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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.
Duration of benefit of one-time screening sigmoidoscopy (June 2017)
Sigmoidoscopy is one of several methods to screen for colorectal cancer in average-risk persons. In extended follow-up of a randomized trial, a one-time screening flexible sigmoidoscopy for people aged 55 to 64 years was associated with reduced colorectal cancer incidence and mortality even 17 years after the initial screening exam [1]. Similar benefits had been seen at 11-year follow-up. Although these findings support one-time flexible sigmoidoscopy as a potential screening method, most groups that include sigmoidoscopy as a screening option currently recommend repeated testing, although the optimal repeat interval is not known. In agreement with recommendations of the US Preventive Services Task Force, when flexible sigmoidoscopy is chosen as a screening modality, we offer flexible sigmoidoscopy alone every five years or flexible sigmoidoscopy every 10 years plus fecal immunochemical testing (FIT) every year. (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".)
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 [2]. 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'.)
USPSTF statement on screening for celiac disease (April 2017)
Testing for celiac disease in the absence of suggestive signs or symptoms is controversial. A US Preventive Services Task Force report has concluded that there are insufficient data to support screening for celiac disease [3]. However, we continue to test for celiac disease in asymptomatic first-degree relatives of patients with a confirmed diagnosis of celiac disease because of their increased risk for disease. We also recommend screening asymptomatic children with several conditions associated with celiac disease, including type 1 diabetes and Down syndrome. Our recommendations are consistent with guidelines from the American College of Gastroenterology and from Pediatric Gastroenterology societies [4]. (See "Diagnosis of celiac disease in adults", section on 'Who should be tested'.)
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 [5]. 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 [6]. (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 [7]. 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 [8]. 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 [9]. 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'.)
Spinal manipulative therapy for acute low back pain (June 2017)
Spinal manipulative therapy (SMT) has been used for acute low back pain, but the literature has shown inconsistent results. In a recent systematic review and meta-analysis of 26 randomized controlled trials, 15 showed moderate-quality evidence of improvement in pain and 12 showed moderate-quality evidence of improvement in function [10]. The magnitude of clinical benefit was modest, and there were no serious adverse effects. Prior reviews have reported less consistent benefit. We offer SMT to patients based on their individual preferences and access to this intervention. (See "Treatment of acute low back pain", section on 'Spinal manipulation'.)
Respiratory tract infections and antibiotic overuse (June 2017)
Upper respiratory tract infection (URI) and acute bronchitis are among the most common reasons for antibiotic overprescription, and reducing use for these indications is a global health care priority. A prospective cohort study assessing over 28,000 adults with acute cough lasting <3 weeks without radiographic evidence of pneumonia found no difference in rates of major complications, including hospital admission and death, when comparing patients given immediate antibiotic prescriptions with delayed prescription or no prescription [11]. This study adds further support for the lack of benefit for routine use of antibiotics for patients with acute bronchitis and can be used to reassure patients that they are not more likely to develop complications if they are not treated with antibiotics. (See "Acute bronchitis in adults", section on 'Avoiding antibiotic overuse'.)
Goal blood pressure in older adults (May 2017)
Goal blood pressure in older hypertensive adults is controversial. A meta-analysis of over 10,000 hypertensive adults 65 years or older combined results from the older subgroup in the SPRINT trial with three other large randomized trials evaluating goal blood pressure [12]. At three-year follow-up, compared with less intensive therapy, more intensive blood pressure lowering reduced the rates of major adverse cardiovascular events, cardiovascular mortality, and heart failure. In general, UpToDate recommends a systolic blood pressure goal of 125 to 135 mmHg if standard manual blood pressure measurements are used or 120 to 125 mmHg if unattended automated oscillometric measurements are used. If attaining goal blood pressure proves difficult or burdensome for the patient, the systolic blood pressure that is reached with two or three antihypertensive agents (even if above target) may be a reasonable interim goal. (See "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension", section on 'Goal blood pressure'.)
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 [13]. 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 glucocorticoids 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 pain relief at 24 hours and there was only a small difference in symptom relief at 48 hours (35 versus 27 percent with placebo) [14]. These results support our suggestion to not prescribe glucocorticoids routinely for acute pharyngitis and to limit their use to severely symptomatic patients. (See "Symptomatic treatment of acute pharyngitis in adults", section on 'Limited role of glucocorticoids'.)
