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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
Evening primrose oil or borage oil for atopic dermatitis
Oral preparations of evening primrose oil and borage oil, which are rich in the essential fatty acid gamma-linolenic acid, have been promoted as complementary and alternative medicine treatments for atopic dermatitis. A meta-analysis of 19 randomized trials of evening primrose oil and eight trials of borage oil for the treatment of eczema in children and adults found no significant difference in global eczema symptoms (assessed by both participants and clinicians) between the active treatment and the placebo group [1]. Since there were some adverse gastrointestinal effects with use of these oils, and because long-term safety data are not available, we suggest that patients not take these oils for management of eczema symptoms. (See "Treatment of atopic dermatitis (eczema)", section on 'Dietary supplements'.)
Vitamin C for the common cold
Vitamin C is often touted as a natural remedy for the common cold. Although a 2013 meta-analysis concluded that regular vitamin C supplementation (at least 200 mg/day) slightly reduced the duration of cold symptoms, this 8 percent reduction was unlikely to be clinically important [2]. High doses of vitamin C started after symptom onset have not been shown to reduce symptom duration or severity. In addition, there is no consistent benefit of vitamin C on prevention of the common cold in the general population. (See "The common cold in adults: Treatment and prevention", section on 'Vitamin C'.)
Reassurance provided by diagnostic testing
Diagnostic tests are often ordered for patients with a low pretest probability of serious disease to provide reassurance, as well as to rule out illnesses. A meta-analysis of three open label randomized trials compared initial diagnostic testing (eg, cranial magnetic resonance imaging) with no testing in more than 700 patients with a low probability of disease (eg, headache) [3]. Illness worry (concern that symptoms may represent serious illness) was comparable for both groups in the short term (≤3 months) and long term (>3 months). Additional analyses found that testing did not reduce nonspecific anxiety or resolve symptoms, but did lead to a small decrease in the number of subsequent visits to primary care. (See "Somatization: Epidemiology, pathogenesis, clinical features, medical evaluation, and diagnosis", section on 'Laboratory evaluation'.)
Cardiotoxicity in women with breast cancer after radiation therapy
A case-control study of women treated for breast cancer with surgery and radiation therapy (RT) found that incidental radiation to the heart is associated with an increased risk for a significant coronary event (myocardial infarction, revascularization, or death from ischemic heart disease) [4]. The increased risk can be seen after relatively-low doses of radiation and the presence of cardiac risk factors markedly increased the impact of radiation. Despite this, the absolute risk associated with RT appears to be small and to be outweighed by the benefits in patients for whom radiation is typically recommended. (See "Cardiotoxicity of radiation therapy for malignancy", section on 'Effect of radiation dose to the heart'.)
Long-term regular aspirin use and age-related macular degeneration
In a longitudinal population-based study of individuals aged 46 to 83 years at baseline, regular aspirin use was associated with a small increased risk of age-related macular degeneration (AMD) [5]. The estimated incidence of late AMD, comparing individuals with regular aspirin use (twice or more a week for at least three months) for at least ten years and non-users of aspirin, was 1.76 and 1.03 percent respectively. Aspirin use started five years before retinal examination was not associated with increased risk for AMD. (See "Age-related macular degeneration: Clinical presentation, etiology, and diagnosis", section on 'Risk factors'.)
Patient understanding of acetaminophen dosing
Accidental acetaminophen overdose remains a major cause of morbidity and mortality. According to a prospective study of 500 patients tested about their understanding of acetaminophen dosing at one academic and one community internal medicine practice, up to 46 percent of patients would ingest excessive amounts of acetaminophen because they misunderstand dosing directions or fail to recognize that acetaminophen is found in more than one medication they are using [6]. Such errors occur most often among patients with limited literacy or frequent acetaminophen use. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis", section on 'Epidemiology'.)
Proactive, intermittent therapy for long-term control of atopic dermatitis
The long-term control of skin inflammation is a major challenge in the management of patients with atopic dermatitis. The 2012 European and American guidelines for the treatment of atopic dermatitis recommend proactive, intermittent topical therapy [7,8]. After induction of remission with continuous topical therapy, twice weekly application of topical corticosteroids to eczema-prone areas may prevent relapses in both adults and children with atopic dermatitis. (See "Treatment of atopic dermatitis (eczema)", section on 'Prevention of relapses'.)
Acute kidney injury after synthetic cannabinoid use
Synthetic cannabinoids, including tetrahydrocannabinol [THC], cannabidiol [CBD], and cannabinol [CBN], are analogs of naturally-occurring chemicals found in marijuana. In two small case series, synthetic cannabinoid or “Spice” use has been associated with reversible acute kidney injury necessitating renal replacement therapy [9,10]. Pathologically, the injury is characterized by acute tubular necrosis and interstitial nephritis. In some instances, these previously-healthy young adults reported smoking a blueberry- or bubblegum-flavored synthetic cannabinoid. A unique synthetic cannabinoid, 1-((5-fluoropentyl)-1H-indol-3yl) (2,23,3,-tetramethylcyclopropyl) methanone (also called XLR-11) was found in clinical specimens and product samples [10]. However, the specific chemical agent responsible for causing renal toxicity is not known. (See "Designer drugs of abuse", section on 'Clinical manifestations'.)
