Cost-effectiveness and pricing of caffeine.

In a formal economic evaluation ancillary to the Caffeine for Apnea of Prematurity trial, caffeine was shown to reduce costs while simultaneously improving clinical outcomes. Although these results still apply, the current price of caffeine is substantially higher than when it was introduced. Such pharmaceutical price growth contributes appreciably to medical costs and inflation. In this review, the examples of caffeine and surfactant show how prices are determined for the neonatology formulary. Drivers include small market size, government-imposed barriers to competition designed to encourage innovation, high willingness-to-pay, failure of government buyers to exercise their market power, and asymmetries in knowledge about costs and effects between producers and patients. Many of these factors are exercised at the national policy or market levels. However, by conducting rigorous clinical trials and economic evaluations, neonatologists can still ensure that the drugs they prescribe are both efficacious and represent good use of societal resources.

A global trend of caffeine consumption over time and related-environmental impacts.

Caffeine is one of the most consumed substances, and it has been largely detected in aquatic ecosystems. We investigated the trends in caffeine consumption over three decades and its relationships with gross domestic product (GDP) and human development index (HDI) to understand global patterns and to identify potential hotspots of contamination. The total caffeine consumption is increasing mainly due to population growth. Moreover, caffeine consumption per capita is also increasing in some countries, such as Brazil, Italy, and Ethiopia. A high positive correlation between caffeine consumption per capita with HDI and GDP was found for coffee-importing countries in Europe, while a high negative correlation was found for coffee-exporting countries in Africa. The literature review showed that the highest caffeine concentrations coincide with countries that present an increasing caffeine consumption per capita. Also, approximately 35% of the caffeine concentrations reported in the literature were above the predicted no-effect concentration in the environment and, again, overlaps with countries with increasing per capita consumption. Despite the high degradation rate, caffeine consumption tends to increase in a near future, which may also increase the overall amount of caffeine that comes into the environment, possibly exceeding the thresholds of several species described as tolerant to the current environmental concentrations. Therefore, it is essential to prevent caffeine from reaching aquatic ecosystems, implementing sewage treatment systems, and improving their efficiency.

Perceptions and Knowledge of Caffeinated Energy Drinks: Results of Focus Groups With Canadian Youth.

OBJECTIVE: To examine use, knowledge, and perceptions of caffeinated energy drinks (CEDs) among youth. DESIGN: Qualitative research using focus group discussions (n = 4). SETTING: Two Canadian cities (Toronto and Montreal). PARTICIPANTS: Youth aged 12-18 years (n = 41). PHENOMENON OF INTEREST: Perceived definitions of CEDs, reasons for use, knowledge of health effects, use with alcohol, marketing perceptions, and use and understanding of cautionary statements on packaging. ANALYSIS: Data were analyzed using a modified grounded-theory approach. RESULTS: Youth identified CEDs as products that provide energy and contain caffeine and sugar. Compared with mainstream CED brands and energy shots, youth were less likely to perceive Gatorade, Coca-Cola, and a Starbucks beverage as energy drinks, despite some ambiguity. The majority of participants believed that CEDs, including mixed with alcohol, were not necessarily harmful in moderation and that marketing was targeted toward older youth and young adults. Awareness of cautionary statements on CEDs was low; cautionary statements were perceived as difficult to find and read owing to the design and small font. CONCLUSIONS AND IMPLICATIONS: Findings suggest a need to increase public education regarding the potential risks of CED consumption, including enhancements to the mandated cautionary statements, with greater attention to the impact of CED marketing on youth.

Caffeine for apnea of prematurity: a neonatal success story.

