The “Oregon Experiment” at 2 Years.

A lottery for Medicaid enrollment simulates a randomized trial.

In 2008, Oregon modestly expanded its Medicaid program through a lottery. From a list of 90,000 names on a Medicaid waiting list, 30,000 were drawn randomly; ultimately, about 10,000 of the lottery “winners” applied for state Medicaid services and were enrolled. Eligibility was based on age (19–64) and financial need (income, <100% of the federal poverty level; assets,

Researchers compared selected 2-year outcomes for about 6000 people who acquired Medicaid coverage through the lottery and for 6000 controls (people who entered the lottery but weren’t selected). Data were acquired by questionnaires and by limited cardiovascular risk assessments. The following statistically significant outcomes were noted in the Medicaid group, compared with controls:

• Lower prevalence of positive depression screens (21% vs. 30%)
• Better self-reported health-related quality of life
• Fewer financial hardships due to medical expenses
• Better access to medical care
• More Pap smears and mammograms completed
• More outpatient visits but not hospital admissions

Mean blood pressure, lipid levels, and glycosylated hemoglobin (HbA_1c) levels were similar in the two groups.

Comment: One month ago, I saw an uninsured 45-year-old woman who had noted an enlarging breast mass for 9 months. She had not sought medical attention because “it wasn’t the cost of the mammogram or biopsy that concerned me . . . it was the cost of what would happen next if I have cancer.” Unfortunately, a biopsy showed breast cancer.

This case exemplifies a key reason for medical insurance — it enables people to access medical care when they need it, without fear of financial ruin. By that standard, the Oregon experiment is a success for Medicaid expansion. The lack of difference in cardiovascular risk factors is not important, given the short follow-up and the relatively normal values: Mean blood pressure, total cholesterol levels, and HbA_1c in both groups were about 120/75 mm Hg, 200 mg/dL, and 5.3%, respectively.

 

Source:Journal Watch General Medicine

 

Continued Warfarin Better Approach to Cardiac Device Surgery.

Higher-risk patients undergoing cardiac device surgery are better off continuing warfarin than switching to heparin as guidelines recommend, according to a New England Journal of Medicine study.

The study included nearly 700 patients at moderate-to-high risk for thromboembolic events who were taking warfarin and required nonemergency pacemaker or implantable cardioverter-defibrillator surgery. Patients were randomized to either continue warfarin (target INR: 3.0 or less; 3.5 or less for patients with mechanical valves) or receive bridging therapy with heparin as recommended by the American College of Chest Physicians.

The study was stopped early after an interim analysis found that the primary outcome — device-pocket hematoma — had occurred four times as often with heparin as with warfarin (16% vs. 3.5%). Continued warfarin didn’t increase major perioperative bleeding.

One explanation for the “counterintuitive” finding, the authors write, “is the concept of an ‘anticoagulant stress test.’ That is, if patients undergo surgery while receiving full-dose anticoagulation therapy, any excessive bleeding will be detectable and appropriately managed while the wound is still open. In contrast, if bridging therapy with heparin is used, such bleeding may be apparent only when full-dose anticoagulation therapy is resumed postoperatively.”

Source: NEJM 

Lower Oxygen Saturation Levels in Preemies Associated with Higher Mortality by Discharge .

The question of which oxygen-saturation level is best for very premature infants remains open after the publication of two studies over the weekend. Commentators suggest that levels under 90% should be avoided, however.

Researchers in the BOOST II study (published in the New England Journal of Medicine) report outcomes at hospital discharge for some 2400 infants randomized to lower (85 to 89%) or higher (91 to 95%) saturation levels. Interpretation is muddied somewhat by the fact that the oximeters had a measurement flaw that wasn’t discovered until halfway through the study. Among infants measured with corrected oximeters, mortality was higher for those receiving lower oxygen saturation (23% vs. 16%). Retinopathy was lower with lower saturation.

In JAMA, COT study researchers found no significant differences in the rates of mortality or retinopathy by 18 months in some 1200 infants similarly studied.

Commentators say the best interim course would be to target saturation levels between 90% and 95%, realizing the dangers of retinopathy.

Source: NEJM 

 

 

Genomic Studies Allow Better Classification of Leukemias, Endometrial Tumors.

Two studies, one of leukemia and the other of endometrial tumors, show the usefulness of genomics studies in finding unsuspected classifications, possibly useful for treating these cancers.

One study, published in the New England Journal of Medicine, examined 200 cases of acute myeloid leukemia. Genomic studies allowed the researchers to discern nine distinct categories, revealing “many potentially important biologic relationships.” For instance, certain mutations were associated with distinct patterns of RNA activity. The authors point out that the significance of such findings “is not yet clear.”