Zolpidem dosing for insomnia in women
Zolpidem is a nonbenzodiazepine sedative that is widely used for treatment of insomnia and is known to cause residual daytime sedation, drowsiness, cognitive impairment, and motor incoordination in some individuals. Recent studies reviewed by the US Food and Drug Administration (FDA) suggest that 15 percent of women and 3 percent of men have next-morning zolpidem blood levels capable of impairing driving after a 10 mg dose [11]. Based on these findings, the FDA has recommended lowering the usual dose of zolpidem in women to 5 mg. (See "Treatment of insomnia", section on 'Nonbenzodiazepines'.)
GERIATRICS
Discontinuing antipsychotic agents in patients with dementia
Because antipsychotic agents are associated with an increased risk of mortality in patients with dementia, it has been recommended that discontinuation of these agents should be attempted at regular intervals. One trial showed that this is not always possible. Among 180 patients with Alzheimer disease and psychosis or agitation who had initially responded to treatment with a 16 week course of risperidone, those randomly assigned to immediate drug discontinuation had an increased risk of relapse of psychosis or agitation over 16 weeks of followup (60 versus 33 percent) [12]. Those who were assigned to drug discontinuation after an additional 16 weeks of treatment also had a higher rate of relapse over the ensuing 16 weeks compared to those who continued treatment throughout (48 versus 15 percent). (See "Treatment of behavioral symptoms related to dementia", section on 'Antipsychotic drugs'.)
PREVENTION
Fish oil and cardiovascular mortality
The Risk and Prevention Study enrolled patients with multiple cardiovascular risk factors or known vascular disease and, after a median follow-up of five years, found no reduction in coronary heart disease (CHD) death with n-3 polyunsaturated fatty acid supplementation compared with placebo (82 versus 76 deaths, hazard ratio 1.07) [13]. This result contrasts with early trials of fish oil but is consistent with more recent studies. Additional large trials with long-term follow-up are needed to clarify whether n-3 fatty acid supplementation might have different effects on cardiac mortality depending on whether patients are also receiving aggressive treatment for primary or secondary prevention of CHD. (See "Fish oil and marine omega-3 fatty acids", section on 'CHD death and sudden cardiac death'.)
Breastfeeding and obesity
There is increasing evidence that breastfeeding does not reduce the risk of infant obesity. A follow-up study from a cluster-randomized trial of over 17,000 breastfeeding mother-infant pairs reported on outcomes of children at 11.5 years of age, and confirmed findings from 5 years earlier that there were no differences in the body mass index or rates of obesity and overweight [14]. Thus, although breastfeeding is encouraged for its many health advantages, population strategies to increase the duration and exclusivity of breastfeeding are unlikely to impact the obesity epidemic. (See "Infant benefits of breastfeeding", section on 'Obesity'.)
Aspirin for the primary prevention of cardiovascular disease and cancer
Meta-analyses of randomized trials have shown aspirin to reduce the risk of non-fatal myocardial infarction [15], and long-term aspirin use reduces overall cancer risk [16]. While several published guidelines have considered the benefit of aspirin for the prevention of either cardiovascular disease (CVD) or cancer versus the risk of increased bleeding, most have not addressed the potential net benefit of aspirin in preventing both CVD and cancer. A meta-analysis addressing this combined outcome suggests that aspirin use in 1000 average risk patients at age 60 years would be expected to result, over a 10-year period, in six fewer deaths, 19 fewer non-fatal myocardial infarctions, 14 fewer cancers, and 16 more major bleeding events (table 1). For individuals age 50 years or greater without excess bleeding risks, we suggest daily aspirin at a dose of 75 to 100 mg. Patients who are more concerned about the bleeding risks than the potential benefits may reasonably choose to not take aspirin for primary prevention. (See "Aspirin in the primary prevention of cardiovascular disease and cancer", section on 'Recommendations for primary prevention'.)
Mediterranean diet and prevention of cardiovascular disease
A large randomized trial compared three diets in patients at high cardiovascular risk: a Mediterranean diet supplemented with olive oil, a Mediterranean diet supplemented with mixed nuts, and advice to reduce dietary fat [17]. The trial was stopped early after a median follow-up of 4.8 years. For the primary composite cardiovascular endpoint of myocardial infarction, stroke, and cardiovascular death, event rates were similar for the Mediterranean diets supplemented with olive oil and mixed nuts, and lower than for the control diet (8.1 and 8.0 events per 1000 person-years respectively, versus 11.2 events per 1000 person-years; HR for both Mediterranean diets combined 0.71). Although this trial suggests possible substantial cardiovascular benefits from a Mediterranean diet, there was a surprisingly large reduction in events, a low total number of events (288), and the trial was stopped early for benefit. This raises concerns that the apparent benefits of a Mediterranean diet could have been overestimated, since this can be a problem in trials that are stopped early for benefit, particularly when there are also relatively few events [18-20]. (See "Lipid lowering with diet or dietary supplements", section on 'Mediterranean diet'.)
Role of folate or folic acid in cancer prevention
The role of folate or folic acid in cancer prevention is uncertain. Several large observational studies have suggested a decrease in risk of colorectal and other cancers with dietary folate, while some randomized trials of folic acid supplementation have raised the possibility of harm (increased cancer risk) from folic acid supplementation. In the largest meta-analysis of individual patient data from randomized trials of folic acid for the prevention of cardiovascular disease (10 trials, n = 49,969) and colorectal adenoma (3 trials, n = 2652), during an average of 5.2 years of treatment, there was no significant difference in overall cancer incidence for patients assigned to folic acid or placebo [21]. There was also no significant effect on the incidence of specific cancers, including cancers of the large intestine, prostate, lung, or breast. (See "Cancer prevention", section on 'Folate and other B vitamins'.)
