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What's new in primary care
Official reprint from UpToDate® ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
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What's new in primary care
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2017. | This topic last updated: Dec 06, 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.


IUD use associated with lower cervical cancer incidence (November 2017)

Prior studies have suggested that intrauterine devices (IUDs), one of the most reliable forms of long-acting reversible contraception, are associated with a reduction in cervical cancer. Now, a meta-analysis including 16 studies reported that the incidence of cervical cancer was reduced by about one-third in IUD users compared with nonusers [1]. This protective effect is particularly important for women at higher risk of cervical cancer, such as those who have not received the human papillomavirus vaccine or who do not have access to cervical cancer screening. It is not known if the type of device influences the reduction in cervical cancer risk. (See "Intrauterine contraception: Devices, candidates, and selection", section on 'Benefits'.)

Insufficient sleep and cardiometabolic risk (November 2017)

Short sleep duration has been associated with a variety of adverse cardiovascular outcomes in cross-sectional and small prospective studies. In the largest prospective study to date of over 160,000 healthy, nonobese adults, self-reported sleep duration <6 hours per day was associated with the development of multiple cardiometabolic risk factors over an 18-year follow-up period, including central obesity, elevated fasting glucose, hypertension, low high-density lipoprotein cholesterol, hypertriglyceridemia, and metabolic syndrome [2]. Increases in relative risk ranged from 6 to 12 percent for each individual factor. Healthy sleep behavior is recommended by the American Heart Association and others to promote optimal cardiac health. (See "Insufficient sleep: Definition, epidemiology, and adverse outcomes", section on 'Cardiovascular morbidity'.)

Chemical constituents released by heat-not-burn (HNB) tobacco cigarettes (August 2017)

Heat-not-burn (HNB) tobacco cigarettes use an electric blade to heat a tobacco stick to a temperature much below that at which traditional tobacco cigarettes burn. In a laboratory study, HNB tobacco cigarettes released lower amounts of harmful constituents (nicotine, polycyclic aromatic hydrocarbons, and carbon monoxide) than conventional tobacco cigarette smoke [3]. Whether this translates to lower health risks is uncertain. HNB products are not currently available in many countries, including the United States. (See "Patterns of tobacco use", section on 'Heat-not-burn tobacco cigarettes'.)

Bisphosphonates not protective against breast cancer in postmenopausal women (August 2017)

Although some studies have suggested a protective effect of bisphosphonates against breast cancer, others, including a large observational cohort of over 64,000 postmenopausal women followed for approximately seven years [4], have not. Studies may be confounded by the frequent use of bisphosphonates to treat osteoporosis, and women with osteoporosis are more likely to have a lower estrogen environment and therefore a lower baseline risk of breast cancer regardless of bisphosphonate exposure. (See "Factors that modify breast cancer risk in women", section on 'Bisphosphonates'.)

Changes in diet quality and mortality (July 2017)

Recommendations for a healthy diet focus on increasing intake of fruits, vegetables, legumes, nuts, and whole grains and limiting intake of saturated and trans fat, free sugars, and salt. In a pooled analysis of two large cohort studies, greater improvement in diet quality over a 12-year period was associated with decreased all-cause mortality over the next 12 years [5]. A 20-percentile increase in quality score, which could be accomplished by increasing consumption of nuts and legumes from no servings to one serving per day and reducing the consumption of red and processed meats from 1.5 servings per day to little consumption, for example, was associated with a nearly 20 percent decrease in risk of death over 12 years. These observations support our recommendations for a healthy diet. (See "Healthy diet in adults", section on 'Types of diet'.)


Canadian Task Force on Preventive Health Care's new abdominal aortic aneurysm screening guidelines (September 2017)

Risk factors for abdominal aortic aneurysm (AAA) include older age, male sex, and smoking. In new guidelines, the Canadian Task Force on Preventive Health Care (CTFPHC) recommends one-time screening for AAA with ultrasonography in men aged 65 to 80 years [6]. The CTFPHC recommendation extends the upper age limit (75 years) recommended by others, including the US Preventive Services Task Force (USPSTF), and does not differentiate by smoking status. UpToDate and the USPSTF recommend screening men age 65 to 75 who smoke and only selectively screening never-smokers. (See "Screening for abdominal aortic aneurysm", section on 'Canadian guidelines'.)

Genome sequencing in healthy people (August 2017)

Whether exome or genome sequencing (DNA sequencing of all genes, or all genes plus non-coding regions, respectively) provides clinical value for healthy people is not known. In a trial in one network of academic primary care practices, 100 healthy patients were randomly assigned to receive genetic risk information based on family history alone or family history plus genome sequencing [7]. Health care use, patient outcomes, and patient behavior changes were assessed at six months. The appropriateness of primary care physician (PCP) management of results was assessed by a group of clinician-geneticists. Compared with family history alone, gene sequencing information led to more new clinical actions (34 versus 16 percent) and more patients making behavior changes (41 versus 30 percent). Geneticists judged that PCP management of gene testing results was appropriate nearly three-quarters of the time. These results demonstrate that findings from genomic testing are most often managed appropriately by PCPs, but the long-term benefits versus harms and costs of routine genome sequencing in healthy people remains to be determined. (See "Principles and clinical applications of next-generation DNA sequencing", section on 'Healthy people'.)

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 [8]. 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".)


Coffee consumption and health (December 2017)

For most nonpregnant adults, moderate coffee consumption appears to be safe. In a review of meta-analyses of largely observational studies of multiple health outcomes, coffee consumption was more often associated with benefit than with harm [9]. Drinking three to four cups of coffee per day was associated with the greatest benefit. Harmful associations were largely absent after adjustment for smoking except in pregnancy, where high consumption was associated with an increase in risk of low birth weight, preterm delivery, and pregnancy loss. Given the limitations of observational studies, UpToDate neither promotes nor discourages coffee consumption in nonpregnant adults but discourages more than 200 to 300 mg of caffeine intake per day in women who are pregnant or attempting to conceive. (See "Benefits and risks of caffeine and caffeinated beverages" and "The effects of caffeine on reproductive outcomes in women".)

Prevalence of high blood pressure in United States adults under the 2017 revised definition of hypertension (November 2017)

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines changed the definition of hypertension in adults (now defined as a systolic pressure ≥130 mmHg and/or a diastolic pressure ≥80 mmHg). This has substantially changed the prevalence of hypertension among adults in the United States. According to NHANES data from 2011 to 2014, 46 percent of adults 18 years and older had hypertension [10]. Based upon the size of the adult population, this translates into 103 million adults in the United States with hypertension. (See "The prevalence and control of hypertension in adults", section on 'Prevalence of hypertension'.)

