Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Interval to colonoscopy following a positive fecal immunochemical test (May 2017)
How soon follow-up colonoscopy should be done to evaluate a positive fecal immunochemical test (FIT) is uncertain. In a retrospective cohort study of over 70,000 patients aged 50 to 70 years who had a positive FIT, rates of detection of any colorectal cancer (CRC) or advanced-stage CRC increased with increased time intervals between positive FIT and colonoscopy . Based on these findings, we encourage follow-up colonoscopy as soon as possible (and definitely within a few months) for patients who have a positive FIT. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'A suggested approach'.)
Flexible sigmoidoscopy and colorectal cancer screening in older women (January 2017)
Flexible sigmoidoscopy is one of several screening modalities recommended by the US Preventive Services Task Force for colorectal cancer (CRC) screening. However, sigmoidoscopy is less effective at detecting lesions in the right side of the colon (beyond the 60 cm reach of the sigmoidoscope) than the left side, and right-sided lesions are more common in older women. A study that pooled results from three randomized trials (nearly 300,000 individuals) comparing screening by sigmoidoscopy with no screening found that the incidence of CRC at 10 to 12 years was decreased in men but, in women, only in those younger than 60 years . Current screening recommendations do not indicate gender-based preferences for screening options, but these findings call into question the effectiveness of flexible sigmoidoscopy as a screening modality for women over age 60 years. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)
Fecal immunochemical testing for colorectal cancer screening (January 2017)
Multiple test strategies are available for screening in people with average risk for colorectal cancer (CRC). Annual stool testing for occult blood using a guaiac reagent (gFOBT) has been widely implemented and is one of the screening strategies endorsed by the US Preventive Services Task Force. Fecal immunochemical testing (FIT) is another option and has the potential advantages of better test performance (improved sensitivity for CRC and advanced adenomas) and better patient adherence (one stool sample, no diet restrictions) compared with gFOBT. The US Multi-Society Task Force has published consensus guidelines recommending FIT over gFOBT when occult blood stool testing is elected for CRC screening . (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Immunochemical tests for fecal blood' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)
Effectiveness of screening colonoscopy in older adults (January 2017)
The effectiveness of screening for colorectal cancer (CRC) in older adults is uncertain. Randomized trials of screening colonoscopy have not been completed, and trials currently underway do not include adults 75 years and older. A study of Medicare beneficiaries found that undergoing colonoscopy believed to be for screening modestly decreased the risk of CRC (2.2 versus 2.6 percent in the no-screening group) over an eight-year period for those aged 70 to 74 years, with a smaller, but statistically non-significant, decrease in risk (2.8 versus 3.0 percent in the no-screening group) for those 75 to 79 years . Adverse events following colonoscopy occurred in less than 1 percent. The decision whether to recommend screening for a patient at any age, but especially those over 75 years of age, should depend upon the patient's health status, anticipated life expectancy, risk for colorectal cancer (CRC), and personal values. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Screening in older adults'.)
Screening interval for lung cancer (January 2017)
The optimal strategy for screening high-risk individuals for lung cancer is the subject of active study. In new results from the NELSON trial, in which almost 16,000 current or former smokers were randomly assigned to low-dose computed tomography (LDCT)-based screening versus observation only, extending the screening interval from 1 to 2.5 years reduced the proportion of cancers detected at an early stage . These data support our approach to screen annually with LDCT when screening patients who are at high risk for lung cancer. (See "Screening for lung cancer", section on 'Other trials'.)
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'.)
GENERAL INTERNAL MEDICINE
Updated ACP guideline on management of low back pain (April 2017)
The American College of Physicians (ACP) recently published an updated guideline for the management of acute, subacute, and chronic low back pain . Notable changes from their previous guideline include emphasis of nonpharmacologic therapy as an initial management approach and preference for nonsteroidal anti-inflammatory drugs (NSAIDs) for first-line pharmacotherapy over acetaminophen. Our recommendations are generally consistent with the updated ACP guideline. (See "Treatment of acute low back pain" and "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment".)
