Valproate reduces intake of alcoholic beverage among rats

SETTING: University of Malaya Medical Centre, Kuala Lumpur, Malaysia. OBJECTIVE: To assess the awareness of the ozone layer and the acceptance of the new non-chlorofluorocarbon (CFC) propellant hydrofluoroalkane 134a salbutamol pressurised metered dose inhaler (MDI) Airomir among asthmatic patients. DESIGN: A total of 113 consecutive asthmatic patients aged 12 years and above from the out- and in-patient services of the hospital were interviewed using a questionnaire. RESULTS: Sixty-five per cent of the patients were aware of the existence of the ozone layer, 23% that CFCs play a role in ozone depletion, and only 10% that current MDIs contained CFCs. All the patients felt that pressurised MDIs should be made CFC-free after they had considered the role of CFCs in the destruction of the ozone layer. Eighty-one per cent of 94 patients who preferred the Airomir inhaler over a multi-dose dry powder inhaler for administering bronchodilator medications were willing to switch to the new inhaler once it became available on the market. CONCLUSION: Awareness of the damaging effect of CFCs on the ozone layer among asthmatic patients would encourage them to change to an ozone-friendly, CFC-free pressurised MDI.     

Influence of temperature on the emitted dose of an oral metered dose inhaler

The performance of metered dose inhalers is critical for the efficient delivery of drugs to the intended site of deposition in the respiratory tract. The temperature at which metered dose inhaler products are used by patients may influence the physicochemical characteristics of the emitted dose. Product performance characteristics of a metered dose inhaler containing beclomethasone dipropionate and oleic acid in a blend of chlorofluorocarbon propellants, Freon-11 and Freon-12, were determined by cascade impaction analysis and dose delivery through the valve after the metering chamber was loaded and actuated at 4 degrees C, 23 degrees C, and 40 degrees C. The dose delivered from the valve was not affected by the temperature at which the metering chamber was loaded and actuated. The mass median aerodynamic particle size of the emitted aerosol decreased and the percentage respirable fraction increased as the temperature was increased. The geometric standard deviation of the particle size distribution was not significantly affected by the temperature at which the metering chamber was loaded and actuated. The temperature at which a metered dose inhaler is used by a patient may influence the amount of drug that is potentially respirable; therefore, the dose expected to be delivered and the corresponding therapeutic effect may also be affected.     

Serological cross-reactions between Coxiella burnetii and Legionella micdadei

PURPOSE: The bronchodilator effect of salbutamol formulated in hydrofluoroalkane-134a (HFA-134a), a chlorofluorocarbon (CFC)-free propellant for metered dose inhalation (MDI) devices, was compared with that of salbutamol formulated in CFC in anesthetized dogs. METHODS: Bronchospasms were induced by the intravenous injection of histamine, and bronchial resistance was measured by the method of Konzett and Rossler. RESULTS: While the placebo vehicles (HFA-134a and CFC propellants) had no significant effect on histamine-induced bronchospasms, the salbutamol/HFA-134a and salbutamol/CFC MDI formulations had equivalent dose-related inhibitory effects. CONCLUSIONS: These data indicated that salbutamol formulated in HFA-134a and that in CFC propellant are bioequivalent.     

Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease

AIMS: To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease. METHODS: Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n = 10), each infant was given 200 micrograms of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small medication cup. The infants were monitored for heart rate, transcutaneous pO2, pCO2, and oxygen saturation, respiratory system resistance and compliance before and after each treatment. Infants in study 2 (n = 10) were similarly studied except for the use of a different jet nebuliser. RESULTS: The mean (SEM) maximum percentage decreases in respiratory system resistance, observed at 30 minutes after aerosol delivery were study 1: MDI: 44.3 (4.3)%; jet: 32.3 (3.4)%; ultrasonic: 56.1 (3.2)%; study 2: MDI: 28.6 (1.0)%; jet: 16.9 (1.4)%; ultrasonic: 42.1 (1.6)%. During the first hour after treatment, a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies. The use of the ultrasonic nebuliser but not the other devices also resulted in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2. CONCLUSIONS: These findings suggest that among the devices tested, the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser, and least with the jet nebulisers.     

