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What's new in family medicine

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2014. | This topic last updated: Sep 24, 2014.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ADULT GENERAL INTERNAL MEDICINE

Acetaminophen in the treatment of acute low back pain (September 2014)

In a randomized trial of 1645 patients with acute low back pain (less than six weeks duration), there was no difference in recovery time or other measures of pain and function between patients treated with placebo, as-needed acetaminophen, and regular acetaminophen use [1]. Potential reasons for the apparent lack of effect include that some patients also used other treatments during the trial period and the actual amount of medicine (median dose of 2660 mg) taken may not have been sufficient. A treatment trial of acetaminophen for acute low back pain remains a reasonable treatment option. (See "Treatment of acute low back pain", section on 'Acetaminophen'.)

KEEPS hormone therapy trial in newly menopausal women (September 2014)

The Women's Health Initiative (WHI), a set of menopausal hormone therapy (MHT) trials in older postmenopausal women (average age 63 years) reported an excess risk of coronary heart disease (CHD) with MHT. Emerging data, including secondary analyses from the WHI, now suggest that use of MHT in the early menopausal years is not associated with excess CHD risk. The Kronos Early Estrogen Prevention Study (KEEPS) is the first randomized trial of MHT in younger menopausal women (727 women ages 45 to 54 years) [2]. When combined with cyclical monthly oral progesterone, low dose oral conjugated estrogen (0.45 mg daily) or transdermal estradiol (50 mcg daily) for four years relieved menopausal symptoms. While several markers of cardiovascular risk improved in the MHT group, there was no significant effect on surrogate markers of atherosclerosis progression (coronary artery calcium and carotid intima-medial thickness) when compared to placebo. This trial provides additional reassurance that early use of MHT is safe for the treatment of menopausal symptoms, though it does not support a role for MHT in prevention. (See "Menopausal hormone therapy and cardiovascular risk", section on 'Timing of exposure'.)

Oral emergency contraception in overweight women (August 2014)

In Europe, product labeling for levonorgestrel-based emergency contraception (NorLevo) was updated in February 2014 to indicate that it may be less effective in women ≥75 kg (165 pounds). In July 2014, the European Medicines Association concluded that the available data were not robust enough to be certain the contraceptive efficacy of levonorgestrel emergency contraception is reduced with increased bodyweight and that the benefits of taking the medication outweighed any risks [3]. We counsel overweight and obese women of potentially reduced efficacy of levonorgestrel emergency contraception as BMI increases above the normal range (25 kg/m2) or at weights ≥75 kg (165 pounds), and offer them a copper-releasing IUD as first-line therapy to prevent pregnancy. If the IUD is not an option, ulipristal is more likely to be effective than levonorgestrel. (See "Emergency contraception", section on 'Overweight and obese women'.)

Recurrence of Stevens-Johnson syndrome/toxic epidermal necrolysis (June 2014)

Although there are reports of recurrence of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the overall risk of recurrence is unknown. In a 10-year population-based cohort of 708 patients hospitalized for a first episode of SJS or TEN, 7.2 percent of 581 survivors were hospitalized for a second episode and 1.4 percent had multiple recurrences; lack of direct access to medical records precluded information about medication exposures [4]. The median time to first recurrence was 315 days. The high risk of recurrence after a first episode of SJS/TEN may reflect a long-lasting vulnerability or a genetic predisposition to severe drug reactions. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'Recurrence'.)

Oral contraceptives versus oral antibiotics for the treatment of acne vulgaris (June 2014)

Oral contraceptives and oral antibiotics are commonly used for the treatment of acne vulgaris in women, but studies directly comparing these treatments are lacking. The first meta-analysis to address this issue included randomized trials with at least one investigational arm that consisted of oral antibiotic or oral contraceptive treatment [5]. Efficacy data from individual trials were pooled. Compared with placebo, the two treatments yielded similar reductions in acne lesions after six months, but antibiotics had a faster onset of action. Given the heterogeneity in treatment protocols and patient populations, head-to-head trials are necessary to confirm these results. (See "Hormonal therapy for women with acne vulgaris", section on 'Comparison to oral antibiotic therapy'.)

New risk calculator for the estimation of cardiovascular risk (April 2014)

The American Heart Association/American College of Cardiology (AHA/ACC) guidelines and the Joint British Societies (JBS3) guidelines both discuss consideration of lifetime risk as well as 10-year risk for CV events [6], and JBS3 recommends use of a lifetime risk calculator in patients at low 10-year risk [7].

A problem with using lifetime risk calculations in making decisions about treating lipids is the lack of long-term data on the effects of statin therapy. We have very limited evidence regarding either comparative benefits or harms with longer-term compared with shorter-term statin therapy, and there is substantial evidence that statin therapy can produce marked improvements in outcomes soon after it is initiated. We continue to suggest using calculators that focus on 10-year risk in making decisions about whether to initiate statin therapy. (See "Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease", section on 'Trials showing mortality benefits' and "Treatment of lipids (including hypercholesterolemia) in primary prevention", section on 'Lifetime risk'.)

The lifetime risk calculator allows for the estimated impact of lifestyle modifications on future risk and may be helpful in promoting behaviors such as smoking cessation. A link to this calculator can be found at the JBS3 risk website. (See "Estimation of cardiovascular risk in an individual patient without known cardiovascular disease", section on 'JBS3 risk score (2014)'.)

Chronic idiopathic urticaria and food/drug additives (March 2014)

Although food and drug additives are felt to cause chronic urticaria only rarely, if at all, many patients with chronic urticaria believe that additives are partly or entirely to blame. In a referral center study of 100 patients with chronic urticaria, including 43 who suspected they were sensitive to one or more additives, subjects were systematically challenged with common food and drug additives [8]. In an initial challenge with a combination of 11 additives, two patients had significant worsening of symptoms. Neither patient reacted to a series of subsequent double-blind placebo-controlled challenges with each additive. Thus, none of the 100 patients was sensitive to any of the additives tested. This study should prove helpful in communicating with patients who suffer from this vexing disorder, while research into its true etiology(ies) continues. (See "Allergic and asthmatic reactions to food additives", section on 'Patients with chronic urticaria'.)

Acid suppression and pneumonia (March 2014)

Previous observational studies reported an association between proton pump inhibitor (PPI) use and community acquired pneumonia (CAP), but a new meta-analysis suggests the observation might have been due to confounding. The meta-analysis included eight cohort studies with over 4 million new users of nonsteroidal antiinflammatory drugs (NSAIDs), of which nearly 100,000 were treated prophylactically with PPIs and about 50,000 were treated with histamine 2 receptor antagonists (H2RAs) [9]. On adjusted analysis, neither the use of PPIs nor H2RAs was associated with an increased risk of hospitalization for CAP during the six months following initiation of NSAIDs. (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Pneumonia'.)

Access to guns and risk of suicide (March 2014)

Access to firearms may increase the risk of suicide in adolescents and adults. A meta-analysis of 14 observational studies found that the risk of completed suicide was three times greater among individuals with access to firearms compared with those without access [10]. Other observational studies suggest that restricting access to guns decreases the risk of suicide. Management of patients with suicide plans and intent should include asking questions about the availability of firearms and making them temporarily unavailable with the aid of family members and the police. (See "Suicidal ideation and behavior in adults", section on 'Reduce immediate risk'.)

