Review of Literature

A review of recent articles relevant to today's practicing physicians. Publication does not suggest an endorsement of content or a validation of conclusions. It is recommended that prior to incorporating any of this information into your practice, you carefully review the citations here, as well as related articles.

Anticoagulation
Comparison of 10-mg and 5-mg Warfarin Initiation Nomograms Together with Low-Molecular-Weight Heparin for Outpatient Treatment of Acute Venous Thromboembolism - A Randomized, Double Blinded Controlled Trial

The authors compared a 10-mg dosing nomogram with a 5-mg nomogram for warfarin initiation.

This was a randomized, controlled, multi center trial. All patients were treated with subcutaneous low-molecular- weight heparin for a minimum of five days until a therapeutic international normalized ratio (INR) was achieved. Patients were randomly assigned to initially receive a 10-mg or 5-mg dose of warfarin. The primary end point was time in days to therapeutic INR. Secondary end points were the proportion of patients who had achieved a therapeutic INR by day five, the total number of INR assessments, the number of INR measurements greater then 5.0, incidents of recurrent thromboembolism, and major bleeding, and survival.

Of the 210 consecutive patients meeting the inclusion criteria, nine were excluded and 201 were randomly assigned to study groups (104 to the 10-mg group, 97 to the 5-mg group). Demographic characteristics of both groups were similar. Patients in the 10-mg group achieved therapeutic INR 1.4 days earlier than patients in the 5-mg group (P < 0.001). Eighty-three percent of patients in the 10-mg group achieved a therapeutic INR by day five versus 46 percent in the 5-mg group (P < 0.001). Fewer INR assessments were performed in the 10-mg group than in the 5-mg group (8.1 vs 9.1, P = 0.04). There were no significant differences between the two groups in recurrent events, major bleeding, survival and number of INR measurements greater than five.

The authors concluded that the 10-mg warfarin initiation program nomogram is superior to the 5-mg nomogram because it allows more rapid achievement of therapeutic INR. (MB)

Kovacs et al, Annals of Internal Medicine, May 6, 2003, 138:9, pp 714-719.

Cardiology
Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope.

This study was designed to determine if pacemaker therapy reduces the risk of syncope in patients with vasovagal syncope.

This was a multi center, randomized controlled double blind study. A total of 100 patients who had a median of four episodes of syncope (range 2-15) in the year prior to randomization. All patients had implantation of a dual chamber pacemaker. The patients were then randomly assigned to receive dual chamber pacing with drop rate response (DDD), or to have only sensing without pacing (ODO). The outcome measure was the first recurrence of syncope.

Of 52 patients that had sensing without pacing, 22 (42%) had recurrent syncope within six months compared with 16 (33%) of 48 patients in the dual chamber pacing group. The cumu- lative risk of syncope at six months was 40 percent for the ODO group and 31 percent for the DDD group.

The authors conclude that pacing did not reduce the risk of recurrent syncope in patientss with vasovagal syncope. The authors further state that because of the weak evidence of the efficacy of pacemaker therapy and the risk of complications, pacemaker therapy should not be recommended as first-line therapy for patients with recurrent vasovagal syncope. (MB)

Connolly et al, JAMA May 7, 2330 289:17, pp 2224-2229.

Emergency Medicine
Comparison of lorazepam, diazepam, and placebo for treatment of out-of-hospital status epilepticus

This was a randomized, controlled double blind trial where 205 patients with outpatient seizures were randomized into three groups, lorazepam (66 patients), diazepam (68 patients) and placebo (71 patients). Status epilepticus was terminated on arrival at the ED in 59.1 percent of the lorazepam patients, 42.6 percent of the diazepam patients and 21.1 percent of the placebo patients.

