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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ADULT GENERAL INTERNAL MEDICINE
Relative cardiovascular safety of celecoxib, naproxen, and ibuprofen (December 2016)
The cardiovascular (CV) safety of celecoxib, the COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), compared with other NSAIDs, is a matter of debate. In a randomized trial (PRECISION) involving over 24,000 patients with arthritis and either known CV disease or CV risk factors, the CV safety of celecoxib was noninferior to both naproxen and ibuprofen, two nonselective NSAIDs . Depending upon the analysis, about 2 to 5 percent of subjects experienced a CV event during follow-up, which was slightly lower than the expected event rate. Despite some limitations, this trial suggests that celecoxib in moderate doses can be administered, when indicated, without concern about increased CV risk compared with the nonselective nonsteroidal agents naproxen and ibuprofen. (See "COX-2 selective inhibitors: Adverse cardiovascular effects", section on 'Celecoxib' and "Nonselective NSAIDs: Adverse cardiovascular effects", section on 'Risk of myocardial infarction, stroke, and death'.)
No role for routine serologic screening for genital herpes infection (December 2016)
Genital herpes, which can be caused by herpes simplex virus type 1 or 2 (HSV-1 or HSV-2), is one of the most common sexually transmitted infections, and sexual transmission can occur even in the absence of symptoms. Despite this, routine serologic screening for herpes simplex is not recommended in asymptomatic adolescents and adults due to significant limitations of available tests, as highlighted in a recent US Preventive Services Task Force statement . Limitations include the low specificity and high false positive rate of serologic tests for HSV-2 and the inability of serologic tests for HSV-1 to differentiate oral from genital infection. Furthermore, there are no specific treatment interventions for asymptomatic patients, so the anxiety and disruption of personal relationships associated with a positive test outweigh any potential benefits. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Screening'.)
FDA warning removed from varenicline for smoking cessation (December 2016)
In 2009, the US Food and Drug Administration (FDA) required varenicline packaging to include a boxed warning about potential neuropsychiatric side effects, but this warning has been removed in 2016 , based on results of a randomized trial that found no difference in adverse neuropsychiatric events comparing varenicline with nicotine patch or placebo in patients with or without a coexisting psychiatric disorder . As with any medication, we advise that patients should be told to contact their clinician if they or their family notice any unusual behavior or mood symptoms as well as any new or worsening symptoms of cardiovascular disease. (See "Pharmacotherapy for smoking cessation in adults", section on 'Safety'.)
Inadequate sleep and adverse cardiometabolic outcomes (December 2016)
The adverse health outcomes of inadequate sleep duration (<7 hours per night) and quality are increasingly recognized. A new scientific statement from the American Heart Association reviews data linking sleep restriction with adverse cardiometabolic outcomes and recommends that healthy sleep behavior be addressed in public health campaigns to promote ideal cardiac health, alongside blood pressure, cholesterol, diet, blood glucose, physical activity, weight, and smoking cessation . (See "Insufficient sleep: Definition, epidemiology, and adverse outcomes", section on 'Cardiovascular morbidity'.)
E-cigarette use and respiratory symptoms in adolescents (November 2016)
Use of e-cigarettes has been rising among adolescents in the United States, and the long-term health consequences of e-cigarette use are unknown. A survey of 11th and 12th grade students in California found an association between self-reported chronic bronchitic symptoms (chronic cough, phlegm, bronchitis in the past year) and current or past e-cigarette use that remained after adjustment for confounders such as cigarette smoking or secondhand smoke exposure; risk of respiratory symptoms increased with frequency of current use of e-cigarettes . (See "E-cigarettes", section on 'Adverse health effects'.)
Alpha-1-blocker therapy for symptoms from benign prostate hyperplasia (November 2016)
Drug treatment can reduce symptoms from benign prostatic hyperplasia (BPH), but the comparative effectiveness of different drug treatments has not been well studied. A meta-analysis commissioned by the Agency for Healthcare Research and Quality (AHRQ) compared drugs or combinations of drugs developed in the past 10 years for treatment of BPH with monotherapy using older drugs . Treatment with a newer alpha-1-blocker (AB) (silodosin), a combination of an anticholinergic drug (fesoterodine, tolterodine, or solifenacin) with an AB, or a phosphodiesterase type 5 (PDE-5) inhibitor (tadalafil) resulted in similar short-term symptom relief but a greater risk of adverse effects compared with treatment with an older AB (primarily tamsulosin). There was insufficient evidence to draw conclusions about other newer drugs. Thus, we suggest initial treatment of BPH symptoms with an AB alone, and choose the AB based upon cost, side effects (particularly hypotension), and potential medication interactions (especially with PDE-5 inhibitors). (See "Medical treatment of benign prostatic hyperplasia", section on 'Efficacy and administration'.)
Treatment of degenerative meniscal tears (September 2016)
Acute meniscal tears often benefit from surgical treatment, but the appropriate management of chronic, degenerative tears, particularly in middle-aged adults, has been a source of debate. A recent trial randomly assigned 140 middle-aged adults (mean age 49.5) with a degenerative meniscal tear (and no evidence of osteoarthritis on magnetic resonance imaging [MRI]) to receive exercise therapy or partial meniscectomy . The trial found no clinically significant difference in knee function or pain at two years of follow-up. This finding is consistent with several other small randomized trials that have reported no clinically significant benefit from arthroscopic surgery in such patients. In the absence of persistent joint effusions or mechanical dysfunction, we suggest physical therapy as the initial management for middle-aged patients with degenerative meniscal tears. (See "Meniscal injury of the knee", section on 'Chronic degenerative meniscal injury'.)
Clinical manifestations of severe synthetic cannabinoid toxicity (July 2016)
Synthetic cannabinoids consist of a heterogeneous group of chemical compounds that act as agonists at cannabinoid receptors with 2 to 800 times the potency of delta-9 tetrahydrocannabinol (THC), the active component of cannabis (marijuana). They have emerged as a popular recreational drug in the United States and Europe. In an observational study of a multicenter, hospital-based registry of medical toxicology consultations, over two-thirds of 277 patients with single-agent exposure to synthetic cannabinoids had altered mental status including severe agitation, toxic psychosis, hallucinations, seizures, and coma . Rhabdomyolysis and acute kidney injury were present in approximately 5 percent of these patients. There were three deaths, including a 17-year-old adolescent with sudden death after first-time inhalational use. Thus, unlike cannabis, synthetic cannabinoids have significant potential to cause serious and life-threatening toxicity among recreational users. (See "Synthetic cannabinoids: Acute intoxication", section on 'Clinical manifestations'.)
