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What's new in family medicine
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What's new in family medicine
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2017. | This topic last updated: Jun 22, 2017.

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

New guidelines for management of peanut and tree nut allergies (June 2017)

The most straightforward approach in managing any food allergy is complete avoidance of the culprit food and all similar foods, particularly for peanut and tree nuts. However, some patients may find this approach too burdensome. Reflecting a shift in clinical practice, the recent British Society of Allergy and Clinical Immunology guidelines permit, with certain restrictions, consumption of similar foods after confirming that they are safe, if the patient and family prefer this approach [1]. This guideline for the management of peanut and tree nut allergy is consistent with our approach. (See "Peanut, tree nut, and seed allergy: Management", section on 'Clinical scenarios'.)

Spinal manipulative therapy for acute low back pain (June 2017)

Spinal manipulative therapy (SMT) has been used for acute low back pain, but the literature has shown inconsistent results. In a recent systematic review and meta-analysis of 26 randomized controlled trials, 15 showed moderate-quality evidence of improvement in pain and 12 showed moderate-quality evidence of improvement in function [2]. The magnitude of clinical benefit was modest, and there were no serious adverse effects. Prior reviews have reported less consistent benefit. We offer SMT to patients based on their individual preferences and access to this intervention. (See "Treatment of acute low back pain", section on 'Spinal manipulation'.)

Respiratory tract infections and antibiotic overuse (June 2017)

Upper respiratory tract infection (URI) and acute bronchitis are among the most common reasons for antibiotic overprescription, and reducing use for these indications is a global health care priority. A prospective cohort study assessing over 28,000 adults with acute cough lasting <3 weeks without radiographic evidence of pneumonia found no difference in rates of major complications, including hospital admission and death, when comparing patients given immediate antibiotic prescriptions with delayed prescription or no prescription [3]. This study adds further support for the lack of benefit for routine use of antibiotics for patients with acute bronchitis and can be used to reassure patients that they are not more likely to develop complications if they are not treated with antibiotics. (See "Acute bronchitis in adults", section on 'Avoiding antibiotic overuse'.)

Goal blood pressure in older adults (May 2017)

Goal blood pressure in older hypertensive adults is controversial. A meta-analysis of over 10,000 hypertensive adults 65 years or older combined results from the older subgroup in the SPRINT trial with three other large randomized trials evaluating goal blood pressure [4]. At three-year follow-up, compared with less intensive therapy, more intensive blood pressure lowering reduced the rates of major adverse cardiovascular events, cardiovascular mortality, and heart failure. In general, UpToDate recommends a systolic blood pressure goal of 125 to 135 mmHg if standard manual blood pressure measurements are used or 120 to 125 mmHg if unattended automated oscillometric measurements are used. If attaining goal blood pressure proves difficult or burdensome for the patient, the systolic blood pressure that is reached with two or three antihypertensive agents (even if above target) may be a reasonable interim goal. (See "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension", section on 'Goal blood pressure'.)

Updated ACP guideline on management of low back pain (April 2017)

The American College of Physicians (ACP) recently published an updated guideline for the management of acute, subacute, and chronic low back pain [5]. Notable changes from their previous guideline include emphasis of nonpharmacologic therapy as an initial management approach and preference for nonsteroidal anti-inflammatory drugs (NSAIDs) for first-line pharmacotherapy over acetaminophen. Our recommendations are generally consistent with the updated ACP guideline. (See "Treatment of acute low back pain" and "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment".)

Dexamethasone for acute pharyngitis pain in adults (April 2017)

Studies of oral glucocorticoids for acute pharyngitis pain have generally found only modest benefit but have been limited by confounding factors, such as concurrent antibiotic use. In an office-based randomized trial that compared a single dose of dexamethasone with placebo for adults who visited a primary care clinician for acute pharyngitis and were not given an immediate prescription for antibiotics, there was no difference in the proportion of patients who achieved full pain relief at 24 hours and there was only a small difference in symptom relief at 48 hours (35 versus 27 percent with placebo) [6]. These results support our suggestion to not prescribe glucocorticoids routinely for acute pharyngitis and to limit their use to severely symptomatic patients. (See "Symptomatic treatment of acute pharyngitis in adults", section on 'Limited role of glucocorticoids'.)

Adverse events with short-term oral glucocorticoid use in adults (April 2017)

Chronic steroid use is associated with a wide spectrum of adverse effects. However, there is a paucity of clinical data on the adverse effects associated with short-term use. A retrospective cohort study and self-controlled case series assessed the risk of three adverse events (sepsis, venous thromboembolism [VTE], and fracture) in over 300,000 adults younger than 65 who received at least one short-term (<30 days) outpatient prescription for oral glucocorticoids over a three-year period [7]. The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Within 30 days of drug initiation, there was a two- to fivefold increase in the rates of sepsis, VTE, and fracture, which then decreased over the subsequent 31 to 90 days. These findings suggest that even short courses of oral steroids are associated with adverse effects that should be considered before prescribing. (See "Major side effects of systemic glucocorticoids", section on 'Dose effects'.)

Fluctuations in body weight and risk of CHD (April 2017)

While obesity is associated with an increased risk for coronary heart disease (CHD) and sustained weight loss reduces the risk of CHD, the effects of frequent weight gain and loss on CHD risk are unknown. A post hoc analysis of data from a secondary prevention statin study involving over 9000 patients with established CHD and LDL cholesterol below 130 mg/dL (3.4 mmol/L) found that patients in the highest quintile of weight fluctuation (mean variability of 3.9 kg) had significantly higher risks of any CHD event, any cardiovascular disease event, and total mortality, compared with those in the quintile with the lowest weight variation, and that risk increased with each standard deviation change in magnitude of weight fluctuation [8]. These findings suggest that frequent cycles of weight gain and weight loss are associated with an increased risk of CHD and cardiovascular disease events, with greatest magnitude of risk among those who were overweight or obese at baseline. (See "Overview of the risk equivalents and established risk factors for cardiovascular disease", section on 'Obesity'.)

Rivaroxaban versus aspirin for indefinite treatment of venous thromboembolism (April 2017)

The optimal antithrombotic agent for patients with venous thromboembolism (VTE) who have indications for indefinite therapy to reduce the risk of recurrent VTE is unclear. A randomized trial compared rivaroxaban (a direct factor Xa inhibitor) and aspirin for long-term treatment of patients who had completed a 6- to 12-month course of therapeutic anticoagulation [9]. Rivaroxaban, either at a treatment (20 mg daily) or a prophylactic (10 mg daily) dose, was superior to aspirin in preventing VTE recurrence for up to 12 months, without increasing the risk of major bleeding. While rates of recurrence were comparable between both doses of rivaroxaban, further studies are warranted before reduced intensity regimens can be recommended. For most patients with VTE requiring long-term treatment, we suggest full intensity anticoagulation rather than low intensity regimens or aspirin. (See "Rationale and indications for indefinite anticoagulation in patients with venous thromboembolism", section on 'Factor Xa and direct thrombin inhibitors'.)

ACP/AAFP guidelines for hypertension treatment in older adults (March 2017)

The American College of Physicians/American Academy of Family Physicians (ACP/AAFP) have issued guidelines for pharmacologic treatment of hypertension in older adults, addressing targets for blood pressure [10]. These guidelines depart from our recommendations and from other recent guidelines (the 2016 Canadian Hypertension Education Program [CHEP] guidelines and the 2016 National Heart Foundation of Australia guidelines) released after publication of the SPRINT trial. The ACP/AAFP suggest a goal systolic pressure of <150 mmHg in adults 60 years of age and older, with consideration of a goal <140 mmHg in patients at high cardiovascular risk. However, we continue to recommend lower goals for such patients, consistent with guidelines from other groups. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Recommendations of others'.)

AASM guideline on pharmacotherapy for chronic insomnia in adults (March 2017)

The American Academy of Sleep Medicine (AASM) has released a new clinical practice guideline on the pharmacologic treatment of chronic insomnia in adults [11]. The guideline reviews evidence of effectiveness for a variety of medications (including benzodiazepines, nonbenzodiazepine hypnotics, ramelteon, doxepin, and suvorexant) and notes limitations and potential biases to the evidence, leading to low confidence in the overall estimation of risk-to-benefit ratio. The potential short-term benefits of pharmacologic therapy need to be balanced with the risk of side effects and dependence with long-term use. We continue to prefer behavioral therapy, rather than pharmacotherapy, as an initial treatment approach in most patients. (See "Treatment of insomnia in adults", section on 'Choice of an agent'.)