Cost issues surrounding the use of computerized telemedicine for obstetric ultrasonography

Whole-body plethysmography is not included in guidelines from regulatory authorities for the development of treatments or delivery devices for lung disease, despite its potential advantages compared to spirometry. Two separate studies were undertaken to assess the use of specific airway conductance (sGaw) as a pharmacodynamic endpoint for the comparison of two bronchodilator delivery systems (a novel dry powder inhaler and a standard metered dose inhaler). The first pilot study involved delivery of a single dose of salbutamol (200 micrograms) to 12 healthy volunteers and determination of sGaw up to 120 min after treatment. The second study involved delivery of cumulative doses of salbutamol (100, 200 and 400 micrograms) to 19 healthy volunteers with demonstrated reversibility of sGaw to the bronchodilator and measurement of sGaw up to 240 min after treatment. In both studies, increases in sGaw after treatment were significant compared to placebo and larger than the recorded increases in FEV1. Increases in sGaw were similar for both delivery devices and support the therapeutic equivalence of the two products. Power calculations indicated that the second study had appropriate statistical power to discriminate between treatments. It is concluded that the assessment of sGaw in healthy volunteers may be a useful and sensitive pharmacodynamic endpoint for use in the development of bronchodilators and their delivery devices.     

A review and economic evaluation of bronchodilator delivery methods in hospitalized patients

BACKGROUND: Bronchodilator delivery by metered dose inhaler (MDI) to treat airflow obstruction is considered to be less expensive and as effective as nebulized therapy. OBJECTIVES: To document the utilization of bronchodilator delivery methods in a tertiary care Canadian university teaching hospital and to perform an economic evaluation. METHODS: A prospective 6-week audit of 4 preselected hospital wards (respiratory, thoracic surgery, general surgery, and a general internal medicine clinical teaching unit) and a cost-minimization economic evaluation were performed. Bronchodilator (salbutamol and ipratropium bromide) doses, frequency, and delivery methods, either MDI or wet nebulizer (WN), were recorded for 95 patients treated with aerosolized bronchodilators. Direct costs for medications and hourly wages including benefits and equipment were obtained. Time and motion studies identified time allocated to MDI and WN delivery. We used sensitivity analyses to test assumptions that could significantly affect treatment costs, especially assumptions about medications, labor, and spacer devices. Costs are expressed in Canadian dollars (Can$1 = US$0.75). RESULTS: Sixty-seven patients (70.5%) were treated with WN, 6 (6.3%) with MDI, and 22 (23.2%) with both WN and MDI. Self-administration of salbutamol by MDI was the least expensive: $1.27 for 200-microgram doses and $1.73 for 400-microgram doses compared with $2.62 for a 2.5-mg dose delivered by WN. The difference in cost between equivalent treatments (400-microgram MDI vs 2.5-mg WN) is only $0.89. Sensitivity analyses showed that MDI was the least expensive therapy when self-administration was possible and for all levels of supervision if more than 4 minutes was needed to administer a WN treatment. CONCLUSIONS: Bronchodilator delivery by WN is commonly prescribed for hospitalized patients despite evidence for equivalency of effect using MDI and in the absence of substitution protocols. Previous studies have estimated a far greater cost differential based on unrealistic labor estimates. We found that supervision of patients using MDIs minimized the differential cost between WN and MDI therapy and that cost savings are maximal in patients who can self-administer MDI therapy. Methodologically sound economic evaluations can better identify true cost savings and variables that need further study.     