Long-term use of postmenopausal hormone therapy
The United States Preventive Services Task Force (USPSTF) has published an updated meta-analysis of postmenopausal hormone therapy (nine trials) [22]. Results were largely based upon the two Women's Health Initiative trials, and the mean age of subjects was >60 years. Estrogen plus progestin, as well as unopposed estrogen, decreased fracture risk but increased the risk for stroke, venous thromboembolic events, and gallbladder disease. Estrogen plus progestin increased risk for breast cancer, but unopposed estrogen decreased breast cancer risk. Based upon these data, the USPSTF continues to recommend against the use of both combined estrogen and progestin and unopposed estrogen for prevention of chronic conditions [22,23]. However, they note that this recommendation does not apply to women considering hormone therapy for relief of menopausal symptoms [23,24]. (See "Postmenopausal hormone therapy: Benefits and risks", section on 'Overview'.)
Risk for nonmelanoma skin cancer in users of tanning beds
Tanning bed use has been associated with increased risk for cutaneous squamous cell carcinoma and basal cell carcinoma. A 2012 meta-analysis of observational studies found a 67 percent higher risk for cutaneous squamous cell carcinoma and a 29 percent increased risk for basal cell carcinoma among subjects with a history of any tanning bed use compared with subjects who had never used tanning beds [25]. (See "Epidemiology and risk factors for cutaneous squamous cell carcinoma", section on 'UV light exposure' and "Epidemiology and risk factors for cutaneous squamous cell carcinoma", section on 'UVA radiation'.)
SCREENING
USPSTF recommendations for universal HIV screening
The United States Preventive Services Task Force (USPSTF) has expanded its recommendations for HIV testing and now recommends that clinicians screen adolescents and adults aged 15 to 65 years for HIV infection [26]. Younger adolescents and older adults who are at increased risk for infection, as well as all pregnant women, should also be screened. These recommendations are based on growing evidence that early detection leads to reduced risk for AIDS-related events or death. Universal screening has previously been endorsed by several other organizations, including the Centers for Disease Control and the American College of Physicians. (See "Serologic screening for HIV infection", section on 'United States'.)
AUA prostate cancer screening guideline
The American Urological Association (AUA) has updated its prostate cancer screening guideline [27]. The AUA now recommends against screening men younger than 40 and also does not recommend routine screening for average-risk men ages 40 to 54, men older than 70, or men with a life expectancy of less than 10 to 15 years. Decisions should be individualized for higher-risk men ages 40 to 54, and the AUA noted that some men over age 70 in excellent health might benefit from screening. The guideline panel could find no evidence to support the continued use of digital rectal exam as a first-line method of screening. The AUA stated that a screening interval of two years for men who choose screening may be preferred to annual screening and that screening intervals can be individualized based on baseline prostate specific antigen (PSA) level. (See "Screening for prostate cancer", section on 'Recommendations of others'.)
Screening colonoscopy and incidence of late stage colorectal cancer
There are no randomized trials of the effectiveness of screening colonoscopy in average-risk patients, and some observational data suggest that colonoscopy might not be effective in detecting right-sided (proximal) colon lesions. In a case-control study in four health plans in the United States in which rates of screening colonoscopy were low in both cases and matched controls (reflecting practice patterns going back 17 years), late stage (IIb or higher) colorectal cancer was associated with failure to undergo screening colonoscopy [28]. The association was the same for right- and left-sided cancers. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness'.)
Screening women with a familial ovarian cancer syndrome for ovarian cancer
In the largest cohort study of high-risk women, the United Kingdom Familial Ovarian Cancer Screen Study (UK FOCSS), 3563 women with a familial ovarian cancer syndrome (estimated minimum lifetime risk of 10 percent) who had declined or deferred risk reducing salpingo-oophorectomy (RRSO) were screened annually for a mean of 3.2 years with a combination of transvaginal ultrasound and CA-125 [29]. Sensitivity for the detection of incident ovarian cancer/fallopian tube cancer was 81.0 to 87.5 percent. The positive predictive value of incident screening was 25.5 percent, which exceeds the threshold of 10 percent considered necessary for ovarian cancer screening. 30.8 percent (4 of 13) of incident cancers were stage I or II.
Although RRSO remains the only reliable method of decreasing mortality from ovarian cancer in this high-risk population, this study suggests that screening has the potential to somewhat reduce risk for women who wish to maintain their childbearing potential until they are ready to undergo surgery. (See "Screening for ovarian cancer", section on 'High-risk women'.)
CT colonography for colorectal cancer screening
In a study of colorectal cancer screening comparing optical colonoscopy with laxative-free CT colonography (CTC), in which stool was tagged with orally-ingested contrast material and software was used to “electronically cleanse” the bowel images, the sensitivity and specificity for adenomas ≥10 mm were 91 and 85 percent for CTC and 95 and 89 percent for optical colonoscopy [30]. A survey of the study participants, who underwent both procedures, indicated preference for CTC. The performance characteristics of laxative-free CTC was comparable to the performance of CTC with laxatives reported in other studies.
