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

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ACP InternistWeekly



In the News for the Week of 9-27-11




Highlights

Mortality higher after two days off from dialysis

Longer intervals between hemodialysis sessions are associated with higher mortality and hospital admissions, a new study found. More...

Trimethoprim-sulfamethoxazole plus spironolactone may increase hyperkalemia risk in elderly

Elderly patients taking spironolactone and trimethoprim-sulfamethoxazole may be at increased risk for hospitalization due to hyperkalemia, according to a new study. More...


Test yourself

MKSAP Quiz: sudden loss of vision in one eye

This week's quiz asks readers to evaluate a 75-year-old woman with sudden loss of vision in one eye. More...


Men's health

Model predicts erectile function after prostate cancer

Researchers have developed a new model to predict the risk of erectile dysfunction for men undergoing prostate cancer treatment. More...

Prostate biopsy complications rising with a high rate of post-procedure hospitalizations

Prostate biopsy was associated with a 6.9% hospitalization rate within 30 days, compared to a 2.9% hospitalization rate among a control group of men who did not have a biopsy, researchers found. More...


Neurology

Antiepileptic drugs associated with sevenfold drop in sudden, unexpected deaths

Treatment with adjunctive antiepileptic drugs at efficacious doses may reduce sudden unexpected death in epilepsy by more than seven times compared with placebo in patients with previously uncontrolled seizures. More...

Outpatient stroke prevention clinics may be as effective as organized inpatient care

Outpatient stroke prevention clinics may be as effective as organized inpatient care in patients who have had an ischemic stroke or transient ischemic attack, according to a new study. More...


Resources

Free technical assistance available for new Guided Care model

Free tools are available for Guided Care, a new model of primary care for older adults with chronic conditions and complex health needs that is designed to improve quality of care and efficient resource use. More...


From the College

ACP's Center for Ethics and Professionalism receives grant to advance professionalism

ACP's Center for Ethics and Professionalism has been awarded a grant from the American Board of Internal Medicine Foundation for the advancement of professionalism among practicing physicians. More...


Cartoon caption contest

And the winner is …

ACP InternistWeekly has tallied the voting from its latest cartoon contest, where readers are invited to match wits against their peers to provide the most original and amusing caption. More...


Physician editor: Darren Taichman, MD, FACP




Highlights


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Mortality higher after two days off from dialysis

Longer intervals between hemodialysis sessions are associated with higher mortality and hospital admissions, a new study found.

The study included more than 32,000 participants in the End-Stage Renal Disease Clinical Performance Measures Project. The patients received hemodialysis three times per week, so that they had one two-day interval of no dialysis every week. Researchers compared rates of death and hospital admission on the day after that break with rates on all other days. The results were published in the Sept. 22 New England Journal of Medicine.

During a mean follow-up of 2.2 years, the researchers found that days after the break were associated with higher all-cause mortality (22.1 vs. 18.0 deaths per 100 person-years; P<0.001), mortality from cardiac causes (10.2 vs. 7.5; P<0.001), infection-related mortality (2.5 vs. 2.1; P=0.007), mortality from cardiac arrest (1.3 vs. 1.0; P=0.004), and mortality from myocardial infarction (6.3 vs. 4.4; P<0.001). On that day, there were also more hospital admissions for myocardial infarction (6.3 vs. 3.9; P<0.001), congestive heart failure (29.9 vs. 16.9; P<0.001), stroke (4.7 vs. 3.1; P<0.001), dysrhythmia (20.9 vs. 11.0; P<0.001), and any cardiovascular event (44.2 vs. 19.7; P<0.001).

The findings confirm widespread clinical impressions that two-day intervals are associated with higher risks, the study authors said. The causes and effects cannot be definitely identified, but the researchers believe it unlikely that confounding could be responsible for the results.

In addition to the negative impact of the two-day interval on patients' health, the current setup of dialysis may be increasing health care costs more than the addition of an extra dialysis session would, the authors suggested. They called for a controlled trial of dialysis schedules.

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Trimethoprim-sulfamethoxazole plus spironolactone may increase hyperkalemia risk in elderly

Elderly patients taking spironolactone and trimethoprim-sulfamethoxazole may be at increased risk for hospitalization due to hyperkalemia, according to a new study.

Researchers in Ontario, Canada, performed a population-based case-control study of patients 66 years of age and older who were receiving long-term treatment for spironolactone and were admitted to a hospital for hyperkalemia within two weeks of being prescribed trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin or nitrofurantoin. Each patient was matched with up to four controls from the same cohort by age, sex, chronic kidney disease and diabetes, and receipt of one of the study antibiotics within two weeks of the patient's index date. Data were obtained from government databases on prescriptions and hospital admissions.

