Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses.

There is wide variability in the response of individuals to standard doses of antipsychotic drugs. It has been suggested that this may be partly explained by differences in the cytochrome P450 (CYP450) enzyme system responsible for metabolizing the drugs. We conducted a systematic review and meta-analyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes. High analytic validity in terms of sensitivity and specificity was seen in studies reporting P450 testing. However, there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy, although there was an association between CYP2D6 genotype and extrapyramidal adverse effects. No studies reported on the prospective use of CYP2D6 genotyping tests in clinical practice. In conclusion, evidence of clinical validity and utility of CYP2D6 testing in patients being prescribed antipsychotics is lacking, and thus, routine pharmacogenetic testing prior to antipsychotic prescription cannot be supported at present. Further research is required to improve the evidence base and to generate data on clinical validity and clinical utility.

Physicians medication prescribing in primary care in Riyadh City, Saudi Arabia. Literature review, part 1: variations in drug prescribing.

Rational prescribing is associated with improved safety in drug use, better quality of life for patients and cost-effective care. Medication prescribing is a relatively unexplored area of research in Saudi Arabia and until now most studies have been in the secondary and tertiary health care system. This paper is the first of 3 review articles that form the background for a series of 5 interconnected studies of prescribing patterns and medication errors in the public and private primary health care sectors of Saudi Arabia. A MEDLINE search was conducted to identify papers published in peer-reviewed journals over the previous 3 decades. The paper reviews variations in prescribing patterns and influences on physicians' prescribing behaviour worldwide and in Saudi Arabia.

Physicians' medication prescribing in primary care in Riyadh City, Saudi Arabia. Literature review, part 2: rational prescribing.

Unlike sub-optimal prescribing, rational prescribing, coupled with certain indicators, is associated with improved safety in drug use in terms of selecting appropriate drug for prescribing, better quality of life for patients and cost-effective care. Medication prescribing is a relatively unexplored area of research in Saudi Arabia and until now most studies have been in the secondary and tertiary health care system. This paper is the second of 3 review articles that form the background for a series of 5 interconnected studies of prescribing patterns and medication errors in the public and private primary health care sectors of Saudi Arabia. A MEDLINE search was conducted to identify papers published in peer-reviewed journals over the previous 3 decades. The paper reviews rational prescribing with its indicators, suboptimal prescribing, classification of medication errors, and how to achieve quality in health care prescribing worldwide and in Saudi Arabia.

Physicians' medication prescribing in primary care . in Riyadh City, Saudi Arabia. Literature review, part 3: prescribing errors.

Medication errors are globally huge in magnitude and associated with high morbidity and mortality together with high costs and legal problems. Medication errors are caused by multiple factors related to health providers, consumers and health system, but most prescribing errors are preventable. This paper is the third of 3 review articles that form the background for a series of 5 interconnected studies of prescribing patterns and medication errors in the public and private primary health care sectors of Saudi Arabia. A MEDLINE search was conducted to identify papers published in peer-reviewed journals over the previous 3 decades. The paper reviews the etiology, prevention strategies, reporting mechanisms and the myriad consequences of medication errors.

[Medication prescribing pattern in primary care in Riyadh City, Saudi Arabia]

Physicians' prescribing behaviour is closely linked with patient safety and this area is poorly researched in Saudi Arabia. The objective of this study was to analyse physicians' prescribing patterns and the adequacy of noted information in the primary health care sector in Riyadh city. All medication prescriptions from 5 public (n = 1182) and 5 private (n = 1200) health centres were collected by simple random sampling during 1 working day. Antibiotics were the most commonly prescribed drugs in both sectors. The mean number of drugs per prescription was 2.08 and 2.36 in the public and private sectors respectively. Information and instructions noted on prescriptions varied considerably between private and public health centres. Similarly the medication prescribing pattern differed across the 2 health settings. Primary care physicians in Saudi Arabia need continuing training to improve their prescribing practices.