New criteria for hypertension in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines (November 2017)

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, with input from the American Society of Hypertension (ASH) as well as geriatrics, pharmacist, and nursing organizations, provide guidance for the prevention, detection, evaluation, and management of hypertension in adults [11]. Major changes from prior recommendations include a lower threshold for the diagnosis of hypertension based upon office blood pressure readings (hypertension now defined as a blood pressure ≥130 mmHg systolic or ≥80 mmHg diastolic), and a lower blood pressure goal (<130/<80 mmHg). Pharmacologic therapy is recommended for all hypertensive patients with a higher cardiovascular risk, and for lower-risk patients who have a blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic. Recommendations in UpToDate are broadly consistent with these guidelines. (See "What is goal blood pressure in the treatment of hypertension?" and "Overview of hypertension in adults" and "Blood pressure measurement in the diagnosis and management of hypertension in adults" and "The prevalence and control of hypertension in adults".)

E-cigarette use as a precursor to conventional cigarette smoking (November 2017)

Whether use of e-cigarettes by youth is associated with future initiation of conventional cigarette smoking has important implications for health. A large systematic review and meta-analysis of longitudinal studies among individuals aged 14 to 30 years showed that, compared with e-cigarette never-users, ever-users had a higher probability of initiating cigarette smoking (31 versus 8 percent) [12]. These studies do not distinguish if e-cigarette use increases the desire to smoke conventional cigarettes or whether e-cigarette users have a predisposition to smoke. Nonetheless, the finding of a greater likelihood of future conventional smoking among younger e-cigarette users is useful information for clinicians when educating patients about risks of tobacco use. (See "E-cigarettes", section on 'Effect on smoking initiation among youth'.)

Patterns of sedentary behavior and mortality (October 2017)

Extended sedentary time has been associated with mortality in numerous studies. In addition to the total daily duration of sitting, the risk of mortality may be higher among those who sit for prolonged, uninterrupted periods as compared with those who sit for shorter, interrupted periods. In a study of nearly 8000 middle-aged and older adults, sedentary time was measured with an accelerometer [13]. Both total sedentary time and episodes of prolonged, uninterrupted inactivity were associated with higher risk for death. Those participants with high sedentary time (≥12.5 hours/day) and longer episodes of inactivity (≥10 min/episode) had the highest risk for death. (See "The benefits and risks of exercise", section on 'Physical inactivity and health'.)

Single-dose secnidazole for bacterial vaginosis (September 2017)

Metronidazole is a preferred treatment for bacterial vaginosis (BV) and is given topically or orally as a multi-day course. In September 2017, the US Food and Drug Administration approved secnidazole, a related oral antibiotic with a longer half-life, for the treatment of BV [14]. In an earlier study, a single dose of secnidazole was as effective as, but not superior to, metronidazole for seven days. Secnidazole is an option for BV when a single dose is desired (eg, to enhance adherence), but it is more expensive than other regimens. (See "Bacterial vaginosis: Treatment", section on 'Secnidazole'.)

Gabapentinoids not effective for chronic low back pain (September 2017)

A meta-analysis evaluating gabapentinoids (gabapentin or pregabalin) for the treatment of chronic low back pain included eight randomized trials, which were evaluated as three groups [15]. Gabapentin, compared with placebo, resulted in a minimal and nonsignificant improvement in pain, and gabapentin increased the risk of side effects (primarily dizziness, fatigue, mentation difficulties). Pregabalin as primary therapy was less effective than other analgesics. In the largest study of pregabalin as adjuvant therapy, no additive benefit was found, although the adjuvant studies were too heterogeneous to pool. We suggest not treating patients for chronic low back pain with gabapentinoids. (See "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment", section on 'Antiepileptic medications'.)

Effect of intensive blood pressure lowering on patient-reported quality of life (August 2017)

Intensive blood pressure lowering in patients at high cardiovascular risk reduces cardiovascular events and mortality, but whether intensive therapy adversely affects patients' assessments of their quality of life is unknown. In a secondary analysis of the SPRINT trial comparing outcomes of higher and lower blood pressure targets in nondiabetic patients with hypertension and increased cardiovascular risk, there were no differences between treatment groups in terms of physical and mental health-related quality of life, symptoms of depression, or satisfaction with care [16]. These results suggest that the benefits from intensive blood pressure lowering are not diminished by any effect on quality of life. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Benefit according to overall cardiovascular risk'.)

Evaluation for occult cancer in unprovoked venous thromboembolism (August 2017)

Whether patients with a diagnosis of unprovoked venous embolism (VTE) should be evaluated for occult cancer with an extensive or more limited strategy is controversial. In a meta-analysis of 10 prospective studies (over 2000 patients with unprovoked VTE), the prevalence of cancer at one year was 5 percent [17]. Extensive screening, performed in nearly 60 percent of patients, detected more cancer initially than limited evaluation, but the difference was not significant at one year. The effect on long-term mortality is unknown. Until the benefits of extensive evaluation strategies are proven, we suggest evaluating patients with a single episode of unprovoked VTE using a limited strategy (clinical examination, routine laboratory studies, chest radiography, and age-appropriate screening) for the detection of occult cancer. (See "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors", section on 'First episode of uncomplicated unprovoked VTE'.)

Electroacupuncture for stress urinary incontinence in women (August 2017)

Treatment options for stress urinary incontinence (SUI) in women include lifestyle modifications, bladder training, medications, devices, and surgery. The use of electroacupuncture for SUI has been reported in a multicenter randomized trial in China [18]. Compared with sham treatments, electroacupuncture reduced the volume of urine leaked and number of leakage episodes. Availability of this therapy may limit this option. Additionally, confirmation of these results in other trial settings is needed before its general use can be widely recommended. (See "Treatment of urinary incontinence in women", section on 'Other specialty treatments'.)

Mindfulness-based stress reduction for low back pain (August 2017)

Mindfulness-based stress reduction (MBSR) is a mind-body intervention that can be administered in group settings by laypersons. In a meta-analysis of seven randomized trials involving 864 patients with low back pain of any duration, MBSR led to modest short-term improvements in pain intensity and physical functioning compared with usual care [19]. MBSR is a reasonable option for the management of low back pain. (See "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment", section on 'Mind-body interventions'.)