PREVENTION

Niacin in combination with statins (July 2014)

The HPS2-THRIVE trial examined extended-release niacin plus laropiprant (a selective prostaglandin D2 receptor antagonist, given to reduce flushing from niacin) compared with placebo in patients with known cardiovascular disease who were being treated with simvastatin; some patients also received ezetimibe [11]. After a median follow-up of 3.9 years, there was no reduction with niacin/laropiprant in the primary endpoint of first major vascular event, but there was a statistically nonsignificant increase in mortality (6.2 versus 5.7 percent). Additionally, and despite a run-in period, there was an increase in serious adverse events that included myopathy, with a much greater increased risk in patients from study centers in China than in Europe, and worsened glucose control with both an increase in new cases of diabetes and serious disturbance in diabetes control that typically led to hospitalization. Additionally, there were increases in serious infections (8.0 versus 6.6 percent) and bleeding (2.5 versus 1.9 percent).

It is not possible to determine which effects were due to laropiprant, niacin, or the combination of the two drugs. Given these results, infection and bleeding were subsequently examined in the earlier AIM-HIGH trial, which studied niacin without laropiprant [12]. Infections were increased with niacin (8.1 versus 5.8 percent), and there were only small numbers to assess rates of bleeding (3.4 versus 2.9 percent; p = 0.36). The most likely interpretation of these results is that the observed adverse effects were primarily due to niacin. Given these results, we would not administer niacin to most patients receiving statin therapy. The balance of safety and efficacy of niacin monotherapy is also unclear. (See "Lipid lowering with drugs other than statins and fibrates", section on 'Nicotinic acid (Niacin)'.)

Tanning beds and risk of melanoma (May 2014)

There is a growing body of evidence supporting the association between indoor tanning and risk of melanoma. A meta-analysis of 31 observational studies including nearly 250,000 participants found an overall 16 percent increase of melanoma risk for “ever” versus “never” use of tanning beds [13]. In subgroup analysis, the risk was further increased with more than one year of use (61 percent increase), more than 10 lifetime sessions (34 percent increase), and first use before age 25 (35 percent increase). In light of these findings, children and young adults should avoid the use of tanning beds. (See "Risk factors for the development of melanoma", section on 'Tanning beds'.)

Fat intake and coronary risk (April 2014)

Although it is known that there is a continuous graded relationship between serum cholesterol concentration and coronary heart disease (CHD), and that dietary intake of saturated fat raises total serum cholesterol, a 2014 meta-analysis of prospective observational studies found no association between intake of saturated fat and risk for CHD [14]. The meta-analysis also found no relationship between monounsaturated fat intake and CHD, but suggested a reduction in CHD with higher intake of omega-3 polyunsaturated fats; a benefit with omega-6 polyunsaturated fats remains uncertain. Given these results, we no longer suggest avoiding saturated fats per se, although many foods high in saturated fats are less healthy than foods containing lower levels. In particular, we no longer feel there is substantial evidence for choosing dairy products based on low fat content (such as choosing skim milk in preference to higher fat milk). We continue to advise reducing intake of trans fatty acids. (See "Dietary fat", section on 'Saturated fatty acids'.)

SCREENING

Flexible sigmoidoscopy for colorectal cancer screening (August 2014)

The Norwegian Colorectal Cancer Prevention (NORCCAP) trial randomly assigned individuals aged 50 to 64 years to one time flexible sigmoidoscopy screening (n = 20,572) or no screening (n = 78,220) [15]. One-half of those assigned to sigmoidoscopy screening were also assigned to an immunochemical fecal occult blood test (iFOBT). Screening adherence was 63 percent. After a median follow-up of 10.9 years, there was a decrease in deaths from colorectal cancer in the flexible sigmoidoscopy screening group compared to the control group (31.4 versus 43.1 deaths per 100,000 person years). There was no difference between those who did or did not have additional iFOBT testing. A difference in mortality outcomes was not demonstrable until the ninth year of follow-up. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness'.)

Thirteen-year follow-up data on prostate cancer screening (August 2014)

Thirteen-year follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC) provides additional insights on the long-term implications of screening men aged 50 to 74 years for prostate cancer [16]. Given the indolent course of prostate cancer, shorter-term follow-up from the trial may have been insufficient to accurately estimate the survival benefit. However, the absolute rate reduction in prostate cancer deaths for patients randomized to screening has changed only minimally, comparing rates after 9 and 13 years of follow-up (0.06 fewer deaths versus 0.11 fewer deaths per 1000 person years, respectively). This is equivalent to needing to invite 781 men for screening to prevent one prostate cancer death after 13 years. Furthermore, while the prostate cancer survival benefit from screening was not initially realized until nine years of follow up [17], the burdens of screening and treatment, including harms from overdiagnosis and overtreatment, occur immediately and potentially have lifelong consequences. (See "Screening for prostate cancer", section on 'Evidence from randomized trials'.)

Fecal DNA testing for colorectal cancer screening (March 2014, MODIFIED August 2014)

A newer stool DNA test that also incorporates stool hemoglobin testing and DNA methylation was approved by the US Food and Drug Administration in August 2014. In a comparison of the new assay with one round of a fecal immunochemical test (FIT) in nearly 10,000 people at average risk for colorectal cancer who also underwent colonoscopy, the sensitivity for colorectal cancer of the stool DNA and FIT tests were 92.3 percent and 73.8 percent respectively [18]. Nearly 10 percent of individuals with an entirely negative colonoscopy had a positive stool DNA test; the implications of "false-positive" DNA tests is uncertain. Since screening tests are performed at regular intervals, and intervals for performing repeat FIT testing are likely shorter than for stool DNA testing, results of one round of screening may not represent comparative effectiveness over a period of time. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Fecal DNA tests'.)

Colorectal cancer screening in older adults who have never been screened (July 2014)

For most older adults, it is reasonable to stop screening for colorectal cancer (CRC) at age 75 years, or 85 years at the latest. However, for older adults who have never been screened for CRC (23 percent of US elderly individuals), one-time screening appears to be cost-effective up to age 86 years, based on results of a modeling study [19]. In this simulation study, assuming a willingness to pay $100,000 per quality-adjusted life-year gained, colonoscopy was cost-effective to age 83 years, sigmoidoscopy to 84 years, and fecal immunochemistry testing to 86 years for patients without comorbidity and at average risk for CRC. Colonoscopy was the most effective, and most expensive, strategy for one-time screening. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Older adults with no prior screening'.)

Breast cancer screening with tomosynthesis and mammography (July 2014)

A retrospective study in women from diverse populations in the United States, in both community and academic settings, compared digital mammography alone (n = 280,000) with digital mammography plus tomosynthesis (n = 174,000) [20]. Examinations were performed in two different time periods, and women were not randomly assigned to one or another group. Tomosynthesis plus digital mammography was associated with fewer recalls for suspicious findings, a slightly higher detection rate of invasive cancer, and a higher positive predictive value for recall and for biopsy. However, tomosynthesis increases radiation exposure and there are no prospective large studies with patient outcomes to justify its routine use at the present time. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Tomosynthesis' and "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Tomosynthesis'.)

Screening for Hepatitis B virus infection in the United States (June 2014)

Infection with Hepatitis B virus (HBV) can lead to chronic liver disease and is preventable with vaccination. The US Preventive Services Task Force (USPSTF) has updated its statement on screening for HBV infection in nonpregnant adolescents and adults to recommend that individuals at high-risk for HBV infection be screened if they have not been vaccinated or if they were vaccinated without prior screening [21]. High-risk populations include persons born in regions with a prevalence of HBV ≥2 percent, US–born persons whose parents were born in regions with a prevalence ≥8 percent, injection drug users, men who have sex with men, household contacts of persons with HBV infection, and individuals with HIV infection. Existing guidelines from the Centers for Disease Control and Prevention and the American Association for the Study of Liver Disease also support screening of high-risk individuals in the US. (See "Diagnosis of hepatitis B virus infection", section on 'Who should be tested or screened'.)

