CAN COMPUTERS CAUSE ALLERGIC REACTIONS?

The flame retardant triphenyl phosphate, which is known to cause contact dermatitis in humans, is frequently contained in the plastic covers on computer monitors and can be emitted into the air during use, reported Carlsson et al. The researchers believe that this chemical may be the cause of skin problems related to computer work.

Of the 18 brand-new computer monitors evaluated in a recent study, 10 contained triphenyl phosphate. The concentration of the chemical ranged from 0.3% to 10%. The researchers then evaluated the air concentration of triphenyl phosphate in an office before and after installation of a brand-new computer. This measurement was taken about 2 ft in front of the computer screen.

After one day of computer use, the concentration of triphenyl phosphate increased from 0.7 to 82 ng/m3. This level dropped to 39 ng/m3 after eight days of continuous operation. However, even after 183 days of continuous operation--approximately two years of normal workday use--the concentration was about 10 times higher than that found before computer installation.

Carlsson H, Nilsson U, Östman C. Video display units: an emission source of the contact allergenic flame retardant triphenyl phosphate in the indoor environment. Environ Sci Technol. 2000;34:3885-3889.

REDUCED RISK OF ASTHMA AMONG TWINS

Twins are significantly less likely to have asthma than are singletons, Strachan et al have found. While the cause of this reduced risk is not clear, the authors suggested that the protective effect of twin births on allergic disease may be similar to the protective effect of large families.

All children born in Scotland from 1981 to 1984 were included in the analysis. Strachan et al analyzed rates of hospital admissions for respiratory disease among twins and singletons up to age 10 years.

As shown in Table 1, the overall admission rate for respiratory disease was significantly lower among twins than among singletons. This difference was attributable to a significantly lower risk of admission for asthma among twins. In contrast, the rate of admissions for acute bronchitis and bronchiolitis was significantly higher for twins than for singletons.

Table 1 Annual Admission Rates per 1,000 Children
Hospital admission	Twins (n = 5,068)	Singletons (n = 257,871)	Rate ratio
Asthma	2.11	4.45	0.47
Acute bronchitis/bronchiolitis	2.53	1.84	1.37
Other respiratory diseases	3.04	3.14	0.97
All respiratory diseases	7.68	9.43	0.81
Data extracted from Strachan et al. BMJ. 2000.

Strachan DP, Moran SE, McInneny K, Smalls M. Reduced risk of hospital admission for childhood asthma among Scottish twins: record linkage study. BMJ. 2000;321:732-733.

DRUG IMPROVES RHINORRHEA, SLEEP QUALITY

Azelastine significantly improves rhinorrhea and sleep quality in patients with perennial allergic rhinitis, a new study has shown. Whether this nasal antihistamine also reduces daytime sleepiness and nasal congestion remains unclear.

Golden et al randomized 24 subjects with perennial allergic rhinitis to two sprays of placebo or azelastine twice a day for four weeks. The patients then crossed over to the opposite treatment for four more weeks. All patients made daily ratings of the severity of their rhinitis, using a scale from 0 (none) to 3 (severe). In addition, they maintained a daily diary in which they rated the severity of their nasal congestion, daytime sleepiness and fatigue, and nighttime sleep quality, using a scale of 0 (none) to 4 (severe).

During treatment with azelastine, patients' assessment of the severity of their rhinorrhea dropped by a mean of 0.583. Furthermore, their rating of nighttime sleep quality improved by a mean of 0.912. Both these changes were significant. In addition, active treatment was associated with nonsignificant improvements in nasal congestion and daytime somnolence.

Five patients withdrew from the study early, four of whom were taking azelastine when they left the study. The most common reason for discontinuation among these four patients was a worsening of sedation.

Golden S, Teets SJ, Lehman EB, et al. Effect of topical nasal azelastine on the symptoms of rhinitis, sleep, and daytime somnolence in perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2000;85:53-57.

NOREPINEPHRINE FOR SEPTIC SHOCK

The vasopressor norepinephrine is more effective than high-dose dopamine in the treatment of septic shock in patients with persistent hypotension, a prospective observational study indicates. Although previous studies have suggested that norepinephrine is an effective vasopressor, the drug has not been used regularly in septic shock patients because of the fear of excessive vasoconstriction and because hemodynamic monitoring is not always performed in such patients.

Data from 97 adults with septic shock were included in the analysis. Martin et al recorded 19 clinical, biological, and hemodynamic variables for each patient at study entry and determined which factors were associated with outcome.

All of the patients had persistent hypotension, oliguria, and lactic acidosis despite treatment with antibiotics, respiratory support, fluid resuscitation, and dopamine (5 to 15 µg/kg/min). The patients were then given either high-dose dopamine (16 to 25 µg/kg/min) or the lower dose of dopamine plus norepinephrine (0.5 to 5.0 µg/kg/min).

Those who were still hypotensive were given epinephrine. Patients whose hemodynamic status was stable for at least 24 hours were progressively weaned off of the drugs.

Overall, 70 patients (73%) died in the hospital. The following factors were independent predictors of a poor outcome: pneumonia as a cause of septic shock, organ system failure index of 3 or more, urine flow below 10 mL/h at study entry, and lactate concentration above 4 mmol/h at study entry. On the other hand, use of norepinephrine was significantly associated with a decreased risk of hospital mortality. The mortality rates for patients treated with and without norepinephrine were 62% and 82%, respectively.

