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What's new in primary care
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What's new in primary care
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2016. | This topic last updated: Dec 01, 2016.

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.

PREVENTION

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 [1]. 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 [2-5]; however, LAIV was less effective than IIV in all of these studies [6]. In August 2016, the United States Centers for Disease Control and Prevention recommended that LAIV not be used during the 2016-2017 influenza season [7]. While some countries have elected to continue using LAIV [2], 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'.)

Abrupt smoking cessation compared with gradual smoking reduction (June 2016)

Earlier evidence from randomized trials had suggested that, after a quit date is set, abstinence rates were equivalent for patients who reduced smoking prior to the quit date or stopped smoking abruptly on the quit date. However, more recent studies suggest that among smokers who plan to quit in the near future, quit rates are higher for patients who stop abruptly. The most recent randomized trial included 697 smokers in England and found that gradual smoking cessation (decreasing by 75 percent in the two weeks prior to quitting) was associated with decreased likelihood of abstinence at four weeks when compared with abrupt smoking cessation (39 versus 49 percent) [8]. (See "Overview of smoking cessation management in adults", section on 'Setting a quit date'.)

SCREENING

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 [9]. 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 [10]. 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'.)

USPSTF recommendations for colorectal cancer screening (July 2016)

The United States Preventive Services Task Force (USPSTF) issued new guidelines for colorectal cancer screening in average risk adults [11]. The guidelines make a strong recommendation for screening, starting at age 50 years and continuing to age 75 for most patients, but in a departure from prior recommendations do not give preference for any one of seven screening test strategies over another. Options for screening are shown in a table (table 1). We agree with this screening test strategy based on shared decision making. Incorporating patient personal preferences may increase the likelihood that ongoing screening will occur. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'USPSTF guidelines'.)

Partner involvement in skin self-examination for early melanoma detection (July 2016)

For patients at increased risk of melanoma, having a partner involved in skin self-examination may increase the rates of self-examination and early melanoma detection. The effect of a structured educational intervention on the performance of skin self-examination and early detection of new melanomas was examined in a randomized trial including 494 melanoma patients and their partners [12]. During the two years of follow-up, a total of 66 patients developed a new melanoma. In the group of 395 patient-partner pairs receiving the intervention, 43 melanomas (33 in situ) were identified by patients or their partners and 10 by clinicians; in contrast, all 16 melanomas in the control group were identified by clinicians and none by the patient-partner pairs. (See "Screening and early detection of melanoma", section on 'Self-examination'.)

GENERAL INTERNAL MEDICINE

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 [13]. 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'.)

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) [14]. 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 [15]. 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'.)

Treatment for refractory urgency urinary incontinence in women (October 2016)

Whether onabotulinumtoxinA (BoNT-A) or sacral neuromodulation (SNM) is the better treatment for women with refractory urgency urinary incontinence (UUI) is unclear. In a randomized trial directly comparing the two approaches, the BoNT-A group had greater reductions in daily UUI episodes and bothersome symptoms [16]. However, the small statistical differences may not be clinically significant, particularly since the risk of urinary tract infection increased. Thus, we believe that both treatments are reasonable treatment options for refractory UUI. (See "Use of botulinum toxin for treatment of non-neurogenic lower urinary tract conditions".)

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 [17]. 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'.)

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 [18]. 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'.)

Endocrine Society publishes updated guidelines for primary aldosteronism (June 2016)

In 2016, the Endocrine Society updated their 2008 clinical practice guidelines for the diagnosis and treatment of primary aldosteronism [19]. They continue to recommend case detection and case confirmation in patient groups with a relatively high prevalence of primary aldosteronism (eg, hypertension with hypokalemia, adrenal incidentaloma, or family history early-onset hypertension). However, there are broadened indications for screening to include patients with sustained blood pressure >150 mmHg (systolic) and >100 mmHg (diastolic), and patients with hypertension and sleep apnea. In addition, they emphasize the need for more timely diagnosis and treatment of primary aldosteronism given its prevalence (10 percent in patients with hypertension) and its association with cardiovascular and renal damage. (See "Diagnosis of primary aldosteronism", section on 'Expert guidelines'.)

