Disclosures: David M Rind, MD Employee of UpToDate, Inc. Equity Ownership/Stock Options (Spouse): Bonfire Development Advisors [CBT (iCBT)]. H Nancy Sokol, MD Nothing to disclose. Lee Park, MD, MPH Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ADULT GENERAL INTERNAL MEDICINE
Conception after miscarriage (January 2016)
Although data support the benefits of delaying conception after a live birth, it is not clear if such a delay benefits women after miscarriage. In a study of nearly 1100 women who had a miscarriage at less than 20 weeks of gestation, women who attempted conception within 0 to 3 months of the loss were more likely to achieve a live birth, had a faster time to pregnancy that resulted in a live birth, and had similar pregnancy complications compared with women who waited greater than 3 months to try to conceive . We advise women who have completed a miscarriage that they may attempt conception as soon as they are psychologically ready. (See "Spontaneous abortion: Management", section on 'Interval to conception'.)
Normal-weight central obesity and mortality (December 2015)
Overall obesity, as defined by body mass index (BMI), has been thought to play the major role in the obesity-associated excess risk of cardiovascular morbidity and mortality, with abdominal or central obesity (as defined by an increased waist-to-hip ratio [WHR]) playing an independent but lesser role. However, data from the Third National Health and Nutrition Examination Survey suggest that normal-weight central obesity (normal BMI with increased WHR) is associated with higher mortality than BMI-defined obesity, particularly when compared with individuals without central obesity . In a cross-sectional survey of over 15,000 individuals, men with a normal BMI but central obesity (WHR ≥0.90) had the highest total mortality risk when compared with men without central obesity who were normal weight, overweight, or obese (hazard ratio [HR] 1.87, 2.24, 2.42, respectively). A similar pattern was seen in normal weight women with central obesity, but the excess risk was not as great. A limitation of the study is that central obesity was determined by WHR only; no quantitative imaging studies of adipose tissue were performed. These data suggest that normal weight individuals with central obesity appear to have an increased mortality risk, and should be targeted for lifestyle modification strategies. (See "Obesity in adults: Health hazards", section on 'Normal weight central obesity'.)
Dabigatran reversal agent approved (October 2015)
The lack of a specific reversal agent for the direct thrombin inhibitor dabigatran has been a persistent concern in its use for patients with atrial fibrillation or venous thromboembolism. Idarucizumab (Praxbind) is a reversal agent for dabigatran that was approved by the US Food and Drug Administration in October 2015 to reverse dabigatran effect in the setting of life-threatening or uncontrolled bleeding or emergency surgery [3,4]. Approval was based on studies in healthy volunteers and an interim analysis of the RE-VERSE AD trial, which included a cohort of 90 older adult patients who had clinically significant bleeding or the need for an urgent invasive procedure while taking dabigatran for atrial fibrillation . Idarucizumab produced rapid normalization of clotting times and/or surgical hemostasis; there were five thrombotic events and 18 deaths. Without a control group it is unclear how these outcomes would compare with similar patients who did not receive idarucizumab. For patients with life-threatening bleeding, we would use idarucizumab, if available, along with other measures to decrease bleeding risk, but we would not combine idarucizumab with procoagulant products such as an activated prothrombin complex concentrate (aPCC). Idarucizumab is an antibody-based therapy and does not have known activity against direct factor Xa inhibitors or other anticoagulants. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal'.)
E-cigarette use and use of combustible tobacco products (August 2015)
Studies have associated e-cigarette use with an increased risk of conventional cigarette smoking among youth. A new prospective study was conducted in 2530 ninth-grade students who had never used a combustible tobacco product and compared students who had ever used e-cigarettes with never users . Compared with never users, ever users of e-cigarettes were more likely to report use of any combustible tobacco product at both 6-month (31 versus 8 percent) and 12-month (25 versus 9 percent) follow-up. Additionally, after adjusting for other risk factors for smoking, baseline e-cigarette use was associated with a greater likelihood of use of any combustible tobacco product (OR 2.7), including conventional cigarettes, cigars, and hookahs. (See "E-cigarettes", section on 'Effect on smoking initiation among youth'.)
Cognitive-behavioral therapy for insomnia (August 2015)
Cognitive-behavioral therapy for insomnia (CBT-I) is a safe and effective alternative to medication in patients with chronic insomnia. A 2015 meta-analysis identified 20 randomized trials of CBT-I in over 1100 participants with chronic insomnia; CBT-I approaches incorporated at least three of the following: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation . Compared with inactive control conditions, CBT-I improved sleep on a variety of outcome measures, including sleep onset latency, wake time after sleep onset, and sleep efficiency. CBT-I is a particularly good option for patients who are more susceptible to side effects of medication (eg, older adults, patients with multiple medical comorbidities). (See "Treatment of insomnia", section on 'Cognitive behavioral therapy'.)
2015 revised Beers criteria for potentially inappropriate medication use in older adults (November 2015)
The 2015 revised Beers criteria for potentially inappropriate medication use in older adults are available through the American Geriatrics Society website. The criteria include over 50 medications designated in one of three categories: those that should always be avoided (eg, barbiturates, chlorpropamide); those that are potentially inappropriate in older adults with particular health conditions or syndromes; and those that should be used with caution. New additions since 2012 are a table of non-anti-infective drug interactions and a table of non-anti-infective medications to avoid or adjust for decreased renal function . Other notable changes in the 2015 listings are removal of loratadine from the list of medications with strong anticholinergic properties; a more liberal renal threshold for withholding nitrofurantoin (now creatinine clearance <30 rather than <60 mL/min); avoidance of long-term proton pump inhibitors because of risk of C. difficile infections and bone loss; and stricter guidelines to avoid antipsychotics for behavioral problems unless other options have failed and the older adult is threatening harm to self or others. (See "Drug prescribing for older adults", section on 'Beers criteria'.)
High-dose vitamin D may increase risk of falls (February 2016)
Evidence conflicts on the effectiveness of vitamin D for fall prevention in older adults, with emerging evidence that high-dose vitamin D administered monthly may increase fall risk. A randomized trial compared monthly high-dose vitamin D (60,000 international units of vitamin D3 in one group; 24,000 international units vitamin D3 plus 300 microg calcifediol in another) with a lower dose (24,000 units vitamin D3) in community-dwelling men and women age 70 and older who had a history of a prior fall . Lower extremity function at 12 months did not differ among the groups, but there was a higher incidence of falls and mean number of falls in both groups that received high-dose vitamin D. Of note, there was no placebo group in this trial. See "Falls: Prevention in community-dwelling older persons", section on 'Vitamin D supplementation' and "Vitamin D and extraskeletal health", section on 'Muscle function'.)
2015 US Dietary Guidelines (January 2016)
The 2015 US Dietary Guidelines for Americans have been released . The new guidelines emphasize following a healthy eating pattern across the lifespan. Compared with the 2010 guidelines, the 2015 guidelines no longer restrict total cholesterol to 300 mg a day and recommend that <10 percent of calories should come from added sugars. (See "Healthy diet in adults", section on 'Carbohydrate' and "Dietary fat", section on 'Guidelines'.)