Patterns of tobacco use in the United States (February 2017)

A nationally representative longitudinal study of tobacco product usage in 2013 and 2014 in the United States found that 28 percent of adults used tobacco regularly and 9 percent of youths 12 to 17 years of age had used a tobacco product within the previous 30 days [12]. Two-thirds of adult and one-half of youth tobacco users smoke tobacco cigarettes. Other forms of tobacco (or other nicotine products), including cigar, e-cigarettes, hookah/waterpipe, smokeless tobacco, snus pouch, and dissolvable tobacco, constitute a considerable portion of tobacco use, and 40 percent who reported tobacco use were using more than one form. This study will be repeated over time to establish trends of use. These results illustrate the importance of asking patients not only if they smoke cigarettes, but also if they use one or more other forms of tobacco or nicotine. (See "Patterns of tobacco use", section on 'Tobacco usage: overview'.)

Relative cardiovascular safety of celecoxib, naproxen, and ibuprofen (December 2016)

The cardiovascular (CV) safety of celecoxib, the COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), compared with other NSAIDs, is a matter of debate. In a randomized trial (PRECISION) involving over 24,000 patients with arthritis and either known CV disease or CV risk factors, the CV safety of celecoxib was noninferior to both naproxen and ibuprofen, two nonselective NSAIDs [13]. Depending upon the analysis, about 2 to 5 percent of subjects experienced a CV event during follow-up, which was slightly lower than the expected event rate. Despite some limitations, this trial suggests that celecoxib in moderate doses can be administered, when indicated, without concern about increased CV risk compared with the nonselective nonsteroidal agents naproxen and ibuprofen. (See "COX-2 selective inhibitors: Adverse cardiovascular effects", section on 'Celecoxib' and "Nonselective NSAIDs: Adverse cardiovascular effects", section on 'Risk of myocardial infarction, stroke, and death'.)

No role for routine serologic screening for genital herpes infection (December 2016)

Genital herpes, which can be caused by herpes simplex virus type 1 or 2 (HSV-1 or HSV-2), is one of the most common sexually transmitted infections, and sexual transmission can occur even in the absence of symptoms. Despite this, routine serologic screening for herpes simplex is not recommended in asymptomatic adolescents and adults due to significant limitations of available tests, as highlighted in a recent US Preventive Services Task Force statement [14]. Limitations include the low specificity and high false positive rate of serologic tests for HSV-2 and the inability of serologic tests for HSV-1 to differentiate oral from genital infection. Furthermore, there are no specific treatment interventions for asymptomatic patients, so the anxiety and disruption of personal relationships associated with a positive test outweigh any potential benefits. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Screening'.)

FDA warning removed from varenicline for smoking cessation (December 2016)

In 2009, the US Food and Drug Administration (FDA) required varenicline packaging to include a boxed warning about potential neuropsychiatric side effects, but this warning has been removed in 2016 [15], based on results of a randomized trial that found no difference in adverse neuropsychiatric events comparing varenicline with nicotine patch or placebo in patients with or without a coexisting psychiatric disorder [16]. As with any medication, we advise that patients should be told to contact their clinician if they or their family notice any unusual behavior or mood symptoms as well as any new or worsening symptoms of cardiovascular disease. (See "Pharmacotherapy for smoking cessation in adults", section on 'Safety'.)

GERIATRICS

Antipsychotic drugs and risk of falls and fracture (March 2017)

In a large, population-based sample of Finnish people with Alzheimer disease, new users of antipsychotic medication had an increased risk of hip fractures from the first days of use [17]. Subsequent to multiple similar reports in patients with varied disorders, the US Food and Drug Administration (FDA) issued a warning that antipsychotic drugs may cause falls and fractures as a result of somnolence, postural hypotension, and/or motor and sensory instability, and recommended that a fall risk assessment be completed when initiating antipsychotic treatment and recurrently for patients continuing on long-term antipsychotics. (See "Second-generation antipsychotic medications: Pharmacology, administration, and side effects", section on 'Falls'.)

Structured exercise program and mobility disability in older adults (January 2017)

The randomized multicenter LIFE study, comparing a structured exercise program with a health information program among sedentary adults aged 70 to 89 years without major mobility disability at baseline, had previously reported that exercise decreased the incidence of major mobility disorder (MMD) and risk for permanent MMD. In a new report, the structured exercise also increased the likelihood of transition from MMD, if it occurred, to no MMD [18]. Preserving mobility is essential for maintaining independence and quality of life among older adults. These findings indicate that exercise both prevents initial mobility disability and promotes restored mobility in those who become disabled. (See "Physical activity and exercise in older adults", section on 'Benefits of physical activity'.)

SCREENING

Duration of benefit of one-time screening sigmoidoscopy (June 2017)

Sigmoidoscopy is one of several methods to screen for colorectal cancer in average-risk persons. In extended follow-up of a randomized trial, a one-time screening flexible sigmoidoscopy for people aged 55 to 64 years was associated with reduced colorectal cancer incidence and mortality even 17 years after the initial screening exam [19]. Similar benefits had been seen at 11-year follow-up. Although these findings support one-time flexible sigmoidoscopy as a potential screening method, most groups that include sigmoidoscopy as a screening option currently recommend repeated testing, although the optimal repeat interval is not known. In agreement with recommendations of the US Preventive Services Task Force, when flexible sigmoidoscopy is chosen as a screening modality, we offer flexible sigmoidoscopy alone every five years or flexible sigmoidoscopy every 10 years plus fecal immunochemical testing (FIT) every year. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness' and "Screening for colorectal cancer: Strategies in patients at average risk".)

Interval to colonoscopy following a positive fecal immunochemical test (May 2017)

How soon follow-up colonoscopy should be done to evaluate a positive fecal immunochemical test (FIT) is uncertain. In a retrospective cohort study of over 70,000 patients aged 50 to 70 years who had a positive FIT, rates of detection of any colorectal cancer (CRC) or advanced-stage CRC increased with increased time intervals between positive FIT and colonoscopy [20]. Based on these findings, we encourage follow-up colonoscopy as soon as possible (and definitely within a few months) for patients who have a positive FIT. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'A suggested approach'.)

USPSTF statement on screening for celiac disease (April 2017)

Testing for celiac disease in the absence of suggestive signs or symptoms is controversial. A US Preventive Services Task Force report has concluded that there are insufficient data to support screening for celiac disease [21]. However, we continue to test for celiac disease in asymptomatic first-degree relatives of patients with a confirmed diagnosis of celiac disease because of their increased risk for disease. We also recommend screening asymptomatic children with several conditions associated with celiac disease, including type 1 diabetes and Down syndrome. Our recommendations are consistent with guidelines from the American College of Gastroenterology and from Pediatric Gastroenterology societies [22]. (See "Diagnosis of celiac disease in adults", section on 'Who should be tested'.)

Flexible sigmoidoscopy and colorectal cancer screening in older women (January 2017)

Flexible sigmoidoscopy is one of several screening modalities recommended by the US Preventive Services Task Force for colorectal cancer (CRC) screening. However, sigmoidoscopy is less effective at detecting lesions in the right side of the colon (beyond the 60 cm reach of the sigmoidoscope) than the left side, and right-sided lesions are more common in older women. A study that pooled results from three randomized trials (nearly 300,000 individuals) comparing screening by sigmoidoscopy with no screening found that the incidence of CRC at 10 to 12 years was decreased in men but, in women, only in those younger than 60 years [23]. Current screening recommendations do not indicate gender-based preferences for screening options, but these findings call into question the effectiveness of flexible sigmoidoscopy as a screening modality for women over age 60 years. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)

Fecal immunochemical testing for colorectal cancer screening (January 2017)

Multiple test strategies are available for screening in people with average risk for colorectal cancer (CRC). Annual stool testing for occult blood using a guaiac reagent (gFOBT) has been widely implemented and is one of the screening strategies endorsed by the US Preventive Services Task Force. Fecal immunochemical testing (FIT) is another option and has the potential advantages of better test performance (improved sensitivity for CRC and advanced adenomas) and better patient adherence (one stool sample, no diet restrictions) compared with gFOBT. The US Multi-Society Task Force has published consensus guidelines recommending FIT over gFOBT when occult blood stool testing is elected for CRC screening [24]. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Immunochemical tests for fecal blood' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)

Effectiveness of screening colonoscopy in older adults (January 2017)

The effectiveness of screening for colorectal cancer (CRC) in older adults is uncertain. Randomized trials of screening colonoscopy have not been completed, and trials currently underway do not include adults 75 years and older. A study of Medicare beneficiaries found that undergoing colonoscopy believed to be for screening modestly decreased the risk of CRC (2.2 versus 2.6 percent in the no-screening group) over an eight-year period for those aged 70 to 74 years, with a smaller, but statistically non-significant, decrease in risk (2.8 versus 3.0 percent in the no-screening group) for those 75 to 79 years [25]. Adverse events following colonoscopy occurred in less than 1 percent. The decision whether to recommend screening for a patient at any age, but especially those over 75 years of age, should depend upon the patient's health status, anticipated life expectancy, risk for colorectal cancer (CRC), and personal values. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Screening in older adults'.)