Caffeine, a methylxanthine and nonspecific inhibitor of adenosine receptors, is an example of a drug that has been in use for more than 40 years. It is one of the most commonly prescribed drugs in neonatal medicine. However, until 2006, it had only a few relatively small and short-term studies supporting its use. It is thanks to the efforts of Barbara Schmidt and the Caffeine for Apnea of Prematurity (CAP) Trial Group that we now have high-quality and reliable data not only on short-term but also long-term outcomes of caffeine use for apnea of prematurity. CAP was an international, multicenter, placebo-controlled randomized trial designed to determine whether survival without neurodevelopmental disability at a corrected age of 18 months is improved if apnea of prematurity is managed without methylxanthines in infants at a high risk of apneic attacks. CAP was kept simple and pragmatic in order to allow for maximum generalizability and applicability. Infants with birth weights of 500-1,250 g were enrolled during the first 10 days of life if their clinicians considered them to be candidates for methylxanthine therapy. The most frequent indication for therapy reported in CAP was treatment of documented apnea, followed by the facilitation of the removal of an endotracheal tube. Only about 20% of the neonatologists in the trial started caffeine for the prevention of apnea and the findings of CAP cannot automatically be extrapolated to an exclusive prophylactic indication. However, recent data suggest that the administration of prophylactic methylxanthine by neonatologists is now common practice.

Headache rate and cost of care following lumbar puncture at a single tertiary care hospital.

BACKGROUND: American Academy of Neurology guidelines recommend the use of noncutting needles because of lower rates of headache following lumbar puncture in randomized trials. We sought to determine the rate of headache using cutting needles and the potential cost savings of switching to noncutting needles. METHODS: We retrospectively reviewed the charts of all patients who had a lumbar puncture in the outpatient neurology clinic at a single institution between January 2004 and December 2005. Outcome data included occurrence of headache, back pain, or epidural hematomas within 2 weeks of the procedure. Costs associated with the use of the current system were compared with the projected costs of switching to a noncutting needle system. RESULTS: A total of 274 patients underwent lumbar puncture (62% women, mean age 53 ± 17 years, average weight 178 ± 43 pounds). Of these, 38 (14%) had a post-lumbar puncture headache. Eight patients (3%) reported back pain. No patients had an epidural hematoma. Twelve patients were admitted for a total of 18 hospital days, mainly for headache. Predictors of headache were younger age and no prior aspirin use. The rate of headache associated with the noncutting needle according to published literature is 4%. The estimated cost savings would have been approximately $20,000 per year (or approximately $73 per person). CONCLUSIONS: In this single-institution study, use of a noncutting needle would have potentially been associated with less adverse events and less cost. Further studies are warranted, including the possibility of premedication with aspirin.

Economic evaluation of caffeine for apnea of prematurity.

OBJECTIVE: To determine the cost-effectiveness of treatment with caffeine compared with placebo for apnea of prematurity in infants with birth weights less than 1250 g, from birth through 18 to 21 months' corrected age. METHODS: We undertook a retrospective economic evaluation of the cost per survivor without neurodevelopmental impairment by using individual-patient data from the Caffeine for Apnea of Prematurity clinical trial (N = 1869). We included direct medical costs either to the insurance payer or the hospital but excluded costs to parents and society, such as lost productivity. We used a price of $0.21/mg of generic caffeine citrate for our base-case analysis. All costs were expressed in 2008 Canadian dollars and discounted at 3%. The time horizon for this analysis extended through 18 to 21 months' corrected age to match the clinical trial. RESULTS: The mean cost per infant was $124 466 in the caffeine group and $133 505 in the placebo group (difference: $9039 [-14 749 to -3375]; adjusted P = .014). Cost-effectiveness analysis showed caffeine to be a dominant or "win-win" therapy: in >99% of 1000 bootstrap replications of the analysis, caffeine-treated infants had simultaneously better outcomes and lower mean costs. These results were robust to a 1000% increase in the individual resource items, including the price of caffeine citrate. CONCLUSIONS: In comparison with placebo, caffeine therapy for apnea of prematurity in infants weighing less than 1250 g is economically appealing for infants up to 18 to 21 months' corrected age.

Caffeine fatalities--do sales restrictions prevent intentional intoxications?