Structured exercise program and mobility disability in older adults (January 2017)
The randomized multicenter LIFE study, comparing a structured exercise program with a health information program among sedentary adults aged 70 to 89 years without major mobility disability at baseline, had previously reported that exercise decreased the incidence of major mobility disorder (MMD) and risk for permanent MMD. In a new report, the structured exercise also increased the likelihood of transition from MMD, if it occurred, to no MMD . Preserving mobility is essential for maintaining independence and quality of life among older adults. These findings indicate that exercise both prevents initial mobility disability and promotes restored mobility in those who become disabled. (See "Physical activity and exercise in older adults", section on 'Benefits of physical activity'.)
Declining use of feeding tubes in advanced dementia (August 2016)
Patients with advanced dementia commonly have eating problems in the final stages of illness, and caregivers are faced with decisions about whether to continue oral feeding by hand or place a long-term feeding tube. The available evidence fails to demonstrate any health benefits of tube feeding over ongoing hand feeding, and an increasing number of consensus-based guidelines advocate against feeding tube placement in this setting. In keeping with these recommendations, a recent study in the United States found that the proportion of nursing home residents with advanced dementia who received a feeding tube within one year of the onset of feeding problems decreased by approximately 50 percent between the years 2000 and 2014 . Advance care planning is critical in the management of patients with dementia and should include preparatory discussions about eating problems and other common complications encountered in the advanced stages of the disease. (See "Palliative care of patients with advanced dementia", section on 'Oral versus tube feeding'.)
Inactivated influenza vaccine for 2016-2017 season in the northern hemisphere (August 2016)
The effectiveness of seasonal influenza vaccines varies from season to season and is determined by a number of factors, including the match between circulating influenza strains and influenza strains in the vaccine. During the 2015-2016 influenza season, data from the United States Influenza Vaccine Effectiveness Network indicated that inactivated influenza vaccine (IIV) was 63 percent effective in preventing influenza in children, but live attenuated influenza vaccine (LAIV) was not effective . Findings of poor or lower than expected LAIV effectiveness were also noted during the 2013-2014 and 2014-2015 seasons in the United States. These findings are inconsistent with studies sponsored by the manufacturer and studies from other countries that found LAIV was effective (ranging from 46 to 58 percent) during the 2015-2016 season [13-16]; however, LAIV was less effective than IIV in all of these studies . In August 2016, the United States Centers for Disease Control and Prevention recommended that LAIV not be used during the 2016-2017 influenza season . While some countries have elected to continue using LAIV , we suggest IIV rather than LAIV for the 2016-2017 influenza season in the northern hemisphere. (See "Seasonal influenza in children: Prevention with vaccines", section on 'IIV versus LAIV' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)
Mammography associated with breast cancer overdiagnosis (October 2016)
A study examining data for women age 40 years and older from the Surveillance, Epidemiology, and End Results (SEER) database calculated size-specific breast cancer case fatality rates prior to and after the widespread adoption of mammography screening . The authors estimated that approximately 80 percent of cancers identified by screening would not have caused clinical symptoms. Moreover, the authors calculated that at least two-thirds of the reduction in mortality associated with large tumors may be attributed to improved cancer treatments rather than screening. While acknowledging that cancer overdiagnosis does occur, and that randomized trials demonstrating benefit of mammography were largely conducted prior to modern therapy and imaging, we continue to suggest breast cancer screening for women ages 50 to 74 years, with individualized decision making for those between the ages of 40 and 50 years, given that the overall burden of evidence suggests benefit to screening. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Overdiagnosis'.)
USPSTF recommendations for skin cancer screening (August 2016)
In July 2016, the United States Preventive Services Task Force (USPSTF) updated its statement on skin cancer screening and concluded that there is insufficient evidence to assess the balance of benefits and harms of screening for skin cancer in asymptomatic adults with a clinical visual skin examination . Although we agree with the USPSTF conclusion, we suggest that persons at higher risk for fatal melanoma (eg, white men 50 years of age and over), individuals with multiple moles or at least a few clinically atypical moles, and individuals with the “red hair phenotype” have a total body skin examination performed by a clinician who has had appropriate training in the identification of melanoma. (See "Screening and early detection of melanoma", section on 'Recommendations of expert groups'.)
ADULT ENDOCRINOLOGY AND DIABETES
Metformin use in patients with diabetes and renal impairment, heart failure, or chronic liver disease (January 2017)
The US Food and Drug Administration (FDA) recently revised its labeling of metformin, which will increase its use in patients with renal impairment. This change is supported by the findings of a systematic review of 17 observational studies comparing diabetes regimens with and without metformin; metformin use was associated with lower all-cause mortality among patients with heart failure, renal impairment, or chronic liver disease with hepatic impairment . In addition, metformin use in patients with renal impairment or heart failure was associated with fewer heart failure readmissions. Metformin remains contraindicated in patients with estimated glomerular filtration rate (eGFR) <30 mL/min, concurrent active or progressive liver disease, or unstable or acute heart failure with risk of hypoperfusion and hypoxemia. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.)
Vertebroplasty for osteoporotic compression fractures (November 2016)
The indications for and timing of vertebroplasty for the treatment of osteoporotic compression fractures are controversial. In a trial comparing vertebroplasty or simulated vertebroplasty (sham) in 120 patients with acute (less than six weeks) vertebral fracture and back pain, more patients in the vertebroplasty group achieved clinically significant lower pain scores at 14 days . Two previous sham-controlled trials, however, did not show a significant reduction in pain with vertebroplasty, likely due to differences in study design, including different sham procedures for the control arm and varying definitions of acute vertebral fracture. (See "Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment", section on 'Vertebroplasty'.)
