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What's new in family medicine
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2014. | This topic last updated: Apr 11, 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

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 [1]. 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) [2]. 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 [3]. 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'.)

Tamoxifen in dietary supplements for athletic performance (March 2014)

Tamoxifen, an antiestrogen, has been identified as an unlabeled ingredient in dietary supplements marketed to enhance athletic performance [4]. Bodybuilders and other athletes who take exogenous testosterone frequently take tamoxifen (10 to 20 mg/day) to prevent gynecomastia. Tamoxifen doses in one supplement, EstoSuppress, were as high as 7.6 mg/day, close to the therapeutic doses (10 to 20 mg/day for painful gynecomastia and male breast cancer) that have been associated with venous thromboembolism (VTE) [5]. In athletes using androgens and tamoxifen, inadvertent use of additional tamoxifen from dietary supplements could add to the already elevated VTE risk. (See "Use of androgens and other hormones to enhance athletic performance", section on 'Antiestrogens'.)

Vitamin D and mortality (February 2014)

Some observational studies suggest that low serum 25-hydroxyvitamin D levels are associated with higher mortality. In a meta-analysis of 56 randomized trials that compared any type of vitamin D supplementation with placebo or no intervention, vitamin D resulted in a small but significant reduction in all-cause mortality (12.5 versus 12.7 percent) [6]. When different forms of vitamin D were assessed, only vitamin D3 significantly reduced all-cause and cancer mortality. Since mortality has not been reported in all vitamin D trials, there is the possibility of reporting bias where trials showing a mortality effect would be more likely to include results on mortality. (See "Vitamin D and extraskeletal health", section on 'Mortality'.)

Triamcinolone nasal spray available without a prescription in US (February 2014)

Intranasal glucocorticoid (INGC) sprays alleviate nasal blockage, discharge, sneezing, and other nasal allergy symptoms and are considered first-line treatment for allergic rhinitis in most patients (table 1). Triamcinolone is the first INGC to be available in the United States without a prescription for once-daily treatment of nasal allergy symptoms in adults and children two years of age or older [7].  INGC sprays have been available without prescription outside the US for some time. (See "Pharmacotherapy of allergic rhinitis", section on 'Intranasal glucocorticoids'.)

Vitamin D and muscle strength (January 2014)

Observational studies have shown an association between poor vitamin D status and muscle weakness, but it is not clear if vitamin D supplementation improves muscle strength. Results from previous randomized trials have been conflicting. In a trial from Norway, 251 immigrant adults (from South Asia, Middle East, and Africa, mean age 36 to 39 years) with vitamin D deficiency (mean serum 25(OH)D 10.4 ng/mL [26 nmol/L]) were randomly assigned to vitamin D3 supplementation or placebo [8]. After 16 weeks, there were no differences in measures of proximal leg muscle strength or handgrip strength. (See "Vitamin D and extraskeletal health", section on 'Muscle weakness'.)

Long-term risk of hypogonadism in testicular cancer survivors (February 2014)

Testicular cancer survivors are at risk for long-term treatment-related toxicities, including hypogonadism. In a 20-year follow-up study comparing men treated with orchiectomy alone or with adjuvant therapy (chemotherapy or radiation therapy), risk for lower testosterone levels and higher follicle stimulating and luteinizing hormone levels was greater in men who received adjuvant therapy [9]. These data suggest that men with a history of testicular cancer should be routinely evaluated for hypogonadism, especially if they underwent adjuvant therapy. (See "Treatment-related toxicity in men with testicular germ cell tumors", section on 'Hormonal changes'.)

Long-term surgical outcomes for lumbar disc herniation (January 2014)

Eight-year outcome data are available from the arm of the Spine Patient Outcomes Research Trial (SPORT) evaluating surgery (open discectomy) versus nonoperative treatment for carefully-selected patients with lumbar disc herniation [10]. There was significant crossover to surgery for the group of patients randomly assigned to nonoperative care (49 percent received surgery), affecting interpretation of findings from an intent-to-treat analysis. An as-treated analysis, which is susceptible to bias, found significant benefits for surgery in terms of primary outcome measures of pain, physical function, and the Oswestry Disability Index. Secondary outcomes (sciatica bothersomeness, self-rated improvement, and patient satisfaction with symptoms) were better for the group assigned to surgery, both for intent-to-treat and as-treated analyses, although the nonoperative group also showed significant improvement over time. (See "Subacute and chronic low back pain: Surgical treatment", section on 'Standard open discectomy or microdiscectomy'.)

Guideline-discordant care for low back pain (October 2013)

International and US guidelines for the management of patients with low back pain advise treatment with acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs) as first-line therapy for most patients who require medication, that opioids be used judiciously and on a short-term basis, and that (in the absence of "red flag" symptoms) advanced imaging (CT or MRI scanning) not be performed for initial assessment. However, representative data from two national databases of medical visits in the US, including nearly 24,000 visits for spine disorders (representative of approximately 440 million visits) found that use of NSAIDs and acetaminophen decreased between 2000 and 2010 (from 37 to 29 percent), while use of opioids increased (from 19 to 29 percent) [11]. Additionally, the number of CT and MRI studies increased (from 7 to 11 percent), as did rates of patient referral from primary care to other physicians. (See "Subacute and chronic low back pain: Pharmacologic and noninterventional treatment", section on 'Pharmacologic therapies' and "Diagnostic testing for low back pain", section on 'Guidelines'.)

ACIP recommendations for seasonal influenza vaccination (September 2013)

The United States Advisory Committee on Immunization Practices (ACIP) has published recommendations for seasonal influenza vaccination for the 2013 to 2014 influenza season [12]. As in past years, all individuals six months of age or older should be vaccinated. Both trivalent and quadrivalent vaccines are available for the 2013 to 2014 influenza season (table 2). New vaccines include a trivalent inactivated influenza vaccine produced in cultured mammalian cells (Flucelvax) and a trivalent recombinant hemagglutinin influenza vaccine (Flublok). The choice of vaccine formulation depends upon several factors, including age, comorbidities, pregnancy, and risk of adverse reactions. (See "Seasonal influenza vaccination in adults", section on 'Antigenic composition' and "Seasonal influenza vaccination in adults", section on 'Vaccine formulations' and "Seasonal influenza vaccination in children", section on 'Choice of vaccine'.)

PREVENTION

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

The Joint British Societies (JBS) released a new risk calculator that is based on the QRISK Lifetime cardiovascular risk calculator [13]. The 2014 JBS risk calculator extends the assessment of risk beyond the 10-year window of most prior risk estimators and allows for the estimate of "heart age" and the assessment of risk over longer intervals (eg, 50 years for a 45-year-old patient, 30 years for a 65-year-old patient, etc). The calculator also allows for the estimated impact of lifestyle modifications (ie, smoking cessation) on future risk. 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)'.)

HPV vaccine dosing and genital warts (March 2014)

Three doses of HPV vaccine are recommended in the United States, but missed doses and suboptimal adherence to the schedule are frequent. In a Swedish cohort study of over one million females, aged 10 to 24 years, followed for four years, receipt of two quadrivalent HPV vaccine doses was associated with substantial protection against genital warts, although completion of three doses was slightly superior [14]. The study did not assess other important outcomes such as cervical intraepithelial neoplasia or cervical cancer. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Missed doses/alternate schedules'.)

Statin-associated myalgias (March 2014)

A study used n-of-1 trials in eight patients who developed myalgias within three weeks of initiating statin therapy and who had no clinically significant elevation in creatine kinase (CK) to examine whether statins were actually the cause of the pain [15]. Seven patients underwent two or three pairs of treatments, with each treatment pair consisting of three weeks of therapy with statin (at the dose that had been used clinically in that patient) or placebo, a three-week washout period, and the opposite therapy (placebo or statin). None of the eight patients had a statistically significant difference in pain scores between statin and placebo treatment periods. Five of the eight patients resumed and tolerated open-label statin therapy after learning the results of their n-of-1 trials. It is uncertain whether these results would apply to typical patients in whom the diagnosis of statin myopathy is in doubt who are seen outside of recruitment for a study. (See "Statin myopathy", section on 'Nonmyopathic pain'.)