Dexamethasone for acute pharyngitis pain in adults (April 2017)
Studies of oral corticosteroids for acute pharyngitis pain have generally found only modest benefit but have been limited by confounding factors, such as concurrent antibiotic use. In an office-based randomized trial that compared a single dose of dexamethasone with placebo for adults who visited a primary care clinician for acute pharyngitis and were not given an immediate prescription for antibiotics, there was no difference in the proportion of patients who achieved full relief of sore throat at 24 hours and only a small difference in symptom relief at 48 hours (35 versus 27 percent with placebo) . These results support our suggestion to not prescribe glucocorticoids routinely for acute sore throat and to limit their use to severely symptomatic patients. (See "Symptomatic treatment of acute pharyngitis in adults", section on 'Limited role of glucocorticoids'.)
Fluctuations in body weight and risk of CHD (April 2017)
While obesity is associated with an increased risk for coronary heart disease (CHD) and sustained weight loss reduces the risk of CHD, the effects of frequent weight gain and loss on CHD risk are unknown. A post hoc analysis of data from a secondary prevention statin study involving over 9000 patients with established CHD and LDL cholesterol below 130 mg/dL (3.4 mmol/L) found that patients in the highest quintile of weight fluctuation (mean variability of 3.9 kg) had significantly higher risks of any CHD event, any cardiovascular disease event, and total mortality, compared with those in the quintile with the lowest weight variation, and that risk increased with each standard deviation change in magnitude of weight fluctuation . These findings suggest that frequent cycles of weight gain and weight loss are associated with an increased risk of CHD and cardiovascular disease events, with greatest magnitude of risk among those who were overweight or obese at baseline. (See "Overview of the risk equivalents and established risk factors for cardiovascular disease", section on 'Obesity'.)
Rivaroxaban versus aspirin for indefinite treatment of venous thromboembolism (April 2017)
The optimal antithrombotic agent for patients with venous thromboembolism (VTE) who have indications for indefinite therapy to reduce the risk of recurrent VTE is unclear. A randomized trial compared rivaroxaban (a direct factor Xa inhibitor) and aspirin for long-term treatment of patients who had completed a 6- to 12-month course of therapeutic anticoagulation . Rivaroxaban, either at a treatment (20 mg daily) or a prophylactic (10 mg daily) dose, was superior to aspirin in preventing VTE recurrence for up to 12 months, without increasing the risk of major bleeding. While rates of recurrence were comparable between both doses of rivaroxaban, further studies are warranted before reduced intensity regimens can be recommended. For most patients with VTE requiring long-term treatment, we suggest full intensity anticoagulation rather than low intensity regimens or aspirin. (See "Rationale and indications for indefinite anticoagulation in patients with venous thromboembolism", section on 'Factor Xa and direct thrombin inhibitors'.)
ACP/AAFP guidelines for hypertension treatment in older adults (March 2017)
The American College of Physicians/American Academy of Family Physicians (ACP/AAFP) have issued guidelines for pharmacologic treatment of hypertension in older adults, addressing targets for blood pressure . These guidelines depart from our recommendations and from other recent guidelines (the 2016 Canadian Hypertension Education Program [CHEP] guidelines and the 2016 National Heart Foundation of Australia guidelines) released after publication of the SPRINT trial. The ACP/AAFP suggest a goal systolic pressure of <150 mmHg in adults 60 years of age and older, with consideration of a goal <140 mmHg in patients at high cardiovascular risk. However, we continue to recommend lower goals for such patients, consistent with guidelines from other groups. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Recommendations of others'.)
USPSTF statement on routine pelvic examination (March 2017)
Routine pelvic examination in asymptomatic women is controversial. The US Preventive Services Task Force (USPSTF) recently published a statement that evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women . In 2014, the American College of Physicians (ACP) recommended against such examinations. In 2012, the American College of Obstetricians and Gynecologists (ACOG) recommended annual pelvic examination in nonpregnant women age 21 years or older and is now reviewing its policy in response to the USPSTF statement. As few data about the benefit and harms of routine pelvic examinations are available, we suggest shared decision-making between the patient and clinician. (See "The gynecologic history and pelvic examination", section on 'Indications and frequency for examination'.)
