Comparison of the Diskus inhaler and the Handihaler regarding preference and ease of use.

Many chronic obstructive pulmonary disease (COPD) patients use their inhaler ineffectively and there is a trend towards increased inhaler resistance. We wanted to answer two questions: Is there a difference in preference and ease of use between Diskus (DK) and Handihaler (HH)? How acceptable are inhalation resistances? Sixty COPD patients, naive to DK and HH, but experienced in the use of other inhalers, had to read the instruction leaflet and demonstrate their inhalation technique. If errors were made, instruction was given and inhalation technique was checked again. Patients had to state a preference for DK or HH. Subsequently they inhaled through a range of resistances and scored the acceptability. There was no difference in the number of instructions needed for both inhalers. One third inhaled perfectly after reading the instruction leaflet, which increased to 85% after one instruction. More patients preferred the DK (43) than the HH (16). With decreasing resistance acceptability increases, but it reaches a plateau. Patients have a clear preference for the DK. There is no difference in the number of instructions needed to obtain a perfect inhalation technique, but for some patients one instruction is not enough. The trend to increase the resistance of inhalers has reached a critical point with regard to acceptability.     

Hyperbilirubinemia, hypocarbia and periventricular leukomalacia in preterm infants: relationship to cerebral palsy

This study comprised 103 preterm infants with a gestational age less than 33 weeks who were born in Tampere University Hospital and who were followed up to two years of age. Sixty-four perinatal variables were compared to ultrasound findings in the neonatal period and neurologic handicap at the age of two years. Duration of hypocarbia (PCO2 < or = 30 mmHg) during the first 72 h and hyperbilirubinemia (the mean level of serum total bilirubin) at three days of age were independently and significantly related to periventricular leukomalacia, but not directly to cerebral palsy. The only perinatal variables related independently and significantly to cerebral palsy at two years of age were periventricular leukomalacia and ventriculomegaly. According to these results, periventricular leukomalacia was the main predictor of cerebral palsy in preterm infants. In addition to hypocarbia, hyperbilirubinemia may also be involved in the pathogenesis of extensive (severe cystic) periventricular leukomalacia.     

Myocardial carbohydrate, ketone, and fatty acid uptake in conscious lambs with aortopulmonary shunts.

A left to right shunt increases myocardial work and is often accompanied by increased catecholamine levels. Because both increased myocardial work and increased catecholamine levels may induce increased fatty acid utilization, which could increase resting myocardial oxygen consumption and therefore unfavorably affect coronary reserve, we studied myocardial uptake of glucose, pyruvate, lactate, beta-OH-butyrate, acetoacetate, FFA, and triglycerides in 12 7-wk-old lambs with aortopulmonary left to right shunts (58 +/- 2% of left ventricular output, mean +/- SEM) and in 10 control lambs 2 wk after surgery. Despite the shunt, systemic blood flow in the shunt lambs was maintained at the same level as in the control lambs. This was accomplished by an increased heart rate and stroke volume. Furthermore, the shunt was accompanied by an increased myocardial oxygen consumption in the shunt lambs (834 +/- 70 versus 528 +/- 43 mumol O2.min-1 x 100 g-1; p less than 0.05). There were no significant differences in arterial substrate concentrations between the two groups. The same was true for arteriovenous differences across the myocardium, with the exception of lactate, which was substantially higher in shunt than in control lambs (72 +/- 25 versus 18 +/- 23 mumol/L; p less than 0.05). As a consequence, myocardial lactate uptake in the shunt lambs was increased 15-fold (18 +/- 6 versus 1 +/- 2 mumol.min-1 x 100 g-1; p less than 0.02), whereas uptake of the other substrates merely paralleled the increased myocardial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative cognitive dysfunction in middle-aged patients

BACKGROUND: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent. METHODS: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living. RESULTS: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months. CONCLUSIONS: Postoperative cognitive dysfunction occurs frequently but resolves by 3 months after surgery. It may be associated with decreased activity during this period. Subjective report overestimates the incidence of POCD. Patients may be helped by recognition that the problem is genuine and reassured that it is likely to be transient.     

