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

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ACP InternistWeekly



In the News for the Week of October 23, 2012




Highlights

Routine physicals not associated with improved morbidity, mortality in nongeriatric patients

Routine physicals do not decrease morbidity or mortality and are unlikely to be beneficial, a review concluded. More...

Stopping antipsychotics in Alzheimer's patients with a sustained response may lead to increased rate, shorter time to relapse

Alzheimer's patients with psychosis or agitation that had responded to risperidone therapy for four to eight months had nearly double the risk of relapse after stopping the drug compared to placebo, a study found. More...


Test yourself

MKSAP Quiz: follow up of aplastic anemia

A 24-year-old man undergoes follow-up evaluation for treatment of aplastic anemia. Two of his siblings are HLA-identical matches. Review of the bone marrow biopsy done 2 weeks ago confirms the diagnosis of aplastic anemia, demonstrating an aplastic bone marrow with normal cytogenetics. What is the most appropriate treatment? More...


Neurology

SSRIs associated with increase in brain hemorrhage risk in some patients, but absolute risks appear small

Selective serotonin reuptake inhibitors (SSRIs) may increase risk for brain hemorrhage in some patients, although the absolute risks are probably low, a study found. More...


Meningitis

Fast action, individualized treatment necessary in fungal meningitis outbreak

A research letter and an opinion piece published last week in Annals of Internal Medicine provide details and guidance on caring for patients in the current outbreak of fungal meningitis due to contaminated methylprednisolone. More...


Immunization

ACIP: pneumococcal vaccine schedule outlined for high-risk adults

The Advisory Committee on Immunization Practices (ACIP) outlined recommendations and dosing regimens for the use of 13-valent pneumococcal conjugate vaccine, the Centers for Disease Control and Prevention reported. More...


Patient-physician relationship

ACP co-authors NEJM Sounding Board article against legislative interference in the exam room

ACP joined with four other medical associations to co-author "Legislative Interference with the Patient-Physician Relationship," which was published in the Oct. 18 New England Journal of Medicine. More...


From ACP Hospitalist

The October issue is online

The October issue of ACP Hospitalist is online and includes stories about hospitalists choosing careers in post-acute care, reviewing medications in the elderly, and attempting mobilization within 24 hours of a stroke. More...


From the College

ACP members elected to Institute of Medicine membership

Several ACP members have been elected as Institute of Medicine (IOM) members. 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: Daisy Smith, MD, FACP



Highlights


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Routine physicals not associated with improved morbidity, mortality in nongeriatric patients

Routine physicals do not decrease morbidity or mortality and are unlikely to be beneficial, according to a new Cochrane review.

The review included 16 randomized trials comparing non-geriatric patients who got routine physicals (defined as screening for more than one disease or risk factor in more than one organ system) to those who didn't. Nine of the trials, with a median follow-up of nine years, collected data on total mortality, and in those trials, physicals were associated with a mortality risk ratio of 0.99 (95% CI, 0.95 to 1.03). Additionally, eight trials provided data on cardiovascular or cancer mortality. Physicals had no significant effect on death from cardiovascular disease or cancer (risk ratios, 1.03 and 1.01, respectively).

The reviewers also tried to look at other possible effects of the routine physical but found insufficient data. One trial found a 20% increase in new diagnoses associated with physicals, and others found increased occurrence of hypertension and increased use of antihypertensives. Potential negative outcomes, such as follow-up procedures, specialist visits and psychological effects, were not reported in many of the trials. In general, the reviewers found the included trials to have methodological problems. Results were published in The Cochrane Library on Oct. 17.

The results show that routine screening physicals have not worked as intended, the researchers concluded. One possible reason is that in the older studies, the health checks were very broad and fewer preventive treatments were available. It's also possible that the screenings are used by the patients who need them least, because they are already attentive to their health.

Another issue is that physicians already screen many of their patients who are likely to be high risk based on clinical indications, said the review authors, reducing the benefit of more widespread screening. Although the review's results indicate that this widespread screening is not effective (and should be avoided by public initiatives), that does not mean that physicians should refrain from clinically motivated examination and preventive treatment, they said. Future research should try to identify the effects of physical examination screening for specific diseases and conditions and use mortality, rather than any surrogate marker, as an outcome, the authors advised.


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Stopping antipsychotics in Alzheimer's patients with a sustained response may lead to increased rate, shorter time to relapse

Alzheimer's patients with psychosis or agitation that had responded to risperidone therapy for four to eight months had nearly double the risk of relapse after stopping the drug compared to placebo, as well as a shorter time to relapse and an increased risk of relapse for at least another four months, a study found.

