What affected UK adults' adherence to medicines during the COVID-19 pandemic? Cross-sectional survey in a representative sample of people with long-term conditions.

Aim: Medicines non-adherence is associated with poorer outcomes and higher costs. COVID-19 affected access to healthcare, with increased reliance on remote methods, including medicines supply. This study aimed to identify what affected people's adherence to medicines for long-term conditions (LTCs) during the pandemic. Subject and methods: Cross-sectional online survey of UK adults prescribed medicines for LTCs assessing self-reported medicines adherence, reasons for non-adherence (using the capability, opportunity and motivation model of behaviour [COM-B]), medicines access and COVID-19-related behaviours. Results: The 1746 respondents reported a mean (SD) of 2.5 (1.9) LTCs, for which they were taking 2.4 (1.9) prescribed medicines, 525 (30.1%) reported using digital tools to support ordering or taking medicines and 22.6% reported medicines non-adherence. No access to at least one medicine was reported by 182 (10.4%) respondents; 1048 (60.0%) reported taking at least one non-prescription medicine as a substitute; 409 (23.4%) requested emergency supply from pharmacy for at least one medicine. Problems accessing medicines, being younger, male, in the highest socioeconomic group and working were linked to poorer adherence. Access problems were mostly directly or indirectly related to the COVID-19 pandemic. Respondents were generally lacking in capabilities and opportunities, but disruptions to habits (automatic motivation) was the major reason for non-adherence. Conclusion: Navigating changes in how medicines were accessed, and disruption of habits during the COVID-19 pandemic, was associated with suboptimal adherence. People were resourceful in overcoming barriers to access. Solutions to support medicines-taking need to take account of the multiple ways that medicines are prescribed and supplied remotely. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01813-0.

Improving medication safety for home nursing clients: A prospective observational study of a novel clinical pharmacy service-The Visiting Pharmacist (ViP) study.

WHAT IS KNOWN AND OBJECTIVE: Polypharmacy, medication errors and adverse events are common in older people receiving home nursing medication management support. Access to clinical pharmacists is limited. In Australia, few home nursing clients receive a general practitioner (GP)-initiated pharmacist-led Home Medicines Review, despite their eligibility and community nurses' (CN) efforts to facilitate this. An integrated home nursing clinical pharmacy service, in which CNs directly referred clients to a pharmacist, was therefore developed and piloted. The aim was to explore the number and type of medication-related problems (MRPs) and medication treatment authorization (medication order) discrepancies identified and addressed by clinical pharmacists. METHODS: Two part-time clinical pharmacists were employed. They reviewed and reconciled clients' medications, educated clients/carers about their medicines, provided advice and support to CNs and worked with clients' GPs and other prescribers to optimize medication regimens and revise/update nurses' medication treatment authorizations. Evaluation involved review of clients' medicines data, including treatment authorizations and pharmacist medication review reports. RESULTS AND DISCUSSION: Eighty-four clients (median 86 years, 6 health conditions, 13 medications) were reviewed. The pharmacists identified 334 MRPs (median 4 per client) and 307 medication discrepancies in treatment authorizations (median 2 per client). The pharmacists made 282 recommendations to prescribers to address MRPs; 148 (52.5%) recommendations were acted on, resulting in 190 medication changes for 60 (71.4%) clients (median 2 per client). The pharmacists prepared, or assisted GPs to update, treatment authorizations for 68 (81%) clients. WHAT IS NEW AND CONCLUSION: Integrating pharmacists into a home nursing service identified and addressed MRPs and medication treatment authorization discrepancies, hence contributing to enhanced medication safety.

Impact of pharmacists assisting with prescribing and undertaking medication review on oxycodone prescribing and supply for patients discharged from surgical wards.