Patterns of tobacco use in the United States (February 2017)
A nationally representative longitudinal study of tobacco product usage in 2013 and 2014 in the United States found that 28 percent of adults used tobacco regularly and 9 percent of youths 12 to 17 years of age had used a tobacco product within the previous 30 days . Two-thirds of adult and one-half of youth tobacco users smoke tobacco cigarettes. Other forms of tobacco (or other nicotine products), including cigar, e-cigarettes, hookah/waterpipe, smokeless tobacco, snus pouch, and dissolvable tobacco, constitute a considerable portion of tobacco use, and 40 percent who reported tobacco use were using more than one form. This study will be repeated over time to establish trends of use. These results illustrate the importance of asking patients not only if they smoke cigarettes, but also if they use one or more other forms of tobacco or nicotine. (See "Patterns of tobacco use", section on 'Tobacco usage: overview'.)
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'.)
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'.)
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'.)
PRIMARY CARE ALLERGY AND IMMUNOLOGY
Immunotherapy for stinging insect hypersensitivity in adults (February 2017)
Venom immunotherapy (VIT) for the treatment of patients with anaphylactic reactions to stings of Hymenoptera insects (eg, bees, yellow jackets, wasps, hornets, and fire ants) is highly effective in preventing future anaphylactic reactions. However, in an updated practice parameter from the American Joint Task Force, VIT is no longer suggested for adults with systemic reactions limited to the skin (ie, generalized erythema, pruritus, urticaria, or angioedema) as studies suggest these patients are at low risk for serious future systemic reactions . This change brings the American approach into closer alignment with guidelines of other countries and is similar to the existing recommendation for children. Despite this revision, VIT may be appropriate for certain adults with cutaneous systemic reactions (eg, those with underlying medical conditions or medications that could affect the outcome of a systemic reaction, frequent unavoidable exposure to Hymenoptera, or impaired quality of life due to fear of future stings). (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Patients with past cutaneous systemic reactions'.)
PRIMARY CARE CARDIOVASCULAR MEDICINE
ACE inhibitors or ARBs not routinely indicated in low-risk patients with stable ischemic heart disease (January 2017)
Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs), referred to as renin angiotensin system inhibitors (RASi), improve survival in high-risk patients with stable ischemic heart disease (SIHD), such as those with heart failure or diabetes. However, a 2017 meta-analysis of 24 randomized trials of RASi compared with placebo or to active control in patients with SIHD without clinical heart failure and with a left ventricular ejection fraction ≥40 percent found that benefit was not present in patients enrolled in studies in which the cardiovascular event rates were low . We do not routinely prescribe RASi to patients with SIHD at low risk of adverse cardiovascular events. (See "Prevention of cardiovascular disease events in those with established disease or at high risk", section on 'ACE inhibitors or ARBs'.)
Role of troponin testing in primary prevention (January 2017)
Across a broad range of populations, elevated troponin is associated with an increased risk of cardiovascular disease (CVD) events. In the primary prevention West of Scotland Coronary Prevention Study of individuals at high CVD risk who were randomly assigned to either statin or placebo, individuals in the highest quartile of high-sensitivity troponin were at the greatest risk of a CVD event at one year in both treated and untreated individuals . Studies designed to evaluate the role of troponin testing in patients being considered for statin therapy or in those started on statin therapy are ongoing. (See "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome", section on 'Elevations in patients at high risk'.)
