Declining incidence of episodes of asthma: a study of trends in new episodes presenting to general practitioners in the period 1989-98

BACKGROUND: A study was undertaken to determine trends in the incidence of new episodes of asthma presented to general practitioners participating in the Weekly Returns Service of the Royal College of General Practitioners, comprising 92 practices with a registered population of approximately 680 000 persons well distributed throughout England and Wales. These practices monitor the morbidity presented at every consultation, distinguishing between new episodes of illness and ongoing consultations. METHODS: Age specific weekly rates of new episodes of asthma (and of acute bronchitis) presenting to the general practitioners over the years 1989-98 were examined in four week blocks and analysed by multiple regression, separating secular from seasonal trends. RESULTS: Quadratic trends in episodes of asthma were evident in each of the age groups with peaks in 1993/4. Corresponding analyses for acute bronchitis disclosed similar trends generally peaking in the winter of 1993/4. Mean weekly incidence data (all ages combined) decreased in all quarters since 1993. Regional analysis (North/Central/South) showed similar decreases. CONCLUSIONS: There has been a gradual decrease in the incidence of asthma episodes and of acute bronchitis presenting to general practitioners since 1993. The trend of an increase before 1993 followed by a decrease cannot be explained by changes in the patterns of health care usage or diagnostic preference of doctors.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Stability of aqueous solutions of amoxicillin sodium in the frozen and liquid states

The stability of aqueous admixtures of amoxicillin sodium in both the liquid and frozen (solid) states was studied. Admixtures of amoxicillin sodium were prepared in sterile water for injection to a theoretical concentration of 10 mg/mL. For each experimental run, 2-mL aliquots of the admixture were placed in stoppered glass volumetric flasks and stored at temperatures ranging from 19.5 degrees C to -30 degrees C; 16 flasks were stored at each temperature. After equilibration for approximately 20 minutes, duplicate flasks at each temperature were removed from storage conditions for time-zero assay. Subsequently, duplicate flasks were assayed at various times, depending on the storage temperature, for up to 13 days or until more than 80% of the drug had degraded. All samples were assayed at least in duplicate using high-performance liquid chromatography. When amoxicillin solutions were in the liquid state (at temperatures between 19.5 and 0 degrees C), the time required for the amoxicillin concentration to decrease to 90% of its initial value (t90) increased as temperature decreased. However, between 0 degree C and -7 degrees C, the t90 of frozen solutions decreased from two days to 1.08 hours. As temperature declined further, the rate of degradation decreased until the solution was completely frozen; at -30 degrees C, the t90 had increased to 13 days. Amoxicillin sodium is unstable in aqueous solutions stored between 0 degrees C and -20 degrees C. If admixtures of this drug are to be frozen for later use, the storage temperature should be below -30 degrees C.     

Monitoring information processing efficiency after stroke or head injury: A comparison of four computerised tests for use in single case experiments

Abstract

Single case experiments on cognitive rehabilitation can only be valid if adequate methods of monitoring cognitive change are developed. The sensitivity and reliability of four computer-based tests of information processing efficiency (continuous choice reaction time, visual tracking, memory for pairs, and critical flicker fusion) were compared. Performance of 16 left hemisphere stroke patients and 17 patients with severe closed head injury was compared with age-matched controls. The reaction time task proved the most useful in detecting effects of brain damage in both groups and showing good test-retest reliability.     

The absolute bioavailability of racemic ketamine from a novel sublingual formulation

Aim

The principal study objective was to investigate the pharmacokinetic characteristics of a new sublingual ketamine wafer and to establish its absolute bioavailability and local tolerability.

Methods

The study was of open label, two way randomized crossover design in eight healthy male volunteers. Each participant received either a single 10 mg intravenous dose as a constant rate 30 min infusion or a 25 mg sublingual dose of ketamine wafer in two treatment periods with a 7 day wash out. Pharmacokinetic blood sampling and local tolerability and safety assessments were carried out during 24 h following both dosing occasions. Plasma concentrations were analyzed by non-compartmental methods and local tolerability was assessed using modified Likert scales.

Results

The median (90% CI lower, upper limit) absolute bioavailability of sublingual ketamine was 29% (27, 31%). The first quantifiable plasma ketamine concentration was observed within 5 min for all eight participants for both routes of administration and the median (min–max) time of the peak plasma concentration was 0.75 h (0.25–1.0 h) after sublingual administration. The ketamine wafer had very good local tolerability.

Conclusion

Sublingual administration of the ketamine wafer resulted in rapid absorption. The ketamine wafer has comparable bioavailability with other oral transmucosal formulations of ketamine but with markedly reduced inter-subject variability, warranting further evaluation as an analgesic adjunct.     

Late complications after femoral artery catheterization in children less than five years of age

Fifty-eight children who underwent diagnostic femoral artery catheterization before 5 years of age, from 5 to 14 years before the study, were randomly selected from approximately 300 surviving patients undergoing diagnostic femoral artery catheterization at our institution during the interval. Each patient underwent vascular laboratory segmental pressure and waveform examination and arterial duplex scanning, as well as lower extremity bone length radiographs, which were considered positive if the catheterized leg was greater than or equal to 1.5 cm shorter than the opposite leg. Thirteen children who had only venous catheterization served as controls. No arterial abnormalities were present in the control patients (mean ankle/brachial index, 1.01). Arterial occlusion was present in both limbs of five patients who had bilateral diagnostic femoral artery catheterization and in 14 limbs of 51 patients who had unilateral diagnostic femoral artery catheterization. Thus arterial occlusion was present in 33% of patients (19 of 58) and in 37% of limbs (24 of 65). The mean ankle/brachial index in the catheterized limbs was 0.79. Leg growth retardation was present in four limbs (8%) of 51 children undergoing unilateral diagnostic femoral artery catheterization and in one (8%) control patient. The inverse relationship between ankle/brachial index and leg growth retardation was significant (R = 0.47, p less than 0.0005). Only one patient had symptoms of arterial occlusion (claudication), and one patient had symptoms of leg growth retardation (gait disturbance). We conclude that arterial occlusion is common after diagnostic femoral artery catheterization in children less than 5 years of age, but that excellent collateral supply prevents leg growth retardation and/or symptomatic arterial insufficiency in most children.(ABSTRACT TRUNCATED AT 250 WORDS)