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

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ACP InternistWeekly



In the News for the Week of November 6, 2012




Highlights

Sulfonylureas associated with higher CV risk than metformin

As initial monotherapy for type 2 diabetes, sulfonylureas were associated with more cardiovascular events and deaths than metformin, a new study found. More...

Kidney measures for CKD predict clinical risk across the full age range

Measures of kidney function used to diagnose and stage chronic kidney disease (CKD) are independently associated with end-stage renal disease (ESRD) and mortality regardless of age, according to a new study. More...


Test yourself

MKSAP Quiz: follow-up for elevated liver chemistry tests

A 42-year-old man is evaluated in follow-up for elevated liver chemistry tests. Abdominal ultrasound reveals increased hepatic echotexture consistent with hepatic steatosis. Hepatic configuration is otherwise normal. In addition to weight loss, what is the most appropriate management? More...


Bone health

Bisphosphonate therapy associated with fewer vertebral fractures in men

Two annual injections of zoledronic acid reduced risk of vertebral fracture among men with osteoporosis, according to a study supported by the drug's manufacturer. More...

Self-managed exercise may work for knee osteoarthritis

Self-managed physical therapy exercises such as aerobics, aquatics, strengthening and proprioception were effective for knee osteoarthritis, a literature review concluded. More...


CMS update

ACP to host webinar on PQRS requirements

ACP is hosting an informational webinar for physicians on the reporting requirements for the Physician Quality Reporting System (PQRS) on Nov. 29, 2012. More...


FDA update

All Ameridose unexpired products recalled

All unexpired products distributed by Ameridose, LLC, are being recalled, the FDA announced last week. More...


From ACP Internist

The next issue of ACP Internist is online and coming to your mailbox

The November issue of ACP Internist features stories about individualized treatment goals for diabetics, how to discuss dieting and weight management, and ways to diagnose skin and soft tissue infections. 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: Philip Masters, MD, FACP



Highlights


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Sulfonylureas associated with higher CV risk than metformin

As initial monotherapy for type 2 diabetes, sulfonylureas were associated with more cardiovascular events and deaths than metformin, a new study found.

The retrospective cohort study included about 250,000 patients of the Veterans Health Administration who initiated oral therapy for diabetes and who did not have chronic kidney disease or other serious medical illness. About 150,000 of them took metformin and 99,000 took a sulfonylurea. The groups were compared on a composite outcome of death or hospitalization for acute myocardial infarction or stroke.

annals.jpg

Results appeared in Annals of Internal Medicine on Nov. 6.

Sulfonylurea users had 18.2 composite events per 1,000 person-years compared to 10.4 per 1,000 person-years among metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0]; adjusted hazard ratio, 1.21 [95% CI, 1.13 to 1.30]). The results were consistent when the researchers assessed subgroups by sulfonylurea type (glyburide or glipizide), cardiovascular disease history, age, body mass index, albuminuria and propensity score.

The study suggests that sulfonylureas are associated with an increased risk of cardiovascular disease events and death compared to metformin, and it supports the use of metformin as first-line therapy, the study authors concluded. They cautioned that the study is limited by its mostly white male population and that confounding by indication is a risk. It's also still unknown whether the difference in outcomes results from more harm from sulfonylureas or greater benefit from metformin. Sulfonylureas are associated with increases in weight, lipid levels and hypoglycemia compared to metformin, the authors noted.

Cardiovascular risks have been a concern with sulfonylureas for a long time, noted both the study and an accompanying editorial. A study in 1970 showed increased risk of all-cause and cardiovascular mortality with tolbutamide, but randomized trials comparing cardiovascular outcomes of diabetes drugs have been avoided since then, the editorialist said. This nonrandomized study should be considered hypothesis-generating rather than definitive, but the findings are creditable, important and have implications for millions of patients, according to the editorial.


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Kidney measures for CKD predict clinical risk across the full age range

Measures of kidney function used to diagnose and stage chronic kidney disease (CKD) are independently associated with end-stage renal disease (ESRD) and mortality regardless of age, according to a new study.

Researchers performed an individual-level meta-analysis of over two million people to determine whether age modified the association of estimated glomerular filtration rate (eGFR) and albuminuria with ESRD and death. Both relative and absolute risks were evaluated. The meta-analysis looked at hazard ratios (HRs) of the primary end points, all-cause mortality and ESRD, according to eGFR and albuminuria by age category; data were adjusted for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol level, body mass index and smoking status. HRs and average incidence rates were used to determine absolute risks. Results were published online Oct. 30 by the Journal of the American Medical Association.