Carcinogenicity of red and processed meat (November 2015)
The World Health Organization’s International Agency for Research on Cancer reviewed the evidence linking intake of red and processed meat with colorectal cancer (CRC) . Twelve of 18 cohort studies and six of nine case control studies found an association for consumption of processed meat and CRC, while 7 of 14 cohort studies and 7 of 15 case control studies found a positive association for red meat consumption and CRC. A meta-analysis of 10 cohort studies reported a dose-response relationship between meat consumption and CRC risk, with a 17 percent increased risk per 100 g per day of red meat, and an 18 percent increase in risk per 50 g per day of processed meat. The working group concluded that the evidence was sufficient to classify processed meats as carcinogenic, and red meat as a probable carcinogen. These conclusions were based entirely upon observational studies. Data from randomized trials (eg, the Women's Health Initiative) have not found a lower incidence of colorectal neoplasia in women whose diets are relatively low in fat (including animal fat). In our view, the absolute risk of CRC associated with intake of red and/or processed meat is small, and modest consumption (one to two times weekly at most) is an acceptable part of a healthy balanced diet. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors", section on 'Red and processed meat' and "Cancer prevention", section on 'Red meat'.)
Influenza vaccination and influenza-associated pneumonia (October 2015)
Many studies have demonstrated that influenza vaccination decreases the incidence of laboratory-confirmed influenza infection, but few have evaluated the effect on the serious complications of influenza. Recent data suggest that vaccination is associated with a reduced risk of influenza pneumonia. In a case-control study of adult and pediatric patients hospitalized for community-acquired pneumonia (CAP), those with laboratory-confirmed influenza-associated pneumonia had lower odds of having received an influenza vaccine during the same influenza season compared with those with CAP not associated with influenza . The estimated vaccine effectiveness for preventing influenza-associated pneumonia was 57 percent. (See "Seasonal influenza vaccination in adults", section on 'Trivalent inactivated vaccines' and "Seasonal influenza in children: Prevention with vaccines", section on 'Indications'.)
Early cardiovascular disease in youth with depressive and bipolar disorders (October 2015)
The American Heart Association recently proposed that major depression and bipolar disorder in adolescents be positioned alongside other pediatric diseases that are considered moderate risk conditions for early cardiovascular disease (CVD), which include chronic inflammatory diseases (eg, systemic lupus erythematosus), HIV infection, and nephrotic syndrome . There is growing evidence that major depression and bipolar disorder are associated with accelerated atherosclerosis and early CVD. In addition, traditional risk factors for CVD (eg, obesity, diabetes mellitus, sedentary lifestyle, and smoking) are more prevalent in youth with major depression and bipolar disorder. Although psychotropic medication may contribute to the elevated risk of CVD, particularly in youths with bipolar disorder, it appears that the association between depression and CVD is independent of medication effects. Management of youth with major depression and bipolar disorder should thus include monitoring and management of other CVD risk factors, including body mass index, blood pressure, lipids, and fasting glucose. (See "Diseases associated with atherosclerosis in childhood", section on 'Depressive and bipolar disorders'.)
Revised schedule for pneumococcal vaccination in older adults (September 2015)
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the 13-valent pneumococcal conjugate vaccine (PCV13) for adults ≥65 years of age . In September 2015, the ACIP changed the recommended interval between administration of PCV13 and PPSV23 for immunocompetent adults ≥65 years of age from 6-12 months to ≥1 year to simplify the administration schedule (algorithm 1) . In patients who have already received PPSV23, at least 1 year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Schedule for dual vaccination'.)
PCSK9 antibodies for cardiovascular risk reduction (September 2015)
Monoclonal antibodies that inhibit proprotein convertase subtilisin kexin 9 (PCSK9-abs) reduce LDL-cholesterol levels by as much as 70 percent. Randomized trials with small numbers of events and limited follow-up suggest that at least two of these agents, alirocumab and evolocumab, substantially reduce cardiovascular events and mortality when used for secondary prevention, both as monotherapy and in combination with statin therapy [16,17]. (See "Lipid lowering with drugs other than statins and fibrates", section on 'PCSK9 inhibitors'.)
PCSK9-abs are becoming available for clinical use. The agents require subcutaneous injection every two to four weeks and are very expensive. While awaiting greater experience with these agents, we would use them in situations where the expected reductions in cardiovascular events are likely to outweigh any as yet unknown adverse events from a new therapy. These include using them in combination with statin therapy in very high-risk patients with stable cardiovascular disease, such as those in the proposed NCEP guidelines (table 1), and as monotherapy in very high-risk and higher-risk patients who are intolerant of statin therapy. Other experts, including other authors for UpToDate, would make decisions about adding medications to statin therapy based on goal LDL-cholesterol. (See "Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease", section on 'Stable CVD' and "Treatment of lipids (including hypercholesterolemia) in secondary prevention", section on 'Summary and recommendations'.)
Light and moderate alcohol consumption and cancer risk (August 2015)
Alcohol use has been associated with increased risk for cancer, with heavy use being associated with the highest risk. A prospective cohort study of health professionals in the United States that included over 88,000 women and 47,000 men followed for 30 years found that compared with nondrinkers, light and moderate drinkers had a small but nonsignificant increase in cancer risk . However, in women who had never smoked, there was an increased risk of alcohol-related cancer (defined as colorectum, female breast, oral cavity, pharynx, larynx, liver and esophagus) even with one alcoholic drink a day, mainly driven by an increase in breast cancer. (See "Overview of the risks and benefits of alcohol consumption", section on 'Cancer'.)
Cardiovascular mortality and modifiable risk factors (August 2015)
Cardiovascular disease (CVD) remains the leading cause of death in the United States (US). Improved risk factor modification can decrease CVD mortality. In descriptive data from a nationally representative survey, five modifiable risk factors for CVD (elevated cholesterol, diabetes, hypertension, obesity, and smoking) accounted for one-half of CVD deaths in US adults aged 45 to 79 from 2009 to 2010 . The preventable fraction of CVD mortality associated with these risk factors was 54 percent for men and 50 percent for women. (See "Overview of primary prevention of coronary heart disease and stroke", section on 'Rationale'.)
Influenza vaccine recommendations for 2015-2016 influenza season (August 2015)
In August 2015, the Advisory Committee on Immunization Practices released recommendations for the prevention and control of influenza during the 2015-2016 influenza season in the United States. As in previous seasons, seasonal influenza vaccination is recommended for everyone ≥6 months of age . Changes for the 2015-2016 season include:
●Different influenza A H3N2 and influenza B (Yamagata lineage) antigens than were in the 2014-2015 vaccines
●A simplified dosing algorithm for children six months through eight years (algorithm 2)
●Availability of a quadrivalent intradermal vaccine for adults 18 through 64 years of age (table 2)
2016 ACOG guidelines for cervical cancer screening (January 2016)
The 2016 American College of Obstetricians and Gynecologists (ACOG) guidelines for cervical cancer screening have been released . ACOG continues to recommend screening for cervical cancer beginning at age 21 with cervical cytology, and co-testing (cervical cytology plus human papillomavirus [HPV] testing) for women age 30 and older. However, in agreement with the 2015 American Society for Colposcopy and Cervical Pathology guidelines, ACOG now also considers primary HPV testing as an option for screening in women age 25 years and older. Because HPV tests may be transiently positive in many younger women, UpToDate authors suggest that women age <30 years be screened with cervical cytology (Pap smear). (See "Screening for cervical cancer", section on 'Primary HPV testing'.)
