Disclosures: David M Rind, MD Employee of UpToDate, Inc. Equity Ownership/Stock Options (Spouse): Bonfire Development Advisors [CBT (iCBT)]. H Nancy Sokol, MD Employee of UpToDate, Inc. Lee Park, MD Employee of UpToDate, Inc. Employment (Spouse): Novartis [Age-related macular degeneration (ranibizumab)].
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.
ADULT GENERAL INTERNAL MEDICINE
Revised name and diagnostic criteria for chronic fatigue syndrome (February 2015)
Diagnostic criteria for chronic fatigue syndrome have been revised (table 1) by the Institute of Medicine (IOM), which has also suggested renaming the condition as systemic exertional intolerance disease (SEID) . The IOM diagnostic criteria focus on the most specific features of the disease. Symptoms should be present for at least six months and have moderate, substantial, or severe intensity at least one-half of the time. Other criteria include post-exertional malaise, sleep problems, cognitive impairment, and orthostatic-related symptoms. (See "Clinical features and diagnosis of chronic fatigue syndrome (systemic exertional intolerance disease)", section on 'Definition'.)
Adverse consequences of opioid use in chronic pain (January 2015)
There is uncertainty that opioids have long-term effectiveness in the treatment of fibromyalgia or other chronic pain conditions, and risks of harm from chronic opioid therapy likely outweigh the benefits. The avoidance of opioids in patients with chronic pain is further supported by a 2015 systematic review of the effectiveness and risks of long-term opioid therapy for chronic pain . The review showed evidence of a dose-dependent risk for a range of harms, such as overdose, opioid abuse, fractures, myocardial infarction, and sexual dysfunction, but found insufficient evidence from observational studies to determine the effectiveness of such therapy and no placebo-controlled trials that met inclusion criteria for the review. (See "Treatment of fibromyalgia in adults not responsive to initial therapies", section on 'Analgesics' and "Overview of the treatment of chronic pain".)
Antihypertensive therapy provides benefit in mild hypertension (January 2015)
The benefit of antihypertensive drug therapy has been questioned in patients with mild hypertension (systolic 140 to 159 mmHg and/or diastolic 90 to 99 mmHg) and no preexisting cardiovascular disease. A meta-analysis including 15,266 such patients reported that, compared with placebo or a less intensive regimen, antihypertensive therapy or a more intensive regimen for five years produced significantly lower rates of all-cause mortality (3.9 versus 4.8 percent) and stroke (1.6 versus 2.1 percent), and similar rates of myocardial infarction . Thus, low-risk patients with mild hypertension and no preexisting cardiovascular disease who fail to reduce their blood pressure with lifestyle modification should receive antihypertensive therapy. (See "Hypertension: Who should be treated?", section on 'Low-risk patients'.)
Approval of the direct factor Xa inhibitor edoxaban (January 2015)
The US Food and Drug Administration has approved the oral direct factor Xa inhibitor edoxaban (Savaysa; Lixiana in Japan) for the prevention of stroke in nonvalvular atrial fibrillation and the treatment of venous thromboembolism, based upon earlier randomized trials demonstrating non-inferiority to warfarin [4-6]. Dosing is once daily at a fixed dose without monitoring. There are Boxed Warnings regarding avoidance of edoxaban in patients with atrial fibrillation who have a creatinine clearance >95 mL/minute, spinal/epidural hematoma in patients undergoing neuraxial procedures, and ischemic events following premature discontinuation. (See "Atrial fibrillation: Anticoagulant therapy to prevent embolization" and "Lower extremity deep venous thrombosis: Long-term anticoagulation (10 days to three months)" and "Anticoagulation in acute pulmonary embolism" and "Anticoagulation with direct thrombin inhibitors and direct factor Xa inhibitors", section on 'Edoxaban'.)
Transobturator versus retropubic slings for stress urinary incontinence in women (December 2014)
Five-year follow-up data from the Trial of Midurethral Slings (TOMUS), which randomized women to either a retropubic sling or a transobturator sling, demonstrated decreasing continence rates for women in both treatment groups . The continence rate was higher in retropubic sling patients as compared with transobturator sling patients, but not statistically different (51.3 percent versus 43.4 percent). A greater proportion of women who underwent a transobturator sling procedure reported a "much better or very much better" urinary status. The overall mesh erosion rate was low, but new mesh exposures developed remote from surgery. Both retropubic slings and transobturator slings are reasonable choices for the surgical management of stress urinary incontinence in women, but the continence rates of both procedures decrease with time. (See "Surgical management of stress urinary incontinence in women: Choosing a type of midurethral sling", section on 'Transobturator versus retropubic midurethral slings'.)
Combination of varenicline and nicotine patch improves smoking cessation rates (October 2014)
In a randomized trial, 435 smokers were assigned to treatment with varenicline combined with either a nicotine or a placebo patch . Nicotine or placebo patches were started two weeks before the quit day and varenicline was started one week before the quit day. Both patches and varenicline were continued for 12 weeks. Treatment with varenicline and the nicotine patch resulted in a higher rate of continuous abstinence compared with varenicline and the placebo patch (49 versus 33 percent) at six months after the end of drug treatment. Prior studies have also shown higher rates of abstinence with the combination of nicotine replacement therapy (NRT) and bupropion, and with the combination of varenicline and bupropion. We continue to suggest initiating therapy with medication from a single class (eg, varenicline, bupropion, or NRT), given the increased cost and additional side effects with combining therapies, but combining medication classes is a reasonable option for patients who have failed initial therapy. (See "Pharmacotherapy for smoking cessation in adults", section on 'Patients who fail to quit'.)
Statin-associated adverse muscle events (October 2014)
Terminology around statin-associated adverse muscle events is variable and has changed over time. The 2014 National Lipid Association Statin Muscle Safety Task Force has proposed new definitions for these adverse events , which are reflected in our discussion of statin myopathy. Additionally, we no longer suggest a trial of Coenzyme Q10 (CoQ10) for patients experiencing such statin-associated adverse muscle events. (See "Statin myopathy", section on 'Coenzyme Q10' and "Statin myopathy", section on 'Definitions'.)
Acetaminophen in the treatment of acute low back pain (September 2014)
In a randomized trial of 1645 patients with acute low back pain (less than six weeks duration), there was no difference in recovery time or other measures of pain and function between patients treated with placebo, as-needed acetaminophen, and regular acetaminophen use . Potential reasons for the apparent lack of effect include that some patients also used other treatments during the trial period and the actual amount of medicine (median dose of 2660 mg) taken may not have been sufficient. A treatment trial of acetaminophen for acute low back pain remains a reasonable treatment option. (See "Treatment of acute low back pain", section on 'Acetaminophen'.)
