INTRODUCTION — This section highlights those specific new recommendations and/or updates in this UpToDate release that we anticipate may change usual clinical practice. These concepts are also presented in the specialty-specific What's New topics and are discussed in greater detail in the identified topic reviews.

CARDIOLOGY

(See "What's new in cardiology".)

Optimal rate for patients in atrial fibrillation — We suggest a lenient rate control goal of <110 beats/min, compared to a stricter rate control goal of <80 beats/min, for patients in atrial fibrillation in whom a rate control strategy has been chosen (Grade 2B).

• A strategy of lenient, as opposed to strict, rate control is preferred for most physically active patients in atrial fibrillation. It offers the advantages of less medication (fewer drug side effects, lower cost) and fewer outpatient visits to achieve heart rate control. The randomized RACE II trial compared strategies of lenient rate control strategy (resting heart rate <110 beats per minute) or strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute) [1]. There was no significant difference between the two groups in the primary composite outcome (cardiovascular death, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events) at three years. For patients who continue with unacceptable symptoms at the more lenient goal, an attempt should be made to see if a lower goal lessens symptoms. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy".)

Choice of drug-eluting stent — For patients without diabetes or complex lesions in whom a drug-eluting stent (DES) is chosen, we suggest using an everolimus, a zotarolimus, or a sirolimus-eluting stent in preference to a paclitaxel-eluting stent (Grade 2B).

Four recent randomized trials [2-5], taken into consideration along with previously reported trials comparing paclitaxel to sirolimus and comparing first and second generation drug-eluting stents, support the conclusion that everolimus, zotarolimus, or sirolimus-eluting stents are preferred in most patients who do not have diabetes. (See "Use of drug-eluting intracoronary stents" and "Clinical trials of drug-eluting intracoronary stents: Second generation".)

CARDIOLOGY/DIABETES MELLITUS/NEPHROLOGY AND HYPERTENSION

(See "What's new in cardiology".)

(See "What's new in endocrinology and diabetes mellitus".)

(See "What's new in nephrology and hypertension".)

Goal blood pressure in patients with cardiovascular disease — Prior UpToDate recommendations of a goal blood pressure of less than 130/80 mmHg in patients with cardiovascular disease have been revised to a more lenient target. We recommend antihypertensive therapy to lower the blood pressure to less than 140/90 mmHg.

• Prior recommendations from both UpToDate and societies specified a goal blood pressure of <130/80 mmHg in patients with cardiovascular disease. We now recommend a goal of <140/90 mmHg in all such patients and suggest a goal of <135/85 mmHg for those patients who can tolerate either the addition of one more antihypertensive drug or an increase in the dose of current therapy. A goal blood pressure of less than 140/90 mmHg is reasonable for patients who do not want to increase the intensity of antihypertensive therapy.

This higher target is based on results of two randomized trials, as well as a comprehensive review of older studies in the context of these two new trials. The ACCORD BP trial, in patients with type 2 diabetes and cardiovascular disease (CVD) or additional risk factors for CVD, found no significant difference in defined cardiovascular outcomes for patients assigned to systolic blood pressure targets of <120 or <140 mmHg, but more adverse events occurred in the group assigned to the lower blood pressure goal [6]. The NAVIGATOR trial found no significant difference in defined cardiovascular outcomes in patients with impaired glucose tolerance and CVD or risk factors for CVD who were assigned to valsartan 160 mg/day or placebo [7]. (See "Blood pressure management in patients with atherosclerotic cardiovascular disease" and "Treatment of hypertension in patients with diabetes mellitus" and "What is goal blood pressure in the treatment of hypertension?".)

GASTROENTEROLOGY AND HEPATOLOGY

(See "What's new in gastroenterology and hepatology".)

Peginterferon alfa-2A for chronic hepatitis C infection — We suggest treatment with peginterferon alfa-2a in patients with chronic HCV rather than treatment with peginterferon alfa-2b (Grade 2B).

• A meta-analysis of randomized controlled trials found that peginterferon alfa-2a was superior to peginterferon alfa-2b with regard to sustained virologic response rates in patients with chronic hepatitis C infection, genotypes 1, 2, 3, or 4 [8]. There was no difference between the treatments with regard to adverse events. While previous studies comparing the two peginterferons were less definitive, we now suggest that patients being treated for chronic hepatitis C virus infection receive peginterferon alfa-2a rather than peginterferon alfa-2b. (See "Peginterferon in the treatment of chronic hepatitis C virus infection", section on 'Studies comparing peginterferons'.)

