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

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ACP InternistWeekly



In the News for the Week of July 17, 2012




Highlights

Interaction between proton-pump inhibitors, clopidogrel clinically unimportant

The interaction between proton-pump inhibitors and clopidogrel is clinically unimportant, researchers found. More...

Young women hit, and hurt by, urinary incontinence

Urinary incontinence affects young, nulligravid women and significantly impacts their psychological well-being, a recent survey found. More...


Test yourself

MKSAP Quiz: preoperative evaluation prior to a hysterectomy

This week's quiz asks readers to evaluate a 37-year-old woman prior to a hysterectomy for worsening menstrual bleeding. More...


Geriatrics

Many more elderly people could benefit from drugs to prevent heart disease

Preventive treatments for cardiovascular disease may be underutilized in older patients. Although age and gender inequalities are known to exist for secondary prevention of cardiovascular disease, whether this pertains to interventions focused toward preventing heart disease is less clear. More...


Urinary tract infections

Cranberry may help prevent UTIs

Cranberry-containing products appeared to reduce urinary tract infections (UTIs) in susceptible populations, a new meta-analysis found. More...


Women's health

Diet may improve vasomotor symptoms in postmenopausal women

Eating a healthy diet may help improve vasomotor symptoms in postmenopausal women, according to a new study. More...


FDA update

Troponin and other diagnostic tests recalled

A number of cardiovascular diagnostic tests are being recalled for possible inaccuracy of their results, the FDA announced last week. More...


CMS update

Deadline approaching for Comprehensive Primary Care initiative applications

Physician practices have only a few days left to submit applications for CMS's new Comprehensive Primary Care initiative. More...


From the College

Former ACP Japan Chapter Governor led Fukushima nuclear investigation commission

Former ACP Japan Chapter Governor Kiyoshi Kurokawa, MD, MACP, recently chaired the Fukushima Nuclear Accident Independent Investigation Commission, which was charged with investigating the Fukushima nuclear disaster and was commissioned by the National Parliament of Japan. More...

Attend a chapter meeting

Clinicians can enhance their clinical skills and knowledge and network with colleagues at local ACP chapter meetings. More...


Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for our new cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service. More...


Physician editor: Philip Masters, MD, FACP



Highlights


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Interaction between proton-pump inhibitors, clopidogrel clinically unimportant

The interaction between proton-pump inhibitors and clopidogrel is clinically unimportant, researchers found.

Researchers conducted an observational cohort study and self-controlled case series among 24,471 patients receiving clopidogrel and aspirin, using the United Kingdom General Practice Research Database with linked data from the Myocardial Ischaemia National Audit Project (MINAP) and the Office for National Statistics. Results were published online by BMJ on July 10.

Of the 24,471 patients prescribed clopidogrel and aspirin, 12,439 (50%) were also prescribed a proton-pump inhibitor at some time during the study. Death or myocardial infarction occurred in 1,419 patients (11%) receiving a proton-pump inhibitor compared with 1,341 patients (8%) who were not.

Multivariate analysis showed the hazard ratio for the association between proton-pump inhibitor use and death or incident myocardial infarction was 1.37 (95% CI, 1.27 to 1.48). Comparable results were seen for secondary outcomes and with other cytochrome P450 2C19 (CYP2C19) inhibitors and with non-CYP2C19 inhibitors.

A self-controlled case series design to remove the effect of differences between patients showed no association between proton-pump inhibitor use and myocardial infarction, with a rate ratio of 0.75 (95% CI, 0.55 to 1.01). There was no association with myocardial infarction for other CYP2C19 inhibitors/non-inhibitors.

The association found in the cohort analysis is unlikely to be causal for several reasons, the authors wrote:

  • The effect is not specific to vascular events, as shown by the hazard ratio for non-vascular mortality of 1.61 (95% CI, 1.42 to 1.82).
  • People who are prescribed long-term drug treatment in addition to clopidogrel are inherently at higher risk of harmful outcomes, but not through a causal association with the treatments they receive.
  • Cohort results could be explained by confounding. Results provided no evidence of an increased risk of incident myocardial infarction during periods when patients were exposed to any proton-pump inhibitors (incident rate ratio [IRR], 0.75; 95% CI, 0.55 to 1.01), ranitidine (IRR, 0.57; 95% CI, 0.31 to 1.06) or citalopram (IRR, 0.84; 95% CI, 0.49 to 1.45).

