The following represent additions to UpToDate since the last version that were considered by the authors and editors to be of particular interest. The new material described below represents a small subset of the updating that has been performed, since approximately 40 percent of the topic reviews are updated during each four-month cycle.

ADULT MEDICINE

General internal medicine

Screening

A US study of the diagnosis and treatment of prostate cancer between 1986 (prior to the introduction of screening) and 2005 estimated that 18 men had to be treated for prostate cancer to prevent one death, suggesting that most of the additional cases of prostate cancer found since 1986 represent overdiagnosis [1]. (See "Screening for prostate cancer",)

The value of a clinical breast examination (CBE) as an adjunct to mammography in screening for breast cancer was evaluated in a study that compared a cohort of 290,000 women who underwent screening with both CBE and mammography, and 58,000 women who had mammography alone [2]. CBE plus mammography had greater sensitivity but, for each additional cancer detected by CBE, there were 55 additional false positive screens. (See "Screening for breast cancer".)

Interim results from the Norwegian Colorectal Cancer Prevention trial in which individuals aged 55 to 64 years were randomly assigned to colorectal cancer (CRC) sigmoidoscopy screening (with or without immunochemical fecal occult blood) or no screening found a significant CRC mortality reduction for those who participated in screening [3]. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy".)

A study of patients with colonic adenomas found that patients with a history of an advanced adenoma or multiple adenomas were at increased risk for recurrent adenomas during surveillance colonoscopies, even if the first follow-up study was negative [4]. (See "Approach to the patient with colonic polyps".)

Interim results from the randomized DANTE trial of spiral CT scan for lung cancer screening found that more stage I cancers were found in the CT-screened group, compared with annual clinical follow-up, but the number of advanced lung cancer cases and lung cancer mortality were the same for screened and control patients [5]. Longer follow-up may be required to detect differences in disease-specific mortality. (See "Screening for lung cancer".)

A single question, "How many times in the past year have you had [5 for men, 4 for women] or more drinks in a day?", had moderately good sensitivity and specificity for screening primary care patients for unhealthy drinking [6]. Screening is considered positive for the response 'at least once'. (See "Screening for and diagnosis of alcohol problems".)

Prevention

Patients who had discontinued statin therapy because of myalgias tolerated red yeast rice and achieved significant reductions in LDL-C, in a placebo-controlled randomized trial [7]. There is a lack of standardization of red yeast rice products and it is not known if a lower dose of statin would have been tolerated and could achieve similar LDL-C reductions [8]. (See "Lipid lowering with diet or dietary supplements",)

The US Food and Drug administration has required identical boxed warnings on bupropion and varenicline about the risk of serious neuropsychiatric symptoms (eg, behavior changes, agitation, depressed mood, suicidal thoughts, and attempted suicide) and noted the overlap with typical symptoms of nicotine withdrawal [9]. (See "Management of smoking cessation",)

Compared to other age groups, young adults (< 30 years) in the US are less likely to have preventive care visits or medical insurance, and are at increased risk for depression, suicide, substance abuse, sexually transmitted disease, and HIV infection [10]. These risks and other preventive measures should be considered at nearly every medical encounter, rather than only at targeted complete physical examinations. (See "Overview of preventive medicine in adults".)

Geriatrics

The benefits of exercise, including lower mortality and maintaining independence, have been associated with initiating, as well as continuing, exercise in older adults including those ages 78 to 85 years [11]. Additionally, regular exercise and the Mediterranean diet were independently associated with a decreased risk for Alzheimer disease in a prospective study of older adults [12]. (See "Geriatric health maintenance" and "Overview of the benefits and risks of exercise" and "Prudent diet".)

Orthopedics and spinal disease

A systematic review found that spinal fusion surgery may be more effective than unstructured nonsurgical care, but equally effective compared to intense multidisciplinary rehabilitation in patients with disabling nonradicular back pain [13]. Practice guidelines from the American Pain Society recommend that surgery or interdisciplinary rehabilitation be presented as options in shared decision making for these patients. [14]. (See "Subacute and chronic low back pain: Surgical treatment".)

In two blinded trials comparing vertebroplasty with a sham procedure for osteoporotic vertebral compression fracture, there was no immediate or delayed benefit of vertebroplasty for the reduction of pain [15,16]. (See "Clinical manifestations and treatment of osteoporotic thoracolumbar vertebral compression fractures".)

Preoperative management

A randomized trial in patients undergoing elective vascular surgery found that fluvastatin (initiated at least 30 days before surgery) decreased myocardial ischemic events [17]. (See "Management of cardiac risk for noncardiac surgery",)

Psychiatry

A systematic review of second-generation antidepressants found that mirtazapine and paroxetine were associated with more weight gain than fluoxetine, sertraline, trazodone, and venlafaxine [18]. (See "Initial treatment of depression in adults".)