Estimating the cost of lost productivity in dyspepsia

In a two-day, randomised, double-blind, double-dummy, cross-over multicenter study, the bronchodilating effect of 100 micrograms of salbutamol (CAS 18559-94-9) inhaled from a new metered dose powder inhaler (MDPI; Taifun) was compared with that of an identical dose of salbutamol inhaled from a conventional pressurised metered dose inhaler connected to a spacer (pMDI + S). Thirty-six non-smoking, adult asthmatic outpatients with a baseline forced expiratory volume in 1 s (FEV1) between 35 and 70% of the predicted value participated in the study. After inhalation of the study medication pulmonary function, FEV1 and airway resistance (R(aw)), blood pressure (BP), and heart rate (HR) were measured up to 6 h. Area under the FEV1 vs. time curve (AUCFEV1) was used as the primary efficacy parameter, and the 90% confidence intervals (CI) were used to judge clinical equivalence. Other efficacy parameters were used in supportive analyses as secondary parameters. Both treatments produced a clear improvement in pulmonary function. The mean +/- SD AUCFEV1 were 893 +/- 281 and 889 +/- 2761.min after MDPI and pMDI + S, respectively. The 90% CI for the relative efficacy of the MDPI is from 98 to 103% of that of the pMDI + S. Also the other efficacy parameters gave similar results without significant differences: the mean +/- SD values of percent increase in FEV1 were 47.2 +/- 19.3 and 44.7 +/- 20.8, the maximum absolute value of FEV1 were 2.87 +/- 0.77 and 2.86 +/- 0.77, the maximum percent decrease in R(aw) 53.2 +/- 20.5 and 55.0 +/- 19.1, and the minimum absolute value of R(aw) 0.27 +/- 0.11 and 0.30 +/- 0.12 kPa.s.l-1 for the MDPI and pMDI + S, respectively. The salbutamol doses had no significant effect on BP or HR, and were equally well tolerated. Furthermore, 57.5% of the patients preferred the MDPI, 35% the pMDI + S, and 7.5% considered that there was no difference between the devices. In conclusion, this study demonstrates that the new MDPI is as effective and safe a device as a conventional pMDI connected to a spacer in administering inhaled salbutamol for asthmatic patients. Further, most patients considered the MDPI easier to handle, and preferred it over the pMDI + S.     

Is asthma treatment affordable in developing countries?

BACKGROUND: A study was undertaken to assess whether the therapeutic aspects of published international asthma management guidelines are practically applicable in developing countries. METHODS: Questionnaires were sent to expatriate doctors working in developing countries. RESULTS: Forty one replies were received from 24 countries in Africa and Asia. Oral salbutamol was prescribed "usually" or "often" by 35 of the 41 respondents, theophyllines by 30, inhaled bronchodilators by 12, inhaled steroids by two, and cromoglycate by two. Theophyllines were locally available in all 41 cases, oral salbutamol in 40, inhaled bronchodilators in 34, and inhaled steroids (usually beclomethasone 50 micrograms) in only 15. Where they were available, the median (range) coat of a beclomethasone 50 micrograms inhaler was 20% (6.8-100%) of average local monthly income, salbutamol inhaler 13% (3.3-250%), 90 salbutamol 4 mg tablets 3.8% (0.8-75%), and 90 aminophylline 100 mg tablets 4.5% (0.5-70%). If they were available locally at a cheaper price, 34 (83%) respondents would prescribe more inhaled steroids and 37 (90%) would prescribe more inhaled bronchodilators. CONCLUSIONS: Many asthma patients in developing countries are not receiving adequate treatment because the required drugs are not available in their area or are prohibitively expensive.     

Differences in perceived and presented adverse drug reactions in general practice

BACKGROUND: Postmarketing surveillance (PMS) studies are frequently based on data from general practitioners (GPs). Patients, however, do not always report to their GP suspected adverse drug reactions. SETTING: A postmarketing cohort study on adverse reactions to sumatriptan, performed with assistance of drug dispensing GPs in The Netherlands. METHODS: Questionnaires were sent to all drug-dispensing GPs in The Netherlands, as well as to their patients on sumatriptan. To avoid bias, no specific adverse reactions were mentioned in the questionnaires. RESULTS: Of the GPs, 589 (86%) responded; of the patients, 1202 (70%) responded. The most frequently reported suspected adverse reactions to sumatriptan reported by the GPs were dizziness (1.7%), nausea or vomiting (1.5%), drowsiness or sedation (1.4%), and chest pain (1.3%). The most frequently reported suspected adverse reactions by the patients were paraesthesia (11.7%), dizziness (8.1%), feeling of heaviness (8.0%), and chest pain (7.9%). Neither the GPs nor the patients reported serious adverse reactions. CONCLUSIONS: First, patients experience significantly more suspected adverse reactions than are registered by their GP. In view of this higher frequency of reporting of suspected adverse reactions, postmarketing studies with data from GPs only, may underestimate the cumulative incidence of adverse reactions. Second, we conclude that it is possible to obtain useful additional information about adverse drug reactions from patients by sending them questionnaires via their GP.     