HEMATOLOGY

(See "What's new in hematology".)

Maintenance rituximab in follicular lymphoma — For patients with newly diagnosed follicular lymphoma who have had at least a partial response to initial therapy, we suggest maintenance rituximab rather than observation (Grade 2B).

• The Primary Rituximab and Maintenance (PRIMA) randomized trial of maintenance rituximab after rituximab- containing chemoimmunotherapy for patients with follicular lymphoma (FL) reported that patients who received maintenance rituximab demonstrated improved progression free survival [9]. Further follow-up is needed to measure long-term toxicities and determine if the improvement in progression free survival translates into an overall survival benefit. However, given the available evidence, we have changed our previous suggestion for observation with re-treatment at the time of relapse in patients with newly diagnosed FL following initial treatment, and now suggest maintenance therapy.

When administering maintenance rituximab, it is important to use one of the established regimens, such as that used in the PRIMA study (rituximab every two months for a total of two years). There are no published data regarding the safety or efficacy of therapy extending beyond this; as such rituximab maintenance should NOT exceed two years. (See "Initial treatment of follicular lymphoma", section on 'After chemoimmunotherapy'.)

INFECTIOUS DISEASES

(See "What's new in infectious diseases".)

Treatment of HIV and tuberculosis — In patients with pulmonary tuberculosis (TB) and HIV infection whose CD4 count is <500 cells/mm3, we recommend integrated treatment of TB and HIV infection compared with sequential therapy with antiretroviral medications after TB therapy is complete (Grade 1B).

• The World Health Organization (WHO) recommends the deferment of antiretroviral therapy (ART) until completion of TB therapy in patients with CD4 cell counts of more than 200 cells/mm3. However, the 2010 CAPRISA trial [10] suggests that patients with CD4 cell counts between 200 and 500 cells/mm3 also derive clinical benefit due to a decreased risk of mortality. The optimal time of initiation of ART is unknown; earlier initiation is preferable (eg, closer to two weeks), in the patient with advanced immunosuppression (<200 cells/mm3) who is at risk for other opportunistic infections and increased mortality. (See "Treatment of pulmonary tuberculosis in the HIV-infected patient".)

Universal influenza immunization — The US Advisory Committee on Immunization Practices (ACIP) expanded the recommendation for influenza vaccination to include all individuals 6 months of age and older.

• In 2010, the US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices expanded the recommendation for influenza vaccination to include all individuals 6 months of age and older [11]. This represents a change for adults from previous guidelines, which recommended influenza vaccination for individuals over age 50 and for those at increased risk of influenza complications and close contacts of such individuals. (See "Seasonal influenza vaccination in adults", section on Indications for immunization.)

Starting with the 2010 influenza season in the southern hemisphere and the 2010-2011 season in the northern hemisphere, the trivalent influenza vaccine includes antigen from the 2009 pandemic H1N1 influenza A virus [12,13].

INFECTIOUS DISEASES/ALLERGY AND IMMUNOLOGY

(See "What's new in infectious diseases".)

(See "What's new in allergy and immunology".)

Influenza vaccination in individuals with egg allergy — For the patient who is six months of age or older and has known egg allergy of any severity, except severe anaphylaxis, we suggest administration under observation of a vaccine that contains ≤1 mcg ovalbumin per 0.5 mL as a single dose without prior vaccine skin testing (Grade 2C).

• The ovalbumin content of several brands and lots of the 2009-2010 seasonal and H1N1 influenza vaccines was one or two orders of magnitude lower than the manufacturers' claimed maximum levels in two independent assessments [14,15]. Furthermore, the rate of serious adverse reactions to the vaccine was the same whether vaccine skin testing was performed prior to a two-step administration protocol or not (5 versus 3 percent, respectively) [16]. Therefore, when a vaccine is available that contains ≤1 mcg ovalbumin per 0.5 mL, a two-step protocol may no longer be needed for all patients who report egg allergy. If such a vaccine is not available, or if the history of anaphylaxis to eggs was severe, we suggest administration of the vaccine under observation by a two-step protocol without prior vaccine skin testing. (See "Influenza vaccination in individuals with egg allergy", section on 'Administration protocols'.)

