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Fluticasone plus salmeterol reduces mortality in COPD

Clinical question What is the best inhaled treatment for chronic obstructive pulmonary disease (COPD): a steroid, a beta-agonist, or both?

Bottom line The combination of inhaled salmeterol and fluticasone slightly reduces the risk of exacerbation compared with placebo alone, about one fewer for every 3 years of treatment. There was a trend toward a reduction in mortality, but it was not statistically significant (12.6% vs 16.0%, P = .052). Combination therapy increases the risk of pneumonia (number needed to harm [NNH] = 14). (Level of evidence = 1b)

Synopsis In this study, patients had COPD, defined as a forced expiratory volume in 1 second (FEV₁) of less than 60%, an increase in FEV₁ of less than 10% with bronchodilators, and an FEV₁/forced vital capacity ratio of 0.7 or less. The average age of the 6,112 participants was 65 years, 75% were men, and 43% were current smokers. They were randomized (allocation concealed) to receive either salmeterol (50 mcg), fluticasone (500 mcg), both, or placebo, inhaled twice a day. Analysis was by intention to treat, and patients were followed for 3 years. The primary outcome of death by any cause was adjudicated by researchers unaware of treatment assignment. After 3 years, 16.0% in the fluticasone group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 12.6% in the salmeterol plus fluticasone group had died. There was a trend toward reduced mortality with the combination compared with placebo (hazard ratio [HR] = .825; 95% CI, .68-1.002) but no difference between each agent individually and placebo. Patients receiving the combination had a lower mortality rate than those taking fluticasone alone (HR = .77; .64-.93). Exacerbations of COPD were less frequent with the combination therapy than with placebo (0.85 vs 1.13 per year; P < .001). However, the risk of pneumonia was higher in the combination therapy group (19.6% vs 12.3%; 10-21).

Calverley PM, Anderson JA, Celli B, et al; TORCH investigators. Salmeterol and fluticasone and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775-789.

Three features distinguish PID from appendicitis

Clinical question What clinical variables help distinguish pelvic inflammatory disease (PID) from acute appendicitis in women?

Bottom line In this poorly described study, a clinical decision rule consisting of three variables helped distinguish appendicitis from PID in women of childbearing age: no pain migration, bilateral tenderness, and no nausea and vomiting. This rule needs to be validated. (Level of evidence = 3b)

Synopsis The authors retrospectively assessed the medical records of 181 consecutive women aged 12 to 58 years presenting to the emergency department for the evaluation of acute abdominal pain. The final diagnosis of appendicitis was determined by histopathologic findings. PID was established using the CDC’s minimum criteria: lower abdominal tenderness, adnexal tenderness, and cervical motion tenderness. Three clinical factors were more likely to be associated with a low risk of appendicitis: no pain migration, bilateral tenderness, no nausea and vomiting. Combining these into a prediction model was 99% sensitive (95% CI, 94.4-99.9) for ruling out appendicitis, but only 33.9% specific (23.1-46.6). The positive likelihood ratio was 1.5 (1.25-1.80), and the negative likelihood ratio was 0.03 (.004-.22). This means the clinical criteria were very good at ruling out appendicitis but not good at ruling it in.

Morishita K, Gushimiyagi M, Hashiguchi M, et al. Clinical prediction rule to distinguish pelvic inflammatory disease from acute appendicitis in women of childbearing age. Am J Emerg Med. 2007;25(2):152-157.

H pylori treatment is effective in PPI users

Clinical question Can eradication of Helicobacter pylori decrease symptoms and proton pump inhibitor (PPI) use in long-term users?