Tomato-based products and lycopene effects on prostate cancer risk (February 2014)

Consumption of lycopene-containing foods, especially tomato-based products, has been extensively studied for its impact on the risk of prostate cancer, but early reports have given conflicting results. A prospective study in a cohort of over 50,000 men from the Health Professionals Follow-up Study suggests that dietary intake of lycopene is associated with a lower incidence of prostate cancer and a decreased risk of lethal prostate cancer [16]. Analysis of biomarkers suggests that these effects may be mediated through inhibition of tumor angiogenesis. It should be noted, however, that nutritional associations found in observational studies frequently are not confirmed when randomized trials are later performed. (See "Risk factors for prostate cancer", section on 'Lycopene and tomato based products' and "Cancer prevention", section on 'Fruits and vegetables'.)

Combination therapy for smoking cessation (January 2014)

There is evidence that some combinations of therapy for smoking cessation result in higher quit rates than monotherapy. There was previously limited evidence on combining varenicline and bupropion, but a randomized trial has now suggested that combining these agents improves smoking abstinence compared with varenicline therapy alone [17]. (See "Pharmacotherapy for smoking cessation in adults", section on 'Adjusting therapy'.)

Multivitamins likely ineffective (January 2014)

A 2013 systematic review, performed for the US Preventive Services Task Force (USPSTF), found limited evidence to support any benefit of vitamin and mineral supplements for preventing cancer or cardiovascular disease [18]. The review included randomized trials evaluating efficacy, and both trials and observational studies evaluating supplement safety. Meta-analysis of two large trials of multivitamin supplements showed a borderline significant reduction in the risk of cancer (relative risk [RR] 0.94, 95% CI 0.89-1.00) and no effect on cardiovascular disease (RR 1.02, CI 0.94-1.10). Multivitamin supplementation also did not appear to reduce the risk of mortality (RR 0.95, CI 0.89-1.01). A separate randomized trial that examined long-term multivitamin supplementation in men found no benefit on cognitive function [19]. Despite their likely lack of efficacy, many patients choose to take vitamins and we suggest that clinicians not struggle against that practice as long as it is harmless. (See "Vitamin supplementation in disease prevention", section on 'Efficacy'.)

New ACC/AHA guidelines for assessment of CVD risk and lipid management (November 2013)

The American College of Cardiology/American Heart Association (ACC/AHA) released guidelines regarding assessment of cardiovascular risk and regarding treatment of lipids [20,21]. These guidelines, while not published as official United States guidelines, essentially replace the Adult Treatment Panel III (ATP III) guidelines from the National Cholesterol Education Program (NCEP). The guidelines state that it is “reasonable” to assess risk factors in most adults every four to six years. For patients without known cardiovascular disease (CVD), the guidelines make recommendations for moderate- or high-intensity statin therapy primarily based on calculated CV risk and presence or absence of diabetes. For most patients with known CVD, the guidelines recommend treatment with high-intensity statin therapy. Unlike ATP III, these ACC/AHA guidelines focus more on intensity of statin therapy, and less on LDL-cholesterol goals and use of nonstatin lipid lowering agents.

While UpToDate authors agree with many of these changes, recommendations from UpToDate for lipid screening, treatment in primary prevention, and treatment in secondary prevention differ in important ways from these guidelines. (See "Treatment of lipids (including hypercholesterolemia) in secondary prevention", section on 'Summary and recommendations' and "Screening for lipid disorders", section on 'Summary and recommendations' and "Treatment of lipids (including hypercholesterolemia) in primary prevention", section on 'Summary and recommendations' and "Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease", section on 'Summary and recommendations'.)

Varenicline in patients with psychiatric disorders (October 2013, MODIFIED January 2014)

Based primarily on post-marketing surveillance data and case reports, there have been concerns that varenicline, an aid to smoking cessation, may have serious neuropsychiatric side effects. Previous randomized trials of varenicline have excluded smokers with a history of major depression or other serious psychiatric conditions. Two small randomized trials have now suggested that varenicline therapy could be safe in some patients with serious psychiatric disorders (see "Pharmacotherapy for smoking cessation in adults", section on 'Neuropsychiatric effects'):

In a multicenter randomized trial in adult smokers with stably-treated current or past major depression, those treated with varenicline or placebo had similar rates of suicidal ideation and suicidal behavior, and neither group showed overall worsening of depression or anxiety; the trial was somewhat limited by a high rate of loss to follow-up [22].

In a small trial in patients with schizophrenia or bipolar disorder, 87 patients who had achieved abstinence while receiving open-label varenicline and cognitive behavioral therapy were randomly assigned to maintenance therapy with varenicline or placebo; all patients continued cognitive behavioral therapy [23]. At 52 weeks, abstinence rates were higher in the varenicline group (60 versus 19 percent), and there was no evidence that treatment with varenicline affected psychiatric symptoms or events. However, because of the small number of participants and the highly selected group of patients, it is difficult to know whether these results generalize to safety of varenicline in all patients with serious psychiatric disorders.

SCREENING

Fecal DNA testing for colorectal cancer screening (March 2014)

A newer stool DNA test that also incorporates stool hemoglobin testing is in development, after withdrawal from the market of a previous stool DNA assay. 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 [24]. 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'.)

Long-term results from the Canadian National Breast Screening Study (February 2014)

Analysis of long-term follow-up data from the Canadian National Breast Screening Study, pooling results for women aged 40 to 49 and 50 to 59, did not find a decrease in breast cancer mortality for women who had mammogram screening [25]. Women aged 50 to 59 enrolled in this trial were randomly assigned to mammography plus a systematic clinical breast examination (CBE) or to CBE alone, so all women in this age group underwent some screening evaluation. The standardized CBE performed in the trial, taking an average of 10 minutes per exam, was far different from typical clinical practice. CBE was not performed in women 40 to 49 years of age. At follow-up extending up to 25 years, the cumulative breast cancer mortality remained the same for mammography and control arms. Overdiagnosis (the identification of breast cancers that would never have become clinically apparent in a woman's lifetime) was seen with 22 percent of mammography-identified lesions, a rate similar to that seen in other studies. (See "Screening for breast cancer: Evidence for effectiveness", section on 'Film mammography' and "Screening for breast cancer: Evidence for effectiveness".)

Fecal immunochemical tests for colorectal cancer screening (February 2014)

Fecal immunochemical tests (FIT) for hemoglobin are more specific than guaiac tests because they respond only to human globin and do not detect upper gastrointestinal bleeding (since globin is digested in transit) or foods with peroxidase activity. In a meta-analysis of 19 studies evaluating the performance of FIT for detecting colorectal cancer in asymptomatic adults, the pooled sensitivity was 0.79 and specificity was 0.94 [26]. Sensitivity for a single sample was about the same as for two or three samples. Compared to stool guaiac testing, FIT has the potential to improve screening compliance since fewer samples are required; and though the FIT test itself is more costly, it may be more cost-effective if fewer colonoscopies are needed for follow-up. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Immunochemical tests for fecal blood'.)

Screening for abdominal aortic aneurysm (February 2014)

A systematic review analyzed four randomized trials of population-based screening for abdominal aortic aneurysm (AAA) in people over age 65, including long-term follow-up data from the largest trial, the Multicenter Aneurysm Screening Study (MASS) [27]. The analysis concluded that an invitation to attend a screening for AAA significantly reduces the risk of AAA-related mortality and risk of AAA rupture in men ages 65 to 74. However, there was no significant reduction in all-cause mortality. Lack of impact on all-cause mortality likely relates to the relative infrequency of AAA as a cause of death (accounting for less than 3 percent of deaths) in this older age population with multiple comorbidities. Screening did not decrease AAA-related or all-cause mortality in women. This analysis serves as the basis for draft revised guidelines from the US Preventive Services Task Force addressing screening for AAA [28]. (See "Screening for abdominal aortic aneurysm", section on 'Effectiveness'.)

