Randomized Clinical Trials

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Content published since 1 January 2007

Most Recent (5 articles)

A Computerized Handheld Decision-Support System to Improve Pulmonary Embolism Diagnosis (2009)

Roy P, Durieux P, Gillaizeau F, et al.

Roy and colleagues developed a program to guide diagnosis of pulmonary embolism for use on a mobile, handheld device. The investigators randomly assigned 20 emergency departments in France to activation of either the decision-support system on the devices or posters and pocket cards that showed diagnostic strategies. The device-based program improved appropriate testing of patients with suspected pulmonary embolism more than paper guidelines alone.

Two Self-management Interventions to Improve Hypertension Control (2009)

Bosworth HB, Olsen MK, Grubber JM, et al.

In this trial, 636 patients with hypertension were randomly assigned to receive usual care; a telephone-delivered, nurse-administered behavioral self-management intervention; home blood pressure self-monitoring; or both of the latter 2 interventions. Compared with usual care, the adjusted improvement in the proportion of patients with blood pressure control at 24 months was 4.3% for the behavioral intervention group, 7.6% for the blood pressure monitoring group, and 11.0% for the combined intervention group. The combined intervention improved blood pressure control and systolic and diastolic blood pressures more than usual care.

Effects of a Short Course of Eszopiclone on Continuous Positive Airway Pressure Adherence (2009)

Lettieri CJ, Shah AA, Holley AB, et al.

Lettieri and coworkers assessed whether a short course of eszopiclone therapy improves long-term adherence to continuous positive airway pressure (CPAP). They randomly assigned 160 adults with severe obstructive sleep apnea to eszopiclone or placebo for the first 14 nights of CPAP, and measured patients' adherence to CPAP weekly for 24 weeks. Patients receiving eszopiclone were less likely to discontinue CPAP and also used CPAP more nights and longer per night than did patients receiving placebo.

Community-Based Interventions to Promote Blood Pressure Control in a Developing Country (2009)

Jafar TH, Hatcher J, Poulter N, et al.

Jafar and colleagues assessed the effectiveness of community-based interventions on blood pressure in 1341 hypertensive adults in Karachi, Pakistan. Participants received home health education (HHE) every 3 months from lay health workers, with or without care from general practitioners (GPs) specially trained in hypertension management, or no intervention. Patients who received HHE plus GP care had greater decreases in systolic blood pressure (10.8 mm Hg vs. 5.8 mm Hg in the other 3 groups).

Effect of Fluticasone With and Without Salmeterol on Pulmonary Outcomes in Chronic Obstructive Pulmonary Disease (2009)

Lapperre TS, Snoeck-Stroband JB, Gosman MM, et al.

Inhaled corticosteroids and long-acting β2-agonists improve chronic obstructive pulmonary disease (COPD) symptoms, but their effects on lung function and inflammation are uncertain. Lapperre and colleagues compared treatment with fluticasone for 6 months or 30 months, fluticasone and salmeterol for 30 months, or placebo in 114 steroid-naive patients who had moderate to severe COPD. They found reduced inflammatory cells in sputum and bronchial biopsies and an attenuated decrease in lung function during fluticasone treatment. Adding salmeterol did not further alter the decrease in lung function.

Allergy and Immunology (3 articles)

Internet-Based Self-management Plus Education Compared With Usual Care in Asthma (2009)

van der Meer V, Bakker MJ, van den Hout WB, et al.

This randomized trial compared Internet-based asthma self-management with usual care in 200 adults with asthma. van der Meer and colleagues found modest improvements in asthma control and lung function with the Internet intervention but no reduction in exacerbations and changes in asthma-related quality of life that were less than clinically significant at 12 months. Although Internet-based self-management improved some asthma outcome measures, the improvements were small, and the program did not affect the number of exacerbations.

Pulse Versus Daily Oral Cyclophosphamide for Induction of Remission in Antineutrophil Cytoplasmic Antibody—Associated Vasculitis (2009)

de Groot K, Harper L, Jayne DR, et al.

Toxicity limits the use of cyclophosphamide for anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis. In this comparison of pulse versus daily oral cyclophosphamide regimens, equal proportions of patients had remissions, but the pulse regimen seemed safer, mainly because of fewer cases of leukopenia. However, patients and providers were not blinded, and the study did not measure differences in relapse rate. Pulse and daily oral cyclophosphamide treatment seem to be equally efficacious for ANCA–associated vasculitis, but pulse therapy may be safer.

Infliximab for Maintenance of Glucocorticosteroid-Induced Remission of Giant Cell Arteritis (2007)

Hoffman GS, Cid MC, Rendt-Zagar KE, et al.

Steroid-sparing treatment would be valuable in giant cell arteritis (GCA) because most patients experience complications of glucocorticoid therapy. Case reports suggest that infliximab might be effective. Hoffman and colleagues randomly assigned 44 patients with GCA in glucocorticoid-induced remission to receive infliximab or placebo at 0, 2, and 6 weeks and every 8 weeks thereafter. Infliximab did not reduce rates of relapse or any secondary end point and is therefore unlikely to be useful in GCA.

Cardiovascular Illness (13 articles)

A Computerized Handheld Decision-Support System to Improve Pulmonary Embolism Diagnosis (2009)

Roy P, Durieux P, Gillaizeau F, et al.

Roy and colleagues developed a program to guide diagnosis of pulmonary embolism for use on a mobile, handheld device. The investigators randomly assigned 20 emergency departments in France to activation of either the decision-support system on the devices or posters and pocket cards that showed diagnostic strategies. The device-based program improved appropriate testing of patients with suspected pulmonary embolism more than paper guidelines alone.

Two Self-management Interventions to Improve Hypertension Control (2009)

Bosworth HB, Olsen MK, Grubber JM, et al.

In this trial, 636 patients with hypertension were randomly assigned to receive usual care; a telephone-delivered, nurse-administered behavioral self-management intervention; home blood pressure self-monitoring; or both of the latter 2 interventions. Compared with usual care, the adjusted improvement in the proportion of patients with blood pressure control at 24 months was 4.3% for the behavioral intervention group, 7.6% for the blood pressure monitoring group, and 11.0% for the combined intervention group. The combined intervention improved blood pressure control and systolic and diastolic blood pressures more than usual care.

Community-Based Interventions to Promote Blood Pressure Control in a Developing Country (2009)

Jafar TH, Hatcher J, Poulter N, et al.

Jafar and colleagues assessed the effectiveness of community-based interventions on blood pressure in 1341 hypertensive adults in Karachi, Pakistan. Participants received home health education (HHE) every 3 months from lay health workers, with or without care from general practitioners (GPs) specially trained in hypertension management, or no intervention. Patients who received HHE plus GP care had greater decreases in systolic blood pressure (10.8 mm Hg vs. 5.8 mm Hg in the other 3 groups).

Effect of Telmisartan on Renal Outcomes (2009)

Mann JF, Schmieder RE, Dyal L, et al.

Mann and colleagues compared the long-term renal effects of telmisartan and placebo in 5927 adults with vascular disease but without macroalbuminuria. They used a composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. Patients receiving telmisartan had the same composite outcome results as those receiving placebo. Albuminuria increased less with telmisartan than with placebo, whereas estimated GFR decreased more with telmisartan. On balance, telmisartan had the same effects as placebo on major renal outcomes.

Red Yeast Rice for Dyslipidemia in Statin-Intolerant Patients (2009)

Becker DJ, Gordon RY, Halbert SC, et al.

Red yeast rice is a dietary supplement that can decrease low-density lipoprotein (LDL) cholesterol levels and could be a treatment option for patients with statin-associated myopathy. Investigators randomly assigned 62 patients with dyslipidemia and a history of intolerance to at least 1 statin to receive red yeast rice, 1800 mg twice daily, or placebo. After 12 and 24 weeks, LDL and total cholesterol levels improved more in the red yeast rice group than in the placebo group. Pain, creatinine phosphokinase, and liver enzyme levels did not differ between the groups.

Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients With Deep Venous Thrombosis (2009)

Prandoni P, Prins MH, Lensing AW, et al.

Prandoni and colleagues randomly assigned 538 patients with proximal deep venous thrombosis (DVT) who had completed 3 months of anticoagulation to receive anticoagulation for a fixed duration or for a flexible duration that depended on results of ultrasonography. During follow-up, 17% versus 12% of the fixed-duration therapy and ultrasonography-guided groups, respectively, had recurrent thromboembolism, whereas 0.7% versus 1.5% had major bleeding events. Individualizing the duration of anticoagulation therapy for DVT may reduce the rate of recurrent venous thromboembolism (VTE).

Using a Drug Facts Box to Communicate Drug Benefits and Harms Two Randomized Trials (2009)

Schwartz LM, Woloshin S, Welch HG

Direct-to-consumer drug advertisements do not provide standardized information about the benefits and harms of the drugs. Schwartz and coworkers tested whether adding a “drug facts box” to consumer-directed drug advertisements would improve consumer knowledge and judgment. The box contained a comparison of outcomes that might occur with 2 drugs. In a randomized experiment, consumers who were shown advertisements that included the box knew more about drug benefits and side effects than consumers shown the advertisements without the box.

B-Type Natriuretic Peptide Testing, Clinical Outcomes, and Health Services Use in Emergency Department Patients With Dyspnea (2009)

Schneider H, Lam L, Lokuge A, et al.

B-type natriuretic peptide (BNP) testing is commonly used to distinguish cardiac from noncardiac causes of dyspnea. In this randomized trial, BNP testing did not reduce health services utilization or improve health outcomes for dyspneic patients who visited emergency departments. Measuring BNP in all dyspneic patients to see whether heart failure is a cause of their symptoms may not be justified.

Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin (2009)

Crowther MA, Ageno W, Garcia D, et al.

Crowther and colleagues measured the effect of oral vitamin K or placebo on prevention of bleeding in 724 patients with international normalized ratios (INRs) of 4.5 to 10.0 who were receiving warfarin. They found that 15.8% of vitamin K recipients and 16.3% of placebo recipients had at least 1 bleeding complication; 2.5% and 1.1%, respectively, had major bleeding events; and 1.1% and 0.8% experienced thromboembolism. Low-dose oral vitamin K lowered the INR but did not reduce bleeding in overanticoagulated patients.

Low-Molecular-Weight Heparin versus Compression Stockings for Thromboprophylaxis after Knee Arthroscopy (2008)

Camporese G, Bernardi E, Prandoni P, et al.

In this trial, 1761 adults who had knee arthroscopy were randomly assigned to receive 7 or 14 days of low-molecular-weight heparin (LMWH) or to wear a full-length graduated compression stocking on the operated leg for 1 week. Fewer than 1% of the patients in any group had significant postsurgical bleeding complications. Fewer patients in the 7-day LMWH group experienced a composite outcome of deep venous thrombosis, pulmonary embolism, or death.

Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism (2007)

Glynn RJ, Ridker PM, Goldhaber SZ, et al.

Short-term aspirin therapy can lower the risk for venous thromboembolism (VTE) in high-risk patients, but whether long-term, low-dose aspirin therapy reduces risk in healthy adults is uncertain. In a secondary analysis of the Women's Health Study, Glynn and colleagues measured VTE rates in 39 876 female health professionals who were randomly assigned to low-dose aspirin or placebo for 10 years. Low-dose aspirin did not affect overall VTE rates or those in women with increased rates because of inherited thrombophilia.

Different Ways to Describe the Benefits of Risk-Reducing Treatments (2007)

Halvorsen PA, Selmer R, Kristiansen IS

Patients respond differently when given equivalent but different descriptions of the outcomes of a treatment. Halvorsen and colleagues randomly assigned 1754 healthy people to receive 1 of 3 surveys with equal but different descriptions of the outcome of a hypothetical drug to prevent either myocardial infarction (MI) or hip fracture. Respondents consented to treatment more frequently when the outcome was described as the number of people who needed to take the drug for 5 years to prevent 1 MI or hip fracture. They consented less frequently when the description said that the treatment delayed the outcome.

Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism (2007)

Ray JG, Kearon C, Yi Q, et al.

In observational studies, elevated plasma homocysteine levels were associated with venous thromboembolism. Ray and colleagues investigated the effect of homocysteine lowering on venous thromboembolism in a multicenter trial of folic acid and B vitamins to reduce cardiovascular events. Five years of therapy with folic acid and vitamins B6 and B12 decreased homocysteine levels compared with placebo, but the incidence of venous thromboembolism was the same in both groups, even in participants with the highest levels of homocysteine.

Endocrinology, Diabetes, and Metabolism (19 articles)

Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients With Newly Diagnosed Type 2 Diabetes (2009)

Esposito K, Maiorino MI, Ciotola M, et al.

Esposito and associates compared the effects of low-carbohydrate, Mediterranean-style and low-fat, calorie-restricted diets on the need for antihyperglycemic drug therapy in 215 overweight patients with newly diagnosed type 2 diabetes. After 4 years, 44% of the Mediterranean-style diet group and 70% of the low-fat diet group required treatment of diabetes, and the Mediterranean-style diet group lost more weight and experienced greater improvements in some glycemic control and coronary risk measures.

Effect of Telmisartan on Renal Outcomes (2009)

Mann JF, Schmieder RE, Dyal L, et al.

Mann and colleagues compared the long-term renal effects of telmisartan and placebo in 5927 adults with vascular disease but without macroalbuminuria. They used a composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. Patients receiving telmisartan had the same composite outcome results as those receiving placebo. Albuminuria increased less with telmisartan than with placebo, whereas estimated GFR decreased more with telmisartan. On balance, telmisartan had the same effects as placebo on major renal outcomes.

Effect of Candesartan on Microalbuminuria and Albumin Excretion Rate in Diabetes (2009)

Bilous R, Chaturvedi N, Sjølie AK, et al.

Bilous and associates compared the renal effects of the angiotensin-receptor blocker candesartan and placebo in a large sample of normoalbuminuric patients with type 1 and type 2 diabetes. The main outcomes were microalbuminuria incidence and rate of change in albuminuria. Candesartan had little effect on the incidence of microalbuminuria; the annual rate of change in albuminuria was 5.53% lower with candesartan than with placebo. Candesartan did not prevent microalbuminuria in mainly normotensive patients with type 1 or type 2 diabetes.

Effects of Calcium Supplementation on Body Weight and Adiposity in Overweight and Obese Adults (2009)

Yanovski JA, Parikh SJ, Yanoff LB, et al.

Some data suggest that body weight is inversely associated with calcium intake. Yanovski and colleagues tested whether supplemental calcium might prevent weight gain among 340 overweight and obese patients randomly assigned to receive supplemental calcium, 1500 mg/d, or placebo. They found no differences in body weight, body mass index, or body fat mass between the groups after 2 years. They conclude that calcium supplementation is unlikely to prevent weight gain in persons who are overweight or obese.

Red Yeast Rice for Dyslipidemia in Statin-Intolerant Patients (2009)

Becker DJ, Gordon RY, Halbert SC, et al.

Red yeast rice is a dietary supplement that can decrease low-density lipoprotein (LDL) cholesterol levels and could be a treatment option for patients with statin-associated myopathy. Investigators randomly assigned 62 patients with dyslipidemia and a history of intolerance to at least 1 statin to receive red yeast rice, 1800 mg twice daily, or placebo. After 12 and 24 weeks, LDL and total cholesterol levels improved more in the red yeast rice group than in the placebo group. Pain, creatinine phosphokinase, and liver enzyme levels did not differ between the groups.

Short-Term Hormone Therapy Suspension and Mammography Recall (2009)

Buist DS, Anderson ML, Reed SD, et al.

