American College of Physicians: Internal Medicine — Doctors for Adults ®

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ACP InternistWeekly



In the News for the Week of 11-15-11




Highlights

A1c targets for type 1 diabetes, dialysis patients discussed at nephrology meeting

PHILADEPHIA—Tight glucose control appears beneficial in preventing kidney function decline in newly diagnosed type 1 diabetics, but not so helpful for diabetics who already have kidney failure, according to data presented at the annual meeting of the American Society of Nephrology. More...

Early tapering of opioid-dependent patients may lead to relapse

Prescription opioid-dependent patients are highly likely to relapse if tapered off buprenorphine-naloxone, even after 12 weeks of treatment and even when receiving additional counseling, researchers found. More...


Test yourself

MKSAP Quiz: diagnosing hematologic abnormalities

This week's quiz asks readers to determine appropriate diagnostic testing for a 26-year-old woman admitted to the hospital with deep venous thrombosis. More...


Mental health

Suicide rating scale offers insights into intent, actions of patients

A suicide assessment exam that quantifies suicidal ideation and suicidal behavior as distinct domains instead of a continuum of behavior is suitable for clinical use, a new study concluded. More...


Antithrombotic therapy

Higher CHADS2 scores can indicate higher risk in patients on anticoagulants

Higher CHADS2 scores pointed to higher risk for adverse outcomes, including stroke, bleeding and death, in patients with atrial fibrillation receiving anticoagulation, according to a new study. More...


Infections

TNF-alpha antagonists may not increase risk for serious infections requiring hospitalization, study indicates

TNF-alpha antagonists may not increase risk for infection-related hospitalizations in patients with autoimmune diseases, according to a new study. More...


FDA update

Deadline this week for rosiglitazone access program

Physicians who want to continue prescribing rosiglitazone-containing medications (Avandia, Avandamet, and Avandaryl) must be enrolled in the Avandia-Rosiglitazone Medicines Access Program by this Thursday, Nov. 17, the FDA reminded last week. More...


CMS update

Version 5010 deadline approaches

As of Nov. 15, there are 46 days before the implementation of version 5010. Effective Jan. 1, 2012, physician practices will need to submit claims not only to Medicare but to all payers using version 5010 in order to be paid. More...


From the College

Poster competition for student members and associates at Internal Medicine 2012

ACP will feature a national poster competition for ACP medical student members and associates at Internal Medicine 2012, which will be held in New Orleans April 19-21. More...


Cartoon caption contest

Vote for your favorite entry

ACP InternistWeekly's cartoon caption contest continues. Readers can vote for their favorite caption to determine the winner. More...


Physician editor: Darren Taichman, MD, FACP



Highlights


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A1c targets for type 1 diabetes, dialysis patients discussed at nephrology meeting

PHILADEPHIA—Tight glucose control appears beneficial in preventing kidney function decline in newly diagnosed type 1 diabetics, but not so helpful for diabetics who already have kidney failure, according to data presented at the annual meeting of the American Society of Nephrology.

In a study that was also published online by the New England Journal of Medicine, researchers used follow-up data from the Diabetes Control and Complications Trial (DCCT) to determine the effect of intensive glucose control on glomerular filtration rate (GFR). Patients in the six-year trial were randomly assigned to either three or more insulin daily injections with an A1c target under 6.05% (actual average A1c in the group was 7.3%) or one or two daily injections to prevent symptoms of hyper- and hypoglycemia. Over a median follow-up of 22 years, half as many patients in the intensive group developed impaired GFR or end-stage renal disease (24 patients vs. 46 and 8 vs. 16, respectively). Although the applicability to type 2 diabetes is uncertain, the researchers concluded that the results reinforce current recommendations to target an A1c of 7% in patients with type 1 diabetes.

However, diabetic patients who were already on dialysis had the lowest risk of death if they had higher A1cs, according to two other large studies presented at the conference. In an observational study from 2001 to 2007 of more than 50,000 dialysis patients with diabetes, researchers from the University of California Los Angeles found that the lowest mortality levels were associated with an A1c between 7.0% and 7.9%, with increases in mortality both above and below this level. Serum glucose levels between 150 mg/dL and 175 mg/dL were associated with the lowest mortality, with increases in mortality at higher and lower glycemic levels. "High is bad, but very low is not good either," concluded study author Kamyar Kalantar-Zadeh, MD, PhD, FACP. "We need controlled trials to target certain ranges of A1c to verify these findings."