Acute treatment-related diarrhea during postoperative adjuvant therapy for high-risk rectal carcinoma

STUDY OBJECTIVES: To examine the main therapeutic response patterns to high doses of salbutamol and to determine the factors that contribute to outcome in acute severe asthma. SETTING: The emergency department (ED) of a large, urban hospital with primary and referral care responsibilities. PATIENTS AND DESIGN: One hundred sixteen consecutive patients with acute exacerbations of asthma were enrolled in the trial, using a prospective sequential design. INTERVENTIONS: All patients were treated with salbutamol delivered with a metered-dose inhaler into a spacer device in four puffs (400 microg) at 10-min intervals. The protocol involved 3 h of this treatment (1,200 microg each 30 min). MEASURES AND RESULTS: A dose-response increase in pulmonary function was found, but only 70% improved sufficiently to be discharged. Of these, almost 70% required < or =2.4 mg of the drug within 1 h to reach the discharge threshold, whereas the remainder 30% need > or =3.6 mg. In 30% of subjects, salbutamol was ineffective. These patients were characterized by a more severe disease as judged by previous beta2-agonist use, larger duration of attack before ED visit, and a more severe obstruction at presentation. However, the most important predictors of outcome were peak expiratory flow rate (PEFR) as percent of predicted, PEFR as liters per minute, and PEFR variation over baseline value, all at 30 min. CONCLUSIONS: This study described two different therapeutic response patterns to salbutamol. Almost 70% of patients were sensitive to salbutamol (good response pattern), and in this group, 2.4 to 3.6 mg represents optimal treatment. In the remainder 30% of patients (poor response pattern), salbutamol in high doses had little effect. However, the outcome was not determined by the intensity of the initial symptoms or by the value of the presenting PEFR, but rather by the early (30 min) short-term response to treatment.     

Postoperative analgesia with intramuscular morphine at fixed rate versus epidural morphine or sufentanil and bupivacaine in patients undergoing major abdominal surgery

Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 1.1 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer. A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx. In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.     

Inhalation therapy in children younger than 2 years. II. The practice

Effective inhalation of drugs, even by small children under 2 years, is often faster, simpler, cheaper and better with metered dose inhalers with small antistatic (metal) inhalation chambers than with nebulisation. This is also true during considerable bronchial obstruction. It is mandatory that the inhalation chamber has a small dead space and well functioning valves opening at low flows. Effective dosing in small children is enhanced by more doses, given separately, while choosing the highest dose per spray available. Important factors determining bronchial deposition in small children are breathing frequency, tidal volume and the degree of bronchial obstruction and nasal obstruction, since inhalation goes primarily through the nose. If well-performed medication with a small inhalation chamber is clinically ineffective, it is better to start systemic medication, e.g. a corticosteroid, or even to consider artificial ventilation, rather than to try nebulisation. Better effective deposition is possible with inhalation of drugs in hydrofluoroalkane (HFA) aerosols, which will replace chlorofluorocarbon (CFC) aerosols in the near future.     