Bottom line Identification and eradication of H pylori in long-term users of PPIs results in a small decrease in their use of PPIs over the following year and fewer return office visits. Dyspepsia symptoms were decreased; reflux symptoms were not. (Level of evidence = 1b)

Synopsis The investigators evaluated patients who used PPIs for at least 12 months. The patients stopped their PPI use for 2 weeks and underwent evaluation for H pylori status; 28% were positive. These 184 patients were randomly assigned, using concealed allocation, to receive placebo or 1-week triple therapy for H pylori eradication. PPI use and office visits were monitored for 12 months, and dyspepsia and reflux symptoms were measured after 12 months. H pylori was eradicated in 94% of patients. PPI prescriptions were reduced in the treated patients from 9.2 to 7.4 prescriptions, whereas prescription rates remained the same in the placebo-treated patients. On average, treated patients had one fewer visit over the year than untreated patients.

Raghunath AS, Hungin AP, Mason J, Jackson W. Helicobacter pylori eradication in long-term proton pump inhibitor users in primary care: a randomized trial. Aliment Pharmacol Ther. 2007;25(5):585-592.

Optimal dosing for thromboprophylaxis in medical inpatients

Clinical question What is the optimal dosing regimen for thromboprophylaxis in hospitalized medical patients?

Bottom line Until a direct comparison study is performed, the best information available suggests that although 3-times-daily dosing of 5,000 units unfractionated heparin (UH) is more effective then twice-daily dosing (approximately 1 fewer pulmonary embolism [PE] and 2 fewer deep vein thromboses [DVTs] per 1,000 patient days), it is associated with more major bleeds (1 per 2,500 patient days). Remember that both regimens are better than doing nothing for high-risk hospitalized medical patients. (Level of evidence = 1a–)

Synopsis Guidelines now recommend thromboprophylaxis with low-dose UH or low-molecular-weight heparin in acutely ill medical inpatients, especially those with heart failure, respiratory disease, who are confined to bed, or who have a previous history of DVT or PE. Some studies have used 5,000 units UH subcutaneously given twice a day, while others have given the same dose three times a day; the two different dosing frequencies have never been directly compared. The authors of this meta-analysis carefully searched the literature for all studies of UH prophylaxis with adequate verification of DVT or PE and performed in a nonsurgical population. They identified a total of 447 articles, of which 435 were excluded, mostly because they had studied a surgical or postoperative population. The mean ages of the enrolled patients in the remaining 12 studies ranged from 58 years to 75 years. Nine of the studies had between 38 patients and 223 patients; the remaining 3 studies had 482, 726, and 5,776 patients, respectively. Most of the patients in these studies were at moderate- to high-risk for DVT or PE. A total of 1,664 patients received 3-times-daily dosing and 6,314 received twice-daily dosing in the 12 studies. The authors found no significant difference between the groups regarding the rate of DVT (5.4 for twice daily vs 3.0 for three times per day per 1,000 patient-days; P = .42), but a trend toward fewer PEs in the three-times-daily dosing group (1.5 vs 0.5 per 1,000 patient-days; P = .09). Bleeding complications were more common in the three times per day group (0.73 vs 0.33 per 1,000 patient-days; P < .001; number needed to treat to harm = 250). The largest study, accounting for more than 90% of patients receiving twice-daily dosing, had no placebo group, did not clearly describe randomization, was not blinded, and used autopsy to confirm the diagnoses of DVT and PE. It therefore reported much lower rates of these outcomes than the other studies. When this study is excluded, the difference between twice-daily and three-times-daily groups regarding the number of venous thromboembolic events increased and became statistically significant, but the differences in bleeding rates lost statistical significance.

King CS, Holley AB, Jackson JL, et al. Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: a meta-analysis. Chest. 2007;131(2):507-516.

Diet, exercise, drugs may prevent diabetes in high-risk patients

Clinical question Can the onset of diabetes be delayed or prevented in people with impaired glucose tolerance?