An earlier report of a randomized trial in the Netherlands compared outcomes for two colorectal cancer screening strategies: invitation for colonoscopy or invitation for screening CT colonography (for which patients did not use a cathartic preparation) [31]. The diagnostic yield for advanced neoplasia was greater for individuals who underwent colonoscopy than for CT colonography. However, participation rates were significantly lower for those invited for colonoscopy than for colonography (22 versus 34 percent), so that the diagnostic yield for advanced neoplasia per 100 invitees was essentially the same for both strategies. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Computed tomographic colonography'.)
Flexible sigmoidoscopy for colorectal cancer screening
Results of the flexible sigmoidoscopy arm of the Prostate Lung Colorectal and Ovarian (PLCO) Screening Trial have been reported [32]. A total of 154,900 men and women aged 55 to 74 were randomly assigned to screening with flexible sigmoidoscopy or to usual care, with median follow-up of 11.9 years. There was a 21 percent reduction in the relative risk of colorectal cancer and a 26 percent reduction in the relative risk of death from colorectal cancer, comparing the screening arm with usual care. Although the incidence of both proximal and distal CRC significantly decreased, a reduction in mortality was seen only for distal cancer. There was significant contamination in the usual care group (among whom 47 percent underwent either sigmoidoscopy or colonoscopy), suggesting that the impact of sigmoidoscopy compared to no screening might be even greater than was seen in this trial. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Sigmoidoscopy'.)
ADULT CARDIOVASCULAR MEDICINE
Fibrinolysis or PPCI in STEMI patients who present early
Older studies have suggested that outcomes are comparable between primary percutaneous coronary intervention (PPCI) and fibrinolysis in patients with ST-elevation myocardial infarction (STEMI) who present early. The STREAM study randomly assigned 1892 patients who presented within three hours to PPCI or fibrinolytic therapy [33]. Patients who could undergo PPCI within one hour were excluded. There was no difference between the two treatments in the primary composite end point of major adverse cardiovascular events at 30 days. However, the rate of intracranial hemorrhage was higher with lytic therapy. We prefer PPCI, if it can be performed in a timely manner, due to concerns about the safety of lytic therapy. (See "Selecting a reperfusion strategy for acute ST elevation myocardial infarction", section on 'Presentation within three hours'.)
Duration of beta blocker after myocardial infarction
Although beta blocker (BB) therapy reduces mortality in patients with recent myocardial infarction (MI), the optimal duration of beta blocker therapy after MI is unknown. Beta blocker therapy is continued indefinitely for many patients, based on studies performed in the 1980s and 1990s. A 2013 observational study evaluated outcomes in over 5000 patients with ST-elevation MI treated with primary percutaneous coronary intervention [34]. Adjusted mortality rates over approximately four years did not differ between patients who did or did not continue BB therapy. However, subgroup analyses revealed that BB treatment was associated with a significantly lower mortality for high-risk patients, such as those with heart failure. We believe the available evidence supports the use of beta blockers in patients with MI for as long as three years. We suggest BB beyond three years in patients with high-risk features such as cardiogenic shock, heart failure, or chronic kidney disease. (See "Beta blockers in the management of acute coronary syndrome", section on 'Duration of therapy'.)
Apixaban for prevention of embolic events in atrial fibrilllation
Apixaban has been approved by the US Food and Drug Administration and the European Medicines Agency for use in patients with atrial fibrillation to reduce the risk of stroke and systemic embolization [35,36]. Approval was based on the results of the large randomized ARISTOTLE trial, which found that apixaban was non-inferior to warfarin in terms of efficacy and superior in terms of safety [37]. In patients with atrial fibrillation who meet criteria for anticoagulation, we prefer either a factor Xa inhibitor (apixaban or rivaroxaban) or a direct thrombin inhibitor (dabigatran) to warfarin. (See "Antithrombotic therapy to prevent embolization in atrial fibrillation", section on 'Apixaban' and "Antithrombotic therapy to prevent embolization in atrial fibrillation", section on 'Indications for and choice of therapy'.)
ADULT ENDOCRINOLOGY AND DIABETES
Cardiovascular benefits of metformin in type 2 diabetes mellitus
In the absence of contraindications, metformin is the first choice for oral treatment of type 2 diabetes, with data suggesting decreased risk for macrovascular complications, particularly in obese patients. A randomized trial, comparing metformin and glipizide in over 300 patients with type 2 diabetes and coronary heart disease (CHD), provides further evidence for the cardiovascular benefits of metformin [38]. Patients were assigned to metformin or glipizide for three years and insulin was added if optimal glycemic control (A1C <7 percent) was not achieved by three months. Both groups achieved similar A1C levels (7.0 and 7.1 percent), but body weight, waist circumference, and BMI were significantly lower in the metformin group. After a median follow-up of five years, there were fewer cardiovascular events (composite of nonfatal myocardial infarction, stroke, or arterial revascularization, death from cardiovascular or any cause) in the metformin group. The main limitation of this trial was the small number of events. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus", section on 'Metformin'.)
ADULT GASTROENTEROLOGY
Blood transfusion thresholds for acute upper GI bleeding
The decision to initiate blood transfusions in patients with acute upper gastrointestinal bleeding is based on the rapidity of bleeding and the patients' comorbid conditions. A randomized trial of patients with and without cardiovascular disease suggests that in patients who are not at increased risk for complications from anemia, outcomes are improved if a lower hemoglobin threshold (<7 g/dL rather than <9 g/dL) is used for initiating blood transfusion [39]. Patients transfused when the hemoglobin was <7 g/dL had lower mortality rates, were less likely to have further bleeding, and were less likely to suffer complications.