In the study, 180 patients with Alzheimer's disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks. The 110 who responded were randomly assigned to one of three regimens: continued therapy for 32 weeks, therapy for 16 weeks followed by placebo for 16 weeks, or placebo for 32 weeks.

Results appeared in the Oct. 18 New England Journal of Medicine.

Relapse rates during the first 16 weeks after the initial treatment were higher in the placebo group than the two treatment groups (60% [24 of 40 patients receiving placebo] vs. 33% [23 of 70 in the two treatment groups]; P=0.004; hazard ratio [HR] with placebo, 1.94; 95% CI, 1.09 to 3.45; P=0.02).

Relapse rates were higher in the group that switched from risperidone to placebo during the next 16 weeks than in the group that continued to receive risperidone (48% [13 of 27 patients switched to placebo] vs. 15% [2 of 13 of those who continued treatment]; P=0.02; HR, 4.88; 95% CI, 1.08 to 21.98; P=0.02).

The researchers noted that while stopping risperidone was associated with a larger rate of relapse, risperidone was not highly effective in reducing psychosis and agitation in Alzheimer's patients. Also, federal regulations for nursing homes strongly urge stopping antipsychotic drugs after three to six months of treatment.

The authors concluded, "Our findings suggest that patients with psychosis or agitation-aggression who have a sustained response to antipsychotic treatment for 4 to 8 months have a significantly increased risk of relapse for at least 4 months after discontinuation, and this finding should be weighed against the risk of adverse effects with continued antipsychotic treatment."



Test yourself


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MKSAP Quiz: follow up of aplastic anemia

A 24-year-old man undergoes follow-up evaluation for treatment of aplastic anemia. Two of his siblings are HLA-identical matches.

Laboratory studies:

Hemoglobin 8.3 g/dL (83 g/L) (following transfusion of 1 unit of irradiated packed erythrocytes last week)
Leukocyte count 500/µL (0.5 × 109/L) with 23% neutrophils, 3% band forms, and 71% lymphocytes
Platelet count 26,000/µL (26 × 109/L)
Reticulocyte count 0.2%
mksap.gif

Review of the bone marrow biopsy done 2 weeks ago confirms the diagnosis of aplastic anemia, demonstrating an aplastic bone marrow with normal cytogenetics.

Which of the following is the most appropriate treatment?

A: Allogeneic hematopoietic stem cell transplantation
B: Antithymocyte globulin, corticosteroids, and cyclosporine
C: Autologous hematopoietic stem cell transplantation
D: Corticosteroids
E: Granulocyte colony-stimulating factor

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


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Neurology


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SSRIs associated with increase in brain hemorrhage risk in some patients, but absolute risks appear small

Selective serotonin reuptake inhibitors (SSRIs) may increase risk for brain hemorrhage in some patients, although the absolute risks are probably low, a new study has reported.

Researchers performed a systematic review and meta-analysis of data from controlled observational studies to determine the risk for brain hemorrhage associated with SSRIs. Studies that compared patients receiving SSRIs with those not receiving SSRIs were included. Hemorrhages were categorized as any intracranial hemorrhage (ICH), hemorrhagic stroke (a composite of intracerebral hemorrhage and subarachnoid hemorrhage), intracerebral hemorrhage alone, and subarachnoid hemorrhage alone.

Results were published online Oct. 17 by Neurology.

A total of 16 studies were included in the analysis. In unadjusted and adjusted analyses, the data showed an association between SSRI use and ICH (rate ratios [RRs], 1.48 [95% CI, 1.22 to 1.78] and 1.51 [95% CI, 1.26 to 1.81], respectively) as well as intracerebral hemorrhage (RRs, 1.68 [95% CI, 1.46 to 1.91] and 1.42 [95% CI, 1.23 to 1.65], respectively). An association with increased risk of bleeding was also seen among patients taking SSRIs plus oral anticoagulants compared with oral anticoagulants alone in a subset of five trials, three involving ICH, one involving hemorrhagic stroke, and one involving intracerebral hemorrhage. Increased odds ratios were also observed by study type: cohort studies, 1.61 (95% CI, 1.33 to 1.83); case-control studies, 1.34 (95% CI, 1.20 to 1.49); and case-crossover studies, 4.24 (95% CI, 1.95 to 9.24).

The authors pointed out that their analysis lacked data on intracerebral hemorrhage subtype and that the included studies used different definitions for some variables, among other limitations. They concluded that SSRI use is associated with increased risk for both intracerebral hemorrhage and ICH and that physicians may want to consider other types of antidepressants in patients who have "intrinsic risk factors," such as previous intracranial bleeding. However, they noted that the absolute risk for brain hemorrhage associated with SSRI use is probably very low.