Screening for diabetes mellitus (January 2016)
Although it has not been firmly established that screening for type 2 diabetes improves long-term outcomes, well-established treatments for diabetes can reduce progression to microvascular disease and early identification of diabetes allows interventions to prevent or limit cardiovascular disease. The US Preventive Services Task Force (USPSTF) has issued new recommendations for diabetes screening. Previously, the USPSTF only recommended screening for diabetes in adults with hypertension, but the new guideline recommends screening for diabetes as part of cardiovascular risk assessment in adults aged 40 to 70 years with body mass index (BMI) ≥25 kg/m2 . The USPSTF suggests screening every three years based on limited evidence. We agree with the new USPSTF guideline and also suggest diabetes screening for adults with hypertension or hyperlipidemia. A fasting plasma glucose (FPG) and/or a glycated hemoglobin (A1C) are the preferred screening tests. (See "Screening for type 2 diabetes mellitus", section on 'A suggested approach'.)
New breast cancer screening guidelines from the American Cancer Society (October 2015)
The American Cancer Society (ACS) has issued revised guidelines for screening women for breast cancer . Significant changes from previous ACS guidelines include recommendations to initiate mammographic screening in average risk women at age 45, to screen women aged 45 to 54 years annually and to screen women 55 years and older biennially as long as they are healthy and have a life expectancy of at least 10 years. Additionally, the guidelines recommend not performing a clinical breast examination. Multiple societies and agencies have developed guidelines with varying recommendations for age and frequency of mammogram screening (table 3). (See "Screening for breast cancer: Strategies and recommendations", section on 'Age to initiate'.)
Frequency of screening mammograms (October 2015)
An analysis of data from the Breast Cancer Surveillance Consortium compared annual and biennial mammogram screening among 15,440 women with breast cancer who were stratified by menopausal status and, if postmenopausal, use of menopausal hormone therapy (MHT) . The proportion of cancers that were less favorable (stage IIB or higher) was higher for women who had biennial screening than for those who had annual screening. This was also the case for women taking MHT, but not for other postmenopausal women in whom tumor characteristics were similar for those screened annually or biennially. Although these data may suggest some benefit for more frequent (eg, annual) screening for premenopausal women, this benefit needs to be weighed against the increased risk of false positive mammogram findings in younger women. In general, for women aged 40 and older at average risk who opt to be screened for breast cancer after counseling and shared decision making, we suggest biennial screening. (See "Screening for breast cancer: Strategies and recommendations", section on 'Frequency of mammography'.)
ACP recommendations for behavioral health (September 2015)
The American College of Physicians (ACP) has issued a new position paper on integrating behavioral health evaluation into primary care. The ACP does not make specific recommendations about screening for depression. However, the ACP supports the integration of behavioral health care (including screening, diagnosis, brief treatment, and referral) into primary care, and encourages addressing behavioral health issues within the limits of available resources . This is consistent with our suggestion to screen adults for depression when staff-assisted supports are in place to ensure appropriate diagnosis, treatment and follow-up. (See "Screening for depression", section on 'United States'.)
ADULT CARDIOVASCULAR MEDICINE
"Warning" symptoms preceding sudden cardiac arrest (January 2016)
“Warning” symptoms may precede sudden cardiac arrest (SCA) in many patients, but symptoms are often unrecognized or minimized. In a community-based study of patients with SCA in whom symptom assessment could be ascertained (either from the surviving patient or from family members, witnesses at the scene of the event, or medical records from the four weeks leading up to the event), more than half of patients had warning symptoms within four weeks preceding SCA . Chest pain and dyspnea were the most common symptoms, with chest pain being more common in men and dyspnea in women. Patients with symptoms concerning for cardiac disease, particularly new or unstable symptoms, should seek prompt medical care for potentially life-saving evaluation and treatment. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Warning symptoms'.)
Chest compressions for cardiac arrest in pregnancy (October 2015)
Chest compressions are the cornerstone of resuscitation after cardiac arrest. The 2015 American Heart Association guideline on cardiac arrest in pregnancy recommends the same hand position for chest compressions in pregnant women and nonpregnant adults . Previous guidelines suggested a more cephalad hand position in pregnancy to adjust for elevation of the diaphragm by the gravid uterus; however, a recent imaging study showed no significant vertical displacement of the heart in the third trimester relative to the nonpregnant state . (See "Cardiopulmonary arrest in pregnancy", section on 'Chest compressions'.)
Modified Valsalva maneuver for treatment of hemodynamically stable supraventricular tachycardia (September 2015)
For both diagnostic and therapeutic purposes, the Valsalva maneuver is commonly used in patients with suspected supraventricular tachycardia (SVT). In a randomized trial of vagal maneuvers for the treatment of hemodynamically stable SVT, patients were assigned to perform the standard Valsalva maneuver (strain generating 40 mmHg pressure for 15 seconds while in a semirecumbent position) with or without supine repositioning and passive leg raise for 15 seconds following the strain phase . Patients performing the modified Valsalva maneuver with supine repositioning and passive leg raise were significantly more likely to have restoration of sinus rhythm at one minute. For patients with hemodynamically stable SVT who are able to effectively perform the maneuver, we recommend the modified Valsalva maneuver as the initial treatment. (See "Atrioventricular nodal reentrant tachycardia", section on 'Vagal maneuvers'.)
Coronary artery embolism as the cause of acute MI (July 2015)
Atherosclerotic coronary artery obstruction is the cause of myocardial infarction (MI) in the overwhelming majority of patients. However, no obstructive coronary atherosclerosis is found in approximately 5 percent of patients; multiple possible causes have been identified. The relationship between MI and coronary artery embolism (CE) due to atrial fibrillation (AF) was evaluated in a study of 1776 patients who presented with an acute MI . The prevalence of CE was about 3 percent and atrial fibrillation was the most likely cause in three quarters of these. In patients with acute MI who do not have obstructive atherosclerotic coronary artery disease as the likely cause, undiagnosed or untreated atrial fibrillation with CE may be the explanation. (See "Myocardial infarction with no obstructive coronary atherosclerosis", section on 'Coronary artery embolism'.)
ADULT ENDOCRINOLOGY AND DIABETES
Empagliflozin in diabetic individuals with overt cardiovascular disease (September 2015)
The cardiovascular effects of diabetes drugs have been evaluated in a growing number of trials. In a trial designed to evaluate the sodium-glucose co-transporter 2 (SGLT-2) inhibitor empagliflozin and cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease (CVD), 7028 patients were randomly assigned to empagliflozin or placebo once daily . The majority of patients were taking metformin, antihypertensives, and lipid-lowering agents, and approximately half in each group were taking insulin.
After three years, the primary outcome (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) occurred in fewer patients assigned to empagliflozin than to placebo (10.5 versus 12.1 percent), driven by a significant reduction in risk of death from cardiovascular causes (3.7 versus 5.9 percent). The difference in glycemia between the groups was minimal (glycated hemoglobin [A1C] 7.8 versus 8.2 percent), suggesting that extra-glycemic effects of the drug were responsible for the CVD outcome. Whether empagliflozin or other SGLT-2 inhibitors will have similar CVD effects in individuals with type 2 diabetes who do not have overt CVD is unknown. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'SGLT2 inhibitors'.)