Screening for lung cancer (January 2014)

The US Preventive Services Task Force (USPSTF) has revised its guidelines for screening for lung cancer, based on a systematic review and an analysis of the benefits and harms of lung cancer screening [29,30]. The USPSTF now recommends annual low-dose CT scan for high-risk adults (30 pack-year smoking history and current smoker or quit within the past 15 years), aged 55 to 80 years, with discontinuation of screening once the individual has not smoked for 15 years or has a limited life expectancy [31]. UpToDate authors support the USPSTF recommendations. Criteria for screening from several other groups vary slightly, setting 74 years as the upper age for screening, consistent with the study population in the National Lung Screening Trial. (See "Screening for lung cancer", section on 'Recommendations for screening by expert groups'.)

Efficacy of counseling to prevent sexually transmitted infections (October 2013)

High-intensity behavioral counseling with multiple sessions over several hours is effective in reducing the incidence of sexually transmitted infections (STIs). However, the benefit of less intense counseling is unclear. In a trial of 5012 individuals presenting to several STI clinics across the United States, there was no difference in cumulative STI incidence (HIV, HSV-2, chlamydia, gonorrhea, trichomoniasis, and syphilis) at six months between those randomly assigned to receive one-time counseling on STI risk reduction (median of 35 minutes total) and those who received only basic information (median of six minutes total); both groups received rapid HIV testing [32]. We continue to advise risk-reduction counseling in general, but screening for STIs, and HIV testing in particular, should occur even in settings where there is only time to provide basic risk-reduction information. (See "Prevention of sexually transmitted infections", section on 'Risk reduction counseling'.)

ADULT CARDIOVASCULAR MEDICINE

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 [33]. 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'.)

Genotyping ineffective for improving warfarin initial dosing (November 2013)

Initial dosing of vitamin K antagonists (eg, warfarin) is uncertain; pharmacokinetics can be affected by polymorphisms in genes that control drug or clotting factor metabolism. Three trials evaluated the role of genotyping in determining the initial drug dose by randomizing patients to clinically-based dosing or dosing based on genotype [34-36]. The time in the therapeutic INR range, a surrogate for efficacy and adverse events, was unaffected by genotype-based dosing in two trials and minimally improved in the third. Overall bleeding rates were similar between arms in all three trials. Thus, we do not use genotyping to guide vitamin K antagonist initial dosing in routine clinical practice. (See "Therapeutic use of warfarin and other vitamin K antagonists", section on 'Use of genotyping'.)

Duration of antiplatelet therapy after drug-eluting stent placement (October 2013)

The optimal duration of dual antiplatelet therapy (aspirin and a platelet P2Y12 receptor blocker) after coronary artery stent placement with drug-eluting stents (DES) is not known. We recommend treatment for one year in most patients who undergo coronary artery drug-eluting stenting. Two recent studies explore alternative durations:

The open label DES LATE trial randomly assigned 5054 low-risk patients who were treated with aspirin and clopidogrel following DES and were free of major adverse cardiovascular events and major bleeding for at least 12 months to receive aspirin alone or to continue clopidogrel plus aspirin [37]. At 24 months, there was no difference between the groups in the risk of the primary composite end point (death from cardiac causes, myocardial infarction, or stroke) or major bleeding. (See "Antiplatelet therapy after coronary artery stenting", section on 'Longer than one year'.)

In the OPTIMIZE trial, patients with stable coronary artery disease or history of low-risk acute coronary syndrome who underwent DES placement were randomly assigned to clopidogrel for 3 or 12 months and aspirin indefinitely [38]. There was no difference in the rate of the primary composite end point including all-cause death, MI, stroke, or major bleeding. The rate of major bleeding was nonsignificantly lower with the shorter duration of clopidogrel. This trial and others raise the possibility that, for some patients who have received DES, dual antiplatelet therapy for less than one year may be a reasonable strategy. (See "Antiplatelet therapy after coronary artery stenting", section on 'One year or less'.)

ADULT ENDOCRINOLOGY AND DIABETES

Mediterranean diet and diabetes prevention (February 2014)

The Mediterranean diet has been associated with several health benefits. In an exploratory analysis of a trial designed to compare the cardiovascular outcomes of two different Mediterranean diets with a low fat diet in men and women at high risk for cardiovascular disease, the incidence of new diabetes could be ascertained in a subgroup of 3541 individuals [39]. The risk of developing diabetes at four-year follow-up was decreased in the groups assigned to the Mediterranean diets. The original trial and the exploratory analysis had several limitations, and randomized trials of Mediterranean diets with diabetes as a primary endpoint are needed before they can be recommended for diabetes prevention. (See "Prevention of type 2 diabetes mellitus", section on 'Diet'.)

Rosiglitazone (December 2013)

The US Food and Drug Administration has reversed restrictions placed in 2010 on the use of rosiglitazone for the treatment of type 2 diabetes [40]. There had been concerns about cardiovascular safety with this drug. However, the RECORD study, published in 2009, and designed as a noninferiority study comparing rosiglitazone with metformin or sulfonylurea with the premise that rosiglitazone would be beneficial for cardiovascular disease, found no difference in cardiovascular hospitalizations or mortality. Reevaluation of the cardiovascular outcomes data by an independent group showed similar results [41]. Sales of rosiglitazone remain suspended in Europe. (See "Thiazolidinediones in the treatment of diabetes mellitus", section on 'RECORD study'.)

Bisphosphonates and risk of atypical femur fractures (October 2013)

An international task force appointed by the American Society of Bone and Mineral Research published a report on atypical diaphyseal and subtrochanteric femoral fractures in 2010, which was updated in 2013 [42,43]. Although long-term use (median treatment seven years) of bisphosphonates increases the relative risk of atypical fractures, the absolute risk is low (3.2 to 50 cases per 100,000 person-years). The risk may rise with duration of bisphosphonate exposure. (See "The use of bisphosphonates in postmenopausal women with osteoporosis", section on 'Atypical femur fractures'.)

DPP-4 inhibitors and cardiovascular safety (October 2013)

There are a growing number of trials evaluating the cardiovascular safety of DPP-4 inhibitors. In two different trials, patients with type 2 diabetes and either a history of cardiovascular disease or multiple risk factors for vascular disease were randomly assigned to one of the DPP-4 inhibitors (saxagliptin, alogliptin) or placebo, in addition to other diabetes medications (predominantly metformin, sulfonylureas, insulin) [44,45]. The primary endpoint (a composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke) occurred in a similar proportion of patients in both groups. Although heart failure was infrequent in both groups, significantly more patients in the saxagliptin group were hospitalized for heart failure. Although these data are reassuring in that there does not appear to be an increased risk of adverse cardiovascular outcomes with short-term (two-year) treatment with DPP-4 inhibitors used in combination with other agents, longer-term clinical trials are needed to definitively assess the cardiovascular safety of DPP-4 inhibitors. (See "Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)

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 [46]. 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 3) early in management of IBS. (See "Treatment of irritable bowel syndrome in adults", section on 'Low FODMAP diet'.)