We recommend giving blood transfusions to maintain the hemoglobin at ≥7 g/dL, rather than ≥9 g/dL, for the majority of patients with acute upper gastrointestinal bleeding who do not have significant comorbid illnesses. However, patients with active bleeding and hypovolemia may require blood transfusion despite an apparently normal hemoglobin. Additionally, we suggest transfusing to maintain the hemoglobin at ≥9 g/dL for patients at increased risk of adverse events in the setting of significant anemia, such as those with unstable coronary artery disease. (See "Approach to acute upper gastrointestinal bleeding in adults", section on 'Blood transfusions' and "Overview of the non-acute management of unstable angina and non-ST elevation myocardial infarction", section on 'Red cell transfusion'.)
ADULT HEMATOLOGY AND ONCOLOGY
Apixaban for secondary prevention of venous thromboembolism
The randomized, double-blind AMPLIFY-EXT study compared the efficacy and safety of apixaban with placebo in over 2000 subjects with venous thromboembolism (VTE) who had completed 6 to 12 months of anticoagulation and for whom there was uncertainty regarding the further continuation of anticoagulation [40]. Symptomatic recurrent VTE or death from VTE occurred in 8.8 and 1.7 percent of those receiving placebo or apixaban, respectively, for an overall 80 percent reduction in the risk of VTE recurrence with apixaban. Major bleeding was not increased in the group receiving apixaban. A randomized trial comparing this agent with standard-dose warfarin will help to determine the future role of apixaban for the continued treatment of VTE. (See "Treatment of lower extremity deep vein thrombosis", section on 'Apixaban' and "Treatment of lower extremity deep vein thrombosis", section on 'Issues to consider'.)
ADULT INFECTIOUS DISEASE
Prophylactic antibiotics for recurrent lower extremity cellulitis
Management of recurrent lower extremity cellulitis can be a challenging problem, and the efficacy of prophylactic antibiotics is uncertain. In a randomized trial of 274 patients with two or more episodes of lower extremity cellulitis, penicillin (250 mg orally twice daily) nearly halved the risk of recurrence during 12 months of prophylaxis, although the protective effect diminished rapidly once the antibiotic was discontinued [41]. Response rates were somewhat lower in patients at highest risk for recurrent cellulitis, such as those with a BMI ≥33, multiple previous episodes of cellulitis, or lymphedema of the leg. (See "Cellulitis and erysipelas", section on 'Recurrent cellulitis'.)
Azithromycin and cardiovascular mortality
In a large cohort study that used Danish national healthcare data to evaluate the association between azithromycin use and cardiovascular death in young and middle-aged adults, the risk of death from cardiovascular causes was significantly increased with current use of azithromycin compared with no use of antibiotics [42]. However, in an adjusted analysis, current azithromycin use was not associated with an increased risk of cardiovascular death compared with penicillin V, suggesting that the increased risk was attributable to underlying patient factors that led to the prescription of antibiotics.
In 2013, the US Food and Drug Administration issued a warning about the risk of QT interval prolongation and potentially fatal torsades de pointes among patients taking azithromycin [43]. The warning was based on a review that followed the publication of a study that showed an increased risk of cardiovascular mortality and all-cause mortality in Medicaid patients receiving azithromycin compared with amoxicillin or no antibiotics [44].
Of note, the population in the Danish study was healthier than the Medicaid population in the earlier analysis. The current study suggests that azithromycin does not increase the risk of cardiovascular death in young and middle-aged persons without preexisting cardiovascular disease. (See "Azithromycin, clarithromycin, and telithromycin", section on 'QT interval prolongation'.)
Fecal microbiota transplant for Clostridium difficile infection
Approximately 25 percent of patients with Clostridium difficile (C. difficile)-associated diarrhea have recurrent disease after an initial course of antibiotic therapy. In an open label randomized controlled trial, 43 patients with recurrent C. difficile infection after at least one course of antibiotic therapy were randomly assigned to one of three treatment arms: duodenal infusion of donor feces preceded by an abbreviated regimen of vancomycin (vancomycin 500 mg four times daily for four days) and bowel lavage; a standard vancomycin regimen (vancomycin 500 mg four times daily for 14 days); or a standard vancomycin regimen with bowel lavage [45]. A single infusion of donor feces resulted in significantly higher rates of resolution of C. difficile-associated diarrhea without relapse at 10 weeks as compared with a standard vancomycin regimen with or without bowel lavage (81, 23, and 31 percent, respectively). (See "Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection", section on 'Administration via nasogastric tube'.)