Semaglutide and cardiovascular outcomes (November 2016)
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist that is in development for the treatment of type 2 diabetes. In a trial in over 3000 patients with type 2 diabetes and established or increased risk for cardiovascular disease, semaglutide reduced the composite primary cardiovascular endpoint (first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo . Diabetic retinopathy complications occurred more frequently in the semaglutide group, particularly among patients with existing retinopathy, whereas new or worsening nephropathy occurred less frequently. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)
Impact of adding activity trackers to behavioral weight loss programs (October 2016)
Wearable devices that monitor and provide feedback on physical activity and diet do not appear to provide additional benefit over standard behavioral weight loss interventions. In a 24-month trial of 470 overweight or obese adults who were randomly assigned to a standard intervention (self-monitoring of diet and exercise) or an enhanced intervention (use of a wearable device with a web interface to monitor diet and physical activity), there were similar improvements in body composition, fitness, physical activity, and diet, but the addition of a wearable device resulted in less weight loss than the standard behavioral weight loss program (3.5 versus 5.9 kg) . (See "Obesity in adults: Role of physical activity and exercise", section on 'Addition of "activity trackers"'.)
Investigational monoclonal anti-sclerostin antibody for postmenopausal osteoporosis (September 2016)
Sclerostin is secreted by osteocytes and inhibits bone formation. Romosozumab, a monoclonal anti-sclerostin antibody under investigation for the treatment of osteoporosis, has been shown to improve bone density in postmenopausal women. In a trial specifically designed to assess radiographic vertebral fracture outcomes, 7180 postmenopausal women with osteoporosis were randomly assigned to romosozumab (210 mg subcutaneously once monthly) or placebo for 12 months . Thereafter, all women received denosumab (60 mg subcutaneously every six months) for an additional 12 months. The incidence of radiographic vertebral fracture was lower in the romosozumab group at 12 months (0.5 versus 1.8 percent) and 24 months (0.6 versus 2.5 percent). There was an increased frequency of injection site reactions in the romosozumab group. Ongoing trials should provide more information about safety and efficacy, including nonvertebral fracture reduction. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Emerging therapies'.)
Postmenopausal estrogen and cognitive function (August 2016)
While limited observational and clinical trial data have suggested that early, but not late, postmenopausal exposure to estrogen provides protection against later cognitive impairment, a new randomized trial found no benefit of estrogen regardless of when it was started. In the Early versus Late Intervention Trial with Estradiol (ELITE), 643 postmenopausal women, stratified according to time since menopause (<6 years [early] versus >10 years [late]), received oral estradiol (with progesterone for women with a uterus) or placebo for a median of five years . When compared with placebo, estradiol, whether it was started early or late, had no effect on verbal memory, executive function, or global cognition. (See "Estrogen and cognitive function", section on 'Younger menopausal women'.)
Microvascular outcomes with empagliflozin in patients with type 2 diabetes (July 2016)
There are few trials evaluating microvascular outcomes in patients taking sodium-glucose co-transporter 2 (SGLT2) inhibitors. Microvascular disease was a prespecified secondary outcome in a recent trial designed specifically to evaluate cardiovascular morbidity and mortality in patients with type 2 diabetes and established cardiovascular disease (CVD) . In this trial, 7028 patients with type 2 diabetes and established CVD were randomly assigned to empagliflozin or placebo once daily; the majority of patients were also taking metformin, antihypertensives, and lipid-lowering agents. Incident or worsening nephropathy occurred in 12.7 and 18.8 percent of patients in the empagliflozin and placebo groups, respectively. The reduction in nephropathy drove the improved composite microvascular endpoint (the initiation of retinal photocoagulation, vitreous hemorrhage, diabetes-related blindness, or incident or worsening nephropathy) for empagliflozin. The mechanism behind the reduction in incident or worsening nephropathy with empagliflozin is likely multifactorial, but is thought to be largely related to a direct renovascular effect of empagliflozin. Whether other SGLT2 inhibitors have similar renal effects is unknown. There have been reports of acute kidney injury, some requiring hospitalization and dialysis, in patients taking canagliflozin or dapagliflozin. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus".)
ADULT HEMATOLOGY AND ONCOLOGY
Initial treatment for localized, low-risk prostate cancer (September 2016)
There are many options for treating men with localized, low-risk prostate cancer. The most extensive data comparing these options come from the Prostate testing for cancer and Treatment (ProtecT) trial, in which 1653 patients with localized, low-risk prostate cancer were randomly assigned to active monitoring of serum PSA, radical prostatectomy, or radiation therapy (RT) [28,29]. At a median follow-up of 10 years, there was no difference in 10-year overall survival, which was approximately 99 percent for all three groups. However, the incidence of metastases was increased in patients randomized to active surveillance (6.3 per 1000 person-years versus 2.4 and 3.0 for those managed with radical prostatectomy or RT). Longer follow-up will be required to know whether the higher incidence of metastatic disease affects cancer-specific mortality, overall mortality, or quality of life. Decisions regarding the choice of treatment continue to be individualized based upon a consideration of patient age, comorbidity, and patient preferences. (See "Initial approach to low- and very low-risk clinically localized prostate cancer", section on 'ProtecT trial'.)
Laboratory testing of donated blood for Zika virus (April 2016, Modified August 2016)
The US Food and Drug Administration (FDA) now recommends universal testing of blood components for Zika virus in the United States and its territories (with a several month implementation period), based on an increasing number of cases of mosquito-borne transmission of Zika virus in Florida and Puerto Rico and the potential for sexual transmission from asymptomatic individuals . The testing involves one of two assays that detect Zika virus RNA. Approximately 1 percent of donations from Puerto Rico, an active transmission area, were positive for Zika virus in June of 2016 . Blood collection facilities also use the donor medical and travel history to disqualify individuals who may be infected with Zika virus. (See "Blood donor screening: Laboratory testing", section on 'Zika virus'.)
Duration of adjuvant endocrine therapy for breast cancer (July 2016)
For postmenopausal women receiving adjuvant treatment with an aromatase inhibitor (AI) for hormone-positive breast cancer, the standard duration of treatment has been five years. However, data from the MA17R trial demonstrated that a longer course of treatment improves disease-free survival (DFS) . Among approximately 1900 postmenopausal women who had completed four and a half to six years of therapy with an AI, treatment for an additional five years improved five-year DFS relative to those who received placebo (95 versus 91 percent). There was no difference between the groups in regards to overall survival. Bone-related toxic effects were more frequent among those receiving extended treatment. Based on these results, we now offer an additional five years of treatment to those who have completed five years of AI therapy. However, it is reasonable for women with low risk of recurrence who are concerned about the risks and toxicities of extended treatment to omit extended treatment after a risk-benefit discussion. (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Duration of endocrine treatment'.)