Adverse events with short-term oral glucocorticoid use in adults (April 2017)
Chronic steroid use is associated with a wide spectrum of adverse effects. However, there is a paucity of clinical data on the adverse effects associated with short-term use. A retrospective cohort study and self-controlled case series assessed the risk of three adverse events (sepsis, venous thromboembolism [VTE], and fracture) in over 300,000 adults younger than 65 who received at least one short-term (<30 days) outpatient prescription for oral glucocorticoids over a three-year period [15]. The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Within 30 days of drug initiation, there was a two- to fivefold increase in the rates of sepsis, VTE, and fracture, which then decreased over the subsequent 31 to 90 days. These findings suggest that even short courses of oral steroids are associated with adverse effects that should be considered before prescribing. (See "Major side effects of systemic glucocorticoids", section on 'Dose effects'.)
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 [16]. 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 [17]. 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 [18]. 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 [19]. 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 [20]. 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 [21]. 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 [22], 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 [23]. 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'.)
Countering the high cost of epinephrine autoinjectors (June 2017)
Physicians and patients in the United States have been struggling with the high cost of epinephrine autoinjectors, and alternatives, as well as ways to maximize the utility of expensive devices, have begun to appear:
●A prefilled syringe (Symjepi) containing 0.3 mg epinephrine per dose was approved by the US Food and Drug Administration (FDA) in June 2017 and should offer a more affordable alternative to autoinjectors [24]. It will be available in upcoming months in just one dose, labeled for use in patients weighing ≥30 kg (66 lbs). (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Prefilled syringes'.)
●A study of 31 expired autoinjectors (EpiPens) found that devices as much as four years past the expiration date still contained 84 to 88 percent of the intended epinephrine dose [25]. Thus, patients should understand that expired devices retain most of their potency and that if anaphylaxis develops, using an outdated device is preferable to not injecting epinephrine at all. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Use of expired autoinjectors'.)
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 [26]. 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'.)
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 [27]. 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 [28]. 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'.)
GLP-1-based therapies for type 2 diabetes and overall mortality (June 2017)
The effect of glucagon-like peptide-1 (GLP-1)-based therapies (GLP-1 receptor agonists and dipeptidyl peptidase-4 [DPP-4] inhibitors) on overall mortality in patients with type 2 diabetes is uncertain. In a systematic review and meta-analysis of 189 trials, there was no difference in all-cause mortality between any GLP-1-based therapy versus control (placebo or other antidiabetic drug) [29]. In subgroup analyses of the cardiovascular outcomes trials, there was a suggestion of reduced all-cause mortality with GLP-1 receptor agonists versus placebo, but no difference with DPP-4 inhibitors versus placebo. Further studies examining the effect of GLP-1 receptor agonists on overall mortality are warranted. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus" and "Dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus".)
Screening interval for diabetic retinopathy (May 2017)
There are few data evaluating the optimal frequency of follow-up retinal examinations after initial screening in patients with diabetes, particularly type 1 diabetes. In an analysis of almost 24,000 retinopathy examinations over 24 years in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study, the probability of progressing from lower to higher categories of retinopathy was dependent upon the previous retinal exam and glycated hemoglobin (A1C), with optimal screening intervals ranging from every three months among patients with severe nonproliferative retinopathy to every four years among those who had no retinopathy [30]. Compared with annual or biannual examinations, this model for an individualized schedule resulted in an overall reduction in the frequency of eye examinations and a substantial reduction in cost. (See "Diabetic retinopathy: Screening", section on 'Frequency of examinations'.)
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 [31,32] 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 [33].
●There was a beneficial effect on anemia [34] and bone density [35].
●Testosterone increased coronary artery noncalcified plaque volume as measured by coronary computed tomographic angiography [36].
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 [37]. 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 [38]. 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 [39]. (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 [40]. 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 [41]. 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 [42]. 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 [43]. 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'.)
ACG guidelines on the treatment of H. pylori (May 2017)
The American College of Gastroenterology has published updated guidelines on the treatment of Helicobacter pylori [44]. According to these guidelines, the choice of initial antibiotic regimen to treat H. pylori should be guided by risk factors for macrolide resistance and penicillin allergy. Risk factors for macrolide resistance include prior exposure to macrolides and local clarithromycin rates ≥15 percent (assumed in the United States). In patients with risk factors for macrolide resistance, bismuth quadruple therapy is a first-line treatment option. (See "Treatment regimens for Helicobacter pylori", section on 'Approach to selecting an antibiotic regimen'.)
