decrease in total daily oral morphine equivalents signifies the value of prescribing in accordance with the WHO analgesic ladder, and the necessity of general practitioner education. The management of chronic pain is complex, and it requires interventions additional to pharmacological therapy. Evaluation by a multidisciplinary team, coupled with experience in and an understanding of analgesic prescribing and rehabilitation provides an effective basis for improving the management of patients with chronic pain.
Acetaminophen↗
Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older.
BACKGROUND: Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported. OBJECTIVE: To describe the long-term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma. METHODS: Male and female patients with chronic, stable asthma (adults aged 15-85 years, children aged 6-14 years), who had completed double-blind, placebo-controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 microg twice daily for adults, beclomethasone 100 microg or equivalent three times daily for children). A double-blind adult extension study was 37 weeks in duration; open-label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively. RESULTS: Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open-label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow-up treatment period. CONCLUSION: Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open-label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.
Acetates↗
Disclosure of minor mental health problems: an exploratory theoretical study.
AIM: The aim of this study was to explore people's experiences, concerns and beliefs about disclosing minor mental health problems by focusing on the ways in which such disclosures are interpreted. BACKGROUND: Approximately half of people with mental health problems do not seek help. The decision to consult represents just one aspect of the process of revealing one's illness to others. People with mental health problems are known to be reluctant to reveal the existence of those problems through fear of how others might then view them. DESIGN: A qualitative approach was employed. In-depth interviews were carried out with 47 users and nonusers of community mental health services. Interviews were tape-recorded, transcribed and analysed. RESULTS: The data suggest that when people reveal minor mental health problems others interpret these in relation to a number of perceived contextual factors. These include perceptions of the severity and duration of any possible causes, the inner 'strength' of the person, the expected ability of the person to either solve or suppress the experience, and the form and context of the expression itself. The data presented included individuals who were seeking help for relatively 'minor' mental health problems (primarily depression and anxiety) and individuals who had no current mental health problems but routinely managed expressions of their own emotions. Throughout the data there appeared to be no distinct difference between these two groups other than one of the severity of psychological experience. CONCLUSION: The key elements involved in the interpretation of people's expressions of sadness were essentially the same as those involved in the interpretation of expressions of depression. An appreciation of these contextual factors influencing the interpretation and disclosure of minor mental health problems may aid the development of more person-centred mental health services and inform the content of health education in the mental health field.
Adaptation, Psychological↗
Valuing people as individuals: development of an instrument through a survey of person-centredness in secondary care.
BACKGROUND: Person-centred care is regarded as the optimum way of delivering health care and is defined as valuing people as individuals (Winefield et al. 1996). So how can practitioners find out if their service 'values people as individuals'? Serious doubts have been expressed about the validity of the concept of patient satisfaction and the ability of instruments to measure patients' views of care. However, qualitative research among people who had experienced problems with their health care has identified an alternative concept better able to articulate patient's complex experiences (Coyle 1997). The study found that that patients' identity was threatened by experiences perceived as dehumanizing, objectifying, disempowering and devaluing. Thus the concept of 'personal identity threat' showed the extent to which people felt valued (or not) as individuals. AIM OF THE STUDY: The aim of the research reported in this paper is to build upon the earlier qualitative work and to identify the frequency and distribution of inpatients' experiences of 'personal identity threat'. DESIGN/METHODS: The study adopted a cross-sectional survey design. Ninety-seven patients from general medical, surgical and otolaryngology wards completed a questionnaire developed from the qualitative study containing items on dehumanization, objectification, disempowerment and devaluation. FINDINGS: Although many patients expressed positive sentiments about their care, problems were highlighted around power/control, involvement in care, and the approachability and availability of staff. The findings also revealed that women were more at risk than men of 'threats to identity' in health care settings. CONCLUSIONS: Improvements are suggested to help promote a service that truly values people as individuals. These include improving health practitioners' understanding of the impact of illness on everyday life, promoting practitioners' listening and enquiring skills, and increasing the 'visibility' and availability of staff. Further research should also explore gender and age differences in perceptions of the lay-practitioner relationship.
Adolescent↗
Developing critical reflection for professional practice through problem-based learning.