Screening interval for lung cancer (January 2017)

The optimal strategy for screening high-risk individuals for lung cancer is the subject of active study. In new results from the NELSON trial, in which almost 16,000 current or former smokers were randomly assigned to low-dose computed tomography (LDCT)-based screening versus observation only, extending the screening interval from 1 to 2.5 years reduced the proportion of cancers detected at an early stage [26]. These data support our approach to screen annually with LDCT when screening patients who are at high risk for lung cancer. (See "Screening for lung cancer", section on 'Other trials'.)

ADULT CARDIOVASCULAR MEDICINE

ACE inhibitors or ARBs not routinely indicated in low-risk patients with stable ischemic heart disease (January 2017)

Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs), referred to as renin angiotensin system inhibitors (RASi), improve survival in high-risk patients with stable ischemic heart disease (SIHD), such as those with heart failure or diabetes. However, a 2017 meta-analysis of 24 randomized trials of RASi compared with placebo or to active control in patients with SIHD without clinical heart failure and with a left ventricular ejection fraction ≥40 percent found that benefit was not present in patients enrolled in studies in which the cardiovascular event rates were low [27]. We do not routinely prescribe RASi to patients with SIHD at low risk of adverse cardiovascular events. (See "Prevention of cardiovascular disease events in those with established disease or at high risk", section on 'ACE inhibitors or ARBs'.)

Role of troponin testing in primary prevention (January 2017)

Across a broad range of populations, elevated troponin is associated with an increased risk of cardiovascular disease (CVD) events. In the primary prevention West of Scotland Coronary Prevention Study of individuals at high CVD risk who were randomly assigned to either statin or placebo, individuals in the highest quartile of high-sensitivity troponin were at the greatest risk of a CVD event at one year in both treated and untreated individuals [28]. Studies designed to evaluate the role of troponin testing in patients being considered for statin therapy or in those started on statin therapy are ongoing. (See "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome", section on 'Elevations in patients at high risk'.)

ADULT ENDOCRINOLOGY AND DIABETES

GLP-1-based therapies for type 2 diabetes and overall mortality (June 2017)

The effect of glucagon-like peptide-1 (GLP-1)-based therapies (GLP-1 receptor agonists and dipeptidyl peptidase-4 [DPP-4] inhibitors) on overall mortality in patients with type 2 diabetes is uncertain. In a systematic review and meta-analysis of 189 trials, there was no difference in all-cause mortality between any GLP-1-based therapy versus control (placebo or other antidiabetic drug) [29]. In subgroup analyses of the cardiovascular outcomes trials, there was a suggestion of reduced all-cause mortality with GLP-1 receptor agonists versus placebo, but no difference with DPP-4 inhibitors versus placebo. Further studies examining the effect of GLP-1 receptor agonists on overall mortality are warranted. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus" and "Dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus".)

Screening interval for diabetic retinopathy (May 2017)

There are few data evaluating the optimal frequency of follow-up retinal examinations after initial screening in patients with diabetes, particularly type 1 diabetes. In an analysis of almost 24,000 retinopathy examinations over 24 years in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study, the probability of progressing from lower to higher categories of retinopathy was dependent upon the previous retinal exam and glycated hemoglobin (A1C), with optimal screening intervals ranging from every three months among patients with severe nonproliferative retinopathy to every four years among those who had no retinopathy [30]. Compared with annual or biannual examinations, this model for an individualized schedule resulted in an overall reduction in the frequency of eye examinations and a substantial reduction in cost. (See "Diabetic retinopathy: Screening", section on 'Frequency of examinations'.)

Testosterone therapy in older men with low testosterone (April 2017)

The role of testosterone replacement to treat the decline in serum testosterone concentration that occurs in aging men (in the absence of identifiable pituitary or hypothalamic disease) was addressed in the multicenter Testosterone Trials (TTrials), an integrated set of seven trials in nearly 800 men over age 65 years with low testosterone and sexual dysfunction, physical dysfunction, and reduced vitality, who were randomly assigned to testosterone gel or placebo for 12 months. Initial results suggested that testosterone had a beneficial effect on sexual function, depressive symptoms, and mood, and possibly physical function (walking distance), but not on vitality [31,32] Results from recently published individual trials showed the following:

There was no effect of testosterone replacement on cognitive function in men with age-associated memory impairment [33].

There was a beneficial effect on anemia [34] and bone density [35].

Testosterone increased coronary artery noncalcified plaque volume as measured by coronary computed tomographic angiography [36].

While the small size and short duration of the subtrials are important limitations, the coronary artery plaque trial raises important concerns about the safety of testosterone therapy in older men. (See "Overview of testosterone deficiency in older men".)

Treatment with levothyroxine provides no symptomatic benefit in older adults with subclinical hypothyroidism (April 2017)

Subclinical hypothyroidism is defined biochemically as an elevated serum thyroid-stimulating hormone (TSH) and a normal serum-free thyroxine (T4) level. Some patients with subclinical hypothyroidism may have vague, nonspecific symptoms. Although virtually all experts recommend treatment of subclinical hypothyroidism when serum TSH concentrations are ≥10 mU/L, treatment of patients with TSH values between the upper reference limit and 9.9 mU/L remains controversial, particularly in older patients who are more likely to have complications from unintended overtreatment. In a randomized trial evaluating the effect of levothyroxine versus placebo on quality of life measures in over 700 older patients (mean age 74.4 years) with mean TSH 6.4 mU/L, there was no difference in hypothyroid symptoms or tiredness scores after one year [37]. We do not routinely treat older patients with TSH between the upper reference limit and 9.9 mU/L (algorithm 1). (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Hypothyroid signs and symptoms'.)

Vitamin D and prevention of cancer (April 2017)

In a trial comparing the effect of vitamin D and calcium supplementation with placebo on the incidence of cancer in over 2000 postmenopausal women, there was no difference between groups in the incidence of cancer at four years [38]. An analysis by cancer site showed no difference in the incidence of breast cancer between the two groups; there were too few cancers at other sites to analyze. Although several study limitations may have contributed to the absence of an effect, including enrollment of patients with a relatively high baseline vitamin D level and permission to take vitamin D supplements (up to 800 international units daily) outside of the intervention, vitamin D supplementation for the prevention of cancer is not warranted. (See "Vitamin D and extraskeletal health", section on 'Cancer'.)

Types of cancers associated with obesity (April 2017)

Excess weight is associated with an increased risk of developing and dying from cancer, but the number and types of cancers are inconsistent across studies. In a review of 204 meta-analyses that investigated the association between indices of adiposity and developing 36 primary cancers and their subtypes, associations were identified for esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract, pancreas, breast (in women who had never taken hormones), endometrium, ovary, and kidney [39]. (See "Obesity in adults: Health consequences", section on 'Cancer'.)

Vitamin D and prevention of infection (March 2017)

In a meta-analysis of 25 trials (almost 11,000 patients) evaluating the incidence of acute respiratory infection, vitamin D supplementation slightly reduced the proportion of patients experiencing one acute respiratory tract infection [40]. In prespecified subgroup analyses, supplementation was most effective in patients with vitamin D levels <10 ng/mL and in those treated with daily or weekly, rather than bolus, doses. As the meta-analysis showed significant effects predominantly in patients with very severe vitamin D deficiency, who require treatment regardless of infection prevention because of the risk of osteomalacia, vitamin D supplementation for the prevention of infection alone is not warranted. (See "Vitamin D and extraskeletal health", section on 'Innate'.)