Bottom line Diet, exercise, or diet and exercise changes, at least those in study situations, will slow the progression of diabetes by approximately 50% in patients with impaired glucose tolerance. Drug therapy with either oral diabetes drugs or the weight-loss drug orlistat will also slow progression. The preventive effect of the drugs is not maintained when they are stopped, and research has not been conducted for long enough to determine whether diabetes onset is prevented or just delayed. (Level of evidence = 1a)

Synopsis To answer this question, researchers completed a thorough search of 4 databases, contacted experts, and checked references of identified studies. They included only randomized controlled trials—most were not blinded—that evaluated medicine or lifestyle changes to prevent the onset of type 2 diabetes in patients with impaired glucose tolerance. They included research in all languages. Two authors independently assessed the validity of and abstracted data from the studies, excluding six studies not considered appropriately randomized and three studies for which they could not obtain additional data from the investigators. Since not all data were reported in the same way in all of the studies, the authors had to estimate some data. However, they used the more conservative random effect model when combining the data. The authors included 17 studies of 8,084 patients in their analysis, including two studies conducted in Japan and three done in China. Most of the studies were several years in length. The baseline risk of diabetes in the studies was 37% over 5 years. Overall, the interventions decreased the onset of frank diabetes by approximately half (hazard ratio [HR] = .51; 95% CI, .44-.60). Diet changes, exercise, or a combination produced a similar reduction in risk (HR = ~.50). Two types of drug therapy were used. The oral diabetes drugs acarbose, glipizide, metformin, or the biguanide flumamine decreased the onset of diabetes by 30% (HR = .7; .62-.79). The anti-obesity drug orlistat also decreased the likelihood by a similar amount (HR = .44; .28-.69). Using rough estimates, the number needed to treat to prevent one patient from developing diabetes would be in the range of 5 to 10 for lifestyle changes or drug treatment. Although less well studied, it seems that the rate of diabetes returns to baseline once drug therapy is stopped, and no studies have been conducted for long enough to determine whether diabetes is truly prevented or simply delayed.

Gillies CL, Abrams KR, Lambert PC, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007;334(7588):299.

Surgery is better treatment for first-time anterior shoulder dislocation

Clinical question Should patients with a first-time anterior shoulder dislocation and injuries to the capsule or labrum receive surgical repair or conservative therapy?

Bottom line In this study, primary open surgical repair in patients aged 15 to 39 years after a first-time traumatic anterior shoulder dislocation results in fewer subsequent dislocations, decreased instability, and improved patient satisfaction. This represents a major change in the current standard of care of conservative therapy for first dislocations and surgery for recurrent dislocations only. (Level of evidence = 1b–)

Synopsis Appropriate treatment following first-time anterior shoulder dislocation remains an area of controversy. Currently, most patients receive conservative therapy, with surgical repair reserved for subsequent dislocations. These investigators enrolled 80 consecutive patients presenting to the emergency department with traumatic anterior shoulder dislocation. Patients were aged 15 to 39 years and had no history of previous shoulder injury. After initial reduction, patients underwent arthroscopy within 1 week. A total of 76 patients (93.5%) with confirmed capsular and/or labral injury randomly received (uncertain allocation concealment) either open surgical repair or conservative therapy (immobilization in a fixed sling for 2 days, followed by a nonfixed sling for 1 week). Both groups received similar rehabilitation. Complete follow-up occurred for 98% of patients for 10 years. Blinding of outcome assessors to group assignment is uncertain, but primary outcomes (recurrent dislocation and patient-reported satisfaction) were unlikely to be affected. Using intention-to-treat analysis, recurrent dislocation within 10 years was significantly less likely with primary surgical repair than with conservative treatment (9% vs 62%; number needed to treat = 2; 95% CI, 1-3). Overall, 72% of patients in the surgical group reported good or excellent results, while 74% of patients in the control group reported unsatisfactory results. No significant complications were seen in the surgical group. It remains to be seen whether primary surgical repair will result in a similar benefit in populations at a higher risk of surgical complications, such as elderly and inactive patients with a lower baseline rate of redislocation.

Jakobsen BW, Johannsen HV, Suder P, Sojbjerg JO. Primary repair versus conservative treatment of first-time traumatic anterior dislocation of the shoulder: a randomized study with 10-year follow-up. Arthroscopy. 2007;23(2):118-123.

Levels of evidence in Bottom line are explained at www.infopoems.com/levels.html.