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.

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.

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.

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.

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,

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.

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.

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.

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.

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.

The effect of in vivo oestrogen pretreatment on the contractile response of rat isolated detrusor muscle.

1. The effect of oestradiol pretreatment was investigated on the response of rat isolated detrusor muscle to cholinergic, electrical and 5-hydroxytryptamine (5-HT) stimulation with and without diethylstilbestrol (DES) (2 microM) in the organ bath. 2. Virgin female Wistar rats were injected subcutaneously for 8 days with oestradiol benzoate 150 micrograms kg-1. Control rats received no injections or injection only with the vehicle, ethyl oleate. 3. Detrusor muscle from treated rats showed a decreased sensitivity to acetylcholine (ACh) and carbachol-induced contractile responses. The dose-response curves to these agonists showed a 44% reduction in maximum contractile response for ACh (P < 0.001), and a 38% reduction in maximum contractile response for carbachol (P < 0.05). The addition of 2 microM DES to the bathing medium further significantly reduced the maximum contractile response by 56 and 57% of control respectively. 4. Electrically stimulated detrusor muscle from treated rats showed a significant 49% reduction in the maximum contractile response (P < 0.001). The addition of 2 microM DES to the bathing medium further significantly reduced the maximum contractile response by 66% of control. The tetrodotoxin resistant responses were smaller in pretreated rats, suggesting a reduced sensitivity of the smooth muscle to direct electrical stimulation. 5. The response to 5-HT stimulation by detrusor muscle samples from oestradiol-treated rats showed a non-significant reduction in maximum contractile response, but the addition of 2 microM DES to the bath chamber resulted in a 67% reduction in the response (P < 0.001). 6. Oestradiol pretreatment did not affect the potassium dose-response curve.7. Oestradiol pretreatment reduced the rat detrusor muscle sensitivity to the blocking effect of atropine on the response to electrical field stimulation. Pretreatment also reduced the potentiating effect of physostigmine on the same response.8. These results suggest that oestradiol pretreatment had a modulating effect on cholinergic responses.The addition of oestrogen to the tissue environment enhances this inhibitory effect.

K(ATP) channels mediate the beta(2)-adrenoceptor agonist-induced relaxation of rat detrusor muscle.

We propose that ATP-sensitive K(+) (K(ATP)) channels are normally inactive but involved in beta(2)-adrenoceptor stimulated relaxation of the rat bladder. Spontaneous detrusor muscle contractions were unaffected by glibenclamide (K(ATP) channel blocker) but were reduced when pinacidil (K(ATP) channel opener) concentrations exceeded 10(-5) M. Inhibition by beta(2)-adrenoceptor agonist clenbuterol [10(-6) M] of 1 Hz electrical field stimulated contractions was abolished by glibenclamide [10(-6) M]. Glibenclamide [10(-6) M] decreased forskolin-induced relaxation [10(-9)-10(-4) M] in bladder muscle stimulated with 1 Hz electrical field. In the presence glibenclamide (10(-6) M) or myristoylated protein kinase A inhibitor (2)x[10(-6) M], clenbuterol [10(-9)-10(-5) M] failed to inhibit bladder contraction in response to 1 Hz electrical field stimulation. Therefore, K(ATP) channel opening and the subsequent hyperpolarization of cell membranes in response to beta(2)-adrenoceptor activation is mediated by raised cyclic-AMP levels and activation of protein kinase A. This counteracts ATP-stimulated depolarization in bladder muscle, thereby reducing cell contraction.

Inhibition of the contractile response of the rat detrusor muscle by the beta(2)-adrenoceptor agonist clenbuterol.

The action of clenbuterol, beta(2)-adrenoceptor agonist, on the contractile response of isolated rat detrusor muscle strips was investigated in vitro. Clenbuterol (10(-5) M) inhibited the detrusor muscle frequency response (1-40 Hz, p<0.02) with a more pronounced effect at 1 Hz than 40 Hz. Clenbuterol (10(-6) M) significantly inhibited the contractile response to exogenous ATP (10(-4) to 10(-2) M, p<0.05) but not to carbachol (10(-9) to 10(-4) M). The presence of 10(-5) M ICI 118, 551, beta(2)-adrenoceptor antagonist, shifted significantly the clenbuterol dose-response to 1 Hz electrical field stimulation (EC(50) 3.4x10(-6) M (+/-2.2x10(-6) M) for clenbuterol alone, to 4.1x10(-4) M (+/-8.8 x10(-5) M), P<0.05). In conclusion, clenbuterol inhibits electrical field and ATP-stimulated contractions of detrusor muscle. Reversal of the clenbuterol inhibition of detrusor muscle contraction by ICI 118, 551 shows that clenbuterol is probably acting through postsynaptic beta(2)-adrenoceptors, which modulate the response to ATP released from purinergic nerves.

The lateral scalp flap for anterior hairline reconstruction.

The lateral scalp flap is a valuable addition to the armamentarium of the trained surgeon who manages the problem of male pattern baldness. With careful patient selection and frank counselling, the quality of reconstruction of the anterior hairline can be enhanced for some patients. The transfer of a large number of hair follicles in their normal pattern of density is an obvious advantage over free graft techniques. The disadvantages of a posterior direction of hair growth in the transposed flap, although readily overcome by careful grooming in most patients, may provide a stimulation for microvascular free flap acceptance in the future. At the present time, the magnitude of the latter procedure and the associated expense preclude consideration of this approach for the usual patient, and it is beyond the capability of many surgeons. Only with accurate reporting of complications and long-term results can one ultimately determine the rightful place of this technique. It is our continuing responsibility to inform patients of the changing options and guide them to a proper treatment based on their individual desire and need. The future generation of physicians and surgeons will undoubtedly dwarf our best effort with their accomplishments. I hope and trust that some day patients with male pattern baldness will no longer require surgery for relief. The ideal hope of the future is discovery of a safe method for prevention or medical treatment.

Otoplasty: a combined approach.

The described procedures, alone or in combination, provide the flexibility to correct the vast majority of prominent ears. The techniques are easy to learn and very reliable. The deformed scapha, hidden helix, lobule prominence, asymmetry, and recurrent deformity should become historical. An esthetic degree of protrusion and natural appearance of the reconstructed ear can be achieved in almost every case.

Use of nasolabial skin flap to cover intraoral defects.

Several fresh surgical defects of the maxillary alveolus, palate, and tonsillar area, resulting from the excision of cancer, have been repaired in a single operation by pulling through an inferiorly-based nasolabial flap with a subcutaneous pedicle. Patient rehabilitation has been rapid.