Glycated hemoglobin (A1C) in sickle cell trait (March 2017)

In a retrospective cohort study evaluating glycated hemoglobin (A1C) in African Americans with and without sickle cell trait, A1C was lower at any fasting glucose value in patients with sickle cell trait compared with controls [41]. However, the study is limited by its methodology, as mean glucose levels were estimated on the basis of very few measurements, usually a single fasting glucose level or oral glucose tolerance test. A1C correlates best with mean blood glucose over 8 to 12 weeks, raising the possibility that if measured appropriately with frequent glucose measurements over time (multiple daily measurements or continuous glucose monitoring), mean glucose levels may actually have been different between the study populations, with the putative different A1C levels accurately reflecting these different mean glucose levels. We continue to use A1C as one option to diagnose diabetes in patients with sickle cell trait. (See "Estimation of blood glucose control in diabetes mellitus", section on 'Racial variation'.)

Treatment of subclinical hypothyroidism and maternal hypothyroxinemia during pregnancy (March 2017)

In parallel multicenter trials, over 600 pregnant women with subclinical hypothyroidism (median thyroid-stimulating hormone [TSH] 4.4 mU/L, normal free T4) or isolated maternal hypothyroxinemia (low free T4, normal TSH) were randomly assigned to levothyroxine or placebo [42]. There was no significant effect of treatment on adverse pregnancy outcomes or on neurodevelopmental outcomes in the children at five years of age. The main limitation of the study is the late initiation of treatment at a mean gestational age of almost 17 weeks, at which time fetal thyroid tissue is beginning to function. We suggest levothyroxine (with earlier initiation when possible) for pregnant women with subclinical hypothyroidism, defined as a TSH above a trimester-specific normal reference range (or above 4.0 mU/L if trimester-specific range unavailable) with normal free T4. (See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Effect of thyroid hormone replacement'.)

Glycemic outcomes following bariatric surgery in obese patients with type 2 diabetes (February 2017)

Additional follow-up from a bariatric surgery trial in obese patients with type 2 diabetes (134 patients in follow-up study, 150 patients in initial trial) continues to show reduced glycated hemoglobin (A1C) in the two surgical arms at five years, although there has been some regression in all groups from the one-year results [43]. The proportion of patients with A1C ≤6 percent was 29 percent for gastric bypass and 23 percent for sleeve gastrectomy, compared with 5 percent for controls (intensive medical therapy). While these results are encouraging, we require longer-term follow-up with documentation of improved clinically important outcomes, such as reduced vascular complications or reduced mortality, before routinely recommending bariatric surgery for obesity-related type 2 diabetes that is resistant to multiple medications. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Surgical treatment of obesity'.)

Metformin use in patients with diabetes and renal impairment, heart failure, or chronic liver disease (January 2017)

In a systematic review of 17 observational studies comparing diabetes regimens with and without metformin, metformin use was associated with lower all-cause mortality among patients with heart failure, renal impairment, or chronic liver disease with hepatic impairment [44]. In addition, metformin use in patients with renal impairment or heart failure was associated with fewer heart failure readmissions. This study supports a recent US Food and Drug Administration (FDA) labeling revision for metformin, which will increase use in patients with renal impairment. Metformin remains contraindicated in patients with estimated glomerular filtration rate (eGFR) <30 mL/min, concurrent active or progressive liver disease, or unstable or acute heart failure with risk of hypoperfusion and hypoxemia. Recommendations regarding metformin use in patients with an eGFR between 30 and 45 mL/min vary and UpToDate authors individualize decisions about metformin use in such patients. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.)

ADULT GASTROENTEROLOGY

ACG guidelines on the treatment of H. pylori (May 2017)

The American College of Gastroenterology has published updated guidelines on the treatment of Helicobacter pylori [45]. According to these guidelines, the choice of initial antibiotic regimen to treat H. pylori should be guided by risk factors for macrolide resistance and penicillin allergy. Risk factors for macrolide resistance include prior exposure to macrolides and local clarithromycin rates ≥15 percent (assumed in the United States). In patients with risk factors for macrolide resistance, bismuth quadruple therapy is a first-line treatment option. (See "Treatment regimens for Helicobacter pylori", section on 'Approach to selecting an antibiotic regimen'.)

Treatment of acute diverticulitis without antibiotics (February 2017)

Acute diverticulitis is typically treated with antibiotics. However, in a Dutch trial (DIABOLO) that randomly assigned over 500 low-risk patients with first-episode, acute, uncomplicated diverticulitis confirmed with computed tomography to either observation or antibiotic therapy, outcomes were similar for both groups [46]. Because almost all of the patients were admitted to the hospital for one or more days, this trial did not establish the safety of avoiding antibiotic therapy in low-risk outpatients. Thus, until further data become available, UpToDate continues to recommend antibiotic treatment of acute diverticulitis in patients meeting criteria for outpatient management. (See "Acute colonic diverticulitis: Medical management", section on 'Outpatient treatment' and "Acute colonic diverticulitis: Medical management".)

ACG guidelines on the evaluation of abnormal liver chemistries (January 2017)

The American College of Gastroenterology has published new guidelines on the evaluation of abnormal liver chemistries [47]. These guidelines define normal alanine aminotransferase (ALT) ranges as 29 to 33 international units/L for males and 19 to 25 international units/L for females, which are lower than the reference ranges of many clinical laboratories. They recommend that ALT levels repeatedly above these upper limits of normal be evaluated. In addition, they provide a framework for the evaluation of elevated ALT, aspartate aminotransferase (AST), and alkaline phosphatase levels (which should be characterized as liver chemistries or tests rather than markers of liver function) based on the degree and pattern of elevations. (See "Approach to the patient with abnormal liver biochemical and function tests", section on 'Aminotransferases'.)

ADULT HEMATOLOGY AND ONCOLOGY

Underdosing of direct oral anticoagulants (February 2017)

The oral direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban (collectively called direct oral anticoagulants [DOACs]) have been available for several years. A real-world study of over 1500 patients with venous thromboembolism (VTE) who were treated with a DOAC found that dosing differed from the recommended product dosing in 20 to 50 percent of cases, depending on the agent [48]. These deviations (mostly underdosing) correlated with an increased frequency of VTE recurrence. Clinicians should familiarize themselves with prescribing information to avoid adverse outcomes. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Clinician familiarity with dosing'.)

Duration of adjuvant endocrine therapy for breast cancer (July 2016, Modified February 2017)

For postmenopausal women receiving adjuvant treatment with an aromatase inhibitor (AI) for hormone-positive breast cancer, the minimum duration of treatment is five years. While data from the MA17R trial demonstrated that extending the duration from 5 to 10 years improved recurrence-free survival [49], preliminary results from the NSABP-B42, DATA, and IDEAL trials, reported at the San Antonio Breast Cancer Symposium, have not confirmed this benefit [50-52]. No study has demonstrated a benefit in overall survival with extended adjuvant AI therapy, and bone-related toxic effects are more frequent among those receiving extended treatment. While variations in methodology likely account for the differences in recurrence-free survival between the studies, the magnitude of any potential benefit is likely to be greatest for those at highest risk for recurrence. While we previously had recommended an extended course of AI adjuvant therapy for most postmenopausal women with nonmetastatic hormone-positive disease, based on the new data, we now suggest offering extended adjuvant aromatase inhibitor therapy to those with high-risk disease (eg, node-positive or ≥T3 disease). (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Duration of endocrine treatment'.)

ADULT INFECTIOUS DISEASE

Treatment of nonpurulent cellulitis (June 2017)

Empiric antibiotic therapy for nonpurulent cellulitis (ie, with no purulent drainage and no associated abscess) should be active against beta-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus (MSSA) but not necessarily methicillin-resistant S. aureus (MRSA). This approach is supported by a randomized trial of nearly 500 patients with nonpurulent cellulitis, in which cephalexin plus placebo (active against beta-hemolytic streptococci and MSSA) and cephalexin plus trimethoprim-sulfamethoxazole (TMP-SMX, which adds activity against MRSA) resulted in statistically similar clinical cure rates (69 versus 76 percent) [53]. Although there was a trend toward higher cure rates with the addition of TMP-SMX, the results were likely skewed by a relatively large number of patients who did not complete the full course of therapy. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Cellulitis'.)

