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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: Jun 2014. | This topic last updated: Jul 23, 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

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 [1]. 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 with at least one investigational arm that consisted of oral antibiotic or oral contraceptive treatment [2]. 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 [3], and JBS3 recommends use of a lifetime risk calculator in patients at low 10-year risk [4].

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 [5]. 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) [6]. 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 [7]. 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 [8]. 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) [9]. 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) [10]. 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 [11].  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 [12]. 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 [13]. 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 [14]. 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'.)

PREVENTION

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 [15]. 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 [16]. 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'.)

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 [17]. 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 [18]. 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 [19]. 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 [20]. (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 [21]. 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 [22]. 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'.)

SCREENING

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 [23]. 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) [24]. 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 [25]. 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 [26]. 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 [27]. 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 [28]. 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'.)

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 [29]. 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 [30]. 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 and harms", section on 'Film mammography' and "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Overdiagnosis'.)

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 [31]. 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) [32]. 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 [33]. (See "Screening for abdominal aortic aneurysm", section on 'Effectiveness'.)

ADULT CARDIOVASCULAR MEDICINE

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) [34]. 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 [35]. 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 [36]. 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 [37]. 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 [38]. 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 [39]. 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 [40]. 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 [41]. (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 [42]. 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) [43]. (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 [44]. 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'.)

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 [45]. 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'.)

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 2) 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 [47]. 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'.)

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 [48,49]. 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'.)

ADULT INFECTIOUS DISEASE

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 1) [50]. 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 [51]. 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 [52]. 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 [53]. 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 [54-56]. In the United States, dalbavancin and tedizolid were approved for skin and skin structure infections by the Food and Drug Administration in May and June 2014, respectively, and oritavancin is expected to undergo review shortly. (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", section on 'Oritavancin'.)

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 issued new recommendations for less frequent monitoring in patients who have achieved consistent viral suppression and CD4 cell counts >300 cells/microL on at least two years of ART [57]. In such patients, CD4 cell count monitoring can be performed every 12 months when counts are 300 to 500 cells/microL and is optional when >500 cells/microL. 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'.)

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) [58,59]. 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, MODIFIED April 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 all patients with genotype 1 hepatitis C virus (HCV) infection. Genotype 1 infection is the most common in North America and Europe. Several trials in genotype 1 infected patients have evaluated different interferon-free regimens, some of which were also ribavirin-free [60-67]. Reported SVR rates have exceeded 90 percent, even among subgroups that traditionally had suboptimal response (ie, patients with cirrhosis, with prior treatment failure, or of black race). 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 (or even ribavirin) 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'.)

ADULT NEPHROLOGY AND HYPERTENSION

Failure of renal denervation in resistant hypertension (April 2014)

The utility of catheter-based radiofrequency ablation of renal sympathetic nerves (also known as renal denervation) in patients with resistant hypertension has not been established. Although several unblinded studies suggested that renal denervation could substantially lower blood pressure in patients with resistant hypertension, a blinded randomized trial (SYMPLICITY-HTN-3) failed to demonstrate benefit [68]. In SYMPLICITY-HTN-3, 535 patients with treatment-resistant hypertension (systolic pressure >160 mmHg despite three or more antihypertensive medications, including a diuretic) were assigned to renal denervation or a sham procedure; blood pressure decreased to a similar degree in both groups at six months and there was no difference in the incidence of serious adverse events. Due to the lack of benefit, a larger ongoing international trial (SYMPLICITY-HTN-4) was stopped early. (See "Treatment of resistant hypertension", section on 'Catheter-based radiofrequency ablation of renal sympathetic nerves'.)

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 [69]. 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)'.)

ADULT NEUROLOGY AND PSYCHIATRY

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 [70]. 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 [71]. 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 [72]. 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 [73]. 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 abuse and dependence", section on 'Prevention of lethal overdose'.)

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".)

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'.)

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 [82]. 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 [83]. 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'.)

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'.)

GYNECOLOGY

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 [85]. 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 [86]. 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 [87]. 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'.)

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) [88,89]. 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'.)

OBSTETRICS

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 [90]. 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 [91]. 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) [92]. 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 [93]. 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) [94]. 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 [95]. 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 [96]. 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 [97]. 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 [98]. 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 [99]. 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 [100]. 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 and estimated date of delivery", 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) [101]. 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'.)

PEDIATRICS: GENERAL PEDIATRICS

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 [102]. 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 [103]. 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 [104]. 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 [105]. (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 [106]. 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'.)

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 placebo effect. However, a 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 [107]. 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 [108]. 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 [109]. 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 [110]. 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 [111]. 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) [112]. 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 [113]. (See "Acute appendicitis in children: Clinical manifestations and diagnosis", section on 'Pediatric appendicitis score'.)

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  [114]. 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 [115]. 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 or by dose. Two recent studies address these questions:

In a study that used an insurance claims database and medical records of more than 38,000 youth who were treated with fluoxetine, citalopram, escitalopram, paroxetine, sertraline, or venlafaxine, 419 patients with medically-treated suicide attempts were identified [116]. After adjusting for potential confounders, the rate of suicide attempts was comparable in subjects exposed to each of the agents evaluated.

Another study compared the incidence of suicide attempts in depressed teenagers and young adults who started selective serotonin reuptake inhibitors at usual doses (eg, fluoxetine 20 mg per day) versus higher than usual doses [117]. The risk of deliberate self harm was twofold greater in patients who initiated treatment at the higher dose. Although data were adjusted for potential confounders, it remains possible that patients started at higher doses were also at greater risk for suicidal behavior due to a history of treatment nonresponse or treatment response only at higher doses. (See "Effect of antidepressants on suicide risk in children and adolescents", section on 'Observational studies'.)

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) [118]. 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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