OBJECTIVE: Caffeine is widely available in beverages and in different over-the-counter products, including tablets containing 100 mg caffeine. Because intentional fatal intoxications with caffeine occur, the maximum quantity of caffeine tablets that can be bought over the counter in a single purchase was restricted from 250 to 30 in Sweden in the year 2004. The objective of this article was to study the effect of this decision on the number of fatal caffeine intoxications. METHOD: In Sweden 95% of all cases undergoing forensic autopsy are screened for a number of drugs including caffeine. All cases during January 1993-September 2009 with a caffeine concentration above 80 microg/g blood were recorded. RESULTS: During the study period toxicological investigations were performed in 83,580 forensic autopsies. Caffeine contributed to the fatal outcome in 20 cases (0.02%). Thirteen (65%) of these fatalities occurred before the introduction of the sales restriction. However, no fatal intoxications where caffeine contributed to the cause of death was recorded between May 2007 and September 2009. CONCLUSION: Overdoses of tablets containing caffeine can be fatal, suicides as well as accidents occur. Restricting the maximum quantity of caffeine tablets available over the counter seemed to be effective in preventing suicides because of caffeine although some time elapsed until the effect was noted. Further monitoring is required to ensure that the observed lower caffeine mortality is a sustained effect.

[Almotriptan vs. ergotamine plus caffeine for acute migraine treatment. A cost-efficacy analysis]. / Almotriptán frente a ergotamina más cafeína en el tratamiento de las crisis agudas de migraña. Análisis de coste-eficacia.

INTRODUCTION: Almotriptan has proven to be more efficacious and tolerable than ergotamine plus caffeine but is more expensive, thus raising the question about its cost-efficacy. METHODS: The course of migraine attacks during 24 hours treated with almotriptan and ergotamine plus caffeine was modelled with a decision tree, using efficacy data from a recent randomized, double-blind clinical trial comparing the two drugs. Costs were calculated from the social perspective (including indirect costs due to absenteeism and loss of productivity) and from the Spanish National Health System (NHS) perspective (only including drug costs). The impact on quality of life was estimated using utilities assigned in the literature to different health states of migraine patients. RESULTS: Treatment response was 57.7% for patients treated with almotriptan vs. 44.5% with ergotamine plus caffeine. Sustained pain-free status was achieved by 20.3% vs. 11.5%. Working days lost due to absenteeism and reduced productivity amounted to 0.24 vs. 0.38 days. Quality of life during attacks was estimated at an average utility of 0.548 vs. 0.422. From the NHS perspective, incremental costs per attack treated with almotriptan vs. ergotamine plus caffeine was euro 5.05, rendering an incremental cost-efficacy ratio of euro38.26 per additional response, euro57.39 per additional complete response, and euro14,709 per quality- adjusted life-year gained. From the social perspective almotriptan saved euro7.50 vs. ergotamine plus caffeine. CONCLUSIONS: Almotriptan can be considered cost-efficacious vs. ergotamine plus caffeine from the NHS perspective and is the dominant option (both more efficacious and more economical) from the social perspective.

Almotriptán frente a ergotaminamás cafeína en el tratamientode las crisis agudas de migraña. Análisis de coste-eficacia / Almotriptan vs. ergotamine plus caffeine for acute migraine treatment. A cost-efficacy analysis