"Taken together, a plausible explanation for our results is that the increased risk of both vascular and non-vascular harmful outcomes seen in patients receiving proton pump inhibitors and other long term drugs could be caused by confounding between people," the authors wrote. "Although accounting for such confounding can be difficult, the use of approaches such as the self-controlled case series, which is less prone to differences between people, can solve this problem. The lack of association seen between proton pump inhibitor use and myocardial infarction with this approach argues against a clinically relevant interaction between clopidogrel and proton pump inhibitors."

An editorial expanded on the use of a self-controlled study to resolve residual confounding and offered clinical advice.

"Because patients with cardiovascular disease are at an especially high risk for morbidity and mortality after an acute gastrointestinal haemorrhage, clinicians should strongly consider prescribing a PPI to all patients who use dual antiplatelet drugs, especially in the presence of additional risk factors for gastrointestinal complications, such as age over 60; concomitant use of non-steroidal anti-inflammatory drugs, other anticoagulants, or corticosteroids; and important medical comorbidities," the editorial stated.


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Young women hit, and hurt by, urinary incontinence

Urinary incontinence (UI) affects young, nulligravid women and significantly impacts their psychological well-being, a recent survey found.

Researchers surveyed about 1,000 Australian women, ages 16 to 30, at university campuses and off-campus medical clinics. The mean age of the participants was 22.5 years. Overall, 12.6% of them reported having urinary incontinence (95% CI, 10.5% to 14.7%), with slightly more students than nonstudents reporting the problem (13.2% vs. 10.6%). Incontinence was highest among students who were sexually active and not using combined oral contraceptives (21.5%; 95% CI, 16.7% to 27.3%).

annals.jpg

This study, published in the July 17 Annals of Internal Medicine, may be the first to examine urinary incontinence in nulligravid women, and it shows that the problem is fairly common, the authors said. The association with sexual activity could result from biomechanical effects or altered urogenital tract flora, they suggested. Previous research on incontinence and contraceptive use has produced conflicting results, but major previous studies did not take sexual activity without contraceptive use into account.

The effect of incontinence on the surveyed women's self-reported well-being was significant. Affected women scored worse on measures of anxiety, depression, positive well-being and self-control. The difference in well-being between women with and without incontinence in this study was similar to differences reported in previous research by young women with and without invasive breast cancer. The results show that "the consequences of UI for young women are not limited to bothersome symptoms but include adverse effects on behavior and psychological well-being," the authors wrote.

The study's findings are likely conservative estimates of urinary incontinence, given the relative healthiness of the studied population, the authors noted. They called for further investigation of the prevalence of incontinence in nulligravid women and the apparent relationship with sexual activity and contraceptive use.



Test yourself


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MKSAP Quiz: preoperative evaluation prior to a hysterectomy

A 37-year-old woman undergoes preoperative evaluation prior to a hysterectomy for worsening menstrual bleeding of several years' duration caused by uterine fibroids. She has a recent history of recurrent epistaxis and bleeding after recent dental work but denies thromboembolism and a family history of unusual bleeding. The patient is otherwise healthy. Her only medication is an occasional aspirin.

The pelvic examination reveals a slightly enlarged, irregular uterus. The remainder of the physical examination is normal.

Laboratory studies:

Hemoglobin 11 g/dL (110 g/L)
Platelet count 182,000/µL (182 × 109/L)
INR 1.1
Activated partial thromboplastin time (aPTT) 52 s

Which of the following is the most appropriate next diagnostic test?

A) Anticardiolipin antibody assay
B) aPTT mixing study
C) Factor VIII assay
D) von Willebrand factor assay

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


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Geriatrics


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Many more elderly people could benefit from drugs to prevent heart disease

Preventive treatments for cardiovascular disease may be underutilized in older patients. Although age and gender inequalities are known to exist for secondary prevention of cardiovascular disease, whether this pertains to interventions focused toward preventing heart disease is less clear.

To establish whether age and sex deter physicians from assigning primary preventive treatment for cardiovascular disease in a primary care population, researchers conducted a cross-sectional study of all 41,250 patient records of patients ages 40 and older at 19 general practices in the West Midlands, United Kingdom.