Sofosbuvir and simeprevir for genotype 1 chronic hepatitis C infection (December 2013)

Sofosbuvir, a hepatitis C virus (HCV) polymerase inhibitor, and simeprevir, a HCV protease inhibitor, are currently becoming available in the United States and elsewhere for treatment of chronic genotype 1 HCV infection. Regimens that include these agents offer high sustained virological response (SVR) rates, more favorable adverse effect profiles than earlier regimens, ease of administration, and relatively short treatment durations [47-50]. However, regimens for genotype 1 infection generally continue to include interferon. Interferon-free regimens are expected in the near future, and it is reasonable for many patients to defer treatment while awaiting newer therapies. Most patients with chronic genotype 1 HCV infection who are candidates for and desire therapy at this time should be treated with peginterferon, weight-based ribavirin, and a direct-acting antiviral (DAA). If available, we recommend the DAAs sofosbuvir or simeprevir rather than telaprevir or boceprevir. Choice of regimens for specific populations of patients are further discussed in the topic. A joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America has also released guidelines on the use of these agents for the treatment of chronic hepatitis C infection [51]. (See "Treatment regimens for chronic hepatitis C virus genotype 1".)

Sofosbuvir for genotype 2 and 3 chronic hepatitis C infection (December 2013)

Sofosbuvir, a hepatitis C virus (HCV) polymerase inhibitor, is becoming available in the United States and elsewhere for the treatment of genotype 2 and genotype 3 chronic HCV infection. Despite relatively high sustained virologic response (SVR) rates with only 24 weeks of peginterferon and ribavirin among most patients with genotype 2 or 3 infection, the many contraindications and side effects associated with interferon have precluded therapy for many patients. Thus, the introduction of sofosbuvir, which offers the possibility of an effective, well-tolerated, all-oral, interferon-free regimen for most genotype 2 and 3 infected patients [47,52,53], represents a major milestone in the management of chronic HCV infection. Where available, for most patients with genotype 2 and 3 chronic HCV infection, we recommend the combination of sofosbuvir and ribavirin, rather than peginterferon and ribavirin. Choice of regimens for specific populations of patients are further discussed in the topic. A joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America has also released guidelines on the use of these agents for the treatment of chronic hepatitis C infection [51]. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3".)

ADULT HEMATOLOGY AND ONCOLOGY

Radical prostatectomy versus watchful waiting in early prostate cancer (March 2014)

In the Scandinavian Prostate Cancer Group 4 trial, nearly 700 men with newly diagnosed localized prostate cancer were randomly assigned to radical prostatectomy or watchful waiting with active therapy deferred until advanced disease was present [54,55]. With a median follow up of 13 years, there was a significant improvement in overall survival, a decrease in cancer deaths, a decrease in the incidence of metastases, and a decrease in the use of androgen deprivation therapy for men assigned to radical prostatectomy. The benefits were most pronounced in those less than age 65 years, and in those with intermediate risk disease. (See "Radical prostatectomy for localized prostate cancer", section on 'Survival impact of radical prostatectomy'.)

Anastrozole for breast cancer prevention (December 2013)

In women at high risk for breast cancer, selective estrogen receptor modulators (SERMs, tamoxifen or raloxifene) are often prescribed prophylactically. Data suggest that the aromatase inhibitors (AIs) are also effective agents. In the International Breast cancer Intervention Study (IBIS-II) approximately 4000 postmenopausal women at high risk of breast cancer were randomly assigned to treatment with anastrozole or placebo for five years [56]. As presented at the 2013 San Antonio Breast Cancer Symposium, anastrozole significantly reduced the incidence of both invasive and in situ breast cancer compared to placebo. These results are similar to previously published results from a randomized trial that evaluated the AI, exemestane, as chemoprevention. Based on these data, both the SERMs and the AIs are reasonable options for breast cancer prevention in high-risk postmenopausal women. (See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention", section on 'Aromatase inhibitors'.)

ADULT INFECTIOUS DISEASE

ACIP immunization recommendations (March 2014)

New immunization recommendations for 2014 for adults in the United States have been issued by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) (figure 1 and figure 2) [57,58]. Changes to the updated schedule include the addition of Haemophilus influenza b (Hib) vaccine recommendations for adults with asplenia, sickle cell disease, stem cell transplant, or planned splenectomy. HIV infection is not an indication for Hib vaccination. (See "Approach to immunizations in healthy adults", section on 'Immunization schedule for healthy adults'.)

Potential for interferon-free regimens in chronic HCV genotype 1 infection (January 2014)

Rapid progress is being made towards developing all-oral, interferon-free regimens that achieve excellent rates of sustained virologic response (SVR), and thus effective cure, for genotype 1 hepatitis C virus (HCV) infection, even among patients who had not previously responded to peginterferon and ribavirin. Genotype 1 infection is the most common in North America and Europe and has traditionally been difficult to treat. In two trials of different interferon-free regimens in genotype 1 infected patients without cirrhosis, including both treatment-naive and experienced individuals, SVR was achieved in 83 to 98 percent, depending on the specific regimen [59,60]. Although most of the agents in these regimens are not currently available, these results highlight the feasibility of cure of genotype 1 HCV infection without the need for interferon and should thus inform the decision on whether to defer antiviral treatment to wait for these new agents. (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Deciding when to treat' and "Investigational therapies for hepatitis C virus infection", section on 'Interferon-free DAA combinations'.)

2013-2014 seasonal influenza surveillance (January 2014)

The United States Centers for Disease Control and Prevention and the World Health Organization track influenza virus isolates worldwide. Surveillance between September 29 and December 7, 2013 found that approximately 90 percent of isolates in the United States were influenza A viruses [61]. Among influenza A isolates, 90 percent were 2009 pandemic H1N1 viruses, which have been associated with severe respiratory illness in young and middle-aged adults early in the 2013-2014 influenza season [62]. Although it is not possible to predict whether this pattern will continue throughout the season, if it does, young and middle-aged adults may be disproportionately affected. This influenza strain is included in the 2013-2014 seasonal influenza vaccine, but vaccine efficacy remains to be determined. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Influenza activity' and "Epidemiology of influenza", section on 'Influenza activity'.)

Fluoroquinolones and retinal detachment (December 2013)

Two observational studies report conflicting findings regarding an association between fluoroquinolone use and retinal detachment. A previously published case-control study of patients in Canada who visited an ophthalmologist found a small increased rate of retinal detachment in patients receiving an oral fluoroquinolone [63]. In contrast, a cohort study from a nationwide registry in Denmark that more comprehensively controlled for potential confounders did not find an association between fluoroquinolone use and risk of retinal detachment [64]. Additional studies are required to determine whether fluoroquinolones are associated with retinal detachment. (See "Fluoroquinolones", section on 'Retinal detachment'.)

Coprescription of clarithromycin and calcium channel blockers (November 2013)

In a population-based study of older adults, coprescribing clarithromycin with a calcium channel blocker (compared with azithromycin plus a calcium channel blocker) was associated with a small but statistically significant increase in risk of hospitalization with acute kidney injury [65]. Coprescription with clarithromycin was also associated with a higher risk of hospitalization with hypotension and all-cause mortality. Although the risks associated with the combined use of clarithromycin and calcium channel blockers appear to be small, they should be considered when deciding whether to use these agents in combination in older patients or other patients at risk for acute kidney injury. (See "Azithromycin, clarithromycin, and telithromycin", section on 'Drug interactions'.)

Early treatment of HIV infection (November 2013)

In a highly publicized case, an infant diagnosed with HIV infection and initiated on antiretroviral therapy (ART) at 30 hours of age maintained an undetectable HIV viral load one year following the discontinuation of ART at 18 months of age [66]. Although some experts remain unconvinced that the infant was truly infected, the case report joins other small observational studies that demonstrate very low viral reservoirs or persistent control of viral replication in some patients who initiated ART at the earliest time points after HIV infection [67-69]. Discontinuation of ART, regardless of when it is initiated, is not recommended because of poor clinical outcomes associated with treatment interruption in the setting of chronic HIV infection. Nevertheless, this possibility of an alteration in disease course with its potential implications for future cure strategies, in addition to the known benefits of early treatment, overall support the initiation of ART during acute or early HIV infection. (See "Acute and early HIV infection: Treatment", section on 'Can ART in early infection alter disease course?'.)