AIMS: To explore the influence of current learning traditions in nursing on the development of reflection and critical reflection as professional practice skills and to offer suggestions for nursing education that will specifically facilitate the development of critical reflection. ORGANIZATIONAL CONSTRUCTS: Mezirow's transformative learning theory, Barrows conceptualization of problem-based learning (PBL). METHODS: Integrative literature review of published literature related to nursing, health science education and professional education from 1983-2000. FINDINGS: Professional education scholars concur that specialized knowledge is clearly essential for professional practice, however, they also suggest that self-consciousness (reflection) and continual self-critique (critical reflection) are crucial to continued competence. While strategies to facilitate reflection have been outlined in the literature, specific strategies to facilitate the development of critical reflection and implications for nursing education are much less clear. Advocates of reflective and critically reflective practice suggest that the development of these abilities should be inextricably linked to professional development and can be developed through active repeated guided practice. In health care, PBL based on constructivism, has been identified as one way to facilitate the development of these skills. CONCLUSIONS: Nursing learners exposed to PBL develop the ability to be reflective and critically reflective in their learning and acquire the knowledge and skill within the discipline of nursing by encountering key professional practice situations as the stimulus and focus of their classroom learning. The learners' ability to be both reflective and critically reflective in their learning is developed by critical questioning of the faculty tutor during situational analysis, learning need determination, application of knowledge, critique of resources and personal problem-solving processes, and summarization of what was learned.
Education, Nursing↗
Metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin by human hepatic CYP isoforms: evidence for selectivity towards CYP3A4.
1. The metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (BFBFC) to 7-hydroxy-4-trifluoromethylcoumarin (HFC) was studied in human liver microsomes and in cDNA-expressed human liver CYP isoforms. For purposes of comparison, some limited studies were also performed with 7-benzyloxyquinoline (7BQ). 2. Initial interactive docking studies with a homology model of human CYP3A4 indicated that BFBFC was likely to be a selective substrate for CYP3A4 with a relatively high binding affinity, due to the presence of several key hydrogen bonds with active site amino acid residues. 3. Kinetic analysis of NADPH-dependent BFBFC metabolism to HFC in three preparations of pooled human liver microsomes revealed mean (+/- TSEM) Km and Vmax = 4.6 +/- 0.3 microM and 20.0 +/- 3.8 pmol/min/mg protein, respectively. 4. The metabolism of BFBFC to HFC was determined in a characterized bank of 24 individual human liver microsomal preparations employing a BFBFC substrate concentration of lO microM (i.e. around twice Km). Good correlations (r2 = 0.736-0.904) were observed between BFBFC metabolism and markers of CYP3A isoforms. 5. While 10O microM BFBFC was metabolized to HFC by cDNA-expressed CYP3A4, little or no metabolism was observed with cDNA-expressed CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 6. The metabolism of 10 microM BFBFC in human liver microsomes was markedly inhibited by 5-50 microM troleandomycin and 0.2-5 microM ketoconazole, but stimulated by 0.2-10 microM alpha-naphthoflavone. The metabolism of 10 microM BFBFC in human liver microsomes was also markedly inhibited by an antibody to CYP3A4. 7. Kinetic analysis of NADPH-dependent 7BQ metabolism to 7-hydroxyquinoline (7HQ) in human liver microsomes revealed Km and Vmax = 70 microM and 3.39 nmol/min/mg protein, respectively. 8. While 80 microM 7BQ was metabolized to 7HQ by cDNA-expressed CYP3A4, only low rates of metabolism were observed with cDNA-expressed CYPIA2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 9. In summary, by correlation analysis, the use of cDNA-expressed CYP isoforms, chemical inhibition and inhibitory antibodies, BFBFC metabolism in human liver microsomes appears to be primarily catalysed by CYP3A4. BFBFC may be a useful fluorescent probe substrate for human hepatic CYP3A4, but compared with 7BQ has only a low rate of metabolism in human liver microsomes.
Coumarins↗
Evaluation of 7-benzyloxy-4-trifluoromethylcoumarin, some other 7-hydroxy-4-trifluoromethylcoumarin derivatives and 7-benzyloxyquinoline as fluorescent substrates for rat hepatic cytochrome P450 enzymes.