ADULT INFECTIOUS DISEASE
Guidelines on diagnosis of tuberculosis (January 2017)
Guidelines from the American Thoracic Society, Infectious Diseases Society of America, and the Centers for Disease Control and Prevention on the diagnosis of tuberculosis in adults and children were published in December 2016 . They state that an interferon-gamma release assay (IGRA) is generally preferred for diagnosis of latent tuberculosis infection (LTBI) in individuals five years or older who have low-to-intermediate risk of progression to active disease (table 1), although the tuberculin skin test (TST) is an acceptable alternative if IGRA is not available or too costly. For those who have high risk of progression to active disease, either IGRA or TST is acceptable, but many guideline panel members noted using the alternative test if the initial one was negative and considering a positive result from either test to indicate LTBI. The evaluation of suspected tuberculosis disease should include three sputum specimens for acid-fast bacilli (AFB) smear and culture and one or more specimens for nucleic acid amplification (NAA) testing. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults" and "Diagnosis of pulmonary tuberculosis in HIV-uninfected patients" and "Latent tuberculosis infection in children" and "Tuberculosis disease in children".)
WHO recommendations on HIV self-testing (December 2016)
The World Health Organization (WHO) recently updated its HIV testing guidelines to advocate expanded use of self-testing with rapid home diagnostic tests as an effort to improve HIV testing uptake [34,35]. This recommendation is supported by trials that found higher rates of HIV testing with self-testing compared with facility-based testing among couples and individuals at high risk for infection (eg, men who have sex with men and partners of HIV-infected individuals). Self-testers with a reactive test should undergo confirmatory testing by a trained provider. (See "Screening and diagnostic testing for HIV infection", section on 'Resource-limited settings'.)
Meningococcal conjugate vaccination for HIV-infected patients (November 2016)
Growing evidence has suggested that HIV-infected individuals have a disproportionate incidence of invasive meningococcal disease, with an estimated risk 5 to 13 times that of the general population. Because of this, the Centers for Disease Control and Prevention in the United States now recommends meningococcal conjugate vaccination (with MenACWY-CRM [Menveo] or MenACWY-D [Menactra]) for all HIV-infected individuals older than two months . This includes a primary vaccine series for those who have not previously received it and interval booster doses every several years; the precise schedule depends on the age of the patient (table 2). Individuals may also have separate indications for serogroup B meningococcal vaccination. Evidence of vaccine efficacy in HIV-infected patients is limited to immunologic outcomes. (See "Immunizations in HIV-infected patients", section on 'Meningococcal vaccine' and "Meningococcal vaccines".)
Incidence of sexually transmitted infections in the United States (November 2016)
The total number of cases of chlamydia (over 1.5 million), gonorrhea (nearly 400,000), and syphilis (nearly 24,000) reported to the Centers for Disease Control and Prevention in the United States in 2015 was the highest ever recorded in a given year . Chlamydia and gonorrhea continued to occur most commonly among 15 to 24 year olds, and men who have sex with men accounted for the majority of gonorrhea and primary/secondary syphilis cases. These surveillance data highlight the importance of sexually transmitted infection prevention efforts, screening, and treatment among at-risk individuals. (See "Epidemiology of Chlamydia trachomatis infections", section on 'Incidence' and "Epidemiology and pathogenesis of Neisseria gonorrhoeae infection", section on 'Incidence' and "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Epidemiology' and "Screening for sexually transmitted infections".)
Cranberry products and urinary tract infection in women (October 2016)
Numerous clinical studies on the effects of cranberry products on recurrent urinary tract infection (UTI) in women have failed to clearly demonstrate a preventive benefit. In a year-long randomized trial among female nursing home residents, cranberry capsules similarly did not reduce adjusted rates of bacteriuria plus pyuria or symptomatic UTI compared with placebo . While we do not suggest cranberry products to reduce the risk of recurrent UTI, there is likely little harmful effect. (See "Recurrent urinary tract infection in women", section on 'Cranberry products'.)
HBV reactivation during HCV antiviral therapy (October 2016)
Reactivation of hepatitis B virus (HBV) infection, including cases with fatal fulminant hepatitis, has been reported in several patients receiving direct-acting antiviral therapy for hepatitis C virus (HCV) infection . Patients should be tested for HBV coinfection prior to initiation of HCV therapy, with HBV treatment initiated for those who meet criteria (table 3). HBV surface antigen (HBsAg) positive patients who do not initially meet HBV treatment criteria should be monitored with HBV DNA testing during HCV treatment. In patients with a positive HBV core antibody (HBcAb) but negative HBsAg, we check liver enzymes during HCV treatment and perform reflex HBsAg and HBV DNA testing for unexplained elevations. (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 'Other laboratory testing'.)
Condom use in HIV serodiscordant couples (August 2016)
HIV serodiscordant couples may question whether continued condom use is necessary for HIV prevention if the HIV-infected partner is on antiretroviral therapy (ART). One observational study followed over 900 serodiscordant couples (both heterosexual couples and men who have sex with men [MSM]) in whom the HIV-infected partner was virally suppressed on ART and who chose not to use condoms . After more than 1200 couple-years of follow-up, there were no intra-couple transmission events. Ten MSM and one heterosexual partner acquired HIV infection during the study period, but viral sequence analysis suggested that these infections were not transmitted from the long-term HIV-infected partner. We continue to encourage condom use in HIV serodiscordant couples, as condoms offer protection from other sexually transmitted infections and provide back-up for potential periods of loss of virologic suppression. We advise couples who choose not to use condoms that the risk of HIV transmission in the setting of stable virologic suppression of the infected partner, while apparently negligible, cannot be ruled out completely. (See "HIV infection: Risk factors and prevention strategies", section on 'Serodiscordant couples'.)
