Electroacupuncture plus standard of care for managing refractory functional dyspepsia: protocol of a pragmatic trial with economic evaluation.

INTRODUCTION: This trial proposes to compare the effectiveness and cost-effectiveness of electroacupuncture (EA) plus on-demand gastrocaine with waiting list for EA plus on-demand gastrocaine in providing symptom relief and quality-of-life improvement among patients with functional dyspepsia (FD). METHODS AND ANALYSIS: This is a single-centre, pragmatic, randomised parallel-group, superiority trial comparing the outcomes of (1) EA plus on-demand gastrocaine group and (2) waiting list to EA plus on-demand gastrocaine group. 132 (66/arm) endoscopically confirmed, Helicobacter pylori-negative patients with FD will be recruited. Enrolled patients will respectively be receiving (1) 20 sessions of EA over 10 weeks plus on-demand gastrocaine; or (2) on-demand gastrocaine and being nominated on to a waiting list for EA, which entitles them 20 sessions of EA over 10 weeks after 12 weeks of waiting. The primary outcome will be the between-group difference in proportion of patients achieving adequate relief of symptoms over 12 weeks. The secondary outcomes will include patient-reported change in global symptoms and individual symptoms, Nepean Dyspepsia Index, Nutrient Drink Test, 9-item Patient Health Questionnaire (PHQ9), and 7-item Generalised Anxiety Disorder Scale (GAD7). Adverse events will be assessed formally. Results on direct medical costs and on the EuroQol (EQ-5D) questionnaire will also be used to assess cost-effectiveness. Analysis will follow the intention-to-treat principle using appropriate univariate and multivariate methods. A mixed model analysis taking into account missing data of these outcomes will be performed. Cost-effectiveness analysis will be performed using established approach. ETHICS AND DISSEMINATION: The study is supported by the Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region of China. It has been approved by the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee. Results will be published in peer-reviewed journals and be disseminated in international conference. TRIAL REGISTRATION NUMBER: ChiCTR-IPC-15007109; Pre-result.

Ready-to-use pre-filled syringes of atropine for anaesthesia care in French hospitals - a budget impact analysis.

BACKGROUND: Patient safety is improved by the use of labelled, ready-to-use, pre-filled syringes (PFS) when compared to conventional methods of syringe preparation (CMP) of the same product from an ampoule. However, the PFS presentation costs more than the CMP presentation. OBJECTIVE: To estimate the budget impact for French hospitals of switching from atropine in ampoules to atropine PFS for anaesthesia care. METHODS: A model was constructed to simulate the financial consequences of the use of atropine PFS in operating theatres, taking into account wastage and medication errors. The model tested different scenarios and a sensitivity analysis was performed. RESULTS: In a reference scenario, the systematic use of atropine PFS rather than atropine CMP yielded a net one-year budget saving of €5,255,304. Medication errors outweighed other cost factors relating to the use of atropine CMP (€9,425,448). Avoidance of wastage in the case of atropine CMP (prepared and unused) was a major source of savings (€1,167,323). Significant savings were made by means of other scenarios examined. The sensitivity analysis suggests that the results obtained are robust and stable for a range of parameter estimates and assumptions. STUDY LIMITATIONS: The financial model was based on data obtained from the literature and expert opinions. CONCLUSION: The budget impact analysis shows that even though atropine PFS is more expensive than atropine CMP, its use would lead to significant cost savings. Savings would mainly be due to fewer medication errors and their associated consequences and the absence of wastage when atropine syringes are prepared in advance.

Cost-effectiveness of cycloplegic agents: results of a randomized controlled trial in nigerian children.