Mediterranean compared with low-fat or low-carbohydrate diet for weight loss (May 2016)

The impact of specific dietary composition on weight change remains uncertain. In a systematic review of five trials with follow-up ≥12 months, a Mediterranean diet resulted in similar weight loss (-4.1 to -10.1 kg) as a low-carbohydrate diet (-4.7 to -7.7 kg) and greater weight loss than a low-fat diet (2.9 to -5 kg) [20]. There was a similar reduction in lipid levels among the diets studied. The degree of adherence to the diet, irrespective of the particular macronutrient composition, is an important determinant of weight loss. We suggest choosing a diet or eating plan based upon patient preferences, which may improve long-term adherence. The diet should emphasize reductions in refined carbohydrates, processed meats, foods high in sodium and trans fat and higher intakes of fruits, nuts, fish, vegetables, and whole grains. (See "Obesity in adults: Dietary therapy", section on 'Weight loss diets'.)

PRIMARY CARE ALLERGY AND IMMUNOLOGY

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 [21]. 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 [22]. (See "Recognition and management of allergic disease during pregnancy", section on 'Glucocorticoid nasal sprays'.)

PRIMARY CARE DERMATOLOGY

Risks of oral ketoconazole for fungal skin and nail infections (May 2016)

In 2013, the US Food and Drug Administration (FDA) approved label changes for oral ketoconazole tablets to remove the indications for fungal skin and nail infections because of serious risks of oral ketoconazole treatment (serious liver damage, adrenal gland problems, and harmful drug interactions). In May 2016, based upon an FDA safety review that found continued prescribing of oral ketoconazole for fungal skin and nail infections (including one treatment-related patient death), the FDA released a drug safety communication warning healthcare professionals to avoid prescribing oral ketoconazole for skin and nail infections [23]. The risks of oral ketoconazole treatment for these indications outweigh the benefits. (See "Tinea versicolor (Pityriasis versicolor)", section on 'Other therapies'.)

PRIMARY CARE ENDOCRINOLOGY AND DIABETES

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 [24]. 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 [25]. 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) [26]. (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 [27]. 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 [28]. 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) [29]. 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".)

Liraglutide and cardiovascular outcomes (June 2016)

Glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control. However, there are few studies assessing clinically important cardiovascular health outcomes.

In one trial, 9340 patients with type 2 diabetes (mean A1C 8.7 percent) and underlying cardiovascular disease (prior myocardial infarction or stroke) or risk factors were randomly assigned to liraglutide or placebo [30]. Many patients were taking metformin (76 percent), sulfonylureas (50 percent), and/or insulin (44 percent). After a median follow-up of 3.8 years, the primary endpoint (time to first occurrence of a composite endpoint [death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke]) occurred in fewer patients in the liraglutide group (13 versus 14.9 percent).

In another trial of liraglutide versus placebo in 300 patients (59 percent with type 2 diabetes) with established heart failure and reduced left ventricular ejection fraction who were recently hospitalized, liraglutide had no significant effect on the composite outcome (time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level) [31]. In a prespecified subgroup analysis, there was no effect of liraglutide compared with placebo on heart failure outcomes in the subset of patients with diabetes.

The choice of additional therapy in metformin-treated patients with type 2 diabetes and persistent hyperglycemia should be individualized based upon patient characteristics, preferences, and costs. Among these considerations, a prior history of myocardial infarction or stroke might favor choosing liraglutide as the second drug to be added to metformin. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)

PRIMARY CARE GASTROENTEROLOGY

Colonoscopy preparation and sessile-serrated polyp detection rates (September 2016)

Previous studies have not demonstrated an association between split-dose colonoscopy preparation (ie, one half the evening prior to the colonoscopy and the second half the morning of) and improvement in sessile-serrated polyp detection rates. In a randomized trial, 341 patients were assigned to 2 liters of polyethylene glycol electrolyte lavage solution with ascorbic acid either as single-dose or split-dose regimen [32]. Split-dose lavage resulted in significantly lower duration and intensity of bowel movements, less disruption of sleep, and better quality of bowel preparation. There were no differences in adenoma detection rates between the two groups; however, split-dose lavage resulted in significantly higher sessile-serrated polyp detection rates (10 versus 2 percent). These data support current recommendations that colonoscopy preparations be administered as split-dose rather than being given entirely the evening prior to the colonoscopy. (See "Bowel preparation for colonoscopy and flexible sigmoidoscopy in adults", section on 'Split-dose lavage'.)