KEEPS hormone therapy trial in newly menopausal women (September 2014)
The Women's Health Initiative (WHI), a set of menopausal hormone therapy (MHT) trials in older postmenopausal women (average age 63 years) reported an excess risk of coronary heart disease (CHD) with MHT. Emerging data, including secondary analyses from the WHI, now suggest that use of MHT in the early menopausal years is not associated with excess CHD risk. The Kronos Early Estrogen Prevention Study (KEEPS) is the first randomized trial of MHT in younger menopausal women (727 women ages 45 to 54 years) . When combined with cyclical monthly oral progesterone, low dose oral conjugated estrogen (0.45 mg daily) or transdermal estradiol (50 mcg daily) for four years relieved menopausal symptoms. While several markers of cardiovascular risk improved in the MHT group, there was no significant effect on surrogate markers of atherosclerosis progression (coronary artery calcium and carotid intima-medial thickness) when compared to placebo. This trial provides additional reassurance that early use of MHT is safe for the treatment of menopausal symptoms, though it does not support a role for MHT in prevention. (See "Menopausal hormone therapy and cardiovascular risk", section on 'Timing of exposure'.)
Epidural glucocorticoid injections not effective for lumbar spinal stenosis (August 2014)
The available evidence does not support the use of epidural injections of glucocorticoids in lumbar spinal stenosis (LSS). In a randomized trial of 400 patients with LSS, moderate to severe leg pain, and disability, those patients who received one or two epidural injections of glucocorticoids plus lidocaine had similar pain and disability outcomes at six weeks as those who received injections of lidocaine alone . Adverse events (such as pain, headache, fever, and infection) were nonsignificantly higher in the glucocorticoid group (21.5 versus 15.5 percent). Since this study did not include a sham control group, it does not rule out a potential benefit from the injection of the local anesthetic. (See "Lumbar spinal stenosis: Treatment and prognosis", section on 'Epidural injections'.)
Home modifications to prevent falls (January 2015)
Fall prevention for community dwelling older adults has the potential to significantly improve quality of life and impact morbidity and mortality, but few fall prevention interventions have been shown to be effective. A cluster-randomized trial evaluated a standardized set of home safety interventions (installation of stair hand rails, grab rails in bathrooms, improved lighting, slip-resistant deck surfacing, non-slip bathmats, pamphlet on home safety), comparing injury-related insurance claims in households that were randomized to the intervention with those that were wait-listed . Over a three year period, there was a 26 percent decrease in fall-related injuries in the intervention group compared to the control group. (See "Falls: Prevention in community-dwelling older persons", section on 'Environment/assistive technology'.)
Trimethoprim-sulfamethoxazole and sudden death (December 2014)
While trimethoprim-sulfamethoxazole (TMP-SMX) has generally been felt to be well tolerated, a case-control study found an association between sudden death, possibly due to hyperkalemia, and prescription of TMP-SMX among older patients who were also receiving an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) .Those who received TMP-SMX had an increased seven-day risk of sudden death compared with those who received amoxicillin (adjusted odds ratio 1.38, 95% CI 1.09-1.76). However, other factors that affected the choice of antibiotic may have confounded these results, and higher quality evidence is needed to determine whether this association is causal. (See "Trimethoprim-sulfamethoxazole: An overview", section on 'Life threatening effects'.)
CPAP therapy for older adults with obstructive sleep apnea (October 2014)
Continuous positive airway pressure (CPAP) is the mainstay of therapy for most adults with obstructive sleep apnea (OSA), but previous clinical trials have enrolled primarily younger adults. In a multicenter trial that included 278 adults ≥65 years of age with newly diagnosed OSA, patients randomized to receive CPAP therapy plus best supportive care had improvement in daytime sleepiness compared with those assigned to best supportive care alone . The benefits of CPAP were present at both three- and 12-month time points and were greater in those with higher CPAP usage and higher baseline sleepiness scores. Secondary endpoints, including quality of life, mobility, cognitive function, and cardiovascular events, were similar between groups. A major limitation of the trial was the lack of a sham CPAP control arm. (See "Sleep apnea and other causes of impaired sleep in older adults", section on 'Treatment'.)
Impact of prolonged sedentary time (February 2015)
A 2015 systematic review and meta-analysis adds to the mounting evidence of the negative effects of prolonged sedentary time . The review found that prolonged sedentary time was associated with increased risk for mortality, cardiovascular disease, diabetes, and cancer. The increased risks were not mitigated by participation in physical exercise, though the effects were more pronounced at lower levels of physical activity. (See "The benefits and risks of exercise", section on 'Physical inactivity and health'.)
New human papillomavirus (HPV) vaccine targets nine HPV types (February 2015)
Infection with human papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58 is implicated in approximately 90 percent of invasive cervical cancers. The US Food and Drug Administration has approved Gardasil 9, a 9-valent HPV vaccine that targets those seven HPV types in addition to the two types associated with genital warts (6 and 11), for the prevention of HPV-related disease . In a trial that included approximately 14,000 females randomly assigned to receive the 9-valent or quadrivalent HPV vaccine, immune responses with the two vaccines were comparable for the HPV types targeted by both (6, 11, 16, and 18). Additionally, the 9-valent HPV vaccine was 97 percent effective for preventing precancerous and cancerous lesions of the cervix, vagina, and vulva associated with the other targeted HPV types (31, 33, 45, 52, and 58). Safety profiles were overall similar. We favor the 9-valent HPV vaccine for its broader HPV type coverage.
Routine immunization should be offered to boys and girls aged 11 to 12, but can be administered as early as nine years of age. Catch-up vaccination should be offered for males between the ages of 13 to 21 and females between 13 to 26 years who have not been previously vaccinated. Repeat vaccination with the 9-valent vaccine is likely not warranted for individuals who have completed a series with a different HPV vaccine.
Lower HMG CoA reductase activity increases risk of diabetes (January 2015)
A Mendelian randomization study found that decreased genetic HMG CoA reductase activity is associated with a higher risk of type 2 diabetes, such that at least some of the risk of diabetes seen with statin therapy appears to be due to its inhibition of HMG CoA reductase . Since this inhibition is thought responsible for the primary efficacy of statin therapy, this finding means that any effective statin will probably increase the risk of diabetes . (See "Statins: Actions, side effects, and administration", section on 'Diabetes mellitus'.)
Tamoxifen prevention in women at high risk of breast cancer (January 2015)
Women at an increased risk of breast cancer are often prescribed a five-year course of tamoxifen for cancer prevention, but whether the benefits of tamoxifen extend beyond the course of treatment has not been clear. A new study suggests that tamoxifen confers long-term breast cancer prevention beyond the initial five years of treatment . The International Breast Cancer Intervention Study I (IBIS-1) assigned over 7000 high risk women to tamoxifen 20 mg daily or placebo for five years. With 16 years of follow-up, tamoxifen significantly reduced the risk of breast cancer, with risk extending beyond the first ten years of follow-up. The risk reduction was primarily seen for hormone receptor-positive breast cancer. (See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention", section on 'Tamoxifen'.)
Pneumococcal conjugate vaccine in adults ≥65 years of age (September 2014)
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In September 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the pneumococcal conjugate vaccine (PCV13) for all adults ≥65 years of age . Current recommendations for individuals ≥65 years of age who have not previously received either PCV13 or PPSV23 are to administer PCV13 followed 6 to 12 months later by PPSV23 (algorithm 1). In patients who have already received PPSV23, at least one year should elapse before they are given PCV13.
