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Biomedical subjects

P Davey

Publications and source records attributed to P Davey.

At least 73 records · Page 4Linked to original sources

Intravenous antimicrobial therapy in the community: underused, inadequately resourced, or irrelevant to health care in Britain?

The NHS Executive is keen to promote "hospital at home" services in Britain, as part of its philosophy of keeping more care in the community and also to relieve the increasing demand for hospital beds. One such service is the provision of intravenous antimicrobial therapy in the community. Yet, compared with the United States, where home or outpatient intravenous antimicrobial therapy programmes are well developed, experience in Britain and Europe is limited, reflecting a difference in cultural attitudes and healthcare structures between the two continents. Only a few units in Britain currently run home intravenous antimicrobial therapy programmes, and several issues need to be addressed if more treatment is to be provided outside hospital. These include an assessment of the need for community intravenous antibiotic treatment and which patient groups many benefit. The main motive for community intravenous treatment should be better patient care and not simply a reduction in healthcare costs. At present the pace of change is being set by a few clinical enthusiasts and by commercial organisations, whereas the NHS deserves a more organised strategy for purchasing treatment with intravenous antibiotics in the community.

Anti-Bacterial Agents↗

Radiosurgery for the treatment of previously irradiated recurrent primary brain tumors and brain metastases: initial report of radiation therapy oncology group protocol (90-05).

PURPOSE: To determine the maximum acutely tolerable dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors or brain metastases. METHODS AND MATERIALS: Between August 1990 and September 1993, 102 analyzable patients were entered on Radiation Therapy Oncology Group (RTOG) protocol 90-05, 38 of whom had recurrent primary brain tumors (median prior dose 60 Gy), and 64 of whom had recurrent brain metastases (median prior dose 30 Gy) < or = 40 mm in maximum diameter. Unacceptable toxicity was defined as irreversible Grade 3, any Grade 4, or Grade 5 central nervous system (CNS) toxicity according to the RTOG CNS criteria, occurring in > 20% of patients per treatment arm within 3 months of radiosurgery. RESULTS: Patients were initially entered onto one of three treatment arms according to the maximum diameter of the recurrent lesion. Twelve to 22 patients were entered on each arm. The dose levels were: arm 1, < or = 20 mm, 18 Gy; arm 2, 21-30 mm, 15 Gy; and arm 3, 31-40 mm, 12 Gy. Subsequently, doses were escalated as follows: arm 4, < or = 20mm, 21 Gy; arm 5, 21-30 mm 18 Gy; and arm 6, 31-40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebral edema occurred in 0, 7 and 5% of patients on Arms 1, 2 and 3, respectively, and in no patients on arms 4, 5, or 6. Multivariate analysis revealed that tumor volume > or = 8200 mm(3) and a ratio of maximum dose to prescription dose (MD/PD) > or = 2 were significantly associated unacceptable toxicity. Of 15 patients with both tumor volume > or = 8200 mm(3) and MD/PD > or = 2, unacceptable toxicity occurred in 2 of 4 treated with a single isocenter and 1 of 11 treated with multiple isocenters. Subsequently, operation for symptomatic radionecrosis was required in 6% of patients. CONCLUSION: We found that the incidence of acute toxicity was acceptable at 0-7% in patients with recurrent, previously irradiated primary brain tumors or brain metastases < or = 40 mm in maximum diameter treated according to the protocol described.

Adult↗

Impact of an infection consultation service for bacteraemia on clinical management and use of resources.

Since 1993, the infection consultation service for bacteraemia has seen 310 patients in the Medical and Surgical Directorates at Ninewells Hospital and Kings Cross Hospital. A random sample of 100 was audited. Case-notes were incomplete for five patients, leaving 95 fully-audited patients. Clinical outcome measures were death from infection, and readmission within 2 weeks of discharge. Initial treatment was inconsistent with antibiotic policy in 46 patients (48%). Antibiotic treatment was changed in 37 (80%) of these patients: increased in intensity in 19 (41%) and decreased in 18 (39%). Changes were also made in 30 (61%) of the 49 patients whose initial treatment was consistent with sepsis policy-increased in seven (14%) and decreased in 23 (47%). Median daily antibiotic costs were lowered in patients whose initial treatment was consistent with sepsis policy (pounds 10.10 vs. pounds 7.28, p = 0.0274). However, in the other patients, savings were balanced by increases (p = 0.7696). Consultation required one consultant session per week (3.5 h) and the audit required an additional 16 consultant sessions. Seven patients died, but only one death was directly related to infection. Six patients were readmitted to hospital within 2 weeks, in three due to recurrence of infection. Changes to treatment were recommended in the majority of patients, regardless of whether initial treatment complied with the sepsis policy. The service primarily redistributed resources rather than reducing costs. A fully audited service requires considerable consultant time, but we believe such time is well spent.