Bevacizumab for macular edema associated with central retinal vein occlusion (August 2017)

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are first-line therapy for macular edema associated with central retinal vein occlusion (CRVO). In the United States, bevacizumab, which is considerably less expensive than other anti-VEGF drugs, is not approved to treat this condition. In a randomized trial of 362 patients with CRVO, improvements in the visual acuity letter score were comparable in patients treated with intravitreal bevacizumab or aflibercept after six months of therapy [20]. We offer bevacizumab as one anti-VEGF option for the treatment of CRVO. (See "Retinal vein occlusion: Treatment", section on 'Evidence of effectiveness for CRVO'.)

ACC/AHA/HRS guideline for the evaluation and management of syncope (July 2017)

In 2017 the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) published guidelines on evaluation and management of patients with syncope, the first major new syncope guidelines in eight years [21]. The guidelines present an approach to the evaluation and management of patients with syncope that is consistent with the approach advocated by UpToDate experts. Both UpToDate and the ACC/AHA/HRS guidelines emphasize the importance of a detailed medical history, physical examination, and review of an electrocardiogram as the initial evaluation in all patients. An echocardiogram should be performed in patients with known or suspected structural heart disease, with selected additional testing directed by the results of the initial evaluation. (See "Syncope in adults: Clinical manifestations and diagnostic evaluation", section on 'Initial evaluation'.)

Worldwide tobacco use patterns (July 2017)

New data show that smoking patterns differ greatly among countries. The Global Burden of Disease, Injuries, and Risk Factors Study 2015 (GBD), a systematic analysis of smoking prevalence among 195 countries, found that for men, the worldwide age-standardized prevalence of daily smoking was 25 percent, with the country-specific rate varying from 4 to 47 percent, and for women, the worldwide average was 5 percent, with the country-specific rate varying from 1 to 44 percent [22]. Smoking rates also varied by a sociodemographic index (SDI), with worldwide smoking rates higher in higher SDI quintiles, but with an inverse relationship in the United States where smoking rates were highest among those with less income and education. Understanding smoking prevalence patterns may help to inform smoking eradication efforts. (See "Patterns of tobacco use", section on 'Prevalence'.)

Psychiatric side effects of finasteride and dutasteride therapy (June 2017)

Concerns have been raised about possible psychiatric side effects of 5-alpha-reductase inhibitors for the management of benign prostatic hyperplasia. In a retrospective cohort study of over 90,000 men prescribed finasteride or dutasteride between 2003 and 2010, there was no increased risk of suicide compared with matched controls [23]. However, 5-alpha-reductase inhibitors were associated with an increased risk of self-harm and depression during the initial 18 months of therapy. Discontinuation of these medications may be appropriate if depression develops. (See "Medical treatment of benign prostatic hyperplasia", section on 'Side effects'.)

Intradiscal glucocorticoid injection and chronic low back pain with active discopathy (June 2017)

Chronic back pain exacerbations are sometimes related to inflammation of an intervertebral disc ("active discopathy"), which can be detected on magnetic resonance imaging (MRI) scan. In a randomized trial of 135 patients with chronic low back pain and active discopathy comparing a single injection of prednisolone and contrast with contrast alone, pain reduction at one month was greater in the prednisolone group (55 versus 33 percent) [24]. The groups did not differ in pain intensity at 12 months or in secondary outcomes at one or 12 months. In general, we do not suggest intradiscal glucocorticoid injections for patients with chronic low back pain. More research is needed to confirm its effectiveness and potential risks in the subgroup of patients that were studied. (See "Subacute and chronic low back pain: Nonsurgical interventional treatment", section on 'Intradiscal injection'.)

Comprehensive geriatric assessment before elective vascular surgery (June 2017)

Older adults undergoing vascular surgery have a high incidence of medical co-morbidities that increase the risk for perioperative morbidity and mortality. In a trial that compared comprehensive geriatric versus standard preoperative assessment in patients at least 65 years old undergoing major elective vascular surgical procedures, comprehensive geriatric assessment reduced postoperative complications and length of stay, with a trend toward fewer discharges to a higher level of dependency [25]. This trial underscores the need to accurately assess medical risk prior to undertaking elective vascular surgery in older adults. (See "Overview of lower extremity peripheral artery disease", section on 'Revascularization'.)

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 [26]. 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 [27].

In a cohort of low-risk patients 66 years and older who presented to their primary care physician with acute upper respiratory infection, 46 percent were treated with an antibiotic, with overprescribing rates highest for patients with acute bronchitis [28]. Physicians who saw high volumes of patients and mid- to late-career physicians were more likely to prescribe antibiotics.

These studies add further support to overuse and lack of benefit for routine use of antibiotics for patients with acute bronchitis. (See "Acute bronchitis in adults", section on 'Avoiding antibiotic overuse'.)

Lifetime risk of revision after total hip or knee replacement (June 2017)

Determining the best timing for total hip or knee replacement surgery for end-stage arthritis is challenging in younger patients because the replacement can fail over time. A population-based study evaluated the lifetime risk of revision surgery in adults aged 50 or older using data from a registry with over 63,000 total hip replacements and 54,000 total knee replacements [29]. The lifetime risk of revision surgery for either total hip or knee replacement in patients older than 70 years was about 5 percent, with no difference between men and women. The risk increased with decreasing age and was highest for men in their early 50s. For men aged 50 to 54, the lifetime risk of revision for total hip and knee replacement was 30 and 35 percent, respectively. These data suggest that there may be some benefit to delaying surgery, particularly among younger men. (See "Total hip arthroplasty", section on 'Indications' and "Total knee arthroplasty", section on 'Indications'.)


Countering the high cost of epinephrine autoinjectors (June 2017)

Physicians and patients in the United States have been struggling with the high cost of epinephrine autoinjectors, and alternatives, as well as ways to maximize the utility of expensive devices, have begun to appear:

A prefilled syringe (Symjepi) containing 0.3 mg epinephrine per dose was approved by the US Food and Drug Administration (FDA) in June 2017 and should offer a more affordable alternative to autoinjectors [30]. It will be available in upcoming months in just one dose, labeled for use in patients weighing ≥30 kg (66 lbs). (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Prefilled syringes'.)

A study of 31 expired autoinjectors (EpiPens) found that devices as much as four years past the expiration date still contained 84 to 88 percent of the intended epinephrine dose [31]. Thus, patients should understand that expired devices retain most of their potency and that if anaphylaxis develops, using an outdated device is preferable to not injecting epinephrine at all. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Use of expired autoinjectors'.)

Systemic symptoms in patients with chronic idiopathic urticaria (June 2017)

Patients with chronic idiopathic urticaria (CIU) sometimes report accompanying systemic symptoms, although the prevalence of such symptoms has not been specifically examined. In a study of 155 CIU patients presenting to a referral allergy clinic, 66 percent reported systemic symptoms, including headache, fatigue, joint pain or swelling, wheezing, flushing, gastrointestinal symptoms, and palpitations [32]. Patients with systemic symptoms had a greater disease burden compared with those without symptoms. Although this study population was probably skewed towards more severe disease, it is helpful to recognize that systemic symptoms are not uncommon in CIU. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Systemic symptoms'.)