Anxiety related to false-positive screening mammograms (June 2014)

Concern has been raised about the psychological consequences of false-positive screening mammograms. In a study that compared anxiety scores, assessed by telephone survey shortly after mammography and one year subsequently, for women with and without false-positive mammograms, anxiety was higher for women with false-positive mammography at the initial survey, but there was no significant difference between groups at one year [22]. Women who had a false-positive mammogram, compared with women without false-positive results, reported a greater likelihood of future screening. Women who participated in this study were volunteer participants in a randomized trial comparing types of mammogram screening and may have been more committed to screening than the general population. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Anxiety related to false-positive findings'.)

Cobas HPV test and cervical cancer screening (May 2014)

The cobas HPV test for cervical cancer screening detects the presence of HPV types 16 and 18 with a pooled result for 12 additional high-risk types. HPV types 16 and 18 confer the highest risk for cervical cancer among HPV types. The cobas HPV test was approved by the US Food and Drug Administration (FDA) in April 2014 for use alone as primary screening in women 25 years of age and older [23]. Evidence regarding use of the cobas HPV test as stand-alone testing is not yet publicly available. Awaiting review of this evidence, we continue to recommend cytological (Pap smear) screening for cervical cancer in women 21 to 30 years of age, and either Pap smear alone or co-testing with Pap and HPV testing in women age 30 and older. (See "Screening for cervical cancer: Rationale and recommendations", section on 'HPV testing'.)

Screening colonoscopy and adenoma detection rate (April 2014)

Detection rates for colonic adenomas during screening colonoscopy depend upon the experience and technique of the colonoscopist, and so may be an important marker of quality. In a study of over 300,000 colonoscopies, rates of adenoma detection among 136 gastroenterologists varied from 7.4 to 52.5 percent [24]. Patients who had screening colonoscopy performed by gastroenterologists with higher rates of detecting adenomas were at lower risk for both interval advanced-stage colorectal cancer (CRC) and fatal interval CRC. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Sensitivity of colonoscopy'.)

ADULT CARDIOVASCULAR MEDICINE

The role of digoxin in rate control for patients with AF (August 2014)

The role of digoxin in ventricular rate control in patients with atrial fibrillation (AF) has been limited due to relative poor efficacy and the possibility of an increase in mortality in patients without heart failure. The observational TREAT-AF study evaluated mortality in over 120,000 patients with a recent diagnosis of nonvalvular atrial fibrillation [25]. In this new study, digoxin use was associated with a nearly 25 percent increase in all-cause mortality across all subgroups, including those with and without heart failure. Important limitations of this study include its retrospective design and the absence of a detailed evaluation of the potential impact of digoxin levels. We limit the use of digoxin in AF patients without heart failure to those in whom beta blockers and calcium channel blockers have not achieved adequate rate control and who are not considered candidates for non-pharmacologic therapy to control rate. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Digoxin'.)

Beta blockers in stable coronary heart disease (August 2014)

Although beta blocker therapy improves survival in patients who have sustained an acute myocardial infarction (MI), there is no convincing evidence for this benefit in patients with stable disease. In an observational study of over 26,000 patients discharged after a first coronary heart disease event (an acute coronary syndrome or coronary artery revascularization) and followed for nearly four years, there was no difference in the risk of death in the subgroup without recent MI between those who did or did not receive beta blocker [26]. In patients with stable coronary heart disease who have not had a recent acute MI, beta blockers are indicated to treat angina but not to improve survival. (See "Secondary prevention of cardiovascular disease", section on 'Beta blockers'.)

Running and cardiovascular risk (August 2014)

Several professional society guidelines recommend at least 30 minutes of moderate-intensity exercise five to seven days per week, but this is not achievable for all patients. In a prospective cohort study with a mean follow-up of over 15 years, over 55,000 adults (mean age 44 years) reported duration, distance, frequency, and speed of any running or jogging [27]. Runners had significantly lower risks of all-cause and cardiovascular mortality compared to non-runners. Additionally, the derived mortality benefit was similar for all runners regardless of the total running time, including for those who ran less than 51 minutes per week. These findings from a non-randomized study may represent unidentified confounding factors, and do not prove causation. However, these data support the concept that even small amounts of exercise are better than no exercise while at least 30 minutes of moderate-intensity exercise five to seven days per week remains a reasonable goal for most patients. (See "Exercise and fitness in the prevention of cardiovascular disease", section on 'Type, intensity, and duration of exercise'.)

Prophylactic ICD implantation for patients with LVEF 30 to 35 percent (July 2014)

Although most studies of prophylactic implantable cardioverter-defibrillator (ICD) implantation have included patients with a left ventricular ejection fraction (LVEF) ≤35 percent, most study patients had LVEF <30 percent, resulting in uncertainty regarding benefit in patients with LVEF between 30 and 35 percent. In a retrospective cohort study using data from two large registries of patients with and without ischemic disease (National Cardiovascular Data Registry of patients who underwent ICD implantation and Get With The Guidelines-Heart Failure patients without an ICD) in which the benefits of ICD implantation were separately evaluated for patients with LVEF <30 percent and those with LVEF 30-35 percent, all-cause mortality was significantly lower in patients with an ICD and any level of LVEF, compared with those without an ICD [28]. These data, although not from a randomized trial, support our recommendation to implant an ICD in patients with heart failure and an LVEF of 35 percent or lower. (See "Role of implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death after myocardial infarction", section on 'LVEF and risk'.)

Bleeding risk with heparin or rivaroxaban increased by concomitant NSAID use (June 2014)

The bleeding risk of adding antiplatelet agents to anticoagulants has not been well quantified. A prospective analysis of over 8000 patients treated for venous thromboembolism with low molecular weight heparin or rivaroxaban (an oral direct factor Xa inhibitor) found a higher rate of major bleeding in patients also receiving an NSAID or aspirin compared with an anticoagulant alone (6.5 versus 2.0 bleeds per 100 patient-years) [29]. Gastrointestinal bleeds accounted for only 14 percent of clinically relevant bleeds. (See "Therapeutic use of heparin and low molecular weight heparin", section on 'Bleeding and protamine reversal'.)

Aspirin and noncardiovascular surgery (May 2014)

Many patients who are scheduled to undergo surgery are taking aspirin for the primary or secondary prevention of cardiovascular disease. The best evidence regarding the impact of aspirin on outcomes comes from the POISE-2 trial in which 10,010 patients scheduled for noncardiac surgery, with or at risk of atherosclerotic disease, were randomly assigned to either aspirin or placebo [30]. The primary outcome of death or nonfatal myocardial infarction (MI) at 30 days was similar in both groups as well as between those who were taking long-term aspirin and those who were not. As expected, major bleeding was more common in the aspirin group. Based on POISE-2, we recommend discontinuing aspirin about seven days before noncardiovascular surgery. While some patients in POISE-2 underwent vascular surgery, we are awaiting further data before revising recommendations about aspirin use in such patients. (See "Management of cardiac risk for noncardiac surgery", section on 'Antiplatelet therapy'.)

Aldosterone antagonist therapy in diastolic heart failure (April 2014)

The efficacy of aldosterone antagonist therapy in patients with diastolic heart failure is uncertain. In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, patients with symptomatic heart failure and a left ventricular ejection fraction of ≥45 percent were randomly assigned to receive either spironolactone or placebo [31]. Treatment with spironolactone did not reduce the primary composite outcome (death from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure). However, subgroup analyses suggested regional heterogeneity in patient populations and possible benefit from spironolactone therapy in patients with heart failure confirmed by elevated natriuretic peptide levels. (See "Treatment and prognosis of diastolic heart failure", section on 'Aldosterone antagonists'.)

