In the News
for the Week of 7-27-10
- HPV vaccine protects against low-grade lesions
- AIDS society updates antiretroviral recommendations for U.S. adults
- MKSAP Quiz: generalized malaise and fatigue
- Rehab with optional later knee surgery works for ACL tears
- Routine, opt-out HIV tests detect modestly more cases
- AMA survey shows impact of consult code elimination
From the College
- 2009-2010 Report of the Executive Vice President available online
- ACP releases joint statement with ACC and AHA on heart failure
- College-supported organization launches internal medicine program in Bhutan
Cartoon caption contest
- Vote for your favorite entry
Physician editor: Darren Taichman, FACP
HPV vaccine protects against low-grade lesions
The human papillomavirus (HPV) vaccine substantially reduces the incidence of low-grade neoplasia and genital warts (condyloma) for more than three years after vaccination, according to a new study.
The data were gathered from two international randomized, controlled trials of the quadrivalent HPV vaccine (Gardasil) conducted by the vaccine manufacturer. The trials included more than 17,000 women ages 16 to 26. Participants were excluded for a history of more than four sexual partners, abnormal cervical smear test results or pregnancy. They were given three doses of the vaccine (which targets HPV types 6, 11, 16 and 18) or placebo. The follow-up was continued for 42 months, and the study was published online by BMJ on July 21.
Among participants who tested negative for the relevant HPV types at the start of the study, the vaccine was almost totally effective against lesions caused by HPV type 6, 11, 16 or 18: 96% effective for cervical intraepithelial neoplasia grade I, 100% for vulvar and vaginal intraepithelial neoplasia grade I and 99% for condyloma. When lesions caused by other HPV types were included, the vaccine’s effectiveness was substantially lower. Overall, it was 30% effective at preventing cervical neoplasia grade I, 75% for the vulvar type, 48% for vaginal and 83% for condyloma.
The study had a longer follow-up period than previous research, the study authors noted. The vaccine’s efficacy against low-grade lesions is important because these occur far more often than higher-grade lesions, and prevention can reduce patient anxiety, morbidity and health care costs, the authors noted. The control group of the trial also allowed the researchers to estimate the overall incidence of condyloma in unvaccinated women, which they put at 1% per year..
AIDS society updates antiretroviral recommendations for U.S. adults
New data about untreated HIV and expanded treatment options led a panel to update recommendations for antiretroviral therapy (ART) in U.S. adults.
The International AIDS Society-USA guidelines recommend when to start ART, what type to choose, how to monitor and when to change therapies. Recommendations appear in the July 21 Journal of the American Medical Association.
Patients must be ready to undertake lifelong ART, the guidelines said. Therapy is recommended for symptomatic patients regardless of CD4 cell count, and for asymptomatic individuals with CD4 cell counts <500/µL. Risk reduction counseling should be done at each patient-clinician interaction.
When selecting a regimen, clinicians should consider resistance-testing results and predicted virologic efficacy, toxicity and tolerability, pill burden, dosing frequency, drug-drug interactions, comorbidities, patient and practitioner preference, and cost and affordability. Current evidence supports combining two nucleoside reverse transcriptase inhibitors and a potent third agent from another class. Fixed-dose formulations and once-daily regimens are preferred.
Effective therapy should suppress HIV to less than 50 copies/mL (polymerase chain reaction) or 75 copies/µL (branched DNA) by 24 weeks. To detect failure, testing of HIV-1 RNA should be repeated two to eight weeks after initiation, every four to eight weeks until suppressed, and then every three to four months for at least the first year. CD4 cell counts should be monitored at least every three to four months after starting therapy, especially in patients with counts <200/µL, to assess whether prophylaxis is needed for opportunistic infections. Patients who have changed therapy because of virologic failure need more frequent monitoring. Even if one or more regimens have failed, the therapeutic goal should still be undetectable plasma HIV-1 RNA levels. This goal is achievable with new drugs and regimens, the guidelines said.
If an elevation in viral load occurs after complete suppression is achieved, physicians should consider poor adherence, drug-drug interactions, concurrent infections and recent vaccinations as possible causes before changing regimens. Testing for an isolated detectable viral load should be repeated to exclude errors or self-resolving low-level viremia.
When changing regimens after first- or multiple-regimen failure, physicians should consider the stage of HIV, nadir and current CD4 cell count, comorbidities, treatment history, current and previous drug resistance tests, and drug interactions. At least two drugs, and preferably three fully active drugs, should be included and drugs from new classes should be considered.
Single-agent switches to decrease toxicity, avoid drug interactions, or improve convenience and adherence are possible, provided the potency of the regimen is maintained and drug interactions are managed. Boosted protease inhibitor monotherapy is not recommended, except when other drugs raise issues of toxicity or tolerability. Delaying such switches may affect adherence and risk development of resistance.