Low dose rivaroxaban versus aspirin for secondary cardiovascular disease prevention (November 2017)

Rivaroxaban, an oral direct factor Xa inhibitor, has been evaluated for secondary prevention of cardiovascular disease (CVD). In a randomized trial, over 27,000 patients with stable CVD were assigned to a very low dose of rivaroxaban added to aspirin, rivaroxaban alone, or aspirin alone, with a mean follow-up of 23 months [33]. Compared with aspirin alone, rivaroxaban plus aspirin reduced cardiovascular mortality and ischemic stroke but not myocardial infarction. There were more major bleeding events in the rivaroxaban plus aspirin group, while the risk of intracranial hemorrhage was comparable with aspirin. The cardiovascular outcome was not different comparing rivaroxaban alone with aspirin alone, but there was more bleeding with rivaroxaban. Given the long clinical experience with aspirin, we generally prefer aspirin alone for patients with stable CVD. (See "Prevention of cardiovascular disease events in those with established disease or at high risk".)

Anacetrapib, a CETP inhibitor, improves cardiovascular outcomes (September 2017)

Cholesteryl ester transfer protein (CETP) inhibitors raise high density lipoprotein cholesterol (HDL-C) and lower low density lipoprotein cholesterol (LDL-C). However, previous randomized clinical trials of four different CETP inhibitors, for the most part, have found no benefit and some potential harm. In the recent REVEAL trial, over 30,000 adults with atherosclerotic vascular disease who were receiving intensive statin therapy were randomly assigned to receive the CETP inhibitor anacetrapib once daily or placebo [34]. During a median follow-up of over four years, fewer cardiovascular events occurred in the treatment group and there was no evidence of serious adverse events with anacetrapib. Most of the benefit could be attributed to LDL-C lowering. Further investigation is required to determine the role of CETP inhibitors in the management of dyslipidemia. (See "HDL cholesterol: Clinical aspects of abnormal values", section on 'CETP inhibition'.)

Statin awareness and reported muscle-related adverse events (August 2017)

In clinical practice, side effects with statins are common, which could be related in part to a heightened awareness of adverse reactions traditionally attributed to the drugs. In a randomized double-blind, placebo-controlled trial involving over 10,000 patients, atorvastatin therapy did not increase the rate of muscle-related adverse events (AEs) [35]. By contrast, in the non-randomized, non-blinded extension of the study, muscle-related AEs were reported more often in patients taking atorvastatin compared with placebo. These results suggest that some muscle-related AEs attributed to atorvastatin are not causally linked to the drug. (See "Statins: Actions, side effects, and administration", section on 'Side effects'.)


Selective androgen receptor modulators: Composition of products sold on the internet (November 2017)

Selective androgen receptor modulators (SARMs) are a class of compounds that have become popular as performance-enhancing drugs. None are approved for use, but many SARM products are sold via the internet, the majority with inaccurate labeling. In a study of 44 SARM products purchased from the internet and analyzed using procedures approved by the World Anti-Doping Agency, only 18 had accurate labeling (eg, they contained the correct SARM and dosage) [36]. Four products contained no active compounds at all, and the remainder were inaccurately labeled (most had at least one additional unapproved drug or substance [eg, growth hormone secretagogues and/or androgens]). (See "Use of androgens and other hormones by athletes", section on 'SARMs'.)

Thyroid hormone assay interference with biotin supplements (October 2017)

A growing number of reports have noted that ingestion of 5 to 10 mg of biotin (marketed over the counter to prevent hair loss) can cause artifactually low serum thyroid stimulating hormone (TSH) and high triiodothyronine (T3) and thyroxine (T4) in assays using biotin-streptavidin affinity systems in their design [37,38]. Thyroid tests should be repeated at least two days after discontinuation of biotin supplements. (See "Laboratory assessment of thyroid function", section on 'Assay interference with biotin ingestion'.)

Effect of insulin degludec and insulin glargine on hypoglycemia and CVD outcomes (July 2017)

Long-acting basal insulin preparations include glargine, detemir, and degludec. Several recent studies have compared outcomes for insulin degludec and insulin glargine.

In two similarly designed crossover trials comparing once-daily insulin degludec with insulin glargine in patients with type 1 and type 2 diabetes mellitus at high risk for hypoglycemia, the rate of overall symptomatic and nocturnal hypoglycemia was lower with degludec [39,40]. Limitations of the trials include a high rate of loss to follow-up and lack of generalizability to patients at lower risk for hypoglycemia.

In a two-year noninferiority trial comparing once-daily insulin degludec with insulin glargine in over 7500 patients with type 2 diabetes and cardiovascular disease, the primary cardiovascular composite outcome (death from cardiovascular causes, or first occurrence of a nonfatal myocardial infarction or nonfatal stroke) occurred in a similar proportion of patients (8.5 and 9.3 percent of the patients receiving degludec and glargine, respectively) [41]. Glycemic control was similar throughout the trial; rates of severe and nocturnal hypoglycemia were lower in patients taking degludec.

The choice of basal insulin (NPH, glargine, detemir, or degludec) primarily depends upon patient preference, lifestyle, and cost issues. (See "Insulin therapy in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus", section on 'Basal insulin' and "Management of blood glucose in adults with type 1 diabetes mellitus", section on 'Basal insulin'.)

Racial variation in glycated hemoglobin (July 2017)

Several studies have shown that glycated hemoglobin (A1C) concentrations are higher in black than in white persons with diabetes, although it is uncertain if the difference is due to worse glycemic control or racial variation in the glycation of hemoglobin. In a prospective, 12-week study comparing A1C with mean glucose values measured by continuous glucose monitoring (CGM) in black and white persons with type 1 diabetes, both average CGM glucose (191 versus 180 mg/dL [10.6 versus 10 mmol/L]) and A1C (9.1 versus 8.3 percent) were higher in black than white individuals [42]. The mean A1C in black compared with white individuals was 0.4 percentage points higher for any given mean glucose concentration. The racial variation explained only a proportion of the difference in mean A1C levels between the two groups, with higher mean glucose values likely accounting for the rest. The small difference in A1C has not been shown to modify the association between A1C and microvascular and macrovascular outcomes, and diagnostic criteria and target A1C goals remain unchanged. (See "Estimation of blood glucose control in diabetes mellitus", section on 'Racial variation'.)