Rising rates of HCV infection in young women in the United States (May 2017)

In parallel with the opioid and injection drug use epidemic in the United States, rates of hepatitis C virus (HCV) infection have been increasing over the past decade. In particular, the annual number of acute HCV cases among women aged 15 to 44 years rose 3.6-fold from 2006 to 2014 [54]. An estimated 29,000 women with HCV infection gave birth each year between 2011 and 2014; since the risk of vertical transmission is approximately 5.8 percent, this implies that an estimated 1700 infants were infected annually during this time. These numbers highlight the importance of screening at-risk individuals and arranging follow-up for those with HCV infection. (See "Vertical transmission of hepatitis C virus", section on 'Incidence' and "Hepatitis C virus infection in children", section on 'Epidemiology'.)

HBV reactivation during HCV antiviral therapy (May 2017)

Reactivation of hepatitis B virus (HBV) can occur during direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection. Among 29 cases reported to the US Food and Drug Administration (FDA) or described in the literature between 2013 and 2016, reactivation occurred at an average of 53 days into DAA treatment and was not associated with a particular HCV genotype or DAA regimen [55]. Two cases were fatal, and one patient required liver transplant. Patients should be tested for HBV coinfection prior to initiation of HCV therapy, with HBV treatment initiated for those who meet criteria (table 1). HBV coinfected patients who do not initially meet HBV treatment criteria should be monitored for reactivation during HCV treatment. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'HBV coinfection' and "Overview of the management of chronic hepatitis C virus infection", section on 'Monitoring during antiviral therapy'.)

Decreased susceptibility to fluoroquinolones in Shigella infection (April 2017)

When treatment for Shigella infection is indicated, susceptibility testing should be performed to guide antimicrobial selection. In the United States, an increasing proportion of Shigella isolates have minimum inhibitory concentrations (MIC) to ciprofloxacin of 0.12 to 1 mcg/mL [56]. Although these MIC values are considered susceptible and their impact on treatment outcomes in Shigella is unknown, they are associated with resistance genes that result in worse outcomes with fluoroquinolone treatment in other Enterobacteriaceae. Clinicians should request the MIC to ciprofloxacin if it is not provided with susceptibility results and avoid fluoroquinolones if the MIC is ≥0.12 mcg/mL. (See "Shigella infection: Clinical manifestations and diagnosis", section on 'Susceptibility testing' and "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic selection'.)

Guidelines on diagnosis of tuberculosis (January 2017)

Guidelines from the American Thoracic Society, Infectious Diseases Society of America, and the Centers for Disease Control and Prevention on the diagnosis of tuberculosis in adults and children were published in December 2016 [57]. They state that an interferon-gamma release assay (IGRA) is generally preferred for diagnosis of latent tuberculosis infection (LTBI) in individuals five years or older who have low-to-intermediate risk of progression to active disease (table 2), although the tuberculin skin test (TST) is an acceptable alternative if IGRA is not available or too costly. For those who have high risk of progression to active disease, either IGRA or TST is acceptable, but many guideline panel members noted using the alternative test if the initial one was negative and considering a positive result from either test to indicate LTBI. The evaluation of suspected tuberculosis disease should include three sputum specimens for acid-fast bacilli (AFB) smear and culture and one or more specimens for nucleic acid amplification (NAA) testing. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults" and "Diagnosis of pulmonary tuberculosis in HIV-uninfected adults" and "Latent tuberculosis infection in children" and "Tuberculosis disease in children".)

ADULT NEPHROLOGY AND HYPERTENSION

Multitarget therapy and progression of kidney disease in type 2 diabetes (March 2017)

The optimal therapeutic approach to the treatment of diabetic nephropathy may be intensive multifactorial risk factor reduction targeting behavior (ie, counseling on diet, exercise, and smoking cessation), glycemic control, blood pressure, and dyslipidemia. The efficacy of implementing this approach for eight years, compared with usual care, in patients with type 2 diabetes and increased albuminuria was examined in the Steno type 2 trial. At the end of the trial phase, all patients were offered intensive multitarget therapy [58]. After an additional 20 years of follow-up, those who were assigned to intensive multitarget therapy had a significantly lower annual decline in glomerular filtration rate and a higher likelihood of survival without end-stage renal disease (approximately 50 versus 30 percent). (See "Treatment of diabetic nephropathy", section on 'Type 2'.)

Effect of antihypertensive drug class on fracture rates (January 2017)

Thiazide diuretics stimulate distal tubular reabsorption of calcium, leading to a decrease in urinary calcium excretion and a possible benefit on bone mineral density. The rates of hip or pelvic fractures among patients treated with thiazide-like diuretics, angiotensin converting enzyme (ACE) inhibitors, or calcium channel blockers were compared in a post-hoc analysis of the ALLHAT trial [59]. At approximately five years, those randomly assigned chlorthalidone had fewer hip or pelvic fractures as compared with those assigned to either lisinopril or amlodipine. Thus, if monotherapy is appropriate in a patient with hypertension and osteoporosis, thiazide-like diuretics may have advantages over ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Thiazide diuretics'.)

ADULT NEUROLOGY AND PSYCHIATRY

High-risk drug prescribing in adults with dementia (February 2017)

Older adults with dementia are at heightened risk for adverse drug effects from anticholinergic drugs, benzodiazepines, and opioids, among many others. Despite these risks, polypharmacy remains common in this population. In a study that included over 75,000 adults with dementia, 44 percent of patients were prescribed at least one potentially unsafe medication (mostly drugs with high anticholinergic activity), and rates were consistently higher in patients receiving care from multiple providers [60]. These results highlight the need for careful monitoring of drug therapy in patients with dementia and the importance of communication among providers before starting new therapies. (See "Safety and societal issues related to dementia", section on 'Polypharmacy'.)

ADULT PULMONOLOGY

Spirometry and asthma diagnosis (February 2017)

The importance of confirming reversible airflow limitation when making a diagnosis of asthma was illustrated in a study of 701 randomly selected adults who had a physician diagnosis of asthma in the previous five years [61]. Current asthma was excluded in 33 percent and, among these, less than half had previous testing to confirm airflow limitation. This observation suggests that a clinical diagnosis of asthma, if not supported by spirometry, may be incorrect and reinforces guideline recommendations that spirometry pre- and post-bronchodilator be obtained at the time of an initial diagnosis of asthma.

(See "Diagnosis of asthma in adolescents and adults", section on 'Diagnosis'.)

ADULT RHEUMATOLOGY

New guidelines for management of gout (February 2017)

Several professional organizations have recently published guidelines for the management of gout, including the European League Against Rheumatism (EULAR) [62], an international task force [63], and the American College of Physicians (ACP) [64]. The ACP guidelines depart from recommendations of the American College of Rheumatology (ACR), EULAR, the international task force, and others by suggesting a treat-to-avoid-symptoms approach (ie, monitoring the adequacy of urate-lowering drug dosing based on the frequency and severity of acute attacks) rather than a treat-to-target approach based on serum urate levels. We concur with the ACR, EULAR, and international guidelines groups, based upon the available clinical evidence and an understanding of the pathophysiology of gout, and we continue to recommend monitoring serum urate levels and using such data to make treatment choices and titrate dosing. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Recommendations of major groups'.)

Lack of benefit of chondroitin and glucosamine for knee osteoarthritis (January 2017)

The use of glucosamine and chondroitin for osteoarthritis (OA) has been controversial, with most studies showing little to no evidence of clinically meaningful benefit. In a multicenter randomized trial, 164 patients with moderate to severe knee osteoarthritis were treated with either placebo or chondroitin sulfate plus glucosamine [65]. At six months' follow-up, the mean reduction in the global pain score was greater in the placebo group, and there were no between-group differences in patient-reported function or other outcomes. Although the study was limited by the small size and potentially inadequate dosing of chondroitin and glucosamine, it is likely that the combination of glucosamine and chondroitin is no better than placebo in patients with knee osteoarthritis.

