PROPHYLAXIS FOR VTE: TOO LITTLE, TOO LATE?

In hospitalized patients, the new onset of venous thromboembolism (VTE) does not always reflect a failure to provide prophylaxis, suggests a retrospective study from Brigham and Women’s Hospital in Boston. More than half the time, it may result from inadequate provision of preventive measures.

Goldhaber et al reviewed the medical records of 384 patients who were diagnosed with secondary VTE during a two-year period; 272 had deep venous thrombosis (DVT) alone, 62 had pulmonary embolism (PE) alone, and 50 had both. Of the 384 patients, 169 (44%) were receiving general medical or medical oncology services. Less than one quarter of the patients had undergone general or orthopedic surgery.

Slightly less than half—183 (48%)—of the patients had not been given therapies to prevent VTE. Of the 201 patients (52%) who had been treated prophylactically, 112 had received an anticoagulant, 31 were prescribed mechanical prophylaxis, and 58 had been administered pharmacologic and mechanical prophylaxis combined.

Overall, 33 patients died. PE was a major factor in 13 deaths, for a mortality of 3.4% due to secondary PE. Only one of these 13 patients had not been treated prophylactically. The authors acknowledge that the silent nature of DVT and PE makes it likely that more patients had secondary VTE than were actually identified. They suggest that the possibility of successful outcomes may be enhanced by more frequent use of low-molecular-weight heparin, pneumatic compression boots, or both.

Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is caused more often by prophylaxis failure than by withholding treatment. Chest. 2000;118:1680-1684.

AUGMENTATION THERAPY AIDS ALPHA-1 ANTITRYPSIN-DEFICIENT PATIENTS

In alpha1-antitrypsin (AAT)–deficient patients, augmentation therapy with human alpha1-proteinase inhibitor (alpha1-PI) is associated with a marked reduction in the frequency and severity of lung infections, reports the author of a questionnaire-based survey.

Lieberman obtained completed questionnaires from 96 patients who had a ZZ phenotype for AAT deficiency and were receiving augmentation therapy with alpha1-PI and from 47 similar but untreated patients who served as controls. The 50 men and 46 women in the treated group had been given a diagnosis of AAT deficiency at a median age of 40 and 42 years, respectively. Ninety-three had been smokers, compared with 35 of the 47 controls.

Among the patients in the treatment group, 54 were receiving weekly infusions of alpha1-PI, 35 received biweekly infusions, and seven were administered monthly infusions. Before the start of alpha1-PI treatment, most patients were experiencing from three to five infections yearly.

Of the 89 patients who had been receiving augmentation therapy for more than one year, 74 reported that they had benefited, 12 were uncertain about the benefits of treatment, and three said they had not benefited. From the start of treatment, the number of patients who had no or only one infection per year rose from 27 to 73. However, one patient who was treated for three years with alpha1-PI was unable to continue because of a severe allergic reaction to the preparation.

Lieberman J. Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency: a new hypothesis with supporting data. Chest. 2000;118:1480-1485.

DELAYED ANTIBIOTIC USE IS FEASIBLE IN ACUTE OTITIS MEDIA

For children with acute otitis media, a wait-and-see approach before prescribing antibiotics is a feasible course of action that most parents can accept. Although immediate antibiotic use reduces the duration of illness, treatment is associated with adverse side effects and strengthens parental reliance on drug therapy, report the authors of a randomized, controlled trial.

Little et al compared immediate antibiotic therapy with a 72-hour wait-and-see policy in 315 children ages 6 months to 10 years who presented with acute otitis media. Symptom duration was determined in 135 (89%) of the 151 children randomized to immediate treatment and in 150 (91%) of the 164 children who were assigned to delayed treatment.

Immediate antibiotic use was associated with significantly fewer days of discharge at the eardrum, reduced acetaminophen consumption, and less crying and nighttime disturbance. However, there were no significant differences between the two groups in mean pain scores, episodes of distress, or school absence. Diarrhea developed in 19% of the immediate treatment group, compared with 9% of those managed on a delayed basis.

Only 36 children in the delayed treatment group eventually used antibiotics. Nevertheless, 77% of the parents of these children reported being very satisfied with treatment. Satisfaction with treatment was 91% among the parents of children given immediate treatment.

Little and colleagues note that the benefits associated with immediate antibiotic therapy were realized in large part only after the first 24 hours, when symptoms were already abating. The authors also point out that the immediate prescribing of antibiotics strengthens parental belief in their effectiveness, encourages the future administration of antibiotics, and increases the possibility of antibiotic resistance.

Little P, Gould C, Williamson I, et al. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ. 2001;322:336-342.

SELF-HYPNOSIS EFFECTIVE FOR CHRONIC DYSPNEA IN CHILDREN

Self-hypnosis is a useful tool in the management of chronic dyspnea in children, says the author of a retrospective study from the State University of New York Upstate Medical Center in Syracuse.

Anbar reviewed the medical records of 17 patients, ages 8 to 18 years, with chronic dyspnea. Fifteen of the 17 patients had at least one other symptom (eg, cough, wheeze, chest tightness, or tachycardia). Thirteen patients reported dyspnea with activity only, and two each reported dyspnea at rest only or both at rest and when active. Nine patients had a psychosocial condition that may have been related to the dyspnea. The duration of dyspnea ranged from one month to five years (mean, two years).

One patient (who had a history of psychogenic cough) refused the offer to be instructed in self-hypnosis. The other patients were taught self-hypnosis individually in one or two 15- to 45-minute sessions. They were followed for two to 15 months (mean, nine months) after the final session.