The authors of an accompanying editorial agreed with the study's results. "For patients with a clear indication for SSRI use, the absolute increase in risk of ICH should not deter clinicians from prescribing these agents," the editorialists wrote. "However, these findings emphasize the importance of appropriate patient selection and avoidance of inappropriate prescribing, which assumes particular importance in patients at increased risk of ICH."



Meningitis


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Fast action, individualized treatment necessary in fungal meningitis outbreak

A research letter and an opinion piece published last week in Annals of Internal Medicine provide details and guidance on caring for patients in the current outbreak of fungal meningitis due to contaminated methylprednisolone.

annals.jpg

The research letter details the case of one of the index patients in the outbreak, a 51-year-old woman who sought care in the emergency department for a headache after receiving a steroid injection in her neck. The patient had not received previous injections, was not immunocompromised, and was not taking any long-term medications. She was discharged after a normal physical exam and head CT but returned the next day with neurological symptoms and was hospitalized. Her condition deteriorated rapidly, and she died on hospital day 10.

Exserohilum species was found in the patient's cerebrospinal fluid, and autopsy revealed severe damage to her brain and spinal cord. The authors stressed that this case demonstrates the aggressive, invasive nature of Exserohilum species as well as its short incubation time. Rapid recognition and treatment are necessary, they said, to limit morbidity and mortality.

The opinion piece was written by a physician who treated patients during another fungal meningitis outbreak, involving Exophiala dermatitidis and also due to contaminated methylprednisolone, in 2002. Voriconazole, which was used successfully in the 2002 outbreak, appears to be the logical drug of choice in the current outbreak as well, but the author stressed that exact dosing, outcomes, and drug level monitoring have not been determined and must be based on expert opinion.

"Individual physicians cannot wait for definitive answers and must act decisively at an early stage of infection," he wrote. Appropriate duration of therapy, use of empirical voriconazole and screening methods are also unknown and management will need to be individualized according to each patient's circumstances, he said.

The author reminded readers about the "importance of sterility and the powerful disease-producing interactions between corticosteroids and fungi" and stressed that regulation of pharmacy compounding at state and national levels will need to be revisited.

"Productive discourse between pharmacy societies, the FDA, the pharmaceutical industry, and the legislatures can hopefully balance the demand for individualized, designer products for patient care against the risks for outbreaks that cause suffering and death and that erode trust in public health systems," he wrote. "Otherwise, this will surely happen again."

Updated information on the outbreak from the CDC and the FDA is also available online.



Immunization


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ACIP: pneumococcal vaccine schedule outlined for high-risk adults

The Advisory Committee on Immunization Practices (ACIP) outlined recommendations and dosing regimens for the use of 13-valent pneumococcal conjugate vaccine, the Centers for Disease Control and Prevention reported.

ACIP issued the recommendation June 20, and it was given a Category A recommendation according to the report published in the Oct. 12 MMWR.

There should be routine use of 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13, Wyeth Pharmaceuticals, Inc.) for those age 19 years or older with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leaks or cochlear implants. PCV13 should be administered to eligible adults in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23, Merck & Co.), which is also recommended for this patient population.

This population should receive a dose of PCV13 first, followed by a dose of PPSV23 at least eight weeks later. Subsequent doses of PPSV23 should follow current PPSV23 recommendations for adults at high risk.

Additionally, those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years, or later if at least five years have elapsed since their previous PPSV23 dose.

Those who previously received at least one dose of PPSV23 should be given a PCV13 dose a year or later after the previous PPSV23 dose. For those who require additional doses of PPSV23, the first such dose should be given no sooner than eight weeks after PCV13 and at least five years after the most recent dose of PPSV23.

All adults are eligible for a dose of PPSV23 at age 65 years, regardless of previous PPSV23 vaccination; however, a minimum interval of five years between PPSV23 doses should be maintained.



Patient-physician relationship


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ACP co-authors NEJM Sounding Board article against legislative interference in the exam room

ACP joined with four other medical associations to co-author "Legislative Interference with the Patient-Physician Relationship," which was published in the Oct. 18 New England Journal of Medicine.

The Sounding Board article, developed in conjunction with the American College of Obstetricians and Gynecologists (ACOG), the American Academy of Family Physicians (AAFP), the American Academy of Pediatrics (AAP), and the American College of Surgeons (ACS), expresses concern over U.S. legislators' recent attempts to dictate the nature and content of doctor/patient interactions. Earlier this year ACP released a related policy paper, "Statement of Principles on the Role of Governments in Regulating the Patient-Physician Relationship."



From ACP Hospitalist


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The October issue is online

The October issue of ACP Hospitalist is online and includes stories about the following.