Potential adverse impact of morphine in patients with MI (March 2014)

Some observational evidence suggests that patients with acute MI who have been treated with morphine for control of chest pain have higher mortality than patients who don’t receive morphine, after controlling for other factors. The potential mechanism for this association may be an adverse impact of morphine on clopidogrel metabolism. This hypothesis was tested in a randomized trial in 24 healthy subjects who received clopidogrel and either intravenous morphine or placebo [32]. Morphine significantly delayed clopidogrel resorption, reduced plasma levels of its active metabolite, and delayed its platelet effect. We usually reserve morphine for patients with MI who have an unacceptable level of pain. (See "Overview of the acute management of unstable angina and non-ST elevation myocardial infarction", section on 'Morphine' and "Overview of the acute management of ST elevation myocardial infarction", section on 'Morphine'.)

ADULT ENDOCRINOLOGY AND DIABETES

Inhaled insulin (July 2014)

In June of 2014, the US Food and Drug Administration (FDA) approved a formulation of inhaled insulin (Afrezza) to improve glycemic control in adults with diabetes mellitus [33]. The approval includes a Risk Evaluation and Mitigation Strategy, which consists of informing healthcare professionals about the serious risk of acute bronchospasm associated with use in patients with asthma or other chronic lung diseases. Because of this risk, Afrezza is contraindicated in patients with chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD). Afrezza, which is administered at the beginning of a meal, is expected to become available for clinical use in early 2015. Until more published data about safety and efficacy are available, the role of this insulin preparation is uncertain. (See "Inhaled insulin therapy in diabetes mellitus", section on 'Dose and administration'.)

Automated closed-loop insulin pump (July 2014)

Small studies have compared overnight glycemic control using a fully automated closed-loop system of insulin delivery (eg, patients do not adjust dosing) with conventional insulin pump therapy. In two crossover trials in adults and adolescents, an automated bihormonal (insulin and glucagon) closed-loop system was compared with conventional insulin pump therapy over a five-day period [34]. The delivery of insulin and glucagon during the closed-loop arm was determined automatically by an algorithm that adjusted doses based on continuous glucose monitoring. On days 2 through 5 of the closed-loop system, as compared with the control period, the mean glucose level was lower in both adults and adolescents. There were no severe hypoglycemic events during the closed-loop period. Although these preliminary results are promising, additional trials are needed. (See "Insulin therapy in adults with type 1 diabetes mellitus", section on 'Automated closed-loop insulin pump'.)

Testosterone products: Revised labeling for venous thromboembolism risk (July 2014)

While previous labeling of testosterone products in the United States has included information about the risk of venous thromboembolism (VTE) as a consequence of erythrocytosis, a recent study found that venous thromboses and pulmonary emboli may occur unrelated to polycythemia in patients taking testosterone [35]. In this study, among 40 men who had thrombotic events at a median of five months after starting testosterone therapy, 39 were found to have previously undiagnosed thrombophilia-hypofibrinolysis, highlighting the importance of a careful personal and family VTE history prior to initiating treatment. Routine screening for thrombophilias in men considering testosterone therapy is not currently suggested. The US Food and Drug Administration (FDA) will now require a more general warning about the risk of thrombosis in the labeling of all approved testosterone products [36]. (See "Testosterone treatment of male hypogonadism", section on 'Erythrocytosis' and "Testosterone treatment of male hypogonadism", section on 'Venous thromboembolism'.)

Nasal testosterone gel for male hypogonadism (June 2014)

The first nasal testosterone gel (Natesto) has been approved in the United States for the treatment of male hypogonadism [37]. The gel is administered into the nostrils via a metered-dose pump applicator. One advantage over other formulations is the minimal risk of gel transfer to a partner or child. On the other hand, some men may find the three times daily regimen inconvenient, and those with allergies or underlying nasal or sinus pathology may have trouble tolerating the formulation as rhinorrhea, nasopharyngitis, and sinusitis are among the most common side effects. Until further published data are available, we suggest using other available testosterone gels, patches, or injectable esters over this new formulation. (See "Testosterone treatment of male hypogonadism", section on 'Other'.)

Decline in diabetes-related complications (May 2014)

Morbidity from diabetes is a consequence of both macrovascular and microvascular disease. The progression of these complications can be slowed with interventions such as aggressive management of glycemia, blood pressure, and lipids; laser therapy for advanced retinopathy; and administration of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker for nephropathy. These interventions appear to be reducing the incidence of several diabetes-related complications, including myocardial infarction (MI), stroke, lower-extremity amputation, and end-stage renal disease. In the United States, the greatest absolute declines have been reported for acute MI and stroke (between 1990 and 2010, 95.6 and 58.9 fewer cases per 10,000 persons per year for MI and stroke, respectively) [38]. (See "Overview of medical care in adults with diabetes mellitus", section on 'Diabetes-related complications'.)

ACE inhibitors and ARBs in diabetic patients (May 2014)

A meta-analysis of 48 trials in patients with diabetes that compared angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) with either placebo or another antihypertensive drug found that ACE inhibitors, but not ARBs, significantly reduced mortality compared with placebo [39]. However, differences in patient populations may explain some of these findings; the overall mortality in the trials comparing ARBs with placebo was substantially lower than trials comparing ACE inhibitors with placebo. Both ACE-inhibitors and ARBs had similar, nonsignificant benefits on mortality when compared with another antihypertensive drug, and both agents had significant benefits on heart failure. Other meta-analyses in both diabetic and nondiabetic patients have reported that ACE inhibitors and ARBs have identical effects on mortality and kidney disease. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'Overall approach to selecting a therapy'.)

ADULT GASTROENTEROLOGY

Low FODMAP diet in irritable bowel syndrome (March 2014)

A diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) has been recommended in patients with irritable bowel syndrome (IBS) but evidence to support this recommendation has been limited. In a randomized, single-blind, cross-over trial, 30 patients with IBS and 8 healthy controls were assigned to 21 days of either a diet low in FODMAPs or a moderate FODMAP Australian (Western) diet [40]. Subjects with IBS but not controls had significantly lower overall gastrointestinal symptoms scores with improvement in scores for abdominal pain, bloating, flatulence, and dissatisfaction with stool consistency while on a low FODMAP diet as compared with both the moderate FODMAP diet and their usual diet. This study supports our current approach, which incorporates a low-FODMAP diet (table 1) early in management of IBS. (See "Treatment of irritable bowel syndrome in adults", section on 'Low FODMAP diet'.)

ADULT HEMATOLOGY AND ONCOLOGY

Chemohormonal therapy for metastatic prostate cancer (June 2014)

Historically, androgen deprivation therapy (ADT) has been the initial therapy for men with metastatic prostate cancer, and docetaxel chemotherapy has been reserved for patients with castration-resistant disease. In the CHAARTED trial, men with no prior hormonal therapy for metastatic prostate cancer (castration-sensitive disease) were randomly assigned to ADT plus docetaxel or to ADT alone [41]. Initial chemohormonal therapy with the combination produced a statistically significant and clinically meaningful improvement in overall survival compared with ADT alone. Based on these results, we recommend chemohormonal therapy for men with castration-sensitive, high-volume metastatic prostate cancer. (See "Initial therapy for castration sensitive metastatic prostate cancer", section on 'Chemohormonal therapy'.)