Risk of colon cancer in patients with diverticulitis (April 2017)
The utility of routine colonoscopy after acute diverticulitis is debated. An analysis of data from a Danish registry showed that patients hospitalized for diverticulitis were twice as likely to develop colon cancer over the 18-year study period as those without diverticulitis, and over 50 percent of colon cancers were diagnosed within one year of diagnosis of diverticulitis [45]. This study underscores the importance of endoscopic surveillance in patients with diverticular disease and supports our recommendation for performing a colonoscopy after the complete resolution of an episode of acute diverticulitis in patients who have not had a colonoscopy within a year. (See "Acute colonic diverticulitis: Medical management", section on 'Colonoscopy for all patients'.)
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 [46]. 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'.)
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 [47]. 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'.)
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 [48,49]. (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 [50]. 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 [51], preliminary results from the NSABP-B42, DATA, and IDEAL trials, reported at the San Antonio Breast Cancer Symposium, have not confirmed this benefit [52-54]. 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'.)
Treatment of nonpurulent cellulitis (June 2017)
Empiric antibiotic therapy for nonpurulent cellulitis (ie, with no purulent drainage and no associated abscess) should be active against beta-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus (MSSA) but not necessarily methicillin-resistant S. aureus (MRSA). This approach is supported by a randomized trial of nearly 500 patients with nonpurulent cellulitis, in which cephalexin plus placebo (active against beta-hemolytic streptococci and MSSA) and cephalexin plus trimethoprim-sulfamethoxazole (TMP-SMX, which adds activity against MRSA) resulted in statistically similar clinical cure rates (69 versus 76 percent) [55]. Although there was a trend toward higher cure rates with the addition of TMP-SMX, the results were likely skewed by a relatively large number of patients who did not complete the full course of therapy. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Cellulitis'.)
Rising rates of HCV infection in young women in the United States (May 2017)
In parallel with the opioid and injection drug use epidemic in the United States, rates of hepatitis C virus (HCV) infection have been increasing over the past decade. In particular, the annual number of acute HCV cases among women aged 15 to 44 years rose 3.6-fold from 2006 to 2014 [56]. An estimated 29,000 women with HCV infection gave birth each year between 2011 and 2014; since the risk of vertical transmission is approximately 5.8 percent, this implies that an estimated 1700 infants were infected annually during this time. These numbers highlight the importance of screening at-risk individuals and arranging follow-up for those with HCV infection. (See "Vertical transmission of hepatitis C virus", section on 'Incidence' and "Hepatitis C virus infection in children", section on 'Epidemiology'.)
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 [57]. 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 [58]. 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 [59]. 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 [60,61]. 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 [62]. 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".)
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 [63]. 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 [64]. 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'.)
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 [65]. 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'.)
Revised follow-up for a solitary pulmonary nodule (June 2017)
Fleischner Society guidelines have been updated to reflect the accumulating data on the malignancy risk of incidental pulmonary nodules and growth rates of lung cancer [66]. Important changes include guidance on identifying benign nodules with minimal follow-up imaging. For patients with a solid or subsolid (ground glass or part-solid) solitary pulmonary nodule measuring <6 mm, follow-up computed tomography (CT) is optional, but no longer required. A solitary pulmonary nodule that is solid and unchanged on serial CT over a two-year period, or subsolid and unchanged over a five-year period, is likely benign and does not need further diagnostic evaluation. Recommendations in UpToDate have been revised to reflect these new guidelines. (See "Diagnostic evaluation and management of the solitary pulmonary nodule", section on 'Management strategy' and "Diagnostic evaluation and management of the solitary pulmonary nodule", section on 'Solid nodules ≤8 mm'.)
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 [67]. 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.
(See "Diagnosis of asthma in adolescents and adults", section on 'Diagnosis'.)
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 [68]. 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'.)
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) [69], an international task force [70], and the American College of Physicians (ACP) [71]. 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 [72]. 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.
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 [73]. 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 [74]. 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 [75]. 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 [76]. 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 [77]. However, efficacy has also been shown for treatment of OIC in cancer patients [78], 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 [79]. (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 [80]. 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'.)
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- Qaseem A, Harris RP, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2017; 166:58.
- Roman-Blas JA, Castañeda S, Sánchez-Pernaute O, et al. Combined Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows No Superiority Over Placebo for Reduction of Joint Pain and Functional Impairment in Patients With Knee Osteoarthritis: A Six-Month Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Arthritis Rheumatol 2017; 69:77.
- Kennedy-Hendricks A, Gielen A, McDonald E, et al. Medication Sharing, Storage, and Disposal Practices for Opioid Medications Among US Adults. JAMA Intern Med 2016; 176:1027.