Medication errors in primary care in Riyadh City, Saudi Arabia.

Medication errors can cause a variety of adverse drug events but are potentially preventable. This cross-sectional study analysed all medication prescriptions from 5 public and 5 private primary health care clinics in Riyadh city, collected by simple random sampling during 1 working day. Prescriptions for 2463 and 2836 drugs from public and private clinics respectively were examined for errors, which were analysed using Neville et al.'s classification of prescription errors. Prescribing errors were found on 990/5299 (18.7%) prescriptions. Both type B and type C errors (major and minor nuisance) were more often associated with prescriptions from public than private clinics. Type D errors (trivial) were significantly more likely to occur with private health sector prescriptions. Type A errors (potentially serious) were rare (8/5299 drugs; 0.15%) and the rate did not differ significantly between the 2 health sectors. The development of preventive strategies for avoiding prescription errors is crucial.

Determinants of physicians' medication prescribing behaviour in primary care in Riyadh City, Saudi Arabia.

This study in Saudi Arabia explored the determinants of physicians' prescribing behaviour in primary care in Riyadh city. A self-administered questionnaire designed to explore factors influencing prescribing (sociodemographic factors; practice setting; continuing education; access to educational materials; pharmaceutical company representatives; and patient factors) was completed by 87 PHC physicians. A factor analysis of 56 variables extracted 7 factors that explained 46% of the variance. Of these, 4 components positively related to perceived good prescribing behaviour could be summarized as: clinical experience of physicians; use of educational materials for continuous updating of medical knowledge; enhanced levels of continuing medical education and willingness to involve patients in decision-making; and working as a team using pharmacists for consultation and emphasizing the role of medical education. The other 3 factors derived from the analysis were less easy to interpret and may have been statistical anomalies (or measurement errors).

Predictors of quality of medication prescribing in primary care in Riyadh City, Saudi Arabia.

Identifying the indicators of good quality medication prescribing assists physicians in preventing medication errors. This study in Riyadh city aimed to examine the relationship between physicians' self-reported influences on prescribing and the quality of their prescribing, defined as the completeness and accuracy of their prescription documentation. A sample of 600 randomly selected prescriptions written by 87 physicians were rated as high or low quality. The same physicians completed a questionnaire to determine the indicators of quality prescribing. The 7 components identified with factor loadings +0.5 or -0.5 were subjected to binary logistic regression modelling. While a range of potential quality indicators of drug prescribing were identified, none of the variables underpinning the 7components/factors survived the binary logistic regression mode. More studies are needed that take into account other quality indicators of medication prescribing in Saudi Arabia.

Effectiveness of three interventions on primary care physicians' medication prescribing in Riyadh City, Saudi Arabia.

A number of strategies have been shown to improve the quality of drug prescriptions. The objective of this study was to implement and assess the effectiveness of 3 interventions on physicians' prescribing and cost containment: training physicians about quality prescribing; regulatory and administrative measures to improve rational drug prescribing; and a multi-faceted approach using 2 these strategies plus additional elements. Three public health centres, 1 for each intervention, were randomly selected; 61 physicians were trained in drug prescribing and completed a pre- and post-training questionnaire; and 100 post-intervention prescriptions from each centre were compared. All 3 interventions effectively improved the quality of drug prescriptions and the notation of drug-related information and trainees returned positive evaluations of the training course. Whether or not physicians' improvement in prescribing will be sustained is unclear and therefore subsequent follow-up evaluations are needed.

Benefit of statins in daily practice? A six-year retrospective observational study.

This observational retrospective study analysed the association of adherence to statins with the achievement of a target total cholesterol level (CL, <200mg/dl), and any association of adherence with the time to first hospital admission for coronary event in hypercholesterolemic patients treated with statins, in one Italian Local Health Authority between 1998 and 2003. The study population consisted of 3516 patients who were prescribed statins and for whom full cholesterol results were available. After three months of treatment, there were significant reductions in CL (p<0.001) in the three treatment groups stratified by adherence (good adherents -24%, poor adherents -22%, and nonadherents -14%). Patients more likely to achieve the target CL were older, male and more adherent to the statins. The risk of first hospitalization was associated positively with increased age and male gender. Patients with co-treatments were more likely to be hospitalized. Surprisingly, better adherence to statin treatment increased the risk of hospitalization.