The study's main outcome measures were the odds ratio (OR) for the association between hospital admission and use of a study antibiotic in the previous 14 days, with adjustments for conditions and other drugs that could affect hyperkalemia risk. Results appear in the Sept. 17 BMJ.

Between April 1, 1992 and March 1, 2010, 6,903 patients were admitted for hyperkalemia. Three hundred six patients were admitted within two weeks of antibiotic use, and of these, 248 (81%) were matched with 783 controls. Overall, 17,859 of 165,754 patients taking long-term spironolactone (10.8%) had also received at least one trimethoprim-sulfamethoxazole prescription. Compared with amoxicillin, trimethoprim-sulfamethoxazole was associated with a substantially increased risk for hospital admission due to hyperkalemia (adjusted OR, 12.4; 95% CI, 7.1 to 21.6). Nitrofurantoin was also associated with increased risk (adjusted OR, 2.4; 95% CI, 1.3. to 4.6), while norfloxacin was not (adjusted OR, 1.6; 95% CI, 0.8 to 3.4).

The authors noted that their study used only administrative data, that outpatient episodes of hyperkalemia could not be quantified, and that residual confounding might have been present, among other limitations. However, they concluded that prescribing trimethoprim-sulfamethoxazole to elderly patients taking spironolactone significantly increased risk for hospitalization due to hyperkalemia compared with the other antibiotics studied.

"Increased awareness of this drug interaction among pharmacists and physicians is needed to ensure that the potential for life threatening hyperkalemia with this drug combination is minimized, either by selection of alternative antibiotics when appropriate or by close monitoring of patients treated with both drugs," the authors wrote.

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Test yourself


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MKSAP Quiz: sudden loss of vision in one eye

A 75-year-old woman is evaluated for a sudden loss of vision in the left eye that began 30 minutes ago. She has a 2-week history of fatigue; malaise; and pain in the shoulders, neck, hips, and lower back. She also has a 5-day history of mild bitemporal headache.

On physical examination, temperature is 37.3 °C (99.1 °F), blood pressure is 140/85 mm Hg, pulse rate is 72/min, and respiration rate is 16/min. BMI is 31. The left temporal artery is tender. Funduscopic examination reveals a pale, swollen optic disc. Range of motion of the shoulders and hips elicits moderate pain.

Laboratory studies:

Hemoglobin 9.9 g/dL (99 g/L)
Leukocyte count 7300/µL (7.3 × 109/L)
Platelet count 456,000/µL (456 × 109/L)
Erythrocyte sedimentation rate 116 mm/h

Which of the following is the most appropriate next step in this patient's management?

A) Brain MRI
B) High-dose intravenous methylprednisolone
C) Low-dose oral prednisone
D) Temporal artery biopsy

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

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Men's health


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Model predicts erectile function after prostate cancer

Researchers have developed a new model to predict the risk of erectile dysfunction for men undergoing prostate cancer treatment.

The model was developed using pre- and post-treatment data for more than 1,000 men who had prostatectomy, external radiotherapy or brachytherapy for prostate cancer at one of several academic medical centers between 2003 and 2006. The model's ability to predict erectile dysfunction two years after treatment was then validated in a community-based cohort of almost 2,000 men. The results were published in the Sept. 21 Journal of the American Medical Association.

Two years after treatment, post-treatment erections were reported by 37% of the overall patient group (95% CI, 34% to 40%) and 48% of the men who had functional erections before treatment (95% CI, 45% to 52%). Of those men who were potent before treatment, erectile dysfunction was reported posttreatment in 60% of the prostatectomy group (95% CI, 55% to 65%), 42% of the external radiotherapy group (95% CI, 33% to 51%) and 37% of the brachytherapy group (95% CI, 30% to 45%).

The researchers identified several factors in addition to the method of treatment that appeared to affect the rate of posttreatment dysfunction, including pretreatment function (measured by a sexual health-related quality-of-life score), age, serum prostate-specific antigen (PSA) level, race/ethnicity, and body mass index. The model's predictions of erectile function ranged from 10% to 70% depending on individual patient characteristics. The validation cohort indicated that the model performed well at predicting dysfunction.

The study also looked at the treatments men used to assist with erectile function. Phosphodiesterase-5 inhibitors were the most commonly used, and intracorporal penile injections were the least used but the most effective. Due to limitations of the observational design of the study, the results should be used not to determine treatment superiority, but rather to help set physicians' and patients' expectations after prostate cancer treatment, the authors said.