ADULT INFECTIOUS DISEASE

ACIP recommendations for the 2014-2015 influenza season (August 2014)

In August 2014 the United States Advisory Committee on Immunization Practices (ACIP) released updated recommendations for the prevention of seasonal influenza with vaccines [42]. Important changes from previous recommendations include:

A preferential recommendation for the nasal spray vaccine (live attenuated influenza vaccine, LAIV) over the intramuscular injection (inactivated influenza vaccine, IIV) for children two through eight years of age who do not have specific contraindications to the nasal vaccine (eg, asthma, egg allergy, diabetes, immunosuppression). UpToDate agrees with this recommendation, but also prefers LAIV for children older than eight years. If LAIV is not immediately available, IIV should be administered to avoid missing an opportunity for influenza immunization. (See "Seasonal influenza in children: Prevention with vaccines", section on 'LAIV compared with IIV'.)

Changes to the dosing schedule for children six months through eight years of age (algorithm 1). (See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule'.)

Recommendations for adults are largely unchanged. (See "Seasonal influenza vaccination in adults", section on 'Overview'.)

Efficacy of high-dose influenza vaccine in elderly adults (August 2014)

Due to concern that standard-dose influenza vaccines may be less effective in elderly adults than in younger adults, a high-dose influenza vaccine, Fluzone high-dose, has been developed. In a trial that included more than 30,000 adults ≥65 years of age, Fluzone high-dose was modestly more effective than standard-dose Fluzone [43]. Among individuals in the high-dose group, 1.4 percent had laboratory-confirmed influenza associated with an influenza-like illness compared with 1.9 percent in the standard-dose group (relative efficacy 24.2 percent). The rates of serious adverse events were similar with the high-dose and standard-dose vaccines. For individuals ≥65 years of age, we prefer Fluzone high-dose when available rather than a standard-dose inactivated vaccine. However, the United States Advisory Committee on Immunization Practices has not stated a preference for Fluzone high-dose over the standard-dose inactivated influenza vaccine in older adults [42,44]. (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)

Testing algorithms to diagnose HIV infection (July 2014)

We agree with new recommendations from the United States Centers for Disease Control and Prevention (CDC) to use a combination assay that detects HIV antigen and antibodies as the initial test for laboratory-based HIV screening and diagnosis for patients two years and older (algorithm 2) [45]. If the initial test is reactive, an HIV-1/HIV-2 differentiation assay should be performed as a confirmatory test. Testing with an antibody-only assay followed by a confirmatory Western blot is no longer recommended. In comparison, the new algorithm is better able to diagnose acute infection when antibody may not yet be detectable (eg, "window period of acute HIV infection") and can provide information as to whether the patient is infected with HIV-1, HIV-2, or both. Reactive rapid antibody tests performed in community-based settings should be confirmed using this new algorithm as well. (See "Screening and diagnostic testing for HIV infection", section on 'Testing algorithm'.)

Next-generation DNA sequencing for pathogen identification (June 2014)

Next-generation sequencing (NGS) is a method for determining DNA sequence by analyzing multiple DNA fragments in parallel; it allows sequencing of an exponentially greater number of genes than conventional DNA sequencing. Although NGS has been applied to the diagnosis of complex genetic disorders, a new report suggests it may also be helpful in identifying an infectious pathogen when microbial or serologic testing is unrevealing [46]. NGS was performed on the cerebrospinal fluid of a 14-year-old boy with unexplained fever and progressive neurologic deterioration in whom an extensive infectious disease evaluation had been negative. A species of Leptospira was identified, and antibiotic therapy was initiated with rapid clinical improvement. Subsequent testing confirmed the diagnosis. (See "Principles and clinical applications of next-generation DNA sequencing", section on 'Indications for next-generation sequencing'.)

Cardiovascular outcomes and azithromycin use for pneumonia (June 2014)

Large observational studies have shown conflicting results with regards to a possible increase in cardiovascular mortality associated with azithromycin use. A more recent large cohort study evaluated the association between azithromycin use and all-cause mortality and cardiovascular events in more than 60,000 United States veterans ≥65 years of age who were hospitalized with pneumonia [47]. Ninety-day mortality was significantly lower in those who were treated with an azithromycin-containing regimen versus those who received other guideline-concordant antibiotics. Compared with patients who did not receive azithromycin, those who received azithromycin were slightly more likely to have a myocardial infarction, but not arrhythmias, heart failure, or any cardiac event. An analysis of these data suggested that seven deaths were averted for each non-fatal myocardial infarction associated with azithromycin use, reflecting a net benefit of azithromycin for patients ≥65 years of age with pneumonia. (See "Azithromycin, clarithromycin, and telithromycin", section on 'QT interval prolongation and cardiovascular events'.)

Guidelines on pre-exposure prophylaxis for HIV prevention (June 2014)

Pre-exposure prophylaxis (PrEP) with daily use of tenofovir-emtricitabine, a combination antiretroviral agent, can reduce the risk of HIV acquisition in uninfected individuals who are at high risk of infection. In 2014, the US Public Health Service formally released clinical practice guidelines to help providers decide which patients may benefit from PrEP [48]. The guidelines also advise on the evaluation and monitoring of patients who decide to initiate PrEP. To optimize the efficacy of PrEP, they stress the importance of a comprehensive approach to care that includes HIV testing prior to and during treatment, as well as adherence and risk reduction counseling. UpToDate recommendations are largely consistent with these guidelines. (See "Pre-exposure prophylaxis against HIV infection", section on 'Approach to pre-exposure prophylaxis against HIV'.)

New antibiotics with activity against MRSA for skin and skin structure infections (June 2014, MODIFIED June 2014)

Antibiotic options for the treatment of skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are growing. Dalbavancin and oritavancin have a similar mechanism of action and spectrum of activity to vancomycin, but can be administered as once-weekly intravenous doses because of long half-lives. Tedizolid is from the same antibiotic class as linezolid and can be administered intravenously or orally once daily. In several large randomized trials of adults with acute cellulitis, wound infections, and abscesses, including infections caused by MRSA, these new agents had efficacy and safety profiles similar to vancomycin and/or linezolid with more convenient dosing [49-51]. Dalbavancin, tedizolid, and oritavancin have been approved for skin and skin structure infections by the U.S. Food and Drug Administration in 2014. (See "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults", section on 'Dalbavancin' and "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults".)

CD4 cell count monitoring for well-controlled HIV-infected patients (May 2014)

For HIV-infected individuals, CD4 cell count monitoring informs prognosis and the need for continued prophylaxis to prevent opportunistic infections. Among patients on stable antiretroviral therapy (ART) whose CD4 cell count has stabilized at a level well above the threshold for developing an opportunistic infection, CD4 cell count monitoring has traditionally been performed every 6 to 12 months. In 2014, the Department of Health and Human Services of the United States and the International Antiviral Society-USA panel issued new recommendations for less frequent monitoring in patients who have achieved consistent viral suppression and CD4 cell counts well above the threshold for opportunistic infections (eg, >300 cells/microL) on at least two years of ART [52,53]. In such patients, we monitor the CD4 cell count every 12 months if the CD4 cell count is between 300 and 500 cells/microL. If the CD4 cell count is >500 cells/microL, CD4 cell count monitoring is optional. More frequent testing is warranted for changes in clinical status (ie, receipt of immunosuppressive therapy or virologic failure). (See "Patient monitoring during HIV antiretroviral therapy", section on 'CD4 cell count monitoring'.)