GYNECOLOGY

IUD use does not impact human papillomavirus infection (March 2017)

A reduction in cervical cancer rates among intrauterine device (IUD) users has been observed and attributed to favorable effects of the device on human papillomavirus (HPV) clearance. However, a prospective cohort study that controlled for sexual and behavioral confounders reported no difference in HPV acquisition or clearance among women and girls with or without an IUD [66]. Thus, IUD use does not appear to impact HPV infection. (See "Intrauterine contraception: Devices, candidates, and selection", section on 'IUDs cause infection'.)

USPSTF statement on routine pelvic examination (March 2017)

Routine pelvic examination in asymptomatic women is controversial. The US Preventive Services Task Force (USPSTF) recently published a statement that evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women [67]. In 2014, the American College of Physicians (ACP) recommended against such examinations. In 2012, the American College of Obstetricians and Gynecologists (ACOG) recommended annual pelvic examination in nonpregnant women age 21 years or older and is now reviewing its policy in response to the USPSTF statement. As few data about the benefit and harms of routine pelvic examinations are available, we suggest shared decision-making between the patient and clinician. (See "The gynecologic history and pelvic examination", section on 'Indications and frequency for examination'.)

OBSTETRICS

Tranexamic acid for management of postpartum hemorrhage (May 2017)

Tranexamic acid, an antifibrinolytic drug, reduces bleeding in surgical and trauma patients. In a pragmatic randomized trial involving over 20,000 women with postpartum hemorrhage in over 20 countries (the World Maternal Antifibrinolytic Randomized Trial [WOMAN]), tranexamic acid, compared with placebo, reduced the relative risk of death due to bleeding by 20 to 30 percent, reduced the incidence of laparotomy to control bleeding, and was not associated with an increase in adverse effects [68]. Overall mortality was not reduced. We now recommend administration of tranexamic acid as a component of the treatment for postpartum hemorrhage. (See "Management of postpartum hemorrhage at vaginal delivery".)

USPSTF guidelines on screening for preeclampsia (May 2017)

The US Preventive Services Task Force (USPSTF) affirmed the long-standing practice of screening pregnant women for preeclampsia with blood pressure measurements throughout pregnancy [69]. In contrast to traditional practice, they concluded that evidence does not support point-of-care urine testing to screen for preeclampsia. We suggest testing for proteinuria at the first prenatal visit to establish a baseline and, given the possibility for false-positives and false-negatives, repeating the test in asymptomatic normotensive patients on at least one subsequent prenatal visit. (See "Preeclampsia: Clinical features and diagnosis", section on 'Screening'.)

Maternal Tdap vaccination and prevention of infant pertussis (May 2017)

Immunization with the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended for women during each pregnancy in order to provide passive protection against pertussis to their infants. Although passive transfer of maternal antibodies can blunt the infant's own immune response to infant doses of the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine, it does not appear to interfere with clinical vaccine efficacy. In a retrospective study of nearly 150,000 infants at every level of DTaP vaccine exposure, infants exposed in utero to Tdap vaccine were better protected against pertussis during the first year of life than infants not exposed in utero [70]. (See "Immunizations during pregnancy", section on 'Rationale, efficacy, and safety'.)

Computerized interpretation and alerts for intrapartum fetal monitoring not beneficial (April 2017)

Two randomized trials (FM-ALERT [71] and INFANT [72]) have evaluated the use of continuous intrapartum fetal monitoring with computerized interpretation and real-time alerts versus usual care (continuous intrapartum fetal monitoring with clinician interpretation). In both trials, use of the intervention did not improve any maternal or neonatal outcome. In the larger INFANT trial, which included over 47,000 pregnancies at or near term, developmental assessment at age two years was similar for both groups [72]. Thus, a change in the standard clinical approach to intrapartum fetal heart rate monitoring is unwarranted. (See "Intrapartum fetal heart rate assessment", section on 'Use of decision aids'.)

Expulsion following immediate postpartum intrauterine device insertion (March 2017)

Women may choose to have a copper or levonorgestrel-releasing intrauterine device (IUD) inserted immediately postpartum. In a prospective study, the expulsion rate for the levonorgestrel-releasing IUD was higher than that for the copper IUD at six months postpartum (17 versus 4 percent) [73]. Although further data from a large trial are required to confirm this finding, we counsel women that the risk of expulsion may be higher with the levonorgestrel-releasing device and discuss the need to check for the IUD thread intermittently. (See "Postpartum contraception", section on 'Device selection'.)

Sensitivity of short cervix and fetal fibronectin for preterm birth (March 2017)

Cervical length is measured sonographically in the midtrimester because a short cervix is predictive of preterm birth, and the risk may be reduced by administration of progesterone. A new large prospective study reported the sensitivity for preterm birth among nulliparous women with singleton gestations and cervical length ≤25 mm was 8 percent at 16 to 22 weeks of gestation and 23 percent at 22 to 30 weeks [74]. Although these values are lower than previously reported in nonintervention studies, a major limitation of the study was unblinding when the cervix was very short (<15 mm), and probable intervention in these patients. The study also confirmed previous data that midtrimester measurement of fetal fibronectin in asymptomatic nulliparous women performs poorly for prediction of preterm birth. We continue to obtain a cervical length measurement in nulliparous women during ultrasound examinations at 18 to 24 weeks of gestation and treat those with a short cervix with vaginal progesterone. (See "Second-trimester evaluation of cervical length for prediction of spontaneous preterm birth in singleton gestations", section on 'Universal versus selective screening' and "Preterm birth: Risk factors and interventions for risk reduction", section on 'Biomarkers'.)

Pregnancy outcomes with HPV vaccination (March 2017)

Human papillomavirus (HPV) vaccination during pregnancy is not recommended, but mounting evidence suggests that it is safe. In a large cohort study from Denmark, the risks of spontaneous abortion, major birth defects, preterm birth, and low birth weight were comparable among women who received quadrivalent HPV vaccine during pregnancy (mostly during the first trimester) and matched controls who did not [75]. Women who inadvertently receive HPV vaccine during pregnancy can be reassured that it does not increase their risk of adverse pregnancy or fetal outcomes. (See "Immunizations during pregnancy", section on 'Human papillomavirus'.)

New classification and guidance regarding suboptimally dated pregnancy (March 2017)

The American College of Obstetricians and Gynecologists now classifies pregnancies as "suboptimally dated" in the absence of an ultrasound examination before 220/7ths weeks of gestation [76]. Because fetal biometry after 22 weeks is not sufficiently accurate to change menstrual dating without correlative sonographic follow-up, serial examinations three to four weeks apart are advised in these cases to assess growth over time. Normal interval growth supports the sonographic estimate of gestational age, while suboptimal or accelerated interval growth suggests that the gestational age may be further along or less advanced than predicted by ultrasound. (See "Prenatal assessment of gestational age and estimated date of delivery", section on 'Assigning the estimated date of delivery'.)

Recommended immunization schedule—United States, 2017 (March 2017)

The Advisory Committee on Immunization Practices has released the 2017 recommended immunization schedule for children and adolescents in the United States [77,78]. New recommendations include the following:

All infants should now receive monovalent hepatitis B vaccine within 24 hours of birth; earlier recommendations allowed some infants born to hepatitis B surface antigen-negative mothers to receive the vaccine after discharge. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Mother's HBsAg status unknown, birth weight ≥2 kg'.)

When administered during pregnancy, the tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine should be given as early as possible between 27 and 36 weeks of gestation. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

For individuals receiving the meningococcal serogroup B vaccine MenBFHbp (Trumenba), two doses are recommended for healthy adolescents and young adults who are not at increased risk for meningococcal disease. Three doses are recommended for individuals ≥10 years of age at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks (table 3). Previously, three doses were recommended for all recipients. The dosing frequency and interval for the other serogroup B vaccine, MenB-4C (Bexsero), have not changed. (See "Meningococcal vaccines", section on 'Serogroup B meningococcus vaccines'.)