The clinical effectiveness and cost-effectiveness of central venous catheters treated with anti-infective agents in preventing bloodstream infections: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of central venous catheters (CVCs) treated with anti-infective agents in preventing catheter-related bloodstream infection (CRBSI). DATA SOURCES: Major electronic databases were searched from 1985 to August 2005. REVIEW METHODS: The systematic clinical and economic reviews were conducted according to accepted procedures. Only full economic evaluations (synthesis of costs and benefits) comparing the use of anti-infective central venous catheters (AI-CVCs) with untreated CVCs or other treated catheters were selected for inclusion in the economic review. RESULTS: A total of 32 trials met the clinical inclusion criteria. Seven different types of AI-CVC were identified, with the most frequently tested being chlorhexidine and silver sulfadiazine (CHSS) (externally treated), CHSS (externally and internally treated) and minocycline rifampicin (internally and externally treated). In general, the trials were of a poor quality in terms of reported methodology, microbiological relevance and control of confounding variables. The pooled result suggests a statistically significant advantage for AI-CVCs in comparison to standard catheters in reducing CRBSI [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.34 to 0.60, 24 studies, I-squared = 0%, fixed effects]. Analysis by subgroups of catheters demonstrates that antibiotic-treated catheters and catheters treated internally and externally decrease CRBSI rates significantly (OR 0.26, 95% CI 0.15 to 0.46, six studies, I-squared = 0%, fixed effects, and OR 0.43, 95% CI 0.26 to 0.70, nine studies, I-squared = 0%, fixed effects, respectively). Catheters treated only externally demonstrate a wider CI and non-significant effect (OR 0.67, 95% CI 0.43 to 1.06, nine studies, I-squared = 0%, fixed effects). A treatment effect was also found for trials with an average duration of between 5 and 12 days, and for the one study with a mean duration of over 20 days. There was a statistically significant treatment effect for both femoral and jugular insertion sites and for those studies reporting a mix of insertion sites. The treatment effect was not observed in trials using exclusively subclavian insertion sites. Of the four trials that compared treated catheters, one reported a benefit of antibiotic-treated catheters over catheters treated externally with CHSS. All three sensitivity analyses testing for study design differences reported a statistically significant treatment effect. The review was limited owing to the quality of the trials included, marked differences in the definitions and methods of diagnosis of CRBSI, and inconsistent reporting of risk factors and patient population factors. Furthermore, two-thirds of trials were commercially funded. The economic performance (cost-effectiveness and potential cost-savings) of using AI-CVCs to reduce the number of CRBSIs in patients requiring a CVC was also reviewed. Results show that the use of AI-CVCs instead of standard CVCs can lead to a reduction in CRBSIs and decreased medical costs. To complement the reviews, a basic decision-analytic model was constructed to explore a range of possible scenarios for the NHS in England and Wales. Results show that for every patient who receives an AI-CVC there is an estimated cost-saving of 138.20 pounds. The multivariate sensitivity analyses estimate potentially large cost-savings, depending on the size of the population, under a wide range of cost and clinical assumptions. However, those considering the purchase of AI-CVCs should ensure that their patient populations and the important characteristics of local clinical practice are indeed similar to those described in this economic evaluation. CONCLUSIONS: Overall, AI-CVCs are clinically effective and relatively inexpensive and therefore their integration into clinical practice can be justified. However, the use of these anti-infective catheters without the appropriate use of other practical care initiatives will have only a limited success on the prevention of CRBSIs. Comparative trials are required to determine which, if any, of the treated catheters is the most effective. Pragmatic research related to the effectiveness of bundles of care that may reduce rates of CRBSI is also warranted.

Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of pemetrexed disodium in combination with cisplatin for the treatment of unresectable pleural mesothelioma in chemotherapy-naive patients. DATA SOURCES: Electronic databases were searched up to May 2005. REVIEW METHODS: The systematic review was conducted following accepted guidelines. An assessment of the economic submission received from the manufacturer of pemetrexed was also carried out. This comprised two sections, each employing an economic model. One of these models was then reformulated in order to carry out a separate exploration of economic performance. RESULTS: One randomised controlled trial comparing pemetrexed and cisplatin with cisplatin alone, and involving a total study population of 448 patients, met the inclusion criteria. Pemetrexed in combination with cisplatin in this trial showed a 2.8-month gain in median survival compared with cisplatin alone in an intention-to-treat (ITT) population (12.1 and 9.3 months, respectively, p = 0.020, hazard ratio of 0.77). During the trial, increased reporting of severe toxicity in the pemetrexed arm led to a change in the protocol to add folic acid and vitamin B12 supplementation to therapy. For fully supplemented patients (n = 331) the hazard ratio for median survival in favour of pemetrexed plus cisplatin was also comparable (0.75), but of borderline significance between treatment arms (p = 0.051). The trial inclusion criteria restricted recruitment to those with a Karnofsky performance status of 70 or greater (equivalent to ECOG/WHO 0 or 1 scales more widely used in the UK). Quality of life scores using the Lung Cancer Symptom Scale demonstrated significantly greater improvement for pain and dyspnoea for patients in the combination group compared with those in the cisplatin group. In the ITT population, the incidence of serious toxicities with pemetrexed plus cisplatin was higher compared with cisplatin alone. However, the grade 3/4 toxicities of the combination arm, particularly leucopenia, neutropenia and diarrhoea, were found to be greatly improved by the addition of vitamin B12 and folic acid. The existing published economic literature was very limited. The economic evaluation conducted by the study (and that submitted by the manufacturer) suggested that pemetrexed is unlikely to be considered cost-effective at conventionally accepted thresholds in the UK for all patients, mainly because of the high cost of pemetrexed itself compared with cisplatin. These findings were better for some patient subgroups, e.g. especially for fully supplemented (FS) patients with good performance status (0/1) and advanced disease (AD). These findings seem robust. The estimated cost-effectiveness results were for the FS population, incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained = pound59,600; for the FS with AD population, ICER per QALY = pound47,600; for the FS with performance status 0/1 population, ICER per QALY = pound49,800; and for the FS with performance status 0/1 and AD population, ICER per QALY = pound36,700. CONCLUSIONS: The new therapy examined in this document demonstrates an extension of life expectancy and palliation, as measured by time to progression of disease and other end-points. However, the absolute benefit obtained is small, and it needs to be weighed against the benefits of effective palliative care services. The limited benefit was also at the expense of considerable toxicity to patients. The economic evaluation conducted in this study and that of the manufacturers suggest that pemetrexed is not cost-effective at conventional thresholds for all patients. Cost-effectiveness seems better for some patient subgroups, e.g. especially for patients with good performance status and with advanced diseases, where it is estimated the ICER per QALY would be pound36,700. Given the relatively small number of patients with mesothelioma, albeit increasing, the overall budget impact of pemetrexed would be unlikely to be more than pound5 million per year at present costs. Much more research is needed into the optimum chemotherapy for patients with mesothelioma and a clear definition of what constitutes best supportive care.