- McDonald EM, Kennedy-Hendricks A, McGinty EE, et al. Safe Storage of Opioid Pain Relievers Among Adults Living in Households With Children. Pediatrics 2017; 139.
- https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm551185.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on April 07, 2017).
- Hale ME, Wild J, Reddy J, et al. Efficacy and Safety of Naldemedine for the treatment of opioid-induced constipation in subjects with chronic non-cancer pain receiving opioid therapy: results from two Phase 3 clinical trials (abstract 598). Data presented at the 2016 Digestive Disease Week, San Diego, CA, May 21, 2016. Abstract available online at http://www.gastrojournal.org/article/S0016-5085(16)30515-7/pdf (Accessed on March 30, 2017).
- https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/208854Orig1s000ltr.pdf (Accessed on March 30, 2017).
- Katakami N, Oda K, Tauchi K, et al. Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients With Cancer. J Clin Oncol 2017; :JCO2016708453.
- http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-001893-PIP01-15/pip_001533.jsp&mid=WC0b01ac058001d129 (Accessed on March 30, 2017).
- Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med 2017; 13:307.


text:
External Links
A site for solving at least some of your technical problems...
A site for solving at least some of your technical problems...
Extensible markup language. First mainly used on the Internet, XML was born out of a constrained version of HTML (SGML). It is now used for all sorts of data.
Today I started testing a lot of my JavaScript / jQuery code from a website I am building for a customer. I got an error, at some point, saying:
SCRIPT5007: Unable to get property 'replace' of undefined or null reference
The error was in link with the 'replace' function being referenced on an innerHTML of an element. More specifically, one of those XML element (probably the top most one.)
The fact is that Internet Explorer does not support innerHTML in an XML document. Not to be too surprised about that, XML is not HTML so there is really no reason why innerHTML should be ...
If you are like me and write DTDs to check your XML files to make sure you don't have too many mistakes in them, then you probably have had this problem before.
The #PCDATA has a very special behavior and it is really restrained as follow:
Something like this:
does not work because you use + and #PCDATA is within a sub-group.
What you need ...
Since December 2008, I have noticed that many RSS feeds include invalid ampersand characters. XML has a very specific way to handle the ampersand character, you have to write & and not just &. Although it is similar in HTML, in XML it is actually enforced.
This is neat, it ensures that your files are really valid.
Last night I found a problematic module... Specifically, it was XML Sitemap, but I do not think it was specific to that module.
The problem? I lost the XML Sitemap menu. I could not access it at all. So I decided to run the update.php code to see whether that would wake it up. Did not work. Then I tried going in the Modules list and disabling the modules. Did not work! Wow! I could not disable these modules!!! How weird...
Today I bumped in another problem.
Some QuickBooks tables cannot properly be updated with QODBC. In my case it was the SalesOrderLine table. The first error I got was:
Error parsing complete XML return string (8)
I just couldn't be sure what that meant...
I had looked at the XML output closely and noticed that the identifier of a line was improperly shown in a separate tag.
The fact is, I just could not update multiple lines with FQSaveToCache flag set to 1.
An RSS feed is very common on all new websites. It has been around for years now. As of today you could listen to thousands of RSS feeds and be totally swamped by all the news...
But what is an RSS feed?
The way users know about RSS feed is in the form of a URL. The URL points to a file on a website that includes data. That data file uses the specific RSS or RDF format, which uses XML as the base format.
So it is in fact very easy to generate an RSS feed. All you have to do is write an XML file with the proper tags and attri as defined on the W3C and AtomEnabled ...
Use at your own risk! These are links to other pages outside of this website:
GNU Free Documentation License Version 1.3, 3 November 2008 Copyright (C) 2000, 2001, 2002, 2007, 2008 Free Software Foundation, Inc. Everyone is permitted to copy and distribute verbatim copies of this license document, but changing it is not allowed. 0.
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subset: commoncrawl


text:
Unfortunately, The Deck is currently closed on Deliveroo.
Chicken, Sausage, Bacon and Cheese£0.00
Chicken. Sausage. Pesto and Cheese£0.00
Chicken, Pepper, Olive and Pesto£0.00
Bacon, Sun dried tomato, Onion and Mushroom£0.00
Mushroom, Pesto, Spinach and Onion£0.00
Sun dried tomato, Olive, Pesto and Pepper£0.00
Spinach, Pesto, Sun dried tomato and Olive£0.00
Spinach, Cheese, Mushroom and Pepper£0.00
Good To Know


text:
Mumbai, Jun 28: Tata Motors, India's top automaker launched its two of the costliest brands Jaguar and Land Rover (JLR) in India on Sunday Jun 28 which it had brought from US Ford Motors.