The ACIP revision was prompted by results from the CAPiTA trial. This randomized placebo-controlled trial, including approximately 85,000 adults ≥65 years of age in the Netherlands, demonstrated the efficacy of PCV13 against vaccine-type pneumococcal pneumonia, vaccine-type nonbacteremic pneumococcal pneumonia, and vaccine-type invasive pneumococcal disease . However, some concern has been raised that since this trial began before PCV13 was used routinely in infants in the Netherlands, it might not answer the question of whether its use in adults is efficacious in countries that routinely vaccinate infants. (See "Pneumococcal vaccination in adults", section on 'Indications'.)
Interim guidelines for cervical cancer screening with primary HPV testing (February 2015)
Interim guidelines from the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology are the first US guidelines to suggest primary human papillomavirus (HPV) testing as an option for cervical cancer screening in women starting at age 25 years (table 2) . This option is provided based on a randomized trial comparing primary HPV testing with cytology (Pap test) or co-testing (Pap test and HPV testing) . Among women ≥25 years, primary HPV testing was more sensitive for the detection of cervical intraepithelial neoplasia (CIN) 3 or greater. However, the study is limited by having only three years of follow-up, use of a surrogate outcome (CIN3 rather than cancer), and highly structured follow up protocols that may not be feasible in practice. Given these limitations, we continue to suggest that women age <30 years not be screened for cervical cancer with primary HPV testing. (See "Screening for cervical cancer", section on 'Primary HPV testing'.)
Breast cancer mortality differences by race may reflect tumor biology (February 2015)
Breast cancer incidence in the United States is slightly lower in black women than white women, but breast cancer mortality is higher in blacks. Greater breast cancer mortality among black women may be due to differences in screening, cancer treatment, tumor biology, or comorbidity. In an observational study, based on the SEER database, of nearly 375,000 women with invasive breast cancer followed for a median of 38 months, black women were less likely to be diagnosed with stage 1 disease, and those with small-sized tumors were more likely to die of breast cancer than white women, after adjustment for estrogen receptor status . This adds to emerging evidence that greater breast cancer mortality among black women relates, at least in part, to intrinsic differences in breast tumor biology between black and white women. (See "Screening for breast cancer: Strategies and recommendations", section on 'Epidemiology'.)
Supplemental ultrasound screening for women with dense breasts and normal mammography (January 2015)
In the United States, multiple states have passed legislation that advises supplemental whole breast ultrasound screening for women with dense breast tissue on mammography. A modeling study estimated that, for women ages 50 to 74 with heterogenously or extremely dense breasts and a negative mammogram, supplemental ultrasound screening would cost more than $100,000 per quality adjusted life year (QALY) gained, and thus would not meet generally accepted thresholds for cost-effectiveness . Compared with mammography alone, for 1000 women screened biennially for 25 years, supplemental ultrasound was predicted to prevent 0.36 additional cancer deaths, and lead to an additional 354 biopsies. To date, there have been no randomized trials in average-risk women comparing mammography alone with combination ultrasound and mammography. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'As adjunct to mammography for screening'.)
Flexible sigmoidoscopy for colorectal cancer screening (August 2014)
The Norwegian Colorectal Cancer Prevention (NORCCAP) trial randomly assigned individuals aged 50 to 64 years to one time flexible sigmoidoscopy screening (n = 20,572) or no screening (n = 78,220) . One-half of those assigned to sigmoidoscopy screening were also assigned to an immunochemical fecal occult blood test (iFOBT). Screening adherence was 63 percent. After a median follow-up of 10.9 years, there was a decrease in deaths from colorectal cancer in the flexible sigmoidoscopy screening group compared to the control group (31.4 versus 43.1 deaths per 100,000 person years). There was no difference between those who did or did not have additional iFOBT testing. A difference in mortality outcomes was not demonstrable until the ninth year of follow-up. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness'.)
Thirteen-year follow-up data on prostate cancer screening (August 2014)
Thirteen-year follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC) provides additional insights on the long-term implications of screening men aged 50 to 74 years for prostate cancer . Given the indolent course of prostate cancer, shorter-term follow-up from the trial may have been insufficient to accurately estimate the survival benefit. However, the absolute rate reduction in prostate cancer deaths for patients randomized to screening has changed only minimally, comparing rates after 9 and 13 years of follow-up (0.06 fewer deaths versus 0.11 fewer deaths per 1000 person years, respectively). This is equivalent to needing to invite 781 men for screening to prevent one prostate cancer death after 13 years. Furthermore, while the prostate cancer survival benefit from screening was not initially realized until nine years of follow up , the burdens of screening and treatment, including harms from overdiagnosis and overtreatment, occur immediately and potentially have lifelong consequences. (See "Screening for prostate cancer", section on 'Evidence from randomized trials'.)
ADULT CARDIOVASCULAR MEDICINE
Optimal duration of dual antiplatelet therapy after coronary stenting (December 2014)
All patients who undergo percutaneous coronary intervention with stenting receive dual antiplatelet therapy (DAPT), which is the combination of aspirin and a P2Y12 receptor blocker. However, the optimal duration of DAPT is not known; 12 months has been the commonly recommended duration. The DAPT trial randomly assigned 9961 such patients, who had been successfully treated with 12 months of aspirin and a P2Y12 receptor blocker (either clopidogrel or prasugrel), to continue receiving the P2Y12 receptor blocker or placebo for another 18 months; all patients continued aspirin . The rates for each of the co-primary end points of stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death from any cause, MI, or stroke) were lower with continued P2Y12 therapy (0.4 versus 1.4 percent and 4.3 versus 5.9 percent). However, the rate of moderate or severe bleeding was increased (2.5 versus 1.6 percent). Based on available evidence, including the DAPT trial, we recommend DAPT for 12 months in patients not at high risk of bleeding, which is the major complication of this therapy. After 12 months of uncomplicated DAPT therapy, we suggest an additional 18 months of treatment. (See "Antiplatelet therapy after coronary artery stenting", section on 'Drug-eluting stents'.)
Genetic predisposition to hyperlipidemia associated with aortic valve disease (December 2014)
Plasma low-density lipoprotein cholesterol (LDL-C) is associated with risk of calcific aortic valve disease but the genetic contribution to this risk is uncertain. A Mendelian randomization study found an association between the weighted genetic risk score (GRS, a measure of the genetic predisposition to elevation in plasma lipids) for low-density lipoprotein cholesterol (LDL-C) and aortic valve calcium in 6942 participants in community-based studies . The LDL-C GRS was also associated with incident aortic stenosis in a separate community-based population. Trials of lipid lowering therapies in patients with aortic stenosis have not shown convincing benefit but the potential effect of lipid lowering therapy initiated earlier is uncertain. (See "Aortic valve sclerosis and pathogenesis of calcific aortic stenosis", section on 'Genetic factors'.)
Risk of myocardial infarction and nonobstructive coronary heart disease (November 2014)
Given the slow progression of atherosclerosis, patients with coronary heart disease (CHD) may be asymptomatic for years, and the prognosis related to nonobstructive coronary lesions is uncertain. Nonobstructive CHD refers to stenosis ≥20 percent but <70 percent, while obstructive CHD is identified when at least one stenosis is ≥70 percent. In a retrospective cohort study of over 37,000 patients (96 percent male) without prior CHD events who underwent elective coronary angiography and were followed for one year, the risk of myocardial infarction (MI) increased with the extent of both nonobstructive and obstructive lesions . Compared to patients without CHD, the risk of MI trended higher for patients with one vessel nonobstructive CHD and was significantly greater for two and three vessel nonobstructive CHD. Patients found to have nonobstructive CHD should be treated with usual secondary prevention measures. (See "Epidemiology of coronary heart disease", section on 'Non-obstructive CHD'.)