ADULT NEPHROLOGY AND HYPERTENSION

Risk of ESRD among kidney donors (February 2014)

A large cohort study reported an increased risk of end stage renal disease (ESRD) among over 90,000 kidney donors compared with over 20,000 healthy matched controls from a US database [70]. The risk of ESRD was highest among black donors compared with Hispanic and white donors, but for every group and every age studied, the risk was higher among donors compared with nondonors. The absolute risk of ESRD among both donors and nondonors was quite low (90 per 10,000 donors and 14 per 10,000 healthy nondonors). The risk of ESRD may have been underestimated in the nondonor group, which would impact the study findings. (See "Evaluation of the living kidney donor and risk of donor nephrectomy", section on 'End-stage renal disease (ESRD)'.)

Eighth Joint National Committee (JNC-8) guidelines for hypertension (December 2013)

The eighth Joint National Committee (JNC-8) has released new guidelines for the treatment of hypertension [71]. The major change compared with the older JNC-7 guidelines is a higher blood pressure goal for older adults (60 years and older) and for patients with diabetes mellitus or chronic kidney disease. These new guidelines are largely consistent with previous UpToDate recommendations. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'Goal blood pressure' and "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension", section on 'Goal blood pressure'.)

The CORAL trial of stenting in renal artery stenosis (November 2013)

In a randomized trial comparing revascularization plus medical therapy with medical therapy alone in 947 patients with atherosclerotic renal artery stenosis and either poorly controlled hypertension or a decreased estimated glomerular filtration rate (eGFR <60 mL/min/1.73m2), revascularization had no effect at 3.6 years on the primary outcome (a composite of cardiovascular or renal death, stroke, myocardial infarction, hospitalization for heart failure, a reduction in eGFR by more than 30 percent, or end-stage renal disease) or any individual component of the primary outcome [72]. Serious adverse events associated with revascularization were uncommon; the most frequent was renal artery dissection, which occurred in 11 revascularized patients (2.2 percent). (See "Treatment of unilateral atherosclerotic renal artery stenosis", section on 'Revascularization versus medical therapy alone'.)

Combination ACE inhibitor and ARB therapy in diabetic nephropathy (November 2013)

Combination therapy with an ACE inhibitor plus an ARB should not be used in patients with diabetic nephropathy. The VA NEPHRON-D trial randomly assigned 1448 patients with diabetic nephropathy to lisinopril or placebo; all patients also received losartan [73]. The trial was discontinued early (after a median of 2.2 years) because of safety concerns. The primary event rate (a 50 percent or 30 mL/min/1.73m2 decline in estimated GFR, end-stage renal disease, or death) occurred with similar frequency in both groups, while acute kidney injury requiring hospitalization or occurring during hospitalization was significantly more common with combination therapy (18.0 versus 11.0 percent), as was severe hyperkalemia (9.9 versus 4.4 percent). (See "Treatment of diabetic nephropathy", section on 'Combination ACE inhibitor and ARB therapy'.)

ADULT NEUROLOGY AND PSYCHIATRY

Blood pressure management in the acute phase of ischemic stroke (February 2014)

Although long-term antihypertensive therapy is known to reduce the risk of recurrent stroke, management of hypertension in the acute phase of stroke is controversial, partly because of concerns that the ischemic penumbra may be at risk if cerebral blood flow is reduced. In an open-label randomized trial, over 4000 adults with acute ischemic stroke were assigned to intensive blood pressure control or discontinuation of all antihypertensive therapies within the first 48 hours of stroke onset [74]. At 14 and 90 days post-stroke, there were no differences in rates of death or major disability between the groups. The lack of an observed benefit from aggressive blood pressure control is consistent with our current approach to avoid excessive lowering of blood pressure within the first 24 hours after ischemic stroke. (See "Initial assessment and management of acute stroke", section on 'Interventions'.)

Gabapentin treatment for alcohol use disorder (January 2014)

Previous clinical trials suggested that gabapentin may reduce alcohol consumption in patients with alcohol dependence (DSM-IV), but these trials had small sample sizes and other methodological limitations. In a new randomized trial of 150 patients with alcohol dependence, subjects receiving gabapentin were more likely to remain abstinent or avoid heavy drinking, and less likely to experience craving compared to those receiving placebo [75]. These findings in combination with the earlier results support the use of gabapentin as one of several agents that can be tried in patients with alcohol use disorder (revised in DSM-V from alcohol dependence) who do not respond to naltrexone or acamprosate. (See "Pharmacotherapy for alcohol use disorder", section on 'Gabapentin'.)

Pregabalin versus pramipexole for the treatment of restless legs syndrome (February 2014)

Two major classes of drugs are used to treat restless legs syndrome (RLS) in adults: dopamine agonists and alpha-2-delta calcium channel ligands. Both classes have been shown to be effective compared with placebo, but the classes have not been compared head-to-head. In a randomized trial that included over 700 adults with RLS, both pregabalin and pramipexole reduced the symptom burden of RLS more than placebo but augmentation, a complication of dopaminergic therapy that can limit long-term effectiveness, occurred less frequently with pregabalin [76]. Overall, however, pregabalin was less well tolerated than pramipexole, leading to a higher rate of treatment discontinuation due to side effects. More comparative trials are needed to better understand the long-term safety and tolerability profile of treatment options for RLS. (See "Treatment of restless legs syndrome in adults", section on 'Pregabalin'.)

Randomized trial of unruptured brain arteriovenous malformations (February 2014)

In the Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), patients with unruptured arteriovenous malformations (AVMs) were assigned to medical versus interventional (surgery, radiotherapy, and/or endovascular therapy) treatment [77]. The trial was halted early with outcome data on 223 patients followed for a mean of 33 months. Composite rates of symptomatic stroke (ischemic and hemorrhagic) and death were higher in the interventional compared to medical treatment group (31 versus 10 percent). Patients will continue to be followed for an additional five years of follow-up. These results corroborate previous findings from observational studies that suggest that interventional treatment of unruptured AVMs is associated with worse outcomes than conservative management. (See "Brain arteriovenous malformations", section on 'Ruptured versus unruptured AVM'.)

Valproate as a first-line option for maintenance treatment of bipolar disorder (February 2014)

Bipolar disorder is usually a recurrent disease that requires maintenance treatment lasting for years; first-line maintenance treatments include lithium and lamotrigine, although valproate has also been used for maintenance treatment. A recent meta-analysis indicates that valproate should be considered as an additional first-line option. The meta-analysis included six randomized trials that compared valproate either with placebo or with lithium in nearly 900 euthymic bipolar patients treated for 6 to 24 months [78]. In two trials comparing valproate with placebo, fewer recurrent mood episodes occurred with valproate, although valproate side effects included weight gain, tremor, and alopecia. In four trials comparing valproate with lithium, recurrence rates were comparable, and discontinuation of treatment due to intolerance or nonadherence occurred less often with valproate. (See "Bipolar disorder in adults: Maintenance treatment", section on 'Valproate'.)

Occupation and risk of suicide (January 2014)

Past studies examining suicide risk have gathered data about employment, but the role of occupation had not been systematically evaluated. A meta-analysis of 34 studies found that the risk of suicide was greater among the least skilled workers (eg, laborers and office cleaners who perform simple manual tasks) compared with the general working-age population [79]. By contrast, the risk of suicide was lower in the most skilled workers (eg, general managers who solve complex problems). (See "Suicidal ideation and behavior in adults", section on 'Occupation'.)

Vitamin E supplementation in mild to moderate Alzheimer dementia (January 2014)

The value of antioxidants in patients with Alzheimer dementia (AD) is debated, with small randomized trials reporting conflicting results. In a recent trial that included over 600 patients with mild to moderate AD who were randomly assigned to vitamin E, memantine, vitamin E plus memantine, or placebo, patients assigned to vitamin E experienced a slower time to functional decline compared with those assigned to placebo [80]. Combination therapy was less beneficial than vitamin E alone, and none of the treatment arms were associated with improved cognitive function. While memantine remains a treatment option for moderate to severe AD, these results add support to existing data suggesting that vitamin E therapy has modest benefits in patients with mild to moderate AD. (See "Treatment of dementia", section on 'Vitamin E'.)