HIV treatment to prevent sexual transmission (August 2016)
Growing evidence has bolstered the concept that successful antiretroviral therapy (ART) of HIV-infected individuals substantially reduces the risk of sexual HIV transmission. Final analysis of a multinational randomized trial (HPTN 052) of over 1700 HIV serodiscordant heterosexual couples demonstrated that early ART for the HIV-infected partner, compared with delaying ART until certain clinical parameters were met, reduced HIV transmission risk by 93 percent . All participants received condoms and risk reduction counseling. There were no linked transmissions (determined by detecting the same virus in both partners through viral sequencing) from HIV-infected individuals who had achieved stable viral suppression on ART; all eight linked transmissions from HIV-infected individuals using ART occurred within three months of ART initiation or in the setting of ART failure. This preventive benefit of ART is one of the reasons that early ART is recommended for all HIV-infected individuals, regardless of CD4 cell count. (See "HIV infection: Risk factors and prevention strategies", section on 'Treatment as prevention' and "When to initiate antiretroviral therapy in HIV-infected patients", section on 'Benefits of antiretroviral therapy'.)
Mosquito-borne transmission of Zika virus in the continental United States (August 2016)
Zika virus is a mosquito-borne infection associated with congenital microcephaly and other birth defects among babies born to women infected during pregnancy. Mosquito-borne transmission of Zika virus was detected in Florida in July 2016, and in August 2016 the United States Centers for Disease Control and Prevention (CDC) issued an advisory recommending that pregnant women avoid travel to affected areas . Updates regarding areas with Zika may be found on the CDC website (http://www.cdc.gov/zika/). (See "Zika virus infection: An overview", section on 'Travel advisories for pregnant women'.)
Sofosbuvir-velpatasvir for all genotypes of chronic HCV infection (July 2016)
All-oral, direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have proliferated over the past two years. Sofosbuvir-velpatasvir, a coformulated combination of an NS5B and an NS5A inhibitor, is the first such regimen that has high, well-established efficacy for all genotypes, even in patients with cirrhosis or prior treatment failure with interferon-based regimens [43-45]. This agent was approved by the US Food and Drug Administration in June 2016 and is now our preferred or one of our preferred regimens for adults with chronic HCV infection of any genotype because of its efficacy, simplicity of administration, and limited drug interactions (algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4). Sofosbuvir-velpatasvir is given for 12 weeks for all genotypes. For genotype 3 infection, the addition of ribavirin may be warranted, depending on the presence of cirrhosis, the prior treatment history, and the presence of mutations associated with NS5A resistance. (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'.)
Treatment failure of pharyngeal gonorrhea following combination antimicrobial therapy (July 2016)
Because of concerns about the decreasing susceptibility of Neisseria gonorrhoeae to several classes of antibiotics, combination antimicrobial therapy with ceftriaxone plus a second agent, preferably azithromycin, is the recommended treatment for uncomplicated gonorrhea. However, treatment failure following combination therapy has now been reported, in a heterosexual man from the United Kingdom who presented with both urogenital and pharyngeal infection . Although the urogenital infection was successfully treated with ceftriaxone plus azithromycin, the pharyngeal infection persisted, and decreased susceptibility to both agents was detected in the post-treatment isolate. This report, in addition to surveillance reports suggesting increasing rates of decreased susceptibility to azithromycin in N. gonorrhoeae isolates in the United States , highlights the need for novel treatment strategies for gonorrhea in the face of rising antimicrobial resistance. (See "Treatment of uncomplicated gonococcal infections", section on 'Monitoring for and managing treatment failure' and "Treatment of uncomplicated gonococcal infections", section on 'Rationale for dual therapy'.)
ADULT NEPHROLOGY AND HYPERTENSION
Effect of antihypertensive drug class on fracture rates (January 2017)
Thiazide diuretics stimulate distal tubular reabsorption of calcium, leading to a decrease in urinary calcium excretion and a possible benefit on bone mineral density. The rates of hip or pelvic fractures among patients treated with thiazide-like diuretics, angiotensin converting enzyme (ACE) inhibitors, or calcium channel blockers were compared in a post-hoc analysis of the ALLHAT trial . At approximately five years, those randomly assigned chlorthalidone had fewer hip or pelvic fractures as compared with those assigned to either lisinopril or amlodipine. Thus, if monotherapy is appropriate in a patient with hypertension and osteoporosis, thiazide-like diuretics may have advantages over ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Thiazide diuretics'.)
Outcomes in severe asymptomatic hypertension (hypertensive urgency) (November 2016)
There is no proven benefit from rapid reduction of blood pressure in patients with severe asymptomatic hypertension (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg). In one retrospective study of over 59,000 patients who presented in the ambulatory setting with severe asymptomatic hypertension, there was no difference in major adverse cardiovascular events, or prevalence of uncontrolled hypertension six months later, for patients sent to the emergency department or sent home from the office for outpatient blood pressure management . Hospitalization rates were higher for those sent to the emergency department. This cohort study suggests that most patients with asymptomatic hypertensive urgency who present in the ambulatory setting can be managed as outpatients. (See "Management of severe asymptomatic hypertension (hypertensive urgencies) in adults", section on 'Rapidity of blood pressure lowering'.)
Angioplasty in renal artery stenosis (November 2016)
In patients with atherosclerotic renal artery stenosis, a meta-analysis of trials comparing percutaneous transluminal renal angioplasty (PTRA) with stent placement plus medical therapy with medical therapy alone found no benefit from PTRA on mortality, end-stage renal disease, major cardiovascular events, or blood pressure control . One or more major periprocedural complications occurred in 7.1 percent of patients who underwent PTRA. Thus, in patients with renal artery stenosis and clinical characteristics similar to those enrolled in these trials, we suggest not revascularizing and instead treating with medical therapy alone. (See "Treatment of unilateral atherosclerotic renal artery stenosis", section on 'Revascularization versus medical therapy alone'.)
J-shaped relationship between blood pressure and cardiovascular outcomes (November 2016)
There may be a blood pressure threshold below which tissue perfusion is reduced and risk is increased for cardiovascular and renal events and mortality (a J-shaped curve between blood pressure and event rate). In a large international prospective observational study of patients with stable coronary artery disease and treated hypertension, achieved diastolic pressures below 70 and above 80 mmHg were independently associated with increased risk for adverse outcomes (figure 1) . Similarly, achieved systolic pressures below 120 and above 140 mmHg were independently associated with increased risk for adverse outcomes (figure 2). However, these data are observational, and other evidence disputes the importance of these J-shaped curves, particularly for systolic pressure. Based upon the available evidence and the physiology of coronary perfusion, we generally try to avoid lowering the diastolic blood pressure to a value of <60 mmHg in most patients. (See "What is goal blood pressure in the treatment of hypertension?", section on 'J-shaped diastolic curve'.)