Women screened for breast cancer are often recalled for additional testing when mammography findings are unclear. This randomized trial in middle-age and older women found that briefly stopping hormone therapy reduced breast density slightly but did not decrease mammography recall rates. Recall rates after screening mammograms were 12.3% (stopping for 1 month), 9.8% (stopping for 2 months), and 11.3% (continuing to take hormone therapy). Menopausal symptoms increased in the groups that stopped therapy.

Using a Drug Facts Box to Communicate Drug Benefits and Harms Two Randomized Trials (2009)

Schwartz LM, Woloshin S, Welch HG

Direct-to-consumer drug advertisements do not provide standardized information about the benefits and harms of the drugs. Schwartz and coworkers tested whether adding a “drug facts box” to consumer-directed drug advertisements would improve consumer knowledge and judgment. The box contained a comparison of outcomes that might occur with 2 drugs. In a randomized experiment, consumers who were shown advertisements that included the box knew more about drug benefits and side effects than consumers shown the advertisements without the box.

Comparison of Methods for Delivering a Lifestyle Modification Program for Obese Patients (2009)

Digenio AG, Mancuso JP, Gerber RA, et al.

Obese people have difficulty changing their lifestyle to eat less. In their randomized trial, Digenio and coworkers compared 5 ways of providing support for lifestyle modification in obese patients who were taking sibutramine, an antiobesity drug. They found that high-frequency telephone contact with a dietitian led to the same weight loss as in-person contact and more weight loss than low-frequency contact, e-mail contact, or no contact. Telephone contacts with dietitians may be a more efficient way to help obese patients lose weight.

Motivational Enhancement Therapy with and without Cognitive Behavior Therapy to Treat Type 1 Diabetes (2008)

Ismail K, Thomas SM, Maissi E, et al.

Psychological issues can interfere with management of type 1 diabetes. Ismail and colleagues examined whether psychological therapy might improve diabetes control. They compared motivational enhancement therapy with and without cognitive behavior therapy with usual care in 344 adults with type 1 diabetes (average baseline hemoglobin A1c level, 9.4%). Motivational enhancement therapy plus cognitive behavior therapy achieved a greater decrease in hemoglobin A1c over 12 months than did usual care (difference between groups, 0.46%). No other improvements were observed.

Addition of Neutral Protamine Lispro Insulin or Insulin Glargine to Oral Type 2 Diabetes Regimens for Patients with Suboptimal Glycemic Control (2008)

Esposito K, Ciotola M, Maiorino MI, et al.

Many patients with type 2 diabetes that is poorly controlled with oral agents take bedtime insulin. In 2 previous trials, neutral protamine lispro (NPL) insulin achieved better glycemic control than neutral protamine Hagedorn insulin. Esposito and associates randomly assigned patients with poor control of type 2 diabetes taking oral medications to receive either bedtime insulin glargine or NPL insulin. Over 36 weeks, the 2 groups had similar glycemic control and rates of hypoglycemic events.

Safety and Efficacy of a Testosterone Metered-Dose Transdermal Spray for Treating Decreased Sexual Satisfaction in Premenopausal Women (2008)

Davis S, Papalia M, Norman RJ, et al.

Davis and colleagues evaluated the effects of 3 doses of exogenous testosterone and placebo, all administered with a metered-dose transdermal spray, on sexual function. They randomly assigned 261 premenopausal women who reported a decrease in satisfying sexual activity and had a morning serum free testosterone level less than 3.8 pmol/L (<1.1 pg/mL). After 16 weeks, the daily 90-µL dose of transdermal testosterone improved self-reported sexual satisfaction by a mean of 0.8 satisfactory sexual event per month. The rate with higher and lower testosterone doses did not differ from the rate with placebo.

Effects of Aerobic Training, Resistance Training, or Both on Glycemic Control in Type 2 Diabetes (2007)

Sigal RJ, Kenny GP, Boulé NG, et al.

Aerobic or resistance exercise improves glycemic control in type 2 diabetes, but no studies show whether combined aerobic and resistance training have similar effects. Sigal and colleagues randomly assigned 251 adults with type 2 diabetes to aerobic training, resistance training, combined training, or a sedentary control group. They found better reduction in hemoglobin A1c values in patients in the combined training program than in patients in the aerobic training or resistance training programs. The sedentary control group had worse glucose control than the aerobic or resistance training groups, and adverse events were more common in the exercise groups.

Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes (2007)

Stranges S, Marshall JR, Natarajan R, et al.

Many people supplement their dietary intake with selenium. To evaluate the safety of this practice, Stranges and colleagues examined the incidence of type 2 diabetes in participants in a large randomized trial designed to assess the effect of selenium supplementation on cancer incidence. During 7.7 years of taking the supplements or placebo, participants assigned to selenium supplementation were more likely to develop type 2 diabetes than were participants assigned to placebo. Diabetes, however, was self-reported and was a secondary end point in the parent trial.

Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women (2007)

Marini H, Minutoli L, Polito F, et al.

Studies suggest that isoflavone phytoestrogens, which are found in soy products, reduce bone loss in women, but the evidence is not definitive. Marini and colleagues compared the phytoestrogen genistein with placebo in 389 osteopenic postmenopausal women. At 24 months, women who took genistein had a greater increase in bone mineral density than did those who took placebo. Genistein improved markers of bone metabolism. It did not increase endometrial thickness, but it did cause gastrointestinal side effects.

The Effect of Adding Exenatide to a Thiazolidinedione in Suboptimally Controlled Type 2 Diabetes (2007)

Zinman B, Hoogwerf BJ, Durán García S, et al.

Clinical trials have measured the effect of adding exenatide to several oral hypoglycemic drugs in patients with poorly controlled type 2 diabetes. As yet, no one has studied the addition of exenatide to thiazolidinediones (TZDs). The investigators randomly assigned 233 adults with type 2 diabetes that was not controlled with TZDs (with or without metformin) to twice-daily mealtime injections of exenatide or placebo. At 16 weeks, exenatide reduced hemoglobin A1c levels, fasting glucose levels, and body weight more than placebo. Nausea and vomiting were more common in the exenatide group.

Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer (2007)

Greenspan SL, Nelson JB, Trump DL, et al.

Androgen deprivation therapy (ADT) for prostate cancer increases risk for bone loss and fractures. The researchers randomly assigned patients with prostate cancer receiving ADT to alendronate or placebo. At baseline, 39% of men had osteoporosis and 52% had low bone mass. During the first year, alendronate increased bone mineral density by 3.7% at the spine and 1.6% at the femoral neck and increased bone turnover. The groups had the same rates of adverse events.

Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis (2007)

Greenspan SL, Bone HG, Ettinger MP, et al.

To determine the safety of parathyroid hormone (PTH) and its effect on the incidence of vertebral fractures in postmenopausal women with osteoporosis, the authors randomly assigned 2532 postmenopausal women with osteoporosis to receive PTH or placebo. Parathyroid hormone decreased new vertebral fractures. However, the amount of reduction in risk is uncertain because one third of participants prematurely withdrew from the trial. Adverse effects included hypercalciuria, hypercalcemia, and nausea.

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery (2007)

Gandhi GY, Nuttall GA, Abel MD, et al.

To determine whether rigorous intraoperative glycemic control reduces death and morbidity in cardiac surgery patients, the authors randomly assigned 400 cardiac surgical patients to tight glycemic control during surgery or to usual intraoperative care. All patients received tight glycemic control in the cardiac intensive care unit. The groups had the same rate of perioperative adverse events. However, the intensive treatment group had more strokes (8 vs. 1 in the control treatment group) and more deaths (4 vs. 0 in the control treatment group). Tight intraoperative control of blood glucose offered no advantage and may cause harm.

Agalsidase-Beta Therapy for Advanced Fabry Disease (2007)

Banikazemi M, Bultas J, Waldek S, et al.