The authors conclude that benzodiazepines can be safely and effectively used by paramedics for treatment of out-patient status epilepticus in adults, with lorazepam being more effective then diazepam. (MB)

Alldredge et al, Annals of Emergency Medicine October 2002, 40:4, pp 631-637

Pelvic Fractures
The utility of clinical examination in screening for pelvic fractures in blunt trauma

This study looked at the predictive value of the clinical examination in trauma patients for detecting pelvic fractures. Over almost three years, 2,176 consecutive blunt trauma patients who presented with Glasgow Coma Scores of 14 or 15 were evaluated. After clinical evaluation was completed the results were placed in a sealed envelope. Inspection focused on abrasions or contusions over bony prominences, ecchymosis about the pelvis, perineum, scrotum, or blood at the urethral meatus. Physical exam consisted of posterior compression of the iliac wings, compression of the pubic symphysis, inspection for limb length inequalities, hip flexion, inward and outward rotation of both hips and rectal exam for gross blood. Next, pelvic x-rays were obtained in all patients, and again the results were placed in a sealed envelope. All patients in the study were admitted for at least 23-hour observation. Patients with negative examination and negative films underwent serial exams. Patients with positive exam findings or who had positive or equivocal x-rays underwent additional x- rays or CT.

Overall, 4.5 percent of the patients in the study had pelvic fractures. Physical exam was 93 percent sensitive, and none of the seven missed fractures required surgical intervention. Pelvic x-rays were only 87 percent sensitive, missing thirteen injuries. Twenty of the patients in the study with pelvic fractures had blood alcohol levels greater than 100 mg/dl, and of these only one was missed on exam.

The authors conclude that in patients with GCS of 14 or 15, clinical exam is at least as good as pelvic x-rays, and that a normal exam precludes the need for the routine pelvic film currently recommended by ATLS guidelines. Elevated alco- hol levels do not change these findings.

Editor note: As was the case with neck x-rays after trauma, it is time to put the routine 'shot gun' x-rays we order for trauma aside, and to go back to the basics of a competent history and physical examination to evaluate our patients. This was a well designed study, with enough statistical predictive power to justify changing clinical practice. It would be nice to see a repeat of this study in another institution to insure that these findings are generalizable. (JH)

RP Gonzalez et al, J AM Coll Surg, 194:2, Feb 2002

Hypertension
This was a network metanalysis, taking medline searches and journals from January 1995 - December 2002. Studies used in the analysis were long term, randomized controlled studies where major cardiovascular disease endpoints as an outcome. Studies included both placebo and untreated control groups, as well as actively treated control groups. A total of 42 studies with 192,478 patients randomized to seven treatment strategies were used in the meta-analysis.

The authors do comment that "none of the other treatment strategies was significantly better than low-dose diuretics for any major cardiovascular disease outcome." They further note that of 30 drug to drug comparisons, eight showed diuretics were "significantly Better," 13 "favored" diuretics, five favored other therapies and four were indifferent.

The authors concluded that low-dose diuretics are the most effective first line treatment for the prevention of cardiovascu- lar disease morbidity and mortality. The authors also recom- mended that treatment guidelines reflect this evidence. (MB)

Psaty et al, JAMA, May 21, 2003 289:19, pp 2534-2544

Lyme Disease
Duration of Antibiotic therapy for early lyme disease This study evaluated different durations of oral doxycycline treatment and the combination of oral doxycycline and a single dose of ceftriaxone for treatment of patients with early lyme disease.

This was a randomized, double blind, placebo controlled study which took place at a single center university hospital. There were 180 patients with erythema migrans who received either 10 days of oral doxycycline with or without a single dose of ceftriaxone, or 20 days of oral doxycycline. Outcomes was based on clinical observation and neurocognitive testing. Efficacy was assessed at 20 days, 3 months, 12 months and 30 months.

At all time points, the complete response rate was similar for the three treatment groups in both on-study and intention-to-treat analyses. In the on-study analysis, the complete response rate at 30 months was 83.9 percent in the 20 day doxycycline group, 90.3 percent in the 10-day doxycycline group and 86.5 percent in the doxycycline-ceftriaxone group. The only patient with treatment failure (10-day doxycycline group) developed meningitis on day 18. There were no significant differences in the results of neurocognitive testing among the three treatment groups and a separate control group without lyme disease. Diarrhea occurred significantly more often in the doxycycline-ceftriaxone group (35%) than in either of the other two groups.