Safety of oral terbinafine: results of a postmarketing surveillance study in 25,884 patients

OBJECTIVE: To broaden the safety database for oral terbinafine by determining the incidence of adverse events, particularly rare risks, that accompany its uncontrolled use in actual clinical practice. DESIGN: Four open, prospective, uncontrolled, postmarketing surveillance studies were conducted in unselected patients in 4 countries. No exclusion criteria were applied. The only treatment instructions participating physicians received were the manufacturer's product information. Physicians monitored patients for adverse events at baseline, during treatment, and at the end of treatment. Serious events were identified according to study protocol, which was consistent for all 4 studies, allowing data to be pooled and analyzed collectively. SETTING: Patients were recruited from dermatology, general, and family practices in the United Kingdom, the Netherlands, Germany, and Austria. PATIENTS: Of the 25884 patients who entered the study, 38.6% had concomitant diseases, 42.8% were taking other medications, and 22.7% were older than 60 years. The predominant indication for terbinafine treatment was onychomycosis (72.2%). INTERVENTIONS: Data on treatment duration was available for 25091 patients. Median duration of treatment was 12 weeks (mean, 13.2 weeks). Treatment extended beyond 6 weeks in 76.0% of patients and for at least 12 weeks in 59.3%. MAIN OUTCOME MEASURES: The incidence of adverse events as reported by physicians, with their opinions regarding relationship to terbinafine therapy. RESULTS: The incidence of adverse events was 10.5%; the majority involved the gastrointestinal system (4.9%) or skin (2.3%). These tended to be mild, transient, and reversible. Terbinafine was considered a possible or probable cause of 11 (0.04%) serious adverse events. No drug interactions were reported, even in patients taking oral antidiabetic agents, astemizole, terfenadine, or cimetidine hydrochloride. CONCLUSIONS: The positive safety profile established during controlled clinical trials of oral terbinafine extends to its uncontrolled use in clinical practice. No previously unrecognized risks were identified.     

Recent developments in respiratory care pharmacology

Bronchoactive inhaled aerosol drugs target the respiratory tract directly and seek to minimize systemic exposure and reduce side effects. Common delivery devices such as the metered dose inhaler, the small volume nebulizer, or the dry powder inhaler each deliver approximately the same fraction of dose (10%) to the lungs, although their dose amounts are not equivalent. Major respiratory drug groups are reviewed, and include the beta-adrenergic and anticholinergic bronchodilators, mucolytic agents, corticosteroids, mediator antagonists, anti-infective agents, and exogenous surfactants. New agents in each group are identified and briefly described, along with the clinical use and most commonly observed side effects for each class of drugs.     

Immunohistochemical demonstration of androgen receptors in human salivary glands

One hundred and eighty-one children with asthma were entered into a randomized, controlled, crossover study comparing sodium cromoglycate via a metered dose inhaler (MDI) and a breath-actuated inhaler (Autohaler). There were no significant differences in pulmonary function tests (FEV1, FVC, PFER), symptom scores and bronchodilator use between the two devices. However both patients' and clinicians' opinions of sodium cromoglycate effectiveness were significantly better (P < 0.01) for the Autohaler. Autohaler was also thought to be easier to use (P < 0.001) and better for co-ordination of actuation with inhalation (P < 0.001). The Autohaler is as efficacious as the metered dose inhaler used by good co-ordinators. It seems to be the significantly better device with respect to ease of use, actuation and co-ordination which may aid compliance.     

Bronchodilating effect of terbutaline powder in acute severe bronchial obstruction

The bronchodilating effect of terbutaline dry powder inhaled via Turbuhaler was compared with terbutaline inhaled via a conventional, chlorofluorocarbon (CFC) inhaler and Nebuhaler (750 ml spacer) in 68 consecutive patients attending the emergency department with acute severe bronchial obstruction. The study was of an open, randomized, parallel group design with one study day. Patients were treated with 2.5 mg of terbutaline 15 min apart, either as dry powder via Turbuhaler or with a CFC inhaler in conjunction with Nebuhaler. Data from 62 patients were analyzed. The mean baseline FEV1 values were 0.81 L (SD, 0.64; range, 0.14 to 2.74 L) in the Turbuhaler group (n = 33), and 0.90 L (SD, 0.90; range, 0.27 to 2.60 L) in the Nebuhaler group (n = 29). The mean increases in FEV1 from baseline were 0.40 L (SD, 0.40; range, 0.06 to 2.36 L) and 0.21 L (SD, 0.25; range, -0.05 to 0.95 L) 10 min after the last inhalation via Turbuhaler and Nebuhaler, respectively. The difference between mean values of the increase in FEV1 after terbutaline treatment with Turbuhaler and the CFC inhaler and Nebuhaler was statistically significant (p = 0.0004, ANOVA). This study showed that inhalation of terbutaline via Turbuhaler produced a significantly greater increase in FEV1 compared with the same dose of terbutaline administered via the CFC inhaler and Nebuhaler in patients attending the emergency department with acute severe bronchial obstruction.     