PRIMARY CARE ENDOCRINOLOGY AND DIABETES
Testosterone therapy in older men with low testosterone (April 2017)
The role of testosterone replacement to treat the decline in serum testosterone concentration that occurs in aging men (in the absence of identifiable pituitary or hypothalamic disease) was addressed in the multicenter Testosterone Trials (TTrials), an integrated set of seven trials in nearly 800 men over age 65 years with low testosterone and sexual dysfunction, physical dysfunction, and reduced vitality, who were randomly assigned to testosterone gel or placebo for 12 months. Initial results suggested that testosterone had a beneficial effect on sexual function, depressive symptoms, and mood, and possibly physical function (walking distance), but not on vitality [25,26] Results from recently published individual trials showed the following:
●There was no effect of testosterone replacement on cognitive function in men with age-associated memory impairment .
●Testosterone increased coronary artery noncalcified plaque volume as measured by coronary computed tomographic angiography .
While the small size and short duration of the subtrials are important limitations, the coronary artery plaque trial raises important concerns about the safety of testosterone therapy in older men. (See "Overview of testosterone deficiency in older men".)
Treatment with levothyroxine provides no symptomatic benefit in older adults with subclinical hypothyroidism (April 2017)
Subclinical hypothyroidism is defined biochemically as an elevated serum thyroid-stimulating hormone (TSH) and a normal serum-free thyroxine (T4) level. Some patients with subclinical hypothyroidism may have vague, nonspecific symptoms. Although virtually all experts recommend treatment of subclinical hypothyroidism when serum TSH concentrations are ≥10 mU/L, treatment of patients with TSH values between the upper reference limit and 9.9 mU/L remains controversial, particularly in older patients who are more likely to have complications from unintended overtreatment. In a randomized trial evaluating the effect of levothyroxine versus placebo on quality of life measures in over 700 older patients (mean age 74.4 years) with mean TSH 6.4 mU/L, there was no difference in hypothyroid symptoms or tiredness scores after one year . We do not routinely treat older patients with TSH between the upper reference limit and 9.9 mU/L (algorithm 1). (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Hypothyroid signs and symptoms'.)
Vitamin D and prevention of cancer (April 2017)
In a trial comparing the effect of vitamin D and calcium supplementation with placebo on the incidence of cancer in over 2000 postmenopausal women, there was no difference between groups in the incidence of cancer at four years . An analysis by cancer site showed no difference in the incidence of breast cancer between the two groups; there were too few cancers at other sites to analyze. Although several study limitations may have contributed to the absence of an effect, including enrollment of patients with a relatively high baseline vitamin D level and permission to take vitamin D supplements (up to 800 international units daily) outside of the intervention, vitamin D supplementation for the prevention of cancer is not warranted. (See "Vitamin D and extraskeletal health", section on 'Cancer'.)
Types of cancers associated with obesity (April 2017)
Excess weight is associated with an increased risk of developing and dying from cancer, but the number and types of cancers are inconsistent across studies. In a review of 204 meta-analyses that investigated the association between indices of adiposity and developing 36 primary cancers and their subtypes, associations were identified for esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract, pancreas, breast (in women who had never taken hormones), endometrium, ovary, and kidney . (See "Obesity in adults: Health consequences", section on 'Cancer'.)
Vitamin D and prevention of infection (March 2017)
In a meta-analysis of 25 trials (almost 11,000 patients) evaluating the incidence of acute respiratory infection, vitamin D supplementation slightly reduced the proportion of patients experiencing one acute respiratory tract infection . In prespecified subgroup analyses, supplementation was most effective in patients with vitamin D levels <10 ng/mL and in those treated with daily or weekly, rather than bolus, doses. As the meta-analysis showed significant effects predominantly in patients with very severe vitamin D deficiency, who require treatment regardless of infection prevention because of the risk of osteomalacia, vitamin D supplementation for the prevention of infection alone is not warranted. (See "Vitamin D and extraskeletal health", section on 'Innate'.)