Participants from the Chronic Kidney Disease Prognosis Consortium, which is made up of 33 general population cohorts and 13 CKD cohorts in Asia, Australasia, Europe and North and South America, were included. Patients were followed for a mean of 5.8 years between 1972-2011. The mean patient age was 49.4 years, and 7.3% of patients were older than age 75.

Deaths (112,325 people) and ESRD (8,411 events) were higher in patients with lower eGFR and higher albuminuria in every age category. In both general and high-risk cohorts, relative mortality risk decreased with increasing age for reduced eGFR (adjusted HRs, 3.50 [95% CI, 2.55 to 4.81], 2.21 [95% CI, 2.02 to 2.41], 1.59 [95% CI, 1.42 to 1.77], and 1.35 [95% CI, 1.23 to 1.48] for an eGFR of 45 mL/min/1.73 m2 vs. 80 mL/min/1.73 m2 in patients age 18 to 54 years, 55 to 64 years, 65 to 74 years, and ≥75 years, respectively; P<0.05 for age interaction). Absolute risk differences increased with age for the same comparisons (9.0 excess deaths per 1,000 person-years [95% CI, 6.0 to 12.8], 12.2 excess deaths per 1,000 person-years [95% CI, 10.3 to 14.3], 13.3 excess deaths per 1,000 person-years [95% CI, 9.0 to 18.6], and 27.2 excess deaths per 1,000 person-years [95% CI, 13.5 to 45.5], respectively).

Reduced relative risk with increasing age was less marked for increased albuminuria. However, absolute risk differences were higher by older age category: 7.5 excess deaths per 1,000 person-years (95% CI, 4.3 to 11.9), 12.2 excess deaths per 1,000 person-years (95% CI, 7.9 to 17.6), 22.7 excess deaths per 1,000 person-years (95% CI, 15.3 to 31.6), and 34.3 excess deaths per 1,000 person-years (95% CI, 19.5-52.4), respectively, for an albumin-creatinine ratio of 300 mg/g compared with 10 mg/g. Adjusted relative hazards of mortality did not decrease with age in cohorts of patients with CKD, and in all cohorts, relative risks and absolute risk differences for ESRD at lower eGFRs or higher albuminuria values were comparable by age.

The authors noted that serum creatinine measurements were not standardized among studies, that no gold standard exists for measuring urine albumin, that the cohorts were heterogeneous, and that their results are based on models adjusted for traditional risk factors and therefore require careful interpretation. However, they concluded, "Although some variation in management of CKD should be considered by age based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staggering of CKD based on eGFR and albuminuria for all age groups."

The author of an accompanying editorial wrote that older adults with CKD are at high risk for death, usually from cardiovascular disease, and that clinicians should make every effort to offer proven treatment strategies in this population.

"Preventing progression of CKD may be an important goal in some patients, but most older patients with CKD will not progress to ESRD," the author wrote. He also stressed that some treatments that are effective in middle-aged adults with normal kidneys may have different benefits and risks, especially drug-related adverse effects, in older patients. "To move forward," he wrote, "CKD identification must be coupled with new treatment strategies tailored to patients with CKD, including older patients with CKD."



Test yourself


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MKSAP Quiz: follow-up for elevated liver chemistry tests

A 42-year-old man is evaluated in follow-up for elevated liver chemistry tests. He is asymptomatic. He has a 6-year history of type 2 diabetes mellitus, hyperlipidemia, and hypertension. His current medications are metformin, simvastatin, and lisinopril. He does not drink alcohol.

mksap.gif

On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 130/74 mm Hg, pulse rate is 82/min, and respiration rate is 14/min. BMI is 32 kg/m2. Abdominal examination discloses mild hepatomegaly and active bowel sounds.

Laboratory studies:

Alkaline phosphatase 90 units/L
Alanine aminotransferase 120 units/L
Aspartate aminotransferase 85 units/L
Total bilirubin 1.1 mg/dL (18.8 µmol/L)
LDL cholesterol 100 mg/dL (2.59 mmol/L)
Hemoglobin A1c 7.2%
Iron 75 µg/dL (13 µmol/L)
Total iron-binding capacity 300 µg/dL (54 µmol/L)
Hepatitis B surface antigen Negative
Antibody to hepatitis B surface antigen Positive
Hepatitis C virus antibody Negative

Abdominal ultrasound reveals increased hepatic echotexture consistent with hepatic steatosis. Hepatic configuration is otherwise normal.