Canagliflozin in diabetic individuals with overt CVD (June 2017)

The cardiovascular effects of diabetes drugs have been evaluated in a growing number of trials. Two trials evaluated the effects of canagliflozin, compared with placebo, on cardiovascular, renal, and safety outcomes in patients with type 2 diabetes and high cardiovascular risk [43]. The primary composite cardiovascular outcome (cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke), as well as progression of albuminuria, occurred in fewer patients in the canagliflozin group. However, there was an increase in the risk of lower limb amputations and fractures in the canagliflozin group, tempering enthusiasm for this drug. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)

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) [44]. 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 [45]. 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'.)


Revised recommendations for endoscopy in the evaluation of dyspepsia (November 2017)

The American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) have published guidelines on the evaluation and management of dyspepsia [46]. The recommended age threshold for routine upper endoscopy in patients with dyspepsia, to exclude upper gastrointestinal neoplasia, has been raised to ≥60 years, in contrast to earlier guidelines advising ≥55 years. The new guidelines also recommend that patients <60 years with dyspepsia be tested for Helicobacter pylori and treated if positive. For patients <60 years, upper endoscopy is reserved for those with significant weight loss, overt gastrointestinal bleeding, more than one alarm feature (table 1), or rapid progression of one or more alarm features. The rationale for these revised recommendations is the low risk of gastric cancer in younger patients, the low positive predictive value of any single alarm feature in detecting gastrointestinal neoplasia, and the inherent risk and cost of performing upper endoscopy. Our management approach is generally consistent with these guidelines (algorithm 1). (See "Approach to the adult with dyspepsia", section on 'Diagnostic strategies and initial management'.)

PPI use and mortality (July 2017)

It is unclear if proton pump inhibitor (PPI) use is associated with an increase in risk of death. In an observational cohort study, the incident death rate among 275,977 new PPI users was higher than among 73,335 new histamine-2 receptor antagonist (H2RA) users over a median follow-up of 5.7 years (4.5 versus 3.3 per 100 person-years) [47]. After adjusting for potential confounders, PPI use was associated with increased all-cause mortality compared with H2RA use (HR 1.25); the risk of death increased with the duration of PPI use. Limitations of the study include its generalizability as the study cohort primarily consisted of older white males and lack of data on the cause of mortality. The underlying basis for this apparent increased risk of death with PPI use is not known, and further studies are needed to evaluate whether the association is due to unmeasured confounding. However, we continue to recommend that PPIs be prescribed at the lowest dose for the shortest duration appropriate for the condition being treated. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Mortality'.)

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 [48]. 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'.)


Methylphenidate for apathy in patients with Alzheimer disease (October 2017)

Apathy is a common and understudied symptom of dementia that can emerge early in the disease course and contribute to functional impairment and caregiver burden. In a randomized trial of 77 patients with mild Alzheimer disease (AD), methylphenidate improved apathy scores compared with placebo over a 12-week treatment period [49]. Adverse effects were similar between groups. These results add support to low-dose methylphenidate as an option in patients with persistent and distressing apathy despite a cholinesterase inhibitor and treatment of depression. (See "Management of neuropsychiatric symptoms of dementia", section on 'Apathy'.)


Risk of late recurrence after five-year course of adjuvant endocrine therapy for breast cancer (November 2017)

Endocrine therapy consistently improves survival for women with non-metastatic, hormone receptor-positive breast cancer. However, a meta-analysis that included over 60,000 women with estrogen receptor-positive breast cancer who were disease-free after five years of scheduled endocrine therapy found that the risk of distant recurrence continued for at least 15 years after discontinuation of endocrine therapy at five years [50]. The risk of recurrence correlated strongly with lymph node status, tumor size, and tumor grade. These data support our suggestion to extend adjuvant endocrine treatment to 10 years for patients with higher-risk features and to offer it as an option for patients with lower-risk disease who are tolerating treatment well and who wish to minimize their risk of new or recurrent breast cancers. (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Duration of endocrine treatment'.)

Frequency for dosing of oral iron (November 2017)

For many years, iron deficiency has been treated with oral iron given at least once per day, despite significant gastrointestinal side effects in the majority of individuals. A small, unblinded randomized trial has now demonstrated that giving oral iron every other day rather than every day resulted in greater iron absorption and fewer gastrointestinal side effects [51]. Alternate-day dosing is also supported by mechanistic studies that showed favorable effects on hepcidin, a negative regulator of intestinal iron absorption and iron release from macrophages. We now suggest that patients treated with oral iron for iron deficiency take the iron every other day rather than daily. (See "Treatment of iron deficiency anemia in adults", section on 'Dosing and administration (oral iron)'.)


Low effectiveness of the influenza vaccine in Australia (December 2017)

During the 2017 influenza season in the southern hemisphere, Australia reported very high numbers of influenza cases, multiple institutional outbreaks, and increased numbers of hospitalizations and deaths [52]. Influenza A H3N2, which usually causes more severe disease than other strains, predominated. The overall adjusted vaccine effectiveness in Australia was estimated to be 33 percent, but only 10 percent for H3N2. Since the vaccine for the 2017-2018 influenza season in the northern hemisphere has the same composition as the vaccine used in the southern hemisphere during the 2017 season, there is concern that regions in the northern hemisphere could experience a severe influenza season, particularly if influenza A H3N2 virus circulates widely [53]. (See "Seasonal influenza vaccination in adults", section on 'Low effectiveness in the Southern Hemisphere during the 2017 season'.)

Transmission of Shiga toxin-producing E. coli through raw flour (December 2017)

Ingestion of contaminated beef is the primary means of Shiga toxin-producing Escherichia coli (STEC) transmission, but other foods contaminated with cattle or deer feces can also be sources of infection. A 2016 multistate outbreak of STEC in the United States was traced to a flour production facility when a case-control evaluation identified consumption of raw flour and raw homemade dough as risk factors for infection [54]. This outbreak highlights the variety of food potentially contaminated with STEC and the importance of food safety (eg, not eating raw dough) in preventing infection. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)

IDSA guidelines on acute diarrhea (November 2017)

The Infectious Diseases Society of America updated its guidelines on the diagnosis and management of infectious diarrhea [55]. They recommend confirmatory stool culture and susceptibility testing when culture-independent diagnostic tests are positive for clinically important bacterial pathogens. They highlight the need for careful interpretation of multiplex molecular panels, which simultaneously test for multiple organisms by detecting genetic material, do not always indicate infection with a viable organism, and frequently identify more than one potential pathogen. The guidelines also emphasize reserving empiric antibiotic therapy for select patients, including those with severe illness or immunocompromising conditions. Our approach is generally consistent with these guidelines. (See "Approach to the adult with acute diarrhea in resource-rich settings".)