Patients were subdivided into five-year age brackets up to 85 years old, and researchers assessed prescribing trends across the population by estimating the proportion of patients prescribed an antihypertensive drug or statin, or both, in each group. Results were published online July 12 by BMJ.

The proportion of patients receiving antihypertensive drugs increased with age, from 5% of those ages 40 to 44 to 57% of those older than 85. The likelihood of prescription of an antihypertensive drug increased with each five-year age increment, with patients ages 45 to 49 having an odds ratio (OR) of receiving an antihypertensive of 1.8 (95% CI, 1.6 to 2.0; P<0.001) and patients ages 80 to 84 having an OR of 25.8 (95% CI, 22.2 to 30.1; P<0.001) compared to a reference standard of 40- to 44-year-olds.

Use of statin drugs also increased with age up to 74, from 3% of patients ages 40 to 44 to 29% of 70- to 74-year-olds. In those age 75 and over, however, only 23% were prescribed statins. In those age 75 and older, the odds of receiving a statin prescription decreased with every five-year bracket from ages 75 to 79 (OR compared to ages 40 to 44, 12.9; 95% CI, 10.8 to 15.3; P<0.001) to age 85 and older (OR, 5.7; 95% CI, 4.6 to 7.2; P<0.001).

The proportion of men and women prescribed antihypertensive drugs was similar in all age groups apart from those ages 65 to 69 and 75 to 79, in whom prescriptions were more common for women (39% of women compared to 34% of men for ages 65 to 69; 55% to 48%, respectively, for ages 75 to 79). Overall, women were 10% more likely to receive antihypertensive drugs than men (P<0.001).

Statin prescriptions were more common in men than women below age 60 (6% in women compared to 8% in men, for ages 40 to 59) but were more common in women over age 75 (28% in women compared to 22% in men, for ages 75 to 84). Overall, men were more likely to receive statin prescriptions than women (OR, 1.1; 95% CI, 1.1 to 1.2; P<0.001).

The authors wrote, "[T]here is a striking contrast between use of statins and use of antihypertensive drugs in older people, which does point to possible underuse of statins. To better understand the clinical implications of our findings, more research is needed to determine why general practitioners refrain from prescribing primary preventive treatment in elderly people, the attitudes of older people towards preventive drugs, and the costs and benefits of prescribing in this age group."



Urinary tract infections


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Cranberry may help prevent UTIs

Cranberry-containing products appeared to reduce urinary tract infections (UTIs) in susceptible populations, a new meta-analysis found.

The review was intended as an update of a 2008 Cochrane review that had found favorable effects from cranberry juice. Searching MEDLINE, EMBASE and the Cochrane Central Register, the authors found a number of randomized controlled trials of cranberry-containing products for preventing UTIs published since the last review, which they analyzed together with older trials. In total, the analysis included 10 trials, with about 1,500 participants.

Cranberry users had a 38% lower risk of UTI compared to nonusers (random-effects pooled risk ratio [RR], 0.62; 95% CI, 0.49 to 0.80), the analysis found, with a moderate degree of heterogeneity among trials (I2=43%). Some subgroups appeared to benefit more from cranberry consumption, including women with recurrent UTIs (risk ratio [RR], 0.53; 95% CI, 0.33 to 0.83), women generally (RR, 0.49; 95% CI, 0.34 to 0.73) and children (RR, 0.33; 95% CI, 0.16 to 0.69). The results were published in the July 9 Archives of Internal Medicine.

Cranberry juice appeared to be more effective than capsules or tablets (RR for juice drinkers, 0.47; 95% CI, 0.30 to 0.72), although researchers noted some potential limitations of this finding. While the effect might come from some additive or synergistic effect of a substance in the juice, it might also be that the juice drinkers were better hydrated than other cranberry consumers. In addition, consuming a large quantity of sugared cranberry juice might be problematic for diabetic patients, the authors noted.

Frequent consumption of cranberry appeared to improve effectiveness; relative risk was 0.58 for participants who consumed the products more than twice daily (95% CI, 0.40 to 0.84). The analysis was not able to determine the most effective dose of cranberry, however. Included trials had a wide variation in the proanthocyanidin (PAC) content of their cranberry products. Researchers called for specification of PAC content in future trials and on cranberry products.