Bariatric surgery for diabetic patients and glycemic control (September 2015)
Bariatric surgical treatment of obese patients with diabetes results in significant sustained weight loss (20 to 30 percent after one to two years) and, in parallel, large improvements in blood glucose control. However, there are few data on long-term success rates in maintaining weight loss and glucose control. In a report of five-year outcomes (53 patients) from a randomized trial evaluating gastric bypass, biliopancreatic diversion, or medical therapy (pharmacologic therapy, education, lifestyle modification) in 60 patients with obesity and type 2 diabetes, diabetes remission (A1C <6.5 percent without diabetes medication) was maintained in only 56 percent of patients in the surgical groups who had experienced remission at two years . Compared with the medical group, patients treated surgically had significantly lower diabetes and cardiovascular medication use, serum total and LDL cholesterol, and weight, although weight regain occurred in both surgical groups (+6.09 and +4.56 kg, respectively). The study was not powered to assess long-term diabetes complications. Longer-term follow-up of microvascular and macrovascular complications and mortality are required before laparoscopic banding or other bariatric surgery procedures can be routinely recommended for the treatment of persistent hyperglycemia in obesity-related type 2 diabetes. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Surgical treatment of obesity'.)
Testosterone therapy did not improve symptoms in ejaculatory disorders (September 2015)
Although low serum testosterone concentrations have been associated with ejaculatory dysfunction in observational studies, exogenous testosterone does not appear to be an effective therapy for ejaculatory disorders, suggesting that the relationship is not causal. This was illustrated in a randomized trial of 76 men with one or more ejaculatory symptoms (delayed ejaculation, anejaculation, low ejaculate volume, and/or decreased force of ejaculation) and low serum testosterone concentrations (<300 ng/dL [<10.41 nmol/L]), comparing 16 weeks of testosterone solution (2%, 60 mg) or placebo applied to the axilla . Although testosterone therapy increased mean serum testosterone concentrations to the normal male range, there were no improvements in parameters of ejaculatory function. (See "Treatment of male sexual dysfunction", section on 'Other'.)
FTO variant and obesity (September 2015)
Large genome wide association studies have demonstrated that variants in the FTO gene have the strongest association with obesity risk in the general population, but the mechanism of the association has been unclear. However, a nonocoding causal variant in FTO has now been identified that changes the function of adipocytes from energy utilization (beige fat) to energy storage (white fat) with a fivefold decrease in mitochondrial thermogenesis . When the effect of the variant was blocked in genetically engineered mice, thermogenesis increased and weight gain did not occur, despite eating a high-fat diet. Blocking the gene's effect in human adipocytes also increased energy utilization. This observation has important implications for potential new anti-obesity drugs. (See "Pathogenesis of obesity", section on 'FTO variants'.)
SGLT2 inhibitors may predispose to DKA (July 2015)
Sodium-glucose co-transporter 2 (SGLT2) inhibitors promote the renal excretion of glucose and thereby modestly lower elevated blood glucose levels in patients with type 2 diabetes. “Euglycemic” (usually meaning plasma glucose <250 mg/dL) diabetic ketoacidosis (DKA) has been reported in patients with type 2 diabetes taking SGLT2 inhibitors [35,36]. The absence of substantial hyperglycemia delayed recognition of DKA by both the patients and the clinicians. Thus, serum ketones should be obtained in any patient with nausea, vomiting, or malaise while taking SGLT2 inhibitors, and SGLT2 inhibitors should be discontinued if acidosis is confirmed. A warning about SGLT2 inhibitors and ketoacidosis was issued by the US Food and Drug Administration in May 2015. Given the absence of long-term efficacy and safety data, we do not recommend SGLT2 inhibitors for routine use in patients with type 2 diabetes. In addition, off-label use in type 1 diabetes is discouraged in the absence of sufficient safety data. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'SGLT2 inhibitors'.)
Liraglutide for the treatment of obesity (July 2015)
Along with diet, exercise, and behavior modification, drug therapy may be a helpful component of treatment for select patients who are overweight or obese. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, used for the treatment of type 2 diabetes, and can promote weight loss in patients with diabetes, as well as those without diabetes.
●In a randomized trial in nondiabetic patients who had a body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 with dyslipidemia and/or hypertension, liraglutide 3 mg once daily, compared with placebo, resulted in greater mean weight loss (-8.0 versus -2.6 kg with placebo) . In addition, cardiometabolic risk factors, glycated hemoglobin (A1C), and quality of life improved modestly. Gastrointestinal side effects transiently affected at least 40 percent of the liraglutide group and were the most common reason for withdrawal (6.4 percent). Liraglutide is an option for select overweight or obese patients, although gastrointestinal side effects (nausea, vomiting) and the need for a daily injection may limit the use of this drug. (See "Obesity in adults: Drug therapy", section on 'Liraglutide'.)
●In a trial designed specifically to evaluate the effect of liraglutide on weight loss in overweight or obese patients with type 2 diabetes (mean weight 106 kg), liraglutide, compared with placebo, resulted in greater mean weight loss (-6.4 kg and -5.0 kg for liraglutide 3 mg and 1.8 mg, respectively, versus -2.2 kg for placebo) . Treatment with liraglutide was associated with better glycemic control, a reduction in the use of oral hypoglycemic agents, and a reduction in systolic blood pressure. Although liraglutide is not considered as initial therapy for the majority of patients with type 2 diabetes, it is an option for select overweight or obese patients with type 2 diabetes who fail initial therapy with lifestyle intervention and metformin. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Weight loss'.)
Progression from acute to chronic pancreatitis (December 2015)
There are limited data on the natural history of acute pancreatitis. In a meta-analysis that included over 8000 patients with acute pancreatitis, the pooled prevalence of recurrent acute pancreatitis and chronic pancreatitis were 22 and 10 percent, respectively . The prevalence of chronic pancreatitis following the first episode and following recurrent acute pancreatitis were 10 and 36 percent, respectively. Among individuals with a history of smoking or alcohol use, the prevalence of chronic pancreatitis was 65 and 61 percent, respectively. The risk of progression to chronic pancreatitis was higher in men than in women after controlling for age and severity of acute pancreatitis. (See "Clinical manifestations and diagnosis of acute pancreatitis", section on 'Disease course'.)
Acute diverticulitis: Risk of recurrence (December 2015)
There are limited data on the natural history of acute diverticulitis. In a population-based study that included over 3000 patients with acute diverticulitis, recurrent diverticulitis in a 10-year period after the index and second diverticulitis episode occurred in 22 and 55 percent of patients, respectively . The risk of recurrence was higher in younger individuals and in women. Increasing age was associated with a higher risk of both local and systemic complications. (See "Clinical manifestations and diagnosis of acute diverticulitis in adults", section on 'Disease course'.)
