Captagon: use and trade in the Middle East.

BACKGROUND: Fenetheylline, a psychostimulant drug, often branded as Captagon, is a combination of amphetamine and theophylline. Since the cessation of its legal production in 1986, counterfeited products have been produced illicitly in south-east Europe and far-east Asia. Its profitable trade has been linked to terrorist organizations, including Islamic State of Iraq and the Levant. This study aims to reach up-to-date data, concerning the Captagon e-commerce and use in the Middle East. METHODS: A multi-staged and multi-lingual literature search was carried out. A list of prespecified keywords was applied across medical and paramedical databases, web and Dark web, search engines, social communication media, electronic commerce websites, media networks, and the Global Public Health Intelligence Network database. RESULTS: The use of Captagon as a stimulant in terrorist settings has been marginally covered in the literature. Data can widely be retrieved from Google and AOL search engines, YouTube, and Amazon e-commerce websites, and to a lesser extent from Alibaba and eBay. On the contrary, Middle Eastern e-commerce websites yielded almost no results. Interestingly, the Dark web generated original data for Captagon e-commerce in the Middle East. CONCLUSION: Further investigations are needed on the role that psychoactive drugs play in terrorist attacks and civil war zones. Unless a comprehensive methodological strategy, inclusive of unconventional methods of research, is implemented, it will not be feasible to face such a threat to humanity.

The effect of doxofylline in asthma and COPD.

Theophylline is still one of the most widely prescribed drugs for the treatment of asthma and COPD in developing countries because the majority of asthma and COPD medicines are largely unavailable and also because it is a cheap option. In any case, its anti-inflammatory effects and capacity to reverse corticosteroid resistance deserve consideration, but it can induce numerous side effects and drug-drug interactions and frequently requires measurement of drug levels in plasma. In order to overcome the problems posed by theophylline, other xanthines have been developed. Doxofylline is a newer generation xanthine with both bronchodilating and anti-inflammatory activities and for this reason it has been called "novofylline". It differs substantially from theophylline at the pharmacological level. Clinical studies have shown substantial differences between doxofylline and theophylline. In particular, efficacy/safety profile of doxofylline is better than that of theophylline.

Characteristics of chronic obstructive pulmonary disease in Spain from a gender perspective.

BACKGROUND: The objective of this study was to analyze the clinical and management characteristics of chronic obstructive pulmonary disease (COPD) in men and women, to determine possible gender-associated differences between the two groups of patients. METHODS: An observational and descriptive epidemiological study (EPIDEPOC study). The study included patients with stable COPD and aged >or= 40 years, evaluated in primary care. Data were collected relating to sociodemographic variables, clinical characteristics, quality of life (SF-12), severity of disease and treatment. The results obtained in men and women were compared. RESULTS: A total of 10,711 patients (75.6% males and 24.4% females) were evaluated. Significant differences were found between males and females in relation to the following parameters: age (67.4 +/- 9.2 years in men vs 66.1 +/- 10.8 in women, p < 0.05), smoking (91.9% of the men were smokers or ex-smokers vs 30% of the women), comorbidity (the frequency of hypertension, diabetes, anxiety and depression was greater in women, while ischemic heart disease was more common in men), mental component of quality of life (49.4 +/- 10.3 in men vs 44.6 +/- 11.9 in women, p < 0.05) and severity of disease (56.5 +/- 13.3% in men vs 60.7 +/- 3.2 in women, p < 0.05). As regards treatment, the percentage use of long-acting b2-adrenergic agonists, anticholinergic agents, theophyllines and mucolytic agents was significant greater in men. The total annual cost of COPD was greater in males than in females (1989.20 +/- 2364.47 euro vs 1724.53 +/- 2106.90, p < 0.05). CONCLUSION: The women with COPD evaluated in this study were younger, smoked less and have more comorbidity, a poorer quality of life, and lesser disease severity than men with COPD. However, they generated a lesser total annual cost of COPD than men.

Treatment plan comparison in acute and chronic respiratory tract diseases: an observational study of doxophylline vs. theophylline.

BACKGROUND: The main objective of this article is to estimate the global cost related to the use of the two drugs (associated drugs, specialist visits, hospital admissions, plasma drug monitoring). METHODS: The drug prescriptions were extracted from the Information System of the Pharmaceutical Prescriptions of the Marche Region for each ATC code in the years 2008-2012 and the number of patients per year and other outcomes measure were obtained. RESULTS: 13,574 patients were treated with theophylline and 19,426 patients with doxophylline. The number of patients treated was approximately 5,000 per year. Co-prescription with other drugs, use of corticosteroids, mean number of visits and hospital admissions (per 100 patients) were lower for doxophylline vs theophylline (1.55vs5.50, 0.3vs0.7, 2.05vs3.73 and 1.57vs3.3 respectively). The annual mean cost per patient was €187.4 for those treated with doxophylline and €513.5 for theophylline. CONCLUSIONS: In our study, doxophylline resulted to be associated with a reduction of the overall cost.