A cohort study of people 65 years and older found that depressed individuals were more than twice as likely to develop diabetes compared to those without depression, regardless of antidepressant treatment [19]. In addition, specific antidepressants may be associated with an increased risk of diabetes. A nested case-control study in patients with depression found that long-term use (>24 months) of some antidepressants (amitriptyline, fluvoxamine, paroxetine, and venlafaxine) in moderate to high doses was associated with a significantly increased risk of diabetes [20]. (See "Initial treatment of depression in adults", section on Antidepressants, Side effects.)

A randomized trial in patients with psychotic depression found that the combination of an antipsychotic plus an antidepressant was superior to an antipsychotic alone [21]. (See "Initial treatment of depression in adults".)

Primary care cardiology

The RE-LY trial demonstrated that an alternative oral anticoagulant (dabigatran) may be superior in efficacy and safety to adjusted-dose warfarin in patients with atrial fibrillation [22]. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".)

A large observational study evaluated the net clinical benefit of warfarin to prevent embolization in patients with nonvalvular atrial fibrillation (AF) [23]. Benefits in patients with CHADS2 scores below 2 were small, with confidence intervals that included the possibility of net harm with anticoagulation. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".)

Two randomized trials in patient with STEMI who were treated with fibrinolytic therapy found that transfer for possible percutaneous coronary intervention was superior to ischemia guided treatment in local hospitals [24,25]. These results have led to a change in our recommendations for the management of patients after fibrinolysis. (See "Percutaneous coronary intervention after fibrinolysis for acute ST elevation myocardial infarction".)

Cardiac resynchronization therapy (CRT) has known benefit in patients with more severe heart failure (HF). A randomized trial found benefits in patients with milder HF as well, mainly in those patients with a QRS duration > 150 msec [26]. (See "Cardiac resynchronization therapy in heart failure".)

A benign prognosis for primary first degree atrioventricular (AV) block was suggested in early studies. However, a large prospective cohort study of individuals from the Framingham Heart Study found that, compared with a normal PR interval, individuals with first degree AV block were more likely to develop atrial fibrillation, had a greater risk of receiving a permanent pacemaker, and a higher all-cause mortality [27]. (See "First degree atrioventricular block".)

Primary care dermatology

In 2009, the World Health Organization International Agency for Research on Cancer Monograph working group classified ultraviolet-light emitted from tanning devices as carcinogenic to humans [28]. (See "Risk factors for the development of melanoma".)

Primary care endocrinology

Due to reports of severe propylthiouracil (PTU)-related liver failure, the American Thyroid Association and the US Food and Drug Administration have published preliminary new recommendations for PTU use [29]. We agree with their recommendations and suggest that PTU not be prescribed as the first line drug in most children or adults. PTU is still preferred to methimazole during the first trimester of pregnancy and in patients with life-threatening thyrotoxicosis or thyroid storm. (See "Pharmacology and toxicity of thionamides" and "Diagnosis and treatment of hyperthyroidism during pregnancy".)

Data regarding use of insulin analogs and risk of cancer are conflicting for insulin glargine and, pending more data, there is insufficient evidence to make a recommendation against glargine [30-34]. (See "General principles of insulin therapy in diabetes mellitus", section on 'Human versus analogs'.)

In a five-year trial in over 1000 patients with type 2 diabetes, there was no difference in the risk of retinopathy progression in patients randomly assigned to twice daily NPH versus once daily glargine [35]. (See "General principles of insulin therapy in diabetes mellitus", section on 'Human versus analogs'.)

Acute pancreatitis in patients using sitagliptin has been reported in postmarketing reports [36]. Pancreatitis should be considered in patients with persistent severe abdominal pain and sitagliptin should be discontinued in such patients. (See "GLP-1-based therapies for the treatment of type 2 diabetes mellitus".)

In a trial in overweight patients with newly diagnosed type 2 diabetes, patients randomly assigned to a low carbohydrate Mediterranean diet were significantly less likely to require antihyperglycemic drugs than those assigned to a low fat diet [37]. (See "Nutritional considerations in type 2 diabetes mellitus".)

Primary care gastroenterology

A meta-analysis of seven controlled trials in populations at high risk for gastric cancer found a significantly lower rate of gastric cancer following H. pylori eradication (1.1 versus 1.7 percent) [38]. (See "Association between Helicobacter pylori infection and gastrointestinal malignancy", section on 'Does treatment reduce risk of gastric cancer?'.)