Lower risk of fatal bleeding with target specific oral anticoagulants versus warfarin (November 2014)
All anticoagulants carry a risk of bleeding, and the lack of an antidote for direct factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) and the direct thrombin inhibitor dabigatran increases concerns about this risk. Reassuringly, a meta-analysis of 12 randomized trials in patients with atrial fibrillation or venous thromboembolism that compared bleeding risk with these agents versus vitamin K antagonists found lower rates of fatal bleeding, major bleeding, and intracranial bleeding with the direct factor Xa and direct thrombin inhibitors . Individual patient factors continue to play a role in anticoagulant choice and the development of reversal agents for the factor Xa and thrombin inhibitors is underway. (See "Management of bleeding in patients receiving target-specific oral anticoagulants", section on 'Risk of bleeding'.)
Beta blockers in stable coronary heart disease (August 2014)
Although beta blocker therapy improves survival in patients who have sustained an acute myocardial infarction (MI), there is no convincing evidence for this benefit in patients with stable disease. In an observational study of over 26,000 patients discharged after a first coronary heart disease event (an acute coronary syndrome or coronary artery revascularization) and followed for nearly four years, there was no difference in the risk of death in the subgroup without recent MI between those who did or did not receive beta blocker . In patients with stable coronary heart disease who have not had a recent acute MI, beta blockers are indicated to treat angina but not to improve survival. (See "Secondary prevention of cardiovascular disease", section on 'Beta blockers'.)
ADULT ENDOCRINOLOGY AND DIABETES
Glycemic control and mortality in type 1 diabetes mellitus (January 2015)
In a report from the Diabetes Control and Complications Trial (DCCT) and follow-up Epidemiology of Diabetes Interventions and Complications Study (EDIC), representing a mean follow-up period of 27 years (1429 patients), there was a modest reduction in all-cause mortality in patients with type 1 diabetes initially assigned to intensive insulin therapy (43 deaths in the intensive therapy group versus 64 in the conventional group) . The median A1C values for the intensive therapy and conventional therapy groups during the 6.5 year DCCT were 7.2 and 9.1 percent, respectively. However, the A1C levels equalized during the subsequent EDIC study. Thus, compared with conventional therapy, intensive insulin therapy for 6.5 years during the DCCT reduced the risk of mortality over at least the next 20 years, despite an absence of a difference in A1C values during the post-DCCT period. (See "Glycemic control and vascular complications in type 1 diabetes mellitus", section on 'Mortality'.)
Long-term effect of intensive glycemic control on macrovascular outcomes in type 2 diabetes (October 2014)
The ADVANCE trial randomly assigned 11,140 patients with long-standing type 2 diabetes to either standard therapy or modified release gliclazide plus other drugs as required to achieve an A1C of <6.5 percent, and found no benefit of intensive therapy on the primary composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke after a median of five years. Of the 10,082 surviving trial participants, 8494 enrolled in a post-trial monitoring study . A 2000-patient random subset of the surviving cohort that agreed to participate in the post-trial monitoring study had periodic laboratory testing for A1C, fasting blood glucose, serum creatinine, blood pressure, and weight. Mean A1C, which had been significantly different during the trial, became similar by the first post-trial visit and remained similar throughout the monitoring period (7.2 and 7.4 percent in the original intensive and standard groups, respectively). After a median total follow-up of 9.9 years, similar to the findings in the randomized trial, there was no benefit of intensive therapy on macrovascular outcomes. (See "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'ADVANCE'.)
Combination bupropion-naltrexone for the treatment of obesity (October 2014)
In September 2014, the combination of bupropion-naltrexone was approved in the United States by the Food and Drug Administration (FDA) as an adjunct to diet and exercise in patients with BMI ≥30 kg/m2 or ≥27 kg/m2 in the presence of at least one weight-related comorbidity . Because bupropion-naltrexone can raise blood pressure and heart rate, the FDA is requiring post-marketing studies to evaluate cardiovascular outcomes and the effect of the combination on cardiac conduction. Pending these further studies, we prefer to use orlistat or lorcaserin when medical treatment of obesity is indicated, rather than bupropion-naltrexone. (See "Obesity in adults: Drug therapy", section on 'Bupropion-naltrexone'.)
Long-term effect of antihypertensive therapy in diabetic patients (October 2014)
The ADVANCE trial randomly assigned 11,000 diabetic patients to a fixed combination of perindopril-indapamide or placebo for approximately four years. The trial included both patients with and without hypertension, and concomitant therapy with other blood pressure medication during the trial was at the discretion of the patient's physician. Patients in the perindopril-indapamide group had lower rates of cardiovascular mortality (3.8 versus 4.6 percent) and all-cause mortality (7.3 versus 8.5 percent). A post-trial, open-label cohort (8500 patients) were followed for an additional six years . Blood pressures between the treatment and placebo groups, which were different during the trial (135/74 versus 140/76 mmHg), became similar within six months after completion of the trial and remained similar throughout the cohort phase. Compared with those originally assigned placebo, those who had received perindopril-indapamide had a lower death rate during the cohort phase (15.3 versus 16.7 percent), as well as a lower incidence of major cardiovascular events (13.3 versus 14.2 percent). Combining both the trial and cohort phases together (approximately 10 years of follow-up), all-cause mortality was significantly lower among those in the treatment group (hazard ratio 0.91, 95% CI 0.84-0.99). Thus, blood pressure lowering is associated with long-term benefits on mortality and cardiovascular disease in diabetic patients. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'ADVANCE trial'.)
Weight loss diets (September 2014)
If adhered to, any diet that reduces caloric intake below expenditure will result in weight loss that is related to the energy deficit. This was illustrated by the findings of a meta-analysis of 48 randomized trials (7286 individuals) comparing different dietary programs (predominantly low carbohydrate, moderate macronutrient, or low fat) with a comparator (no diet or competing dietary program) . Compared with no diet, all diet programs resulted in significant weight loss (approximately 6 to 8 kg at six months). At 12-month follow-up, the average weight losses of all diet programs were 1 to 2 kg less than at six-month follow-up. Weight loss differences between individual diets were minimal. (See "Obesity in adults: Dietary therapy", section on 'Weight loss diets'.)
Interferon-free regimens for chronic genotype 1 HCV infection (December 2013, MODIFIED January 2015)
Several highly effective and well tolerated interferon-free options are now available for chronic genotype 1 hepatitis C virus (HCV) infection. Ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir plus dasabuvir, and simeprevir plus sofosbuvir all achieve sustained virologic response (SVR) rates, and thus effective cure, in excess of 90 percent in genotype 1 infected patients [39-47]. The duration of the regimen and the decision of whether to add weight-based ribavirin depend on the treatment history, presence of cirrhosis, and, for the ombitasvir-paritaprevir-ritonavir plus dasabuvir regimen, the infecting subtype (1a or 1b) (algorithm 2). The choice between the regimens depends primarily on the potential for drug interactions and drug toxicity. Additionally, in the United States, options will be limited by the individual's insurance provider. If cost or insurance coverage is not an issue, we generally favor the regimen of ledipasvir-sofosbuvir for its favorable adverse effect profile, its minimal drug interactions, and its ease of administration (a single pill once daily). (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Selection of treatment regimens'.)