[Cost and management of asthma exacerbations in Spanish hospitals (COAX study in hospital services)]. / Coste y manejo de una crisis asmática en el ámbito hospitalario de nuestro medio (estudio COAX en servicios hospitalarios).

OBJECTIVE: The prevalence and associated health cost of asthma have been increasing in developed countries, and 70% of the overall disease cost is due to exacerbations. The primary objective of this study was to determine the hospital cost of an asthma exacerbation in Spain. The secondary objective was to determine what maintenance treatments patients were using to control asthma before the exacerbation and how the exacerbation was treated. The study formed part of a broader study (COAX II), with the same objectives in each of the 8 participating European countries. PATIENTS AND METHODS: Prospective observational study that enrolled 126 patients with an asthma exacerbation treated in the usual way in 6 Spanish hospitals over a 3-month period (from January 1 to March 31, 2000). RESULTS: According to the criteria of the Global Initiative for Asthma, 33.3% of the exacerbations were mild, 38.9% moderate, 26.2% severe, and 1.6% were associated with risk of imminent respiratory arrest. Use of corticosteroids was widespread among patients with moderate and severe asthma, but only 68% of the patients with severe asthma used long-acting beta2 agonists. The mean cost was 1555.70 Euros (95% confidence interval [CI], 1237.60 Euros-1907.00 Euros), of which 93.8% (1460.60 Euros; 95% CI, 1152.50 Euros-1779.40 Euros) was due to direct costs, and 6.2% (95.10 Euros; 95% CI, 35.50 Euros-177.00 Euros) to indirect costs. Cost rose with increasing severity of the exacerbation--292.60 Euros for a mild exacerbation, 1230.50 Euros for a moderate exacerbation, and 3543.10 Euros for a severe exacerbation. CONCLUSIONS: The mean cost was 1555.70 Euros. The costs of moderate and severe exacerbations were 4 and 12 times that of a mild exacerbation, respectively. Long-acting beta2 agonists were less widely used than recommended by the guidelines for treatment of moderate and severe persistent asthma leading to asthma exacerbations.

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014.

Comparative cost-effectiveness analysis of theophylline and ipratropium bromide in chronic obstructive pulmonary disease. A three-center study.

The charts of 311 patients receiving theophylline (T) and 289 patients receiving ipratropium bromide (IB) for COPD were reviewed to determine the total costs and cost-effectiveness of these 2 agents in 3 different health-care settings. A direct cost-accounting method assessed cost, and a Markov decision-analysis model calculated cost-effectiveness. Costs to treat toxic effects were greater for T versus IB. The types and incidences of toxic effects, by drug, were similar among the three centers. Overall costs for T were $121.40 per patient per therapy-month versus $84.56 per patient per therapy-month for IB, as determined by the cost-accounting method. The marginal cost was $366 for T over IB when extrapolated over 1 year using the Markov model. The Markov model also predicted that patients receiving IB had a greater number of complication-free therapy-months (measurement of effectiveness) than patients receiving T. We conclude that treatment with IB was less costly and more cost-effective than T.

Vulnerability of patients with chronic obstructive pulmonary disease according to gender in China.

BACKGROUND: Little information is available regarding the vulnerability of patients with chronic obstructive pulmonary disease (COPD) in China. We aimed to assess this according to patient gender. METHODS: A cross-sectional study was conducted in the rural area of Xuzhou in China. We interviewed and administered questionnaires to 2825 male and 2825 female patients with COPD and subjected the data generated to statistical analysis. We compared differences between proportions of male and female patients using the χ(2) test. RESULTS: The rate of current smoking in men was 30.1%, whereas that in women was 10.9%, and 31.5% of men had a history of using biomass fuel compared with 75.3% of women. Further, 26.0% of the male patients and 16.4% of the female patients did not take theophylline regularly when their disease was stable. During acute exacerbations, 65.8% of the male patients and 39.7% of the female patients took theophylline or similar drugs. The average potential shortening of life expectancy was 1.76 years for men and 1.18 years for women. The average indirect economic burden was 11158.4 yuan for men and 7481.2 yuan for women. The quality of life was worse in female patients than in male patients. CONCLUSION: We found that patients with COPD were vulnerable and that factors determining vulnerability were different for men than for women. Therefore, we recommend adopting different measures for men and women when attempting to prevent, control, and treat COPD, rehabilitate these patients, and improve their quality of life.