Martin et al acknowledged that their findings are limited by the study design, and thus they called for a randomized clinical trial to confirm the results.

Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med. 2000;28:2758-2765.

COST-EFFECTIVE RSV CONTROL PROGRAM

A hospital-based infection-control intervention is a cost-effective approach to preventing the transmission of respiratory syncytial virus (RSV) infection, Macartney et al found in a recent case-control study.

The researchers compared the number of RSV cases that occurred in the four years before and after initiation of an RSV infection-control program. The components of the intervention are listed in Table 2.

Table 2 Components of an RSV Infection-Control Intervention

Educate staff Confirm cases of RSV infection Use contact precautions Isolate RSV patients in a separate room Designate nursing staff to care only for isolated RSV patients Discourage staff with symptoms of RSV infection from working in the intensive care unit or with immunocompromised patients; encourage staff with RSV symptoms to wear a mask when caring for other patients Restrict visits from family members with RSV symptoms Appoint infection-control staff to monitor compliance and alert nursing unit managers of nosocomial RSV cases

Data extracted from Macartney et al. Pediatrics. 2000. RSV, respiratory syncytial virus.

The rate of nosocomial RSV infections was 39% lower in the postintervention period than in the preintervention period; this difference was statistically significant. The researchers estimated that the intervention prevented 10 RSV cases per season.

The cost of preventing a single case of RSV nosocomial infection was estimated at $1,563, while the cost to the hospital for each patient with a nosocomial RSV infection was estimated at $9,419 per case. Thus, an estimated $6 was saved for every dollar spent on the infection-control intervention.

Macartney KK, Gorelick MH, Manning ML, et al. Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control. Pediatrics. 2000;106:520-526.

BOSENTAN IN PULMONARY HYPERTENSION

Intravenous bosentan, an endothelin receptor antagonist, reduced pulmonary resistance in patients with isolated pulmonary hypertension in a recent study, but the drug was not selective for the pulmonary vasculature at the doses tested. Furthermore, bosentan caused systemic hypotension and other adverse events that may limit its use in patients with severe pulmonary hypertension, Williamson et al reported.

The study consisted of two parts. The first part was an open-label, dose-ranging trial that was designed to examine the safety and efficacy of intravenous bosentan in patients with isolated pulmonary hypertension. The seven patients enrolled received 50-mg, 150-mg, and 300-mg infusions of the drug at two-hour intervals. In the second part, these patients were randomized to receive either bosentan or placebo as part of an eight-week, double-blind, placebo-controlled trial. However, the study was ended early because many of the patients experienced serious adverse events.

In the first part of the study, bosentan was found to cause dose-dependent reductions in mean pulmonary artery pressure and total pulmonary resistance. At the highest doses, these measurements fell by 10.6% and 20.0%, respectively; however, only the decrease in total pulmonary resistance was significant.

Furthermore, the vasodilative effects of this drug were not limited to the pulmonary vasculature. Systemic vascular resistance fell by 26.2% and mean arterial pressure dropped by 19.8%. The researchers also noted a slight rise in the cardiac index and a dose-dependent increase in endothelin-1 levels.

The study was terminated early after two patients died within 36 hours of randomization to placebo. Both of these subjects had a very poor exercise tolerance. Sepsis could not be excluded as a cause of death in one of the patients. No specific cause other than pulmonary hypertension was found in the second patient. A third subject, who was also randomized to receive placebo, showed no adverse cardiorespiratory effects.

Of the four patients who were randomized to bosentan, only one completed the eight-week treatment protocol before the study was terminated. Among the serious adverse events experienced by these subjects were increasing dyspnea, peripheral edema, respiratory tract infection with significant cardiac decompensation, Clostridium difficile diarrhea with metabolic acidosis, and severe hypoxemia (in a patient who was also treated for a urinary tract infection). Other adverse events included hypotension, peripheral edema, headache, and urinary tract infections.

The researchers noted that the high doses used in the trial may have contributed to the high rate of adverse events. They also recommended that patients with significantly elevated right atrial pressures or severely impaired exercise tolerance be excluded from future trials.

Williamson DJ, Wallman LL, Jones R, et al. Hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation. 2000;102:411-418.

CLOSURE OF PATENT DUCTUS ARTERIOSUS

Ibuprofen is as effective as indomethacin in the treatment of patent ductus arteriosus among preterm infants with respiratory distress syndrome, according to findings from a recent study. Furthermore, in this study, ibuprofen was less likely to cause renal dysfunction than was indomethacin.

A total of 148 preterm infants with respiratory distress syndrome and patent ductus arteriosus were randomized to three intravenous doses of either indomethacin or ibuprofen. The treatments were initiated three days after birth. At baseline, the two groups had similar clinical and echocardiographic characteristics. Ductal closure occurred in a similar proportion of the two groups (70% in the ibuprofen group and 66% in the indomethacin group). The groups also had a similar number of infants who required a second pharmacologic treatment for ductus closure or surgical ductal ligation.

The following four factors were significant independent predictors of treatment failure in the overall cohort: gestational age of 26 weeks or less, use of antenatal indomethacin treatment at 48 hours or less before birth, receipt of high-frequency oscillatory ventilation, and elevated pulmonary artery pressure.

The incidence of oliguria was significantly lower in the ibuprofen group (7%) than in the indomethacin group (19%). Otherwise, the two groups had a similar incidence of complications and other side effects, the researchers found.

Van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000; 343:674-681.