Intermittent dosing of proton pump inhibitors for peptic ulcer bleeding (October 2014)
Treatment with proton pump inhibitors (PPIs) leads to elevation of gastric pH levels, which stabilizes blood clots and improves clinical outcomes. As a result, PPIs are recommended for all patients with peptic ulcer bleeding. High-dose continuous infusions of intravenous (IV) PPIs have traditionally been recommended for patients presenting with upper gastrointestinal bleeding. However, several meta-analyses of randomized trials have failed to show superior outcomes with high-dose continuous IV proton pump administration compared with intermittent dosing (eg, 40 mg IV twice daily). In addition, intermittent dosing could lead to decreased resource utilization and cost. In the most recent meta-analysis, intermittent dosing was not inferior to high-dose continuous infusions with regard to rebleeding, mortality, need for surgery or repeat intervention, or the need for urgent intervention in patients with peptic ulcers with high-risk stigmata (active bleeding, adherent clot, or a visible vessel) . There was also a trend toward a decreased risk of rebleeding with intermittent dosing. Based on this cumulative evidence, for patients presenting with upper gastrointestinal bleeding, we now recommend treatment with IV pantoprazole, esomeprazol, or omeprazole (where available) at a dose of 40 mg twice daily rather than a high-dose continuous infusion. (See "Overview of the treatment of bleeding peptic ulcers", section on 'Summary and recommendations' and "Overview of the treatment of bleeding peptic ulcers", section on 'Continuous versus intermittent dosing'.)
ADULT INFECTIOUS DISEASE
Interferon-free regimens to treat HCV in HIV/HCV coinfected patients (February 2015)
Patients coinfected with HIV and hepatitis C virus (HCV) traditionally had lower response rates to HCV treatment with peginterferon and ribavirin compared with individuals without HIV infection. However, with the use of direct-acting antiviral (DAA) agents in HCV treatment, HIV infection is no longer a negative predictor of response. In two studies of HIV/HCV genotype 1 coinfected individuals, sustained virological response rates to two interferon-free DAA regimens (ledipasvir-sofosbuvir or ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin) were greater than 90 percent, comparable to rates in populations infected with HCV alone [49,50]. The major consideration in HCV antiviral regimen selection for HIV/HCV coinfected patients is the potential for drug interactions between antiretroviral and HCV antiviral agents. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)
Pneumonia and long-term cardiovascular risk (February 2015)
Community-acquired pneumonia has been associated with increased short-term risk of cardiac events. In two cohorts of community-dwelling adults, hospitalization for pneumonia was also associated with increased long-term risk of new-onset cardiovascular disease (myocardial infarction, cerebrovascular accident, or fatal coronary heart disease), even after adjusting for traditional cardiovascular risk factors . In one of the cohorts, the risk of cardiovascular events among patients with pneumonia was highest during the first year after hospitalization and remained higher than among controls through 10 years. In the other cohort, the risk of cardiovascular events was elevated during the first two years following pneumonia hospitalization, but not thereafter. (See "Prognosis of community-acquired pneumonia in adults", section on 'Association with cardiovascular events'.)
Oseltamivir for the treatment of influenza in adults (January 2015)
Oseltamivir has been demonstrated to shorten the duration of influenza symptoms and to reduce the duration of viral shedding. However, studies and meta-analyses have provided contradictory results regarding the effect of oseltamivir on influenza-related lower respiratory tract complications in healthy adults. A 2015 meta-analysis evaluated all manufacturer-sponsored randomized trials, published and unpublished, of oseltamivir for the treatment of influenza in adults . Among those with documented influenza, oseltamivir reduced the time to alleviation of all symptoms (median time 98 versus 123 hours), reduced lower respiratory tract complications requiring antibiotics, and reduced hospital admissions for any cause compared with placebo. In contrast to an earlier meta-analysis that aggregated study results and did not demonstrate a benefit with regards to complications, this meta-analysis pooled individual patient data from the trials, which is generally considered a more rigorous method . These results support our recommendations to use an antiviral agent such as oseltamivir in patients with confirmed or suspected influenza and severe illness or at high risk of complications. (See "Treatment of seasonal influenza in adults", section on 'Efficacy of oseltamivir'.)
Rapid nucleic acid amplification test for seasonal influenza (January 2015)
A rapid nucleic acid amplification test for influenza, the Alere i influenza A & B test, is available in several countries in Europe. In January 2015, the US Food and Drug Administration allowed use of the test in non-traditional laboratory sites, including physicians' offices, emergency rooms, health department clinics, and other healthcare facilities . This test uses a nasal swab sample and provides results (reports influenza A or B, but not subtypes) in as few as 15 minutes. It is performed on a small proprietary machine. Nucleic acid amplification tests are generally more sensitive than antigen and immunofluorescence techniques, which most other rapid influenza tests utilize. (See "Diagnosis of seasonal influenza in adults", section on 'Nucleic acid tests' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Approach to testing'.)
Circulating influenza A H3N2 viruses and influenza vaccine effectiveness in the United States (December 2014, MODIFIED January 2015)
In December 2014, the United States Centers for Disease Control and Prevention (CDC) released a health advisory stating that more than half of influenza A H3N2 viruses collected and analyzed in the United States in October and November 2014 were antigenically different (drifted) from the H3N2 antigen included in this season's influenza vaccines . Most isolated influenza viruses to date have been H3N2 strains. During previous seasons in which influenza A H3N2 viruses have predominated, higher hospitalization and mortality rates have been reported among older people, very young children, and individuals with certain medical conditions. In seasons where predominant circulating influenza viruses have antigenically drifted, decreased vaccine effectiveness has been observed. Nevertheless, vaccination typically provides some cross-protection against drifted viruses and should still reduce hospitalization and death. As of early January 2015, overall vaccine effectiveness against laboratory-confirmed influenza associated with medically attended acute respiratory illness was only 23 percent . Influenza vaccination is still highly recommended . The CDC health advisory was issued to reemphasize the importance of the use of neuraminidase inhibitors (eg, oseltamivir, zanamivir) when indicated for the treatment and prevention of influenza infection as an adjunct to vaccination. (See "Seasonal influenza vaccination in adults", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season' and "Seasonal influenza in children: Prevention with vaccines", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season'.)
Intravenous peramivir for influenza (December 2014)
Peramivir was approved by the US Food and Drug Administration (FDA) in December 2014 for treating uncomplicated influenza infection in adults who have been ill for ≤2 days [57,58]. Peramivir is the first IV neuraminidase inhibitor to be approved by the FDA, although it has been in use in Japan and South Korea for several years. It is administered as a single intravenous dose of 600 mg. In a randomized trial, those who received peramivir had their influenza symptoms alleviated an average of 21 hours sooner and became afebrile approximately 12 hours sooner than those who received placebo. Patients who cannot receive zanamivir or oseltamivir (eg, those who cannot tolerate inhaled or enteral agents) should receive IV peramivir. Although the FDA has only approved IV peramivir for patients with uncomplicated influenza, we think it is also reasonable to use it for patients with severe influenza who cannot receive oral oseltamivir or inhaled zanamivir; in such patients, we would use either oseltamivir by a nasogastric tube or IV peramivir. (See "Treatment of seasonal influenza in adults", section on 'Efficacy of peramivir' and "Treatment of seasonal influenza in adults", section on 'Choice of antiviral drug'.)