Aspirin for prevention of preeclampsia (February 2017)

Low-dose aspirin therapy during pregnancy reduces the occurrence of preeclampsia in high-risk women, but questions remain about optimum dosing and timing. In one recent meta-analysis, the optimum aspirin dose appeared to be 100 to 150 mg, with favorable effects limited to initiation before 16 weeks of gestation [79]. In another recent meta-analysis with a different design, aspirin was similarly effective whether initiated before or after 16 weeks of gestation; optimum dosing was not assessed [80]. For women at high risk of developing preeclampsia, we continue to suggest initiating aspirin 81 mg daily at the end of the first trimester because this dose is readily available and early initiation is both safe and effective. If aspirin is not initiated at this time, initiation after 16 weeks, but before symptoms develop, also appears to be effective. (See "Preeclampsia: Prevention", section on 'Meta-analysis'.)

Folic acid supplementation for prevention of neural tube defects (February 2017)

Folic acid supplementation and food fortification have reduced the incidence of neural tube defects (NTDs). A 2017 systematic review by the US Preventive Services Task Force (USPSTF) noted that post-food fortification studies of folic acid supplementation have not demonstrated a protective association [81], suggesting that current levels of food fortification may be sufficient to prevent most folate-sensitive NTDs. However, the USPSTF also reaffirmed its 2009 recommendation that all women of reproductive age planning or capable of pregnancy take a supplement containing 0.4 to 0.8 mg of folic acid daily to reduce their risk of having a child with a NTD [82]. Given the limitations of the post-food fortification studies, we agree with this recommendation. (See "Folic acid supplementation in pregnancy".)

Delayed cord clamping (January 2017)

Delaying umbilical cord clamping for at least 30 to 60 seconds after birth in both term and preterm vigorous infants is the recommendation of an updated committee opinion by the American College of Obstetricians and Gynecologists (ACOG) [83]. Previously, ACOG had recommended individualizing the timing of cord clamping in term infants. Although the optimal amount of time before cord clamping has not been studied extensively, we believe data support a minimum duration of delay of at least one minute in term births and 30 seconds in preterm births. (See "Management of normal labor and delivery", section on 'Cord clamping'.)

PEDIATRICS: GENERAL PEDIATRICS

Low-dose ferrous sulfate for iron deficiency anemia (June 2017)

For infants and children with iron deficiency anemia, standard oral iron dosing is 3 to 6 mg/kg elemental iron per day, but the optimal dose and preparation have not been established. Now, a study reports that ferrous sulfate 3 mg/kg once daily without food was effective in most patients and was more effective than an equivalent dose of an iron polysaccharide complex formulation [84]. These findings support administering ferrous sulfate at the low end of the standard dose range as first-line treatment for nutritional iron deficiency in children. (See "Iron deficiency in infants and young children: Treatment", section on 'Dose and scheduling'.)

Self-administered hypnotherapy for functional abdominal pain in children and adolescents (June 2017)

Increasing evidence suggests that gut-directed hypnotherapy reduces pain frequency and intensity in children and adolescents with functional abdominal pain disorders (FAPDs). In a trial of this therapy that randomly assigned children (age 8 to 18 years) with FAPDs to a self-administered home-based approach using a compact disc or to individual therapy with a qualified therapist for three months, over 60 percent of each group had ≥50 percent reduction in pain frequency and intensity at one-year follow-up [85]. These findings suggest that self-directed hypnotherapy is a reasonable option for children and adolescents with FAPDs, particularly if trained therapists are not available. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Improved coping'.)

New guidelines for management of peanut and tree nut allergies (June 2017)

The most straightforward approach in managing any food allergy is complete avoidance of the culprit food and all similar foods, particularly for peanut and tree nuts. However, some patients may find this approach too burdensome. Reflecting a shift in clinical practice, the recent British Society of Allergy and Clinical Immunology guidelines permit, with certain restrictions, consumption of similar foods after confirming that they are safe, if the patient and family prefer this approach [1]. This guideline for the management of peanut and tree nut allergy is consistent with our approach. (See "Peanut, tree nut, and seed allergy: Management", section on 'Clinical scenarios'.)

Updated American Academy of Pediatrics guidelines on fruit juice for infants (June 2017)

Updated guidelines from the American Academy of Pediatrics (AAP) recommend avoiding fruit juice for infants younger than 12 months; previous guidelines recommended avoiding fruit juice for infants younger than 6 months [86]. Fruit juice provides no nutritional benefit over mashed or puréed whole fruit and may have adverse consequences, such as undernutrition, overnutrition, diarrhea, flatulence, abdominal distension, and dental caries. We agree with the AAP recommendation and now suggest mashed or puréed whole fruit rather than fruit juice for infants age 6 to 12 months. (See "Introducing solid foods and vitamin and mineral supplementation during infancy", section on 'Beverages to avoid'.)

Medical use of prescription opioid medications and misuse in adolescents (May 2017)

Surveys of high school seniors in the United States over 40 years show that the use of prescription opioids is strongly correlated with misuse in adolescents and that misuse typically follows medical use by the patient [87]. Thus, health care providers should follow safe prescribing guidance for prescription opioids, including use of alternatives (eg, acetaminophen or ibuprofen) to control pain whenever possible, using the lowest effective dose and minimum quantity of prescription opioid medications when they are needed, and utilizing prescription drug monitoring programs, where available, to identify patients or caregivers who might be misusing (ie, abusing or diverting) prescription opioid medications. (See "Opioid intoxication in children and adolescents", section on 'Safe prescribing'.)

Safe storage of prescription opioids (May 2017)

Although safe storage of prescription opioid medications (eg, locked cabinet) is recommended, it infrequently occurs. In a United States nationally representative survey of over 1000 adults with prescription opioid use in the past 12 months, only 9 percent reported safe storage of their medications [88]. In further analysis of those adults with children younger than 18 years of age in the household, safe storage was reported in less than one-third of households with young children and 12 percent of households with children older than six years of age [89]. These results support the need for anticipatory guidance by health care providers, emphasizing opioid safe storage and how it may limit opioid misuse and overdose, especially in households with children and adolescents. Further research should focus on developing and implementing effective means of secure storage in households. (See "Opioid intoxication in children and adolescents", section on 'Safe storage'.)

Persistence of neurotoxicity of childhood lead poisoning into adulthood (May 2017)

Detectable blood lead levels (BLLs) are associated with irreversible neurocognitive deficits in children and a BLL lower limit for this toxicity has not been established. Previous studies had shown that this effect persists into adolescence. In a longitudinal cohort study of over 1000 patients, lead exposure, based upon BLLs obtained at 11 years of age, was associated in a dose-dependent fashion with lower intelligence quotient (IQ) and lower socioeconomic status at age 38 years after adjustment for maternal IQ, child IQ, and childhood socioeconomic status [90]. Thus, childhood lead exposure causes neurotoxicity that persists into adulthood. Primary prevention of lead exposure, including in pregnant women, can prevent these effects. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Neurologic'.)

Safety warnings issued for codeine and tramadol in breastfeeding women and children under age 12 years (April 2017)

The US Food and Drug Administration (FDA) issued a strong warning to restrict use of codeine and tramadol in breastfeeding women and children <12 years old because of increasing reports of life-threatening respiratory depression in young children exposed to these drugs [91]. Children who are ultra-rapid metabolizers metabolize these drugs faster than normal, leading to dangerously high levels of active drug. We suggest avoiding codeine and tramadol in breastfeeding women and children <12 years old. (See "Evaluation and management of pain in children", section on 'Agents not recommended'.)

Prevention of concussion in children playing hockey (April 2017)

Evidence is limited regarding specific interventions to prevent sport-related concussion. In a prospective study of the effect of a Canadian rule change on age eligibility for body checking in youth hockey, the rate of concussions decreased by 64 percent among 11- and 12-year-old hockey players after the eligible age for checking was raised to 13 years [92]. Thus, limiting types of contact until an older age appears to be an effective strategy to reduce the risk of concussion in younger players, although prior studies suggest that the risk of injuries other than concussion may be increased when players are introduced to body checking in subsequent seasons. (See "Concussion in children and adolescents: Management", section on 'Prevention'.)

High risk for vascular complications in youth with type 2 diabetes (April 2017)

In a large prospective study following outcomes in youth who had been diagnosed with diabetes before age 20, those with type 2 diabetes mellitus (T2DM) had high rates of diabetic kidney disease, retinopathy, and neuropathy (20, 9, and 18 percent, respectively) after a mean diabetes duration of eight years [93]. Moreover, the risk of these complications was more than twofold higher than in those diagnosed with type 1 diabetes mellitus (T1DM), after adjustment for age, disease duration, glycemia, and obesity. These findings emphasize the need to monitor youth with either T2DM or T1DM for development of complications. (See "Comorbidities and complications of type 2 diabetes mellitus in children and adolescents", section on 'Introduction'.)