ONCOLOGY

(See "What's new in oncology".)

Initial chemotherapy for metastatic pancreatic cancer — We suggest FOLFIRINOX rather than gemcitabine for patients with metastatic disease who have a good ECOG performance status and a serum total bilirubin level that is <1.5 times the upper limit of normal (Grade 2A).

• The superiority of short-term infusional 5-FU, leucovorin, oxaliplatin plus irinotecan (FOLFIRINOX) over gemcitabine monotherapy was shown in a randomized phase III trial conducted in 250 patients with previously untreated metastatic pancreatic cancer, a good performance status, and serum bilirubin level less than 1.5 times the upper limit of normal (ULN) [17]. In a preliminary report presented at the 2010 ASCO meeting, FOLFIRINOX was associated with significantly higher objective response rates (31 versus 9 percent), median progression-free survival, and overall survival (11.1 versus 6.8 months). These benefits were achieved at the cost of significantly more toxicity. These results establish FOLFIRINOX as the preferred initial chemotherapy regimen in patients with metastatic pancreatic cancer who have a good performance status, and a serum total bilirubin level less than 1.5 times the ULN. 

For patients who are willing to sacrifice some survival benefit for a less toxic regimen, gemcitabine alone or gemcitabine plus capecitabine is a reasonable option. We suggest gemcitabine monotherapy rather than FOLFIRINOX for patients with an ECOG performance status other than 0 to 1 (table 1). (See "Chemotherapy for advanced exocrine pancreatic cancer", section on 'FOLFIRINOX'.)

Sipuleucel-T (Provenge) vaccine for metastatic prostate cancer — For minimally symptomatic or asymptomatic patients with castration-resistant prostate cancer that is not progressing rapidly, we suggest treatment with sipuleucel-T before using cytotoxic chemotherapy (Grade 2B).

• The US Food and Drug Administration approved the therapeutic dendritic cell vaccine sipuleucel-T in April 2010 for the treatment of asymptomatic or minimally symptomatic men with castrate-resistant metastatic prostate cancer [18]. Approval was based upon the results of three randomized trials that demonstrated an improvement of four months in overall survival compared to placebo. This is the first approved therapeutic cancer vaccine in the United States. (See "Immunotherapy for metastatic prostate cancer", section on 'Sipuleucel-T'.)

PEDIATRICS

(See "What's new in pediatrics".)

13-valent pneumococcal conjugate vaccine (PCV13) — A pneumococcal vaccine with additional serotype coverage was licensed in the United States in February 2010 and will replace the 7-valent vaccine for routine childhood immunization.

• The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed by the United States Food and Drug Administration in February 2010 for use in children 6 weeks through 71 months of age [19]. PCV13 replaces the 7-valent pneumococcal conjugate vaccine (PCV7) in the routine childhood immunization schedule and catch-up schedule.

The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommends a supplemental dose of PCV13 for healthy children aged 14 through 59 months who were fully immunized with PCV7 and for children younger than 71 months with medical conditions that increase the risk of pneumococcal disease (table 2). (See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children", section on 'Supplemental dose'.)

PULMONARY MEDICINE

(See "What's new in pulmonary, critical care, and sleep medicine".)

High PEEP in patients with acute respiratory distress syndrome — For patients with acute respiratory distress syndrome (ARDS, PaO2/FiO2 ≤200 mmHg) who require mechanical ventilation, we recommend using a strategy of high PEEP (Grade 1B).

• Mechanical ventilation using high positive end-expiration pressure (PEEP) may improve mortality in patients with acute respiratory distress syndrome (ARDS, defined as a PaO2/FiO2 ≤200 mmHg). A meta-analysis that included 1892 such patients found that those who were mechanically ventilated using a high PEEP strategy had lower ICU mortality than those who were mechanically ventilated using a low PEEP strategy [20]. A preferred approach to determining the optimal level of high PEEP has not been established, although several reasonable techniques exist. (See "Mechanical ventilation in acute respiratory distress syndrome", section on 'High PEEP'.)

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