MKSAP Quiz: generalized malaise and fatigue
A 52-year-old woman is evaluated for a 6-week history of generalized malaise and fatigue. She received a kidney transplant 15 years ago for hypertension-related renal failure. Her current medications include cyclosporine and azathioprine.
The vital signs and general physical examination are normal.
Complete blood count is normal. The blood urea nitrogen level is 56 mg/dL (20 mmol/L), and the serum creatinine level is 3.0 mg/dL (265.2 µmol/L) compared with a value 2 months ago of 1.7 mg/dL (150.3 µmol/L). Urinalysis is significant for 19 leukocytes/hpf, no erythrocytes, 2+ protein, and many squamous and renal tubular epithelial cells, some of which have intranuclear inclusions.
Infection with which of following is the most likely cause of this patient’s worsening kidney function?
B) Epstein-Barr virus
C) Human herpesvirus-8
D) Polyomavirus BK virus
E) Polyomavirus JC virus
Click here or scroll to the bottom of the page for the answer and critique.
Rehab with optional later knee surgery works for ACL tears
Patients who tried rehabilitation instead of immediately having surgery on their torn anterior cruciate ligaments (ACL) did as well as patients who had early ACL reconstruction, a new study found.
The randomized, controlled trial included 121 young, active Swedish adults with acute ACL injuries. The patients were assigned to either rehabilitation plus early ACL reconstruction or rehabilitation with the option of later ACL surgery if needed. Of the 59 patients in the latter group, 23 eventually had ACL reconstruction.
The primary outcomes of the study were knee pain, symptoms, function in sports and recreation and knee-related quality of life, compared at baseline and after two years. There were no significant differences between the groups’ improvement on these outcomes, and an additional post hoc as-treated analysis also found no significant differences in outcomes among patients who got early reconstruction, late reconstruction or no surgery at all. The patients in the delayed surgery group were more likely to have surgery on the meniscus.
The study authors concluded that in this patient population, the strategy of early reconstruction with rehabilitation is not superior to rehabilitation with the option of delayed reconstruction. They noted that more than half of the potential reconstructions were avoided by employing the rehab with optional surgery strategy.
However, an accompanying editorial noted that two years of follow-up is insufficient to definitively determine the long-term effects of the strategy. The editorialist recommended that decisions about surgical reconstruction of ACLs be made based on the individual knee and patient. The study and editorial were published in the July 22 New England Journal of Medicine.
Routine, opt-out HIV tests in ED detect modestly more cases
Screening all patients in the emergency department on a routine, opt-out basis modestly detected more patients with HIV, most of whom were late in the course of disease, reports a study that appears in the July 21 Journal of the American Medical Association.
Researchers alternated routine opt-out rapid HIV screening and physician-directed diagnostic rapid HIV testing in four-month spans at Denver Health Medical Center, an urban public safety-net hospital with an approximate annual emergency department census of 55,000 patient visits between April 2007 and April 2009.
The opt-out phase included 28,043 patients, of whom 6,933 patients (25%) completed HIV testing. (Doctors could perform diagnostic testing in this phase so they could still provide standard emergency medical care.) Ten of 6,702 patients (0.15%; 95% CI, 0.07% to 0.27%) had new HIV diagnoses, as did five of 231 patients (2.2%; 95% CI, 0.7% to 5.0%) diagnostically tested in this phase. The diagnostic phase included 29,925 eligible patients, of whom 243 (0.8%) completed HIV testing. Four patients (1.6%; 95% CI, 0.5% to 4.2%) had new diagnoses.
The prevalence of new HIV diagnoses (including those diagnostically tested) was 15 in 28,043 (0.05%; 95% CI, 0.03% to 0.09%) in the opt-out phase and four in 29,925 (0.01%; 95% CI, 0.004% to 0.03%) in the diagnostic phase. Non-targeted opt-out HIV screening was independently associated with new HIV diagnoses (risk ratio, 3.6; 95% CI, 1.2 to 10.8) when adjusting for patient demographics, insurance status and whether diagnostic testing was performed in the opt-out phase.
The median CD4 cell count for those with new HIV diagnoses in the opt-out phase (including those diagnostically tested) and in the diagnostic phase was 69/µL (interquartile range [IQR], 17 to 430) and 13/µL (IQR, 11 to 15), respectively (P=0.02).
Emergency department crowding was not affected by HIV screening. Waiting, length of stay and boarding times differed slightly between the study phases, but were not clinically meaningful. A validated composite measure of emergency department crowding showed no differences between routine and physician-directed screening.
AMA survey shows impact of consult code elimination
The American Medical Association recently released the results of a new survey showing that Medicare’s elimination of consultation codes has had a negative impact on physician efforts to improve care coordination and reduced the treatment options available to Medicare patients.
The survey of 5,500 physicians also showed that many have taken cost-cutting steps to offset revenue losses from the elimination of these codes. Highlights of the survey are available on the AMA website.