Another limitation of the study was that an outlier study had to be excluded in order to show a significant effect of cranberry products. With that study included, the overall risk ratio associated with cranberry consumption would have been 0.68 with a 95% CI of 0.47 to 1.00. The outlier trial used a lower bacteruria threshold and had a much lower overall incidence rate of UTI. In conclusion, the analysis authors said that consumption of cranberry products may protect certain populations against UTIs, but they urged that results be interpreted cautiously, given the heterogeneity of the trials.



Women's health


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Diet may improve vasomotor symptoms in postmenopausal women

Eating a healthy diet may help improve vasomotor symptoms in postmenopausal women, according to a new study.

Researchers set out to determine whether a diet that reduced fat intake and increased intake of fruit, vegetables and whole grains, along with resulting weight loss, would improve vasomotor symptoms of menopause, such as night sweats and hot flashes. They examined data from participants in the Women's Health Initiative Dietary Modification Trial who were not taking hormone replacement therapy. Women in the intervention group followed a low-fat diet (20% of energy from fat) with high intake of fruit and vegetables (five servings a day) and whole grains (six servings a day) and received group sessions with a nutritionist or dietitian, while women in the control group received written information on healthy diets. The study results were published online July 9 by Menopause.

Overall, 17,743 women from 50 to 79 years of age were included in the study. At baseline, 74% reported no hot flashes, 19% reported mild hot flashes, 6% reported moderate hot flashes, and 1% reported severe hot flashes. In addition, 73% reported no night sweats while 20% reported mild night sweats, 6% reported moderate night sweats, and 1% reported severe night sweats.

Multivariate-adjusted analyses that were also adjusted for intervention and for weight change found that women in the dietary intervention group who had vasomotor symptoms at baseline were significantly more likely to report symptom cessation than those assigned to the control group (odds ratio [OR], 1.14 [95% CI, 1.01 to 1.28]). Those who had symptoms at baseline but lost at least 10 pounds (OR, 1.23 [95% CI, 1.05 to 1.46]) or at least 10% of their body weight (OR, 1.56 [95% CI, 1.21 to 2.02]) by year 1 were also significantly more likely to report symptom cessation than those who maintained their baseline weight.

When the authors looked at the combined effect of dietary modification and weight loss, they found that women who lost at least 10% of their body weight via the intervention had a better chance of eliminating vasomotor symptoms than women in the control arm who lost the same amount, although the difference was not significant (ORs, 1.89 [95% CI, 1.39 to 2.57] vs. 1.40 [95% CI, 0.92 to 2.13]). An association was seen between large weight loss (i.e., over 22 pounds) and elimination of moderate to severe symptoms, but this association was not seen for dietary changes.

The authors noted that they didn't use objective measures of symptoms and didn't measure frequency, among other limitations. However, they concluded that the type of diet examined in this trial appeared to alleviate vasomotor symptoms in postmenopausal women, "over and above the effect of weight change." Their findings support the idea that weight loss and changes in diet could be used as alternatives to hormone replacement therapy for vasomotor symptom relief in this population, they said.



FDA update


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Troponin and other diagnostic tests recalled

A number of cardiovascular diagnostic tests are being recalled for possible inaccuracy of their results, the FDA announced last week.

The Class I recall affects Alere Triage products, including CardioProfiler Panel PN 97100CP, Cardiac Panel PN 97000HS, Profiler SOB Panel PN 97300, BNP PN 98000XR, and D-dimer PN 98100.

According to the FDA, almost 100,000 test kits have the potential to be defective. Defective kits may have significantly lower precision than expected, which could result in increased frequency of false-positive or false-negative results. These false results are unpredictable within lots and may not be detected by quality control testing. Troponin I results of over 0.05 ng/mL for samples found to be below 0.05 ng/mL upon additional testing have been reported, as well as patients receiving inappropriate clinical management that may have been due to such erroneous results.

All of the recalled tests should be immediately discarded, although there may not currently be sufficient unaffected product to supply the product demand for all laboratories, the FDA warned.