Toronto consensus for treatment of Helicobacter pylori (June 2016)

The Toronto consensus has published new guidelines for the treatment of Helicobacter pylori in adults [33]. These guidelines recommend a longer duration of treatment for all eradication regimens (14 versus 10 days), limiting the use of triple therapy to areas with low clarithromycin resistance or high eradication rates, and using quadruple (bismuth-containing or non-bismuth) therapy as a first line in all other areas. This is consistent with our approach. (See "Treatment regimens for Helicobacter pylori", section on 'Sequential therapy'.)

Rome IV criteria for functional gastrointestinal disorders (June 2016)

The Rome Foundation has released revised criteria (Rome IV) for the diagnosis of functional gastrointestinal disorders [34]. Examples of notable revisions include the changes to the criteria for irritable bowel syndrome and its subtypes, new criteria for reflux hypersensitivity, and inclusion of diagnoses with known etiologies that alter gut-brain interaction (eg, opioid-induced constipation). (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'Diagnostic criteria'.)

PRIMARY CARE GERIATRICS

Medication modification following fracture in older adults (September 2016)

Adverse drug effects are a particularly important issue for geriatric patients and may be unrecognized as a cause of illness or injury. A study reviewed data from a sample of 168,000 Medicare patients seen for treatment of hip, shoulder, or wrist fractures [35]. In the four months prior to presentation, three-quarters of the patients had been taking a nonopioid drug associated with increased fracture risk (eg sedatives, atypical antipsychotics, tricyclic antidepressants, or antihypertensives). In the four months after the fracture, such drugs were discontinued for 7 percent but were newly prescribed for another 7 percent. Review of drug therapy, with assessment of the need for ongoing therapy and discontinuation of nonessential medications, is indicated when patients present with an injury or illness that might relate to an adverse effect of a medication. (See "Drug prescribing for older adults", section on 'Review current drug therapy'.)

PRIMARY CARE 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) [36,37]. 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 [38]. 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 [39]. 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) [40]. 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'.)

Dosing of direct oral anticoagulants in obese patients (June 2016)

Limited data are available to guide dosing of direct oral anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) in patients with obesity. The International Society of Thrombosis and Hemostasis (ISTH) has issued guidance on this subject [41]. The major recommendations include use of DOACs at standard doses for those with a body mass index (BMI) ≤40 kg/m2 or weight <120 kg, and avoidance of DOACs in individuals with a BMI >40 kg/m2 or weight ≥120 kg. (See "Direct oral anticoagulants: Dosing and adverse effects".)

PRIMARY CARE INFECTIOUS DISEASES

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 [42]. 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 [43]. 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 [44]. 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'.)

M. chimaera infections associated with cardiac surgery (October 2016)

Clusters of disseminated infection with Mycobacterium chimaera in the United States and Europe have been linked to exposure to contaminated Stockert 3T heater-cooler devices during cardiac surgery [45]. In the United States, the Food and Drug Administration recommends retiring 3T heater-cooler devices and accessories that have tested positive for M. chimaera or that have been linked to known infections and refraining from using any 3T heater-cooler device manufactured before September 2014 except in emergency situations. Providers of patients who have undergone cardiac surgery should be aware of the possibility of M. chimaera infection, even months to years following the procedure. (See "Overview of nontuberculous mycobacterial infections in HIV-negative patients", section on 'Disseminated disease'.)

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 [46]. 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 [47]. 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 [48]. 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 [49]. 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 [50-52]. 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 [53]. 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 [54], 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'.)

USPSTF recommendations on syphilis screening in nonpregnant adults and adolescents (June 2016)

In June 2016, the United States Preventive Services Task Force updated its statement on syphilis screening in asymptomatic nonpregnant adolescents and adults to recommend screening for those who are at high risk for infection [55]. These include sexually active men who have sex with men (MSM), HIV-infected patients, and individuals with a history of incarceration or commercial sex work. The optimal frequency of routine screening in high-risk patients without a clear exposure is yet to be determined. Consistent with other expert guidelines, we suggest annual screening for sexually active MSM and HIV-infected individuals, with more frequent screening for those with high-risk behaviors, such as multiple or anonymous sexual partners. (See "Syphilis: Screening and diagnostic testing", section on 'Asymptomatic patients' and "Screening for sexually transmitted infections".)