An accompanying editorial noted that the study was also limited by its failure to include men who chose watchful waiting over active surveillance and by the development of the model at academic medical centers, which may have better results.

After cautioning that the findings should be used cautiously, the editorialist offered a informal synopsis: "[F]or most scenarios, the take-away message is that if the patient has chosen surgery, he will more than likely lose erectile function, whereas if he has chosen radiotherapy, he has a better than even chance of preserving it, at least for 2 years."

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Prostate biopsy complications rising with a high rate of post-procedure hospitalizations

Prostate biopsy was associated with a 6.9% hospitalization rate within 30 days, compared to a 2.9% hospitalization rate among a control group of men who did not have a biopsy, researchers found.

Also, the study found a significant rise in complications, such as bleeding and infection, as well as flare-ups of underlying medical conditions, such as heart failure or breathing disorders, the study found, And while mortality rates in men undergoing prostate biopsies did not increase, those hospitalized with infections had a 12-fold higher risk of death compared to men who did not have a biopsy.

Johns Hopkins researchers published their results online Sept. 23 at The Journal of Urology.

The study examined the frequency of biopsy-related complications that required hospitalization in more than 17,400 Medicare beneficiaries from 1991 to 2007, as identified by carrier or outpatient claims, compared to a cohort of 134,977 men who did not undergo a biopsy.

The 30-day hospitalization rate was 6.9% (1,209 men) within 30 days of prostate biopsy, which was substantially higher than the 2.7% in the control population. Infectious complications were the primary diagnosis in 67 biopsied patients (0.38%) compared to 257 controls (0.19%; P<0.0001). Noninfectious biopsy-related complications were also significantly more frequent in the biopsy than in the control group (53 or 0.30% vs. 53 or 0.04%; P<0.0001). Compared to controls, biopsy was associated with a significantly greater risk of hospitalization for infectious (odds ratio [OR], 2.26; 95% CI, 1.71 to 2.99; P<0.0001) and noninfectious (OR, 8.48; 95% CI, 5.68 to 12.64; P<0.0001) complications.

After adjustment for variables, biopsy was associated with a 2.65-fold (95% CI, 2.47 to 2.84; P<0.0001) increased risk of hospitalization within 30 days compared to the control population.

Men hospitalized for infections were at increased risk for death within 30 days compared to those who weren't (OR, 12.02; 95%, CI, 8.59 to 16.80; P<0.0001).

There was also a steady rise in the rate of serious infection-related complications, researchers reported. In 1991, fewer than 0.5% of men were admitted to the hospital because of an infection following a prostate biopsy. In 2000, rates of infection-related complications began to increase, reaching more than 1.2% in 2007.

A likely explanation for the increase in infectious complications is increasing antimicrobial resistance, researchers wrote. Fluoroquinolones are the prophylaxis of choice in the procedure, but resistance to the drug class has increased in the last decade.

"We could not examine prophylactic antibiotic use in this study," the authors wrote. "Regardless, the increasing number of serious infectious complications during the study interval highlights the need to reevaluate the optimal prophylactic regimen for prostate biopsy and other invasive procedures."

The researchers emphasize that their results act as a warning for physicians to carefully weigh the risks and benefits of biopsy and to discuss them with patients, as well as strictly adhere to medical guidelines about screening and take all precautions to prevent infections and other complications.

"If similar results were found in a randomized trial, we estimated that 1 additional hospitalization would occur for each 24 biopsies performed," they wrote. "These results suggest the importance of better patient selection for prostate biopsy and the identification of those at highest risk for complications."

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Neurology


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Antiepileptic drugs associated with sevenfold drop in sudden, unexpected deaths

Treatment with adjunctive antiepileptic drugs at efficacious doses may reduce sudden unexpected death in epilepsy (SUDEP) by more than seven times compared with placebo in patients with previously uncontrolled seizures.

Researchers performed a meta-analysis of double-blind, placebo-controlled, randomized trials of add-on antiepileptic drugs done in adult patients with uncontrolled partial or primary generalized tonic-clonic seizures. The number and causes of death in patients allocated to antiepileptic drugs at efficacious doses were compared to outcomes in patients given antiepileptic drugs at non-efficacious doses or placebo. Results were published online Sept. 20 by The Lancet Neurology.

SUDEP was defined as a sudden, unexpected, non-traumatic and nondrowning death of patients with epilepsy with or without evidence of a seizure, excluding documented status epilepticus, while in a reasonable state of health (apart from their epilepsy), without any obvious medical cause.

SUDEP was classified into three categories:

  • definite, for cases that fulfilled the definition,
  • probable, for cases in which post-mortem data were not available, but all other criteria were fulfilled, and
  • possible, for cases in which there was missing information about the circumstances of death or because there was a plausible competing explanation for death.