Egg-free influenza vaccine
A trivalent inactivated influenza vaccine (Optaflu), produced using cultured mammalian cells, was approved in Europe for use in adults beginning in the 2007-2008 influenza season. This same vaccine (called Flucelvax) was approved for individuals ≥18 years of age for the 2012-2013 season by the US Food and Drug Administration in November 2012 (table 2) [46,47]. A second egg-free vaccine (Flublok), made using an insect virus (baculovirus) expression system and recombinant DNA technology, was approved in January 2013 by the FDA for adults aged 18 to 49 years. The efficacy and rates of serious adverse events seen with both egg-free vaccines were comparable to standard available influenza vaccines. For patients age 18 or older with egg allergy, we recommend administration of an age-appropriate, egg-free, trivalent inactivated influenza vaccine (TIV) rather than an egg-based inactivated vaccine. However, if the an egg-free vaccine is not readily available, immunization should proceed with egg-based vaccination with appropriate precautions (eg, observation for 30 minutes following vaccination in patients with mild allergic reactions to egg, and immunization supervised by an allergy specialist for patients with a history of severe egg allergic reactions).
We recommend not using the egg-free vaccine in patients younger than age 18, since the baculovirus/recombinant DNA-based vaccine appears to be less immunogenic in young children and the immunogenicity of these vaccines and the rates of side effects in this population are otherwise not known. (See "Influenza vaccination in individuals with egg allergy", section on 'Alternative methods of vaccine production' and "Influenza vaccination in individuals with egg allergy", section on 'Options for testing and administration'.)
ADULT NEUROLOGY AND PSYCHIATRY
Increasing rates of suicide in the United States among middle-aged adults
Suicide is a public health concern and appears to be increasing in the United States among middle-aged adults. Age-adjusted suicide rates for adults aged 35 to 64 years increased approximately 28 percent (from 14 to 18 per 100,000) from 1999 to 2010 [48]. By contrast, rates for persons aged 10 to 34 years rose 7 percent and rates for adults ≥65 years of age decreased 6 percent. (See "Suicidal ideation and behavior in adults", section on 'Epidemiology'.)
Deep brain stimulation for early Parkinson disease
The potential benefit of deep brain stimulation (DBS) in early Parkinson disease (PD) is illustrated by the results of the EARLYSTIM trial that evaluated 251 adults (mean age 53 years) with levodopa-responsive PD, mild motor complications, and no dementia [49]. Compared with the medical therapy group at two years, patients in the DBS plus medical therapy group showed a statistically-significant and clinically-meaningful improvement in quality of life [50]. In addition, the DBS group had significant improvements in motor disability, activities of daily living, levodopa-induced motor complications, and time with good mobility and no dyskinesia. (See "Surgical treatment of Parkinson disease", section on 'Effectiveness in early PD'.)
Updated guidelines for early management of acute ischemic stroke
The American Heart Association/American Stroke Association has published updated guidelines for the early management of acute ischemic stroke. One important change is that a number of conditions previously considered strict exclusions for the use of intravenous thrombolysis are now considered relative exclusions (table 3) [51]. These include minor or rapidly improving stroke symptoms, major surgery or serious trauma in the previous 14 days, gastrointestinal or urinary tract bleeding in the previous 21 days, myocardial infarction in the previous three months, and seizure at the onset of stroke with postictal neurologic impairments. (See "Intravenous fibrinolytic (thrombolytic) therapy in acute ischemic stroke: Therapeutic use", section on 'Role of eligibility criteria'.)
ADULT RHEUMATOLOGY
Arthroscopy versus physical therapy for meniscal tear and osteoarthritis
Arthroscopic debridement has been widely used as a treatment for patients with symptomatic osteoarthritis (OA) of the knee; however, whether outcomes are better for patients with symptomatic OA and meniscal tear who undergo operative or nonoperative (eg, physical therapy) management are not known. The multicenter Meniscal Tear in Osteoarthritis Research (METEOR) trial is the largest randomized trial to examine the benefits of arthroscopic intervention in such patients [52]. In this trial, 351 symptomatic patients with a medial meniscal tear and mild to moderate OA were randomly assigned to either arthroscopic partial meniscectomy with removal of loose fragments of cartilage and bone, followed by a defined physical therapy program, or to physical therapy alone. Based upon initial assignment, there was no significant difference in physical function scores between the two groups at six months, although 30 percent of the patients assigned to the physical therapy group had undergone arthroscopic surgery. (See "Surgical therapy of osteoarthritis", section on 'Arthroscopic debridement'.)
Lack of benefit from vitamin D in osteoarthritis
Low levels of vitamin D have been associated with an increased risk of progression of osteoarthritis (OA) but not with the development of OA. A randomized trial involving 146 patients with symptomatic knee OA sought to determine whether supplementation with vitamin D (oral cholecalciferol, 2000 international units daily or greater to achieve a serum level of 25-hydroxyvitamin D greater than 36 ng/mL) was beneficial for treatment of the OA [53]. The trial found no significant differences between groups treated for two years with either vitamin D or placebo in patient-reported knee pain, knee function, or cartilage volume loss on magnetic resonance imaging, suggesting a lack of therapeutic benefit from such supplementation. (See "Nonpharmacologic therapy of osteoarthritis", section on 'Diet and vitamins'.)
GYNECOLOGY
Management of abnormal cervical cytology in women aged 21 to 24 years
Revised guidelines for the evaluation and treatment of abnormal cervical cytology and histology have been issued by the American Society for Colposcopy and Cervical Pathology (ASCCP) in collaboration with multiple professional societies and the Centers for Disease Control and Prevention [54]. A major change from previous recommendations is the differentiation of management of abnormal cytology in women ages 21 to 24 years from those age 25 or older, based upon the higher prevalence of human papillomavirus infection and low risk of cervical cancer in younger women. Thus, for younger women, HPV testing is not used in the evaluation of most abnormalities and colposcopy is advised only if abnormal cytology results are severe or recurrent. (See "Cervical cytology: Evaluation of atypical squamous cells (ASC-US and ASC-H)", section on 'Women ages 21 to 24' and "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)", section on 'Women ages 21 to 24' and "Cervical cytology: Evaluation of high-grade squamous intraepithelial lesions (HSIL)", section on 'Women ages 21 to 24'.)