In addition to weight loss, which of the following is the most appropriate management?

A: Discontinue simvastatin
B: Initiate entecavir
C: Phlebotomy
D: Serial monitoring of aminotransferases

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


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Bone health


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Bisphosphonate therapy associated with fewer vertebral fractures in men

Two annual injections of zoledronic acid reduced risk of vertebral fracture among men with osteoporosis, according to a study supported by the drug's manufacturer.

Researchers conducted a multicenter, double-blind, placebo-controlled trial that randomly assigned nearly 1,200 men ages 50 to 85 with osteoporosis to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at the initiation of the study and a repeat infusion at 12 months into the study.

Men were eligible to participate if they had a bone mineral density T score of –1.5 or less at the total hip or femoral neck and one to three prevalent vertebral fractures of mild or moderate grade. Men without fractures were eligible if they had a bone mineral density T score of –2.5 or less at the total hip, femoral neck or lumbar spine.

The study was designed and supported by Novartis. Results appeared online Nov. 1 at the New England Journal of Medicine.

New morphometric vertebral fractures occurred in 1.6% of the treatment group and 4.9% of the placebo group (relative risk, 0.33; 95% CI, 0.16 to 0.70; P=0.002). Men in the treatment group also had fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss (P=0.002) compared to those on placebo. Men in the active treatment group also had higher bone mineral density and lower bone-turnover markers (P<0.05 for both comparisons).

The trial supports the idea that antiresorptive treatments are effective in both men and women, researchers wrote. "Despite the fact that current public health efforts to detect osteoporosis and prevent fractures in men are inadequate, the ability to establish detection and treatment recommendations has been limited because of the absence of unambiguous evidence of effective antifracture therapies in men," researchers wrote. "Although our findings with zoledronic acid do not imply that all data on drugs for osteoporosis in women can be extrapolated to men, our study should provide the confidence to proceed."


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Self-managed exercise may work for knee osteoarthritis

Self-managed physical therapy exercises such as aerobics, aquatics, strengthening and proprioception were effective for knee osteoarthritis, a literature review concluded.

annals.jpg

Researchers conducted a literature review of physical therapy interventions for community-dwelling adults with knee osteoarthritis, finding 193 randomized, controlled trials (RCTs) published from 1970 to February 2012. Researchers extracted means of outcomes, interventions and risk of bias to pool standardized mean differences. Results appeared in the Nov. 6 Annals of Internal Medicine.

Four RCTs including 247 patients undergoing proprioception exercise found it improved pain but not composite function or gait function. Eleven RCTs of 1,553 patients trying aerobic exercise found it led to statistically significant improvements in pain lasting longer than 26 weeks and disability, but not in psychological disability or health perception. Within three months, aerobic exercise also improved composite function and gait function (walking speed difference, −0.11 m/s [95% CI, −0.15 to −0.08 m/s]). At 12 months, the benefits of aerobic exercise continued for gait function (walking speed difference, −0.11 m/s [95% CI, −0.17 to −0.05 m/s]) but not for composite function.

Three RCTs among 348 participants found that aquatic exercise reduced disability but had no statistically significant effects on pain relief or quality of life. Nine RCTs among 1,982 participants found that strengthening exercise had no statistically significant effect on disability or quality of life but did improve pain relief, composite function and gait function. The improvements in pain and composite function were clinically important. Two RCTs among 511 participants showed that education programs had no statistically significant effect on pain relief.

Future studies should compare combined interventions, which is how physical therapy is generally administered for pain associated with knee osteoarthritis, researchers noted.

"Our analyses further indicate a possible association between high adherence to exercise and improvement in knee pain and function," researchers wrote. "Thus, therapeutic exercise programs should focus on achieving higher adherence rather than increasing the amount or intensity of exercise."



CMS update


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ACP to host webinar on PQRS requirements

ACP is hosting an informational webinar for physicians on the reporting requirements for the Physician Quality Reporting System (PQRS) on Nov. 29, 2012.

The webinar will focus on the new changes to the PQRS regulations and how physicians can utilize the PQRIwizard tool to comply with reporting regulations. The PQRIwizard is an online tool designed to help physicians and other eligible professionals quickly and easily participate in the PQRS requirements. ACP members can purchase the PQRIwizard at a discounted rate.

The webinar will feature a general overview on the PQRIwizard, current and future payment risk/rewards for PGRS, eRx and other programs. More information on the webinar is available online.



FDA update


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All Ameridose unexpired products recalled

All unexpired products distributed by Ameridose, LLC, are being recalled, the FDA announced last week.