"It's quite a memorable day in the history and heritage of Tata Motors...JLR has been well received and well established in India (in the past), but over the years this brand has been disconnected from India," Tata group chief Ratan Tata told reporters.
Tata said, "Now, we have decided to extend the penetration of the two brands in India." He also said, "I think the cars will exhibit the levels of technology and levels of performance here."
"The two brands would give Indian public an opportunity to experience the pleasure of driving the superior technology", Tata added.
OneIndia News


text:
Nobody put it more frankly than UW goaltender Brian Elliott Sunday night.
Once again, he surrendered just two goals. Once again, the Badger offense was stymied. And once again, Wisconsin lost.
The Minnesota Gophers capped off a weekend sweep of the Badgers with a 3-1 victory. The defending national champions have now lost five straight contests and seven of their last eight.
"These things that you go through, they never turn themselves quickly," UW head coach Mike Eaves said. "It's like a big ship in the ocean, it takes time to bring it around."
But this latest stretch has many Badger faithful hoping that the ship is not taking on water.
For a few brief moments, it looked like Wisconsin had caught the break that it so badly needed to get the ball rolling.
Sophomore center Ben Street found the back of the net late in the second period when his centering pass attempt deflected off a defenseman, ricocheted off netminder Jeff Frazee and into the goal.
Street's second of the year gave the Badgers a 1-0 lead that even Minnesota head coach Don Lucia thought might hold up.
But he rallied his troops in the second intermission and they responded by killing nearly four consecutive minutes of penalties to open the third frame before scoring three goals in the final 16 minutes.
Minnesota sophomore Ryan Stoa evened things up at 4:49 of the third. After his initial shot was blocked he followed the puck behind the net and was able to throw it off the back of Elliott's equipment, banking it into the goal.
The Gophers got another good bounce nearly 10 minutes later. Elliott stopped an initial shot by Minnesota and as it caromed through the air tried to catch it in his glove. But traffic built up around the net and the senior All-American was thrown off kilter.
Sprawled out in the crease, the puck settled near his skates and freshman Tony Lucia dove in to scoop it into the empty right side of the net.
"I think all the goals tonight was just the puck going to the net and taking bounces off legs and off feet and then finding an opening," Street said. "That was the way it went all night and they got a couple more bounces than we did. That's the way it goes, that's hockey."
That was all the Gophers would need, though Blake Wheeler pocketed an empty-net goal with 47 seconds left to stick a fork in the Badgers.
"We played a little better tonight, (but we're) still looking for that timely goal," Eaves said. "You go through these times in your life and you have to persevere through them to build some character."
It was not as if the Badgers didn't have their chances. In particular, with a little more than a minute remaining in the second period, they had a golden opportunity to double their lead.
Jake Dowell found a wide-open Michael Davies towards the right of the slot. But Frazee was there to deny Davies.
"We're getting chances, and he made a great save on that, there's not much that you can do," Street said.
"We'll take any goal, any time right now," Eaves said.
It was another heart-breaker for Elliott, who has surrendered more than two goals in a game just once in his past six outings.
Even Street, who hadn't scored in nearly a month, could not find much satisfaction.
"I would have much rather taken two points for our team," Street said.
While it will not officially go down as a one-goal loss, that is essentially what it was for the third straight game. During the five-game losing streak, UW has never lost by more than two goals.
"You've just got to stay persistent with it," Street said. "Sooner or later those things are going to even out."
Those things are going to need to even out sooner rather than later, however. With the loss, the Badgers are now 4-8-2 on the year and have just six league points through 10 WCHA games—good for a tie in seventh place, 10 points behind the Gophers.
Asked if he was positive that the Badgers could turn things around, Street responed: "I hope so, I guess. The hockey gods have got to even it out sooner or later."
Perhaps things will start evening out during some non-conference action. The Badgers will host Michigan State and Michigan in the College Hockey Showcase next weekend.