A randomized trial demonstrated that maintenance lactulose after an episode of hepatic encephalopathy significantly reduced the incidence of recurrent episodes of hepatic encephalopathy (20 versus 47 percent) during 14 months of follow-up [39]. The study helps confirm a preventive approach in such patients. (See "Treatment of hepatic encephalopathy".)

A new guideline from the American Association for the Study of Liver Diseases re-emphasizes that screening patients with hepatitis B for hepatocellular carcinoma should be performed by obtaining an ultrasound every six months rather than by measuring serum alpha-fetoprotein. (See "Surveillance for hepatocellular carcinoma in adults with chronic liver disease".)

Primary care hematology

Because of the use of a new reference standard, unfractionated heparin products manufactured in the United States after October 8, 2009 will be 10 percent less potent [40]. This may have clinical significance in some situations, such as when heparin is administered as a bolus intravenous dose and an immediate anticoagulant effect is clinically important. (See "Therapeutic use of heparin and low molecular weight heparin".)

Primary care infectious disease

Although in children the live attenuated (intranasal) influenza vaccine may be more effective than the inactivated (intramuscular) vaccine, the inactivated vaccine was superior to the live attenuated vaccine in preventing influenza infection in adults in a randomized trial during the 2007 to 2008 influenza season [41]. (See "Seasonal influenza vaccination in adults".)

The current pandemic of a novel strain of H1N1 influenza represents a quadruple reassortment of two swine strains, one human strain, and one avian strain of influenza. Treatment and preventive measures are evolving. (See "Epidemiology, clinical manifestations, and diagnosis of pandemic H1N1 influenza ('swine influenza')" and "Treatment of pandemic H1N1 influenza ('swine influenza')" and "Prevention of pandemic H1N1 influenza ('swine influenza')".)

The US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) updated recommendations regarding revaccination of individuals at prolonged increased risk for meningococcal disease [42]. (See "Meningococcal vaccines", section on Revaccination.)

New ACIP guidelines for rabies vaccine administration for post-exposure prophylaxis in unvaccinated persons advise that the five-dose schedule be changed to four doses, eliminating the last dose administered on day 28 [43]. (See "Rabies immune globulin and vaccine".)

Primary care nephrology

The Cardio-Sis trial compared the effects of tight systolic blood pressure control (target <130 mmHg) and usual control (target <140 mmHg) among patients with cardiovascular disease or an additional cardiovascular risk factor [44]. Patients with the lower target had a decreased prevalence of left ventricular hypertrophy and decreased risk of new onset atrial fibrillation and coronary revascularization. (See "Choice of antihypertensive drug and blood pressure goal in patients at increased risk for a cardiovascular event".)

In a randomized trial, treatment with oral bicarbonate slowed progression of chronic kidney disease and improved nutritional status of patients with creatinine clearances between 15 and 30 mL/min per 1.73 m2 [45]. (See "Treatment of metabolic acidosis in chronic kidney disease".)

Because of concerns about the data, UpToDate has previously recommended not relying on the COOPERATE trial when making decisions about using combination therapy with ACE inhibitors and ARBs in treating patients with chronic kidney disease, however some clinicians were still using this combination based on results from COOPERATE. Lancet has now formally retracted its publication of the COOPERATE trial [46]. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease", section on Combination of ACE inhibitors and ARBs.)

Primary care neurology

In a longitudinal study, subjects (mainly women) who had migraine with aura at an initial evaluation had an increased risk of infarct-like lesions on brain MRI 25 years later, compared with those not reporting recurrent headaches at baseline [47]. (See "Headache, migraine, and stroke".)

Surgical decompression for carpal tunnel syndrome had a small benefit of modest clinical significance, compared to nonsurgical treatment (multimodal intervention) in a randomized trial [48]. (See "Treatment of carpal tunnel syndrome",).

Primary care pulmonology and critical care

A meta-analysis including 7042 patients with COPD found no increased risk of pneumonia with inhaled budesonide [49]. (See "Role of inhaled glucocorticoid therapy in stable COPD".)

Primary care rheumatology

A randomized trial in patients with Dupuytren's contractures found that injection of clostridial collagenase into the lesion was beneficial and may be an effective alternative to surgery [50]. (See "Dupuytren's contracture".)

OBSTETRICS/GYNECOLOGY

Obstetrics

Several meta-analyses have demonstrated that maternal administration of magnesium sulfate just prior to preterm delivery is associated with a decreased postnatal risk of cerebral palsy and severe motor dysfunction [51-53]. We suggest administration of magnesium sulfate to pregnant women under 32 weeks of gestation who are likely to have a preterm birth within 24 hours.(See "Neuroprotective effects of in utero exposure to magnesium sulfate".)