Fabry disease is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. In this double-blind multicenter trial, 82 adults with kidney dysfunction from Fabry disease were randomly assigned to bimonthly infusions of enzyme replacement with agalsidase beta or placebo for up to 35 months. Agalsidase beta reduced the frequency of and time to renal, cardiac, and cerebrovascular events and death and caused infusion reactions more often than placebo.

Gastroenterology and Hepatology (8 articles)

Using a Drug Facts Box to Communicate Drug Benefits and Harms Two Randomized Trials (2009)

Schwartz LM, Woloshin S, Welch HG

Direct-to-consumer drug advertisements do not provide standardized information about the benefits and harms of the drugs. Schwartz and coworkers tested whether adding a “drug facts box” to consumer-directed drug advertisements would improve consumer knowledge and judgment. The box contained a comparison of outcomes that might occur with 2 drugs. In a randomized experiment, consumers who were shown advertisements that included the box knew more about drug benefits and side effects than consumers shown the advertisements without the box.

Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon-α2b (2009)

Jensen DM, Marcellin P, Freilich B, et al.

Some patients with chronic hepatitis C do not respond to initial treatment with pegylated interferon plus ribavirin. This randomized trial compared peginterferon-α2a plus ribavirin for either 48 or 72 weeks in 950 patients with hepatitis C who had not responded to peginterferon-α2b plus ribavirin. Re-treatment for 72 weeks increased sustained virologic response rates more than re-treatment for 48 weeks (16% vs. 8%), although the rates were low.

Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding (2009)

Sung JJ, Barkun A, Kuipers EJ, et al.

Most studies of high-dose proton-pump inhibitors after endoscopic treatment of peptic bleeding ulcers have included largely Asian study populations. This multicenter trial included 764 adults from largely Western countries who had a single high-risk bleeding gastric or duodenal ulcer. All patients had successful endoscopic hemostasis and were randomly assigned to receive intravenous high-dose esomeprazole or matching placebo for 72 hours. Fewer esomeprazole recipients than placebo recipients experienced recurrent bleeding (5.9% vs. 10.3%) or needed endoscopic re-treatment (6.4% vs. 11.6%).

Immediate Listing for Liver Transplantation Versus Standard Care for Child–Pugh Stage B Alcoholic Cirrhosis (2009)

Vanlemmens C, Di Martino V, Milan C, et al.

Some have proposed that transplantation in the earlier stages of chronic liver disease would improve outcomes. The authors randomly assigned patients with Child–Pugh stage B alcoholic cirrhosis to immediate listing for transplantation or to standard care; 68% and 25%, respectively, received a liver transplant. Patients assigned to immediate listing had no survival benefit and more cases of extrahepatic cancer than patients in the standard care group who received an early transplant. The results support the current policy of giving the highest priority to the sickest patients.

Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis with Telbivudine or Adefovir (2007)

Chan HL, Heathcote EJ, Marcellin P, et al.

The best way to suppress viral replication in chronic hepatitis B remains an open question. In this 52-week open-label trial, 135 adults with hepatitis B e antigen–positive chronic hepatitis were randomly assigned to telbuvidine or adefovir for 52 weeks, or adefovir for 24 weeks followed by telbivudine for 28 weeks. At 52 weeks, the reduction in viral load was similar in the telbivudine-only and adefovir-to- telbivudine groups and greater than that in the adefovir-only group.

Phosphatidylcholine for Steroid-Refractory Chronic Ulcerative Colitis (2007)

Stremmel W, Ehehalt R, Autschbach F, et al.

In patients with chronic active ulcerative colitis, clinicians have few options when immunosuppressant drugs fail or cause intolerable side effects. Stremmel and associates randomly assigned 60 adults who had steroid-refractory chronic ulcerative colitis with continued symptoms or intolerable side effects during immunosuppressant drug therapy to receive phosphatidylcholine or placebo for 12 weeks. More phosphatidylcholine recipients than placebo recipients improved and could stop receiving corticosteroids. Bloating was more common with phosphatidylcholine than placebo.

Adalimumab Induction Therapy for Crohn Disease Previously Treated with Infliximab (2007)

Sandborn WJ, Rutgeerts P, Enns R, et al.

Patients with Crohn disease often respond to infliximab initially but then become intolerant or unresponsive to it. Sandborn and colleagues randomly assigned 325 patients with Crohn disease who were intolerant of or unresponsive to infliximab to receive adalimumab (another tumor necrosis factor antagonist) or placebo. After 4 weeks, adalimumab induced more remissions than did placebo (21% vs. 7%). The study did not address long-term maintenance of response or the immunogenicity of adalimumab.

Sequential Therapy versus Standard Triple-Drug Therapy for Helicobacter pylori Eradication (2007)

Vaira D, Zullo A, Vakil N, et al.

Eradication rates of Helicobacter pylori infection are decreasing worldwide because of increasing resistance to antimicrobials. In this double-blind trial, 300 adults with dyspepsia or peptic ulcers were randomly assigned to a 10-day sequential regimen (pantoprazole, amoxicillin, and placebo taken for 5 days followed by pantoprazole, clarithromycin, and tinidazole taken for 5 days) or standard 10-day therapy (pantoprazole, clarithromycin, and amoxicillin). The eradication rate was higher with the sequential regimen than with standard therapy, especially in patients with clarithromycin-resistant strains. The incidence of side effects did not differ between groups.

Hematology (1 articles)

Pulse Versus Daily Oral Cyclophosphamide for Induction of Remission in Antineutrophil Cytoplasmic Antibody—Associated Vasculitis (2009)

de Groot K, Harper L, Jayne DR, et al.

Toxicity limits the use of cyclophosphamide for anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis. In this comparison of pulse versus daily oral cyclophosphamide regimens, equal proportions of patients had remissions, but the pulse regimen seemed safer, mainly because of fewer cases of leukopenia. However, patients and providers were not blinded, and the study did not measure differences in relapse rate. Pulse and daily oral cyclophosphamide treatment seem to be equally efficacious for ANCA–associated vasculitis, but pulse therapy may be safer.

HIV Infection (2 articles)

Stepped-Dose Versus Full-Dose Efavirenz for HIV Infection and Neuropsychiatric Adverse Events (2009)

Gutiérrez-Valencia A, Viciana P, Palacios R, et al.

About one half of patients who take efavirenz develop disturbing neuropsychiatric side effects. This randomized trial involving 114 patients compared full-dose efavirenz with stepped-dose efavirenz during the first 2 weeks of treatment. Patients who received stepped-dose therapy had fewer side effects during the first week of treatment, and after 24 weeks, HIV RNA levels and CD4+ cell counts were similar in both groups.

Risk for Opportunistic Disease and Death after Reinitiating Continuous Antiretroviral Therapy in Patients with HIV Previously Receiving Episodic Therapy (2008)

The SMART Study Group

A previously published randomized, controlled trial showed that episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. In a continuation of this trial, the SMART Study Group measured the effect of reinitiating continuous antiretroviral therapy on the excess risk for opportunistic disease or death due to episodic treatment. Resumption of continuous therapy rapidly suppressed HIV RNA and reduced—but did not eliminate—the excess risk for opportunistic disease or death.

Infectious Disease (10 articles)

Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households (2009)

Cowling BJ, Chan K, Fang VJ, et al.

Few data are available on the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission. In this cluster randomized trial of 259 people with confirmed influenza virus infection and 794 household contacts, hand washing and facemasks seemed to prevent influenza virus transmission when healthy people started these measures within 36 hours of symptom onset in an infected family member. Although adherence to the interventions varied, these findings suggest that nonpharmaceutical interventions may help to mitigate pandemic and interpandemic influenza.

Stepped-Dose Versus Full-Dose Efavirenz for HIV Infection and Neuropsychiatric Adverse Events (2009)

Gutiérrez-Valencia A, Viciana P, Palacios R, et al.