[Experience in scaling up the film coating process for theophylline sustained-release pellets in mass production]. / Erfahrungen bei der Ubertragung des Filmcoating-Prozesses für Theophyllin-Retardpellets in den Produktionsmassstab.

The scale-up of the film coating process for the production of Bronchoretard pellets (theophylline, CAS 58-55-9) is an example for the successful setup of a modern production technology designed to meet the increasing GMP requirements while taking into consideration ecological and economical aspects. This technology provides a reduction in polymer losses on drying from approx. 20% to under 5% and a distinct improvement in the reproducibility of the in vitro dissolution profiles. Double batch sizes and higher spray rates allow for a substantially higher batch turnover. A production line installed exclusively for Bronchoretard pellets and specific process optimization measures resulted in considerably lower lag-times of the equipment.

Decrease in emergency room or urgent care visits due to management of bronchial asthma inpatients and outpatients with pharmaceutical services.

OBJECTIVE: To evaluate pharmaceutical care of bronchial asthma over a 1-year period and to investigate whether such care is effective. METHODS: 79 male and 97 female asthma patients who were treated with theophylline and other drugs between June 1994 and September 1996 were studied. The 15 subjects received pharmaceutical care (group 1) and were all inpatient asthmatics who had been admitted to the hospital for treatment. The other patients acted as controls. RESULTS: In 1994, the average medication cost of asthma patients without pharmaceutical care was $199/month and $295/month when such care was provided in the outpatient clinic. The drug treatments which patients received generally included inhaled anti-inflammatory agents and theophylline, but the 161 non-pharmaceutical services patients (group 2) received fewer inhaled anti-inflammatory agents than group 1 patients. The number of visits to the emergency room and hospital admissions were significantly lower in patients after receiving pharmaceutical services than inpatients before receiving pharmaceutical services during our observation period. The serum theophylline concentrations of group 1 patients generally attained levels sufficient for favourable therapeutic effect after patients received pharmaceutical care. CONCLUSION: Pharmaceutical care offered at the hospital is effective in the management of asthma patients.

A cost analysis on the pattern of asthma prescribing in the UK.

There is a need to establish the proportion of adult asthmatics at each step of the recommended asthma management guidelines, the cost of their prescribed treatment, and a revised cost of treatment assuming patients who were suboptimally controlled were moved up a step. Actual prescription and cost figures and a theoretical projection of an ideal scenario was calculated from a sample of general practices in Great Britain from the Doctors Independent Network. They comprised 102 nationally distributed practices and 17,206 adult patients with a diagnosis of, and prescription related to, asthma recorded between October 1993 and March 1994. Ninety-one per cent of patients received treatment within a recognized step of the guidelines. Of these, 80% were at steps 1 and 2. Employing excess inhaled beta-agonist use as a proxy for control of asthma, between 55% and 69% of patients at Steps 1-3 should receive treatment at a higher step. This could lead to an increased expenditure of up to Pound Sterling 4.66 per adult patient per month. This would imply a rise in the annual UK cost of antiasthma prescriptions for adults from Pound Sterling 388m to a possible Pound Sterling 533m. The United Kingdom Government audit commission has suggested that current expenditure on asthma treatment appears to be insufficient. Using an entirely different approach this study has confirmed that a significant increase in asthma prescribing costs is likely to be needed if optimal control of asthma is to be achieved.

Reduction in health care resource utilization associated with extended-release theophylline.

BACKGROUND: People with airway disease are high utilizers of health care resources. Few studies document the value of alternative therapies in reducing utilization. Studies examining theophylline, which demonstrate reduction in resource utilization, have been primarily of short duration in hospitalized settings with small samples. OBJECTIVE: The purpose of this study was to examine the role of oral extended-release theophylline in reducing health care utilization over an extended period of time when added to existing inhaler therapy for ambulatory patients with airway disease. METHODS: We used a retrospective, pretest/posttest design in examining the 1990-1993 South Carolina Medicaid database to compare health care utilization of 455 ambulatory patients for 4 months before and 6 months after extended-release theophylline was added to their treatment regimen. We assessed the following three outcomes: inhaler use, physician office visits, and emergency department visits, all measured in units/person/month. RESULTS: Our sample consisted of patients taking beta2-agonist only (n = 393), steroid only (n = 25), and beta2-agonist plus steroid (n = 37). Inhaler use and physician office visits declined significantly among beta2-agonist users, as well as within the entire sample. Initiation of extended-release theophylline therapy was associated with a 30% decline in utilization of inhaler and physician office visits, influenced mostly by the decline with the beta2-agonist group. CONCLUSION: The results of this effectiveness study using an administrative claims database are consistent with the published randomized clinical trials that document the value of extended-release theophylline when added to existing inhaler therapy.