Data on 33 deaths, including 20 cases of SUDEP, were extracted from 112 eligible randomized trials, including 106 (95%) in refractory partial epilepsy and six (5%) in refractory primary generalized tonic-clonic seizures. The trials included a total of 21,224 patients and 5,589 patient-years. Eighteen deaths were classified as definite or probable SUDEP and two as possible SUDEP.

Definite or probable SUDEP, all SUDEP, and all causes of death were significantly less frequent in the efficacious antiepileptic drug group than in the placebo group, with odds ratios of 0.17 (95% CI, 0.05 to 0.57; P=0.0046), 0.17 (95% CI, 0.05 to 0.57; P=0.0046), and 0.37 (95% CI, 0.17 to 0.81; P=0.0131), respectively. Rates of definite or probable SUDEP per 1,000 person-years were 0.9 (95% CI, 0.2 to 2.7) in patients who received efficacious doses and 6.9 (95% CI, 3.8 to 11.6) in patients who received placebo.

Despite the small scale and short duration of the trials and the low rate of SUDEP, the authors wrote, "[T]he more than seven-fold difference in SUDEP incidence noted between patients randomly assigned to placebo and those receiving antiepileptic drugs at efficacious doses points to a significant finding with magnitude that cannot be ignored." An editorial commented that the study provides strong evidence for adjunctive therapy in patients with refractory seizures, that seizure control could be extremely important for SUDEP prevention, and that polytherapy does not increase risk of SUDEP during the short time period of a randomized trial.

"This alone is very useful clinical information, and the overall results highlight the importance of revision of treatment in patients with refractory epilepsy, such as addition of an extra antiepileptic drug when appropriate to enhance seizure control," the editorial said.

Also, the editorial criticized practices in epilepsy research and noted that the significantly higher incidence of SUDEP should prompt serious discussions about minimizing clinical trial durations, especially for patients who do not respond to treatment, as well as about the practice of using suboptimal doses of antiepileptic drugs as placebos in trials.

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Outpatient stroke prevention clinics may be as effective as organized inpatient care

Outpatient stroke prevention clinics may be as effective as organized inpatient care in patients who have had an ischemic stroke or transient ischemic attack (TIA), according to a new study.

Although research has shown that organized inpatient care for stroke decreases morbidity and mortality across age, stroke severity, and stroke subtype, data are limited on the effectiveness of outpatient care models, such as stroke prevention clinics. Researchers in Ontario, Canada, performed a retrospective cohort study to determine the effectiveness of outpatient stroke prevention clinics in preventing mortality and repeated hospital admission in patients with an initial hospital admission for stroke or TIA.

Included patients were those seen in the emergency department or admitted to the hospital for TIA or ischemic stroke between July 1, 2003 and March 31, 2008. Data were obtained from government databases. The primary outcome measure was all-cause mortality one year after an index hospital visit for stroke or TIA. Secondary outcome measures included readmission for stroke or TIA one year after the index visit, along with receipt of neuroimaging, carotid imaging and carotid endarterectomy, prescription of antihypertensive and lipid-lowering drugs, and number of physician visits within six months. Study results were published online Sept. 15 by Stroke.

Data were available for 16,468 patients with ischemic stroke or TIA. Of these, 7,700 (47%) were referred to a stroke prevention clinic for follow-up care. At one year after index admission, mortality rates were lower in patients referred to stroke prevention centers than in those who were not (5.9% vs. 15.5%; P<0.001). This finding remained consistent after adjustment for age, sex, ethnicity, income, comorbidities, stroke symptoms and severity, use of thrombolysis, stroke unit care, discharge location and functional status when discharged (adjusted hazard ratio, 0.67; 95% CI, 0.60 to 0.75). After propensity matching, survival analysis indicated a reduction of 26% in one-year mortality among those referred to outpatient clinics (hazard ratio, 0.74; 95% CI, 0.65 to 0.84). One-year rates of hospital readmissions or emergency department visits, however, did not differ between groups.

Patients referred to stroke prevention clinics had more physician visits, were more likely to receive antiplatelet and lipid-lowering therapy, and were more likely to have magnetic resonance and carotid imaging, echocardiography, and Holter monitoring, but were less likely to undergo carotid revascularization. Rates of computed tomography, antihypertensive therapy and warfarin therapy for atrial fibrillation did not differ significantly between groups.

The authors acknowledged that their study might be affected by residual confounding because of its observational design. They also noted that they were unable to determine whether all patients who were referred to outpatient stroke prevention clinics were actually seen there, and that they could not determine the specific care provided at the clinics.