Glycated hemoglobin (A1C) in sickle cell trait (March 2017)
In a retrospective cohort study evaluating glycated hemoglobin (A1C) in African Americans with and without sickle cell trait, A1C was lower at any fasting glucose value in patients with sickle cell trait compared with controls . However, the study is limited by its methodology, as mean glucose levels were estimated on the basis of very few measurements, usually a single fasting glucose level or oral glucose tolerance test. A1C correlates best with mean blood glucose over 8 to 12 weeks, raising the possibility that if measured appropriately with frequent glucose measurements over time (multiple daily measurements or continuous glucose monitoring), mean glucose levels may actually have been different between the study populations, with the putative different A1C levels accurately reflecting these different mean glucose levels. We continue to use A1C as one option to diagnose diabetes in patients with sickle cell trait. (See "Estimation of blood glucose control in diabetes mellitus", section on 'Racial variation'.)
Glycemic outcomes following bariatric surgery in obese patients with type 2 diabetes (February 2017)
Additional follow-up from a bariatric surgery trial in obese patients with type 2 diabetes (134 patients in follow-up study, 150 patients in initial trial) continues to show reduced glycated hemoglobin (A1C) in the two surgical arms at five years, although there has been some regression in all groups from the one-year results . The proportion of patients with A1C ≤6 percent was 29 percent for gastric bypass and 23 percent for sleeve gastrectomy, compared with 5 percent for controls (intensive medical therapy). While these results are encouraging, we require longer-term follow-up with documentation of improved clinically important outcomes, such as reduced vascular complications or reduced mortality, before routinely recommending bariatric surgery for obesity-related type 2 diabetes that is resistant to multiple medications. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Surgical treatment of obesity'.)
Metformin use in patients with diabetes and renal impairment, heart failure, or chronic liver disease (January 2017)
In 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. This study supports a recent US Food and Drug Administration (FDA) labeling revision for metformin, which will increase use in patients with renal impairment. 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. Recommendations regarding metformin use in patients with an eGFR between 30 and 45 mL/min vary and UpToDate authors individualize decisions about metformin use in such patients. (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'.)
PRIMARY CARE GASTROENTEROLOGY
ACG guidelines on the evaluation of abnormal liver chemistries (January 2017)
The American College of Gastroenterology has published new guidelines on the evaluation of abnormal liver chemistries . These guidelines define normal alanine aminotransferase (ALT) ranges as 29 to 33 international units/L for males and 19 to 25 international units/L for females, which are lower than the reference ranges of many clinical laboratories. They recommend that ALT levels repeatedly above these upper limits of normal be evaluated. In addition, they provide a framework for the evaluation of elevated ALT, aspartate aminotransferase (AST), and alkaline phosphatase levels (which should be characterized as liver chemistries or tests rather than markers of liver function) based on the degree and pattern of elevations. (See "Approach to the patient with abnormal liver biochemical and function tests", section on 'Aminotransferases'.)
PRIMARY CARE GERIATRICS
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'.)
PRIMARY CARE HEMATOLOGY AND ONCOLOGY
Cardiovascular risk in sickle cell trait (March 2017)
Sickle cell trait is a benign carrier state, but concerns have been raised about increased cardiovascular risk factors. Analyses from several large cohorts have now provided reassuring evidence that there are no differences in the risks of diabetes, hypertension, or heart failure in blacks with sickle cell trait compared with the general black population [42,43]. (See "Sickle cell trait", section on 'No increased risk of hypertension, diabetes, or heart failure'.)
Underdosing of direct oral anticoagulants (February 2017)
The oral direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban (collectively called direct oral anticoagulants [DOACs]) have been available for several years. A real-world study of over 1500 patients with venous thromboembolism (VTE) who were treated with a DOAC found that dosing differed from the recommended product dosing in 20 to 50 percent of cases, depending on the agent . These deviations (mostly underdosing) correlated with an increased frequency of VTE recurrence. Clinicians should familiarize themselves with prescribing information to avoid adverse outcomes. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Clinician familiarity with dosing'.)