Anti-Bacterial Agents↗

Bipedal lymphography in the management of carcinoma of the anal canal.

The purpose of this study was to determine the extent of metastatic pelvic lymph nodes evident on bipedal lymphography in a group of patients under consideration for combined radiation therapy and chemotherapy as definitive treatment for carcinoma of the anal canal. Lymphography was attempted in 32 patients and successful bilateral cannulation and opacification of nodes was achieved in 28 (88%). Seven patients had lymphographic evidence of external iliac node metastases (25%). When patients were categorized according to the extent of clinically evident disease at presentation, 0/15 patients with T1/T2 tumours had positive lymphograms whereas 7/13 patients with T3/T4 tumours and/or positive inguinal or peri-rectal nodes had positive lymphograms (Fisher's exact test p = 0.0015). All patients with a positive lymphogram had undergone CT scanning of the pelvis and in only one patient was external iliac node involvement detected. In none of these patients was visceral or more extensive nodal metastases discovered. Subsequently, the external iliac nodes with radiological evidence of metastases on lymphography were included in the treatment volume taken to radical dosage. The projected cause specific actuarial 5 year survival for this cohort of patients is 86% (median follow-up 4 years). Since the prognosis for patients who relapse in pelvic nodes is poor, bipedal lymphography is advocated as a staging procedure in patients with advanced primary tumours and in all patients with clinically positive inguinal or peri-rectal lymph nodes who are being considered for curative therapy.

Adult↗

Using pharmacoeconomics to assess the comparative value of antibacterials. A UK perspective.

In the UK there is increasing pressure on prescribers to contain drug costs, the only aspect of the healthcare budget about which information is readily accessible. However, this information is often incomplete, making choices between drugs difficult. By following a defined series of steps based on identification of clinical and practical differences between 2 drugs and an evaluation of the economic consequences of these differences, prescribers can use pharmacoeconomics to make difficult decisions regarding drug choices. In doing so, prescribers can ensure that the health service spends money to provide the maximum benefit for patients.

Anti-Infective Agents↗

Decision analysis of Helicobacter pylori eradication therapy using omeprazole with either clarithromycin or amoxicillin.

In patients with duodenal ulcer, omeprazole plus clarithromycin (OC) has achieved Helicobacter pylori eradication rates of about 80%, compared with 50% for omeprazole plus amoxicillin (OA). The drug acquisition costs for OC are 102.92 pounds sterling (pounds) compared with 38.96 pounds for OA using generic amoxicillin and 51.63 pounds using the proprietary brand 'Amoxil' (costs for 2-week regimens in 1995). The aim of this analysis was to estimate the total healthcare costs to the general practitioner (GP) of eradication therapy using a simple generalised model. Data about current practice in the UK were obtained from 502 respondents in a survey of hospital specialists and GPs. It was assumed that patients would derive no benefit from eradication therapy unless they had a duodenal ulcer, and that all OA patients received generic amoxicillin. The survey confirmed that OA was the commonest eradication therapy prescribed by UK GPs at that time. Three distinct patient groups were identified: patients with proven duodenal ulcer who were already receiving maintenance treatment with a histamine H2 receptor antagonist, and new patients with dyspepsia who were subdivided into those aged above or below 45 years. Patients receiving maintenance treatment for a duodenal ulcer would be prescribed eradication therapy by their GP without further endoscopy. If dyspepsia recurred after eradication therapy, they would be referred to a gastroenterologist, who would perform an endoscopy to confirm the recurrence of ulceration. In this model, the expected total healthcare costs (i.e. the costs of drug acquisition and subsequent treatment when required) following prescription of eradication therapy were lower for OC (157 pounds) than for OA (173 pounds). New patients aged over 45 years would be referred for endoscopy because of the risk that dyspepsia might be the initial presentation of gastric cancer. If duodenal ulceration was found, eradication therapy would be prescribed and, if dyspepsia remained or recurred, the patient would be referred back to the gastroenterologist. In this case, it was considered unlikely that a further endoscopy would be performed. Thus, the healthcare costs associated with failure of eradication in these patients were less than for patients on maintenance treatment, and the expected total healthcare costs were higher for OC (349 pounds) than for OA (335 pounds). Finally, a new patient aged under 45 years with dyspepsia would have eradication therapy prescribed on the basis of a clinical diagnosis of duodenal ulcer plus serological evidence of infection with H. pylori. Continuation or recurrence of dyspepsia would result in referral to a gastroenterologist, who would perform an endoscopy. The total expected healthcare costs were higher for OC (253 pounds) than for OA (251 pounds). The cost effectiveness of OA was sensitive to changes in the default costs (i.e. the average costs from the survey used in the decision analysis), particularly in patients < 45 years old. In these patients, OC would become the cheaper option if amoxicillin were prescribed by brand name instead of in generic form. In this patient group, the outcome was crucially dependent on the accuracy of the clinical diagnosis of duodenal ulcer; if this was at least 60%, then OC would be the cheaper regimen. Overall, the model clearly shows that the higher drug cost of OC is likely to be substantially offset by savings in other healthcare costs. If the direct healthcare costs of OC are higher than OA, then the decision maker must consider the indirect and intangible costs associated with failure of eradication therapy.