About one half of patients who take efavirenz develop disturbing neuropsychiatric side effects. This randomized trial involving 114 patients compared full-dose efavirenz with stepped-dose efavirenz during the first 2 weeks of treatment. Patients who received stepped-dose therapy had fewer side effects during the first week of treatment, and after 24 weeks, HIV RNA levels and CD4+ cell counts were similar in both groups.

Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon-α2b (2009)

Jensen DM, Marcellin P, Freilich B, et al.

Some patients with chronic hepatitis C do not respond to initial treatment with pegylated interferon plus ribavirin. This randomized trial compared peginterferon-α2a plus ribavirin for either 48 or 72 weeks in 950 patients with hepatitis C who had not responded to peginterferon-α2b plus ribavirin. Re-treatment for 72 weeks increased sustained virologic response rates more than re-treatment for 48 weeks (16% vs. 8%), although the rates were low.

Adverse Events with 4 Months of Rifampin Therapy or 9 Months of Isoniazid Therapy for Latent Tuberculosis Infection (2008)

Menzies D, Long R, Trajman A, et al.

Nine-month isoniazid treatment of latent tuberculosis infection is hepatotoxic and is complicated by poor patient adherence. Menzies and colleagues compared the frequency of adverse events and treatment completion between 4-month rifampin therapy and 9-month isoniazid therapy among 847 patients randomly assigned to either treatment. Patients who took rifampin had fewer adverse events and were more likely to complete treatment. The investigators did not compare efficacy of the 2 treatments, so their data justify a larger trial to compare the efficacy of these 2 treatments for latent tuberculosis infection.

Risk for Opportunistic Disease and Death after Reinitiating Continuous Antiretroviral Therapy in Patients with HIV Previously Receiving Episodic Therapy (2008)

The SMART Study Group

A previously published randomized, controlled trial showed that episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. In a continuation of this trial, the SMART Study Group measured the effect of reinitiating continuous antiretroviral therapy on the excess risk for opportunistic disease or death due to episodic treatment. Resumption of continuous therapy rapidly suppressed HIV RNA and reduced—but did not eliminate—the excess risk for opportunistic disease or death.

Empirical Fluconazole versus Placebo for Intensive Care Unit Patients (2008)

Schuster MG, Edwards JE, Sobel JD, et al.

This multicenter trial tested the effect of empirical antifungal treatment in febrile intensive care unit patients. Investigators randomly assigned 270 patients with fever despite taking broad-spectrum antibiotics to either fluconazole, 800 mg/d, or placebo for 2 weeks. About 40% of patients in each group achieved all 4 components of successful treatment: resolution of fever, no invasive fungal infection, no stopping therapy because of toxicity, and no need for a nonstudy systemic antifungal medication. Compared with placebo, empirical antifungal fluconazole therapy had no effect in high-risk intensive care unit patients.

Comparison of 2 Interventions for Liquid Aspiration on Pneumonia Incidence (2008)

Robbins J, Gensler G, Hind J, et al.

To test strategies for avoiding aspiration pneumonia in cognitively impaired elderly patients, Robbins and colleagues randomly assigned 515 patients age 50 years or older with dementia or Parkinson disease to drink liquids in a chin-down posture or to consume nectar-thick or honey-thick liquids. The cumulative incidence of pneumonia at 3 months was 9.8% in the chin-down posture group, 8.4% in the nectar-thick liquid group, and 15.0% in the honey-thick liquid group. The confidence bounds of the differences in these rates between groups were wide, and the study was inconclusive.

Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis with Telbivudine or Adefovir (2007)

Chan HL, Heathcote EJ, Marcellin P, et al.

The best way to suppress viral replication in chronic hepatitis B remains an open question. In this 52-week open-label trial, 135 adults with hepatitis B e antigen–positive chronic hepatitis were randomly assigned to telbuvidine or adefovir for 52 weeks, or adefovir for 24 weeks followed by telbivudine for 28 weeks. At 52 weeks, the reduction in viral load was similar in the telbivudine-only and adefovir-to- telbivudine groups and greater than that in the adefovir-only group.

Infection Risk with Nitrofurazone-Impregnated Urinary Catheters in Trauma Patients (2007)

Stensballe J, Tvede M, Looms D, et al.

Indwelling urinary catheters increase risk for bacteriuria and clinically significant urinary tract infection. In a randomized trial, Stensballe and colleagues found that trauma patients who received a nitrofurazone-impregnated catheter were less likely than those who received a silicone catheter to develop catheter-associated bacteriuria and funguria or to need a change in or addition of new antibiotics. Use of nitrofurazone-impregnated catheters should therefore be considered in trauma patients. Whether other patients requiring indwelling urinary catheters would benefit from these catheters should be assessed in a randomized clinical trial.

Sequential Therapy versus Standard Triple-Drug Therapy for Helicobacter pylori Eradication (2007)

Vaira D, Zullo A, Vakil N, et al.

Eradication rates of Helicobacter pylori infection are decreasing worldwide because of increasing resistance to antimicrobials. In this double-blind trial, 300 adults with dyspepsia or peptic ulcers were randomly assigned to a 10-day sequential regimen (pantoprazole, amoxicillin, and placebo taken for 5 days followed by pantoprazole, clarithromycin, and tinidazole taken for 5 days) or standard 10-day therapy (pantoprazole, clarithromycin, and amoxicillin). The eradication rate was higher with the sequential regimen than with standard therapy, especially in patients with clarithromycin-resistant strains. The incidence of side effects did not differ between groups.

Nephrology (6 articles)

Effect of Telmisartan on Renal Outcomes (2009)

Mann JF, Schmieder RE, Dyal L, et al.

Mann and colleagues compared the long-term renal effects of telmisartan and placebo in 5927 adults with vascular disease but without macroalbuminuria. They used a composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. Patients receiving telmisartan had the same composite outcome results as those receiving placebo. Albuminuria increased less with telmisartan than with placebo, whereas estimated GFR decreased more with telmisartan. On balance, telmisartan had the same effects as placebo on major renal outcomes.

Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function (2009)

Bax L, Woittiez AJ, Kouwenberg HJ, et al.

Renal stents are commonly used to treat atherosclerotic renal artery stenosis (ARAS). In this randomized trial, Bax and coworkers compared medical treatment of ARAS (anti-hypertensive treatment, a statin, and aspirin) with medical treatment plus stenting among 140 patients with ARAS and impaired renal function. Patients who underwent stenting had no clear benefits, and several complications occurred, including 2 procedure-related deaths.

Behavioral Therapy to Enable Women with Urge Incontinence to Discontinue Drug Treatment (2008)

Burgio KL, Kraus SR, Menefee S, et al.

The authors sought to determine whether behavioral therapy would help women with urge urinary incontinence to stop drug therapy for this condition. In this multicenter trial, 307 women with urge-predominant incontinence were randomly assigned to receive 10 weeks of tolterodine plus behavioral training or tolterodine alone. Six months later, 41% of women in both groups reported a 70% or greater reduction in the frequency of incontinence episodes and did not require treatment. Even with behavioral therapy, short-term treatment does not provide sustainable improvement in urge urinary incontinence.

Infection Risk with Nitrofurazone-Impregnated Urinary Catheters in Trauma Patients (2007)

Stensballe J, Tvede M, Looms D, et al.

Indwelling urinary catheters increase risk for bacteriuria and clinically significant urinary tract infection. In a randomized trial, Stensballe and colleagues found that trauma patients who received a nitrofurazone-impregnated catheter were less likely than those who received a silicone catheter to develop catheter-associated bacteriuria and funguria or to need a change in or addition of new antibiotics. Use of nitrofurazone-impregnated catheters should therefore be considered in trauma patients. Whether other patients requiring indwelling urinary catheters would benefit from these catheters should be assessed in a randomized clinical trial.

Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer (2007)

Greenspan SL, Nelson JB, Trump DL, et al.