Prior to the release of the survey results, ACP joined with the AMA and other physician organizations in sending a letter requesting that CMS improve its policy. The College continues to look for opportunities to work with internal medicine subspecialty organizations to find viable solutions to this problem.
From the College.
2009-2010 Report of the Executive Vice President available online
The 2009-2010 Report of the Executive Vice President is now available on ACP’s website as well as on the Regents' Information Center (RIC) and the Governors' Information Center (GIC).
The EVP Report outlines the year's events at the College, including new programs, services and clinical resources, as well as news in quality improvement, research and advocacy. This year’s report was printed on 30% post-consumer fiber paper..
ACP releases joint statement with ACC and AHA on heart failure
ACP, along with the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), has released a clinical statement on heart failure.
The statement further defines the skill set required of specialists treating patients with the most advanced forms of heart failure and those undergoing heart transplantation. As advances in cardiac care have improved longevity and quality of life for patients, the demand for specialty care to manage the care of these patients has risen, the authors explain. The statement aims to provide a roadmap for physicians who are interested in training in this area..
College-supported organization launches internal medicine program in Bhutan
Health Volunteers Overseas (HVO), an ACP-supported organization, announced the opening of a new internal medicine program in Bhutan at the National Referral Hospital (NRH) and the Royal Institute of Health Sciences (RIHS).
ACP sponsors HVO's internal medicine overseas section, which supports training programs for internal medicine generalists and subspecialists in five international locations: Bhutan, Cambodia, India, Peru and Uganda. A private, non-profit organization, HVO designs and implements clinical and didactic education programs in child health, primary care, trauma and rehabilitation, essential surgical care, oral health, blood disorders and cancer, infectious disease, nursing education, and wound management. In more than 25 resource-poor countries, HVO volunteers train, mentor, and provide critical professional support to clinicians who care for the neediest populations in the most difficult of circumstances.
Volunteers in internal medicine who might be interested in serving HVO in Bhutan or any of their international sites can get more information online. To learn more about improving global health, visit the HVO website or contact them via e-mail.
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.
"The beer is nice and all, but I still feel sick ... I really think I need a shot."
"I've found this product to be the best for producing a urine sample quickly."
"I told you you'd like our new patient-centered medical home."
Go online to pick the winner, who receives a $50 gift certificate good toward any ACP program, product or service. Voting continues through Monday, August 2, with the winner announced in the August 3 issue..
MKSAP answer and critique
The correct answer is D) Polyomavirus BK virus. This item is available to online to MKSAP 15 subscribers as item 47 in the Infectious Diseases module
This presentation is typical for polyomavirus BK virus–induced nephropathy in a patient with a transplanted kidney. Polyomavirus BK virus is acquired asymptomatically early in childhood by as many as 90% of all persons. The virus persists throughout life but rarely causes problems in normal hosts. However, it may result in serious disorders in immunosuppressed patients and is an important cause of kidney allograft failure. The virus may be reactivated in 30% or more of kidney transplant recipients as evidenced by shedding of “decoy cells” (tubular or transitional cells with intranuclear viral inclusions) or viremia, which may be characterized by fatigue, myalgia, and malaise. Further confirmation can be obtained by identifying the virus in urine or blood or by kidney biopsy, which is the gold-standard diagnostic test. Quantification of the virus is useful in assessing and managing the effects of treatment, which may include reducing immunosuppressive therapy or using experimental medications, such as leflunomide, cidofovir, or fluoroquinolones.
After the first posttransplantation month, cytomegalovirus (CMV) is one of the infectious agents most likely to affect graft survival and cause life-threatening complications. CMV infection typically involves the gastrointestinal tract and is associated with fever, pain, ulcerations, and hepatitis. CMV alone does not lead to nephropathy, although it may have additive effects in the presence of the BK virus.
The Epstein-Barr virus may cause posttransplantation lymphoproliferative disease, but it is not known to cause nephropathy. Posttransplantation lymphoproliferative disease is characterized by symptoms suggestive of infectious mononucleosis followed by a progressive deteriorating course that may involve the brain, liver, bone marrow, and transplanted organ.
Human herpesvirus-8 infection causes Kaposi sarcoma and is associated with Castleman disease and primary effusion lymphoma but does not appear to cause hepatitis, encephalitis, or nephropathy.
Polyomavirus JC virus may cause progressive multifocal leukoencephalopathy but not renal disease in patients with transplanted kidneys.
- Polyomavirus BK virus is a common cause of nephropathy in patients with transplanted kidneys.
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A 53-year-old woman is evaluated for a 3-month history of swelling of the face, hands, and feet. She has untreated hepatitis C virus infection. She takes lithium for bipolar disorder. She has no additional symptoms. After a physical exam, lab results and kidney biopsy, what is the most likely cause of this patient's nephrotic syndrome?
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