HPV triage for women ages 30 and older with LSIL on cervical cytology
Recommendations regarding management of low-grade squamous intraepithelial lesion (LSIL) on cervical cytology have been revised, in accord with updated guidelines for the evaluation and treatment of abnormal cervical cytology and histology issued by the American Society for Colposcopy and Cervical Pathology (ASCCP) [54]. For women ages 30 and older with LSIL, results of human papillomavirus (HPV) testing should be used to triage further evaluation. Women with LSIL and a negative HPV test should be followed with repeat cytology and HPV co-testing at 12 months. Women with LSIL and a positive HPV test should be evaluated with colposcopy. Women with LSIL who were initially screened with cytology alone and do not have an HPV test result should also be evaluated with colposcopy. In general, the ASCCP guidelines incorporate co-testing rather than cytology alone into the follow-up of many abnormalities for women in this age group.
For women ages 25 to 29 years, cytology alone without HPV testing is recommended for cervical cancer screening. Recommendations for management of LSIL in this age group have not changed. Women ages 25 to 29 years with LSIL, even those who inadvertently had HPV testing, should be managed based upon cytology alone and should be evaluated with colposcopy. (See "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)", section on 'Women ages 25 and older' and "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)", section on 'Role of HPV testing'.)
New levonorgestrel-releasing IUD
A lower-dose (13.5 mg) levonorgestrel-releasing intrauterine device (IUD; Skyla) became available in the United States in 2013 [55]. It is smaller in size than the 52 mg levonorgestrel IUD (Mirena) and thus may be easier to insert in nulliparous women. Because of the lower levonorgestrel dose, it is approved for up to three years of use (the 52 mg dose is approved for up to five years) [56]. (See "Overview of intrauterine contraception", section on 'Levonorgestrel-releasing IUDs' and "Levonorgestrel: Drug information".)
Levonorgestrel intrauterine device for menorrhagia
The levonorgestrel intrauterine device (LNG-IUD) is an effective treatment for menorrhagia. Quality of life outcomes were evaluated for the first time in a randomized trial that assigned women to the LNG-IUD (Mirena) or treatment with other medical therapy [57]. Women in the LNG-IUD group had significantly higher scores in six domains of daily life at six months and two years. Significantly more women in the LNG-IUD group continued treatment at two years (64 versus 38 percent). (See "Chronic menorrhagia or anovulatory uterine bleeding", section on 'Levonorgestrel-IUD'.)
OBSTETRICS
Prolonged exposure to magnesium affects fetal bones
Retrospective epidemiologic studies have reported a significant increase in radiographic bone abnormalities in neonates with in utero exposure to magnesium sulfate for more than seven days, and a significant difference in the serum values of magnesium, calcium, phosphorus, and osteocalcin (a marker of bone formation) at birth between neonates exposed to magnesium sulfate and those who were not. Based on these and other data, in May 2013, the US Food and Drug Administration advised healthcare professionals in the United States against using magnesium sulfate injection for more than five to seven days to stop preterm labor [58]. We agree with this recommendation, given the potential for adverse fetal effects and because tocolytic therapy is generally less effective after 48 hours. (See "Inhibition of acute preterm labor", section on 'Maternal and fetal side effects'.)
Vitamin D deficiency in pregnancy
Whether vitamin D deficiency affects pregnancy outcomes is controversial. A 2013 meta-analysis of observational studies reported vitamin D deficiency was associated with gestational diabetes, preeclampsia, small for gestational age, bacterial vaginosis, and low birthweight [59]. However, both the absence of a dose-response relationship between 25-hydroxyvitamin D levels and the reported complications and the inclusion of studies that measured the 25-hydroxyvitamin D levels with variable precision raise significant doubt about the effects of vitamin D deficiency on the reported outcomes. Screening all pregnant women for vitamin D deficiency is not recommended. (See "Calcium physiology in pregnancy", section on 'Vitamin D'.)
New drug for nausea and vomiting of pregnancy
In April 2013, Diclegis, a fixed-dose combination of doxylamine succinate and pyridoxine hydrochloride, was approved in the United States by the Food and Drug Administration for treatment of nausea and vomiting of pregnancy in women who have not responded adequately to dietary and lifestyle changes [60,61]. This formulation is the same as that for the previously available drug Bendectin. (See "Treatment and outcome of nausea and vomiting of pregnancy", section on 'Doxylamine succinate and pyridoxine'.)
Tdap during pregnancy
The prevalence of pertussis in the United States has been increasing, in part because pertussis immunity after vaccination or disease wanes over time. Infants younger than three months of age are at highest risk of morbidity and mortality from this infection, and many infants contract pertussis from their mothers. Vaccination of the mother can thus significantly decrease the risk of infant exposure, and placental transfer of maternal antibodies may additionally provide a degree of passive protection to the infant for two to six months. In 2013, the United States Advisory Committee on Immunization Practices (ACIP) recommended that all pregnant women receive the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during each pregnancy, optimally between 27 and 36 weeks of gestation, regardless of prior vaccination status, to increase the likelihood of optimal protection against pertussis for both the mother and her infant during the first few months of the infant’s life [62]. Previously, Tdap was recommended only for pregnant women who had not previously received the acellular pertussis vaccine during adulthood. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, pertussis (Tdap)'.)