The authors concluded extending treatment with doxycycline from 10 to 20 days or adding one dose of ceftriaxone to the beginning of a 10 day course did not enhance therapeutic efficacy in patients with erythema migrans. Regardless of regimen, objective evidence of treatment failure was extremely rare. (MB)

Wormser et al, Annals of Internal Medicine, May 6, 2003, 138;9, pp 697-704.

Osteoporosis
Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women.

This was a randomized, double blinded, placebo controlled study. Following a three month open label run-in phase with hormone replacement and placebo alendronate, 373 patients were randomly assigned in a 2x2 factorial design to receive hormone replacement therapy (conjugated equine estrogen 0.625mg/day with or without medroxyprogesterone, 2.5mg/day) and alendronate 10mg/day, both agents or neither. All patients received Calcium and Vitamin D supplementation throughout the trial. At three years, the combination therapy patients had significantly increased total hip bone mineral density. Therapy was well tolerated with 90 percent patient retention at three years.

The authors conclude that therapy with alendronate was superior to HRT, and combination therapy was superior to either alendronate or HRT therapy alone. (MB)

Greenspan et al, JAMA May 21, 2003, 289:19, pp2525-2533

Pediatrics
Oral dexamethasone for the treatment of pain in children with acute pharyngitis

This was a randomized, double blinded controlled prospective study looking at the efficacy of dexamethasone in treating pain from pharyngitis in children. A total of 184 children were randomized. A rapid streptococcal antigen test was done on each child. Of 85 children positive for the antigen, 45 were randomized to the dexamethasone group and 40 to placebo. Of 99 children antigen negative, 47 received dexamethasone and 52 placebo.

In the antigen positive group, the median time to significant pain relief was six hours in the dexamethasone group and 11.5 hours in the placebo group, and time to total pain relief was 36 hours for the placebo group and 40 hours for the dexamethasone group. In the antigen negative group, the median time to significant pain relief was 13 hours in the dexamethasone group and nine hours in the placebo group. The medi- an time to complete relief was 48 hours in placebo group and 50 hours in the dexathemasone group.

The authors conclude that for all children with acute pharyngitis, oral dexamethasone does not decrease the time to onset of clinically significant pain relief or time to complete pain relief. However in the subset of children with positive antigen detection test results, there is a statistically significant improvement in time to onset of pain relief, but it is of marginal clinical importance. (MB)

Bulloch et al, Ann Emerg Med, May2003, 41:5, pp601-608

Pulmonary A Randomized Trial Comparing Lung-Volume-Reduction Surgery with Medical Therapy for Severe Emphysema

A total of 1218 patients with severe emphysema underwent pulmonary rehabilitation and were randomly assigned to undergo lung-volume-reduction surgery or to receive continued medical treatment.

Overall mortality was 0.11 death per person-year for both treatments. After 24 months, exercise capacity had improved by more than 10W in 15 percent of the surgery group, as compared with three percent of patients in the medical-thera- py group. Exercise capacity after 24 months had improved by more than 10W in 16 percent of patients in the surgery group, as compared to three percent of patients in the med- ical-therapy group. Among patients with predominantly upper-lobe emphysema and low exercise capacity, mortality was lower in the surgery group then in the medical-therapy group. Among patients with non-upper-lobe emphysema and high exercise capacity, mortality was higher in the surgery group then the medical-therapy group.

The authors conclude that overall, lung-reduction surgery increases the chance of improved exercise capacity, but does not confer a survival advantage over medical therapy. It does yield a survival benefit for patients with both predominantly upper-lobe emphysema and low baseline exercise capacity. Patients previously reported to be at high risk and those with non-upper-lobe emphysema and high baseline exercise capacity are poor candidates for lung-reduction volume surgery, because of increased mortality and negligible functional gain. (MB)

National Emphysema Treatment Trial Research Group. NEJM May 22, 2003; 348:21, pp 2059-2073

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