Androgen deprivation therapy (ADT) for prostate cancer increases risk for bone loss and fractures. The researchers randomly assigned patients with prostate cancer receiving ADT to alendronate or placebo. At baseline, 39% of men had osteoporosis and 52% had low bone mass. During the first year, alendronate increased bone mineral density by 3.7% at the spine and 1.6% at the femoral neck and increased bone turnover. The groups had the same rates of adverse events.

Agalsidase-Beta Therapy for Advanced Fabry Disease (2007)

Banikazemi M, Bultas J, Waldek S, et al.

Fabry disease is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. In this double-blind multicenter trial, 82 adults with kidney dysfunction from Fabry disease were randomly assigned to bimonthly infusions of enzyme replacement with agalsidase beta or placebo for up to 35 months. Agalsidase beta reduced the frequency of and time to renal, cardiac, and cerebrovascular events and death and caused infusion reactions more often than placebo.

Neurology (4 articles)

Effect of Telmisartan on Renal Outcomes (2009)

Mann JF, Schmieder RE, Dyal L, et al.

Mann and colleagues compared the long-term renal effects of telmisartan and placebo in 5927 adults with vascular disease but without macroalbuminuria. They used a composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. Patients receiving telmisartan had the same composite outcome results as those receiving placebo. Albuminuria increased less with telmisartan than with placebo, whereas estimated GFR decreased more with telmisartan. On balance, telmisartan had the same effects as placebo on major renal outcomes.

Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function (2009)

Bax L, Woittiez AJ, Kouwenberg HJ, et al.

Renal stents are commonly used to treat atherosclerotic renal artery stenosis (ARAS). In this randomized trial, Bax and coworkers compared medical treatment of ARAS (anti-hypertensive treatment, a statin, and aspirin) with medical treatment plus stenting among 140 patients with ARAS and impaired renal function. Patients who underwent stenting had no clear benefits, and several complications occurred, including 2 procedure-related deaths.

Comparison of 2 Interventions for Liquid Aspiration on Pneumonia Incidence (2008)

Robbins J, Gensler G, Hind J, et al.

To test strategies for avoiding aspiration pneumonia in cognitively impaired elderly patients, Robbins and colleagues randomly assigned 515 patients age 50 years or older with dementia or Parkinson disease to drink liquids in a chin-down posture or to consume nectar-thick or honey-thick liquids. The cumulative incidence of pneumonia at 3 months was 9.8% in the chin-down posture group, 8.4% in the nectar-thick liquid group, and 15.0% in the honey-thick liquid group. The confidence bounds of the differences in these rates between groups were wide, and the study was inconclusive.

Agalsidase-Beta Therapy for Advanced Fabry Disease (2007)

Banikazemi M, Bultas J, Waldek S, et al.

Fabry disease is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. In this double-blind multicenter trial, 82 adults with kidney dysfunction from Fabry disease were randomly assigned to bimonthly infusions of enzyme replacement with agalsidase beta or placebo for up to 35 months. Agalsidase beta reduced the frequency of and time to renal, cardiac, and cerebrovascular events and death and caused infusion reactions more often than placebo.

Oncology (4 articles)

Positron Emission Tomography in Staging Early Lung Cancer (2009)

Maziak DE, Darling GE, Inculet RI, et al.

Maziak and colleagues compared 2 preoperative imaging strategies for patients with early non–small cell lung cancer: whole-body positron emission tomography and computed tomography (PET-CT) plus cranial imaging versus conventional staging plus cranial imaging. Trial results suggested that compared with conventional staging, a PET-CT–based imaging strategy may help identify advanced disease and prevent futile thoracotomy in patients with non–small cell lung cancer, but it also may give false-positive results that incorrectly upstage disease in some patients.

Short-Term Hormone Therapy Suspension and Mammography Recall (2009)

Buist DS, Anderson ML, Reed SD, et al.

Women screened for breast cancer are often recalled for additional testing when mammography findings are unclear. This randomized trial in middle-age and older women found that briefly stopping hormone therapy reduced breast density slightly but did not decrease mammography recall rates. Recall rates after screening mammograms were 12.3% (stopping for 1 month), 9.8% (stopping for 2 months), and 11.3% (continuing to take hormone therapy). Menopausal symptoms increased in the groups that stopped therapy.

Massage Therapy versus Simple Touch to Improve Pain and Mood in Patients with Advanced Cancer (2008)

Kutner JS, Smith MC, Corbin L, et al.

Little is known about the effectiveness of massage in managing pain during palliative care. Kutner and colleagues randomly assigned 380 patients with advanced cancer to either massage therapy or simple-touch sessions. Pain and mood improved more after massage therapy than after simple touch, but the 2 treatments had equal effects on pain, quality of life, and analgesic use as measured over 3 weeks. Adverse effects were infrequent and similar in both groups.

Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer (2007)

Greenspan SL, Nelson JB, Trump DL, et al.

Androgen deprivation therapy (ADT) for prostate cancer increases risk for bone loss and fractures. The researchers randomly assigned patients with prostate cancer receiving ADT to alendronate or placebo. At baseline, 39% of men had osteoporosis and 52% had low bone mass. During the first year, alendronate increased bone mineral density by 3.7% at the spine and 1.6% at the femoral neck and increased bone turnover. The groups had the same rates of adverse events.

Otolaryngology (3 articles)

Effects of a Short Course of Eszopiclone on Continuous Positive Airway Pressure Adherence (2009)

Lettieri CJ, Shah AA, Holley AB, et al.

Lettieri and coworkers assessed whether a short course of eszopiclone therapy improves long-term adherence to continuous positive airway pressure (CPAP). They randomly assigned 160 adults with severe obstructive sleep apnea to eszopiclone or placebo for the first 14 nights of CPAP, and measured patients' adherence to CPAP weekly for 24 weeks. Patients receiving eszopiclone were less likely to discontinue CPAP and also used CPAP more nights and longer per night than did patients receiving placebo.

Diagnosis and Initial Management of Obstructive Sleep Apnea without Polysomnography (2007)

Mulgrew AT, Fox N, Ayas NT, et al.

The authors sought alternatives to polysomnography for making a diagnosis of obstructive sleep apnea (OSA). They created a clinical algorithm that used clinical methods and overnight home oximetry to calculate the probability of OSA. Sixty-eight patients with a probability of OSA of 90% or greater were randomly assigned to usual care (polysomnography before starting continuous positive airway pressure [CPAP]) or ambulatory management (start CPAP without doing polysomnography). After 3 months, the 2 groups had the same results on overnight polysomnography.

Effects of Folic Acid Supplementation on Hearing in Older Adults (2007)

Durga J, Verhoef P, Anteunis LJ, et al.

Observational studies have shown that a low folate level is associated with poor hearing. In this study, the investigators randomly assigned 728 older adults to receive daily folic acid or placebo for 3 years. The study took place in a country that does not mandate folic acid enrichment of food. The patients had high homocysteine levels but no known ear conditions. Folic acid reduced hearing loss by 0.7 dB, a just noticeable amount.

Psychiatry (7 articles)

Case Management for Depression by Health Care Assistants in Small Primary Care Practices (2009)

Gensichen J, von Korff M, Peitz M, et al.

Gensichen and colleagues evaluated whether telephone case management facilitated by health care assistants can reduce depression symptoms and improve the process of care for patients with major depression in small primary care practices. Among the 626 adults with depression, those randomly assigned to receive case management reported slightly greater improvements in depression symptoms, better adherence to antidepressant therapies, and more favorable assessments of the quality of their care than did patients randomly assigned to receive usual care.

Effect of Varying Levels of Disease Management on Smoking Cessation (2009)

Ellerbeck EF, Mahnken JD, Cupertino AP, et al.

Successful smoking cessation may require repeated or intensive interventions. In this multicenter trial, 750 primary care patients who smoked at least 10 cigarettes daily were randomly assigned to pharmacotherapy (nicotine patch or bupropion), pharmacotherapy supplemented with up to 2 calls from trained counselors, or pharmacotherapy supplemented with up to 6 counseling calls. Abstinence over the 24-month study was highest in the high-intensity counseling group. Point prevalences of abstinence at 2 years were 23%, 24%, and 28%, respectively.