New adjuvanted recombinant hepatitis B vaccine (November 2017)

Hepatitis B vaccination is the best way to prevent hepatitis B virus transmission. Available nonadjuvanted recombinant vaccines are effective and extremely safe, although they require three doses and 5 to 10 percent of patients do not respond. In November 2017, the US Food and Drug Administration granted conditional approval of a new adjuvanted vaccine (HEPLISAV-B) for adults 18 years and older [56]. This vaccine, given in two doses, appears more immunogenic than the nonadjuvanted vaccines and is generally well tolerated. However, there are ongoing safety concerns regarding a potentially increased risk of acute myocardial infarction and immune mediated disorders, which will be further evaluated in a phase 4 study. The optimal use of this vaccine is thus still to be determined. (See "Hepatitis B virus vaccination", section on 'Single antigen vaccines'.)

Glucocorticoids for symptomatic therapy of sore throat (November 2017)

Symptomatic relief of sore throat is an important goal for patients presenting with pharyngitis. In a systematic review and meta-analysis, one to two days of adjunctive glucocorticoids (in addition to antibiotics, if warranted, and other analgesics) reduced time to onset of sore throat pain relief by five hours and time to complete pain resolution by 11 hours compared with placebo, without increased adverse effects [57]. However, we continue to suggest not using glucocorticoids on a routine basis for acute sore throat pain, because of their modest benefit, the well-described toxicities of even short-term glucocorticoid use, and the availability of other effective options. (See "Symptomatic treatment of acute pharyngitis in adults", section on 'Limited role of glucocorticoids'.)

Inactivated zoster vaccine in the United States (October 2017)

To date, only a live zoster vaccine has been available to prevent herpes zoster and postherpetic neuralgia; it is contraindicated in highly immunocompromised patients, and its efficacy is reduced in patients ≥70 years old. In October 2017, the US Food and Drug Administration approved an inactivated recombinant zoster vaccine that reduces the risk of herpes zoster by ≥90 percent, even among older individuals [58]. The Advisory Committee on Immunization Practices has recommended the recombinant (administered in two doses) rather than the live attenuated vaccine for all adults ≥50 years old, although not all committee members agreed given the lack of data in minority groups and on the long-term vaccine safety and effectiveness in real-world settings [59]. The optimal use of the inactivated vaccine continues to be assessed. Recommendations by the Centers for Disease Control and Prevention are forthcoming. (See "Vaccination for the prevention of shingles (herpes zoster)", section on 'Vaccine formulations'.)

Syphilis incidence in the United States (October 2017)

Syphilis causes a wide range of clinical syndromes and is associated with HIV transmission. The United States Centers for Disease Control and Prevention reported an approximately 18 percent increase in the rate of primary and secondary syphilis (the most infectious stages of the disease) in 2016, with 8.7 cases per 100,000 population, the highest rate since 1993 [60]. More than 600 cases of congenital syphilis were also reported. Although syphilis rates increased among men and women, the rise was primarily attributable to men who have sex with men (MSM). These findings stress the importance of screening and treatment for sexually transmitted infection, especially in MSM and pregnant women. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Epidemiology'.)

Comparison of influenza diagnostic tests (October 2017)

Conventional reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the preferred test for influenza due to its high sensitivity and specificity. Newer tests include rapid molecular assays using nucleic acid amplification and digital immunoassays (DIAs) using automated antigen detection. Both provide results more quickly than conventional RT-PCR and have higher sensitivity than traditional antigen detection tests. In a meta-analysis that compared various influenza assays with conventional RT-PCR for influenza A, the pooled sensitivities of rapid molecular assays and DIAs were 92 and 80 percent, respectively [61]. Both had higher sensitivity than traditional rapid antigen tests (sensitivity 54 percent). If available, a rapid molecular assay can be used as an alternative to conventional RT-PCR. (See "Diagnosis of seasonal influenza in adults", section on 'Molecular assays' and "Diagnosis of seasonal influenza in adults", section on 'Choice of diagnostic test' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Approach to testing'.)

Third dose of MMR for prevention of mumps in an outbreak setting (September 2017)

In the setting of a mumps outbreak, in addition to ensuring that incompletely immunized individuals receive the standard two-dose measles, mumps, and rubella (MMR) vaccine series, public health authorities may recommend a third dose of the MMR vaccine under certain circumstances (eg, two-dose vaccination coverage >90 percent, intense exposure setting, high attack rate). During a mumps outbreak at a university with over 20,000 enrolled students, almost all of whom had previously received two vaccine doses, nearly 5000 students received a third MMR dose [62]. The mumps attack rate (259 cases overall) was lower among students who had received three rather than two vaccine doses (6.7 versus 14.5 cases per 1000 persons); in an adjusted analysis, the third MMR dose was associated with a 78 percent lower risk of mumps. (See "Mumps", section on 'Prevention'.)

Lack of benefit with corticosteroid use for acute bronchitis (September 2017)

Corticosteroids are frequently used for symptom relief in patients with acute bronchitis, although no data support use for this indication. In a randomized trial comparing oral prednisolone with placebo in 401 adult outpatients with acute cough, symptomatic lower respiratory tract infection, and no indication for antibiotic treatment, there was no difference in symptom severity, duration of cough, or peak flow [63]. Patients with chronic lung disease or asthma were excluded. This study supports our advice to not prescribe corticosteroids in patients with acute bronchitis, apart from those with concurrent asthma or chronic obstructive pulmonary disease (COPD) exacerbations. (See "Acute bronchitis in adults", section on 'For cough'.)

Glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir for chronic HCV infection (August 2017)

Treatment options for patients with chronic hepatitis C virus (HCV) continue to grow. Two new combination therapies, glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir, were recently approved by the Food and Drug Administration in the United States and are expected to be approved in Europe this year. Glecaprevir-pibrentasvir is highly effective for patients with genotypes 1 through 6 infection, offers the possibility of an eight-week regimen for most patients without cirrhosis, and can be used in patients with renal impairment (including those on dialysis) [64-67]. It is now one of our preferred regimens for all genotypes; regimen duration depends on the genotype, the presence of cirrhosis, and the treatment history (algorithm 2 and algorithm 3 and algorithm 4 and algorithm 5). Sofosbuvir-velpatasvir-voxilaprevir is highly effective in patients with genotypes 1 through 6 infection who have failed a prior direct acting antiviral (DAA) regimen and is now the main treatment option for those who have failed an NS5A inhibitor-containing regimen [68]. Like other contemporary DAA regimens, these new combinations are well tolerated, with common but mild side effects. (See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Selection of treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Selection of treatment regimens'.)

