Howard Libman, MD, FACP
Judith A Melin, MA, MD, FACP
Daniel J Sullivan, MD, MPH
H Nancy Sokol, MD
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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.
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 . 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 , 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 . 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 . 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 . 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 . 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 . 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 . 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 . (See "Diagnosis of celiac disease in adults", section on 'Who should be tested'.)
GENERAL INTERNAL MEDICINE
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 . 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 . 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 . 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 . 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 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 . 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."Treatment of urinary incontinence in women".)
Mindfulness-based stress reduction for low back pain (August 2017)
Mindfulness-based stress reduction (MBSR) has been used for the management of low back pain. In a recent systematic review and meta-analysis of seven randomized controlled trials involving 864 patients with low back pain (most with subacute or chronic low back pain), MBSR was associated with modest short-term improvements in pain intensity and physical functioning compared with usual care . We offer MBSR as a nonpharmacologic intervention for patients with subacute or chronic 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 . 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 . 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 . 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 . 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) . 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 . 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 . 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 .
●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 . 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 . 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'.)
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 . 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'.)
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) . 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 . 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'.)
PRIMARY CARE ALLERGY AND IMMUNOLOGY
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 . 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 . 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 . 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'.)
PRIMARY CARE CARDIOVASCULAR MEDICINE
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 . 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) . 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'.)
PRIMARY CARE ENDOCRINOLOGY AND DIABETES
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 [34,35]. 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)
●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 [36,37]. 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) . 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 . 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 . 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) . 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 . 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 [43,44] 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 .
●Testosterone increased coronary artery noncalcified plaque volume as measured by coronary computed tomographic angiography .
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 . 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 . 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'.)
PRIMARY CARE GASTROENTEROLOGY
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) . 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 "Overview and comparison of the proton pump inhibitors for 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 . 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'.)
Risk of colon cancer in patients with diverticulitis (April 2017)
The utility of routine colonoscopy after acute diverticulitis is debated. An analysis of data from a Danish registry showed that patients hospitalized for diverticulitis were twice as likely to develop colon cancer over the 18-year study period as those without diverticulitis, and over 50 percent of colon cancers were diagnosed within one year of diagnosis of diverticulitis . This study underscores the importance of endoscopic surveillance in patients with diverticular disease and supports our recommendation for performing a colonoscopy after the complete resolution of an episode of acute diverticulitis in patients who have not had a colonoscopy within a year. (See "Acute colonic diverticulitis: Medical management", section on 'Colonoscopy for all patients'.)
PRIMARY CARE INFECTIOUS DISEASES
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 . 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 . 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) [56-59]. 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 . 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 . 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 [62,63]. 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 . 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) . 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 . 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 . 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 . 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'.)
PRIMARY CARE NEPHROLOGY AND HYPERTENSION
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 . 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) . (See "Management of hypertension in pregnant and postpartum women", section on 'Long-term prognosis of women with hypertension during pregnancy'.)
PRIMARY CARE NEUROLOGY
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 [71,72]. 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 . 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".)
PRIMARY CARE PULMONOLOGY
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 . 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 and management of the solitary pulmonary nodule", section on 'Management strategy' and "Diagnostic evaluation and management of the solitary pulmonary nodule", section on 'Solid nodules ≤8 mm'.)
PRIMARY CARE PSYCHIATRY
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 . 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'.)
PRIMARY CARE RHEUMATOLOGY
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 . 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'.)
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 . 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'.)
OTHER ADULT PRIMARY CARE
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 . 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) [78-80]. 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'.)
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 . 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 . 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'.)
Direct-to-consumer genetic testing for carrier status (April 2017)
Policies regarding the use of direct-to-consumer (DTC) genetic testing are evolving. The US Food and Drug Administration (FDA) has designated genetic testing for carrier status to be a class II device that does not require premarket approval. As of mid-2017, several companies have begun offering DTC testing for carrier status. As an example, the company 23andMe is marketing DTC testing that would reveal increased risk for a predetermined set of 10 conditions including celiac disease, hereditary hemochromatosis, Parkinson's disease, and others . Results might result in lifestyle modifications and/or discussion with a clinician, which may be of value to the individual. However, clinicians should be aware of a number of concerns that have been raised about the reliability, interpretation, and management implications of this type of testing. (See "Personalized medicine", section on 'Direct-to-consumer testing'.)
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