Of the 16 treated patients, 13 reported resolution of symptoms within one month of the last session. Eleven of the 13 attributed symptom resolution to hypnosis; two who did not had not used self-hypnosis at home. The remaining three patients reported improvement in their dyspnea. Ten of the 16 patients reported that they continued to use self-hypnosis for at least one month after the final instruction session. Two of the seven patients who were receiving chronic anti-inflammatory therapy were able to discontinue their medication without affecting pulmonary function. A third patient was able to discontinue albuterol therapy.

Anbar RD. Self-hypnosis for management of chronic dyspnea in pediatric patients. Pediatrics. 2001;107:e21. Available at: http://www.pediatrics.org/cgicontent/full/107/2/e21. Accessed March 15, 2001.

CPAP LOWERS BLOOD PRESSURE SLIGHTLY IN SLEEP APNEA PATIENTS

Continuous positive airway pressure (CPAP) therapy has been shown to improve those symptoms associated with the sleep apnea–hypopnea syndrome (SAHS), but what about the treatment’s effect on blood pressure? CPAP administration does lower SAHS-related blood pressure, but only to a limited extent, report the authors of a placebo-controlled, crossover study.

Faccenda et al randomized 68 normotensive SAHS patients, ages 29 to 72 years, to either CPAP or oral placebo for four weeks, after which the patients crossed over to the alternative treatment for an additional four weeks. The median apnea–hypopnea index per hour of sleep for these patients was 35. Forty-eight hours before the end of each treatment period, the patients were fitted with an ambulatory blood pressure monitor.

An intention-to-treat analysis showed no significant change with CPAP therapy in systolic blood pressure, but a significant 1.5-mm Hg decrease in diastolic blood pressure, particularly during the period from 2:00 AM to 5:59 AM. The decrease was most pronounced in the 32 patients who used CPAP for more than an average of 3.5 hours per night and in the 14 patients who had more than twenty 4% desaturations per hour at baseline. The researchers found that neither heart rate nor pulse pressure changed significantly when CPAP was used.

CPAP therapy was associated with a significant decrease in the Epworth Sleepiness Scale (the higher the score, the sleepier the patient) and with a significant improvement in three of the four domains (general productivity, social outcomes, activity level, and vigilance) on the Functional Outcomes of Sleep Questionnaire.

Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea–hypopnea syndrome. Am J Respir Crit Care Med. 2001;163:344-348.

OSELTAMIVIR HELPS PREVENT INFLUENZA SPREAD

Oseltamivir is safe and effective in preventing the secondary spread of influenza to household contacts, say the authors of a placebo-controlled, multicenter study.

Researchers with the Oseltamivir Post Exposure Prophylaxis Investigator Group studied 377 subjects (index cases), of whom 163 (43%) had laboratory-confirmed influenza, and 955 household contacts ages 12 years and older. Household clusters were randomized to treatment with the neuraminidase inhibitor oseltamivir (75 mg/d orally for seven days; n = 178 households) or placebo (n = 193 households). Treatment began within 48 hours of the first report of symptoms in an index case.

Among the contacts of influenza-positive index cases, the prophylactic effectiveness of oseltamivir was 89% for individuals and 84% for households; it was also 89% for individuals exposed to influenza outside the household. Actively treated subjects experienced a significantly lower frequency of viral shedding. None of the isolates from those who shed virus showed decreased sensitivity to the active metabolite of oseltamivir.

The drug was well tolerated, with no serious adverse side effects. Gastrointestinal symptoms occurred in 9.3% of the patients in the treatment group and in 7.2% of the placebo controls.

Welliver R, Monto AS, Carewicz O, et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA. 2001;285:748-754.

PREDICTING THE EFECT OF STEROID DOSE REDUCTION IN ASTHMA

Predicting the Effect of Steroid Dose Reduction in Asthma in patients with asthma that is well controlled with inhaled corticosteroids, measurements of airway hyperresponsiveness and sputum eosinophil levels can be used to predict the result of a dose reduction, report the authors of a prospective study.

Leuppi et al studied 50 patients, ages 18 to 69 years, all of whom were able to successfully control their asthma with inhaled corticosteroids; the goal was to identify predictors of the outcome of a dose reduction. During a four-week run-in period, the patients underwent indirect challenge with mannitol powder and direct challenge with histamine, and they had exhaled nitric oxide (NO) and sputum eosinophil levels measured. During the dose-reduction phase of the study, each patient’s daily corticosteroid dosage was halved every eight weeks until the patient either experienced an asthma exacerbation or was successfully weaned from the drug for eight weeks.

Of the 46 patients who completed the study, 39 experienced asthma exacerbations; in 13 patients, the exacerbation occurred after the first dosage reduction; in 19 patients, after the second reduction; in five patients, after the third reduction; and in two patients, after the fourth reduction. The remaining seven patients were completely weaned from corticosteroid use and were well at the eight-week follow-up.

A Kaplan-Meier survival analysis showed that significant predictors of the failure of corticosteroid reduction included:

• Hyperresponsiveness to both mannitol and histamine at baseline and to mannitol during the dose-reduction phase.

• An increase in eosinophil levels during dose reduction in the absence of high levels at baseline.

Patients ages 40 and older also appeared to be at greater risk of exacerbation. Neither lung function nor exhaled NO levels predicted exacerbation.

Leuppi JD, Salome CM, Jenkins CR, et al. Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids. Am J Respir Crit Care Med. 2001;163:406-412.