It wasn't a controlled trial, but the international Dialysis Outcomes and Practice Patterns Study (DOPPS) showed similar results in data presented at the conference. It included more than 8,000 hemodialysis patients and also found a U-shaped association between A1c and mortality, with the lowest risk associated with A1c levels of 7% to 8%. All-cause mortality risk appeared to be greatest at A1c levels of 9% or greater and less than 5%, and a trend toward higher mortality risk was seen at levels below 7%.

The authors of the latter two studies noted that current National Kidney Foundation guidelines recommend the same A1c targets for patients with kidney disease as other diabetics: below 7%. However, Katherine R. Tuttle, MD, FACP, who moderated the press conference at which the results were announced, said new guidelines have been drafted that include revised recommendations for glycemic targets in patients with kidney disease. The guidelines will be released soon for public review, she said.

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Early tapering of opioid-dependent patients may lead to relapse

Prescription opioid-dependent patients are highly likely to relapse if tapered off buprenorphine-naloxone, even after 12 weeks of treatment and even when receiving additional counseling, researchers found.

To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment (Suboxone) with standard and opioid-specific counseling, researchers designed a treatment course intended to approximate clinical practice. Results appeared in the Nov. 7 Archives of General Psychiatry.

The study was a 10-site, randomized clinical trial using a two-phase adaptive treatment research design among 653 treatment-seeking outpatients dependent on prescription opioids. In each phase, patients were randomized to either standard medical management alone or standard management plus dependence counseling.

Patients with a score greater than 8 on the Clinical Opiate Withdrawal Scale received sublingual buprenorphine-naloxone for once-daily dosing at weekly visits. Patients received 4 to 12 mg (in 4-mg doses) on the induction day, depending on their initial response. At each visit, the study physician could adjust the buprenorphine-naloxone dose in increments of up to 8 mg/wk. Physicians could adjust the dose for opioid use, withdrawal symptoms, adverse effects and craving, but not for pain. The allowable dose was 8 to 32 mg/d, consistent with practice guidelines.

Half the patients were randomly assigned to receive opioid dependence counseling in addition to standard medical management. Counseling consisted of 45- to 60-minute sessions by trained substance abuse or mental health professionals. Counselors educated patients about addiction and recovery, recommended self-help groups, and emphasized lifestyle change. Counseling covered a wider range of relapse prevention issues in greater depth than did standard medical management, including coping with high-risk situations, managing emotions and dealing with relationships.

Brief treatment (phase 1) consisted of buprenorphine-naloxone induction, two weeks of stabilization, a two-week taper, and eight weeks of follow-up. Patients who met the "successful outcome" criteria at week 12 exited the study. The definition of "successful outcome" was based on composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports.

Unsuccessful patients entered into extended treatment (phase 2), which consisted of 12 weeks of buprenorphine-naloxone stabilization, a four-week taper, and eight weeks of follow-up.

During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between standard management and opioid counseling. In phase 2, 49.2% (177 of 360) attained successful outcomes during extended buprenorphine-naloxone treatment (week 12), with no difference between groups. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no difference associated with counseling.

In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs. 8.6% [31 of 360], P<0.001). Chronic pain did not affect opioid use outcomes, and a history of ever using heroin was associated with lower phase 2 success rates.

The authors wrote, "The present findings suggest that physicians can successfully treat many patients dependent on prescription opioids, with or without chronic pain, using buprenorphine-naloxone with relatively brief weekly medical management visits; half of the sample did well during this 12-week regimen."

The authors continued that the study supports the national trend toward office-based treatment of opioid dependence. Patients dependent on prescription opioids, with or without chronic pain, are most likely to reduce their opioid use during the first several months of treatment while receiving buprenorphine-naloxone. Tapering creates an overwhelmingly high risk of relapse or dropout from treatment, they concluded.

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Test yourself


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MKSAP Quiz: diagnosing hematologic abnormalities

A 26-year-old woman is admitted to the hospital for treatment of deep venous thrombosis of the right lower extremity confirmed by duplex Doppler ultrasonography. Medical history is noncontributory, and her only medication is an oral contraceptive.

mksap.jpg

On physical examination, there is mild scleral icterus. Temperature is 37.2 ° C (99.9 °F), blood pressure is 110/67 mm Hg, pulse rate is 100/min, and respiration rate is 16/min. Abdominal examination discloses mild splenomegaly.