SSRIs during pregnancy and risk of autism spectrum disorder (January 2014)

Previous studies have suggested an association between use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and an increased risk of autism spectrum disorders in offspring, but a recent national registry study of over 600,000 births provides reassuring data [81]. The study identified nearly 4000 children with autism, including 52 who were exposed in utero to SSRIs. After adjusting for potential confounders, such as maternal parity, age, socioeconomic status, smoking status, psychiatric disorders, and other drugs used during pregnancy, use of SSRIs during pregnancy was not associated with an increased risk of autism. However, there was an increased risk of autism in children of women who received SSRIs before pregnancy but not during pregnancy. The authors concluded that the associations observed between antenatal SSRI exposure and autism in previous studies may have been attributable to the underlying indications for these medications (eg, maternal depression). (See "Infants with antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)", section on 'Autism'.)

Secondary prevention of stroke from intracranial large artery atherosclerosis (October 2013)

The final results of the SAMMPRIS trial confirm that aggressive medical management is superior to angioplasty and stenting for patients with recently symptomatic high-grade intracranial large artery stenosis [82]. At study end, with a median follow-up of 32 months, the rate of primary outcome events (stroke or death within 30 days either of enrollment or a revascularization procedure during follow-up, or subsequent ischemic stroke in the territory of the qualifying artery) remained significantly higher for the stenting group compared with the medical management group. (See "Intracranial large artery atherosclerosis", section on 'SAMMPRIS trial'.)

ADULT PULMONOLOGY

Combination therapy with umeclidinium and vilanterol for COPD (January 2014)

Patients with COPD who have persistent symptoms despite use of a single long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) inhaler sometimes find relief with the combination of two inhalers. A dry powder inhaler containing both a LAMA and LABA (umeclidinium and vilanterol) has been approved for use in COPD in the United States. The combination was compared with each of the individual agents and placebo in a 24-week randomized trial that included over 1500 subjects with COPD [83]. The combination inhaler achieved greater increases in pulmonary function and improved symptom control compared with the individual agents and placebo. Adverse events were infrequent. The efficacy of the umeclidinium/vilanterol inhaler has not been compared with other currently available LAMAs and LABAs. (See "Management of stable chronic obstructive pulmonary disease", section on 'Combined therapy'.)

ADULT RHEUMATOLOGY

Platelet-rich therapy for soft tissue healing (January 2014)

Tissue injections of platelet-rich autologous blood are used by some clinicians to promote healing of tendon and other soft tissues following injury or surgery. However, evidence supporting the efficacy of this therapy is scant. A systematic review of 19 small trials (17 randomized) of mostly limited quality, involving over 1000 participants suffering from a range of conditions including tendinopathy and tendon tears, concluded that there is insufficient evidence to support platelet-rich therapy in the treatment of soft tissue injuries [84]. Well-conducted randomized controlled trials are needed to determine whether platelet-rich therapy is effective. (See "Overview of the management of overuse (chronic) tendinopathy", section on 'Dry needling and autologous blood/platelet rich plasma injection'.)

Effect of diet and exercise on knee osteoarthritis (October 2013)

Lifestyle modifications such as diet and exercise remain a mainstay for the treatment of mild to moderate knee osteoarthritis. In the Intensive Diet and Exercise for Arthritis (IDEA) trial, 454 overweight and obese adults with pain and mild-to-moderate radiographic knee OA were randomized to one of three groups: diet plus exercise, diet, or exercise [85]. At 18 months, adults in the combined diet plus exercise group reported less pain, better health-related quality of life, and improved function scores compared with the other two groups. The effects of weight loss on biomechanical and proinflammatory cytokines were also measured. Knee compressive forces and interleukin-6 levels were lower in the diet only and in the diet plus exercise group when compared with the exercise only group. (See "Nonpharmacologic therapy of osteoarthritis", section on 'Weight loss'.)

GYNECOLOGY

Oral emergency contraception in overweight women (February 2014)

In Europe, product labeling for levonorgestrel-based emergency contraception (NorLevo) was recently updated to indicate that it may be less effective in women ≥75 kg (165 pounds) and not effective in women >80 kg (176 pounds) [86,87]. We counsel overweight and obese women about potentially reduced or absent efficacy of levonorgestrel emergency contraception as body mass index increases above the normal range (25) or at weights ≥75 kg (165 pounds). (See "Emergency contraception", section on 'Overweight and obese women'.)

Levonorgestrel-releasing intrauterine device for women on anticoagulants (December 2013)

Women on anticoagulants are at increased risk of heavy menstrual bleeding. The levonorgestrel-releasing-intrauterine device (LNg-IUD), which is beneficial in reducing menstrual flow in women with heavy bleeding, also appears to be effective in women who are being treated with anticoagulants. In a prospective study of 33 women with thrombophilia and/or history of thrombosis who initiated LNg-IUD use, oral anticoagulant users had similar bleeding patterns to nonusers during the first 12 months after LNg-IUD insertion [88]. Three-quarters of the women developed amenorrhea or infrequent bleeding and no women experienced frequent or prolonged bleeding. (See "Intrauterine contraception (IUD): Overview", section on 'Anticoagulation/bleeding diathesis'.)

OBSTETRICS

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 [89]. 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'.)

Noninvasive prenatal screening in low-risk women (March 2014)

Noninvasive prenatal screening using cell-free DNA is an option for screening women at high risk of fetal aneuploidy (trisomy 21, 18, 13), but test performance is unclear in low-risk women. A recent study compared the performance of cell-free DNA sequencing with standard maternal aneuploidy screening (maternal analyte assay with or without nuchal translucency measurement) in a general obstetrical population of over 1900 women who underwent both screening tests; results of DNA sequencing were concealed [90]. Both screening tests detected all cases of trisomy 21 and trisomy 18. DNA sequencing had a lower false-positive rate (trisomy 21: 0.3 versus 3.6 percent; trisomy 18: 0.2 versus 0.6 percent). Thus, far fewer women would need to be offered invasive diagnostic testing because of a positive screen. However, additional issues need to be addressed before noninvasive prenatal screening using cell-free DNA can be recommended as a primary screening tool in the general obstetrical population. (See "Down syndrome: Prenatal screening overview", section on 'Screening performance of tests used for primary screening'.)

Risk of spontaneous abortion from exposure to NSAIDs (March 2014)

There is uncertainty regarding the risk of spontaneous abortion (SAB) following exposure to nonsteroidal antiinflammatory drugs (NSAIDs) during pregnancy. A recent cohort study linked data from medication dispensing records to information on obstetric outcomes for over 65,000 pregnancies, including about 6500 women with SAB and 4500 pregnant women exposed to NSAIDs [91]. There was no significant increase in the risk of SAB following NSAID exposure up to 20 weeks of pregnancy, after controlling for multiple variables. This was most conclusive for nonselective NSAIDs but appeared true for COX-2-selective NSAIDs as well, although data on the latter agents were limited. These results are reassuring, although some experts continue to advise caution. In addition, NSAIDs should still be avoided in the third trimester due to risk of premature closure of the fetal ductus arteriosus, an issue that was not addressed in this study. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'NSAIDs and aspirin'.)

Contraception and postpartum risk of thrombosis (March 2014)

Because the risk of thrombotic events is elevated in postpartum women, estrogen-progestin contraceptives are not initiated until at least three weeks after delivery. In a large retrospective study, the risk of a thrombotic event was highest in the first three weeks postpartum (odds ratio 18), fell to relatively low levels by seven weeks (odds ratio 2), but did not reach baseline levels until 16 weeks after delivery [92]. This study does not change our approach to postpartum contraception, which allows women without additional risk factors for thrombosis to begin estrogen-progestin contraception after the period of highest risk (first three weeks postpartum) but before ovulation resumes. Although the risk of a thrombotic event remains increased three to six weeks postpartum, there is no direct evidence that initiation of contraception during this period further increases the risk of thrombosis, which continues to fall over time. (See "Postpartum and postabortion contraception", section on 'Estrogen-progestin contraceptives'.)