More hospitalists choose post-acute care. Though they have diverse schedules, responsibilities and backgrounds, post-acute hospitalists all are focused on improving care for nursing home patients. The setting is in some ways a natural one for hospitalists, with its emphasis on processes of care and the health of the facility itself.

Reviewing medications in elderly inpatients. More than 60% of American seniors take at least five drugs, and the risk of adverse drug reactions increases with the number of medications a patient takes. Such reactions are responsible for nearly 11% of hospital admissions in older adults, research has found. Hospitalization provides an opportunity to review and revise a patient's medication roster.

When to mobilize after stroke? Mobilization after stroke is generally considered appropriate therapy for most patients, with its potential to improve recovery and reduce complications and disabilities. There is no firm guidance, however, on how early this mobilization should begin and whether very early mobilization—within the first 24 hours—is a good idea.



From the College


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ACP members elected to Institute of Medicine membership

Several ACP members have been elected as Institute of Medicine (IOM) members. Election to the IOM is considered one of the highest honors in the fields of health and medicine and honors outstanding professional achievement and commitment to service.

New members are elected by current active IOM members through a selective process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care and public health. ACP congratulates Wayne Riley, MD, MACP, a member of ACP's Board of Regents; Lawrence J. Appel, MD, MPH, ACP Member; David A. Brenner, MD, FACP; John M. Carethers, MD, FACP; Myron S. Cohen, MD, FACP; Andrew I. Schafer, MD, MACP; and Kevin G.M. Volpp, MD, PhD, ACP Member, on their election to IOM membership. More information is available online.



Cartoon caption contest


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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-20121023-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 A: Allogeneic hematopoietic stem cell transplantation. This item is available to MKSAP 16 subscribers as item 2 in the Hematology/Oncology section.

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

The most appropriate treatment is allogeneic hematopoietic stem cell transplantation (HSCT). Aplastic anemia is classified by the severity of the neutropenia. Moderate aplastic anemia is diagnosed when the absolute neutrophil count (ANC) is 500 to 1000/µL (0.5 to 1.0 × 109/L). Severe aplastic anemia occurs when two or more of the following are present: ANC 200 to 500/µL (0.2 to 0.5 × 109/L), platelet count less than 20,000/µL (20 × 109/L), and reticulocyte count less than 0.2%. Very severe aplastic anemia is diagnosed when the ANC is less than 200/µL (0.2 × 109/L). ANC is calculated as leukocyte count × percentage of polymorphonuclear cells + band forms. This patient has very severe aplastic anemia. Patients with severe aplastic anemia who have an HLA-identical sibling and are younger than 40 years should be offered allogeneic HSCT as initial therapy. Because of the high mortality rate associated with this procedure, HSCT is generally not recommended as initial therapy for patients older than 40 years or those who are not medically fit to undergo transplantation or who have no HLA-identical sibling; these patients are typically treated with antithymocyte globulin and cyclosporine as initial therapy. Because this patient is young, healthy, and has two siblings who are an HLA-identical match, he should be offered allogeneic transplantation as initial therapy.

In some clinical trials of patients who are not transplant candidates, intravenous antithymocyte globulin plus corticosteroids and cyclosporine can result in partial and complete responses in 60% to 80% of patients. Many of these patients become transfusion independent, although response is often delayed for 3 to 6 months, and relapses can occur when the cyclosporine is tapered.

Autologous HSCT would not be an appropriate treatment choice because this patient has an essentially acellular bone marrow.

Prednisone as a single agent produces a very low response rate in patients with aplastic anemia.

Growth factors such as granulocyte colony-stimulating factor should not be given as primary therapy for aplastic anemia, and the use of growth factors as concomitant therapy is controversial. These agents are expensive, and some reports suggest a lower response rate to immunosuppressive therapy and a higher relapse rate when granulocyte colony-stimulating factor is used.

Key Point

  • Patients with severe aplastic anemia who have an HLA-identical sibling and are younger than 40 years should be offered allogeneic hematopoietic stem cell transplantation as initial therapy.

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Test yourself

A 38-year-old man is evaluated for a mass in his right neck that he first noticed 2 weeks ago while shaving. The patient also reports experiencing a pressure sensation when swallowing solid foods for the past year and daily diarrhea for the past 2 months. His personal medical history is unremarkable. His younger brother has nephrolithiasis, and his father died of a hypertensive crisis and cardiac arrest at age 62 years while undergoing anesthesia induction to repair a hip fracture. Following a physical exam, lab studies, and a chest radiograph, what is the most likely diagnosis?

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:

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

Because the rules are complex and may apply differently depending on when you last certified, ACP has developed a MOC Navigator. This FREE tool can help you understand the impact of MOC, review requirements, guide you in selecting ways to meet the requirements, show you how to enroll, and more. Start navigating now.