Drug-eluting stents: a systematic review and economic evaluation.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of the use of drug-eluting coronary artery stents in percutaneous coronary intervention (PCI) in patients with coronary artery disease. DATA SOURCES: Bibliographic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched from December 2002 to August 2005. Hand-searching was also done. REVIEW METHODS: A systematic literature review of effectiveness was conducted focusing primarily on randomised controlled trials (RCTs). Full economic evaluations that compared two or more options and considered both costs and consequences were eligible for inclusion in the economics review. A critique of manufacturer submissions to the National Institute for Health and Clinical Excellence and an economic evaluation in the form of cost-utility analysis were also carried out. RESULTS: In the 17 RCTs of drug-eluting stents (DES) versus bare metal stents (BMS), no statistically significant differences in mortality or myocardial infarction (MI) were identified up to 3 years. Significant reductions in repeat revascularisations were determined for DES compared with BMS [for example, at 1 year: target lesion revascularisation (TLR) relative risk 0.24; 95% confidence interval (CI) 0.19 to 0.31; and target vessel revascularisation (TVR) relative risk 0.43; 95% CI 0.33 to 0.55]. This estimated benefit appears to be stable from 1 to 3 years. Binary restenosis and late luminal loss also favoured DES. In the eight RCTs of DES versus DES, no statistically significant differences in mortality or MI were detected between DES designs. In meta-analyses of TLR, TVR and composite event rate, marginal improvement in efficacy of Cypher trade mark over Taxus trade mark was observed. These results await confirmation beyond 1 year and differences in study design may have influenced reporting of outcomes. Ten full economic evaluations were included in the review and the balance of evidence indicated that DES are more cost-effective in higher risk patients. The review of submitted models confirmed the view that DES may be cost-effective only under very limited circumstances when realistic assumptions and data values were used. In the cost-utility analysis of DES versus BMS, the use of DES appears to reduce the rate of repeat revascularisations; benefit estimates used in the economic assessment are defined as 'broad' (i.e. cases involving any TLR/TVR irrespective of any other lesions/vessels undergoing revascularisation) and 'narrow' (i.e. cases involving TLR/TVR only). The incremental benefit to the patient is therefore described as the loss of quality-adjusted life-years (QALYs) avoided by not having to undergo a repeat revascularisation. Univariate sensitivity analysis and extreme values analysis indicate that the price premium, numbers of stents used in the index procedure and absolute risk reduction in repeat interventions most significantly influence the cost-effectiveness ratios. Sensitivity analyses also permit a range of values for efficacy and effectiveness to be considered for individual designs of DES. The cost-effectiveness results reveal that, all patients considered together, the calculated cost per QALY ratios are high (183,000-562,000 pounds) and outside the normal range of acceptability. Cost-effectiveness is only achieved for those non-elective patients who have undergone a previous coronary artery bypass graft and have small vessels. 'Real-world' data show that patient numbers in this latter group are very small (one in 3100 of all patients treated with PCI). CONCLUSIONS: The conclusions of the assessment are that the use of DES would be best targeted at the subgroups of patients with the highest risks of requiring reintervention, and could be considered cost-effective in only a small percentage of such patents. This is similar to the conclusion of our previous assessment. Trials of DES compared with new generation BMS and with DES would be useful, as would further evaluation of newer BMS in combination with drug administration.