Adult↗

Frameless stereotaxy for radiosurgical planning and follow-up.

In our centre, 111 patients have been treated with linear accelerator stereotactic radiosurgery. Angiographic, CT and MRI images are generated and the target coordinates calculated in 3 dimensions. For CT scanning, cross sections of perpendicular and oblique fiducial markers are seen. For follow-up CT scans done without the frame, a virtual frame is generated by means of a computer program that places fiducial markers on each CT scan cut, as if the patient had been wearing the OBT frame and the scan produced with the gantry parallel to the base of the frame. The position of the oblique marker may be calculated by knowing the thickness and position of each CT cut. Various natural fiducial markers (bony landmarks) are identified by coordinates in the scan with the patient wearing the real frame and in the scan with the virtual frame applied. A transformation matrix is utilized to establish the equivalence between the original CT scan with the real frame applied and subsequent scans without the real frame but with the virtual frame applied. In effect, the virtual frame is re-applied in exactly the same position as the real frame. Lesion measurements may then be duplicated and growth or regression accurately established. The uncertainty in this system of re-application resides in possible patient movement, CT scan slice thickness and inter-observer error in the identification of natural fiducial markers.

Brain Neoplasms↗

A critical review of health-related economic evaluations in Australia: implications for health policy.

In Australia, as in many other countries, economic evaluation is increasingly seen by health care policy makers as a useful aid to priority setting and resource allocation. In Australia, economic evaluation is now a requirement for new drugs to be listed on the Pharmaceutical Benefits Scheme which provides a government subsidy on the price of listed drugs for purchasers. Yet, despite recognition of the importance of economic evaluation by policy makers, there is a paucity of published evaluations in Australia. We reviewed all of the 33 health-related economic evaluations conducted in Australia and subsequently published since 1978. This study assesses how well informed decision makers might be if they used the results and conclusions of published economic evaluations as an aid to resource allocation. The review highlights several issues: (i) it is difficult to interpret the conclusions or assess the generalisability of individual papers without information on the context of the original study; (ii) the choice of comparator(s) was often unexplained and most papers did not employ marginal analysis; (iii) in the absence of marginal analysis, the comparability of cost-effectiveness ratios in league tables must be questioned as well as the completeness (were all the relevant alternatives included?) of studies; and (iv) the quality of effectiveness evidence varies enormously, with some authors content to use the best available evidence (even if it is of poor quality). The development of standards for economic evaluation methods might ensure a more consistent and scientific approach to evaluative work, but they cannot guarantee it. A more concerted effort to disseminate the principles and methods of economic evaluation to policy makers and non-economist evaluators might be a more important precursor to improving the credibility and usefulness of economic evaluations in priority setting.

Australia↗

Implementation of multiple isocentre treatment for dynamic radiosurgery.

Radiosurgery using the dynamic rotation technique with a single isocentre was introduced at the Toronto-Bayview Regional Cancer Centre (T-BRCC) in 1988. Since then, over 100 patients have been treated. It was soon recognized that 25-30% of patients were referred with either non-spherical lesions or multiple lesions located sufficiently close together that consideration had to be given to the overlapping dose distributions throughout the treated volume. To treat these more complex targets a multiple isocentre technique was developed which also took account of these effects and the resulting normalization problem. This technique was implemented in September 1992. Comparisons between calculated doses and actual doses delivered have been undertaken using a spherical phantom containing radiochromic film. Measured dose distributions agreed with the planned distributions to within +/- 1 mm. The effect of multiple isocentres on the penumbra of dose distributions has been examined. The methods adopted for the normalization of treatment plans and clinical examples illustrating the application of the multiple isocentre technique are presented.

Adolescent↗

The identification of novel gene sequences of the human adult testis.