Viral dynamics and symptom onset in acute HIV infection (May 2016)

A recent study that closely followed 50 acutely HIV-infected patients who had been identified by prospective viral testing of high-risk individuals provides precise information on the clinical features and viral dynamics shortly following infection [56]. Although almost all subjects had at least one reported symptom or sign during the first four weeks of infection, these were mainly short-lived, nonspecific, and unlikely to have brought the individual to clinical attention outside of a study setting. The highest frequency of symptoms and signs were observed just before peak viremia occurred, approximately two weeks after the initial detection of viral RNA. These results highlight the difficulty of suspecting acute HIV infection by clinical features alone and thus, the importance of repeated HIV screening in high-risk individuals. (See "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Clinical features'.)

Shortage of benzathine penicillin G (Bicillin L-A) (May 2016)

In May 2016, the United States Centers for Disease Control and Prevention reported a manufacturing delay of benzathine penicillin G (Bicillin L-A), which is the treatment of choice for all stages of syphilis [57]. In light of potential shortages of this agent, it is important for clinicians to note that only a single dose of benzathine penicillin G is warranted for early syphilis (table 4). Pregnant women with syphilis should be prioritized for benzathine penicillin G, and so alternative regimens, such as doxycycline, may need to be used for nonpregnant adults if supplies are limited. Bicillin C-R (equal concentrations of procaine and benzathine penicillin G) should not be used to treat syphilis. (See "Syphilis: Treatment and monitoring", section on 'Penicillin as the treatment of choice'.)

Restriction of fluoroquinolone use in uncomplicated infections (May 2016)

The US Food and Drug Administration (FDA) has stated that the serious adverse effects associated with fluoroquinolones generally outweigh the benefits for patients with uncomplicated acute sinusitis, acute bronchitis, and urinary tract infections who have other treatment options [58]. For patients with these infections, fluoroquinolones should be reserved for those who have no alternative treatment options. This announcement was based on an FDA safety review showing that systemic fluoroquinolone use is associated with disabling and potentially permanent serious side effects, including those involving the tendons, muscles, joints, nerves, and central nervous system. (See "Fluoroquinolones", section on 'Restriction of use for uncomplicated infections'.)

PRIMARY CARE NEPHROLOGY AND HYPERTENSION

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 [59]. 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 [60]. 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) [61]. 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'.)

Goal blood pressure in older adults (June 2016)

Goal blood pressure in older adults was examined in the Systolic Pressure Intervention Trial (SPRINT) [62]. SPRINT enrolled a subgroup of more than 2600 ambulatory adults aged 75 years or older, including 349 categorized as being fit, 1456 as less fit, and 815 as frail according to a validated frailty index. At 3.1 years, rates of both the primary cardiovascular endpoint and all-cause mortality were significantly lower among those assigned more intensive (goal <120 mmHg) versus less intensive (goal <140 mmHg) systolic blood pressure lowering. The benefit from more intensive blood pressure control was present in both fit and frail older adults. Serious adverse events were similar in the two treatment groups, and did not depend upon frailty. (See "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension", section on 'Goal blood pressure'.)

PRIMARY CARE NEUROLOGY

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 [63]. 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'.)

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 5), and using the lowest doses possible to control symptoms [64]. 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 [65]. 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'.)

PRIMARY CARE PULMONOLOGY

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 [66-68]. 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 [69]. 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'.)

PRIMARY CARE PSYCHIATRY

Psychotropic medication and violent reoffending after prison release (November 2016)

The prevalence of severe mental illness has been estimated at 15 to 25 percent of people in US prisons. Assuring mental health care continuity in the community for people on release from prison may prevent subsequent incarceration. In a cohort study of released prisoners in Sweden, rates of violent reoffending were lower during periods when people received psychotropic medications (antipsychotics, psychostimulants, and/or drugs to treat substance use disorder) compared with periods when they were not medicated [70]. Assuring mental health care continuity in the community for people on release from prison may prevent subsequent incarceration. (See "Clinical care of incarcerated adults", section on 'Psychiatric disorders'.)

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 [71]. 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'.)

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) [72]. 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'.)