Laboratory studies:

Hemoglobin 10.0 g/dL (100 g/L)
Leukocyte count 2,700/µL (2.7 × 109/L)
Platelet count 42,000/µL (42 × 109/L)
Reticulocyte count 8% of erythrocytes
Mean corpuscular volume 70 fL
Total bilirubin 5.0 mg/dL (85.5 µmol/L)
Direct bilirubin 0.8 mg/dL (13.7 µmol/L)
Lactate dehydrogenase 1,126 U/L

Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels are normal. A bone marrow biopsy reveals hypocellular bone marrow, absent iron stores, and signs of early myelodysplasia. The results of a direct and indirect antiglobulin (Coombs) test are negative.

Which of the following is the most appropriate diagnostic test to determine the cause of this patient's hematologic abnormalities?

A) Flow cytometry
B) Hemoglobin electrophoresis
C) Osmotic fragility study
D) Parvovirus B19 serology

Click here or scroll to the bottom of the page for the answer and critique.

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Mental health


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Suicide rating scale offers insights into intent, actions of patients

A suicide assessment exam that quantifies suicidal ideation and suicidal behavior as distinct domains instead of a continuum of behavior is suitable for clinical use, a new study concluded.

The Columbia-Suicide Severity Rating Scale (C-SSRS) (available online) was designed to quantify the severity of suicidal ideation and behavior. To assess C-SSRS's validity compared to other measures of suicidal ideation and behavior, as well as the exam's internal consistency, researchers applied data from three previous studies:

  • a National Institute of Mental Health multisite study of 124 adolescents with a suicide attempt or interrupted attempt 90 days before enrollment;
  • an industry-sponsored multisite, double blind, placebo-controlled, parallel-group, fixed-dose clinical trial to evaluate the efficacy of escitalopram relative to placebo in the treatment of major depressive disorder among 312 adolescents with a diagnosis of major depressive disorder; and
  • a study funded by the American Foundation for Suicide Prevention that evaluated the identification and classification of recent suicide attempts and nonsuicidal self-injurious behavior among 237 adults who presented to an emergency department for psychiatric reasons.

Results were published online Nov. 8 by The American Journal of Psychiatry.

The authors found that the C-SSRS demonstrated good convergent and divergent validity with other suicidal ideation and behavior scales and had high sensitivity and specificity for suicidal behavior classifications compared with other assessment scales. Its ideation and behavior subscales were sensitive to change over time, the authors noted, and the intensity of ideation subscale demonstrated moderate to strong internal consistency.

Other important findings included the following:

  • The C-SSRS severity subscale is sensitive to clinical change. Similarly, the C-SSRS identified almost an identical number of cases with specific types of suicidal behavior as the Columbia Suicide History Form and the suicide evaluation board ratings in study 1.
  • The C-SSRS demonstrated predictive validity, while another scoring system for suicidal ideation did not predict near-term nonfatal suicidal behavior.
  • A history of severe ideation with at least some intent to die may confer a greater risk for suicidal behavior than a history of ideation with no intent to die.

The authors wrote, "Establishing clinically meaningful thresholds that indicate heightened suicide risk and predict which individuals will go on to engage in suicidal behavior have been elusive in efforts at suicide prevention. Because ideation severity can be used to set criteria for clinical referral and inclusion or exclusion criteria in research, operationalization of clinical thresholds could facilitate enrollment of patients with suicidal behavior in research studies, as well as clinical management more broadly."

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Antithrombotic therapy


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Higher CHADS2 scores can indicate higher risk in patients on anticoagulants

Higher CHADS2 scores pointed to higher risk for adverse outcomes, including stroke, bleeding and death, in patients with atrial fibrillation receiving anticoagulation, according to a new study.

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Researchers performed a subgroup analysis of data from the RE-LY study, a randomized, controlled trial comparing dabigatran and warfarin in patients with atrial fibrillation, to determine the prognostic importance of CHADS2 for predicting thrombotic and bleeding complications in this population. The 18,112 study patients were receiving dabigatran, 150 mg or 110 mg twice daily, or open-label warfarin. CHADS2 score, which assigns 1 point each for congestive heart failure, hypertension, age at least 75 years and diabetes and 2 points for stroke, was assessed at baseline. The primary outcomes were stroke or systemic embolism, and the primary safety outcome was major bleeding. Secondary outcomes included intracranial hemorrhage, vascular death and total death. The results of the study, which was funded by Boehringer Ingelheim, appear in the Nov. 15 Annals of Internal Medicine.