Introducción. Almotriptán ha mostrado ser más eficaz y tolerableque ergotamina más cafeína, pero tiene un precio superior, por loque se plantea la pregunta de su coste-eficacia.Métodos. Se modeló mediante un árbol de decisión el curso durante24 h de ataques de migraña tratados con ambos fármacosusando datos de eficacia de un reciente ensayo clínico doble ciegoaleatorizado. Los costes fueron determinados desde las perspectivassocial y del sistema sanitario. El impacto sobre la calidad de vida seestimó a partir de índices asignados en la literatura a los diferentesestados de salud posibles en pacientes con migraña.Resultados. La respuesta al tratamiento fue del 57,7% con almotriptánfrente a 44,5% con ergotamina más cafeína; 20,3 frente a11,5% de pacientes alcanzaron ausencia mantenida de dolor durante24 h. Se perdieron 0,24 frente a 0,38 días laborales por absentismoy baja productividad. La calidad de vida durante el ataque sevaloró en una utilidad media de 0,548 frente a 0,422. Desde la perspectivadel sistema sanitario el diferencial de costes fue de 5,05 por ataque, resultando en un coste incremental de 38,26 por respuestaadicional conseguida con almotriptán, de 57,39 por respuestacompleta adicional y de 14.709 por año de vida ajustado por calidadganado. Desde la perspectiva social, almotriptán ahorró 7,50 por ataque en comparación con ergotamina más cafeína.Conclusiones. Almotriptán puede considerarse coste-eficazfrente a ergotamina más cafeína desde la perspectiva del sistema sanitarioy es la opción dominante (simultáneamente más eficaz y máseconómica) desde la perspectiva social (U)

Introduction. Almotriptan has proven to be more efficaciousand tolerable than ergotamine plus caffeine but is more expensive,thus raising the question about its cost-efficacy.Methods. The course of migraine attacks during 24 hours treatedwith almotriptan and ergotamine plus caffeine was modelledwith a decision tree, using efficacy data from a recent randomized,double-blind clinical trial comparing the two drugs. Costs werecalculated from the social perspective (including indirect costs dueto absenteeism and loss of productivity) and from the Spanish NationalHealth System (NHS) perspective (only including drug costs).The impact on quality of life was estimated using utilities assignedin the literature to different health states of migraine patients.Results. Treatment response was 57.7% for patients treatedwith almotriptan vs. 44.5% with ergotamine plus caffeine. Sustainedpain-free status was achieved by 20.3% vs. 11.5%. Workingdays lost due to absenteeism and reduced productivityamounted to 0.24 vs. 0.38 days. Quality of life during attackswas estimated at an average utility of 0.548 vs. 0.422. From theNHS perspective, incremental costs per attack treated with almotriptanvs. ergotamine plus caffeine was 5.05, rendering an incrementalcost-efficacy ratio of 38.26 per additional response, 57.39 per additional complete response, and 14,709 per quality-adjusted life-year gained. From the social perspective almotriptansaved 7.50 vs. ergotamine plus caffeineConclusions. Almotriptan can be considered cost-efficaciousvs. ergotamine plus caffeine from the NHS perspective and is thedominant option (both more efficacious and more economical)from the social perspective (AU)

Cost-effectiveness analysis of rizatriptan and sumatriptan versus Cafergot in the acute treatment of migraine.

BACKGROUND: Both ergotamine and selective serotonin 5-HT(1B/1D) receptor agonists ('triptans') are currently used in the treatment of moderate to severe migraine. Ergotamine is a traditional therapy with a lower drug acquisition cost compared with triptans. It has been shown that triptans are more efficacious than ergotamine, but the higher acquisition costs and shorter duration of action are disadvantages of triptans compared with ergotamine. OBJECTIVE: The purpose of this study was to provide a comparison of the cost-effectiveness of rizatriptan 10 mg and sumatriptan 50 mg tablets with that of a fixed-dose combination of ergotamine tartrate plus caffeine (Cafergot) in the treatment of an acute migraine attack. The cost-effectiveness of rizatriptan in comparison with sumatriptan was also assessed. METHODS: Three separate decision tree models were developed (model 1: rizatriptan vs Cafergot; model 2: sumatriptan vs Cafergot; model 3: rizatriptan vs sumatriptan). The time horizon was 1 year. Cost-effectiveness analysis was conducted from the societal perspective using cost and effectiveness estimates from the literature. All costs were converted to US dollars (2003). The cost-effectiveness ratio was expressed as incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: Base case evaluation showed that both rizatriptan and sumatriptan dominated Cafergot. The net annual saving associated with use of rizatriptan was US dollars 622.98 per patient, with an incremental QALY of 0.001. Use of sumatriptan resulted in a saving of US dollars 620.90 and an increase in QALY. The cost-effective ratios were not sensitive to changes in key variables such as efficacy, utility, drug costs, hospitalisation cost and patient preference over alternative therapies. The study further showed that rizatriptan is more cost effective than sumatriptan, as evidenced by its lower cost and greater effectiveness. Sensitivity analysis showed that the cost-effectiveness ratios were sensitive to moderate changes in drug efficacy. CONCLUSION: Rizatriptan and sumatriptan were less costly and more effective than Cafergot in the treatment of an acute migraine attack. Rizatriptan was somewhat less costly and more effective than sumatriptan. Additional quality-of-life studies are needed to confirm the benefits of using triptans in the management of migraine.