Antibiotic therapy for skin abscess (July 2017)

Management of skin abscess consists of incision and drainage; the role of antibiotic therapy depends on individual clinical circumstances, including abscess size. In a randomized trial including more than 780 patients with skin abscess ≤5 cm (most were larger than 2 cm) who underwent incision and drainage, higher cure rates were observed among those who received antibiotic therapy with methicillin-resistant Staphylococcus aureus (MRSA) coverage (trimethoprim-sulfamethoxazole or clindamycin) than those who received placebo (82 or 83 percent versus 69 percent); MRSA was isolated in 49 percent of cases [69]. These findings support our approach to management of patients with skin abscess, in which we suggest antibiotic therapy in addition to incision and drainage for patients with skin abscess ≥2 cm. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Role of antibiotic therapy'.)

Delafloxacin for treatment of skin and soft tissue infections (July 2017)

Delafloxacin, a fluoroquinolone, has been approved by the US Food and Drug Administration for treatment of bacterial skin and soft tissue infections. It has activity against staphylococci (including methicillin-resistant strains), gram-negative bacteria (including Pseudomonas aeruginosa and Enterobacteriaceae), and some anaerobes (including Clostridium difficile) but does not have activity against enterococci. In two phase III clinical trials, the drug was statistically noninferior to the combination of vancomycin and aztreonam at the endpoint of early clinical response at 48 to 72 hours [70,71]. Given limited clinical experience with delafloxacin, at this time its use should be reserved for patients who do not respond to or do not tolerate first-line antimicrobial agents. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections", section on 'Delafloxacin'.)

Recombinant hemagglutinin influenza vaccine in older adults (June 2017)

Recombinant hemagglutinin influenza vaccines (Flublok and Flublok Quadrivalent) are produced using recombinant DNA technology and a baculovirus expression system rather than the traditional egg-based methods. In a randomized trial that included adults ≥50 years of age, Flublok Quadrivalent was more effective than the quadrivalent standard-dose inactivated vaccine for preventing influenza [72]. Flublok Quadrivalent has not been compared directly with the high-dose inactivated vaccine, which has been found to be more effective than the standard dose inactivated vaccine in older adults (including a mortality benefit). Flublok Quadrivalent is a reasonable alternative to the high-dose vaccine for older adults. (See "Seasonal influenza vaccination in adults", section on 'Recombinant hemagglutinin vaccine'.)

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) [73]. 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'.)


Long-term risk of hypertension in women with pregnancy-associated hypertension (August 2017)

For women with a history of gestational hypertension, preeclampsia, eclampsia, or HELLP syndrome, at least annual lifelong measurement of blood pressure is important due to their increased risk for chronic hypertension. In a long-term population-based study, the rate of hypertension in the first decade postpartum for primiparous women in their 20s with pregnancy-associated hypertension was 14 percent, compared with 4 percent for those without pregnancy-associated hypertension [74]. For primiparous women in their 40s, the rates were 32 and 11 percent, respectively. The risk of chronic hypertension in this population may be reduced by adherence to a beneficial lifestyle (eg, achieving/maintaining a healthy weight, salt restriction, exercise, limited alcohol intake) [75]. (See "Management of hypertension in pregnant and postpartum women", section on 'Long-term prognosis of women with hypertension during pregnancy'.)


Patent foramen ovale (PFO) device closure for prevention of recurrent ischemic stroke (October 2017)

Treatment for patients with a cryptogenic stroke who have a patent foramen ovale (PFO) has been controversial. In earlier randomized controlled trials, point estimates suggested that percutaneous device closure of a PFO in patients ≤60 years of age was more effective than antiplatelet therapy for reducing recurrent stroke, but the findings did not reach statistical significance. However, the results of three recent randomized trials, RESPECT extended follow-up [76], REDUCE [77], and CLOSE [78], provide stronger evidence that device closure of a PFO plus antiplatelet therapy is more effective than antiplatelet therapy alone for preventing recurrent ischemic stroke in such patients, with absolute risk reductions ranging from 2.2 to 6 percent. Based upon these results, we now suggest percutaneous PFO closure in addition to antiplatelet therapy for patients who meet all of the following criteria: age ≤60 years, embolic-appearing cryptogenic ischemic stroke (ie, no evident source of stroke despite a comprehensive evaluation), and a PFO with a right-to-left interatrial shunt detected by bubble study. (See "Treatment of atrial septal abnormalities (PFO, ASD, and ASA) for prevention of stroke in adults", section on 'Percutaneous closure of PFO'.)

Dementia risk factors and prevention (September 2017)

Two major reports released by a Lancet Commission in the United Kingdom and the Agency for Healthcare Research and Quality in the United States review the literature on risk factors for dementia and the impact of risk factor modification on dementia incidence [79,80]. The Lancet Commission estimates that approximately one-third of dementia cases are attributable to a combination of nine potentially modifiable risk factors: low educational attainment, midlife hypertension, midlife obesity, hearing loss, late-life depression, diabetes, physical inactivity, smoking, and social isolation [79]. While the overall evidence is generally of low quality and does not support any single intervention, there is optimism that intensive risk factor modification, especially during midlife, has the potential to delay or prevent dementia. (See "Risk factors for cognitive decline and dementia" and "Prevention of dementia".)


Revised follow-up for a solitary pulmonary nodule (June 2017)

Fleischner Society guidelines have been updated to reflect the accumulating data on the malignancy risk of incidental pulmonary nodules and growth rates of lung cancer [81]. Important changes include guidance on identifying benign nodules with minimal follow-up imaging. For patients with a solid or subsolid (ground glass or part-solid) solitary pulmonary nodule measuring <6 mm, follow-up computed tomography (CT) is optional, but no longer required. A solitary pulmonary nodule that is solid and unchanged on serial CT over a two-year period, or subsolid and unchanged over a five-year period, is likely benign and does not need further diagnostic evaluation. Recommendations in UpToDate have been revised to reflect these new guidelines. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Management' and "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Solid nodule ≤8 mm'.)