ACIP recommendations for the 2014-2015 influenza season (August 2014)
In August 2014 the United States Advisory Committee on Immunization Practices (ACIP) released updated recommendations for the prevention of seasonal influenza with vaccines . Important changes from previous recommendations include:
●A preferential recommendation for the nasal spray vaccine (live attenuated influenza vaccine, LAIV) over the intramuscular injection (inactivated influenza vaccine, IIV) for children two through eight years of age who do not have specific contraindications to the nasal vaccine (eg, asthma, egg allergy, diabetes, immunosuppression). UpToDate agrees with this recommendation, but also prefers LAIV for children older than eight years. If LAIV is not immediately available, IIV should be administered to avoid missing an opportunity for influenza immunization. (See "Seasonal influenza in children: Prevention with vaccines", section on 'LAIV compared with IIV'.)
●Changes to the dosing schedule for children six months through eight years of age (algorithm 3). (See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule'.)
Recommendations for adults are largely unchanged. (See "Seasonal influenza vaccination in adults", section on 'Overview'.)
ADULT NEPHROLOGY AND HYPERTENSION
Risk of gestational hypertension or preeclampsia in kidney donors (November 2014)
The assessment of risk conferred by living kidney donation is critically important in determining the suitability of individual donor candidates. A retrospective cohort study demonstrated an increased risk of gestational hypertension or preeclampsia compared with well-matched nondonors . Women of childbearing age who wish to donate a kidney should be advised of this increased risk. (See "Evaluation of the living kidney donor and risk of donor nephrectomy", section on 'Maternal and fetal outcomes'.)
Initial imaging in patients with suspected nephrolithiasis (September 2014)
Computerized tomography (CT) and ultrasonography as initial imaging strategies were compared in a large multicenter randomized trial . Patients presenting to an emergency department (ED) with suspected nephrolithiasis (but without signs of another serious diagnosis) were assigned to initial imaging with a non-contrast helical CT scan, ultrasonography performed by a radiologist, or ultrasonography performed at the bedside by an ED physician. Subsequent evaluation and care was at the discretion of the treating clinicians. The sensitivity for stone detection was lower for ultrasonography than CT scan (54 percent if performed by an ED physician or 57 percent performed by a radiologist compared with 88 percent for CT). A CT scan was performed in 41 percent of patients who initially underwent ultrasonography while 5 percent of patients who initially had a CT subsequently had ultrasonography. Despite the lower sensitivity of ultrasonography, the rates of important missed diagnoses that resulted in complications, such as pyelonephritis with sepsis or diverticular abscess, were similar (0.5 percent with ultrasonography versus 0.3 percent with CT). Serious adverse events and return visits to the ED after discharge were also similar. Patients assigned to receive an initial CT were exposed to more than twice as much radiation during the initial ED visit than those assigned ultrasonography although, because many patients assigned ultrasonography ultimately underwent CT, the differences in cumulative radiation exposure at six months were less dramatic. While we previously suggested a non-contrast helical CT scan as the test of choice for most patients with suspected nephrolithiasis, we now consider that both CT and ultrasonography are acceptable initial imaging modalities in patients with suspected nephrolithiasis who have a low clinical suspicion for an alternative serious diagnosis. In such patients, ultrasonography leads to less radiation exposure than CT and equivalent overall outcomes. (See "Diagnosis and acute management of suspected nephrolithiasis in adults", section on 'Tests of choice: Non-contrast CT scan or ultrasonography'.)
ADULT NEUROLOGY AND PSYCHIATRY
Rising number of opioid overdoses in US (November 2014)
Rising rates of opioid use and addiction in recent years have had significant clinical consequences. A study of nationally representative data on US emergency department (ED) visits has found that approximately 731,000 ED visits for opioid overdose occurred from 1993 to 2010; the population-based rate of ED visits for opioid overdose nearly quadrupled over this time period . Increases in overdose rates were seen with both pharmaceutical and non-pharmaceutical opioids. These findings suggest that programs implemented to combat opioid abuse and misuse in the US have been insufficient. (See "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis", section on 'Overdose'.)
Risk of elective noncardiac surgery after acute stroke (September 2014)
Elective surgery should be deferred when possible in the setting of an acute stroke, as adverse outcomes are likely to be increased in this setting. In a Danish nationwide cohort study, the risk of major adverse cardiovascular events (ischemic stroke, acute myocardial infarction, and cardiovascular mortality) and 30-day all-cause mortality was significantly higher in patients with a history of recent stroke . Compared with patients without stroke, the risk of major adverse events was highest in the first three months after stroke (odds ratio 14) and appeared to level off after nine months. (See "Perioperative care of the surgical patient with neurologic disease", section on 'Patients with a history of stroke'.)
Negative D-dimer does not predict recurrence risk in unprovoked VTE (January 2015)
Indefinite anticoagulation is preferred in patients with a first episode of unprovoked venous thromboembolism (VTE). The D-dimer assay has been proposed as a test to identify patients in whom anticoagulant therapy may be safely discontinued. However, a prospective study that measured the VTE recurrence rate in 319 patients with a first episode of unprovoked VTE who had two consecutive negative D-dimer levels does not support this indication for d-dimer testing . The first level was drawn following completion of a standard course of anticoagulant therapy and the second after one month off anticoagulation. The two year recurrence rate was 7 percent per patient-year, with higher rates reported in men (10 percent per patient year) compared with women (5 percent per patient year). These rates are sufficiently high that they support the current recommendation of indefinite anticoagulation in this population; D-dimer measurements do not appear to be useful in identifying candidates for more limited treatment. (See "Rationale and indications for indefinite anticoagulation in patients with venous thromboembolism", section on 'Elevated D-dimer'.)
Relative efficacy of pharmacologic interventions for knee osteoarthritis (February 2015)
A large network meta-analysis of 137 trials involving over 33,000 patients with knee osteoarthritis (OA) compared the relative efficacy of available treatments for knee OA . All treatments, except acetaminophen, showed a clinically significant improvement from baseline pain. Intraarticular (IA) hyaluronic acid was found to be superior to oral and IA placebo, acetaminophen, celecoxib, and naproxen but not to ibuprofen, diclofenac, or IA glucocorticoids for pain relief. There also appeared to be a relative effect of IA administration when compared with oral medications, which was driven by a large placebo effect of IA injections. These findings are limited by the short-term follow-up period of three months as well as the use of indirect comparisons. (See "Treatment of osteoarthritis resistant to initial pharmacologic therapy", section on 'Comparison with intraarticular glucocorticoids'.)