ADULT NEUROLOGY AND PSYCHIATRY

Risk of elective noncardiac surgery after acute stroke (September 2014)

Elective surgery should be deferred when possible in the setting of an acute stroke, as adverse outcomes are likely to be increased in this setting. In a Danish nationwide cohort study, the risk of major adverse cardiovascular events (ischemic stroke, acute myocardial infarction, and cardiovascular mortality) and 30-day all-cause mortality was significantly higher in patients with a history of recent stroke [54]. Compared with patients without stroke, the risk of major adverse events was highest in the first three months after stroke (odds ratio 14) and appeared to level off after nine months. (See "Perioperative care of the surgical patient with neurologic disease", section on 'Patients with a history of stroke'.)

Intravenous alteplase for acute ischemic stroke (August 2014)

A meta-analysis has evaluated individual patient data from over 6700 subjects (including more than 1700 over age 80 years) enrolled in the major randomized trials evaluating intravenous alteplase for acute ischemic stroke [55]. The results confirm that earlier initiation of intravenous alteplase treatment increases its benefit, and that benefit extends to treatment started within 4.5 hours of stroke onset. In addition, alteplase was beneficial regardless of patient age or stroke severity, and despite the increased risk of intracranial hemorrhage in the first days after alteplase treatment. These findings support our approach to administer intravenous alteplase to eligible patients with acute ischemic stroke (table 2), provided treatment is initiated within 4.5 hours of stroke onset. (See "Reperfusion therapy for acute ischemic stroke", section on 'Pooled data'.)

Antidepressants and risk of congenital cardiac defects (August 2014)

A large population-based study has provided reassuring results suggesting that treatment with antidepressants during pregnancy is not associated with congenital cardiac defects [56]. The study used an administrative claims database to compare infants of depressed mothers who were either treated with antidepressants during the first trimester or not treated with antidepressants. After adjusting for confounding, there was no significant difference in risk of congenital cardiac malformations among exposed versus unexposed infants. Seven other analyses examined specific exposure to selective serotonin reuptake inhibitors (as a class), fluoxetine, paroxetine, sertraline, serotonin-norepinephrine reuptake inhibitors, tricyclics, and bupropion; in each analysis, exposure was not associated with an increased risk of cardiac defects. (See "Risks of antidepressants during pregnancy", section on 'Antidepressant composite data'.)

Evaluation for occult atrial fibrillation in patients with cryptogenic stroke or TIA (June 2014)

Two recent trials confirm that paroxysmal atrial fibrillation (AF), an important potential mechanism for ischemic stroke, may be missed using standard cardiac monitoring such as continuous telemetry and 24- or 48-hour Holter monitors:

In the CRYSTAL AF trial, 441 patients with cryptogenic stroke and no evidence of AF during at least 24 hours of ECG monitoring were randomly assigned to prolonged ambulatory cardiac monitoring with a subcutaneous implantable loop recorder or to a control group with conventional follow-up [57]. At six months, AF detection was significantly higher in the implantable recorder group (8.9 versus 1.4 percent in the control group).

In the EMBRACE trial, 572 patients who had a cryptogenic stroke or TIA (and no evidence of AF on routine monitoring) were randomly assigned to additional ambulatory monitoring with a 30-day external loop recorder or a 24-hour Holter monitor [58]. The rate of AF detection was significantly greater in the group monitored for 30 days (16.1 versus 3.2 percent).

Given these findings, we now suggest ambulatory cardiac monitoring for several weeks for patients with a cryptogenic ischemic stroke or TIA. Such patients are characterized by brain ischemia not attributable to a definite source of cardioembolism, large artery atherosclerosis, or small artery disease despite an extensive vascular and cardiac evaluation, including no evidence of AF on standard 12-lead ECG and 24-hour cardiac monitoring. (See "Overview of the evaluation of stroke", section on 'Monitoring for occult atrial fibrillation'.)

Adjunctive olanzapine for maintenance treatment in patients with treatment-resistant depression (June 2014)

For patients with unipolar major depression who have failed multiple treatment regimens and then responded to and tolerated adjunctive second-generation antipsychotics, it is reasonable to continue the antipsychotic to prevent relapse. This approach is supported by a randomized trial in which 444 patients with treatment-resistant depression who responded to open-label acute and continuation therapy with fluoxetine plus olanzapine were randomly assigned to 27-weeks of maintenance therapy with fluoxetine plus olanzapine or fluoxetine monotherapy [59]. Patients who received adjunctive olanzapine had fewer recurrences (16 versus 32 percent). However, adjunctive olanzapine was associated with increased weight gain and adverse changes in glucose, triglycerides, cholesterol, and prolactin. (See "Unipolar depression in adults: Treatment with second-generation antipsychotics", section on 'Maintenance phase'.)

Management of opioid overdose in the community (April 2014)

Education about risks of opioid overdose and provision of take-home naloxone to opioid users, families, and others can prevent deaths due to overdose. Some clinicians, however, are not comfortable prescribing or dispensing take-home naloxone as currently administered, using standard syringes or intranasal spray. A handheld naloxone injection device containing a single dose of naloxone will soon be available for use by non-clinicians [60]. When activated, the device provides verbal instructions to the user and delivers an intramuscular or subcutaneous dose. Future research may indicate whether the device leads to expanded use of naloxone to prevent lethal overdose in the community. (See "Treatment of opioid use disorder".)

ADULT RHEUMATOLOGY

Physical therapy may not benefit hip osteoarthritis (June 2014)

Physical therapy is typically recommended for management of hip osteoarthritis, despite limited evidence regarding its efficacy. In a sham-controlled randomized trial including over 100 patients with painful and radiographically-confirmed hip osteoarthritis, physical therapy (including a home exercise program) provided no benefit on pain and physical function as compared with placebo [61]. Although these findings question the utility of physical therapy for patients with hip osteoarthritis, additional studies are needed to better define the relative risks and benefits of different types of physical activity in the management of this disorder. (See "Nonpharmacologic therapy of osteoarthritis", section on 'Exercise'.)

Wine and increased risk of recurrent gout (June 2014)

Consumption of alcoholic beverages increases the risk of incident (new) and recurrent gout, although earlier data had suggested that beer and hard liquor increased the risk of incident gout, while wine may not. The risks of recurrent gout from alcohol intake were evaluated in an internet-based study including over 700 patients with established gout and at least one acute attack in the prior year; the patients served as their own controls [62]. A significant dose-response relationship was found between the amount of alcohol consumed from any of the three categories (beer, liquor, and wine) and the risk of recurrent gout flare during the subsequent 24 hours. Even moderate amounts of alcohol were associated with an increased risk during this period. The combinations of increased alcohol and high purine intake or diuretic use were associated with higher risk. (See "Prevention of recurrent gout", section on 'Alcohol'.)

GYNECOLOGY

Injectable progestins and risk of venous thrombosis (September 2014)

In contrast to other progestin-only contraceptives, depot medroxyprogesterone acetate (DMPA) use may be associated with an increased risk of venous thrombosis and embolism (VTE). In a case-control study, women with a first episode of VTE were twice as likely to be DMPA users than were controls in the general population [63]. In this study, VTE was not associated with use of progestin-only pills, the levonorgestrel-releasing intrauterine device, or the progestin-only contraceptive implant. However, in the absence of data about absolute risk of VTE in DMPA users, we continue to think that the advantages of using DMPA generally outweigh the risks for women with a history of VTE. (See "Depot medroxyprogesterone acetate for contraception", section on 'Cardiovascular risk'.)

