Pharmacoeconomic aspects in the treatment of chronic obstructive bronchitis

AIM: Analysis of pharmacological cost-efficiency at various stages of medical care for patients with chronic obstructive bronchitis (COB). MATERIAL AND METHODS: The cost of COB patients treatment, including that of hospital stay, ambulance call, outpatient treatment, cost of medicines. RESULTS: In direct medical expenditures, the cost of hospital stay is the highest. Most of this money (80%) is spent on management of severe exacerbation of COB in critical care units. CONCLUSION: It would be valid to set up specialized outpatient service for follow-up and treatment of COB patients.     

Pulmonary prostacyclin is associated with less severe respiratory distress in preterm infants

BACKGROUND: Prostacyclin (PGI(2)) and thromboxane A(2) (TxA(2)) may take part in lung pathology; high concentrations of PGI(2) may protect newborn rabbits against hyperoxic lung injury, and TxA(2) may participate in the development of bronchopulmonary dysplasia (BPD). Aims: To examine in small preterm infants, the relationship between pulmonary PGI(2) and TxA(2) and respiratory distress during the early postnatal period. METHODS: The stable metabolite of prostacyclin, 6-keto-prostaglandinF(1 alpha), and that of thromboxane A(2), thromboxane B(2), were quantified by radioimmunoassays in 284 samples of tracheal aspirates from 48 infants (GA: 27.4+/-2.1 week, BW 959+/-334 g) during the first 12 postnatal days. RESULTS: Mean concentration of 6-keto-prostaglandinF(1 alpha) was 414+/-31 pg/ml (mean+/-S.E.M.), and of thromboxane B(2) was 418+/-37 pg/ml. Correlations existed between 6-keto-prostaglandinF(1 alpha) and gestational age, birth weight, and the initial arterial-alveolar oxygenation ratio. Negative correlations existed between 6-keto-prostaglandinF(1 alpha) and both mean inspiratory oxygen and duration of mechanical ventilation. Indomethacin treatment was associated with lower pulmonary 6-keto-prostaglandinF(1 alpha), but not with lower TxB(2). Thromboxane B(2) correlated positively with gestational age, birth weight, and initial arterial-alveolar oxygenation ratio, and inversely with duration of mechanical ventilation. CONCLUSIONS: In preterm infants, higher pulmonary 6-keto-prostaglandinF(1 alpha) was associated with less severe respiratory distress and with maturity, whereas thromboxane B(2) was associated more strongly with maturity than with respiratory distress.     

Embolic material generated by multiple aortic crossclamping: a perfusion model with human cadaveric aorta

BACKGROUND: Atherosclerosis of the ascending aorta and use of aortic crossclamping are risk factors for neurologic injury during cardiac surgery. OBJECTIVES: Repeated aortic manipulation is part of the surgical approach to most cardiac operations. The aim of this study was to assess the amount and size of particulate matter that is dislodged from the aortic wall as a function of repeated aortic crossclamping. METHODS: In 10 subjects undergoing autopsy the aorta was dissected and mounted in a perfusion model. The ascending aorta was crossclamped and washed out 10 times, with the perfusate collected in aliquots (1 to 10). The aliquots were examined by computerized image processing, both macroscopically and under the microscope for calcified and cellular material. RESULTS: Aortic crossclamping produced substantial output of particulate matter. After repeated aortic crossclamping the number of particles decreased (P =.012) and approached the baseline for aliquots 6 to 10. The average particle diameter was 0.63 +/- 0.03 mm, with a maximum of 4.74 mm. Similar variability in particle outputs were recorded microscopically, with findings of both calcified and cellular material. Nine of 10 aortas had calcifications seen during simple visual inspection. CONCLUSIONS: The washouts of dislodge material at aortic crossclamping had embolic potential. During the initial aortic crossclamping procedures the amount of particles was substantial, both macroscopically and microscopically. On the microscopic scale noncalcified cellular debris represents a significant pool of embolic material. Repeated aortic crossclamping reduced the amount of particles. These findings question surgical techniques associated with repeated aortic crossclamping.     

Ruptured subcapsular hematoma after laparoscopic cholecystectomy attributed to ketorolac-induced coagulopathy

Ketorolac is the first injectable nonsteroidal antiinflammatory drug used as an analgesic in the perioperative period. However, gastrointestinal bleeding is a risk associated with its perioperative administration. A 23-year-old woman was admitted for elective laparoscopic cholecystectomy. Her medical history was unremarkable except for a complaint of intermittent right upper quadrant pain for several months. The operative procedure was uneventful. Thirty milligrams of ketorolac were given intravenously just prior to termination of surgery. Eighteen hours after surgery, the patient developed right upper quadrant pain associated with tachycardia and hypotension. Abdominal computed tomography (CT) scan demonstrated a large subcapsular hematoma of the liver. A few hours later, the hemodynamic condition worsened, and the patient was taken to the operating room. Laparoscopic exploration showed a ruptured subcapsular hematoma with active bleeding. No evidence of parenchymal injury of the gallbladder bed was found. The hematoma was evacuated and hemostasis was performed laparoscopically. Ketorolac has a strong antiplatelet activity and further acts by the inhibition of platelet function, which may last as long as 24 h after the last administration. Surgeons and anesthesiologists should be aware that ketorolac may cause or aggravate bleeding.     