PURPOSE: To compare the cost and effectiveness of three cycloplegic agents among Nigerian children. METHODS: Two hundred thirty-three children aged 4 to 15 years attending outpatient eye clinics in Nigeria were randomized to (1) 1% cyclopentolate, (2) 1% cyclopentolate and 0.5% tropicamide, or (3) 1% atropine drops in each eye (instilled at home over 3 days). Ten children were lost to follow-up, nine from the atropine group. An optometrist measured the residual accommodation (primary outcome), dilated pupil size, pupil response to light, and self-reported side effects (secondary outcomes). Caregivers were interviewed about costs incurred due to cycloplegia (primary outcome). The incremental cost effectiveness ratios (ICERs) were calculated as the difference in cost divided by the difference in effectiveness comparing two agents. The 95% confidence intervals (CI) for ICERs were estimated through bootstrapping. RESULTS: The atropine group had significantly lower mean residual accommodation (0.04 +/- 0.01 D [SE]), than the combined regimen (0.36 +/- 0.05 D) and cyclopentolate (0.63 +/- 0.06 D) groups (P < 0.001). Atropine and the combined regimen produced better results for negative response to light and dilated pupil size than cyclopentolate. Atropine was more expensive, but also more effective, than the other agents. The ICER comparing atropine to the combined regimen was 1.81 (95% CI = -6.31-15.35) and compared to cyclopentolate was 0.59 (95% CI = -3.47-5.47). The combined regimen was both more effective and less expensive than cyclopentolate alone. CONCLUSIONS: A combination of cyclopentolate and tropicamide should become the recommended agent for routine cycloplegic refraction in African children. The combined regimen was more effective than cyclopentolate, but not more expensive, and was preferable to atropine, since it incurred fewer losses to follow-up.

Rapid atropine synthesis for the treatment of massive nerve agent exposure.

STUDY OBJECTIVE: We developed and tested a protocol for compounding a large volume of injectable atropine from powder. The resulting protocol could be used by hospitals to rapidly use large amounts of stockpiled atropine. METHODS: The protocol required 2 g of solid (powdered) atropine and 1 L of normal saline solution. The solution was filtered and mixed. One hundred syringes were filled by using a standard syringe-batching system. Modifications, including hand filling, were studied to reduce the time required to synthesize one hundred 3-mL syringes. RESULTS: A single pharmacist was able to reconstitute one hundred 6-mg atropine syringes in 29 minutes using the batching system. The quickest method for a single pharmacist filling syringes by hand was 34 minutes. The cost to the hospital for 5 g of powdered atropine was 11 dollars versus 5,000 dollars for prefilled syringes. CONCLUSION: Large quantities of atropine syringes can be compounded from a powdered form in a timely manner. Additionally, there is a significant cost advantage to using powdered atropine as a hospital stockpile.

Atropine availability as an antidote for nerve agent casualties: validated rapid reformulation of high-concentration atropine from bulk powder.

STUDY OBJECTIVE: Atropine is the preferred antidote for immediate management of toxicity associated with nerve agents or other cholinergic syndromes. A large-scale exposure to a nerve agent or organophosphate insecticide might result in many victims presenting for care within a short period of time. This situation would require the prompt availability of a large amount of atropine to provide treatment. Antidote stocks at many hospitals are inadequate to meet this demand. Atropine that is commercially available comes supplied at concentrations of either 0.4 mg/mL or 1 mg/mL, thereby requiring intravenous administration because of the volume necessary to administer the commonly recommended initial dose of 2 to 6 mg. Moderately ill victims may not require an intravenous line for other care, and in the setting of overwhelmed resources, intramuscular administration is faster and easier to perform. METHODS: To facilitate the delivery of larger atropine doses, we developed a method of fortifying existing injectable atropine with bulk pharmaceutical-grade atropine powder to a concentration of 2 mg/mL, thereby increasing the amount available and facilitating its intramuscular administration. An independent analysis of the resulting formulation was undertaken to assess its potency, absence of pyrogens, and stability. RESULTS: The amount of atropine initially present varied by less than +/-5%, within the range allowed by the US Pharmacopeia for the original product. The product was pyrogen free and maintained its potency at refrigeration temperature for at least 8 weeks after preparation and at room temperature for 4 weeks. Once all materials were available, the compounding of this preparation required about 1 hour to complete. CONCLUSION: Existing atropine stocks can be readily augmented by fortification with powdered atropine accurately and inexpensively. Common pharmaceutical guidelines recommend refrigeration for compounded products such as this if not completely used within 28 days.