Individually tailored hand exercise program for rheumatoid arthritis (October 2014)
An individualized hand exercise program involving stretching and strengthening may provide additional benefit to patients with rheumatoid arthritis (RA), even those on a stable regimen of disease-modifying antirheumatic drugs. In a randomized trial involving nearly 500 patients with RA, the addition of an individually tailored strengthening and stretching hand exercise program to usual care from a therapist resulted in significantly greater improvement in overall hand function at one year of follow-up compared with usual care alone . (See "Nonpharmacologic therapies and preventive measures for patients with rheumatoid arthritis", section on 'Occupational therapy'.)
Injectable progestins and risk of venous thrombosis (September 2014)
In contrast to other progestin-only contraceptives, depot medroxyprogesterone acetate (DMPA) use may be associated with an increased risk of venous thrombosis and embolism (VTE). In a case-control study, women with a first episode of VTE were twice as likely to be DMPA users than were controls in the general population . In this study, VTE was not associated with use of progestin-only pills, the levonorgestrel-releasing intrauterine device, or the progestin-only contraceptive implant. However, in the absence of data about absolute risk of VTE in DMPA users, we continue to think that the advantages of using DMPA generally outweigh the risks for women with a history of VTE. (See "Depot medroxyprogesterone acetate for contraception", section on 'Cardiovascular risk'.)
Safety of inhaled long-acting beta agonist/glucocorticoid for asthma during pregnancy (February 2015)
An important clinical question for pregnant women with asthma is whether using a combination long-acting beta-agonist (LABA) plus inhaled glucocorticoid confers an increased risk for adverse fetal outcomes, compared with monotherapy using a higher dose of the inhaled glucocorticoid. In a study of 1302 pregnant women with asthma, the risk for a major congenital malformation was not increased when a LABA plus low dose inhaled glucocorticoid was compared with a medium dose inhaled glucocorticoid, or when a LABA plus medium-dose inhaled glucocorticoid was compared with a high-dose inhaled glucocorticoid . (See "Management of asthma during pregnancy", section on 'Long-acting beta-adrenergic agents'.)
Target diastolic blood pressure in pregnancy (February 2015)
In pregnant women with chronic (preexistent) or gestational hypertension, the effect of less-tight versus tight control of hypertension on pregnancy complications is unclear. A randomized trial that assigned pregnant women with gestational or chronic hypertension to diastolic blood pressure treatment targets of 85 or 100 mmHg reported similar maternal, fetal, and neonatal outcomes in both groups . More women in the 100 mmHg target group developed severe hypertension, although this was not associated with an increase in transient ischemic attack or stroke. The trial was not powered to exclude a clinically important increase in fetal growth restriction in the 85 mmHg target group. For these reasons, we continue to suggest a diastolic pressure target of 90 to 100 mmHg for pregnant women with hypertension without end-organ damage. (See "Management of hypertension in pregnant and postpartum women", section on 'Blood pressure goal'.)
Timing of antiretroviral initiation during pregnancy (January 2015)
The risk of HIV transmission from an infected mother to her infant is proportional to the level of maternal viremia at delivery. Among women not already taking an antiretroviral regimen, viral suppression at delivery is more likely when a regimen is initiated earlier during gestation. In a large US cohort of antiretroviral-naïve HIV-infected women who initiated a combination antiretroviral regimen during pregnancy, a detectable viral load at delivery was documented in 13 percent overall, but in 24 percent of those who initiated the regimen during the third trimester . See "Use of antiretroviral medications in pregnant HIV-infected patients and their infants in resource-rich settings", section on 'When to initiate antiretroviral medications during pregnancy'.)
No change to recommendations for pain medicine use in pregnancy (January 2015)
Studies of pain medicine use by pregnant women have suggested associations between prescription nonsteroidal antiinflammatory drugs (NSAIDs) and the risk of miscarriage, the use of acetaminophen and subsequent childhood attention deficit hyperactivity disorder (ADHD), and the use of opioids and the development of fetal neural tube defects. A 2015 US Food and Drug Administration (FDA) Drug Safety Communication has found methodologic limitations to these studies and inconclusive results regarding NSAIDs and acetaminophen use . Further investigation is needed regarding maternal opioid use and the risk of fetal neural tube defects. It is always advisable for pregnant women to avoid medications that are not clearly needed. However, specific recommendations regarding analgesic use need not change based on this current analysis. (See "Initial prenatal assessment and first trimester prenatal care", section on 'Treatment of pain and fever'.)
Low Apgar scores: Predictors of neonatal and infant deaths (November 2014)
Although not used to guide resuscitation, Apgar scores, first introduced in 1953, have been used as a measure of the newborn's overall clinical status and response to resuscitation during the first minutes after delivery. The accurate predictability of low Apgar scores for mortality was confirmed by a study that reviewed discharge and mortality data for all births in Scotland between 1992 and 2010 . Linear regression analysis showed Apgar scores ≤3 at five minutes, compared with normal scores (between 7 and 10), were associated with 300-fold increased risk of early neonatal death (birth to seven days of life), 30-fold increased risk of late neonatal death (7 to 28 days of life), and 50-fold increased infant death (up to one year of age). (See "Neonatal resuscitation in the delivery room", section on 'Apgar scores'.)
Anticoagulation and placenta-mediated complications (October 2014)
Placenta-mediated pregnancy complications include pregnancy loss, severe/early-onset preeclampsia, and birth of small for gestational age infant. Anticoagulation has been recommended to prevent placenta-mediated pregnancy complications in women with thrombophilia, but the effectiveness of this approach is controversial. In a multinational randomized trial (TIPPS), prophylactic use of dalteparin in women with thrombophilia and a history of previous placenta-mediated pregnancy complications did not reduce the occurrence of the composite outcome (pregnancy loss, severe/early-onset preeclampsia, birth of small for gestational age infant, major venous thromboembolism) compared with women who did not receive dalteparin . We believe the available evidence supports not prescribing anticoagulants to prevent adverse obstetrical outcomes in pregnant women with thrombophilia. (See "Inherited thrombophilias in pregnancy", section on 'Prevention of pregnancy complications'.)
Aspirin for preventing preeclampsia (September 2014)
For women at high risk of developing preeclampsia, the US Preventive Services Task Force (USPSTF) now recommends use of low dose aspirin after 12 weeks of gestation to reduce the risk of preeclampsia, preterm birth, and fetal growth restriction . Low dose aspirin prophylaxis results in potentially substantial benefit and no more than minimally harmful effects. This recommendation is consistent with recommendations of other professional organizations. The USPSTF also offered a pragmatic approach for selecting a high risk population, while acknowledging that there are no validated methods for identifying these women. (See "Preeclampsia: Prevention", section on 'Approach to therapy'.)
PEDIATRICS: GENERAL PEDIATRICS
Strict cognitive rest associated with more symptoms in children with concussions (February 2015)
Strict cognitive rest, including avoidance of reading, video games, loud music, and screen time (computer, tablet, television, or smart phone), limitation of social activities, and absence from school, has been advocated as a primary treatment for pediatric concussion. However, evidence for this approach is sparse. In a trial of 99 patients aged 11 to 22 years who were diagnosed with a concussion after pediatric emergency department evaluation (36 percent with loss of consciousness), all subjects reduced physical activity and one group was assigned to strict cognitive rest for five days while the other was assigned to usual care (one to two days of rest followed by gradual return to full cognitive activities) . Strict cognitive rest was associated with significantly more daily reported postconcussive symptoms during the 10 days of follow-up, while there were no differences in neurocognitive function or balance outcomes at three and 10 days after injury. Thus, strict cognitive rest was harmful in this trial. We suggest an individualized approach to cognitive rest, in which patients are instructed to avoid mental activities that worsen symptoms and are followed closely by a clinician with expertise in managing concussions. (See "Concussion in children and adolescents: Management", section on 'Cognitive rest'.)