WHAT IS KNOWN AND OBJECTIVES: Overprescribing of oxycodone is a contributor to the epidemic of prescription opioid misuse and deaths. Practice models to optimize oxycodone prescribing and supply need to be evaluated. We explored the impact of pharmacist-assisted discharge prescribing and medication review on oxycodone prescribing and supply for patients discharged from surgical wards. METHODS: A retrospective audit was conducted on two surgical inpatient wards following a 16-week prospective pre- and post-intervention study. During the pre-intervention period, discharge prescriptions were prepared by hospital doctors and then reviewed by a ward pharmacist (WP) before being dispensed. Post-intervention, prescriptions were prepared by a project pharmacist in consultation with hospital doctors and then reviewed by a WP and dispensed. MAIN ENDPOINTS WERE THE FOLLOWING: Proportion of patients who were prescribed, and proportion supplied, oxycodone on discharge; Median amount (milligrams) of oxycodone prescribed and supplied, for patients who were prescribed and supplied at least one oxycodone-containing preparation, respectively. RESULTS: A total of 320 and 341 patients were evaluated pre- and post-intervention, respectively. Pre-intervention, 75.6% of patients were prescribed oxycodone; after WP review, 60.3% were supplied oxycodone (P<.01); the median amount both prescribed and supplied was 100 milligrams/patient. Post-intervention, 68.6% of patients were prescribed oxycodone; after WP review, 57.8% were supplied oxycodone (P<.01); median amount prescribed and supplied was 50 milligrams/patient (difference in amount prescribed and supplied: 50 milligrams, P<.01). WHAT IS NEW AND CONCLUSION: WP review of doctor-prepared prescriptions reduced the proportion of patients who were supplied oxycodone but not the amount supplied/patient. Having a pharmacist assist with prescribing reduced the amount of oxycodone supplied.

Dietary Supplement Use in Older People Attending Memory Clinics in Australia.

BACKGROUND: Dietary supplement use is common in older adults. There has been limited research in people attending memory clinics. OBJECTIVES: To explore the use of dietary supplements in older people attending Australian memory clinics. DESIGN: Cross-sectional analysis of baseline data from the Prospective Research In MEmory clinics (PRIME) study. PARTICIPANTS: Community-dwelling older people who attended nine memory clinics and had a diagnosis of mild cognitive impairment (MCI) or dementia. MEASUREMENTS: Dietary supplement was defined as a product that contains one or more: vitamin, mineral, herb or other botanical, amino acid or other dietary substance. Non-prescribed supplement was defined as a supplement that is not usually prescribed by a medical practitioner. Polypharmacy was defined as use of five or more medications. RESULTS: 964 patients, mean age 77.6 years, were included. Dietary supplements were used by 550 (57.1%) patients; 353 (36.6%) used two or more. Non-prescribed supplements were used by 364 (36.8%) patients. Supplement use was associated with older age (OR: 1.12, 95% CI: 1.03-1.21), lower education level (OR: 1.53, 95% CI: 1.01-2.32) and a diagnosis of MCI rather than dementia (OR: 1.52, 95% CI: 1.05-2.21). Potential drug-supplement interactions were identified in 107 (11.1%) patients. Supplement users had increased prevalence of polypharmacy compared to non-users (80.5% vs. 48.1%, p<0.001). CONCLUSIONS: Dietary supplements, including non-prescribed supplements, were commonly used by people attending memory clinics. Supplement use increased the prevalence of polypharmacy and resulted in potential supplement-drug interactions. Further research is required to assess the clinical outcomes of supplement use.

Enhanced purinergic contractile responses and P2X1 receptor expression in detrusor muscle during cycles of hypoxia-glucopenia and reoxygenation.

Bladders from patients with detrusor overactivity have an increased atropine-resistant contractile response to nerve stimulation. The bladder has also been shown to be very susceptible to hypoxia-glucopenia and reperfusion injury, leading to the hypothesis that episodes of hypoxia-glucopenia and reoxygenation result in increased atropine-resistant responses to nerve stimulation in the detrusor muscle. Detrusor muscle strips were suspended in a Perspex organ bath chamber of volume 0.2 ml perfused with Krebs solution at 37°C aerated with 21% O2, 5% CO2 and the balance nitrogen. Hypoxia-glucopenia was induced by switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen and 5% CO2. Atropine-resistant contractile responses increased by 40.5 ± 7.3% after four cycles of hypoxia-glucopenia (10 min) and reoxygenation (1 h), whereas α,ß-methylene ATP-resistant responses did not increase. Expression of P2X1 receptors in the bladder was increased after hypoxia-glucopenia and reoxygenation cycling, and ATP release from stimulated bladder strips during cycling was also increased. Other P2X receptor-mediated mechanisms may also be involved in the augmentation of bladder contraction during hypoxia-glucopenia and reoxygenation cycling, because a non-specific P2X antagonist blocked most of the augmented response, whereas a P2X1-specific antagonist prevented only part of the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. In conclusion, four cycles of hypoxia-glucopenia and reoxygenation increased the purinergic, but not the cholinergic, contractile responses to nerve stimulation. Increased P2X1 receptor expression and ATP release may have contributed to the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. Purinergic antagonists may, therefore, be a useful therapeutic option for the treatment of overactive bladder with increased purinergic-mediated contractions.