Management of treatment resistant depression in adults (August 2017)

For patients with treatment resistant depression, there has been little comparative evidence to guide the choice between add-on therapy (augmentation) and switching to a different antidepressant drug. In an open label trial, more than 1500 patients with treatment resistant depression were randomly assigned to one of three treatment strategies: augment the current antidepressant with aripiprazole, augment with bupropion sustained release, or switch to bupropion [82]. At 12 weeks, remission was more likely in the augment-aripiprazole group than the switch group, but the clinical difference was small (29 versus 22 percent). Akathisia, somnolence, weight gain, and laboratory abnormalities were more common with aripiprazole, and anxiety occurred more often in the other groups. Based on these results, we now favor augmentation for managing treatment resistant depression; however, switching remains a reasonable alternative, especially for patients who want to avoid medication side effects. (See "Unipolar depression in adults: Treatment of resistant depression", section on 'Efficacy of augmentation compared with switching'.)


Safety of arthrocentesis and joint injection in patients on direct oral anticoagulants (October 2017)

Until recently, the safety of joint aspiration or injection in patients on anticoagulation was based on studies with warfarin, which reported only a small risk of increased bleeding. The first study to provide data on the risk of bleeding in patients on direct oral anticoagulants (DOACs) undergoing joint aspiration or injection is a retrospective review of 1050 consecutive procedures from Mayo Clinic over a six-year period [83]. There were no bleeding complications during the median follow-up period of five days. Of the 1050 procedures, 22 percent were performed in patients receiving a DOAC plus aspirin, and 1 percent were performed in patients on a DOAC plus clopidogrel. These findings support the safety of arthrocentesis and joint injection in patients receiving uninterrupted DOACs and/or antiplatelet therapy. (See "Joint aspiration or injection in adults: Technique and indications", section on 'Approach to the patient on anticoagulants'.)

EULAR recommendations on the use of imaging for osteoarthritis (September 2017)

The European League Against Rheumatism (EULAR) has published evidence-based recommendations for the use of imaging for the management of symptomatic peripheral joint osteoarthritis (OA) [84]. Among the recommendations are guidance to avoid diagnostic imaging in patients with typical symptoms and to use conventional radiography as the first-choice imaging modality in most patients. Our approach to imaging for peripheral joint OA is generally consistent with these guidelines. (See "Clinical manifestations and diagnosis of osteoarthritis", section on 'Imaging'.)

Role of pharmaceutical-grade chondroitin for knee osteoarthritis (June 2017)

The use of chondroitin for the treatment of knee osteoarthritis (OA) has been controversial due to conflicting data, with more favorable results associated with higher doses and higher-grade formulations. In an industry-sponsored randomized trial of 604 patients with symptomatic knee OA, pharmaceutical-grade chondroitin (800 mg) was statistically superior to placebo and similar to celecoxib in reducing pain and improving function [85]. An important limitation of the study is the uncertain clinical relevance of the modest improvements in pain and functional scores. Also, the number of patients who achieved a clinically important improvement in pain was not different among the three groups. These issues limit the strength of the findings. (See "Management of knee osteoarthritis", section on 'Glucosamine and chondroitin'.)


Severe maternal morbidity in overweight and obese women (December 2017)

In a population-based study including over 740,000 pregnant women, women who were overweight or obese were at increased risk of severe maternal morbidity and mortality compared with women with a normal body mass index (BMI), and the risk increased with increasing BMI [86]. Morbidity included hemorrhage requiring transfusion; serious cardiac, respiratory, cerebrovascular, or hematologic complications; venous thrombosis/embolism; sepsis; shock; hepatic or renal failure; anesthesia-related complications; and uterine rupture. These findings underscore the importance of counseling overweight and obese women about their increased risk for serious complications during pregnancy, as well as for adverse birth outcomes, and encouraging prepregnancy weight loss. (See "Obesity in pregnancy: Complications and maternal management", section on 'Overall risk of severe morbidity or mortality'.)

Contraception counseling and bariatric surgery (November 2017)

Women who undergo bariatric surgery are advised to use contraception during the first 12 to 18 postoperative months to avoid pregnancy during the rapid weight-loss phase. However, a prospective study of over 700 women who underwent bariatric surgery reported that 4 percent actively tried to conceive, and 41 percent had unprotected intercourse during the first postsurgical year [87]. Risk factors for not using contraception included advancing age, being married or cohabitating, and preoperatively rating future pregnancy as important. This study highlights the need for preoperative and postoperative contraceptive counseling, particularly for women with risk factors for unprotected sexual activity. (See "Fertility and pregnancy after bariatric surgery", section on 'Contraception'.)

Ovarian biomarkers for predicting ability to conceive (October 2017)

Serum anti-Müllerian hormone (AMH) and follicle stimulation hormone (FSH) levels are commonly measured to assess ovarian reserve in women wishing to conceive. However, a large prospective cohort study of women age 30 to 44 years, without a history of infertility, reported similar conception rates for women with normal and abnormal AMH and FSH levels [88]. This study adds to the body of evidence suggesting that AMH and FSH levels do not predict the probability of pregnancy in women without a diagnosis of infertility, even among women of older age. The study did not address conception rates for women with a known diagnosis of infertility. For women in this age group with known infertility who are considering in vitro fertilization, these tests do have some prognostic value. (See "Evaluation and management of infertility in women of advancing age", section on 'Diminished ovarian reserve'.)

Home use of topical anesthesia to control pain from corneal abrasions (August 2017)

In a retrospective study of 444 patients with corneal abrasions given a 24-hour supply of topical tetracaine at the initial emergency department visit, there were no documented serious complications or uncommon adverse events [89]. However, definitive outcomes were only known for 120 patients who returned for rechecks. Patients receiving topical tetracaine were more likely to return for emergency department reevaluation compared with patients who did not receive tetracaine. Topical analgesia was prescribed inappropriately in one-third of patients, for lesions other than simple corneal abrasion (eg, large corneal abrasions, retained rust rings, herpes keratitis, anterior uveitis, and corneal erosions). Because of the possibility of overuse (ie, use beyond 24 hours) and the risk of inappropriate administration, we favor other means of pain control and discourage the prescribing of topical anesthetic agents. More evidence is needed to establish the safety of this practice in patients with simple corneal abrasions. (See "Corneal abrasions and corneal foreign bodies: Management", section on 'Pain control'.)

Opana ER withdrawn from the US market (July 2017)

A long-acting abuse-deterrent formulation of oxymorphone, Opana ER, is being voluntarily withdrawn from the United States (US) market at the request of the US Food and Drug Administration due to concerns related to injection abuse, including reports of thrombotic microangiopathy (TMA) when the oral formulation is injected intravenously (IV) [90-92]. The TMA is thought to be due to an inert component that was added to the formulation to make it crush-resistant and thus deter IV injection. Generic extended-release oxymorphone products remain on the US market. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'Oxycodone, hydrocodone, hydromorphone, and oxymorphone' and "Drug-induced thrombotic microangiopathy", section on 'Drugs of abuse'.)

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