Oat cereal for thickening infant bottle feeds (February 2015)
For healthy infants with problematic gastroesophageal reflux who are bottle-fed, thickening feeds with infant cereal slightly improves symptoms. Although rice cereal has traditionally been used for this purpose, oat cereal is now preferred because of concerns about possible contamination of rice cereal with arsenic [76-78]. The US Food and Drug Administration (FDA) is investigating to determine if there are clinically significant traces of arsenic in rice cereal. (See "Gastroesophageal reflux in infants", section on 'Thickening feeds'.)
Bronchodilators not routinely recommended for bronchiolitis in infants and children (January 2015)
In November 2014, the American Academy of Pediatrics released updated guidelines for the diagnosis, management, and prevention of bronchiolitis . The 2014 guideline recommends against the administration of inhaled albuterol or epinephrine in the treatment of bronchiolitis; the previous guideline (2006) included a trial of bronchodilators as an option. We agree that bronchodilators should not be used routinely in the treatment of bronchiolitis and no longer suggest a trial of bronchodilators. Although bronchodilators may provide modest short-term clinical improvement, they do not affect overall outcome, may have adverse effects, and increase the cost of care.
While we no longer routinely suggest inhaled bronchodilators for infants and children with bronchiolitis, a one-time trial of inhaled bronchodilators may be warranted for infants and children with bronchiolitis and severe disease (eg, nasal flaring; retractions; grunting; respiratory rate >70 breaths per minute; dyspnea; or cyanosis) or respiratory failure. (See "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on 'Inhaled bronchodilators'.)
Indications for voiding cystourethrogram after first UTI (December 2014)
Young children with urinary tract infection (UTI) often undergo imaging studies to evaluate for abnormalities such as vesicoureteral reflux (VUR). There is a lack of consensus about the optimal imaging strategy, particularly whether voiding cystourethrogram (VCUG) should be performed after the first UTI. Predictors of renal scarring after a first UTI were investigated in a meta-analysis of individual patient data from nine studies including >1200 children <18 years who underwent renal scintigraphy at least five months after their first UTI . The risk of renal scarring was greatest in patients with Grade IV or V VUR (odds ratio 22.5); approximately two-thirds of children with Grade IV or V VUR had either abnormal renal ultrasonography or the combination of temperature ≥39°C (102.2°F) and a pathogen other than Escherichia coli. Based on these findings, we have added the combination of temperature ≥39°C and a pathogen other than E. coli to our indications for obtaining a VCUG after a first febrile UTI. (See "Urinary tract infections in infants and children older than one month: Acute management, imaging, and prognosis", section on 'Indications'.)
Weight gain after adenotonsillectomy for obstructive sleep apnea (October 2014)
Treatment of obstructive sleep apnea (OSA) by adenotonsillectomy may be associated with weight gain, at least in the short term. In a randomized trial, children with OSA treated with early adenotonsillectomy experienced more weight gain during the first seven months after surgery than those managed with watchful waiting . Those who were overweight at baseline were more likely to become obese at follow-up if they were treated with adenotonsillectomy (52 versus 21 percent). Thus, when children who are at risk for overweight, overweight, or obese require adenotonsillectomy for treatment of OSA, care should be taken to minimize anticipated post-operative weight gain. (See "Management of obstructive sleep apnea in children", section on 'Adenotonsillectomy' and "Management of childhood obesity in the primary care setting", section on 'Prevention'.)
Long-acting reversible contraception for adolescents (October 2014)
The intrauterine device and etonogestrel implant are two types of long-acting reversible contraception (LARC). Although LARC is more effective than other methods, few adolescents choose LARC. Lack of access to services, lack of information, and increased cost may be barriers to LARC for adolescents. Removal of these barriers appears to be associated with increased use of LARC and decreased rates of pregnancy. In a prospective study, 1404 urban adolescents 15 to 19 years of age were educated about reversible contraception (emphasizing the benefits of LARC), provided with their choice of reversible contraception at no cost, and followed for two to three years . Nearly three-quarters of participants chose LARC. The pregnancy rate among participants was nearly five times less than that in a contemporaneous cohort of sexually active teenagers in the United States (34.0 versus 158.5 per 1000). The American Academy of Pediatrics now recommends the etonogestrel implant and intrauterine device as first-line contraceptive options for adolescents . (See "Contraception: Overview of issues specific to adolescents", section on 'Overcoming barriers'.)
How to keep a cast dry (August 2014)
Keeping a cast dry can be challenging, but the various methods used to accomplish this are rarely studied. According to an observational laboratory study comparing six approaches, one effective and inexpensive method for maintaining a dry cast is to enclose the cast in two plastic bags, one over the other, and seal each bag to the skin with duct tape (picture 1) . This approach was substantially more effective than using a single plastic bag sealed with either a rubber band or duct tape, and equally effective as expensive commercial products. (See "General principles of definitive fracture management", section on 'Complications'.)
Updated recommendations for palivizumab RSV prophylaxis (August 2014)
In 2014, the American Academy of Pediatrics updated its guidance for palivizumab prophylaxis for respiratory syncytial virus (RSV) infection . Important changes include:
●Palivizumab prophylaxis is no longer recommended for infants born at ≥29 weeks’ gestation unless they have additional risk factors for RSV (eg, chronic lung disease of prematurity [CLD]).
●Palivizumab prophylaxis is no longer recommended during the second year of life for infants with hemodynamically significant heart disease.
●Continuation of palivizumab prophylaxis is no longer recommended for infants with breakthrough RSV infection.
Recommendations for infants with CLD are largely unchanged. (See "Respiratory syncytial virus infection: Prevention", section on 'Indications for palivizumab'.)
Transcutaneous bilirubin measurements after discontinuation of phototherapy in neonates (November 2014)
In neonates, transcutaneous bilirubin (TcB) measurement devices are used to estimate total serum or plasma bilirubin (TB), thereby reducing the need for blood sampling. While TcB measurements are typically lower than TB, the degree of underestimation is greater in infants with high TB levels (>15 mg/dL [257 micromol/L]), dark-skinned infants, and during phototherapy. In these settings, TB may be needed to accurately determine the magnitude of hyperbilirubinemia. A German study has also reported TcB underestimation of TB is greater within the first eight hours of discontinuation of phototherapy . This difference between TcB and TB measurements subsequently decreases, and returns to pretreatment values 24 hours after discontinuation of phototherapy. As a result, clinicians must take into consideration the timing of TcB measurement in relationship to discontinuation of phototherapy. If there is any question regarding the validity of TcB measurements, TB should be obtained to assess the degree of neonatal hyperbilirubinemia. (See "Evaluation of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Transcutaneous bilirubin'.)
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