Reducing medication regimen complexity for older patients prior to discharge from hospital: feasibility and barriers.

WHAT IS KNOWN AND OBJECTIVE: Older hospital inpatients are often prescribed complex multi-drug regimens; increased regimen complexity is associated with poorer medication adherence and treatment outcomes. There has been little research into methods for reducing regimen complexity. The objective of this study was to explore the feasibility of incorporating medication regimen simplification into routine clinical pharmacist care for older hospital inpatients and identify barriers to regimen simplification at a major teaching hospital. METHODS: Following an educational intervention, clinical pharmacists were encouraged to minimize regimen complexity for their patients by identifying potential simplifications during routine medication regimen reviews (e.g. medication chart reviews, discharge prescription reviews) and discussing these changes with hospital doctors and patients. Pharmacists completed a data collection form for patients aged 60 years or above discharged from their wards during the study period (n = 205; mean age, 81.3 years), indicating whether they had reviewed the patient's medication regimen complexity (and if not why), whether any changes to simplify the regimen were identified, and whether changes were successfully implemented (and if not why). RESULTS AND DISCUSSION: Pharmacists reviewed medication regimen complexity for 173/205 (84.4%) patients and identified 149 potential changes to reduce regimen complexity for 79/173 (45.7%) reviewed patients. Ninety-four (63.1%) changes were successfully implemented in 54/205 (26.3%) patients. Regimens were simplified more often for patients discharged from subacute aged care (geriatric assessment and rehabilitation) wards compared with acute general medicine wards. The most commonly cited reason for not reviewing regimen complexity and not implementing identified simplification-related changes was 'lack of time'. Non-acceptance of pharmacist recommendations by patients or doctors were other common reasons for not implementing changes. WHAT IS NEW AND CONCLUSION: This is the first study to explore pharmacist-led medication regimen simplification and barriers to regimen simplification in the hospital setting. It demonstrates that simplification of older inpatients' regimens is feasible when training in regimen simplification is provided. The main barrier to regimen simplification appears to be lack of pharmacist time.

Impact of a self-administration of medications programme on elderly inpatients' competence to manage medications: a pilot study.

WHAT IS KNOWN AND OBJECTIVES: Changes to medication regimens and failure to involve patients in management of their medications whilst in hospital may result in medication errors or non-adherence at home after discharge. Self-administration of medications programmes (SAMP) have been used to address this issue. The objective of this study was to assess the impact of a SAMP on elderly hospital inpatients' competence to manage medications and their medication adherence behaviours. METHODS: The SAMP comprised three stages: education, progressing to supervised self-administration and finally to independent self-administration. Decisions to progress patients to the next level, and whether they passed or failed the SAMP, were made by the ward pharmacist and nursing staff. The Drug Regimen Unassisted Grading Scale (DRUGS) was used to assess patients' competence to manage medications at various time points. Tablet count and the Tool for Adherence Behaviour Screening (TABS) were used as adherence measures. RESULTS AND DISCUSSION: Participants (n = 24) with a mean age of 77.4 years, were mainly female and generally had a high level of functioning. They were prescribed a mean of 9.0 medications at the time of commencing the SAMP. Twenty-two of the 24 participants successfully completed the SAMP. DRUGS scores at discharge improved significantly (P<0.001) compared with that before commencement of medication self-administration. Participants reported a significant decrease (P = 0.02) in non-adherent behaviour and a trend towards improved adherent behaviour (P=0.08) after participation in the SAMP. WHAT IS NEW AND CONCLUSION: An inpatient SAMP improved elderly patients' ability to competently manage and adhere to their prescribed medications regimen. This finding needs to be confirmed in a larger controlled trial.

Understanding chemotherapy treatment pathways of advanced colorectal cancer patients to inform an economic evaluation in the United Kingdom.