Duration of adjuvant endocrine therapy for breast cancer (July 2016, Modified February 2017)
For postmenopausal women receiving adjuvant treatment with an aromatase inhibitor (AI) for hormone-positive breast cancer, the minimum duration of treatment is five years. While data from the MA17R trial demonstrated that extending the duration from 5 to 10 years improved recurrence-free survival , preliminary results from the NSABP-B42, DATA, and IDEAL trials, reported at the San Antonio Breast Cancer Symposium, have not confirmed this benefit [46-48]. No study has demonstrated a benefit in overall survival with extended adjuvant AI therapy, and bone-related toxic effects are more frequent among those receiving extended treatment. While variations in methodology likely account for the differences in recurrence-free survival between the studies, the magnitude of any potential benefit is likely to be greatest for those at highest risk for recurrence. While we previously had recommended an extended course of AI adjuvant therapy for most postmenopausal women with nonmetastatic hormone-positive disease, based on the new data, we now suggest offering extended adjuvant aromatase inhibitor therapy to those with high-risk disease (eg, node-positive or ≥T3 disease). (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Duration of endocrine treatment'.)
PRIMARY CARE INFECTIOUS DISEASES
HBV reactivation during HCV antiviral therapy (May 2017)
Reactivation of hepatitis B virus (HBV) can occur during direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection. Among 29 cases reported to the US Food and Drug Administration (FDA) or described in the literature between 2013 and 2016, reactivation occurred at an average of 53 days into DAA treatment and was not associated with a particular HCV genotype or DAA regimen . Two cases were fatal, and one patient required liver transplant. Patients should be tested for HBV coinfection prior to initiation of HCV therapy, with HBV treatment initiated for those who meet criteria (table 1). HBV coinfected patients who do not initially meet HBV treatment criteria should be monitored for reactivation during HCV treatment. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'HBV coinfection' and "Overview of the management of chronic hepatitis C virus infection", section on 'Monitoring during antiviral therapy'.)
Decreased susceptibility to fluoroquinolones in Shigella infection (April 2017)
When treatment for Shigella infection is indicated, susceptibility testing should be performed to guide antimicrobial selection. In the United States, an increasing proportion of Shigella isolates have minimum inhibitory concentrations (MIC) to ciprofloxacin of 0.12 to 1 mcg/mL . Although these MIC values are considered susceptible and their impact on treatment outcomes in Shigella is unknown, they are associated with resistance genes that result in worse outcomes with fluoroquinolone treatment in other Enterobacteriaceae. Clinicians should request the MIC to ciprofloxacin if it is not provided with susceptibility results and avoid fluoroquinolones if the MIC is ≥0.12 mcg/mL. (See "Shigella infection: Clinical manifestations and diagnosis", section on 'Susceptibility testing' and "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic selection'.)
E. coli O157:H7 outbreak associated with soy nut butter (March 2017)
Escherichia coli O157:H7, which causes bloody diarrhea and is associated with the hemolytic-uremic syndrome, is typically transmitted through contaminated beef products and produce, but other foods have also been implicated in outbreaks. In the United States, a particular brand of soy nut butter (I.M. Healthy) has been linked to a multistate E. coli O157:H7 outbreak that has affected mainly children . Although the soy nut butter products have been recalled, individuals should be advised to avoid and discard any remaining product, and the possibility of E. coli O157:H7 infection should be considered in exposed patients with diarrheal illnesses. Details on the outbreak can be found on the Centers for Disease Control and Prevention website. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)
Recommended immunization schedule—United States, 2017 (March 2017)
The Advisory Committee on Immunization Practices has released the 2017 recommended immunization schedule for children and adolescents in the United States [52,53]. New recommendations include the following:
●All infants should now receive monovalent hepatitis B vaccine within 24 hours of birth; earlier recommendations allowed some infants born to hepatitis B surface antigen-negative mothers to receive the vaccine after discharge. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Mother's HBsAg status unknown, birth weight ≥2 kg'.)