Pelvic examination in asymptomatic women (July 2014)

Routine pelvic examinations in asymptomatic women are controversial. The American College of Physicians has issued guidelines that advise against performing screening pelvic examinations in asymptomatic, nonpregnant, adult women [64]. The American College of Obstetricians and Gynecologists continues to recommend annual pelvic examination for nonpregnant women age 21 years and older, but suggests that asymptomatic women participate in the decision [65]. We believe the decision whether or not to perform a complete pelvic examination at the time of the periodic health examination for the asymptomatic patient should be a shared decision after a discussion between the patient and her healthcare provider. (See "The gynecologic history and pelvic examination", section on 'Indications and frequency for examination'.)

Topical lidocaine for dyspareunia after treatment for breast cancer (May 2014)

Dyspareunia is a frequent issue for women after treatment for breast cancer. For women with dyspareunia isolated to tenderness in the vulvar vestibule, topical lidocaine appears to provide effective relief. This was shown in a small trial that included 49 women randomly assigned to local treatment with topical lidocaine or normal saline [66]. Compared with normal saline, topical lidocaine resulted in a significant reduction in coital pain scores. While these data suggest that topical lidocaine can effectively treat dyspareunia in women with vulvar vestibule discomfort, its effectiveness for women who have findings of intravaginal or pelvic floor pain is not known. (See "Approach to the patient following treatment for breast cancer", section on 'Sexual health'.)

OBSTETRICS

Aspirin for preventing preeclampsia (September 2014)

For women at high risk of developing preeclampsia, the US Preventive Services Task Force (USPSTF) now recommends use of low dose aspirin after 12 weeks of gestation to reduce the risk of preeclampsia, preterm birth, and fetal growth restriction [67]. Low dose aspirin prophylaxis results in potentially substantial benefit and no more than minimally harmful effects. This recommendation is consistent with recommendations of other professional organizations. The USPSTF also offered a pragmatic approach for selecting a high risk population, while acknowledging that there are no validated methods for identifying these women. (See "Preeclampsia: Prevention", section on 'Approach to therapy'.)

Physical activity reduces risk of type 2 diabetes after gestational diabetes (July 2014)

Increasing evidence suggests that an active lifestyle reduces the risk of developing type 2 diabetes in women with gestational diabetes. In a 16-year prospective observational study, 14 percent of women with a history of gestational diabetes self-reported the development of type 2 diabetes [68]. Women with a total physical activity level equivalent to 150 minutes per week of moderate-intensity physical activity or 75 minutes per week of vigorous-intensity physical activity had a 30 to 50 percent lower risk of developing type 2 diabetes than women with lower levels of physical activity. (See "Gestational diabetes mellitus: Glycemic control and maternal prognosis", section on 'Follow-up and prevention of type 2 diabetes'.)

Benefits of controlled cord traction (June 2014)

We suggest controlled cord traction to facilitate separation and delivery of the placenta. In a 2014 meta-analysis of randomized trials comparing controlled cord traction with a hands-off approach, controlled cord traction resulted in a 30 percent reduction in need for manual removal of the placenta, as well as small reductions in the duration of the third stage (three minutes), mean blood loss (10 mL), and incidence of postpartum hemorrhage (11.8 versus 12.7 percent); the rates of severe postpartum hemorrhage, need for additional uterotonics, and blood transfusion were similar [69]. Although the benefits of controlled cord traction are small, there are no significant harms from the maneuver if performed without excessive traction. (See "Management of normal labor and delivery", section on 'Delivery of the placenta'.)

Fish consumption advisory (June 2014)

Because of the potential fetal benefits of maternal docosahexaenoic acid (DHA) intake, the US Food and Drug Administration and the US Environmental Protection Agency now advise women who might become pregnant, pregnant women, and breastfeeding women to consume 8 to 12 ounces of a variety of fish lower in mercury each week (table 3), rather than "up to 12 ounces" as previously recommended [70]. This is consistent with two to three servings of fish per week. We suggest that pregnant and breastfeeding women try to achieve fish consumption resulting in at least 200 mg/day DHA intake instead of relying on the number of servings of fish, since fish vary widely in DHA content. (See "Fish consumption during pregnancy", section on 'Diet and supplements'.)

Effect of gravity on placental transfusion (April 2014)

The length of time a mother can safely hold her newborn before the umbilical cord is clamped is controversial because of concerns that gravity may decrease the volume of placental transfusion. In the first randomized trial evaluating this issue, the location of the newborn above or below the level of the placenta for two minutes before cord clamping did not affect the volume of placental transfusion (as assessed by change in newborn weight) [71]. This finding suggests that placing the newborn on the maternal abdomen or chest before cord clamping does not adversely affect the volume of placental transfusion. (See "Management of normal labor and delivery", section on 'Cord clamping'.)

Hyperimmune globulin does not prevent congenital CMV infection (April 2014)

Although prospective observational studies have reported that administration of hyperimmune globulin to pregnant women with primary cytomegalovirus (CMV) infection reduced maternal-to-fetal transmission and the severity of congenital infection, a recent randomized trial did not demonstrate a significant benefit. The Congenital Human CMV Infection Prevention (CHIP) trial randomly assigned pregnant women at 5 to 26 weeks of gestation with recent onset primary CMV infection to receive hyperimmune globulin or placebo every four weeks [72]. The overall rate of congenital infection and the proportion of infected infants symptomatic at birth was similar for both groups. (See "Cytomegalovirus infection in pregnancy", section on 'Hyperimmunoglobulin'.)

Vancomycin dose for intrapartum GBS chemoprophylaxis (April 2014)

A study has found that vancomycin dosing recommendations from a 2010 guideline from the US Centers for Disease Control (CDC) regarding intrapartum chemoprophylaxis of neonatal early-onset Group B Streptococcus may provide subtherapeutic levels in neonates. The CDC guidelines recommend vancomycin 1 gram every 12 hours for penicillin allergic women if GBS isolates are resistant to clindamycin or susceptibility results are not available. However, a 2014 study of vancomycin levels in neonatal cord blood noted that therapeutic levels were infrequently achieved in neonates whose mothers received this dose, but usually were achieved with maternal weight-based dosing (20 mg/kg every 8 hours; maximum dose 2 grams) [73]. We now suggest weight-based dosing for vancomycin intrapartum GBS chemoprophylaxis. (See "Neonatal group B streptococcal disease: Prevention", section on 'Patients with penicillin allergy'.)

Maternal intake of highly allergenic foods during pregnancy (March 2014)

To date, most studies have found that maternal avoidance of highly allergenic foods during pregnancy does not reduce the incidence of allergic disease in infants and children at risk for these disorders. However, participants in such studies are often from "high risk" atopic families and thus may not be representative of the general population. A new cohort study in over 1200 unselected mother-child pairs examined the association between maternal intake of common allergenic foods during pregnancy and the development of allergic disorders in the offspring [74]. Data from mid-childhood visits found that diets lower in allergenic foods were not associated with reduction in the incidence of food allergy, asthma, allergic rhinitis, or atopic dermatitis, and in some situations, higher intake in early pregnancy appeared to have a protective effect. These findings support our current suggestion that women not restrict their diets during pregnancy for the purpose of reducing allergic disease in their children. (See "Primary prevention of allergic disease: Maternal avoidance diets in pregnancy and lactation", section on 'Definitions'.)

PEDIATRICS: GENERAL PEDIATRICS

Updated recommendations for palivizumab RSV prophylaxis (August 2014)

In 2014, the American Academy of Pediatrics updated its guidance for palivizumab prophylaxis for respiratory syncytial virus (RSV) infection [75]. Important changes include:

Palivizumab prophylaxis is no longer recommended for infants born at ≥29 weeks’ gestation unless they have additional risk factors for RSV (eg, chronic lung disease of prematurity [CLD]). 