BACKGROUND: Accurate description of current practice within advanced colorectal cancer (CRC) specialties were needed to inform an economic evaluation of the UGT1A1 pharmacogenetic test for irinotecan in the United Kingdom. METHODS: The study was based on a literature review and elicitation of expert opinion. The expert panel comprised 44 consultant oncologists in NHS Hospital Trusts across England. RESULTS: Ten first-line, 10 second-line and 12 third-line chemotherapy regimens were reported, reflecting wide variations in treatment pathways. Predominant pathways emerged with: first-line treatment with oxaliplatin-based regimens, second-line treatment with irinotecan-based regimens and third-line treatment with mitomycin-based regimens. Experts estimated the frequency of febrile neutropaenia 8.4% (95% CI: 6.7-10.0), septic neutropaenia 4.7% (95% CI: 3.4-6.0) and severe diarrhoea 13.1% (95% CI: 10.8-15.5). Approaches for the clinical management of neutropaenia within the NHS were described. CONCLUSIONS: This study identified wide variations in the clinical management of advanced CRC patients. Descriptions of current treatment pathways are necessary for economic evaluations. Variations in clinical practice must be reflected in the model to ensure the findings from an economic evaluation of UGT1A1 testing are sufficient to inform policy regarding the cost-effective use of NHS resources.

A qualitative exploration of multiple medicines beliefs in co-morbid diabetes and cardiovascular disease.

AIM: Multiple medicines are typically prescribed for patients with Type 2 diabetes (T2D) and cardiovascular disease (CVD). Non-adherence to medicines can arise for those who self-manage the complex regimens typical of T2D and CVD. Perceptions about treatment and illness are probable drivers of adherence and self-management behaviours. However, few studies have explored perceptions about multiple medicines and none has examined the complexities of managing medicines used in T2D and CVD. We explored perceptions towards multiple medicines expressed by people managing co-morbid T2D and CVD. METHOD: Nineteen adults managing multiple medicines for T2D and CVD participated in semi-structured interviews. The interviews were analysed using a modified grounded theory framework. RESULTS: Participants were sceptical about the prescription of additional medicines, particularly CVD medicines. Often medicines for T2D management were thought to be more important than medicines prescribed for CVD management. Lifestyle change was thought to be a way of reducing CVD risk and this was related to the lower status given to CVD medication. Lipid-lowering medicines were often thought to be the least important CVD medication prescribed, with some participants considering cessation of medicines to test their necessity. CONCLUSIONS: Despite evidence on the severity of macrovascular complications in T2D being available, participants in this study undervalued their CVD medications. Survey research is needed to assess how widely held these beliefs are and whether these beliefs influence non-adherence. Future research should explore how healthcare professionals can best address such beliefs.

Costing juvenile idiopathic arthritis: examining patient-based costs during the first year after diagnosis.

OBJECTIVES: There are few data on the treatment patterns and associated cost of treating children with inflammatory arthritis including juvenile idiopathic arthritis (JIA), in the short or long term. The aim of this study was to obtain patient-based costs for treating children with JIA in the UK, in the first year from diagnosis and from the secondary health care payer perspective. METHODS: The Childhood Arthritis Prospective Study (CAPS) is an ongoing longitudinal study recruiting children with inflammatory arthritis from four UK hospital centres. Included children are newly diagnosed,

The effect of anaesthetic agents on induction, recovery and patient preferences in adult day case surgery: a 7-day follow-up randomized controlled trial.

BACKGROUND AND OBJECTIVE: To compare induction, pre- and post-discharge recovery characteristics and patient preferences between four anaesthetic regimens in adult day-surgery. METHODS: Randomized controlled trial. In all, 1158 adults assigned to: propofol induction and maintenance, propofol induction with isoflurane/N2O, or sevoflurane/N2O maintenance, or sevoflurane/N2O alone. We prospectively recorded induction and pre-discharge recovery characteristics, collected 7-day post-discharge recovery characteristics using patient diaries and patient preferences by telephone follow-up. RESULTS: Recruitment rate was 73%--of the 425 refusals, 226 were not willing to risk a volatile induction. During induction, excitatory movements and breath holding were more common with sevoflurane only (P < 0.01). Injection pain and hiccup were more common with propofol induction (P < 0.01). In the recovery room and the postoperative ward, both nausea and vomiting were more common with sevoflurane only (P < 0.01). This difference disappeared within 48 h. There was no difference between groups in the mental state on awakening, recovery time, time to discharge or overnight admissions; then was also no difference in pain between the four groups for each of the seven postoperative days (P < 0.01), nor any differences in concentration or forgetfulness. Patients took 6.5 days (95% CI: 6.0-7.0, n = 693) to resume normal activities. Patients who received sevoflurane only were more likely to recall an unpleasant induction and least likely to want the same induction method again (P < 0.01). CONCLUSION: Differences in outcome between the four regimens are transient; sevoflurane is not an ideal sole agent for adult day case anaesthesia and, in this setting, patients base their preferences for future anaesthetics on the method of induction.

Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model.

OBJECTIVES: To compare patient outcomes, resource use and costs to the NHS and NHS Blood Transfusion Authority (BTA) associated with cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion. DATA SOURCES: Electronic databases covering the period 1996-2004 for systematic reviews and 1994-2004 for economic evidence. REVIEW METHODS: Existing systematic reviews were updated with data from selected randomised controlled trials (RCTs) that involved adults scheduled for elective non-urgent surgery. Any resource use or cost data were extracted for potential use in populating an economic model. Relative risks or weighted mean difference of each outcome for each intervention were assessed, taking into account the number of RCTs included in each outcome and intervention and the presence of any heterogeneity. This allowed indirect comparison of the relative effectiveness of each intervention when the intervention is compared with allogeneic blood transfusion. A decision analytic model synthesised clinical and economic data from several sources, to estimate the relative cost-effectiveness of cell salvage for people undergoing elective surgery with moderate to major expected blood loss. The perspective of the NHS and patients and a time horizon of 1 month were used. The economic model was developed from reviews of effectiveness and cost-effectiveness and clinical experts. Secondary analysis explored the robustness of the results to changes in the timing and costs of cell salvage equipment, surgical procedure, use of transfusion protocols and time horizon of analysis. RESULTS: Overall, 668 studies were identified electronically for the update of the two systematic reviews. This included five RCTs, of which two were cell salvage and three preoperative autologous donation (PAD). Five published systematic reviews were identified for antifibrinolytics, fibrin sealants and restrictive transfusion triggers, PAD plus erythropoietin, erythropoietin alone and acute normovolaemic haemodilution (ANH). Twelve published studies reported full economic evaluations. All but two of the transfusion strategies significantly reduced exposure to allogeneic blood. The relative risk of exposure to allogeneic blood was 0.59 for the pooled trials of cell salvage (95% confidence interval: 0.48 to 0.73). This varied by the type and timing of cell salvage and type of surgical procedure. For cell salvage, the relative risk of allogeneic blood transfusion was higher in cardiac surgery than in orthopaedic surgery. Cell salvage had lower costs and slightly higher quality-adjusted life years compared with all of the alternative transfusion strategies except ANH. The likelihood that cell salvage is cost-effective compared with strategies other than ANH is over 50%. Most of the secondary analyses indicated similar results to the primary analysis. However, the primary and secondary analyses indicated that ANH may be more cost-effective than cell salvage. CONCLUSIONS: The available evidence indicates that cell salvage may be a cost-effective method to reduce exposure to allogeneic blood transfusion. However, ANH may be more cost-effective than cell salvage. The results of this analysis are subject to the low quality and reliability of the data used and the use of indirect comparisons. This may affect the reliability and robustness of the clinical and economic results. There is a need for further research that includes adequately powered high-quality RCTs to compare directly various blood transfusion strategies. These should include measures of health status, health-related quality of life and patient preferences for alternative transfusion strategies. Observational and tracking studies are needed to estimate reliably the incidence of adverse events and infections transmitted during blood transfusion and to identify the lifetime consequences of the serious hazards of transfusion on mortality, health status and health-related quality of life.

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling.