ADULT HEMATOLOGY AND ONCOLOGY
New guidance on blood donation deferral for men who have sex with men in the United States (December 2015)
The US Food and Drug Administration has updated its guidance on blood donation for men who have sex with men (MSM). The new guidance specifies a deferral period of 12 months since the last MSM sexual contact rather than indefinite deferral . Prospective donors are instructed not to donate if they have other risk factors for human immunodeficiency virus (HIV) infection such as a recent needle stick injury or blood splash, and permanent deferral remains in place for individuals who have tested positive for HIV, used non-prescription injection drugs, or engaged in sex in exchange for money or drugs. The 12-month deferral has already been in place for other donors who have sex with at-risk individuals, and it aligns the US policy with that of Australia and the United Kingdom. Other countries have deferral periods ranging from six months to indefinite. (See "Blood donor screening: Medical history", section on 'Human immunodeficiency virus'.)
ADULT INFECTIOUS DISEASE
Azithromycin versus doxycycline for uncomplicated chlamydia (January 2016)
The first-line regimens for uncomplicated urogenital chlamydial infection are azithromycin administered as a single dose or a seven-day course of doxycycline administered twice daily. There is emerging evidence that the efficacy of doxycycline may be marginally greater than that of azithromycin, although the reasons for this are unknown. In a trial of 310 adolescents and young adults who screened positive for urogenital Chlamydia trachomatis upon entrance into a correctional facility, microbial cure rates at 28 days were high for both doxycycline and azithromycin (each administered as directly-observed therapy), but were numerically higher for doxycycline (100 versus 97 percent) . Adherence is the main challenge with the doxycycline regimen, and direct observation of the full course is unrealistic in most situations; thus, it is uncertain that doxycycline would achieve a similarly superior cure rate in the community. Given the very high efficacy of azithromycin, we continue to favor directly-observed single-dose azithromycin for treatment of uncomplicated urogenital C. trachomatis infection. (See "Treatment of Chlamydia trachomatis infection", section on 'First-line agents'.)
Tenofovir alafenamide as part of a coformulated antiretroviral regimen (November 2015)
Tenofovir is a preferred nucleoside to use in a combination antiretroviral regimen for the treatment of HIV infection. Until recently, tenofovir was available only as tenofovir-disoproxil fumarate (TDF), which has been associated with renal toxicity and decreased bone mineral density. As of November 2015, a newer formulation, tenofovir alafenamide (TAF), is available in the United States as part of a single tablet co-formulation, elvitegravir-cobicistat-emtricitabine-TAF (ECF-TAF) . This combination agent is as effective as elvitegravir-cobicistat-emtricitabine-TDF (ECF-TDF) in suppressing HIV RNA with fewer adverse renal and bone effects . ECF-TAF can be used for patients with reduced kidney function (estimated glomerular filtration rate [eGFR] ≥30 mL/min/m2), unlike ECF-TDF, which should only be used in patients with an eGFR >70 mL/min/m2. ECF-TAF is considered a recommended regimen by the United States Department of Health and Human Services . TAF is not yet available as a single agent or in other combinations. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Preferred regimens'.)
Statins and influenza vaccine immunogenicity and effectiveness (November 2015)
Statins are used commonly in older adults with hyperlipidemia and are known to have immunomodulatory effects, which could affect vaccine responses. In an observational study conducted in the context of a randomized trial that evaluated influenza vaccines in individuals >65 years of age, hemagglutination inhibition (HAI) geometric mean titers to various influenza strains were substantially lower in those receiving chronic statin therapy than in those not receiving it . In addition, in the adjusted analysis of a large retrospective cohort study, statin use was associated with reduced influenza vaccine effectiveness against medically attended acute respiratory illness . The observed associations between statin use and vaccine effectiveness could be due to confounding, as patients receiving statins are likely to be at differing baseline risk of influenza from those not receiving statins. Although these studies raise the possibility that older patients receiving statins are less likely to be protected by the influenza vaccine, such individuals should still receive statins, when indicated, as well as an influenza vaccine annually. (See "Seasonal influenza vaccination in adults", section on 'Efficacy'.)
Adjunctive glucocorticoids for adults with severe community-acquired pneumonia (August 2015, Modified November 2015)
For hospitalized patients with community-acquired pneumonia (CAP), glucocorticoids as adjunctive therapy to antibiotics have the potential to reduce the inflammatory response and decrease morbidity. A 2015 meta-analysis of randomized trials that included hospitalized patients with CAP suggested a modest mortality benefit for adjunctive glucocorticoids . A reduction in all-cause mortality was of borderline statistical significance (relative risk [RR] 0.67, 95% CI 0.45-1.01; risk difference 2.8 percent). Rates of mechanical ventilation and acute respiratory distress syndrome were decreased, as were time to clinical stability and duration of hospitalization; rates of hyperglycemia requiring treatment increased.
For hospitalized patients with CAP who require intensive care unit admission, we recommend adjunctive glucocorticoids. For other hospitalized patients with CAP, we suggest adjunctive glucocorticoids. Clinicians should make the decision whether or not to give glucocorticoids on a case-by-case basis, especially in patients with an elevated risk of adverse effects. Limited evidence suggests that infections caused by certain pathogens (eg, influenza virus, Aspergillus spp) may be associated with worse outcomes in the setting of glucocorticoid use [49,50]; given these concerns, we avoid adjunctive glucocorticoids if one of these pathogens is detected. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Glucocorticoids'.)
WHO recommendations on HIV treatment and prevention (October 2015)
In 2015, the World Health Organization (WHO) updated its guidelines for the prevention and treatment of HIV infection to recommend initiation of lifelong antiretroviral (ART) for all HIV-infected patients, regardless of CD4 cell count or clinical stage . This recommendation was based, in part, on mounting evidence that the clinical benefit of ART extends to those with very high CD4 cell counts and data demonstrating a dramatic reduction in sexual HIV transmission to uninfected partners with successful ART. The updated guidelines also recommend pre-exposure prophylaxis (PrEP) with a tenofovir-containing regimen as part of the HIV prevention strategy for individuals at substantial risk of HIV infection (ie, those for whom the predicted incidence of infection would be >3 per 100 person years). (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Initiation of antiretroviral therapy' and "Pre-exposure prophylaxis against HIV infection" and "Prevention of mother-to-child HIV transmission in resource-limited settings", section on 'Recommended antiretroviral management'.)
ADULT NEPHROLOGY AND HYPERTENSION
Olmesartan enteropathy (January 2016)
Olmesartan, an angiotensin receptor blocker (ARB), can produce a "sprue-like enteropathy" characterized by severe chronic diarrhea and weight loss, occurring months to years after initiation of the drug. The largest experience comes from a French cohort of over 4 million patients who initiated therapy with olmesartan, a different ARB, or an angiotensin converting enzyme (ACE) inhibitor . Compared with users of ACE inhibitors, intestinal malabsorption severe enough to cause hospitalization occurred substantially more often among patients taking olmesartan for one to two years (adjusted risk ratio 3.7) and among those taking olmesartan for more than two years (adjusted risk ratio 10.6). Risk was not increased in users of other ARBs. Although a large number of patients (ie, 12,550) needed to be treated with olmesartan for two or more years to produce one additional case of enteropathy requiring hospitalization, less severe but still clinically significant cases of enteropathy may have been more frequent. Patients starting olmesartan should be cautioned about the possibility of developing diarrhea and weight loss. The drug should be stopped if these symptoms occur and another cause is not identified. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Enteropathy with olmesartan'.)