Epidural anesthesia and second stage of labor (February 2014)

Epidural anesthesia is known to be associated with a longer second stage of labor. A large retrospective cohort study reported that, compared with no epidural anesthesia, the 95th percentile for the second stage of labor was increased by about 2.3 hours in nulliparous women and 3.0 hours in multiparous women who had epidural anesthesia [93]. These times are significantly longer than reported in previous studies and may reflect specific obstetric and anesthesia practices at a single institution. The results of this study do not change our recommendations for managing the second stage of labor. (See "Overview of normal labor and protraction and arrest disorders", section on 'Neuraxial anesthesia'.)

Tools for estimating delivery date (February 2014)

Calculators for the estimated delivery date (EDD) of a pregnancy and current gestational age are widely available (calculator 1 and calculator 2) and should be used instead of traditional mechanical gestational wheels. Electronic techniques, such as APPs, appear to be more accurate than these wheels. In a study comparing 31 paper gestational wheels from a variety of sources and 20 electronic gestational age calculators, there was significant variation in the EDD determined by the paper wheels [94]. The largest discrepancy was four days short of the EDD predicted by Naegele’s rule (the most common method of pregnancy dating) and two wheels yielded EDDs that differed by seven days. All 20 APPs gave an EDD consistent with Naegele’s rule and all corrected for a leap year, while none of the paper gestational wheels made this adjustment. (See "Prenatal assessment of gestational age", section on 'Calculator'.)

SSRIs in late pregnancy and risk of pulmonary hypertension of the newborn (January 2014)

Studies have yielded contradictory findings regarding the association between use of selective serotonin reuptake inhibitors (SSRIs) during late pregnancy (eg, third trimester) and the risk of persistent pulmonary hypertension of the newborn (PPHN), a potentially fatal condition that occurs in approximately 2 per 1000 live births. In a recent meta-analysis of five observational studies, exposure to SSRIs in late pregnancy was associated with an increased relative risk of PPHN (odds ratio 2.5) [95]. However, the baseline risk of PPHN is low, so the absolute increase due to late pregnancy SSRI exposure is small. The meta-analysis estimated that about 350 women would have to be treated with SSRIs in late pregnancy to cause one additional case of PPHN. (See "Infants with antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)", section on 'Persistent pulmonary hypertension of the newborn'.)

New diagnostic criteria for preeclampsia (November 2013)

In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as an essential diagnostic criterion for preeclampsia. Preeclampsia can now be diagnosed based on new onset of hypertension with either proteinuria or end-organ dysfunction after 20 weeks of gestation [96]. Massive proteinuria and fetal growth restriction have also been removed as characteristics of severe disease. (See "Preeclampsia: Clinical features and diagnosis", section on 'Definitions of pregnancy-related hypertensive disorders'.)

Diagnosis of spontaneous abortion in early gestations (October 2013)

Diagnosis of spontaneous abortion is based upon pelvic ultrasound findings. The criteria had been based mainly on the size of the gestation and presence of appropriate findings. The Society of Radiologists in Ultrasound has added criteria for early gestations (gestational sac <25 mm or embryo <7 mm) based upon lack of development over time [97]. These stipulate that a spontaneous abortion may be diagnosed if the appropriate findings (yolk sac or fetal cardiac activity) are not visualized in a follow-up ultrasound in 11 to 14 days. (See "Spontaneous abortion: Risk factors, etiology, clinical manifestations, and diagnostic evaluation", section on 'Diagnosis'.)

Trial of labor is safe when the first twin is in vertex presentation (October 2013)

The Twin Birth Study showed that planned cesarean delivery does not significantly improve neonatal outcome as compared with planned vaginal delivery when the first twin is in vertex presentation [98]. In this trial, over 1000 women at 32 to 38 weeks of gestation with twin pregnancy and the first twin in vertex presentation were randomly assigned to planned cesarean or planned vaginal delivery at term. No significant difference in the composite outcome (fetal or neonatal death or serious neonatal morbidity) was observed between groups, thus supporting a trial of labor in vertex-presenting twin pregnancy. (See "Twin pregnancy: Labor and delivery", section on 'Should routine cesarean delivery be offered?'.)

PEDIATRICS: GENERAL PEDIATRICS

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 [99]. 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'.)

Non-celiac gluten sensitivity (March 2014)

It remains unclear whether there is a category of patients with symptomatic response to gluten but without serologic evidence of celiac disease, termed “non-celiac gluten sensitivity.” In most cases the gastrointestinal symptoms are not replicated on double-blind food challenge, suggesting a strong placebo effect. However, a small minority of patients may have a true non-celiac gluten sensitivity. This was suggested by a study in a group of children without serologic evidence of celiac disease, but documented gastrointestinal symptoms in response to open challenge with gluten [100]. In this selected group of patients, the symptoms were reproduced after a partially-blinded gluten challenge, in which the child but not the parents were blinded to the gluten. The findings may reflect a true gluten sensitivity, biased expectations of the parent, or symptoms caused by non-gluten carbohydrates in the diet. (See "Clinical manifestations and diagnosis of celiac disease in children", section on 'Non-celiac gluten sensitivity'.)

Topical therapy for tympanostomy tube otorrhea (March 2014)

A number of comparative trials and observational studies have suggested that ototopical therapy is better than oral antibiotics for the treatment of acute uncomplicated tympanostomy tube otorrhea (TTO), although all of these studies had methodologic limitations. An open-label trial of 230 children with uncomplicated acute TTO who were randomly assigned to ototopical drops, oral antibiotics, or initial observation has confirmed these findings [101]. Fewer children treated with combination antibiotic-corticosteroid eardrops (hydrocortisone-bacitracin-colistin) than with oral antibiotics (amoxicillin-clavulanate) or observation had otorrhea at two weeks. Ciprofloxacin-dexamethasone is a more widely available antibiotic-corticosteroid eardrop and is the only one currently approved for treatment of TTO in the United States. (See "Tympanostomy tube otorrhea in children: Causes, prevention, and management", section on 'Uncomplicated acute TTO'.)

American Academy of Pediatrics recommendations for preventive pediatric healthcare (February 2014)

In February 2014, the American Academy of Pediatrics (AAP) released updated recommendations for preventive pediatric healthcare [102]. Major changes from the 2008 periodicity schedule include recommendations to screen:

Newborns for critical congenital heart disease with pulse oximetry before discharge from the birth hospital (See "Congenital heart disease (CHD) in the newborn: Presentation and screening for critical CHD", section on 'Pulse oximetry screening'.) 

Children for dyslipidemia between 9 and 11 years (in addition to between 18 and 21 years as previously recommended) (See "Definition and screening for dyslipidemia in children", section on 'Lipid screening'.) 

 Adolescents for depression annually between 11 and 21 years of age (See "Screening tests in children and adolescents", section on 'Depression screening'.)

Adolescents for HIV between 16 and 18 years of age (See "The adolescent with HIV infection", section on 'Counseling and testing'.)

These recommendations are consistent with previously released guidelines from the AAP or other professional groups (eg, the US Preventive Services Task Force, the National Heart, Lung, and Blood Institute).

Viscous lidocaine in children with herpetic gingivostomatitis (February 2014)

Children with herpetic gingivostomatitis are at risk for dehydration because of decreased intake. Application of viscous lidocaine (with or without other topical agents) is sometimes suggested as a way to decrease pain and improve intake. However, in a placebo-controlled randomized trial, viscous lidocaine did not increase fluid intake in children with acute infectious oral ulcers [103]. We do not suggest topical therapies containing viscous lidocaine for the treatment of children with herpetic gingivostomatitis. (See "Herpetic gingivostomatitis in young children", section on 'Topical therapies'.)