OBJECTIVES: To assess the relative effectiveness, patient acceptability, costs and cost-effectiveness of four strategies for the prevention of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal (GI) toxicity: (1) Cox-1 NSAIDs plus histamine-2 receptor antagonist (H2RA), (2) Cox-1 NSAIDs plus proton pump inhibitors (PPIs), (3) Cox-1 NSAIDs plus misoprostol, and (4) Cox-2 NSAIDs (later expanded to 4a Cox-2 coxibNSAIDs and 4b Cox-2 preferential NSAIDs). DATA SOURCES: Electronic databases up to May 2002. REVIEW METHODS: Relevant studies were selected, assessed and analysed. Pooled relative risk ratios (RR) from the systematic review were combined with up-to-date UK resource use and unit costs data in an incremental economic analysis. A probabilistic decision-analytic model was designed and populated with data to carry out incremental economic analysis. Incremental cost-effectiveness ratios (ICERs) were generated for the outcome measure, endoscopic ulcer or serious GI event averted, against total cost, and non-parametric bootstrapping was used to simulate variance of these ICERs. RESULTS: Of 118 selected trials, including 125 relevant comparisons (which included 76,322 participants) only 138 deaths and 248 serious GI events were reported. Seven comparisons were judged to be at low risk of bias. Comparing the gastroprotective strategies against placebo, there was no evidence of effectiveness of H2RAs against any primary outcomes (few events reported), PPIs may reduce the risk of symptomatic ulcers [RR 0.09, 95% confidence interval (CI) 0.02 to 0.47], misoprostol reduces the risk of serious GI complications (RR 0.57, 95% CI 0.36 to 0.91) and symptomatic ulcers (RR 0.36, 95% CI 0.20 to 0.67), Cox-2 'preferentials' reduce the risk of symptomatic ulcers (RR 0.41, 95% CI 0.26 to 0.65) and Cox-2 'coxibs' reduce the risk of symptomatic ulcers (RR 0.49, 95% CI 0.38 to 0.62) and possibly serious GI events (RR 0.55, 95% CI 0.38 to 0.80). All strategies except Cox-2 'preferentials' reduce the risk of endoscopic ulcers. There were only 12 direct comparisons between gastroprotective strategies. All they suggest is that Cox-2 preferentials are better than misoprostol for preventing GI complications. Indirect comparisons suggested that PPIs may prevent symptomatic ulcers better than Cox-2 coxibs, but this is very weak evidence. For prevention of endoscopic ulcers PPIs and misoprostol appear more successful than H2RAs and misoprostol is better than Cox-2 preferentials. There were no UK head-to-head published economic analyses with regard to the main gastroprotective strategies. There were generally insufficient data with regards to cardiac or renal outcomes, serious GI outcomes or life-years gained to populate the mode. Mean (2.5th and 97.5th percentile) costs per endoscopic ulcer averted compared with Cox-1 NSAIDs alone were as follows: Cox-1 plus H2RAs, -186 pounds (-555 to 804); Cox-1 plus PPIs, 454 pounds (251 to 877); Cox-1 plus misoprostol, 54 pounds (-112 to 238); Cox-2 selective NSAIDs, 263 pounds (-570 to 1280), or Cox-2 specific NSAIDs, 301 pounds (189 to 418). With regard to the prevention of endoscopic ulcers, Cox-1 NSAID plus H2RA is a dominant option. Cost-effectiveness acceptability analysis showed a 95% probability that this combination was less costly and more effective. Cost-effectiveness acceptability frontiers showed that if the decision-maker is willing to pay up to 750 pounds to avoid an endoscopic ulcer, then Cox-1 plus H2RA is the optimal strategy. If the decision-maker is willing to pay over 750 pounds, the optimal strategy is NSAID plus misoprostol. Between 1900 pounds and 3750 pounds, Cox-2 selective inhibitors are optimal, and over 3750 pounds, Cox-2 specific inhibitors become optimal. NSAID plus PPI is never the optimal strategy. Sensitivity and subgroup analyses suggest that Cox-1 NSAID plus H2RA and Cox-1 NSAID plus misoprostol become more cost-effective in the older age group. Some conclusions were associated with high levels of uncertainty. CONCLUSIONS: Although there is a very large body of evidence comparing Cox-2 NSAIDs with Cox-1 NSAIDs, this is not matched by studies of the other types of gastroprotectors or by studies directly comparing active gastroprotective strategies. This lack of direct comparisons led to the use of indirect comparisons to help understand the relative efficacy of these strategies. Indirect evidence in itself is weak and was also hampered by lack of evidence in the underlying studies (where the gastroprotectors were compared with placebo). Economic modelling suggests that Cox-1 NSAID plus H2RA or Cox-1 NSAID plus PPI are the most cost-effective strategies for avoiding endoscopic ulcers in patients requiring long-term NSAID therapy. All strategies other than Cox-2 selective inhibitors reduce the rate of endoscopic ulcer compared with Cox-1 alone. The economic analysis suggests that there may be a case for prescribing H2RAs in all patients requiring NSAIDs. Misoprostol is more effective, but is associated with a greater cost and GI side-effects which may be unacceptable for patients. However, when assessing serious GI events, the economic analysis is sufficiently weakened by the data available as to render clear practice recommendations impossible. Further large, independent RCTs directly comparing various gastroprotective strategies are needed. These should report items such as major outcomes, primary data, adverse events, assessment of practice and patient preference.

Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis.

AIMS: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. METHODS: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. RESULTS: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. CONCLUSIONS: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.

Preventing non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: are older strategies more cost-effective in the general population?

OBJECTIVES: To assess the relative cost-effectiveness of five gastroprotective strategies for patients in the general population not judged to be at high gastrointestinal (GI) risk requiring regular traditional (t) non-steroidal anti-inflammatory drugs (NSAIDs) for over 3 weeks: tNSAID/H(2) receptor antagonists (H(2)RAs); tNSAID/proton pump inhibitors (PPIs); tNSAID/misoprostol; COX-2 preferential NSAIDs or COX-2-specific NSAIDs (COXIBs). METHODS: A systematic review of outcomes and UK cost data were combined in an incremental economic analysis. Incremental cost-effectiveness ratios were generated for quality-adjusted life years (QALYs) gained. RESULTS: Cost-utility analysis showed a tNSAID with a H(2)RA is safer and less costly than tNSAIDs alone, and equally effective and less costly than COXIBs. tNSAID/misoprostol was also dominated by tNSAID/H(2)RA due to withdrawal caused by side-effects reducing overall health status. The incremental increase in QALYs gained by using COXIBs instead of tNSAID/H(2)RA would cost 670,000 pounds per QALY gained. The incremental increase in QALYs gained by using tNSAID/PPI instead of COXIBs would cost 26,000 pounds per QALY gained. If the decision-maker will pay up to 140,000 pounds per extra QALY, the optimal strategy is tNSAID/H(2)RA. If the decision-maker will pay over this the optimal strategy is tNSAID/PPI. CONCLUSION: The economic analysis suggests that there may be a case for prescribing H(2)RAs in all patients requiring NSAIDs. Our recommendations are tentative due to the quality of the data available and the assumptions we have had to make in our model, and it is possible that other strategies may be preferred in patients with higher baseline GI risk.

Clinical and economic choices in the treatment of respiratory infections in cystic fibrosis: comparing hospital and home care.

BACKGROUND: A cost-effectiveness evaluation comparing home-based and hospital-based treatment with intravenous antibiotics for respiratory exacerbations in adults with cystic fibrosis (CF) has not been previously undertaken. METHODS: The study was conducted in a UK adult CF centre from a health service perspective. Clinical outcome and resource use data were obtained from a retrospective one-year study and combined with unit cost data in an incremental economic analysis. The primary outcome measure was percentage change in FEV(1); "effectiveness" was defined as maintenance of baseline average FEV(1) over the one-year study period. RESULTS: 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year, there had been a mean percentage decline in FEV(1) compared with baseline average for home-treated patients but an improvement for hospital-treated patients (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). Treatment was deemed "effective" in more hospital (58.8%) than home (42.6%) patients. The cost of hospital treatment was higher than home treatment (mean difference 9,005 pounds, 95% CI 3,507 to 14,700, p<0.001). The mean ICER was 46,098 pounds (2.5th and 97.5th percentiles -374,044 and 362,472). CONCLUSIONS: Hospital treatment was more effective but more expensive than home treatment. Potential methods to improve outcome at home should be considered but these may have resource implications.

Systematic review of the analgesic efficacy and tolerability of COX-2 inhibitors in post-operative pain control.

OBJECTIVE: To evaluate the relative analgesic efficacy and tolerability of single-dose COX-2 inhibitors in post-operative pain management. METHOD: Systematic review of randomized controlled trials (RCTs). OUTCOME MEASURES: The area under the pain relief vs. time curve was used to evaluate the proportion of patient achieving at least 50% pain relief using validated equations. The proportions of patients experiencing any adverse event or specific adverse events were also examined. RESULTS: In all, 18 RCTs were included which contained 2783 patients. The results of the effects of single-dose analgesics on the basis of 50% of patients achieving pain relief over 6 h from dental pain models suggested that oral rofecoxib 50 mg was more effective than codeine/paracetamol 60/600 mg, and the rate ratio (RR) was 2.11 (95% CI 1.6-2.75). Valdecoxib 40 mg was also more effective than oxycodone/paracetamol 10/1000 mg (RR 1.34; 95% CI 1.11-1.62). There was no significant differences between other oral COX-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs), except that celecoxib 200 mg was less effective than ibuprofen 400 mg (RR 0.66; 95% CI 0.48-0.90) and rofecoxib 50 mg (RR 0.65; 95% CI 0.49-0.87). The results from orthopaedic pain model showed no significant difference between rofecoxib 50 mg and naproxen sodium 550 mg (RR 1.04; 95% CI 0.73-1.49). The adverse effects of single-dose COX-2 inhibitor used in short-term post-operative pain management were generally mild and less than non-selective NSAIDs, although there was no significant difference. CONCLUSIONS: The analgesic efficacy and tolerability of single-dose COX-2 inhibitors were more effective than opioid-containing analgesics and similar to non-selective NSAIDs in post-operative pain management. Further studies are needed to examine the efficacy and tolerability of COX-2 inhibitors compared against active comparators over a longer duration to assess whether these short-term effects are mirrored by longer-term outcomes and to determine their ultimate risk-benefit profile.