Aspergillus endocarditis in chronic granulomatous disease

We report the first case, to our knowledge, of Aspergillus endocarditis in chronic granulomatous disease in a patient who also had an atrial septal defect. A diagnosis was made on culture of the organism from the mass despite extensive prior investigation. The presence of distinctive skin lesions as a diagnostic clue of fungaemia is highlighted. Possible advances in diagnosis by detection of fungal cell wall components and in prophylaxis by use of itraconazole are referred to. We conclude that fungal endocarditis should be considered in this condition, especially in the presence of a structural heart defect.     

Influence of a prostaglandin-inhibiting drug on muscle soreness after eccentric work

Since the time sequence of exercise-induced muscle soreness corresponds well with the time sequence of exercise-induced morphological changes in animal skeletal muscle, it has been suggested that muscle soreness is related to an inflammatory response. Prostaglandins are assumed to play a role in the inflammatory process. The influence of a cyclo-oxygenase-inhibiting drug (flurbiprofen) on the subjective symptoms of soreness and eventual structural changes was investigated in six male subjects. The subjects performed one concentric and two eccentric work bouts of 30 min at 80% of the individual maximal work load on the bicycle ergometer. Muscle biopsies taken before, immediately after, and 24 h after work were used to examine structural, ultrastructural changes as well as for assessment of glycogen content. Plasma levels of muscle enzymes and subjective soreness were determined at regular intervals. Eccentric work elicited muscle soreness in all subjects: however, the soreness was consistently less in the second eccentric trial. No significant enzyme release was noticed in any of the subjects, whereas ultrastructural changes were restricted to the mitochondria. No influence of flurbiprofen on subjective soreness was noticed. After both eccentric trials muscle glycogen was lower 24 h after work compared to the content immediately after work. The results suggest that eccentric exercise interferes with glycogen synthesis and that prostaglandins do not play a major role in exercise-induced muscle soreness.     

Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial

BACKGROUND: Guidelines recommend inhaled corticosteroids (ICS) as maintenance treatment for patients with chronic obstructive pulmonary disease (COPD) with a post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and frequent exacerbations, although they have only a small preventive effect on the accelerated decline in lung function. Combined treatment with ICS and long acting beta2 agonists (LABA) may provide benefit to the stability of COPD, but it is unknown if withdrawal of ICS will result in disease deterioration. METHODS: The effects of 1 year withdrawal of the ICS fluticasone propionate (FP) after a 3 month run-in treatment period with FP combined with the LABA salmeterol (S) (500 microg FP + 50 microg S twice daily; SFC) were investigated in patients with COPD in a randomised, double blind study. 497 patients were enrolled from 39 centres throughout the Netherlands; 373 were randomised and 293 completed the study. RESULTS: The drop out rate after randomisation was similar in the two groups. Withdrawal of FP resulted in a sustained decrease in FEV1: mean (SE) change from baseline -4.4 (0.9)% (S) v -0.1 (0.9)% (SFC); adjusted difference 4.1 (95% CI 1.6 to 6.6) percentage points (p<0.001). Corresponding figures for the FEV1/FVC ratio were -3.7 (0.8)% (S) v 0.0 (0.8)% (SFC) (p = 0.002). The annual moderate to severe exacerbation rate was 1.6 and 1.3 in the S and SFC groups, respectively (adjusted rate ratio 1.2; 95% CI 0.9 to 1.5; p = 0.15). The mean annual incidence rate of mild exacerbations was 1.3 (S) v 0.6 (SFC), p = 0.020. An immediate and sustained increase in dyspnoea score (scale 0-4; mean difference between groups 0.17 (0.04), p<0.001) and in the percentage of disturbed nights (6 (2) percentage points, p<0.001) occurred after withdrawal of fluticasone. CONCLUSIONS: Withdrawal of FP in COPD patients using SFC resulted in acute and persistent deterioration in lung function and dyspnoea and in an increase in mild exacerbations and percentage of disturbed nights. This study clearly indicates a key role for ICS in the management of COPD as their discontinuation leads to disease deterioration, even under treatment with a LABA.