1. The aim of this study was to evaluate a number of derivatives of 7-hydroxy-4-trifluoromethylcoumarin (HFC) and 7-benzyloxyquinoline (7BQ) as novel fluorescent substrates for monitoring rat hepatic cytochrome P450 (CYP) enzyme specificity in a 96- well plate format. The HFC derivatives examined comprised 7-benzyloxy-4-trifluoromethylcoumarin (BFC), 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (BFBFC), 3,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (BTBFC), 2-(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (2TFBFC), 3-(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (3TFBFC) and 3-(trifluoromethoxy)-7-benzyloxy-4-trifluoromethylcoumarin (3TFMeOBFC). 2. The CYP specificity of the fluorescent probe substrates was examined using characterized liver microsomes from male Sprague-Dawley rats treated with beta naphthoflavone (BNF), sodium phenobarbitone (NaPB), isoniazid, pregnenolone-16alpha-carbonitrile (PCN), dexamethasone (DEX) and methylclofenapate to induce CYP1A, CYP2B, CYP2E, CYP3A, CYP3A and CYP4A forms, respectively. Studies were also performed with microsomes from baculovirus-infected insect cells containing rat cDNA-expressed CYP1A1, CYP1A2, CYP2B1, CYP3A1 and CYP3A2. 3. BFC metabolism was most markedly induced by BNF and NaPB, whereas BFBFC metabolism was most markedly induced by PCN and DEX and BTBFC was not metabolized by rat liver microsomes. BFC was a high-affinity substrate for cDNA-expressed CYP1A1 and CYP2B1, whereas BFBFC exhibited a high affinity for CYP3A1 and CYP3A2. 4. The metabolism of 2TFBFC and 3TFBFC was induced by NaPB, PCN and DEX. 3TFBFC was a relatively specific substrate for cDNA-expressed CYP2B1, whereas 2TFBFC could be metabolized by CYP2B1, CYP3A1 and CYP3A2. 5. 3TFMeOBFC metabolism was markedly induced by BNF treatment and 3TFMeOBFC was extensively metabolized by cDNA-expressed CYP1A1. 6. The metabolism of 7BQ to 7-hydroxyquinoline was induced by treatment with PCN and DEX. 7BQ was a substrate for cDNA-expressed CYP3A2 and to a lesser extent for CYP3A1. 7. In summary, some of the HFC derivatives studied and 7BQ are useful fluorescent probe substrates for rat CYP enzymes. BFC appears to be a probe for CYP1A and CYP2B, 2TFBFC for CYP2B and CYP3A and 3TFBFC for CYP2B. While 3TFMeOBFC appears to be a relatively specific probe for CYP1A1, both BFBFC and 7BQ are good probes for the induction of CYP3A.
Animals↗
Impact of private funding on access to elective hospital treatment in the regions of England and Wales. National records survey.
BACKGROUND: The UK National Health Service aims to match access to health care to the level of need and to reduce inequalities in the health of sub-populations. One in ten persons have private medical insurance (PMI). This study describes the impact of private purchasing on access to hospital care in regions according to health need. METHOD: Details of admissions to NHS hospitals in one year and waiting times were obtained from the government's Hospital Episodes Statistics, and of patients in independent hospitals through weighted time samples of records. Data were combined into two groups, state funded and privately funded patients. The prevalence of limiting longstanding illness and the proportions of individuals covered by PMI in Wales and the eight English health regions were obtained from the General Household Survey. Correlation coefficients were calculated for inter-regional relationships between measures of need, provision of resources and levels of activity. RESULTS: Limiting, longstanding illness was significantly associated with NHS resource levels, NHS hospital activity, and total hospital activity, however funded; and inversely with PMI coverage, waiting times for NHS admission and levels of privately funded activity. Waiting times for admission were positively correlated with PMI coverage. CONCLUSIONS: Regionally, NHS resources and activity match need. Private hospital use complements lower levels of NHS service. Private consumption does not distort access according to need but in regions with lower levels of NHS activity those least deprived may make relatively more use of NHS hospitals, thus widening the health gap. Small area studies should explore this.
Elective Surgical Procedures↗
Emergency transfer from independent hospitals to NHS hospitals: risk, reasons and cost.
BACKGROUND: In view of public concern about standards of emergency care in independent hospitals and the impact of transferred patients on NHS facilities we aimed to estimate the number and risk of emergency transfers from independent hospitals to NHS hospitals; to describe the circumstances; and estimate costs to the NHS. METHODS: Patients transferred in three months from 137 independent hospitals were identified from central records systems and local hospital enquiries. Circumstances were described by Directors of Nursing in telephone interviews. Numbers were weighted for whole year activity and non-participating hospitals to estimate total transfers in 1999. Medical Directors of NHS Trusts receiving the patients supplied durations of stay in critical care and other facilities. NHS Reference Costs were applied. RESULTS: There were 158 emergency transfers (plus 105 planned transfers, and 18 as a result of funding problems). Proportionately more emergency transfers were from hospitals lacking intensive care facilities. Patients over 65 years old constituted 61 per cent of transfers but only 25 per cent of all cases. Transfer followed major abdominal surgery in 42 (26 per cent) cases and major orthopaedic surgery in 31 (20 per cent), although these treatments constituted only 2 per cent and 3 per cent of the caseloads. There were an estimated 749 emergency transfers in 1999 (95 per cent confidence interval 640-875), a risk of 1 in 956 (all ages) and 1 in 392 (aged over 65); 729 had been funded privately, of whom two-thirds became NHS patients after transfer, costing Pound Sterling 2.61 million. CONCLUSIONS: The scale of emergency transfer (two per day) and resulting cost to the NHS is small. The risk is reducible if patients and interventions are matched to hospitals' critical care capabilities. Common clinical service guidelines should apply to NHS and independent hospitals.