Overall, 5,775 patients had a CHADS2 score of 0 to 1, 6,455 patients had a score of 2, and 5,882 patients had a score of 3 to 6. The annual rate of stroke or systemic embolism was 0.93% in patients with a CHADS2 score of 0 to 1, 1.22% in patients with a score of 2, and 2.24% in patients with a score of 3 to 6. Patients with higher CHADS2 scores also had higher annual rates of major bleeding and vascular mortality (P<0.001 for all comparisons). Rates of all adverse outcomes increased in both the warfarin and dabigatran groups as CHADS2 scores increased. Rates of stroke or systemic embolism were lower in patients taking 150 mg of dabigatran twice daily than in those taking warfarin, while rates of intracranial bleeding were lower in patients taking either dose of dabigatran than in those taking warfarin.

The authors cautioned that their study involved post hoc, exploratory analyses and that the levels of statistical significance must be interpreted carefully, among other limitations. However, they concluded that increasing CHADS2 scores were associated with increased risk for adverse outcomes, including death, in patients with atrial fibrillation receiving anticoagulation.

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Infections


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TNF-alpha antagonists may not increase risk for serious infections requiring hospitalization, study indicates

TNF-alpha antagonists may not increase risk for infection-related hospitalizations in patients with autoimmune diseases, according to a new study.

Researchers performed a retrospective cohort study using state and national databases to compare TNF-alpha antagonists and nonbiologic regimens in patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis, psoriatic arthritis or ankylosing spondylitis. Cohorts were matched using disease-specific propensity scores, and Cox regression models with nonbiologics were used as the reference. Overall, the study included 10,484 matched pairs with rheumatoid arthritis, 2,323 matched pairs with inflammatory bowel disease, and 3,215 matched pairs with psoriasis and spondyloarthropathies. The study involved patients treated from 1998 to 2007, 20% of whom were at least 65 years of age. The main outcome measure was serious infection requiring hospitalization in the first 12 months after nonbiologic regimens or TNF-alpha antagonists were started. Baseline use of glucocorticoids was evaluated separately. The study results were published online Nov. 6 by the Journal of the American Medical Association.

A total of 1,772 serious infections were identified, mostly pneumonia and skin and soft tissue infections (53%). Hospitalization rates for serious infection were 8.16 versus 7.78 per 100 person-years for patients with rheumatoid arthritis taking TNF-alpha antagonists versus those taking comparator regimens, respectively (adjusted hazard ratio, 1.05; 95% CI, 0.91 to 1.21). For patients with inflammatory bowel disease, these rates were 10.91 versus 9.60 per 100 person-years (adjusted hazard ratio, 1.10; 95% CI, 0.83 to 1.46), and for patients with psoriasis and spondyloarthropathies, these rates were 5.41 versus 5.37 per 100 person-years (adjusted hazard ratio, 1.05; 95% CI, 0.76 to 1.45). In patients with rheumatoid arthritis, infliximab was associated with an increased risk for serious infections compared with etanercept (adjusted hazard ratio, 1.26; 95% CI, 1.07 to 1.47) and adalimumab (adjusted hazard ratio, 1.23; 95% CI, 1.02 to 1.48). The case fatality ratio during hospitalization for serious infection was 3.6% in the rheumatoid arthritis group, 2.1% in the inflammatory bowel disease group and 7.1% for the psoriasis and spondyloarthropathies group. A dose-dependent increase in infections was associated with glucocorticoid use at baseline.

The authors acknowledged that their study used medication data from pharmacy files, which cannot confirm actual medication use, and that some study outcomes may have been misclassified because they were based on claims data, among other limitations. However, they concluded that TNF-alpha antagonists did not appear to increase risk of hospitalization for serious infections compared with nonbiologic regimens in patients with autoimmune diseases. Their results also indicate that infliximab may increase infection risk in patients with rheumatoid arthritis and that glucocorticoid use may have a strong dose-dependent relationship with infection risk, they wrote.

The authors of an accompanying editorial pointed out that residual confounding may have affected the study results, that propensity scores were generated by using data from the year before patients entered the study, and that more patients were censored in the comparison cohort than in the TNF-alpha cohort. They wrote that other trials will need to replicate the current findings but concluded that "the report. . .raises important questions about the comparative safety of immunosuppressant and biologic therapy and may prompt a reevaluation of anti-TNF safety."

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FDA update


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Deadline this week for rosiglitazone access program

Physicians who want to continue prescribing rosiglitazone-containing medications (Avandia, Avandamet, and Avandaryl) must be enrolled in the Avandia-Rosiglitazone Medicines Access Program by this Thursday, Nov. 17, the FDA reminded last week.