Pemetrexed disodium in combination with cisplatin versus other cytotoxic agents or supportive care for the treatment of malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy whose incidence is expected to increase in the United Kingdom, Western Europe, and Australia over the next 20 years as a result of occupational exposure to asbestos fibres. Surgery is feasible in only a small proportion of cases, and radiotherapy and cytotoxic chemotherapy are used in palliation. Pemetrexed is the first and only chemotherapy agent that has been granted a marketing approval for use in combination with cisplatin for the treatment of chemo-naïve patients with unresectable MPM. OBJECTIVES: To examine evidence on the clinical effectiveness of pemetrexed disodium used in combination with cisplatin for the treatment of unresectable malignant pleural mesothelioma in chemotherapy naïve patients compared with other cytotoxic agents used alone or in combination, or supportive care. SEARCH STRATEGY: CENTRAL (Issue 2, 2005), EMBASE (1980-2005), MEDLINE (1980-2005), HTA database (1990-2005), Web of Knowledge (1990-2005) and handsearching (including reference lists of retrieved articles and the pharmaceutical company submission to to NICE), up to October 2005. SELECTION CRITERIA: Randomised Controlled Trials (RCTs) where the use of pemetrexed disodium in combination with cisplatin is compared with other cytotoxic agents, or supportive care for the treatment of malignant pleural mesothelioma (or non-RCTs, in the absence of RCT data ). DATA COLLECTION AND ANALYSIS: Outcomes included overall survival, tumour response, progression-free survival, toxicity and quality of life. Data extraction and quality assessment of included trials was completed independently. Trial data and quality assessment were tabulated and presented narratively. MAIN RESULTS: One RCT involving 448 patients and comparing pemetrexed plus cisplatin versus cisplatin alone for the treatment of unresectable malignant mesothelioma was included in the review. In the intention-to-treat study population, the median survival was statistically significantly longer in the combination arm of pemetrexed plus cisplatin when compared with the cisplatin alone arm. (12.1 and 9.3 months, respectively, p=0.002). The incidence of grade 3/4 toxicities was higher in the combination arm compared with the cisplatin alone arm. AUTHORS' CONCLUSIONS: Pemetrexed disodium in combination with cisplatin and with folic acid and vitamin B(12 )supplementation may improve survival when used in combination with cisplatin in good performance status patients. Further studies including patients with poor performance status are needed in order to generalise the treatment findings. Further studies are also needed into the optimum chemotherapy, and a clear definition of what constitutes best supportive care.

Comparison of conference abstracts and presentations with full-text articles in the health technology assessments of rapidly evolving technologies.

OBJECTIVES: To assess the extent of use of data from conference abstracts and presentations in health technology assessments (HTAs) provided as part of the National Institute for Health and Clinical Excellence (NICE) appraisal process. Also to assess the methodological quality of trials from conference abstracts and presentations, the consistency of reporting major outcomes between these sources and subsequent full-length publications, the effect of inclusion or exclusion of data from these sources on the meta-analysis pooled effect estimates, and the timeliness of availability of data from these sources and full articles in relation to the development of technology assessment reviews (TARs). DATA SOURCES: A survey of seven TAR groups. An audit of published TARs: included all NICE TARs published between January 2000 and October 2004. Case studies of selected TARs. REVIEW METHODS: Analyses of the results of the survey and audit were presented as a descriptive summary and in a tabular format. Sensitivity analyses were carried out to compare the effect of inclusion of data from abstracts and presentations on the meta-analysis pooled effect estimates by including data from both abstracts/presentations and full papers, and data from only full publications, included in the original TAR. These analyses were then compared with meta-analysis of data from trials that have subsequently been published in full. RESULTS: All seven TAR groups completed and returned the survey. Five out of seven groups reported a general policy that included searching for and including studies available as conference abstracts/presentations. Five groups responded that if they included data from these sources they would carry out methodological quality assessment of studies from these sources using the same assessment tools as for full publications, and manage the data from these sources in the same way as fully published reports. All groups reported that if relevant outcome data were reported in both an abstract/presentation and a full publication, they would only consider the data in the full publication. Conversely, if data were only available in conference abstract/presentation, all but two groups reported that they would extract and use the data from the abstract/presentation. In total, 63 HTA reports for NICE were identified. In 20 of 63 TARs (32%) explicit statements were made with regards to inclusion and assessment of data from abstracts/presentations. Thirty-eight (60%) identified at least one randomised controlled trial (RCT) available as a conference abstract or presentation. Of these, 26 (68%) included trials available as abstracts/presentations. About 80% (20/26) of the 26 TARs that included RCTs in abstract/presentation form carried out an assessment of the methodological quality of such trials. In 16 TARs full reports of these trials were used for quality assessment where both abstracts/presentations and subsequent full publications were available. Twenty-three of 63 TARs (37%) carried out a quantitative analysis of results. Of these, ten (43%) included trials that were available as abstracts/presentations in the review; however, only 60% (6/10) of these included data from abstracts/presentations in the data analysis of results. Thirteen TARs evaluated rapidly evolving technologies and only three of these identified and included trial data from conference abstracts/presentations and carried out a quantitative analysis where abstract/presentation data were used. These three TARs were used as case studies. In all three case studies the overall quality of reporting in abstracts/presentations was generally poor. In all case studies abstracts and presentations failed to describe the method of randomisation or allocation concealment. Overall, there was no mention of blinding in 66% (25/38) of the abstracts and in 26% (7/27) of the presentations included in case studies, and one presentation (4%) explicitly stated use of intention-to-treat analysis. Results from one case study demonstrated discrepancies in data made available in abstracts or online conference presentations. Not only were discrepancies evident between these sources, but also comparison of conference abstracts/presentations with subsequently published full-length articles demonstrates data discrepancies in reporting of results. Sensitivity analyses based on one case study indicated a change in significance of effect in two outcome measures when only full papers published to date were included. CONCLUSIONS: There are variations in policy and practice across TAR groups regarding searching for and inclusion of studies available as conference abstracts/presentations. There is also variation in the level of detail reported in TARs regarding the use of abstracts/presentations. Therefore, TAR teams should be encouraged to state explicitly their search strategies for identifying conference abstracts and presentations, their methods for assessing these for inclusion, and where appropriate how the data were used and their effect on the results. Comprehensive searching for trials available as conference abstracts/presentations is time consuming and may be of questionable value. However, there may be a case for searching for and including abstract/presentation data if, for example, other sources of data are limited. If conference abstracts/presentations are to be included, the TAR teams need to allocate additional time for searching and managing data from these sources. Incomplete reporting in conference abstracts and presentations limits the ability of reviewers to assess confidently the methodological quality of trials. Where conference abstracts and presentations are considered for inclusion in the review, the TAR teams should increase their efforts to obtain further study details by contacting trialists. Where abstract/presentation data are included, reviewers should discuss the effect of including data from these sources. Any data discrepancies identified across sources in TARs should be highlighted and their impact discussed in the review. In addition, there is a need to carry out, for example, a sensitivity analysis with and without abstract/presentation data in the analysis. There is a need for research into the development of search strategies specific to identification of studies available as conference abstracts and presentations in TARs. Such strategies may include guidance with regard to identification of relevant electronic databases and appropriate conference sites relevant to certain clinical areas. As there are limited case studies included in this report, analyses should be repeated as more TARs accrue, or include the work of other international HTA groups.