Adolescent↗
Local excision of T2 and T3 rectal cancers after downstaging chemoradiation.
OBJECTIVE: To evaluate the safety and efficacy of local excision in patients with T2 and T3 distal rectal cancers that have been downstaged by preoperative chemoradiation. SUMMARY BACKGROUND DATA: T2 and T3 cancers treated by local excision alone are associated with unacceptably high recurrence rates. The authors hypothesized that preoperative chemoradiation might downstage both T2 and T3 lesions and significantly expand the indications for local excision. METHODS: Local excision was performed after preoperative chemoradiation on patients with a complete clinical response or on patients who were either ineligible for or refused to undergo abdominoperineal resection. Local excision was approached transanally by removing full-thickness rectal wall and the underlying mesorectum. RESULTS: From 1994 to 2000, 95 patients with rectal cancers underwent preoperative chemoradiation and surgical resection for curative intent. Of these, 26 patients (28%), 19 men and 7 women, with a mean age of 63 years (range 44-90), underwent local excision. Pretreatment endoscopic ultrasound classifications included 5 T2N0, 13 T3N0, 7 T3N1, and 1 not done. Pathologic partial and complete responses were achieved in 9 of 26 (35%) and 17 of 26 (65%) patients, respectively. Two of nine partial responders underwent immediate abdominoperineal resection. The mean follow-up was 24 months (median 19, range 6-77). The only recurrence was in a patient who refused to undergo abdominoperineal resection after a partial response. There was one postoperative death from a stroke. This treatment was associated with a low rate of complications. CONCLUSION: Local excision appears to be an effective alternative treatment to radical surgical resection for a highly select subset of patients with T2 and T3 adenocarcinomas of the distal rectum who show a complete pathologic response to preoperative chemoradiation.
Adenocarcinoma↗
Analysis of hematopoietic phenotypes in knockout mouse models.
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Animals↗
Effects of candesartan on cardiac and arterial structure and function in hypertensive subjects.
OBJECTIVES: To study the effect of candesartan cilexetil on left ventricular mass index (LVMI), left ventricular systolic and diastolic function, arterial structure and function and blood pressure (BP) in hypertensive patients. DESIGN AND METHODS: Patients (n=35), aged >20 years, with hypertension and average baseline LVMI of 89 g/m2 were treated for 24 weeks with candesartan, 16 mg o.d., following a four-week placebo run-in period. If diastolic BP remained above 95 mmHg, hydrochlorothiazide, 12.5 mg o.d.,was added. Left ventricular structure and function were assessed using transthoracic echocardiography. Arterial function and structure were assessed using pulse wave analysis to calculate augmentation index (AIx) and forearm plethysmography to calculate minimum vascular resistance. BP was measured in the office and by 24-hour ambulatory BP monitoring (ABPM). RESULTS: The mean reduction in LVMI was 4.4 g/m2(p=0.022). Left ventricular systolic function was not significantly altered from baseline, but diastolic function significantly improved: the mean change in diastolic time was 54 ms (p=0.037), in peak velocity filling 6.3 cm/s (p=0.023); E:A ratio improved by 0.08 (p=0.049). The mean reduction in forearm vascular resistance was 15 units at rest (p=0.001) and 1.3 units after limb ischaemia (p=0.006). AIx decreased significantly, with a mean reduction of 9% (p<0.001). Central BP also significantly reduced(systolic blood pressure/diastolic blood pressure 31/20 mmHg; p<0.001). BP was significantly reduced, both in the office (22/16 mmHg; p<0.001) and by 24-hourABPM (18/12 mmHg; p<0.001). CONCLUSIONS: Treatment with candesartan, 16 mg o.d., with or without hydrochlorothiazide, for 24 weeks, significantly reduced left ventricular mass and arterial hypertrophy in patients with hypertension. In parallel, there were significant improvements in left ventricular diastolic function and arterial function.
Adult↗
Elections 2000: the future of health care.
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Delivery of Health Care↗
Handheld computers making the rounds with physicians. Devices put medical know-how--literally--in the palm of your hand.
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Computer Peripherals↗
Decision to delivery for assisted vaginal vertex delivery.
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Anesthesia, Obstetrical↗
AMA, TMA analyzing new privacy rules for medical records.
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Confidentiality↗