ADULT NEUROLOGY AND PSYCHIATRY
Age of symptom onset and diagnosis of adult ADHD (September 2016)
Attention deficit hyperactivity disorder (ADHD) is conceptualized as a disorder with childhood onset that persists in adulthood. DSM-5 diagnostic criteria for adult ADHD require the presence of several symptoms prior to age 12 years. Multiple recent studies, however, have challenged this understanding of the disorder. One of them, a longitudinal cohort study, followed all children born in Pelotas, Brazil in 1993 up to the ages of 18 or 19 years . Three hundred ninety-three of the 5249 children were diagnosed with ADHD at age 11 and 492 were diagnosed with ADHD at age 18 or 19 years. Only 60 children with ADHD continued to have ADHD as young adults (17.2 percent) and only 60 young adults with ADHD had the disorder in childhood (12.6 percent). The requirement of childhood onset for the diagnosis of adult ADHD is controversial and may be reexamined as further data become available. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis", section on 'Course'.)
Complications of dopaminergic therapy for restless legs syndrome (August 2016)
The main complication of long-term dopaminergic therapy for restless legs syndrome/Willis-Ekbom disease (RLS/WED) is “augmentation,” or an increase in symptom severity with increasing doses of medication. This may present as earlier onset of symptoms during the day, increased intensity of symptoms, or spread to previously uninvolved body parts (eg, arms, trunk). New consensus-based guidelines on the identification and management of augmentation recommend avoiding dopaminergic drugs as first-line therapy for RLS/WED when possible, screening patients on dopaminergic therapy for augmentation as part of routine clinical follow-up (table 4), and using the lowest doses possible to control symptoms . Treatment options for augmentation reviewed in the guideline include altering the dopaminergic dosing schedule, switching to an extended release preparation, and transitioning to an alpha-2-delta calcium channel ligand (eg, gabapentin enacarbil, pregabalin). In addition, alternative causes of worsening symptoms should be sought, such as low iron stores, sleep deprivation, and certain drugs such as serotonergic antidepressants. (See "Treatment of restless legs syndrome/Willis-Ekbom disease and periodic limb movement disorder in adults", section on 'Augmentation'.)
Early benefit of aspirin after TIA or ischemic stroke (July 2016)
The risk of recurrent ischemic stroke is highest in the first days and weeks after a transient ischemic attack (TIA) or ischemic stroke, but the benefit of aspirin in this time period has not been well studied. In a recent pooled analysis of data from over 15,000 subjects in 12 trials evaluating aspirin for secondary prevention, the benefit of aspirin was strongest in the early weeks after TIA or ischemic stroke . Compared with control (mostly placebo), aspirin reduced the relative risk of recurrent ischemic stroke within the first six weeks by 58 percent (1 versus 2.4 percent, absolute risk reduction 1.4 percent). The benefit of aspirin in this time frame was greatest for the subgroup of patients with TIA or minor stroke. These findings emphasize that aspirin should be started as early as possible after the diagnosis of TIA or ischemic stroke is confirmed. (See "Antiplatelet therapy for secondary prevention of stroke", section on 'Aspirin'.)
Treatment of binge eating disorder (July 2016)
Several psychotherapies and medications have been studied for treating binge eating disorder. In a recent systematic review and meta-analysis of trials evaluating the efficacy of different treatment options compared with no treatment or placebo, there was strong evidence supporting the use of therapist-led cognitive-behavior therapy (CBT), lisdexamfetamine, or second-generation antidepressants (eg, selective serotonin reuptake inhibitors) . In addition, less compelling evidence indicated that patients can achieve abstinence with self-help CBT or topiramate. We regard CBT as first-line treatment; however, no head-to-head trials have compared the efficacy of different active treatments. (See "Binge eating disorder in adults: Overview of treatment", section on 'Cognitive-behavior therapy'.)
Safety of inhaled glucocorticoid-LABA combination therapy in asthma (September 2016)
In early studies, a small increase in asthma-related deaths associated with salmeterol led the US Food and Drug Administration to place a boxed warning on the use of long-acting beta agonists (LABAs) in asthma. While concerning, the number of events was small, and it could not be determined if the potential risk of salmeterol could be mitigated by combining LABAs with inhaled glucocorticoids. Three large randomized trials including 30,000 children and adults found no increase in asthma-related adverse events or deaths among patients who used combination inhalers with salmeterol or formoterol plus an inhaled glucocorticoid versus glucocorticoid monotherapy [56-58]. These studies support the safety of these fixed-dose combination inhalers in patients with moderate-to-severe asthma. (See "Beta agonists in asthma: Controversy regarding chronic use", section on 'Potential risk mitigation'.)
CPAP in obstructive sleep apnea does not reduce cardiovascular events (August 2016)
Whether continuous positive airway pressure (CPAP) therapy can reduce the increased risk of cardiovascular morbidity and mortality associated with obstructive sleep apnea (OSA) is unknown. The largest trial to address this issue randomized 2717 patients with moderate to severe OSA and established cardiovascular disease to CPAP therapy plus usual care or usual care alone (eg, education, risk factor modification) and followed patients for 3.7 years . Despite adequate control of OSA, there was no difference in cardiovascular events (eg, cardiovascular deaths, myocardial infarction, or stroke). However, the exclusion of patients who are among the most likely to benefit from CPAP (eg, patients with “sleepy” OSA) and a low adherence rate to therapy (mean was 3.3 hours per night) may have limited the potential benefit from this therapy. While the cardiovascular benefits are unproven, CPAP should be administered for the associated noncardiovascular benefits (eg, improvement in symptoms and quality of life) and should remain the mainstay of therapy for patients with moderate to severe OSA. (See "Obstructive sleep apnea and cardiovascular disease", section on 'Cardiovascular events'.)