After that date, rosiglitazone will no longer be available through retail pharmacies and will only be available by mail order through specially certified pharmacies participating in the program. Prescribers must be enrolled in the access program and they must also enroll their patients for the patients to begin or continue to receive rosiglitazone medicines. Patients are eligible for the program if they are already taking rosiglitazone or unable to achieve glycemic control on other medications and, in consultation with a healthcare provider, have decided not to take pioglitazone for medical reasons.

Enrollment information is available on the Avandia website and information about the FDA's actions regarding the drug is on the agency's website.

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CMS update


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Version 5010 deadline approaches

As of Nov. 15, there are 46 days before the implementation of version 5010. Effective Jan. 1, 2012, physician practices will need to submit claims not only to Medicare but to all payers using version 5010 in order to be paid.

There will be no delay in the implementation date of Jan. 1, 2012. Practices should be testing submission of electronic transactions in version 5010 with all payers right now. Practices risk disrupting their cash flow with stalled payments and claims denials if they fail to test claims in version 5010 before the implementation date.

Testing takes time and cannot be done in just a few days. To help practices get ready for the implementation of version 5010, a preparation checklist and several other informational resources are available on the CMS website, along with an interactive timeline widget.

Physicians who have not started testing yet or who have questions about the testing process can call the EDI department of CMS at 877-386-1056.

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From the College


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Poster competition for student members and associates at Internal Medicine 2012

ACP will feature a national poster competition for ACP medical student members and associates at Internal Medicine 2012, which will be held in New Orleans April 19-21.

Enter for a chance to win recognition among your peers. National winners and finalists receive complimentary registration to the meeting. The deadline for entries is Dec. 1, 2011. More information is online.

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Cartoon caption contest


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Vote for your favorite entry

ACP InternistWeekly's cartoon caption contest continues. Readers can vote for their favorite caption to determine the winner.

acpi-20111115-cartoon.jpg

"Medical homeless…will work for food."

"Hey lady, care to join my concierge practice?"

"My payor mix has got to change."

Go online to pick the winner, who receives a $50 gift certificate good toward any ACP program, product or service.

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MKSAP Answer and Critique



The correct answer is A) Flow cytometry. This item is available to MKSAP 15 subscribers as item 12 in the Hematology and Oncology section. More information about MKSAP 15 is available online.

The coexistence of pancytopenia, hemolytic anemia, and thrombosis should raise the suspicion for paroxysmal nocturnal hemoglobinuria (PNH). PNH is caused by loss of glycosylphosphatidylinositol (GPI)–linked proteins on the cell surface. Two such proteins, CD55 and CD59, help reduce erythrocyte sensitivity to complement. Deficiency of CD55 and CD59 can be detected by flow cytometry. Because of the unopposed actions of complement, patients with PNH have direct antiglobulin (Coombs)–negative hemolysis. Iron deficiency is also a common finding in patients with PNH owing to iron loss in the urine. PNH is associated with thrombosis, perhaps secondary to loss of naturally occurring anticoagulants that are linked to membranes by GPI anchors. Finally, this disorder is associated with aplasia, myelodysplasia, and, rarely, acute leukemia. Recently, eculizumab, a monoclonal antibody to C5, has been reported to offer a sustained response to patients with PNH.

This patient does not have a history suggestive of a congenital hemoglobin disorder necessitating hemoglobin electrophoresis. A hemoglobinopathy would not explain the low leukocyte count or thrombocytopenia in this patient. Erythrocyte osmotic fragility is used to assess hereditary spherocytosis, but that disorder would not explain this patient's pancytopenia nor the deep venous thrombosis (DVT).

Parvovirus B19 may cause anemia or, especially in immunocompromised patients, pancytopenia, but the reticulocyte count should be less than 2%, and there is no association with DVT.

Key Point

  • Paroxysmal nocturnal hemoglobinuria is characterized by direct antiglobulin (Coombs)–negative hemolysis, pancytopenia, and thrombosis.

Click here to return to the rest of ACP InternistWeekly.

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A 69-year-old woman is evaluated for a lump under her arm found on self-examination. She is otherwise healthy and has no other symptoms. Medical and family histories are unremarkable, and she takes no medications. A needle aspirate of the right axillary mass reveals adenocarcinoma. Bilateral mammography and breast MRI are normal. CT scan of the chest, abdomen, and pelvis demonstrates the enlarged axillary lymph node and no other abnormalities. What is the most appropriate initial treatment?

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