text:
About Frank EdwardsFrank Edwards A.k.A Frankrichboy is a member of Christ Embassy Church, popularly called LoveWorld Ministries. He's also a member of LoveWorld Music Ministry, an instrumentalist and member of the Presidential band of Pastor Chris Oyakhilome in Christ Embassy Church.He believes Pastor Chris actually inspired him to do what he is doing today. He never dreamt of Singing, He always wanted to Read On
Ebube Lyrics by Frank Edwards Feat Victor Ike
Ebube Lyrics by Frank Edwards Feat Victor IkeLook at my life, can you see what God has doneLook around, see the beauty of His worksebubeebubeebubeebubee yeaHoly One, You make the sun to rule the dayFaithful God, You made the moon to rule the nightebubeebubeebubeebubee yeaEbube, You're bigger than what people sayEbubeEbube, good God AlmightyYou're bigger than what Read On
Oba Awon Oba Lyrics – Samsung ft midnight crew & frank Edwards
The thing wey You dey doChurchboy, samsong, midnight crew, come on! Come on!The thing wey You dey doJust dey blow my mindNow I cant denyOh oh ohI try to speakYour love is my speechTry to breatheNo air, no airAnd the thing wey You dey do dey make me do that buggie doAlawoteleorun, Lord You make my life completeRefrain:Ohun loba awon oba kabio o siEledumare, Oba aanuOhun loba awon Read On
EL-SHADAAI LYRICS- SAMSUNG FT FRANK EDWARDSEbube-eh..Ebu..Ebube-ehThank YouI go by the name GilRich boy on e beatEbube-eh..Ebu..Ebube-ehChorus::El shaddaiYou're bigger than what the people sayGod,no be lieYeahJehovah JirehAll around the world I've found no one like YouYeahMy lord of Genesis to revelationMy El-shaddaiYou're my elevationYou never lieThe ancient of daysBeen Read On
You too dey bless me (3rd remix) Lyrics Frank Edwards
YOU TOO DEY BLESS ME(3rd Remix) lyrics: oooh oo na so you love me ooh!(in soft tone)You too dey bless me oooh! Na so you love me oooh!eeyee,you too dey bless me ooo...GLASS SHATTERS,THE MAIN SONG BEGINS,PEOPLE SHOUTINGYou too dey bless me,bless meNa so you love meNa wetin i do wey makeYou love me sooo(in a soft tone)You died on the crossJust because of me,me,me,me,meYou shed your blood Read On
MMA MMA DIRIGI LYRICSVERSE 1:People dey wonderNa wetin dey make me dey fine like thisThe are asking meNa wetin dey make me dey shine like thisThey wanna knooowNa wetin dey make me dey smile like thisPeople dey wonderNa wetin dey make me dey dance like thisNa the things wey my God dey doNa im dey make me dey shine like this ooooNa the things wey my Goddy dey doNa im dey make me dey smile Read On


text:
|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|"Keith N. McKenna" <keith.mcke...@comcast.net>
|[User Docs] What do we as a community want for user documentation or AOO
|Sun, 16 Sep 2012 01:18:34 GMT
Greetings All; In order to stimulate some discussion on user documentation I have added the hollowing page to the User Documentation Plan on the Plannig Wiki: https://cwiki.apache.org/confluence/display/OOOUSERS/User+Guides+Revisted. It offers 3 scenarios or the creation of the docs. I believe that we can no longer put this issue aside. Please take a look at the page and eel free to comment there and on this list. Also feel free to add to or change any content there. Regards Keith N. McKenna
|View raw message


text:
3 colors
ADELYN RAE Illusion Yoke Lace Fit & Flare
Wispy eyelash details add intriguing delicacy to this architecturally tailored fit-and-flare dress available in a collectible array of colors. Color(s): black, burgundy, cherry, cobalt, eggplant, electric blue, green, navy, peacock, plum, purple. Brand: ADELYN RAE. Style Name:Adelyn Rae Illusion Yoke Lace Fit & Flare Dress. Style Number: 1155344. Available in ... Learn More
ALEXANDER MCQUEEN Jacquard Lace Dress
Inspired by a trip to the Shetland Islands, this jacquard-knit dress borrows from Scottish tradition and its colorful Fair Isle patterning. Puffed sleeves and a ruffled hem sweeten the look and balance the figure-hugging silhouette. Color(s): navy/ bordeaux/ blue. Brand: ALEXANDER MCQUEEN. Style Name:Alexander Mcqueen Jacquard Lace Dress. Style Number: ... Learn More
CEREMONY BY JOANNA AUGUST 'Lacey' Ruffle Wrap Lace
Wrap styling creates elegance and customizable comfort for a romantic lace gown trimmed with fluttery ruffles at the shoulders and plunging surplice neckline. Crossover straps at the back make a pretty rear view, while the gently gathered skirt flatters a multitude of figures. Color(s): champagne lace. Brand: CEREMONY BY JOANNA ... Learn More