Corneal perforation after conductive keratoplasty with previous refractive surgery

A 56-year-old woman had conductive keratoplasty (CK) for residual hyperopia and astigmatism. Three years before the procedure, the patient had arcuate keratotomy, followed by laser in situ keratomileusis 2 years later for high astigmatism correction in both eyes. During CK, a corneal perforation occurred in the right eye; during the postoperative examination, an iris perforation and anterior subcapsule opacification were seen beneath the perforation site. The perforation was managed with a bandage contact lens and an antibiotic-steroid ointment; it had a negative Seidel sign by the third day. The surgery in the left eye was uneventful. Three months after the procedure, the uncorrected visual acuity was 20/32 and the best corrected visual acuity 20/20 in both eyes with a significant improvement in corneal topography. Care must be taken to prevent CK-treated spots from coinciding with areas in the corneal stroma that might have been altered by previous refractive procedures.     

Chevron v Echazabal: public health issues raised by the "threat-to-self" defense to adverse employment actions

In June of 2002, the US Supreme Court upheld a regulation that allows employers, under the Americans with Disabilities Act, to make disability-related employment decisions based on risks to an employee's own personal health or safety. Previous judicial decisions had allowed employers to make employment decisions based on the threat that a worker's medical condition posed to others but had not addressed the issue of risk posed to an employee's health by his or her own disability. The authors comment on the potential effects of the court's decision for occupational health practitioners charged with assessing the degree of risk and harm of a particular workplace environment and for public health efforts aimed at curbing workplace injury and sickness.     

Myocardial infarction among professional drivers

BACKGROUND: Professional drivers are at an increased risk of myocardial infarction but the underlying causes for this increased risk are uncertain. METHODS: We identified all first events of myocardial infarction among men age 45-70 years in Stockholm County for 1992 and 1993. We selected controls randomly from the population. Response rates of 72% and 71% resulted in 1067 cases and 1482 controls, respectively. We obtained exposure information from questionnaires. We calculated odds ratios (ORs), with and without adjustment for socioeconomic status, tobacco smoking, alcohol drinking, physical inactivity at leisure time, overweight status, diabetes and hypertension. RESULTS: The crude OR among bus drivers was 2.14 (95% confidence interval = 1.34-3.41), among taxi drivers 1.88 (1.19-2.98) and among truck drivers 1.66 (1.22-2.26). Adjustment for potential confounders gave lower ORs: 1.49 (0.90-2.45), 1.34 (0.82-2.19) and 1.10 (0.79-1.53), respectively. Additional adjustment for job strain lowered the ORs only slightly. An exposure-response pattern (by duration of work) was found for bus and taxi drivers. CONCLUSIONS: The high risk among bus and taxi drivers was partly explained by unfavorable life-style factors and social factors. The work environment may contribute to their increased risk. Among truck drivers, individual risk factors seemed to explain most of the elevated risk.     

Evaluation of the novel antiepileptic drug,AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys

AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 microg/kg/injection). When AWD 131-138 (10-100 microg/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 microg/kg i.v. AWD 131-138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low.     

Expression profiling to predict outcome in breast cancer: the influence of sample selection

Gene expression profiling of tumors using DNA microarrays is a promising method for predicting prognosis and treatment response in cancer patients. It was recently reported that expression profiles of sporadic breast cancers could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors. Having observed an overlap in those data between the genes that predict outcome and those that predict estrogen receptor-alpha status, we examined their predictive power in an independent data set. We conclude that it may be important to define prognostic expression profiles separately for estrogen receptor-alpha-positive and estrogen receptor-alpha-negative tumors.     

Health-Related Quality of Life Measured with EQ-5D in Patients Treated for Depression in Primary Care

OBJECTIVE: The objective of the present study was to assess the impact of depression on patients' health-related quality of life (HRQL) with the EQ-5D instrument over 6 months while on antidepressant treatment. METHODS: A total of 447 patients were recruited at 56 primary care centers to this naturalistic longitudinal observational study. Patients older than 18 years with depressive symptoms, and who initiated an antidepressant therapy because of depression were included in the study. Data on patients' sociodemographics, daily activity, and quality of life (EQ-5D) were collected using questionnaires completed during outpatient general practitioner visits for a follow-up period of 6 months. RESULTS: The mean EQ-5D utility score at baseline was 0.47 (0.44-0.49). Milder cases of depression reported a health utility of 0.60, whereas moderately and severely depressed patients reported utility values of 0.46 and 0.27, respectively (P < 0.01). At end of follow up the average utility was 0.69 (0.67-0.72), corresponding to an increase of 0.23 over 6 months (P < 0.01). Regression analyses showed that, all else equal, patients who were on sick leave were associated with 10% lower utility. CONCLUSIONS: Depression has a substantial impact on HRQL. Our results indicate that treatments for depression are associated with significant improvement in EQ-5D index score over a course of 6 months. Self-reported patient valuations are important outcomes for cost-utility analysis of new treatments for depression and the present study provides important evidence for future economic evaluations.