The recall resulted from an ongoing FDA inspection of Ameridose's facility in Westborough, Mass. Preliminary findings of the inspection have raised concerns about a lack of sterility assurance for products produced at and distributed by this facility, according to the FDA. There haven't been any reports of infections associated with any of the products, they noted. The recall was recommended by the FDA and voluntarily conducted by Ameridose out of an abundance of caution.

Health care professionals should stop using Ameridose products at this time and return them to the firm, but they do not need to follow up with patients who received the products, the FDA said. The facility has ceased all pharmacy and manufacturing operations as of Oct. 10, 2012.

Six of the recalled products are on the FDA critical shortage list, the agency noted. Those drugs are injections of sodium bicarbonate, succinylcholine, atropine sulfate, bupivacaine hydrochloride, lidocaine hydrochloride and furosemide. The FDA is asking other current and potential manufacturers of these drugs to ramp up production to provide safe, high-quality supplies.



From ACP Internist


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The next issue of ACP Internist is online and coming to your mailbox

The November issue of ACP Internist features stories about:

acpi-20121106-internist.jpg

'Goldilocks' goal for diabetics and chronic kidney disease. Managing kidney disease in diabetes requires meeting individualized parameters and balancing risks in nephrology and cardiology. Learn whether more aggressive treatment is warranted in this population.

Doctors don't have to dread discussing dieting. Many internists are not discussing obesity and weight loss with their patients, even though they have the best opportunity to offer counseling about diet and new weight-loss drugs.

Spare the emergency visit for skin and soft tissue infections. Internists can save patients the anxiety, time and expense of an emergency department visit by screening for severity of most skin and soft tissue infections, experts say. The focus should be on the level of acuity and the factors surrounding onset of symptoms.

Also, the latest installment of the MKSAP Quiz and the election roster for ACP officer and regent elections are online.



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.

acpi-20121106-cartoon.jpg

"Some refer to my practice as fee-for-service, but I prefer the term a la carte."

"I recommend the liver."

"Since opening my concierge practice, I'm able to offer many new service options. I see the sigmoidoscopy paired with a nice pinot grigio has caught your eye."

Go online to pick the winner, who receives a $50 gift certificate good toward any ACP program, product or service. Voting ends on Monday, Nov. 12, with the winner announced in the Nov. 13 issue.


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MKSAP Answer and Critique



The correct answer is D: Serial monitoring of aminotransferases. This item is available to MKSAP 16 subscribers as item 2 in the Gastroenterology and Hepatology section.

MKSAP 16 released Part A on July 31. More information is available online.

The most appropriate management is serial monitoring of aminotransferases, in addition to weight loss through dietary and lifestyle changes. There is no definitive treatment for nonalcoholic fatty liver disease. The reduction of underlying risk factors is essential. Weight loss, exercise, and aggressive control of plasma glucose, lipids, and blood pressure are the mainstays of treatment. Nonalcoholic fatty liver disease has become a leading cause of liver disease in the Western world, along with hepatitis C and alcoholic liver disease. When hepatic steatosis is associated with liver inflammation, as is seen in this patient with elevated hepatic aminotransferases, nonalcoholic steatohepatitis (NASH) is diagnosed. The association of NASH with the metabolic syndrome (obesity, dyslipidemia, hypertension, insulin resistance) is well established. Although most cases of nonalcoholic fatty liver disease are seen in patients who are overweight, the condition has also been described in patients who have a normal BMI. The cornerstone of management of NASH is typically weight loss through diet and lifestyle modification. Monitoring of hepatic aminotransferases is appropriate to confirm that weight loss results in improved markers of liver inflammation. Associated medical conditions such as dyslipidemia should be treated, and statins such as simvastatin should not be discontinued in this setting. The risks of hepatotoxicity due to the use of medications such as simvastatin are usually outweighed by the benefits derived from these medications in regard to cardiovascular risk reduction.

This patient's hepatitis B serologies indicate immunity to hepatitis B virus; therefore, an antiviral medication such as entecavir is not appropriate.

This patient's iron stores are not elevated, with a transferrin saturation (iron/total iron binding capacity) of less than 45%; therefore, phlebotomy is not warranted as a treatment in this setting.

Key Point

  • Weight loss, exercise, and aggressive control of plasma glucose, lipids, and blood pressure are the mainstays of treatment for nonalcoholic steatohepatitis; monitoring of hepatic aminotransferases is appropriate to confirm that weight loss results in improved markers of liver inflammation.

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