However, they concluded that organized outpatient care after stroke improves patient care and helps significantly reduce mortality. They called for future research to examine specific interventions used at outpatient clinics and determine which are most effective. Cost-effectiveness and patient satisfaction and adherence should also be considered in future studies, they wrote.

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Resources


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Free technical assistance available for new Guided Care model

Free tools are available for Guided Care, a new model of primary care for older adults with chronic conditions and complex health needs that is designed to improve quality of care and efficient resource use.

The model, developed by researchers at Johns Hopkins, includes a registered nurse based in the practice who works in partnership with several primary care physicians to provide coordinated, patient-centered, cost-effective care to 50 to 60 of their chronically ill patients. Additional information about the model, including technical assistance for practices interested in adopting it, is available on the Guided Care website.

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From the College


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ACP's Center for Ethics and Professionalism receives grant to advance professionalism

ACP's Center for Ethics and Professionalism has been awarded a grant from the American Board of Internal Medicine Foundation for the advancement of professionalism among practicing physicians.

As part of the American Board of Internal Medicine's Putting the Charter into Practice initiative, the grant will allow ACP's Center for Ethics and Professionalism to develop case studies and educational programs focusing on the professionalism and stewardship of health care resources. The case studies will be available for CME credit and will be presented at future ACP annual meetings. The full press release is available online.

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Cartoon caption contest


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And the winner is …

ACP InternistWeekly has tallied the voting from its latest cartoon contest, where readers are invited to match wits against their peers to provide the most original and amusing caption.

acpi-20110927-cartoon.jpg

"And they say the solo practitioner is dead."

This issue's winning cartoon caption was submitted by ACP Member Adam Possner, MD. Readers cast 199 ballots online to choose the winning entry. Thanks to all who voted! The winning entry captured 40.2% of the votes.

The runners-up were:

"I thought you wanted to know if you were healthy enough for sax. My bad."

"You don't mind if I play this while the medical student practices abdominal percussion?"

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MKSAP Answer and Critique



The correct answer is B) High-dose intravenous methylprednisolone. This item is available to MKSAP 15 subscribers as item 10 in the Pulmonary and Critical Care Medicine section. More information about MKSAP 15 is available online.

This patient's headache, temporal artery tenderness, acute visual loss, fever, and mild anemia are strongly suggestive of giant cell arteritis (GCA). Immediate high-dose intravenous methylprednisolone is indicated for this patient. Pain in the shoulder and hip girdle accompanied by a significant elevation in the erythrocyte sedimentation rate is consistent with polymyalgia rheumatica, which is present in approximately 33% of patients with GCA. Anterior ischemic optic neuropathy usually causes acute and complete visual loss in patients with GCA, and funduscopic examination of these patients typically reveals a pale, swollen optic nerve.

Rarely, patients with GCA regain vision if treated immediately with high doses of an intravenous corticosteroid such as methylprednisolone (1 g/d or 100 mg every 8 hours for 3 days) followed by oral prednisone (1 to 2 mg/kg/d). More importantly, this aggressive regimen helps to prevent blindness in the contralateral eye. Therefore, although temporal artery biopsy is the gold standard for diagnosing GCA, diagnostic testing should not precede treatment in patients whose clinical presentation is suspicious for this condition.

Even in the absence of visual loss, GCA is a medical emergency. In a patient whose condition is suspicious for GCA but who does not have visual loss, immediate initiation of high-dose oral prednisone before diagnostic testing is performed also is indicated. Whether intravenous corticosteroid therapy is more effective than oral administration of prednisone for patients with GCA and visual loss remains uncertain. Nevertheless, intravenous therapy seems reasonable in this circumstance and is recommended by many experts, even though rigorous studies have not validated this approach. However, it is clear that low-dose oral prednisone, which is an adequate treatment for isolated polymyalgia rheumatica, does not sufficiently treat GCA.

A process in the brain is unlikely to cause monocular visual loss, and patients with GCA typically have normal findings on brain MRI. Therefore, this study would most likely be unhelpful in this patient.

In patients whose condition raises a strong suspicion of GCA, temporal artery biopsy should be performed after corticosteroid therapy is begun. Corticosteroid therapy will not affect the results of temporal artery biopsy as long as biopsy is performed within 2 weeks of initiating this therapy; positive biopsy results have been seen as late as 6 weeks after institution of high-dose corticosteroid therapy, but the yield of biopsy is higher when this study is performed sooner.

Key Point

  • In patients whose clinical presentation is suspicious for giant cell arteritis, corticosteroid therapy should be instituted immediately, before diagnostic testing is performed.

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