Triple-Combination Pharmacotherapy for Medically Ill Smokers (2009)

Steinberg MB, Greenhaus S, Schmelzer AC, et al.

Few studies have examined interventions for smokers with medical illnesses. In this trial, 127 smokers with such conditions as cardiovascular disease or chronic obstructive pulmonary disease were randomly assigned to receive a nicotine patch for 10 weeks or a combination of a nicotine patch, a nicotine oral inhaler, and bupropion for as long as required. Abstinence rates at 26 weeks for the nicotine patch and combination therapy groups were 19% and 35%, respectively. Insomnia (25% vs. 9%) and anxiety (22% vs. 3%) were more common with combination therapy.

Comparison of 2 Interventions for Liquid Aspiration on Pneumonia Incidence (2008)

Robbins J, Gensler G, Hind J, et al.

To test strategies for avoiding aspiration pneumonia in cognitively impaired elderly patients, Robbins and colleagues randomly assigned 515 patients age 50 years or older with dementia or Parkinson disease to drink liquids in a chin-down posture or to consume nectar-thick or honey-thick liquids. The cumulative incidence of pneumonia at 3 months was 9.8% in the chin-down posture group, 8.4% in the nectar-thick liquid group, and 15.0% in the honey-thick liquid group. The confidence bounds of the differences in these rates between groups were wide, and the study was inconclusive.

Risperidone for Treatment-Refractory Major Depressive Disorder (2007)

Mahmoud RA, Pandina GJ, Turkoz I, et al.

When patients with major depression do not respond to first-line monotherapy, physicians often add a second agent despite scant evidence that augmentation therapy is effective. Mahmoud and colleagues added a 6-week course of risperidone or placebo to the treatment of 274 adults with major depression who had not responded adequately to antidepressant monotherapy. Mean depression scale scores improved more in the risperidone group than the placebo group, and more risperidone recipients had response to therapy or remission. Somnolence and dry mouth were more common in risperidone recipients.

The Effect of a Primary Care Practice–Based Depression Intervention on Mortality in Older Adults (2007)

Gallo JJ, Bogner HR, Morales KH, et al.

Many studies have shown that depression is associated with an increased risk for death, but few have evaluated whether an intervention to improve depression can modify this risk. Gallo and colleagues randomly assigned 20 primary care practices to a depression care management program or to usual care. They observed a 45% reduction in the risk for death among patients with major depression who were cared for at the practices assigned to the intervention. The effect seemed to be limited to deaths due to cancer and warrants further investigation.

Brief Intervention for Medical Inpatients with Unhealthy Alcohol Use (2007)

Saitz R, Palfai TP, Cheng DM, et al.

The authors screened all adult medical inpatients at an inner-city teaching hospital and randomly assigned 341 risky drinkers to a 30-minute motivational counseling intervention followed by treatment planning or to usual care. By 3 months, the same proportion of patients from both groups had received alcohol assistance. At 12 months, both groups had reduced their drinking to the same degree. A 30-minute intervention was insufficient to change behavior in these risky drinkers, 76% of whom were alcohol-dependent.

Pulmonary Medicine (12 articles)

A Computerized Handheld Decision-Support System to Improve Pulmonary Embolism Diagnosis (2009)

Roy P, Durieux P, Gillaizeau F, et al.

Roy and colleagues developed a program to guide diagnosis of pulmonary embolism for use on a mobile, handheld device. The investigators randomly assigned 20 emergency departments in France to activation of either the decision-support system on the devices or posters and pocket cards that showed diagnostic strategies. The device-based program improved appropriate testing of patients with suspected pulmonary embolism more than paper guidelines alone.

Effects of a Short Course of Eszopiclone on Continuous Positive Airway Pressure Adherence (2009)

Lettieri CJ, Shah AA, Holley AB, et al.

Lettieri and coworkers assessed whether a short course of eszopiclone therapy improves long-term adherence to continuous positive airway pressure (CPAP). They randomly assigned 160 adults with severe obstructive sleep apnea to eszopiclone or placebo for the first 14 nights of CPAP, and measured patients' adherence to CPAP weekly for 24 weeks. Patients receiving eszopiclone were less likely to discontinue CPAP and also used CPAP more nights and longer per night than did patients receiving placebo.

Effect of Fluticasone With and Without Salmeterol on Pulmonary Outcomes in Chronic Obstructive Pulmonary Disease (2009)

Lapperre TS, Snoeck-Stroband JB, Gosman MM, et al.

Inhaled corticosteroids and long-acting β2-agonists improve chronic obstructive pulmonary disease (COPD) symptoms, but their effects on lung function and inflammation are uncertain. Lapperre and colleagues compared treatment with fluticasone for 6 months or 30 months, fluticasone and salmeterol for 30 months, or placebo in 114 steroid-naive patients who had moderate to severe COPD. They found reduced inflammatory cells in sputum and bronchial biopsies and an attenuated decrease in lung function during fluticasone treatment. Adding salmeterol did not further alter the decrease in lung function.

Positron Emission Tomography in Staging Early Lung Cancer (2009)

Maziak DE, Darling GE, Inculet RI, et al.

Maziak and colleagues compared 2 preoperative imaging strategies for patients with early non–small cell lung cancer: whole-body positron emission tomography and computed tomography (PET-CT) plus cranial imaging versus conventional staging plus cranial imaging. Trial results suggested that compared with conventional staging, a PET-CT–based imaging strategy may help identify advanced disease and prevent futile thoracotomy in patients with non–small cell lung cancer, but it also may give false-positive results that incorrectly upstage disease in some patients.

Internet-Based Self-management Plus Education Compared With Usual Care in Asthma (2009)

van der Meer V, Bakker MJ, van den Hout WB, et al.

This randomized trial compared Internet-based asthma self-management with usual care in 200 adults with asthma. van der Meer and colleagues found modest improvements in asthma control and lung function with the Internet intervention but no reduction in exacerbations and changes in asthma-related quality of life that were less than clinically significant at 12 months. Although Internet-based self-management improved some asthma outcome measures, the improvements were small, and the program did not affect the number of exacerbations.

Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin (2009)

Crowther MA, Ageno W, Garcia D, et al.

Crowther and colleagues measured the effect of oral vitamin K or placebo on prevention of bleeding in 724 patients with international normalized ratios (INRs) of 4.5 to 10.0 who were receiving warfarin. They found that 15.8% of vitamin K recipients and 16.3% of placebo recipients had at least 1 bleeding complication; 2.5% and 1.1%, respectively, had major bleeding events; and 1.1% and 0.8% experienced thromboembolism. Low-dose oral vitamin K lowered the INR but did not reduce bleeding in overanticoagulated patients.

Effects of Home-Based Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease (2008)

Maltais F, Bourbeau J, Shapiro S, et al.

Pulmonary rehabilitation programs improve outcomes, but access to outpatient, hospital-based programs is very limited. In a 10-center, Canadian noninferiority trial, Maltais and coworkers randomly assigned 252 patients to home-based or outpatient, hospital-based exercise training for 8 weeks. At 1 year, both interventions had reduced dyspnea by the same amount, as measured on the dyspnea subscale of the Chronic Respiratory Questionnaire. Home-based pulmonary rehabilitation may be a reasonable alternative to hospital-based programs.

Addition of Sildenafil to Long-Term Intravenous Epoprostenol Therapy in Patients with Pulmonary Arterial Hypertension (2008)

Simonneau G, Rubin LJ, Galiè N, et al.

In a short-term multicenter trial, Simonneau and colleagues randomly assigned 267 patients with pulmonary arterial hypertension who had been receiving intravenous epoprostenol for at least 3 months to receive either oral sildenafil or placebo for 16 weeks. Compared with placebo, sildenafil improved exercise capacity and hemodynamic measurements, lengthened time to clinical worsening, and caused more headaches and dyspepsia. Patients with better baseline exercise capacity improved the most.

Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism (2007)

Glynn RJ, Ridker PM, Goldhaber SZ, et al.

Short-term aspirin therapy can lower the risk for venous thromboembolism (VTE) in high-risk patients, but whether long-term, low-dose aspirin therapy reduces risk in healthy adults is uncertain. In a secondary analysis of the Women's Health Study, Glynn and colleagues measured VTE rates in 39 876 female health professionals who were randomly assigned to low-dose aspirin or placebo for 10 years. Low-dose aspirin did not affect overall VTE rates or those in women with increased rates because of inherited thrombophilia.

Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism (2007)

Ray JG, Kearon C, Yi Q, et al.

In observational studies, elevated plasma homocysteine levels were associated with venous thromboembolism. Ray and colleagues investigated the effect of homocysteine lowering on venous thromboembolism in a multicenter trial of folic acid and B vitamins to reduce cardiovascular events. Five years of therapy with folic acid and vitamins B6 and B12 decreased homocysteine levels compared with placebo, but the incidence of venous thromboembolism was the same in both groups, even in participants with the highest levels of homocysteine.

Tiotropium in Combination with Placebo, Salmeterol, or Fluticasone–Salmeterol for Treatment of Chronic Obstructive Pulmonary Disease (2007)

Aaron SD, Vandemheen KL, Fergusson D, et al.

Scant evidence supports prescribing combinations of inhaled corticosteroids and long-acting β-agonists and anticholinergic bronchodilators for chronic obstructive pulmonary disease (COPD). Investigators randomly assigned 449 adults with moderate or severe COPD to receive tiotropium with placebo, with salmeterol, or with fluticasone–salmeterol for 1 year. The exacerbation rates for the 3 groups were 63%, 65%, and 60%, respectively. Compared with tiotropium alone, 3-drug therapy but not 2-drug therapy had fewer exacerbations requiring hospitalization.

Diagnosis and Initial Management of Obstructive Sleep Apnea without Polysomnography (2007)

Mulgrew AT, Fox N, Ayas NT, et al.

The authors sought alternatives to polysomnography for making a diagnosis of obstructive sleep apnea (OSA). They created a clinical algorithm that used clinical methods and overnight home oximetry to calculate the probability of OSA. Sixty-eight patients with a probability of OSA of 90% or greater were randomly assigned to usual care (polysomnography before starting continuous positive airway pressure [CPAP]) or ambulatory management (start CPAP without doing polysomnography). After 3 months, the 2 groups had the same results on overnight polysomnography.

Rheumatology (9 articles)

Comparison of Tripterygium wilfordii Hook F Versus Sulfasalazine in the Treatment of Rheumatoid Arthritis (2009)

Goldbach-Mansky R, Wilson M, Fleischmann R, et al.

In Chinese medicine, extracts of Tripterygium wilfordii Hook F (TwHF) are used to treat autoimmune and inflammatory conditions. Small clinical trials suggest that TwHF may benefit patients with rheumatoid arthritis. Goldbach-Mansky and associates compared TwHF extract with sulfasalazine in 121 patients with active rheumatoid arthritis who could continue use of oral prednisone and nonsteroidal anti-inflammatory drugs but not disease-modifying antirheumatic drugs. Among those who continued treatment for 24 weeks, achievement of 20% improvement in American College of Rheumatology criteria was greater with TwHF than with sulfasalazine, and adverse event rates were similar.

Splint for Base-of-Thumb Osteoarthritis (2009)

Rannou F, Dimet J, Boutron I, et al.

Base-of-thumb osteoarthritis causes pain and disability and is common in middle-age and elderly adults. Rannou and colleagues assessed the efficacy and safety of a splint for base-of-thumb osteoarthritis. They randomly assigned 112 patients to wear a custom-made splint at night or to usual care. Nighttime splinting had no effect after 1 month, but it significantly reduced pain and disability after 12 months.

Effect of Glucosamine Sulfate on Hip Osteoarthritis (2008)

Rozendaal RM, Koes BW, van Osch GJ, et al.

Although many patients use glucosamine to treat osteoarthritis, available studies have reported inconsistent effects of glucosamine on symptoms and joint changes. In the first trial focusing on hip osteoarthritis, Rozendaal and colleagues randomly assigned 222 patients to glucosamine, 1500 mg/d, or placebo. After 2 years of treatment, they found no clinically significant effect on pain, function, or joint space narrowing. Whatever its effects on osteoarthritis in other joints, glucosamine sulfate was no better than placebo in reducing symptoms and progression of hip osteoarthritis.

Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women (2007)

Marini H, Minutoli L, Polito F, et al.

Studies suggest that isoflavone phytoestrogens, which are found in soy products, reduce bone loss in women, but the evidence is not definitive. Marini and colleagues compared the phytoestrogen genistein with placebo in 389 osteopenic postmenopausal women. At 24 months, women who took genistein had a greater increase in bone mineral density than did those who took placebo. Genistein improved markers of bone metabolism. It did not increase endometrial thickness, but it did cause gastrointestinal side effects.

Infliximab for Maintenance of Glucocorticosteroid-Induced Remission of Giant Cell Arteritis (2007)

Hoffman GS, Cid MC, Rendt-Zagar KE, et al.

Steroid-sparing treatment would be valuable in giant cell arteritis (GCA) because most patients experience complications of glucocorticoid therapy. Case reports suggest that infliximab might be effective. Hoffman and colleagues randomly assigned 44 patients with GCA in glucocorticoid-induced remission to receive infliximab or placebo at 0, 2, and 6 weeks and every 8 weeks thereafter. Infliximab did not reduce rates of relapse or any secondary end point and is therefore unlikely to be useful in GCA.

Infliximab plus Prednisone or Placebo plus Prednisone for the Initial Treatment of Polymyalgia Rheumatica (2007)

Salvarani C, Macchioni P, Manzini C, et al.

Some patients with polymyalgia rheumatica have a chronic relapsing course and require long-term glucocorticoid therapy. A small case series suggested that infliximab could reduce the glucocorticoid dose needed to induce and maintain remission. Salvarani and associates therefore randomly assigned 51 patients with newly diagnosed polymyalgia rheumatica to take placebo or infliximab at weeks 0, 2, 6, 14, and 22. All patients took prednisone in tapering doses. Relapse-free and recurrence-free survival did not differ at 52 weeks.

Comparison of Treatment Strategies in Early Rheumatoid Arthritis (2007)

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al.

First-year results of the BeSt study showed that starting therapy for rheumatoid arthritis with several combinations of drugs produced more rapid clinical improvement and less progression of joint damage than starting with monotherapy. Treating clinicians were free to adjust medication on the basis of disease activity score and reassessed clinical and radiologic outcomes. After 2 years, patients originally assigned to combination therapy groups or to monotherapy had similar disease activity, although treating physicians often converted the patients to combination therapy from monotherapy during follow-up.

Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer (2007)

Greenspan SL, Nelson JB, Trump DL, et al.

Androgen deprivation therapy (ADT) for prostate cancer increases risk for bone loss and fractures. The researchers randomly assigned patients with prostate cancer receiving ADT to alendronate or placebo. At baseline, 39% of men had osteoporosis and 52% had low bone mass. During the first year, alendronate increased bone mineral density by 3.7% at the spine and 1.6% at the femoral neck and increased bone turnover. The groups had the same rates of adverse events.

Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis (2007)

Greenspan SL, Bone HG, Ettinger MP, et al.

To determine the safety of parathyroid hormone (PTH) and its effect on the incidence of vertebral fractures in postmenopausal women with osteoporosis, the authors randomly assigned 2532 postmenopausal women with osteoporosis to receive PTH or placebo. Parathyroid hormone decreased new vertebral fractures. However, the amount of reduction in risk is uncertain because one third of participants prematurely withdrew from the trial. Adverse effects included hypercalciuria, hypercalcemia, and nausea.