●When administered during pregnancy, the tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine should be given as early as possible between 27 and 36 weeks of gestation. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)
●For individuals receiving the meningococcal serogroup B vaccine MenBFHbp (Trumenba), two doses are recommended for healthy adolescents and young adults who are not at increased risk for meningococcal disease. Three doses are recommended for individuals ≥10 years of age at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks (table 2). Previously, three doses were recommended for all recipients. The dosing frequency and interval for the other serogroup B vaccine, MenB-4C (Bexsero), have not changed. (See "Meningococcal vaccines", section on 'Serogroup B meningococcus vaccines'.)
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 3), 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 adults" 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 [55,56]. 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".)
PRIMARY CARE NEPHROLOGY AND HYPERTENSION
Multitarget therapy and progression of kidney disease in type 2 diabetes (March 2017)
The optimal therapeutic approach to the treatment of diabetic nephropathy may be intensive multifactorial risk factor reduction targeting behavior (ie, counseling on diet, exercise, and smoking cessation), glycemic control, blood pressure, and dyslipidemia. The efficacy of implementing this approach for eight years, compared with usual care, in patients with type 2 diabetes and increased albuminuria was examined in the Steno type 2 trial. At the end of the trial phase, all patients were offered intensive multitarget therapy . After an additional 20 years of follow-up, those who were assigned to intensive multitarget therapy had a significantly lower annual decline in glomerular filtration rate and a higher likelihood of survival without end-stage renal disease (approximately 50 versus 30 percent). (See "Treatment of diabetic nephropathy", section on 'Type 2'.)
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'.)
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'.)
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'.)
PRIMARY CARE NEUROLOGY
High-risk drug prescribing in adults with dementia (February 2017)
Older adults with dementia are at heightened risk for adverse drug effects from anticholinergic drugs, benzodiazepines, and opioids, among many others. Despite these risks, polypharmacy remains common in this population. In a study that included over 75,000 adults with dementia, 44 percent of patients were prescribed at least one potentially unsafe medication (mostly drugs with high anticholinergic activity), and rates were consistently higher in patients receiving care from multiple providers . These results highlight the need for careful monitoring of drug therapy in patients with dementia and the importance of communication among providers before starting new therapies. (See "Safety and societal issues related to dementia", section on 'Polypharmacy'.)
PRIMARY CARE PULMONOLOGY
Spirometry and asthma diagnosis (February 2017)
The importance of confirming reversible airflow limitation when making a diagnosis of asthma was illustrated in a study of 701 randomly selected adults who had a physician diagnosis of asthma in the previous five years . Current asthma was excluded in 33 percent and, among these, less than half had previous testing to confirm airflow limitation. This observation suggests that a clinical diagnosis of asthma, if not supported by spirometry, may be incorrect and reinforces guideline recommendations that spirometry pre- and post-bronchodilator be obtained at the time of an initial diagnosis of asthma.
PRIMARY CARE PSYCHIATRY
Antipsychotic drugs and risk of falls and fracture (March 2017)
In a large, population-based sample of Finnish people with Alzheimer disease, new users of antipsychotic medication had an increased risk of hip fractures from the first days of use . Subsequent to multiple similar reports in patients with varied disorders, the US Food and Drug Administration (FDA) issued a warning that antipsychotic drugs may cause falls and fractures as a result of somnolence, postural hypotension, and/or motor and sensory instability, and recommended that a fall risk assessment be completed when initiating antipsychotic treatment and recurrently for patients continuing on long-term antipsychotics. (See "Second-generation antipsychotic medications: Pharmacology, administration, and side effects", section on 'Falls'.)
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 . 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'.)
PRIMARY CARE RHEUMATOLOGY
New guidelines for management of gout (February 2017)
Several professional organizations have recently published guidelines for the management of gout, including the European League Against Rheumatism (EULAR) , an international task force , and the American College of Physicians (ACP) . The ACP guidelines depart from recommendations of the American College of Rheumatology (ACR), EULAR, the international task force, and others by suggesting a treat-to-avoid-symptoms approach (ie, monitoring the adequacy of urate-lowering drug dosing based on the frequency and severity of acute attacks) rather than a treat-to-target approach based on serum urate levels. We concur with the ACR, EULAR, and international guidelines groups, based upon the available clinical evidence and an understanding of the pathophysiology of gout, and we continue to recommend monitoring serum urate levels and using such data to make treatment choices and titrate dosing. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Recommendations of major groups'.)