Barbiturate withdrawal following Internet purchase of Fioricet.

BACKGROUND: The Internet enables businesses to advertise their pharmaceutical products and services without medical supervision. The Internet also allows for the unsupervised purchase of medications that may have neurologic consequences. OBJECTIVE: To describe acute withdrawal delirium following the abrupt discontinuation of Fioricet. PATIENT: The patient was a 37-year-old woman with a history of depression and migraine headaches but not drug abuse. She developed a florid withdrawal delirium following the discontinuation of a drug she purchased online. The medication, which contained butalbital, was self-administered in escalating doses for the treatment of chronic headaches. Daily doses of up to 750 mg to 1000 mg were reported. RESULTS: The patient was admitted to the hospital for the treatment of unexplained seizures that were followed by several days of an intense withdrawal syndrome. Little improvement was noted after the administration of benzodiazepines and phenothiazine. After parenteral phenobarbital administration, her symptoms resolved. CONCLUSIONS: The withdrawal state from barbiturates is similar to that from ethanol. Tolerance can develop with prolonged abuse, leading to escalating drug doses to achieve the desired effect. The suggested management of both types of withdrawal syndromes is similar, but the relative resistance of the behavioral and autonomic features in patients was remarkable. Physicians should be aware of the ease with which medications can be purchased without supervision from Internet pharmacies. The magnitude of the number of drugs that are made available through this means creates a proclivity to withdrawal states.

The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment.

Reports of symptoms when regular caffeine consumption is stopped have appeared in the medical literature, but the frequency and significance of this phenomenon have remained controversial. The objective of this study was to collect information on the prevalence and severity of caffeine withdrawal in the general population and determine the incidence and type of symptoms reported on blind abrupt and gradual caffeine cessation among coffee drinkers reporting past episodes of caffeine-withdrawal symptoms. A community-based telephone survey was followed by a stratified, randomized, double-blind controlled study. Participants included 11,112 persons spontaneously calling to inquire about studies not related to caffeine and 57 regular caffeine users selected from among the callers because of self-reported caffeine-withdrawal symptoms. Gradual or abrupt withdrawal from caffeine was compared to continuation of the same caffeine level. In a survey of 11,112 persons, 61% reported daily caffeine consumption, and 11% of the caffeine consumers reported symptoms upon stopping caffeine. Among the regular caffeine users, only 0.9% of males and 5.5% of females reported symptoms significant enough to interfere with normal activities when they abruptly stopped caffeine. A group of those reporting withdrawal symptoms were randomly assigned to three subsamples. In the group subjected to abrupt withdrawal (N = 18), 6 (33.3%) reported symptoms (e.g., headaches and tiredness). Including decreases in functional ratings, a total of 7 of the 18 (38.8%) could be considered to have experienced caffeine withdrawal. The gradual withdrawal group (N = 20) reported minimal if any caffeine withdrawal symptoms. A third group (N = 18) was kept on a level dose of caffeine for comparison. When participants are unaware of the caffeine-withdrawal focus of the study, these results suggest that both the frequency and severity of caffeine-withdrawal symptoms are much lower than found in some previous reports and that clinically significant symptoms may be uncommon events among the general population.