Safety and efficacy of influenza vaccination in pregnancy
Influenza vaccination is recommended for pregnant women because both mother and fetus are at increased risk of complications related to this infection, including fetal death. In addition, maternal vaccination provides passive protection to the infant. However, concerns about vaccine safety have interfered with compliance in this patient group. The safety and efficacy of vaccination of pregnant women were confirmed in a retrospective analysis of over 100,000 pregnancies during the 2009 influenza A (H1N1) pandemic in Norway [63]. Vaccination during pregnancy substantially reduced the risk of a maternal influenza diagnosis (adjusted hazard ratio, 0.30) and was associated with a trend in reduction of fetal death. All women who are pregnant or will be pregnant during influenza season should receive the inactivated influenza vaccine, regardless of pregnancy trimester. (See "Influenza and pregnancy", section on 'Vaccination'.)
PEDIATRICS: GENERAL PEDIATRICS
Colic as an early form of migraine
The etiology of infantile colic remains uncertain, although multiple hypotheses have been proposed. A large case-control study, in which a history of infantile colic was more common among children with migraine headaches than children without migraine headaches or children with tension headaches, adds support to the hypothesis that infantile colic is an early manifestation of childhood migraine [64]. However, prospective studies are necessary to confirm this hypothesis. (See "Clinical features and etiology of colic", section on 'Early form of migraine'.)
Diagnosis of hypertension in childhood requires repeated blood pressure measurements
The need for confirmation of the diagnosis of hypertension based on three blood pressure (BP) measurements at separate clinical vists was illustrated in a large cohort study of children cared for in community-based practices [65]. In the United States, normative BP percentiles are based upon data on gender, age, height, and blood pressure measurements from the National Health and Nutrition Examination Survey (NHANES) and other population-based studies (table 4 and table 5). Initial BP measurement was normal (below the 90th percentile), prehypertensive (systolic or diastolic BP between the 90th or 95th percentile) and hypertensive (systolic or diastolic BP ≥95th percentile) in 82, 13, and 5 percent of children. At follow-up, subsequent hypertensive measurements were observed in only 4 percent of the 10,848 children who had initial hypertensive values. In this cohort, the overall prevalence of hypertension was 0.3 percent. (See "Definition and diagnosis of hypertension in children and adolescents", section on 'Diagnosis'.)
Topical ivermectin for pediculosis capitis
The emergence of resistance to treatments for pediculosis capitis (head lice) has fueled the desire to identify additional effective treatments for this condition. In two randomized trials, a single 10-minute application of topical ivermectin was superior to a placebo lotion for the eradication of lice [66]. A combined analysis of the trial results revealed that among the index patients (youngest household member with at least three live lice detected on examination), 131 of 138 (95 percent) treated with topical ivermectin and 46 of 147 (31 percent) treated with the placebo lotion were free of live lice on day two. By day 15, live lice were absent in 74 and 18 percent of patients, respectively. Adverse events were infrequent and occurred at similar rates in both groups. (See "Pediculosis capitis", section on 'Topical ivermectin'.)
Oseltamivir treatment approved for infants ≥2 weeks
In December 2012, the US Food and Drug Administration approved oseltamivir for the treatment of influenza in infants ≥2 weeks of age [67]. Oseltamivir had previously been approved in the US for treatment of influenza in children ≥1 year of age. For prophylaxis of influenza in the US, oseltamivir continues to be approved only for infants ≥1 year of age. (See "Antiviral drugs for the prevention and treatment of seasonal influenza in children", section on 'Neuraminidase inhibitors'.)
PEDIATRICS: DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
Prevalence of autism spectrum disorders
In the 2011-2012 National Survey of Children’s Health, the prevalence of parent-reported autism spectrum disorder (ASD) among 6- to 17-year-old children in the United States was 1 in 50, an increase from 1 in 86 in 2007 [68]. The increase was largely due to newly diagnosed ASD in 6-to 13-year-old children, suggesting that the increase is related to improved awareness and ascertainment of ASD. (See "Terminology, epidemiology, and pathogenesis of autism spectrum disorders", section on 'Prevalence'.)
PEDIATRIC IMMUNIZATIONS
Combination vaccine for meningococcus and Haemophilus influenzae type b
A combination conjugate vaccine against meningococcus serogroups C and Y and Haemophilus influenzae type b (MenHibrix, HibMenCY) was approved by the US Food and Drug Administration in June 2012 for infants and children 6 weeks to 18 months of age [69,70]. In prelicensure trials, this vaccine was safe, immunogenic, and did not interfere with immune responses to routine immunizations. In January 2013, the United States Advisory Panel on Immunization Practices began recommending HibMenCY for certain infants and toddlers at increased risk for meningococcal disease, beginning at two months of age (table 6) [71,72]. It is the first meningococcal vaccine to be recommended in the United States for use in infants younger than nine months of age. (See "Meningococcal vaccines", section on 'Combination conjugate vaccine against meningococcus and Haemophilus influenzae type b' and "Meningococcal vaccines", section on 'In infants and toddlers'.)
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.
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