CITY CHIC Fit & Flare Dress with Delicate
The peekaboo sheerness of the scribble-patterned lace insets amps up the flirt factor of this charming cap-sleeve dress. The waist-whittling silhouette is accentuated with a slim patent belt. Color(s): black, cobalt, red. Brand: CITY CHIC. Style Name:City Chic Fit & Flare Dress With Delicate Lace Insets (Plus Size). Style Number: ... Learn More
CITY CHIC Mono Print Maxi Dress
Black-and-white patterning adds graphic appeal to a breezy scoop-neck maxi dress with a drawstring waist to call attention to your curves and a shirttail hem to flash a glimpse of pretty ankles. Color(s): black. Brand: CITY CHIC. Style Name:City Chic Mono Print Maxi Dress (Plus Size). Style Number: 5286478. Available ... Learn More
HINGE 'Dorin City' Sandal
An on-trend, minimalist sandal shaped from soft, supple leather is topped with woven straps and grounded by a stacked block heel for a chic update to your everyday, warm-weather style. Color(s): cognac suede, sand suede. Brand: HINGE. Style Name:Hinge 'Dorin City' Sandal (Women). Style Number: 5081611. Available in stores. Learn More
INGRID & ISABEL® Ingrid & Isabel Lace Maternity
A form-fitting dress crafted from stretch lace accommodates your changing curves while completing your party look with ladylike elegance. Color(s): berry, black combo, hibiscus, ivory, jet black, true navy, winter white. Brand: Ingrid & Isabel. Style Name:Ingrid & Isabel Lace Maternity Dress. Style Number: 842996. Learn More
KIMI AND KAI Estelle Lace Maternity Dress
Delicate floral lace panels highlight the crisp shutter pleats on this bump-flattering LBD that's perfect your next special event. A bateau neckline and elbow-length sleeves frame the form-fitting silhouette for an elegant finish. Color(s): black. Brand: Kimi and Kai. Style Name:Kimi And Kai Estelle Lace Maternity Dress. Style Number: 5252160. ... Learn More


text:
IPC President and CEO John Mitchell introduces IPC's Global Policy Framework, a living document that lists IPC's guiding principles and specific policy concerns, and guides all of the association's advocacy work.
Recent Posts
- Electronics Industry Pioneer Jim Raby Passes Away
- Three RoHS Exemption Extensions are Official
- President Donald Trump Launches Workforce Development Week
- Advancing U.S Manufacturing: A Focus on Federal Investment in R&D Infrastructure
- DOL Withdraws Troublesome Guidance on Independent Contractor Classification
CategoriesAssembly Automotive Electronics Boards Certification Committees Compliance Conflict Minerals Design Economy electronics Environment, Health and Safety Executive Management Government Relations IPC Lead Free Legislation Manufacturing Market Research Materials Membership OEM President's Message printed electronics Regulations Standards Suppliers Technical Trade Show Training Uncategorized
IPC's on Twitter
- #Dusseldorf #Electronics bursting with life and opportunities! Join us 27-28 June #IPCEUForum bit.ly/2pbSSo3 2 days ago
- RT @THOMASNET: "More women entering #MFG and succeeding is good for women and for the industry."- @WomeninMFG bit.ly/2l4aixI 2 days ago
- RT @john_hasselmann: Today at #MFGSummit @SpeakerRyan discussed how tax reform will lead to job growth for American businesses. 2 days ago
- #IPCNEWS: @zentechman First to Recertify for IPC Qualified Manufacturers Listing #IPCValidationServices owl.li/n3MY30cKOP3 2 days ago
- RT @john_hasselmann: @IPCassociation commends @VP for his comments today at #MFGSummit supporting American manufacturing. 2 days ago


text:
Exceptional. Fascinating. Sporty. A glance at the high-tech package proves that the new CLA 45 AMG also possesses the typical DNA and represents Driving Performance perfectly. Because the new four-door high-performance coupé offers an exceptional combination between fascinating sporty driving experience, extravagant design and high-level individuality.
Passionate dynamism on wheels. The dynamic design idiom expresses itself in muscular proportions and flowing contours. And the expressive design is continued in high-value materials in the vehicle interior, too.
The most powerful 4-cylinder engine in the world. Under the bonnet the most powerful series-production 4-cylinder engine in the world with a peak output of 265 kilowatts and a maximum torque of 450 newton metres[1] delivers its whole dynamism. And the performance-orientated AMG 4MATIC all-wheel drive transmits the power in just the right measure to the road.