Lack of benefit of chondroitin and glucosamine for knee osteoarthritis (January 2017)
The use of glucosamine and chondroitin for osteoarthritis (OA) has been controversial, with most studies showing little to no evidence of clinically meaningful benefit. In a multicenter randomized trial, 164 patients with moderate to severe knee osteoarthritis were treated with either placebo or chondroitin sulfate plus glucosamine . At six months' follow-up, the mean reduction in the global pain score was greater in the placebo group, and there were no between-group differences in patient-reported function or other outcomes. Although the study was limited by the small size and potentially inadequate dosing of chondroitin and glucosamine, it is likely that the combination of glucosamine and chondroitin is no better than placebo in patients with knee osteoarthritis.
OTHER ADULT PRIMARY CARE
Safe storage of prescription opioids (May 2017)
Although safe storage of prescription opioid medications (eg, locked cabinet) is recommended, it infrequently occurs. In a United States nationally representative survey of over 1000 adults with prescription opioid use in the past 12 months, only 9 percent reported safe storage of their medications . In further analysis of those adults with children younger than 18 years of age in the household, safe storage was reported in less than one-third of households with young children and 12 percent of households with children older than six years of age . These results support the need for anticipatory guidance by health care providers, emphasizing opioid safe storage and how it may limit opioid misuse and overdose, especially in households with children and adolescents. Further research should focus on developing and implementing effective means of secure storage in households. (See "Opioid intoxication in children and adolescents", section on 'Safe storage'.)
Direct-to-consumer genetic testing (April 2017)
Policies regarding the use of direct-to-consumer (DTC) genetic testing are evolving, with the company 23andMe most actively seeking regulatory approval. In early 2017, the US Food and Drug Administration began allowing 23andMe to market DTC testing that would reveal increased risk for a predetermined set of 10 conditions, including celiac disease, hereditary hemochromatosis, Parkinson's disease, and others . Results might result in lifestyle modifications and/or discussion with a clinician, which may be of value to the individual. However, clinicians should be aware of a number of concerns that have been raised about the reliability, interpretation, and management implications of this type of testing. (See "Personalized medicine", section on 'Direct-to-consumer testing'.)
Naldemedine for opioid-induced constipation (March 2017)
The benefit of naldemedine, an oral peripherally acting opioid receptor antagonist, for opioid-induced constipation (OIC) was shown in two identically designed 12-week phase III randomized trials conducted in patients with noncancer chronic pain and OIC . In a preliminary report, naldemedine, compared with placebo, decreased constipation and was well tolerated with no signs or symptoms of opioid withdrawal or decrease in opioid analgesic efficacy. Naldemedine has been approved in the United States for OIC in adult patients with chronic noncancer pain . However, efficacy has also been shown for treatment of OIC in cancer patients , and naldemedine can be used off label in this population. The European Medicines Agency has approved naldemedine for treatment of OIC without restriction to noncancer pain . (See "Cancer pain management with opioids: Prevention and management of side effects", section on 'Other oral agents'.)
AASM guideline on pharmacotherapy for chronic insomnia in adults (March 2017)
The American Academy of Sleep Medicine (AASM) has released a new clinical practice guideline on the pharmacologic treatment of chronic insomnia in adults . The guideline reviews evidence of effectiveness for a variety of medications (including benzodiazepines, nonbenzodiazepine hypnotics, ramelteon, doxepin, and suvorexant) and notes limitations and potential biases to the evidence, leading to low confidence in the overall estimation of risk-to-benefit ratio. The potential short-term benefits of pharmacologic therapy need to be balanced with the risk of side effects and dependence with long-term use. We continue to prefer behavioral therapy, rather than pharmacotherapy, as an initial treatment approach in most patients. (See "Treatment of insomnia in adults", section on 'Choice of an agent'.)
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)'.)
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