Obesity usually is established before school entry (February 2014)

Longitudinal studies reveal that a substantial component of adolescent obesity is established before five years of age. In a large study from the United States, children who were overweight at entry into kindergarten were four times as likely to become obese by eighth grade as compared with normal-weight children [104]. Moreover, the severity of obesity was an important predictor of persistence. Among children who had mild obesity at entry into kindergarten (mean age 5.6 years), 47 percent remained obese in eighth grade (mean age 14.1 years). Among those who had severe obesity (BMI 99th percentile) in kindergarten, more than 70 percent remained obese in eighth grade (figure 3). These observations provide support for the concept of interventions early in life to prevent and treat obesity. (See "Definition; epidemiology; and etiology of obesity in children and adolescents", section on 'Persistence into adulthood'.)

Cognitive-behavioral therapy for chronic migraine in children and adolescents (January 2014)

In a 20-week randomized trial of 135 children and adolescents with chronic migraine, a significantly greater proportion of children assigned to treatment with 10 sessions of cognitive-behavioral therapy (CBT) plus daily amitriptyline achieved a ≥50 percent reduction in days with headache compared with those assigned to headache education plus amitriptyline (66 versus 36 percent) [105]. In addition, a reduction in headache disability to mild or none was significantly greater with CBT plus amitriptyline (75 versus 56 percent). However, widespread use of CBT may be limited by restricted availability and high cost. (See "Management of migraine headache in children", section on 'Behavioral interventions'.)

Diagnosis of pediatric appendicitis (January 2014)

The Pediatric Appendicitis Score (PAS) is a tool that utilizes history, physical examination, and laboratory results to categorize the risk of appendicitis in children with abdominal pain on a 10 point scale (table 4). In a prospective observational study of 196 children with abdominal pain who were evaluated using a clinical pathway based upon the PAS in a children’s hospital emergency department, the sensitivity and specificity of the pathway for appendicitis was 92 and 95 percent, respectively [106]. (See "Acute appendicitis in children: Clinical manifestations and diagnosis", section on 'Pediatric appendicitis score'.)

Clinical score for testicular torsion in children (November 2013)

The best approach to assessing children with possible testicular torsion is debated, and imaging may be overutilized. In a prospective study of 338 children with an acute scrotum (15 percent with testicular torsion) evaluated at a single institution, a clinical scoring system for testicular torsion was derived based upon five clinical criteria [107]. A score ≥5 diagnosed testicular torsion with a sensitivity of 76 percent, specificity of 100 percent, and a positive predictive value of 100 percent. A score ≤2 excluded testicular torsion with a sensitivity of 100 percent, a specificity of 82 percent, and a negative predictive value of 100 percent. The scoring system was evaluated retrospectively in a validation sample of 116 children with similar results. Thus, children with a score ≥5 warrant prompt evaluation by a surgeon with pediatric urologic expertise, rather than imaging. However, further validation is needed before this system is routinely used to exclude testicular torsion without a confirmatory ultrasound in children with a score ≤2. (See "Causes of scrotal pain in children and adolescents", section on 'Diagnosis'.)

New definition of severe obesity in children and adolescents (October 2013)

A new statement from the American Heart Association defines severe obesity in children and adolescents as a BMI that is either ≥120 percent of the 95th percentile or ≥35 kg/m2 (whichever is lower) (figure 4A-B) [108]. This threshold corresponds to approximately the 99th percentile (Z-score 2.33). Approximately 5 percent of children and adolescents currently have severe obesity in the United States. These children will almost always remain in the obese range as adults, and 65 percent will have Class III obesity as adults (BMI ≥40). (See "Surgical management of severe obesity in adolescents", section on 'Defining severe obesity' and "Definition; epidemiology; and etiology of obesity in children and adolescents", section on 'Definitions'.)

Brace treatment for adolescent idiopathic scoliosis (October 2013)

The multicenter Bracing in Adolescent Idiopathic Scoliosis Trial confirms findings from observational studies that bracing reduces the risk of curve progression in skeletally immature patients with adolescent idiopathic scoliosis (AIS) during the adolescent growth spurt [109]. Skeletally immature adolescents with AIS at risk for progression (Cobb angle 20° to 40°) were randomly assigned to bracing for ≥18 hours/day or observation (randomized cohort) or were permitted to choose bracing or observation (preference cohort). Bracing reduced the risk of curve progression to Cobb angle ≥50° (the threshold for surgery) in the entire study population and in the randomized cohort. Approximately one-half of adolescents who were not braced or who wore their brace ≤6 hours/day also had Cobb angle <50° at skeletal maturity, suggesting room for refinement in bracing indications. (See "Adolescent idiopathic scoliosis: Treatment and prognosis", section on 'Efficacy of bracing'.)

PEDIATRICS: DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS

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 [110]. 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'.)

Antidepressants and risk of suicide attempts in children and adolescents (February 2014)

Pooled analyses of randomized trials suggest that antidepressants may slightly increase the risk of suicidal thoughts and behavior in children and adolescents, but it is not known if the risk varies among specific antidepressants. A recent observational study examining this risk with newer selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) suggests that it does not differ among particular medications. The study used an insurance claims database and medical records that included more than 38,000 youth who were treated with fluoxetine, citalopram, escitalopram, paroxetine, sertraline, or venlafaxine, and identified 419 patients with medically treated suicide attempts [111]. After adjusting for potential confounders, the analyses found that the rate of suicide attempts was comparable in subjects exposed to each of the agents evaluated. (See "Effect of antidepressants on suicide risk in children and adolescents", section on 'Observational studies'.)

ADHD treatment and priapism (January 2014)

In December 2013, the US Food and Drug Administration (FDA) issued a safety communication about priapism as a rare adverse effect of methylphenidate treatment of attention deficit hyperactivity disorder [112]. The FDA identified 15 cases of methylphenidate-associated priapism between 1997 and 2012. Most cases occurred in boys <18 years. Priapism occurred after increased dose, increased dosing interval, and temporary or permanent discontinuation of methylphenidate. Priapism is also a rare adverse effect of atomoxetine. Male patients who are being treated for ADHD with methylphenidate or atomoxetine should be educated about the signs and symptoms of priapism and the importance of seeking immediate medical attention if priapism occurs. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents", section on 'Priapism' and "Pharmacotherapy for adult attention deficit hyperactivity disorder".)

Increased risk of suicide attempts in adopted adolescents (December 2013)

Suicide is one of the leading causes of death among adolescents, and efforts to identify patients who are at risk may facilitate prevention. A new study suggests the risk of attempting suicide may be increased among teens who were adopted. In this prospective study, over 1100 adopted and nonadopted adolescents with a mean age of 15 years were enrolled and followed for approximately three years [113]. After controlling for suicide risk factors (eg, psychiatric disorders), the investigators found that the probability of a suicide attempt was nearly four times greater among adoptees. (See "Suicidal behavior in children and adolescents: Epidemiology and risk factors", section on 'Adoption'.)

PEDIATRIC IMMUNIZATIONS

Pediatric influenza mortality (November 2013)

Influenza mortality is increased among children with risk factors for severe or complicated influenza, but also occurs in children without risk factors. Between 2004 and 2012, 43 percent of children who died of influenza in the United States did not have a high-risk condition [114]. Children without high-risk conditions were more likely than children with high-risk conditions to die before hospital admission and within three days of symptom onset. These findings highlight the importance of fully immunizing all children ≥6 months against influenza; of immunizing household contacts of infants 0 to 6 months of age; and of initiating antiviral treatment as early as possible for children who are hospitalized, have severe illness, have underlying medical conditions, or are younger than two years of age. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Mortality'.)

PEDIATRIC NEONATOLOGY

Neonatal pulse oximetry screening at moderate alitude (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) [115]. 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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