Another study, in Nature, of some 375 endometrial cancers found four distinct classes of the disease, as opposed to the two commonly used to stage treatment. In Journal Watch Oncology and Hematology, Virginia Kaklamani observes that breast cancer was the first to use molecular subtypes to guide treatment. The Nature study, she writes, is “a huge step toward applying this technique in other malignancies.”

Source:NEJM

Azithromycin Does Not Increase Cardiovascular Mortality in the General Population.

The excess cardiovascular mortality previously observed with azithromycin use is attributable to the infection being treated, not the antibiotic, a New England Journal of Medicine study finds.

Using Danish registries, researchers compared 1.1 million episodes of azithromycin use with either 1.1 million episodes of no antibiotic use or 7.4 million episodes of penicillin V use among adults.

The risk for cardiovascular death was roughly three times higher with current azithromycin use than with no antibiotic use. However, cardiovascular death rates did not differ between azithromycin and penicillin. This indicates, the authors write, that “the increased risk … observed in the comparison with no antibiotic use was entirely attributable to the risk of death associated with acute infection” or some other risk factor in patients receiving antibiotics.

The authors add that while previous research showed a link between azithromycin and cardiovascular mortality in a higher-risk (Medicaid) population, the current study “shows that this effect is not present in the general population.”

NEJM commentators still highlight the potential risk for QT prolongation with use of macrolides and emphasize caution in their use for patients with preexisting cardiovascular conditions.

Source: NEJM 

Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options..

Background Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. Methods We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. Results Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). Conclusions In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks.

Source: NEJM

 

Treatment of HCV Infection by Targeting MicroRNA

BACKGROUND

The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid–modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function.

METHODS

In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period. They were followed until 18 weeks after randomization.

RESULTS

Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy. In the miravirsen groups, the mean maximum reduction in HCV RNA level (log₁₀ IU per milliliter) from baseline was 1.2 (P=0.01) for patients receiving 3 mg per kilogram, 2.9 (P=0.003) for those receiving 5 mg per kilogram, and 3.0 (P=0.002) for those receiving 7 mg per kilogram, as compared with a reduction of 0.4 in the placebo group. During 14 weeks of follow-up after treatment, HCV RNA was not detected in one patient in the 5-mg group and in four patients in the 7-mg group. We observed no dose-limiting adverse events and no escape mutations in the miR-122 binding sites of the HCV genome.

CONCLUSIONS

The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance.

Source: NEJM

 

 

Surgery versus Physical Therapy for a Meniscal Tear and Osteoarthritis

 

Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain.

METHODS

We conducted a multicenter, randomized, controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging. We randomly assigned 351 patients to surgery and postoperative physical therapy or to a standardized physical-therapy regimen (with the option to cross over to surgery at the discretion of the patient and surgeon). The patients were evaluated at 6 and 12 months. The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical-function score (ranging from 0 to 100, with higher scores indicating more severe symptoms) 6 months after randomization.

RESULTS

In the intention-to-treat analysis, the mean improvement in the WOMAC score after 6 months was 20.9 points (95% confidence interval [CI], 17.9 to 23.9) in the surgical group and 18.5 (95% CI, 15.6 to 21.5) in the physical-therapy group (mean difference, 2.4 points; 95% CI, −1.8 to 6.5). At 6 months, 51 active participants in the study who were assigned to physical therapy alone (30%) had undergone surgery, and 9 patients assigned to surgery (6%) had not undergone surgery. The results at 12 months were similar to those at 6 months. The frequency of adverse events did not differ significantly between the groups.

CONCLUSIONS

In the intention-to-treat analysis, we did not find significant differences between the study groups in functional improvement 6 months after randomization; however, 30% of the patients who were assigned to physical therapy alone underwent surgery within 6 months.

Source: NEJM

 

Penicillin to Prevent Recurrent Leg Cellulitis

BACKGROUND

Cellulitis of the leg is a common bacterial infection of the skin and underlying tissue. We compared prophylactic low-dose penicillin with placebo for the prevention of recurrent cellulitis.

METHODS

We conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only.

RESULTS

A total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50).

CONCLUSIONS

In patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped.

Source: NEJM

 

A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients.

 

Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.

METHODS

In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance.

RESULTS

There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).

CONCLUSIONS

Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure.

Source: Nejm

 

 

A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients.

 

Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.

METHODS

In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance.

RESULTS

There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).

CONCLUSIONS

Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure.

Source: Nejm