Clinical and economic choices in anaesthesia for day surgery: a prospective randomised controlled trial.

We compared the cost-effectiveness of general anaesthetic agents in adult and paediatric day surgery populations. We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups. Total costs were calculated from individual patient resource use to 7 days post discharge. Incremental cost-effectiveness ratios were expressed as cost per episode of postoperative nausea and vomiting (PONV) avoided. In adults, variable secondary care costs were higher for propofol induction and propofol maintenance (propofol/propofol; p < 0.01) than other groups and lower in propofol induction and isoflurane maintenance (propofol/isoflurane; p < 0.01). In both studies, predischarge PONV was higher if sevoflurane/sevoflurane (p < 0.01) was used compared with use of propofol for induction. In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).

Anaesthesia for day case surgery: a survey of paediatric clinical practice in the UK.

BACKGROUND AND OBJECTIVE: In October 2000, we conducted a national postal survey of day case consultant anaesthetists in the UK to explore the range and variation in practice of anaesthetizing a patient for day case surgery (paediatrics, urology and orthopaedics). This paper reports the findings of this national survey of paediatric day case anaesthetic practice carried out as part of a major two-centre randomized controlled trial designed to investigate the costs and outcome of several anaesthetic techniques during day care surgery in paediatric and adult patients (cost-effectiveness study of anaesthesia in day case surgery). METHODS: The survey used a structured postal questionnaire and collected data on the duration of surgical procedure; the use of premedication; the anaesthetic agents used for induction and maintenance; the fresh gas flow rates used for general anaesthesia; the use of antiemetics; and the administration of local anaesthesia and analgesia. RESULTS: The overall response rate for the survey was 74 and 63% for the paediatric section of the survey. Respondents indicated that 19% used premedication, 63% used propofol for induction, 54% used isoflurane for maintenance, 24% used prophylactic antiemetics and 85%, used a laryngeal mask. The findings of this national survey are discussed and compared with published evidence. CONCLUSIONS: This survey identifies the variation in clinical practice in paediatric day surgery anaesthesia in the UK.

Anaesthesia for day case surgery: a survey of adult clinical practice in the UK.

BACKGROUND AND OBJECTIVE: In October 2000, we conducted a national postal survey of consultant day case anaesthetists in the UK to explore the range and variation in the practice of anaesthetizing a patient for day case surgery (paediatrics, urology and orthopaedics). The survey was carried out as part of a larger study that comprised a major two-centre randomized controlled trial designed to investigate the costs and outcome of several anaesthetic techniques during day care surgery in paediatric and adult patients (cost-effectiveness study of anaesthesia in day case surgery). We report the findings of this national survey of adult urology and orthopaedic day case anaesthetic practice in the UK. METHODS: The survey used a structured postal questionnaire and collected data on the duration of the surgical procedure; the use of premedication; the anaesthetic agents used for induction and maintenance; the fresh gas flows used for anaesthesia; the use of antiemetics; and the administration of local anaesthesia and analgesia. RESULTS: The overall response rate for the survey was 74% (63% for urology, 67% for orthopaedics). The survey indicated the following practice in adult urology and adult orthopaedic day case surgery: 6 and 12% used premedication; propofol was the preferred induction agent (96 and 97%) and isoflurane the preferred maintenance agent (56 and 58%); 32 and 41% used prophylactic antiemetics; 86 and 93% used a laryngeal mask. CONCLUSIONS: This survey identifies the variation in current clinical practice in adult day surgery anaesthesia in the UK and discusses this variation in the context of current published evidence.