SPRINT trial on goal blood pressure (November 2015, Modified December 2015)
Goal blood pressure in most hypertensive patients had been <140/90 mmHg, or <150/90 mmHg in older adults. The potential benefit of lowering the systolic blood pressure goal in nondiabetic older adults with risk factors for cardiovascular disease or with chronic kidney disease was evaluated in the Systolic Blood Pressure Intervention Trial (SPRINT), a multicenter, randomized, open-label trial performed in 9361 hypertensive patients in the United States . Patients were randomly assigned to a standard treatment group (target systolic pressure <140 mmHg) or an intensive treatment group (target systolic pressure <120 mmHg); the diastolic goal in both groups was <90 mmHg. Blood pressure during the trial was measured using automated oscillometric blood pressure (AOBP) and not using manual (ausculatory) blood pressure (perhaps more commonly used in routine practice), typically yielding readings 5 to 10 mm lower than with manual measurement. In the SPRINT trial, consecutive automated blood pressure readings were taken with the patient at rest and averaged. After a median of 3.26 years, intensive as compared with standard treatment reduced the rate of the primary end point, a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death (5.2 versus 6.8 percent), and also reduced mortality (3.3 versus 4.5 percent). Intensive treatment increased the rates of acute kidney injury, syncope, and hyponatremia, but not orthostatic hypotension or falls resulting in hospitalization.
As a result of the SPRINT trial, UpToDate now recommends lower systolic pressure goals (depending on the method of measurement) for nondiabetic adults 50 years and older at high risk for cardiovascular events, and suggests such goals for patients with diabetes. Goals for other groups, including those with proteinuric chronic kidney disease, have not changed based upon the SPRINT data. A trial examining goal blood pressure for patients with diabetes is likely to report findings for this population in 2016. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Benefit according to overall cardiovascular risk' and "Goal blood pressure in patients with cardiovascular disease or at high risk".)
New guidelines on screening and diagnosis of hypertension (October 2015)
New guidelines from the United States Preventive Services Task Force (USPSTF) and the Canadian Hypertension Education Program (CHEP) have been released and suggest that, in nearly all patients who have an elevated blood pressure measured in the office, out-of-office blood pressure readings should be obtained to confirm the diagnosis [54,55]. For out-of-office blood pressure measurement, 24-hour ambulatory blood pressure monitoring (ABPM) is preferred, and home blood pressure monitoring is an acceptable alternative if ABPM is not possible. These guidelines are consistent with our recommendations for confirming elevated blood pressure readings. (See "Overview of hypertension in adults", section on 'Diagnosis'.)
Spironolactone in resistant hypertension (October 2015)
The effect of spironolactone in patients with resistant hypertension has been evaluated in several randomized trials. The best data come from the PATHWAY-2 trial, a randomized crossover study comparing spironolactone (25 to 50 mg/day) with placebo, doxazosin, or bisoprolol in 285 patients with resistant hypertension (mean clinic blood pressure 157/90 mmHg and mean home blood pressure 148/84 mmHg despite therapy with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a diuretic) . Spironolactone significantly reduced mean home systolic pressure at 12 weeks (by 10, 5, and 6 mmHg compared with placebo, doxazosin, and bisoprolol, respectively). Spironolactone (or another mineralocorticoid receptor antagonist) is the treatment of choice in patients with resistant hypertension. (See "Treatment of resistant hypertension", section on 'Mineralocorticoid receptor antagonists'.)
Chlorthalidone and indapamide for hypertension treatment (July 2015)
Two meta-analyses compared thiazide-like diuretics (chlorthalidone and indapamide) with hydrochlorothiazide for the treatment of hypertension.
●In a meta-analysis of 14 trials that compared the blood pressure reduction with one of three dose levels of hydrochlorothiazide (low, intermediate, high) to a corresponding dose level of one of the thiazide-like diuretics, systolic pressure reduction was greater with chlorthalidone and indapamide (by 3.6 and 5.1 mmHg, respectively) .
●In a multiple-treatment (network) meta-analysis of 21 trials that indirectly compared thiazide-type diuretics (such as hydrochlorothiazide) with thiazide-like diuretics (such as chlorthalidone) by evaluating their efficacy against placebo or common comparator drugs, thiazide-like diuretics significantly lowered the relative risk of cardiovascular events by 12 percent and heart failure by 21 percent .
If a diuretic is chosen for treatment of hypertension, we suggest chlorthalidone or indapamide rather than hydrochlorothiazide.
ADULT NEUROLOGY AND PSYCHIATRY
Naloxone intranasal spray for community-based reversal of opioid overdose (January 2016)
Naloxone is an opioid antagonist that rapidly reverses the effects of opioid overdose. Take-home naloxone, along with education and training on its use for overdose, is increasingly provided to opioid-dependent patients and members of their households, making ease of administration a priority. The US Food and Drug Administration recently approved an intranasal naloxone spray (Narcan nasal spray) in a dispenser that delivers a premeasured 4 mg dose . The nasal spray adds to treatment options, which include another easy-to-use device, a handheld naloxone auto-injector (Evzio) that was approved in 2014. Caregivers should contact emergency services as soon as the first dose is given; additional doses may be needed before first responders arrive. (See "Prevention of lethal opioid overdose in the community", section on 'Administration'.)
Mindfulness-based stress reduction for PTSD (August 2015)
Mindfulness-based stress reduction teaches patients to attend to the present moment in a nonjudgmental, accepting manner. A recent clinical trial in patients with posttraumatic stress disorder (PTSD) compared mindfulness-based stress reduction with present-centered group therapy, an active control . After nine weeks of treatment and two months of follow-up, participants in the mindfulness group were more likely to show clinically significant improvement in PTSD symptoms compared with control group participants. The two groups did not differ significantly in the proportion of patients who continued to meet diagnostic criteria for PTSD. Exposure-based cognitive behavioral therapy is first-line treatment for PTSD, but with further study, mindfulness-based stress reduction may provide an effective alternative for the significant proportion of patients who do not accept exposure therapy or do not respond to the treatment. (See "Psychotherapy for posttraumatic stress disorder in adults", section on 'Mindfulness-based stress reduction'.)
Mandibular advancement devices lower blood pressure in sleep apnea (December 2015)
Improved blood pressure control is a benefit associated with continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA) and hypertension. However, it is unclear whether therapeutic modalities other than CPAP result in the same benefit. One meta-analysis of 51 studies of patients with hypertension and OSA reported that compared with patients on placebo or not receiving therapy, mandibular advancement devices (MADs) were associated with a significant reduction in systolic and diastolic blood pressure . The level of reduction was similar to that reported in patients treated with CPAP. While this study does not alter the indications for either therapy, it suggests that patients with OSA who are treated with MADs may derive similar positive effects on blood pressure control as those treated with CPAP. (See "Obstructive sleep apnea and cardiovascular disease", section on 'Impact of treatment'.)