(CLA 45 AMG 4MATIC: Fuel consumption combined: 7.1-6.9 l/100 km, CO2 emissions combined: 165-161 g/km)[2]
[1] Figures for rated output and rated torque in accordance with Directive 80/1269/EEC in the currently applicable version.
[2] The figures shown for fuel consumption and CO2 emissions were obtained in accordance with the prescribed measuring methods (Regulation [EC] 715/2007 in its currently applicable version). The figures are not based on an individual vehicle and do not constitute part of the product offer; they are provided solely for purposes of comparison between different vehicle models.
A-Klases Sedans
Sports Tourer
Uzzini visu par C-Klasi
Uzzini visu par C-Klasi
Uzzini visu par C-Klasi
Atgriež ticību brīnumiem.
Jaunais CLA
Jaunais CLA
CLS-Klases Kupeja
CLS-Klases Shooting Brake
E-Klases Sedans
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E-Klases Kabriolets
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G-Klases Apvidus auto
Jaunais GLC Coupé
GLC-Klases Apvidus auto
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GLS-Klases Apvidus auto
S-Klases Sedans
S-Klases Kupeja
S-Klases Kabriolets
SLC-Klases Rodsters


text:
Having moderate to severe psoriasis puts you at risk for developing other conditions. Your physician may not be able to treat all your ...Read More
Having moderate to severe psoriasis puts you at risk for developing other conditions. Your physician may not be able to treat all your ...Read More
As the long summer nights fade into the chilly evenings of fall, suntans and shades give way to coughing and sneezing. The first signs of the cold and flu season are ...Read More
The last time you saw your dermatologist for your psoriasis, were you satisfied by the information you got? If not, there's a chance you ...Read More
Part 1 of 5
Read More
If you have psoriasis, you know that managing your skin condition is easier said than done. Finding what works for you, and how to keep your flare-ups at bay, can be challenging. But you're not ...Read More
Severe psoriasis causes multiple symptoms and side effects. Treatment results can also differ from person to person. This is why most ...Read More
Healthline has carefully selected these blogs because they are actively working to educate, inspire, and empower their readers with frequent updates and ...Read More
Part 1 of 5
Read More
Part 1 of 5: Overview
Psoriasis is a common chronic immune disease that causes skin cells to grow quickly. The fast growth can lead to scaly, itchy, dry, and ...Read More
If you have psoriasis, you're probably already familiar with flare-ups. In addition to diet and stress, extreme weather conditions play a ...Read More
Psoriasis is a chronic condition. This means that once you've been diagnosed, you'll be managing and treating it for the rest of your life. Because of this, it can be ...Read More


text:
Call our experts: 888.808.FINE
Shop Personalized StationeryCarlson Craft Wedding Invitations Customize any Address Stamp to match your style!
Select a quantity and printing method. Changes are easily made later.
A modern cityscape silhouette serves as the backdrop on this stylish card. The photo of your choice is printed within a thin blue frame on the left side of the card. "Save the Date" is preprinted on the back of the card to complete the look.The size of the photo printed on the sample card is 3.625 x 2.5 inches.
View Prints Charming Paper's digital photo requirements


text:
About the Clan MacPherson Plaid Cover – Bandon Preserve
Golf enthusiasts, meet the clan MacPherson plaid cover. Featuring forest greens, orange, sky blue, and gold from only the most robust kilt grade tartan from the finest mill in Northern Scotland. Seamus Golf has offered to custom engrave the Bandon Preserve logo onto each of their Clan MacPherson covers.
Find other Seamus Golf headcover styles here!
Available in 460CC Driver, Fairway, and hybrid covers (Please see drop down menus).
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*Ground Shipping is the only shipping option for this product.
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text:
|Page (1) of 1 - 11/16/11
|email article
|print page
Attorneys: Whistleblower's secret access restoredAttorneys: Whistleblower who disclosed failures to ship gear to troops gets secret access back
Page: 1
Related Keywords:Whistleblower Reinstated, Armed forces, Military and defense, Government and politics
Source:Copyright 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.. All Rights Reserved


text:
Licensed Realtor & Real Estate Investor with a strong passion, focus and dedication towards Real Estate. I enjoy reading, doing deals, spending time with the family, and traveling. I've taken part in Rehabbing property, property management, acquisition of distressed property and cash flow producing mutli-unit property. I'm looking to network with others.
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