Extended-release naltrexone for prevention of opioid relapse in adults who had been incarcerated (May 2016)

Extended-release naltrexone may help prevent opioid relapse. A randomized trial in 308 community dwelling adults who had been incarcerated and who had a history of opioid dependence compared usual treatment (brief counseling and referral to community treatment programs) with extended-release naltrexone therapy for 24 weeks [73]. Those who received extended-release naltrexone therapy had a longer time to relapse and lower rate of relapse. One year after the treatment (at 78 weeks), there were no overdose events in the intervention group and seven in the control group. However, the rates of opioid-negative urine samples were equal between groups at 78 weeks. (See "Clinical care of incarcerated adults", section on 'Substance use disorders' and "Pharmacotherapy for opioid use disorder", section on 'Long-acting injectable naltrexone'.)

PRIMARY CARE RHEUMATOLOGY

Tocilizumab versus methotrexate for initial therapy of rheumatoid arthritis (July 2016)

Several biologic agents have been compared with methotrexate (MTX) as initial disease-modifying antirheumatic drug (DMARD) therapy for rheumatoid arthritis (RA). In a recent randomized trial involving over 300 DMARD-naïve patients with active early RA and using a treat-to-target strategy, initial treatment with tocilizumab, an interleukin-6 receptor blocking monoclonal antibody, with or without MTX, was more effective than MTX alone in achieving sustained (≥24 weeks) remission while on the initial trial regimen [74]. However, results for the entire two-year trial period, after modifications in the treatment regimens for inadequate response, were more similar, and the trial design had limitations that might have favored the tocilizumab arms. For multiple reasons, MTX remains our initial DMARD of choice for most patients, although the findings provide support for tocilizumab as another possible option in selected patients. (See "Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults", section on 'Tocilizumab'.)

Tai Chi for patients with knee osteoarthritis (June 2016)

Tai Chi, a multicomponent traditional Chinese mind-body practice, combines slow and graceful movements with meditative relaxation techniques and can reduce pain and improve physical function in patients with osteoarthritis (OA), compared with control interventions. In a recent randomized trial involving over 200 patients with knee OA, a Tai Chi program (twice weekly for 12 weeks, with instruction to practice Tai Chi daily), resulted in benefit similar to an active comparator, outpatient physical therapy and a home exercise program [75]. After 12 weeks, both groups exhibited statistically and clinically significant reduction in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score, and differences between the groups were not statistically significant. Benefits were maintained at 52 weeks of follow-up. The Tai Chi group had greater improvements in depression and the physical quality-of-life measure. (See "Nonpharmacologic therapy of osteoarthritis", section on 'Tai Chi'.)

Acetaminophen for knee and hip osteoarthritis (May 2016)

Treatment with acetaminophen (paracetamol, N-acetyl-p-aminophenol [APAP]) appears to be slightly more effective than no treatment in relieving overall pain from osteoarthritis (OA), but generally less effective than nonsteroidal antiinflammatory drugs (NSAIDs). This was recently illustrated in a 2016 network meta-analysis of randomized trials involving nearly 60,000 patients with knee or hip OA receiving either APAP, one of seven NSAIDs, or placebo [76]. The summary estimates of benefit with APAP were extremely low, although statistically significant, for the highest dose of APAP, but less than the predefined minimum clinically important effect. These results do not exclude the possibility that some patients respond, while many others do not. In patients with OA lacking signs or symptoms of inflammation, we initiate pharmacologic therapy with acetaminophen on an as-needed basis. If this is inadequate, we advise a trial of acetaminophen on a scheduled basis up to three to four times daily. Such use is consistent with evidence supporting its modest benefit compared with placebo and its relative safety. (See "Initial pharmacologic therapy of osteoarthritis", section on 'Noninflammatory OA'.)

OTHER ADULT PRIMARY CARE

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 [77]. 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 [78]. 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)'.)

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 [79]. 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'.)

Misclassification of genetic variants in minority populations (September 2016)

When an individual's genome is sequenced, the likelihood of an incidentally identified genetic variant is high. Genetic variants are classified for their pathogenicity based on data from population studies. However, many reference populations are heavily weighted to Caucasians and lack information from underrepresented minorities. In a recent study, five variants that are common in healthy African Americans were misclassified as pathogenic for hypertrophic cardiomyopathy [80]. Clinicians must be aware of the potential for misclassification, especially in underrepresented minorities. (See "Incidental and secondary findings from genetic testing", section on 'Underrepresented ethnicities'.)

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