Safety concerns and FDA panel meeting regarding hysteroscopic sterilization (July 2015, Modified September 2015)
Safety concerns have been raised about female sterilization via hysteroscopic placement of micro-inserts into the fallopian tubes. A prospective study of this procedure reported that, at five years, up to 38 percent of women reported recurrent menstrual irregularities and up to 5 percent reported recurrent pelvic pain . Between 2002 and 2015, the US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database received 5093 adverse event reports related to this device, including over 4700 related to menstrual abnormalities or pelvic pain . In September 2015, the FDA convened a meeting of the Obstetrics and Gynecology Devices Panel to review the safety and effectiveness of hysteroscopic sterilization . The panel discussed and made suggestions regarding a need for better patient information materials, a need for a review of existing and future data on adverse effects, and a need to better select candidates for the procedure. Less suitable candidates include those with hypersensitivity to metal or a history of pelvic inflammatory disease. (See "Hysteroscopic sterilization", section on 'FDA panel'.)
Medication approved for low sexual desire in women (August 2015)
Flibanserin is the first and currently only drug approved by the US Food and Drug Administration (FDA) for female sexual dysfunction . Daily use results in modest increases in the frequency of sexually satisfying events and sexual desire. The clinical role of flibanserin may be limited by the need for daily dosing, common adverse effects (eg, somnolence, dizziness), and by safety concerns or lack of safety data regarding combining flibanserin with alcohol or certain medications (eg, fluconazole, CYP3A4 inhibitors, antidepressants). (See "Sexual dysfunction in women: Management", section on 'Flibanserin'.)
Serum test for prediction of preeclampsia (January 2016)
The ratio of soluble fms–like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is increased in the serum of women with preeclampsia; however, the clinical application for this observation remains unclear. A prospective international observational study (PROGNOSIS) attempted to derive and validate a serum sFlt-1:PlGF ratio that would predict the absence or presence of preeclampsia in women who had signs suggestive of the disease, but who did not meet standard criteria for preeclampsia . An sFlt-1:PlGF ratio cutoff of 38 using a specific automated commercial assay had a negative predictive value (no preeclampsia in the next seven days) of 99.3 percent. Few women in the cohort ultimately developed preeclampsia, resulting in a positive predictive value of only 36.7 percent for preeclampsia diagnosis in the next four weeks. Further study is warranted, including determining whether the cut-off varies among laboratories and patient populations, the best interval for repeat testing, and how this information affects clinical decisions, outcomes and costs. (See "Preeclampsia: Clinical features and diagnosis", section on 'Measurement of angiogenic factors'.)
Zika virus infection in the Americas (January 2016)
Zika virus is a member of the flavivirus family that is spread via mosquito bites. Outbreaks have occurred in Africa, Southeast Asia, and the Pacific Islands; more recently Zika virus has spread to the Americas. More than 20 countries in Latin America have confirmed circulation; cases of Zika virus infection in the United States have occurred among returning travelers. The illness is usually mild; typical symptoms include fever, rash, joint pain, and conjunctivitis. However, Zika virus infection has also been associated with perinatal complications (congenital microcephaly and fetal losses) and Guillain-Barre syndrome . In 2015, more than 3500 cases of microcephaly were reported among newborns in Brazil; this represents a 20-fold increase in the number of cases compared with years prior to the circulation of Zika virus . In January 2016, the United States and European Centers for Disease Control advised that pregnant women consider postponing travel to any area where Zika virus transmission is ongoing and also advised that healthcare providers ask all pregnant women about recent travel, with follow-up testing (ultrasound, laboratory testing, or both) depending on clinical circumstances . Anecdotal reports of apparent sexual transmission have been described . Although this appears to be an infrequent mechanism for Zika virus transmission, it may be prudent for men with symptoms of Zika virus infection who have female sexual partners of childbearing age to defer unprotected sex for at least a few weeks following resolution of symptoms. Zika virus is also transmissible via blood products; outside of areas with local mosquito-borne Zika virus transmission, self-deferral of blood donation for 28 days following potential Zika virus exposure has been advised . (See "Zika virus infection", section on 'Geographic distribution'.)
Membrane sweeping in GBS-colonized women (January 2016)
Some practitioners choose not to sweep/strip fetal membranes to induce labor in group B Streptococcus (GBS)-colonized women because of theoretical concerns of bacterial seeding during the procedure. The first prospective study to compare maternal and neonatal outcomes following membrane sweeping among GBS-positive (n = 135), GBS-negative (n = 361), and GBS-unknown (n = 46) women found no significant difference in adverse maternal or neonatal outcomes between groups . There was no difference in the rate of possible early-onset neonatal infection between the GBS-positive and GBS-negative groups and no cases of neonatal sepsis in the entire cohort. Most GBS-positive women received intrapartum GBS antibiotic prophylaxis. Although these results are reassuring about the safety of membrane sweeping in GBS-positive women, the study did not have adequate power to detect modest differences in outcome and is subject to the limitations of an observational design. We believe GBS colonization is not a contraindication to membrane sweeping as there is no direct evidence of harm, but given the paucity of safety data for the procedure in known GBS carriers, we weigh the potential risks and benefits before performing the procedure in known carriers. (See "Induction of labor", section on 'Membrane stripping'.)
Miscarriage risk with oral fluconazole (January 2016)
The pregnancy effects of oral azoles for treatment of vulvovaginal candidiasis is unclear. Studies have reported an increased risk of birth defects after exposure to high-dose azole therapy (400 to 800 mg/day), but not for the low dose therapy used to treat vulvovaginal infections (eg, fluconazole 150 mg). Prior studies have not reported an increased risk of miscarriage with oral fluconazole. However, a recent cohort study of over 3300 women who received 150 to 300 mg of oral fluconazole between 7 and 22 weeks of pregnancy reported an approximately 50 percent increased risk of miscarriage in exposed women compared with either unexposed women or with women treated with vaginal azole therapy . We continue to offer topical azole treatment during pregnancy and prefer to avoid oral therapy until more data on reproductive outcomes are available. (See "Candida vulvovaginitis", section on 'Pregnancy'.)
Neonatal and maternal outcomes for planned out-of-hospital birth (January 2016)
In the United States (US), the safety of non-hospital births is unclear. Several studies have reported that women who deliver at home or at a birth center have equal or improved neonatal and maternal outcomes compared with those who deliver in a hospital; however, outcomes of women transferred to the hospital intrapartum or postpartum because of complications were often included with the hospital delivery group, which could have impacted results. In a US study that analyzed birth outcomes by planned birth location rather than actual delivery site, approximately 16 percent of women planning out-of-hospital births (combined home births and freestanding birth centers) required hospital transfer and their infants had higher rates of perinatal death, neonatal seizures, and neonatal ventilator support compared with infants of planned in-hospital births . Mothers who planned out-of-hospital births but delivered in a hospital had fewer obstetric interventions and a higher rate of blood transfusion. For women in the United States, this study provides a more accurate understanding of the outcomes associated with planned out-of-hospital versus planned in-hospital birth. (See "Planned home birth", section on 'Retrospective studies'.)
Frozen donor oocyte use impacts live birth rate (August 2015)
Use of donor oocytes (eggs) in assisted reproductive technology has allowed women unable to conceive with their own eggs the opportunity to achieve pregnancy. The use of frozen oocytes is more convenient and less costly compared with fresh oocytes because the donor and recipient don't have to be hormonally synchronized and frozen eggs can be shipped anywhere. Although initial studies reported equivalent pregnancy and live birth rates for donor egg transfers, a study of over 11,000 oocyte donation cycles, including 20 percent using frozen eggs, reported the live birth rate per transfer for frozen donor oocytes was lower than the live birth rate for fresh donor oocytes (47 versus 56 percent) . Despite the possible discrepancy in live birth rate, the improved efficiency and lower cost of cryopreserved donor oocytes makes their use a reasonable and attractive option. (See "Management of infertility and pregnancy in women of advanced age", section on 'Oocyte or embryo donation'.)