Maternal obesity and risk of cerebral palsy (March 2017)

Maternal obesity has been associated with several adverse pregnancy outcomes. Now, a population-based cohort study from Sweden has reported an increasing risk of cerebral palsy in offspring delivered at term as maternal body mass index (BMI) increases [94]. Although this observation requires confirmation, we continue to advise overweight and obese women to try to achieve a normal BMI before becoming pregnant because of established pregnancy and general health benefits. (See "Obesity in pregnancy: Complications and maternal management", section on 'Neurodevelopment'.)

Safety and efficacy of nonoperative treatment of pediatric appendicitis (March 2017)

In a meta-analysis of 10 studies that provided outcomes for over 400 children undergoing nonoperative treatment (antibiotics without immediate surgery) of early, uncomplicated appendicitis, initial treatment was effective in 97 percent of patients and was associated with no appendectomy at reported follow-up in 82 percent of patients [95]. Complications and total length of hospital stay appeared similar during follow-up for nonoperative treatment and appendectomy. Although appendectomy remains the treatment of choice for most children with early, uncomplicated appendicitis, nonoperative management is an alternative option in selected patients based upon caregiver preference. Additional studies are needed to determine which patients are least likely to fail nonoperative treatment. (See "Acute appendicitis in children: Management", section on 'Nonoperative management'.)

Smartphone-integrated infant physiologic monitors not beneficial (March 2017)

A new class of smartphone-integrated infant physiologic monitors with sensors built into socks, clothing, or diaper clips is being marketed directly to consumers. There is no evidence that these devices have any benefit for prevention of sudden infant death syndrome (SIDS) or any other adverse outcome. Moreover, concerns have been raised that parents might feel falsely reassured by the use of such devices and fail to use established SIDS preventive practices [96]. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'No benefit from home monitors'.)

E. coli O157:H7 outbreak associated with soy nut butter (March 2017)

Escherichia coli O157:H7, which causes bloody diarrhea and is associated with the hemolytic-uremic syndrome, is typically transmitted through contaminated beef products and produce, but other foods have also been implicated in outbreaks. In the United States, a particular brand of soy nut butter (I.M. Healthy) has been linked to a multistate E. coli O157:H7 outbreak that has affected mainly children [97]. Although the soy nut butter products have been recalled, individuals should be advised to avoid and discard any remaining product, and the possibility of E. coli O157:H7 infection should be considered in exposed patients with diarrheal illnesses. Details on the outbreak can be found on the Centers for Disease Control and Prevention website. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)

Early initiation of heated humidified high-flow nasal cannula therapy in children with bronchiolitis (February 2017)

In an open randomized trial comparing heated humidified high-flow nasal cannula (HFNC) with standard low-flow oxygen therapy in 200 children with moderately severe bronchiolitis, early initiation of HFNC did not shorten the median duration of oxygen therapy (approximately 22 hours in both groups) [98]. However, HFNC was associated with avoidance of intensive care unit admission when it was used as a rescue therapy for clinical deterioration in children treated with standard therapy. No serious adverse effects occurred. These findings provide additional support for HFNC as a rescue therapy in children with bronchiolitis, although the efficacy of this approach remains unproven. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on 'HFNC and CPAP'.)

Tonsillectomy or watchful waiting for children with recurrent throat infections (February 2017)

A systematic review of studies comparing tonsillectomy with watchful waiting for children with mild to moderate recur­rent throat infections concluded that tonsillectomy provided a modest reduction in number of throat infections and health care utilization in the first postsurgical year, but little to no long-term difference in these outcomes or quality of life [99]. Hence, we suggest not performing tonsillectomy in children who are only mildly or moderately affected. Tonsillectomy is an option for children who are severely affected (ie, ≥7 episodes in one year, ≥5 episodes in each of two years, or ≥3 episodes in each of three years), although watchful waiting is a reasonable alternative. The decision should be made on a case-by-case basis after weighing the risks and benefits in the individual child, and the values and preferences of the family and child. (See "Tonsillectomy and/or adenoidectomy in children: Indications and contraindications", section on 'Mildly or moderately affected children'.)

Updated American Academy of Pediatrics guidelines for developmental dysplasia of the hip (January 2017)

The American Academy of Pediatrics has released updated guidelines for evaluation and referral of infants with developmental dysplasia of the hip (DDH) [100]. Changes from the previous guidelines include the option for infants with a reduced femoral head that is dislocatable or subluxatable (ie, a positive Barlow test) to be followed with serial physical examinations by the primary care clinician rather than an orthopedic surgeon. The update also included breech presentation as a risk factor for male as well as female infants and clarified that breech presentation refers to breech position during the third trimester, whether or not the infant was delivered by cesarean section. (See "Developmental dysplasia of the hip: Clinical features and diagnosis", section on 'Approach to diagnosis and referral'.)

Obesity trends in low-income preschool-aged children (January 2017)

After peaking in 2004, the overall prevalence of obesity in preschool-aged children in the United States has declined, although rates among low-income children remained high. A new study reports a modest decrease in obesity rates from 2010 to 2014 among these low-income children, and this trend was reflected in a majority of states [101]. Nevertheless, obesity rates among low-income children continue to exceed those in the general population, highlighting the continued need for preventive efforts among this high-risk group. (See "Definition; epidemiology; and etiology of obesity in children and adolescents", section on 'Trends'.)

Early physical activity following acute concussion in children and adolescents (January 2017)

Although physical rest is routinely recommended after concussion, there are few data to determine whether avoidance of physical activity hastens recovery. In a prospective, multicenter cohort study of over 2400 children who were diagnosed with an acute concussion during an emergency department visit, early physical activity (within seven days of injury) compared with physical rest was associated with a significantly reduced risk of persistent postconcussive symptoms (PPCS) at 28 days [102]. However, the difference in PPCS may be the result of confounding, and clinical trials are needed to confirm this result. We suggest that children and adolescents with concussions adhere to full physical rest until they have no symptoms of concussion (table 4) and normal balance or return to baseline on standardized testing. In the minority of patients with prolonged symptoms beyond seven days after injury, we introduce light, subsymptom threshold aerobic exercise (eg, light stationary bicycling), which can often be tolerated and may improve symptoms. (See "Concussion in children and adolescents: Management", section on 'Physical rest'.)

Duration of treatment for acute otitis media in children younger than two years (January 2017)

Methodologic limitations in previous studies evaluating duration of treatment for acute otitis media (AOM) in young children were addressed in a trial that randomly assigned more than 500 infants and young children (age 6 through 23 months) with strictly defined AOM to treatment with amoxicillin-clavulanate for 10 days or 5 days; those assigned to 5 day treatment received an additional 5 days of placebo [103]. The 10-day group had lower rates of clinical failure (16 versus 34 percent) without more adverse events. These findings support a standard 10-day course of antimicrobial therapy for AOM in children <2 years. (See "Acute otitis media in children: Treatment", section on 'Duration of therapy'.)

PEDIATRIC IMMUNIZATIONS

Recommended immunization schedule—United States, 2017 (March 2017)

The Advisory Committee on Immunization Practices has released the 2017 recommended immunization schedule for children and adolescents in the United States [77,78]. New recommendations include the following:

All infants should now receive monovalent hepatitis B vaccine within 24 hours of birth; earlier recommendations allowed some infants born to hepatitis B surface antigen-negative mothers to receive the vaccine after discharge. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Mother's HBsAg status unknown, birth weight ≥2 kg'.)

When administered during pregnancy, the tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine should be given as early as possible between 27 and 36 weeks of gestation. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

For individuals receiving the meningococcal serogroup B vaccine MenBFHbp (Trumenba), two doses are recommended for healthy adolescents and young adults who are not at increased risk for meningococcal disease. Three doses are recommended for individuals ≥10 years of age at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks (table 3). Previously, three doses were recommended for all recipients. The dosing frequency and interval for the other serogroup B vaccine, MenB-4C (Bexsero), have not changed. (See "Meningococcal vaccines", section on 'Serogroup B meningococcus vaccines'.)

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