To facilitate the characterization of genetic expression in human adult testis, expressed sequence tag analysis of cDNAs from this tissue has been undertaken. Over 180 kb of DNA sequence has been determined and used to search the GenBank database. The results from the first 359 cDNA clones analyzed indicate that the sequences could be sorted into several categories with a high proportion being novel. Twenty-five clones (7%) showed 100% identity with human genes, 11 (3%) with prokaryotic sequences, 21 (5%) with between 60 and 95% similarity to human genes, 27 (8%) with between 60 and 95% similarity to genes from other species, and 33 (9%) with matches to human repeat sequences. Two hundred forty-two (67%) showed no significant matches and thus are likely to represent novel transcripts. In comparison to similar studies on human brain tissue and a hepatoma cell line, the findings indicate that the matches in the testis transcript population appear to be identifying a different spectrum of gene sequences.

Adult↗

Wound infection rates: the importance of definition and post-discharge wound surveillance.

The importance of definition and post-discharge wound surveillance on reported wound infection rates have been studied, using data taken from a prospective, randomized, placebo-controlled, double-blind trial of the effect of whole body disinfection on postoperative wound infection rates. All patients admitted for an elective clean or potentially contaminated surgical procedure over a 32-month period were recruited into the study. Of the 3733 patients recruited, 3466 completed the study. Wound infection (which is defined for this study) is the main outcome that was examined. The effect of careful post-discharge follow-up of patients to look for wound infections was analysed for age, wound type and presence or absence of a drain. Sixty percent of postoperative wound infections occurred after discharge. A rising wound infection rate with increasing age was observed in the in-hospital cohort whereas the incidence of outpatient wound infections declined with age. This finding is attributed to the longer in-hospital stay encountered in patients above 50 years old (median, 3 vs. 5 days, P < 0.00001). Although clean operations had a significantly lower in-hospital infection rate, potentially contaminated procedures had a lower outpatient infection rate. A similar picture was observed in other subgroups of operations including horizontal versus vertical wounds and use of drains. When assessing reported wound infection rates, the definition of wound infection used and the extent of follow-up must be known to enable accurate assessment of the results.

Age Factors↗

Frameless stereotaxy for pre-treatment planning and post-treatment evaluation of radiosurgery.

In our centre, 111 patients have been treated with linear accelerator stereotactic radiosurgery. Angiographic, CT and MRI images are generated and the target coordinates calculated in 3 dimensions. For CT scanning, cross sections of perpendicular and oblique fiducial markers are seen. For follow-up CT scans done without the frame, a virtual frame is generated by means of a computer program that places fiducial markers on each CT scan cut, as if the patient had been wearing the OBT frame and the scan produced with the gantry parallel to the base of the frame. The position of the oblique marker may be calculated by knowing the thickness and position of each CT cut. Various natural fiducial markers (bony landmarks) are identified by coordinates in the scan with the patient wearing the real frame and in the scan with the virtual frame applied. A transformation matrix is utilized to establish the equivalence between the original CT scan with the real frame applied and subsequent scans without the real frame but with the virtual frame applied. In effect, the virtual frame is re-applied in exactly the same position as the real frame. Lesion measurements may then be duplicated and growth or regression accurately established. The uncertainty in this system of re-application residues in possible patient movement, CT scan slice thickness and inter-observer error in the identification of natural fiducial markers.

Brain Neoplasms↗

The use of fluoroquinolones in neutropenic patients--analysis of adverse effects.

The fluoroquinolones have been extensively used in the neutropenic patient. When fluoroquinolone monotherapy was used as prophylaxis, frequently for extended periods, the rate of adverse effect of ciprofloxacin (6.9%) ofloxacin (11.6%) and norfloxacin (5.5%) were significantly lower than those of the comparator agents--co-trimoxazole, vancomycin and polymycin. Rash and gastrointestinal upset were the commonest adverse effects associated with the fluoroquinolones. When used as monotherapy for bacterial infections, often intravenously and in high dosages, the cumulative rate of adverse effects caused by the fluoroquinolones (12.6%) was similar to that caused by the comparator agents (10.3%), but significantly higher than reported for non-neutropenic patients (6.4%) and for prophylactic use. The main adverse events were also rashes (15.4%) and gastrointestinal upset (6.1%). When fluoroquinolones were used as therapy of bacterial infections in combination with other agents, the incidence of adverse events was 14.9%, which was similar to the comparator agents (13.5%). Adverse events were also similar except that nephrotoxicity was commonest with comparator combinations (4.0%). The data suggest that fluoroquinolone prophylaxis in neutropenic patients, even for prolonged periods, is safer than the comparator agents, but is associated with more frequent adverse events than in non-neutropenic patients. Fluoroquinolone therapy, frequently with high dosages, is associated with similar rate of adverse events as the comparator agents. When used in combination with the other antibiotics, fluoroquinolones are as safe as the comparator agents.

Animals↗