Percutaneous transluminal coronary angioplasty with stents versus coronary artery bypass grafting for people with stable angina or acute coronary syndromes.

BACKGROUND: Coronary artery bypass graft surgery (CABG) replaces obstructed vessels with ones from other parts of the body. Alternatively, obstructions are remodelled using catheter-based techniques such as percutaneous coronary angioplasty with the use of stents. Though less invasive, stenting techniques are limited by the re-narrowing of treated vessels (restenosis). We examined evidence on cardiac-related outcomes occurring after CABG or stenting, with implications for resource use, resource allocation and informing patient choice. OBJECTIVES: To examine evidence from randomised controlled trials (RCTs) on benefit of stents or CABG in reducing cardiac events in people with stable angina or acute coronary syndrome (ACS). SEARCH STRATEGY: CENTRAL (Issue 2 2004), EMBASE (1990 to 2004), MEDLINE (1990 to 2004) and handsearching to July 2004. SELECTION CRITERIA: Only RCTs comparing stents used with PTCA with CABG were included. Participants were adults with stable angina or ACS and unstable angina and had either single or multiple vessel disease. Published and unpublished sources were considered. DATA COLLECTION AND ANALYSIS: Outcomes included composite event rate (major adverse cardiac event, event free survival), death, acute myocardial infarction (AMI), repeat revascularisation and binary restenosis as well as information on design and baseline characteristics. Quality assessment was completed independently. Meta-analyses are presented as odds ratios, 95% confidence intervals (CI) using a fixed-effect model. Heterogeneity between trials was assessed. MAIN RESULTS: Nine studies (3519 patients) were included. Four RCTs included patients with multiple vessel disease, five focused on single vessel disease. Four studies reported beyond 1 year. No statistical differences were observed between CABG and stenting for meta-analysis of mortality or AMI, but there was heterogeneity. Composite cardiac event and revascularisation rates were lower for CABG than for stents. Odds ratios resulting from meta-analysis of event rate data at 1 year were, odds ratio 0.43 (95% CI 0.35 to 0.54) and at 3 years, odds ratio 0.37 (95% CI 0.29 to 0.48). Odds ratios for revascularisation at 1 year were, odds ratio 0.18 (95% CI 0.13 to 0.25) and at 3 years, odds ratio 0.09 (95% CI 0.02 to 0.34). Binary restenosis at 6 months (single vessel trials) favoured CABG, odds ratio 0.29 (95% CI 0.17 to 0.51). AUTHORS' CONCLUSIONS: CABG is associated with reduced rates of major adverse cardiac events, mostly driven by reduced repeat revascularisation. However, the RCT data are limited by follow-up, unrepresentative samples and rapid development of both surgical techniques and stenting. Research on real-world patient population or patient level data meta-analyses may identify risk factors and groupings who may benefit most from one strategy over the other.