Vaginal prasterone for dyspareunia in postmenopausal women (November 2016)
In November 2016, the US Food and Drug Administration approved the use of prasterone (also known as dehydroepiandrosterone [DHEA]) for treatment of dyspareunia in women with vulvovaginal atrophy (VVA) due to menopause . In an earlier randomized trial of women with VVA and moderate to severe dyspareunia, 12 weeks of daily intravaginal DHEA resulted in improved scores for pain during sexual activity and other key domains of female sexual function (desire, arousal, lubrication, orgasm, satisfaction) compared with placebo . However, patients may find daily dosing more cumbersome than twice weekly dosing with vaginal estrogen preparations. (See "Treatment of genitourinary syndrome of menopause (vulvovaginal atrophy)", section on 'Dehydroepiandrosterone (prasterone)'.)
Long-acting reversible contraception and teenage pregnancy rates (November 2016)
In a systematic review of nine studies including nearly 27,000 adolescent and young adult women (≤25 years), the 12-month continuation rate was nearly twice as high with the intrauterine device or contraceptive implant as with other contraceptive methods (approximately 85 percent versus 40 to 50 percent) . Increased contraceptive use, particularly increased use of these highly effective long-acting reversible contraceptive (LARC) methods, contributed to the historically low teenage pregnancy rate in 2015 . These observations support our recommendations to highlight LARC methods when discussing contraception with adolescents and young adults. (See "Pregnancy in adolescents", section on 'Epidemiology' and "Contraception: Overview of issues specific to adolescents", section on 'Long-acting reversible methods'.)
Delayed cord clamping (January 2017)
Delaying umbilical cord clamping for at least 30 to 60 seconds after birth in both term and preterm vigorous infants is the recommendation of an updated committee opinion by the American College of Obstetricians and Gynecologists (ACOG) . Previously, ACOG had recommended individualizing the timing of cord clamping in term infants. Although the optimal amount of time before cord clamping has not been studied extensively, we believe data support a minimum duration of delay of at least one minute in term births and 30 seconds in preterm births. (See "Management of normal labor and delivery", section on 'Cord clamping'.)
Safety of magnetic resonance imaging and gadolinium in pregnancy (September 2016)
Magnetic resonance imaging (MRI) may be used for diagnostic imaging in pregnancy when ultrasound examination is inadequate; however, fetal safety has not been conclusively established. Recently, the largest study of MRI in pregnancy (over 1700 exposed and 1.4 million unexposed births) reported that first-trimester MRI was not associated with significantly increased risks for stillbirth, neonatal death, congenital anomaly, neoplasm, or vision or hearing loss in children followed up to age four years, when adjustments were made for differences between exposure groups . The study also found that gadolinium exposure at any time during pregnancy was associated with an increased risk for stillbirth and neonatal death. Children exposed in utero were at increased risk for rheumatological, inflammatory, or infiltrative skin conditions, but not congenital anomalies or nephrogenic systemic fibrosis (NSF). This study is a major addition to the body of evidence supporting the safety of MRI in pregnancy when medically indicated. It also provides the first data supporting existing recommendations to avoid use of gadolinium-based contrast agents in pregnant women, when possible. (See "Diagnostic imaging procedures during pregnancy", section on 'Magnetic resonance imaging'.)
Safety of intranasal triamcinolone for allergic rhinitis in pregnancy (July 2016)
Intranasal glucocorticoid sprays are highly effective for treatment of allergic rhinitis, but concerns remain about their use in pregnancy. The overall safety of intranasal glucocorticoids in pregnancy was supported by an observational cohort study of over 140,000 pregnant women, of whom 2502 were exposed to these medications during the first trimester . Exposure was not associated with increased rates of miscarriage or overall rates of major congenital malformations compared with non-exposure. Triamcinolone was the only intranasal glucocorticoid of potential concern; first trimester use was associated with abnormalities of the respiratory system and choanal atresia. Although these findings are not conclusive, we prefer to use other intranasal glucocorticoids in the first trimester, such as intranasal mometasone, fluticasone, or budesonide, pending further data . (See "Recognition and management of allergic disease during pregnancy", section on 'Glucocorticoid nasal sprays'.)
PEDIATRICS: GENERAL PEDIATRICS
Early physical activity following acute concussion in children and adolescents (January 2017)
Although physical rest is routinely recommended after concussion, there are few data to determine whether avoidance of physical activity hastens recovery. In a prospective, multicenter cohort study of over 2400 children who were diagnosed with an acute concussion during an emergency department visit, early physical activity (within seven days of injury) compared with physical rest was associated with a significantly reduced risk of persistent postconcussive symptoms (PPCS) at 28 days . However, the difference in PPCS may be the result of confounding, and clinical trials are needed to confirm this result. We suggest that children and adolescents with concussions adhere to full physical rest until they have no symptoms of concussion (table 5) and normal balance or return to baseline on standardized testing. In the minority of patients with prolonged symptoms beyond seven days after injury, we introduce light, subsymptom threshold aerobic exercise (eg, light stationary bicycling), which can often be tolerated and may improve symptoms. (See "Concussion in children and adolescents: Management", section on 'Physical rest'.)
American Academy of Pediatrics guidelines for media use in children (November 2016)
The American Academy of Pediatrics has released updated guidelines on television and digital media use in children and adolescents [69,70]. Key recommendations include discouraging television and digital media use except for video chatting in children <18 months; helping parents choose high-quality programming when introducing media to children 18 to 24 months of age; limiting media use in children 2 to 5 years to ≤1 hour per day of high-quality programming; recommending that parents watch/use digital media with their children; and helping families to develop a "family media plan," which designates specific times and locations as media-free (eg, meal time, bedrooms). (See "Television and media violence", section on 'Family and individual'.)
Persistence of pediatric atopic dermatitis (November 2016)
Atopic dermatitis (AD) is a chronic disease with a highly variable course. Although most children are thought to “outgrow” it before adolescence, little is known about the factors associated with its persistence into adulthood. A meta-analysis including over 110,000 subjects found that 20 percent of children with AD had persistent disease eight years after the diagnosis, and less than 5 percent had persistent disease 20 years later . Children who developed AD before two years of age had a much lower risk of persistent disease than those who developed AD later in childhood or during adolescence. Other predictors of persistent AD were severity and duration of AD and female sex, whereas hypersensitivity to one or more allergens at disease onset did not seem to influence the persistence of disease. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Clinical course and complications'.)