Bronchodilator response to salbutamol after spontaneous recovery from nonspecific bronchial provocation tests in asthma

Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion. However, it is not known whether this can be done accurately. Therefore, this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second (FEV1) in a group of asthmatic subjects. On two separate occasions at the same time of day, concentration-response studies with inhaled histamine or methacholine, or a sham challenge with normal saline were carried out in a blinded, randomized manner. Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer. The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init). Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9% (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge day respectively. It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second. Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients.     

A prospective comparison of four study designs used in assessing safety and effectiveness of drug therapy in hypertension management

The objective of the study was to compare prospectively the impact of study design on drug therapy safety and effectiveness data obtained in hypertension management. The main study was a randomized controlled clinical trial of four different prospective study designs used in postmarketing assessment involving 1008 primary care practices in nine Canadian provinces. Two thousand nine hundred sixty-four patients with mild to moderate hypertension received an angiotensin converting enzyme (ACE) inhibitor daily for 14 weeks in one of four postmarketing studies--a randomized double-blind clinical trial (RCT) (10 to 40 mg fosinopril daily v 5 to 20 mg enalapril daily), two structured open label trials of 10 to 40 mg fosinopril daily (one with free drugs), or an unstructured open label trial of 10 to 40 mg fosinopril daily. Patient demographic and baseline characteristics, systolic and diastolic blood pressures, adverse events reported, and data quality were recorded as the outcome measures. The results showed that the RCT patients were titrated to higher doses of ACE inhibitor than patients in the open studies, P < .008; patients in the open studies were more likely to receive adjuvant diuretic therapy, P < .008. The decrease in blood pressure was similar for patients in all four studies, mean decrease in systolic BP was between 18 and 20 mm Hg, mean decrease in diastolic BP was between 11 and 13 mm Hg. Fewer patients in the unstructured open trial reported adverse events than patients in the RCT; a 55% relative reduction in reported adverse events (P < .008) was associated with the unstructured trial. There were also fewer drug-related adverse events per patient reported in the unstructured study (17 per 100 patients) than in the other studies (27 to 41 per 100 patients), P < .008. Physician preference for rounding off blood pressure measurements to 0 or 5 occurred most often in the unstructured open trial (P < .008). In conclusion, despite differences in dose titration and in the use of adjuvant therapy, antihypertensive drug therapy effectiveness observed in an RCT may be similar to uncontrolled postmarketing studies. Open trials with scheduled follow-up visits are as effective in detecting severe adverse events as RCT, but postmarketing studies with unstructured schedules of follow-up are insufficient in identifying drug-related adverse events and have poorer quality data.     

Outpatient adenotonsillectomy. Is it safe in children younger than 3 years?

OBJECTIVE: To evaluate the safety of ambulatory adenotonsillectomy in children younger than 3 years. MATERIALS AND METHODS: The records of 102 children younger than 3 years who underwent adenotonsillectomy as an outpatient procedure were reviewed during a 3-year period. RESULTS: Ten patients (10%) required overnight hospital admission for an average of 1.4 days. Nine patients were admitted directly from the day-stay unit and 1 patient was admitted 48 hours after surgery. The reason for hospital admission was poor oral intake. None of the patients had postoperative bleeding or respiratory problems or required intensive care unit admission. CONCLUSION: The safety of ambulatory adenotonsillectomy depends on judicious selection criteria and can be performed in children younger than 3 years.