Prescription medications during pregnancy (August 2015)
Concerns have been raised regarding the frequency with which medication is prescribed during pregnancy, especially for those drugs that may have adverse outcomes for the mother or her fetus. In a study of over one million pregnant women in the United States Medicaid program, nearly 40 percent were prescribed a potentially harmful medication (category D, most commonly codeine and hydrocodone) and 5 percent were prescribed a medication contraindicated during pregnancy (category X, most commonly hormonal contraceptives that were prescribed prior to the diagnosis of pregnancy) . Overall, 83 percent were dispensed at least one medication of any kind (most commonly antibiotic or antifungal agents). While medication can be safely used in pregnancy, the lowest risk option is to avoid drug exposure if possible. When medication is to be taken, the risks and benefits must be discussed, particularly for medications with harmful potential, such as addiction. (See "Initial prenatal assessment and first-trimester prenatal care", section on 'Medications commonly used in pregnancy'.)
PEDIATRICS: GENERAL PEDIATRICS
Evaluation of genetic testing to predict progression in adolescent idiopathic scoliosis (February 2016)
Determining the risk of progression is a crucial factor in the management of adolescent idiopathic scoliosis (AIS). Clinical factors used to predict the risk of progression include radiologic markers of skeletal maturity, age, sex, sexual maturity rating, and location and type of curve. However, accurate prediction of progression using clinical factors is limited. The AIS prognostic test (AIS-PT, marketed as ScoliScore) is an algorithm that incorporates saliva-based DNA testing to predict the risk of scoliosis progression in skeletally immature Caucasian patients with mild scoliosis. In an independent evaluation, AIS-PT scores did not differ between patients with and without curve progression . Independent studies in other populations have also failed to validate the AIS-PT. Lack of validation of the AIS-PT in independent cohorts may be related to differences in the test population, genetic variability, or loss to follow-up of patients with nonprogressive scoliosis [77,78]. Until these issues are resolved, we continue to use clinical factors to predict the risk of progression in patients with AIS. (See "Adolescent idiopathic scoliosis: Management and prognosis", section on 'Genetic testing'.)
Updated guidelines for evaluation of the visual system in children (January 2016)
The American Academy of Pediatrics has issued a policy statement with updated guidelines to aid pediatricians in the assessment of the visual system in infants, children, and adolescents . Changes from previous guidelines include recommendations for instrument-based screening beginning at age 12 months and preference of HOTV or LEA charts over other charts for assessment of visual acuity in young children. Our approach is consistent with these new guidelines. (See "Visual development and vision assessment in infants and children", section on 'Overview of vision assessment'.)
Timing of appendectomy (January 2016)
Whether emergent appendectomy is required in all patients with early appendicitis has been debated. In many institutions, children with early appendicitis receive antibiotics and undergo appendectomy based upon operative and professional resources with a preference for performance of the procedure during daytime or evening hours. In a prospective, observational study that evaluated 230 children who underwent appendectomy, patients with symptoms greater than 48 hours had a significantly higher rate of perforation when compared with patients with symptoms ≤48 hours (46 versus 12 to 18 percent) . When evaluated according to time from diagnosis, the perforation rate, length of stay, and operating time were not significantly different. Thus, limiting the total time from symptom onset to surgery rather than from diagnosis to surgery appears to be of greatest importance in preventing adverse outcomes of appendicitis. (See "Acute appendicitis in children: Management", section on 'Timing of operation'.)
Auvi-Q and Allerject epinephrine autoinjectors recalled by manufacturer (October 2015)
A manufacturer's recall was issued in October 2015 of all Auvi-Q epinephrine autoinjectors in the United States, as well as all Allerject devices in Canada, including both the 0.15 and 0.3 mg strengths, due to potentially inaccurate dose delivery [81,82]. Patients should be provided with a prescription for an alternate epinephrine device and return Auvi-Q and Allerject autoinjectors to their pharmacy for replacement and instruction on how to use the new device. Patients should only use Auvi-Q or Allerject if no other device is available in a severe allergic reaction and then immediately contact 9-1-1 or emergency medical services. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Types of autoinjectors'.)
Outdoor activity for prevention of myopia in children (October 2015)
The prevalence of myopia (nearsightedness) increases throughout childhood, particularly during and after puberty. Myopia often progresses as children grow older and high levels of myopia are associated with an increased risk of sight-threatening complications later in life (eg, myopic macular degeneration and retinal detachment). In a recent study, 1913 school children in China were randomized (by school) to an additional daily 40-minute outdoor class or usual activity . The cumulative incidence rate of myopia over three years was lower in the intervention group compared with the control group (30 versus 40 percent). This is the first study to demonstrate an effective preventative strategy. Increasing the amount of time children spend outdoors is a simple intervention and can be discussed with patients and their families as a strategy to reduce the risk of developing myopia and/or slow its progression. (See "Refractive errors in children", section on 'Myopia'.)
Prevention of alcohol use in children and adolescents (October 2015)
Alcohol is frequently used by children and adolescents in the United States and its use is associated with death and serious injury. In August 2015, the American Academy of Pediatrics (AAP) released a clinical report encouraging pediatric clinicians to talk about the dangers of alcohol with children as young as nine years of age, when they may begin to form positive attitudes towards alcohol . The AAP also recommends screening all youth for alcohol use with a structured screening instrument, either as part of more general substance use screening or, if time is limited, with an instrument that focuses on alcohol, such as the two-question screen developed in collaboration with the National Institute on Alcohol Abuse and Alcoholism (table 4). We agree with these recommendations. (See "Screening tests in children and adolescents", section on 'Alcohol and substance use'.)
PEDIATRICS: DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
Genetic testing in autism spectrum disorder (September 2015)
Genetic testing is often performed in children with autism spectrum disorder (ASD) to provide information about prognosis and recurrence. The suggested evaluation has evolved with advances in molecular diagnostic techniques. In a population-based study, the yield of genetic diagnosis with whole-exome sequencing was similar to that with chromosomal microarray (CMA): 8.4 and 9.3 percent, respectively; and 15.8 percent when both tests were performed . Genetic diagnosis was achieved more often in children with higher levels of dysmorphology, suggesting that severity of dysmorphology is predictive of genetic abnormalities . Pending additional studies, we continue to suggest genetic testing by CMA and DNA analysis for fragile X syndrome for all children with ASD, whether or not they have dysmorphic features. (See "Autism spectrum disorder: Diagnosis", section on 'Genetic testing'.)
Acetaminophen alone not effective in reducing neonatal pain (August 2015)
Acetaminophen (paracetamol) has been used in the management of mild to moderate procedural and postoperative neonatal pain. However, a recent systematic review of randomized trials found that acetaminophen alone was not more effective than placebo in preventing or reducing pain associated with heel lance or eye examination in newborns . As a result, we do not recommend using acetaminophen as the sole agent in newborns to reduce pain from painful procedures. (See "Prevention and treatment of neonatal pain", section on 'Lack of efficacy'.)
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