Bag urine specimen testing to determine the need for urine culture in children (October 2016)
A bag urine specimen for a screening urine dipstick and/or urinalysis may prevent the need for a catheterized urine culture in selected patients older than 6 months of age at low risk for a urinary tract infection (UTI). In an observational study of over 800 previously healthy, well-appearing children 6 to 24 months of age presenting to a pediatric emergency department for evaluation of fever, screening of urine obtained by a bag specimen reduced the number of subsequent urine cultures obtained by bladder catheterization from 63 to 30 percent without prolonging the length of stay or increasing rates of revisits or missed UTI . Although potentially helpful for urine screening tests, bag urine samples should not be routinely used to obtain urine samples for culture, especially in situations where contamination of the specimen will complicate further management (eg, young infants or ill-appearing patients who warrant empiric parenteral antibiotics). (See "Urine collection techniques in infants and children with suspected urinary tract infection", section on 'Specimen for urine dipstick or urinalysis'.)
Strategies for preventing obesity and eating disorders (September 2016)
Clinicians and parents may be reluctant to address obesity in children because of concerns for promoting eating disorders. A new clinical report from the American Academy of Pediatrics outlines strategies that can be used to address obesity without promoting disordered eating . These include counseling parents to avoid "weight talk" (comments that focus on weight or weight-related appearance, even if they are not directed at the child) and focusing goals on healthy food choices and healthy eating behaviors rather than dieting (which is distinguished by caloric restriction with a goal of weight loss). (See "Management of childhood obesity in the primary care setting", section on 'Raising the sensitive issue of weight'.)
Infant simulator programs do not prevent teenage pregnancy (September 2016)
Infant simulator programs combine educational sessions with "care" for a doll that is programmed to replicate infant behaviors. They have become popular despite evidence from observational studies that they do not affect teenagers' attitudes toward teenage parenthood. A recent randomized trial provides additional evidence that infant simulator programs are ineffective . In this trial, 57 schools were randomly assigned to provide an infant simulator intervention or standard health education curriculum to 13- to 15-year-old girls who volunteered to participate. By 20 years of age, participants from the simulation schools had higher rates of birth (8 versus 4 percent) and abortion (9 versus 6 percent) than those who received the standard curriculum. We suggest a multifaceted approach to teenage pregnancy prevention, focusing on comprehensive sexuality education, delaying onset of sexual activity, and promotion of consistent and correct use of effective contraception for teenagers who decide to become sexually active. (See "Pregnancy in adolescents", section on 'Prevention'.)
Lipid screening in children and adolescents (August 2016)
Increasing evidence suggests that atherosclerosis begins in childhood and adolescence, yet the optimal strategies for early screening and treatment of the disease remain uncertain. A recent statement of the US Preventive Services Task Force (USPSTF) concluded that the available evidence on screening for lipid disorders in children and adolescents is insufficient to assess the balance of benefits and harms of screening . This position is unchanged from the 2007 USPSTF statement; however, it contradicts the 2011 National Heart, Lung, and Blood Institute (NHLBI) guidelines for cardiovascular health and risk reduction, which recommend screening in all children and adolescents and have been endorsed by the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) . We continue to suggest both age-based universal and selective screening for pediatric dyslipidemia. (See "Dyslipidemia in children: Definition, screening, and diagnosis", section on 'Recommendations of others'.)
Absence of pyuria in children with UTI (July 2016)
The diagnosis of urinary tract infection (UTI) in children is usually based on the finding of significant bacteriuria plus pyuria. However, in a retrospective review of 1181 children <18 years of age with symptomatic UTI and significant growth of a single uropathogen, microscopic urinalysis did not show pyuria in 13 percent . The frequency of pyuria was lower in children with Enterococcus (54 percent), Pseudomonas aeruginosa (62 percent), and Klebsiella (74 percent) than in children with E. coli (89 percent). Therefore, if the urine culture of a child with UTI symptoms demonstrates significant growth (≥50,000 colony-forming units [CFU]/mL from a catheterized specimen or ≥100,000 CFU/mL from a clean voided specimen) of Enterococcus, Klebsiella, or P. aeruginosa, UTI may be diagnosed in the absence of pyuria. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Pyuria'.)
PEDIATRICS: DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
Discontinuation of desmopressin treatment of nocturnal enuresis in children (July 2016)
Desmopressin is an effective short-term treatment for nocturnal enuresis in children, but relapse rates are high after discontinuation. A recent meta-analysis of four randomized trials including 500 patients demonstrated the benefit of tapering desmopressin rather than abrupt discontinuation (sustained response rate: 57 versus 42 percent) . In subgroup analyses, gradually decreasing the effective dose prevented relapse, but increasing the interval between doses did not. When discontinuing daily desmopressin, we suggest decreasing the daily dose rather than extending the interval between doses or abrupt discontinuation. (See "Nocturnal enuresis in children: Management", section on 'Discontinuation'.)
HPV vaccine dosing for individuals younger than 15 years (November 2016)
For individuals younger than 15 years receiving human papillomavirus (HPV) vaccination, two vaccine doses administered at least six months apart are now recommended by the Centers for Disease Control and Prevention in the United States . This new vaccine schedule is similar to schedules used in other countries and is supported by data demonstrating that two vaccine doses in young females have similar immunogenicity to three doses. However, the efficacy of fewer than three doses for prevention of cervical neoplastic disease has not been directly established. Three doses are still recommended for individuals older than 15 years because they have lower immunologic responses to HPV vaccination. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Immunization schedule'.)
Duration of passive protection of the infant from maternal influenza vaccination (September 2016, Modified September 2016)
A randomized trial of trivalent inactivated influenza vaccination of pregnant women reported 86 percent efficacy against laboratory confirmed influenza among infants ≤8 weeks of age and 25 to 30 percent efficacy among infants 8 to 24 weeks of age, compared with placebo vaccination . These data suggest that the passive protection afforded by maternal influenza vaccination declines significantly before the infant is eligible for influenza vaccination at six months of age. (See "Influenza and pregnancy", section on 'Infant protection'.)
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