Palivizumab prophylaxis is no longer recommended during the second year of life for infants with hemodynamically significant heart disease.

Continuation of palivizumab prophylaxis is no longer recommended for infants with breakthrough RSV infection.

Recommendations for infants with CLD are largely unchanged. (See "Respiratory syncytial virus infection: Prevention", section on 'Indications for palivizumab'.)

Discontinuation of daily desmopressin for nocturnal enuresis (August 2014)

Desmopressin is an effective therapy for children with nocturnal enuresis, but has a higher relapse rate than enuresis alarms. Tapering the dose before discontinuation may decrease relapse. In a multicenter randomized trial, relapse rates 12 weeks after discontinuation of desmopressin were lower in children whose dose was tapered (either by giving one-half the usual dose each day or by giving the usual dose every other day) for two weeks before discontinuation (39 and 42 percent, respectively) than in children who received a placebo (53 percent) or had desmopressin discontinued abruptly (55 percent) [76]. When daily desmopressin is discontinued, we suggest tapering rather than abrupt discontinuation. (See "Nocturnal enuresis in children: Management", section on 'Discontinuation'.)

Risk of traumatic brain injury in children with isolated scalp hematomas (August 2014)

Most children with isolated scalp hematomas and no other clinical symptoms do not have clinically important traumatic brain injury (ciTBI), but certain features may increase risk. In particular, hematomas can be an important indicator of potential TBI when they appear in younger infants. In a multicenter observational study of 2998 children younger than 24 months of age with an isolated scalp hematoma, ciTBI occurred in only 12 patients, none of whom died or required neurosurgery [77]. Of 111 patients younger than three months who underwent computed tomography, 21 percent had radiographic findings of TBI (eg, subdural or epidural hematomas, cerebral or subarachnoid hemorrhages, or cerebral contusions). A previously validated clinical score incorporates age, hematoma size, and hematoma location and may help stratify the risk of TBI in young infants (table 4). (See "Minor head trauma in infants and children: Evaluation", section on 'Common findings'.)

Pediatric health effects of public smoking bans (June 2014)

Policies that ban indoor smoking in workplaces and public places have been associated with long-term health benefits in adults. Smoking bans also appear to be associated with immediate health benefits in children. In a meta-analysis of quasi-experimental observational studies, public smoking bans were associated with reductions of approximately 10 percent in preterm births and hospital admissions for asthma [78]. Some of the effects may be mediated through home smoking bans, which often are prompted by public smoking bans. Additional studies are necessary to determine the effects of smoking bans on respiratory tract infections and other child-health outcomes. (See "Control of secondhand smoke exposure", section on 'Public smoking bans'.)

Helmets for positional skull flattening (May 2014)

Most cases of positional skull flattening are managed by changes in positioning. Severe cases typically are treated with a custom-fitted helmet. A randomized trial comparing helmet therapy and observation in 84 children with moderate to severe skull deformation found no difference in outcomes, including improvement in head shape and full recovery (as determined by anthropometric measurements), at two years of age [79]. However, given the study limitations, including low participation rate, inclusion of moderate cases, and exclusion of “very severe” cases, we continue to advise helmet therapy for infants with severe positional flattening. (See "Overview of craniosynostosis", section on 'Positional flattening (positional plagiocephaly)'.)

Prophylactic antibiotics for children with vesicoureteral reflux (May 2014)

The results of the Randomized Intervention for Vesicoureteral Reflux (RIVUR) trial help to clarify treatment options for children with vesicoureteral reflux (VUR). Earlier studies evaluating the effectiveness of prophylactic antibiotics in preventing recurrent urinary tract infection (UTI) or renal scarring have had inconsistent findings and/or were methodologically limited. The RIVUR trial compared daily treatment with trimethoprim-sulfamethoxazole (TMP-SMX) or placebo in 607 children (two months to six years) with grade I to IV VUR diagnosed after a febrile or symptomatic UTI [80]. At the two-year follow-up, the risk of renal scarring was similar, but TMP-SMX reduced the risk of recurrent febrile or symptomatic UTI by 50 percent. These findings support our approach to VUR management. For children with grade III or higher VUR, who are more likely to have recurrent UTI (even with prophylaxis) and renal scarring, we provide prophylactic antibiotics or surgical treatment. For children with grade I or II VUR, who are more likely to have spontaneous resolution, we discuss the risks and benefits of antibiotic prophylaxis versus observation with the family. (See "Management of vesicoureteral reflux", section on 'Intervention versus surveillance/placebo trials'.)

Probiotics for infantile colic (May 2014)

The etiology of infantile colic (defined as crying for no apparent reason for ≥3 hours per day on ≥3 days per week in otherwise healthy infants <3 months of age) is unknown. The observation that intestinal flora in infants with colic differs from that in infants without colic suggested that probiotics may be a useful treatment. In early small trials, administration of Lactobacillus reuteri showed promise, particularly for breast-fed infants. However, a larger randomized trial has found that L. reuteri did not reduce duration of crying and fussing in breast-fed or formula-fed infants with colic [81]. (See "Infantile colic: Management and outcome", section on 'Probiotics'.)

Electronic cigarette exposures in children (April 2014)

Calls to US poison control centers about electronic cigarette exposures have increased steadily since 2010, when tracking of such exposures began [82]. Most of the calls involved ingestion of the nicotine cartridge. Adverse health effects included vomiting, nausea, and eye irritation (with ocular exposure). Approximately one-half of the exposures occurred in children younger than five years, highlighting the importance of storing electronic cigarettes and nicotine refill cartridges out of the sight and reach of children.(See "Prevention of poisoning in children", section on 'Ingested substances' and "Management of toxic plant ingestions and nicotine poisoning in children", section on 'Nicotine poisoning'.)

PEDIATRICS: DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS

Peer victimization (bullying) and suicide attempts (July 2014)

Suicide attempts in children and adolescents are common, and peer victimization (bullying) is one of several risk factors. A meta-analysis of nine studies including more than 70,000 children and adolescents found that suicide attempts were two to three times more likely to occur in children who were victimized than in those who were not  [83]. In addition, suicidal ideation was more strongly related to cyberbullying than traditional bullying. (See "Suicidal behavior in children and adolescents: Epidemiology and risk factors", section on 'Exposure to violence or victimization'.)

Possible adverse effect of in utero exposure to acetaminophen (April 2014)

An epidemiologic study noted a small but statistically significant (OR 1.13) association between in utero exposure to acetaminophen and attention-deficit/hyperactivity disorder–like behavioral problems in offspring at age seven years [84]. These findings are subject to the many limitations of observational studies and should not change current practice. (See "Initial prenatal assessment and first trimester prenatal care", section on 'Acetaminophen'.)

PEDIATRIC NEONATOLOGY

Neonatal pulse oximetry screening at moderate altitudes (March 2014)

Neonatal pulse oximetry is an effective screen for critical congenital heart disease, and some professional groups advocate universal screening before discharge from the birth hospital. However, the criteria for a positive screen were based on studies performed at sea level and have not been validated at altitudes greater than 2660 feet (780 m). In a prospective study, performed at moderate altitude (5560 feet [1694 m]), the rate of positive screens (using sea level criteria) was increased compared with that in studies performed at sea level (1.1 versus 0.2 percent) [85]. Additional studies are necessary to determine optimal criteria for a positive screen at moderate to high altitudes. (See "Congenital heart disease (CHD) in the newborn: Presentation and screening for critical CHD", section on 'AAP, AHA, and ACCF screening approach'.)

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