Autoregulation of tissue blood flow in essential hypertension.

Autoregulation of tissue blood flow is a mechanism by which tissues control their own blood supply. The mechanism is dependent on an intrinsic capacity of tissues to vary their arteriolar resistance in relation to their needs. One view of the nature of the increased peripheral resistance in essential hypertension is that it represents autoregulatory vasoconstriction functioning to hold in check a cardiac output that would otherwise be excessive; in this situation autoregulation would be functioning normally. An alternative view is that the increased peripheral resistance represents the effect of a direct-acting vasoconstrictor substance; in this situation autoregulation would be rendered defective in its vasodilator capacity. A study of autoregulatory vasodilatation in eight subjects with essential hypertension supported an autoregulatory mechanism as the cause of the increased peripheral resistance.

Effects of calcium channel blockers on in vitro platelet function in whole blood using single platelet counting.

The effects of various calcium channel blockers on in vitro platelet aggregation were studied using whole blood platelet counting. Diltiazem and verapamil inhibited aggregation caused by adrenaline 5 microM and collagen 2 micrograms/ml, but only at concentrations far in excess of those seen in clinical use. Nifedipine and nimodipine also inhibited aggregation to these agonists, but this seemed to be due to the solvent used. The solvent for these dihydropyridines contains 15% ethanol, 15% polyethylene glycol and 70% water, and the ethanol component is the most likely to have caused an antiaggregatory effect. Other studies showing an antiaggregatory effect of dihydropyridines may not have taken account of this solvent effect.

Review article: current practice and future perspectives in detection and diagnosis of pancreatic cancer.

Pancreatic cancer is the tenth most prevalent malignancy and the fifth most common cause of cancer death in the developed world. Less than 10% of patients survive for more than 1 year following diagnosis and the 5-year survival rate (0.4%) is the lowest of any cancer. The poor prognosis associated with this diagnosis led in the past to therapeutic nihilism on the part of clinicians who were all too aware of the limitations of their available therapeutic strategies. Breaking this therapeutic impasse requires a significant expansion in the knowledge of clinicians concerning the pathogenesis and behaviour of pancreatic cancer. Recent advances in the scientific understanding of the aetiology of pancreatic cancer has facilitated progress towards the development of promising and innovative approaches to the early detection and diagnosis of pancreatic cancer. While acknowledging that pancreatic cancer will continue to present significant challenges to both scientists and clinicians in the foreseeable future, it is becoming increasingly clear that recent advances in our scientific knowledge base holds the potential to significantly improve prognosis for patients. The challenge facing both scientists and clinicians is how best to translate such promising scientific advances into survival and quality of life benefits to patients.