CMS update


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Deadline approaching for Comprehensive Primary Care initiative applications

Physician practices have only a few days left to submit applications for CMS's new Comprehensive Primary Care (CPC) initiative.

This initiative combines public and private health payers in selected geographical markets to provide monthly care management payments (which will average about $20 per beneficiary per month from CMS, plus additional payments from the other participating payers) to primary care practices who better coordinate care for their patients, and after two years offer them the chance to share in any savings they generate.

All applications are due by 5:00 p.m. Eastern Time on July 20. If you're an interested practice from one of the selected markets participating in this program, please visit the CPC section of the CMS website.



From the College


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Former ACP Japan Chapter Governor led Fukushima nuclear investigation commission

Former ACP Japan Chapter Governor Kiyoshi Kurokawa, MD, MACP, recently chaired the Fukushima Nuclear Accident Independent Investigation Commission, which was charged with investigating the Fukushima nuclear disaster and was commissioned by the National Parliament of Japan.

The panel, which recently released a final report, interviewed 1,167 people and collected 900 hours of public testimony. The panel called for a complete revamp of Japan's nuclear industry and regulatory structure and made recommendations to increase safety and public health.

This commission is the first such assignment in the history of modern Japan since the occupation by the U.S. after World War II in 1945. ACP congratulates Dr. Kurokawa on being asked to assume this prominent leadership position.

More information on the task force and the final report are available online.


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Attend a chapter meeting

Clinicians can enhance their clinical skills and knowledge and network with colleagues at local ACP chapter meetings.

ACP members and nonmembers alike can gain insight into recent medical advances, discuss local and national issues affecting internal medicine, and learn about the benefits of membership. ACP chapter meetings will help clinicians meet not only their needs as general internists, subspecialty internists, family practitioners, fellows in subspecialty training, allied health practitioners, or residents, but also the needs of the patients they serve.

More information about upcoming meetings, CME offerings and registration is available online.



Cartoon caption contest


.
Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.

acpi-20120717-cartoon.jpg

E‑mail all entries to acpinternist@acponline.org. ACP staff will choose finalists and post them online for an online vote by readers. The winner will appear in an upcoming edition.


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MKSAP Answer and Critique



The correct answer is B) aPTT mixing study. This item is available to MKSAP 15 subscribers as item 33 in the Hematology and Oncology section. MKSAP 16 will release Part A on July 31. More information is available online.

This patient has a prolonged activated partial thromboplastin time (aPTT). The first diagnostic step in determining the cause of an abnormal aPTT or prothrombin time (PT) is to perform an inhibitor mixing study. In a mixing study, the patient's plasma is mixed in a 1:1 ratio with normal pooled plasma, and the clotting tests with abnormal results are repeated. A mixing study that corrects to normal indicates a factor clotting deficiency, whereas one that does not correct (or only poorly corrects) indicates the presence of a clotting inhibitor or antibody. Once the results of the inhibitor mixing study are established, other assays to identify the deficient clotting factor or the type of clotting inhibitor can be done.

Although this patient might have von Willebrand's disease, hemophilia A, or the antiphospholipid antibody syndrome with a mild factor VIII deficiency causing an elevated aPTT, understanding the mechanism responsible for the elevated aPTT is necessary before performing tests to rule out these diagnoses.

Key Point

  • Performing an inhibitor mixing study is the first step in identifying the cause of an abnormal activated partial thromboplastin time or prothrombin time.

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Test yourself

A 50-year-old man is evaluated in follow-up for a recent diagnosis of cirrhosis secondary to nonalcoholic steatohepatitis. He has a history of asthma, type 2 diabetes mellitus, hyperlipidemia, and obesity. His current medications are inhaled fluticasone, montelukast, insulin glargine, insulin lispro, simvastatin, and lisinopril. Following a physical exam, lab studies, and upper endoscopy, what is the most appropriate treatment?

Find the answer

MKSAP 16 Holiday Special: Save 10%

MKSAP 16 Holiday Special:  Save 10%

Use MKSAP 16 to earn MOC points, prepare for ABIM exams and assess your clinical knowledge. For a limited time save 10% when you use priority code MKPROMO! Order now.

Maintenance of Certification:

What if I Still Don't Know Where to Start?

Maintenance of Certification: What if I Still Don't Know Where to Start?

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