A multicenter randomized trial (HYPITAT) found that women with mild preeclampsia or gestational hypertension who underwent induction of labor at ≥37 weeks gestation had a lower risk of developing severe hypertension and a lower cesarean delivery rate than women managed expectantly with maternal/fetal monitoring [54]. (See "Management of preeclampsia".)

A multicenter trial randomly assigned women with mild gestational diabetes (GDM) to a regimen of diet/blood glucose monitoring/insulin as needed or routine obstetrical care [55]. The treatment group had a significant reduction in the rate of macrosomia, shoulder dystocia, cesarean delivery, and preeclampsia/gestational hypertension. (See "Treatment and course of gestational diabetes mellitus".)

Gynecology

Office gynecology

In a retrospective study, previously undiagnosed endometrial cancer was found less frequently in women who underwent a follow-up curettage after office endometrial biopsy than in those who had a repeat biopsy or no repeat sampling [56]. (See "Endometrial hyperplasia".)

Preoperative transvaginal sonography had a reasonable sensitivity and specificity (83 and 85 percent respectively) for the diagnosis of adenomyosis, in a meta-analysis of 14 studies in which women underwent hysterectomy with pathologic confirmation of adenomyosis [57]. (See "Adenomyosis".)

Gynecologic surgery

Two randomized trials found that menstrual flow reduction and patient satisfaction were similar for microwave ablation compared with endometrial resection or thermal balloon ablation [58,59]. Microwave ablation was associated with a shorter operating time and fewer device failures [59]. (See "Endometrial ablation".)

The rates of serious infection in women who underwent mifepristone/misoprostol abortion dropped significantly after the introduction of two protocol changes: routine use of prophylactic doxycycline and buccal, rather than vaginal, administration of misoprostol [60]. (See "Mifepristone for the medical termination of pregnancy".)

Urogynecology

A meta-analysis compared traditional vaginal repairs, sacrocolpopexy and vaginal mesh kits for apical prolapse [61]. Vaginal mesh kits had the highest rates of severe complications (12.9 percent) and reoperations (8.5 percent). (See "Reconstructive materials in urogynecology: Clinical applications".)

PEDIATRICS

General pediatrics

When initiating atomoxetine therapy for attention deficit hyperactivity disorder, an observational study suggests that evening administration of once-daily atomoxetine is associated with fewer adverse effects than morning administration [62]. (See "Attention deficit hyperactivity disorder in children and adolescents: Pharmacotherapy".)

Due to a shortage of 0.5 percent erythromycin ophthalmic ointment in the US, the Food and Drug Administration (FDA) recommends that this ointment be used only for neonatal prophylactic eye care [63]. If 0.5 percent erythromycin ophthalmic ointment is unavailable, the Center of Disease Control (CDC) recommends 1 percent azithromycin ophthalmic solution (1 to 2 drops placed in the conjunctival sac of each eye) for neonatal prophylactic eye care [64]. (See "Overview of the routine management of the newborn infant".)

Unfractionated heparin (UFH) manufactured in the US and shipped after October 8, 2009 will be less potent than previous products, with a 10 percent lower activated partial thromboplastin time (aPTT) per USP unit of heparin [65]. Children who receive UFH should be monitored by both aPTT and heparin levels. (See "Diagnosis and treatment of venous thromboembolism in infants and children".)

The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization to permit the use of oseltamivir for the treatment of influenza in infants younger than one year of age [66]. (See "Antiviral drugs for the prevention and treatment of influenza in children",)

A safety review indicates an increased risk of lymphoma and other cancers associated with use of tumor necrosis factor (TNF) inhibitors in children and adolescents, and the US Food and Drug Administration has required that this information be included in a boxed warning for TNF inhibitors [67]. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy".)

Pediatric cardiology

The American Academy of Pediatrics and the American Heart Association have concluded that it remains uncertain whether neonatal pulse oximetry screening for congenital heart disease (CHD) should become standard of care [68]. Although data have shown that most cases of CHD are detected by neonatal pulse oximetry, the cost effectiveness of screening is unknown. (See "Suspected heart disease in the newborn: Criteria for referral".)

The US Food and Drug Administration (FDA) was not able to verify a relationship between the use of stimulant therapy for ADHD and sudden unexpected death (SUD) and found methodological limitations with a retrospective study that reported this association [67,69].

Pediatric endocrinology

The incidence of childhood type 1 diabetes is rising rapidly worldwide, particularly in younger children [70]. Reasons for this increase are unknown. (See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents".)

Pediatric gastroenterology

The timing and manner of gluten exposure may affect the risk for celiac disease. Observational studies suggest that the risk might be reduced by continuing breastfeeding while introducing gluten into an infant's diet, and by introducing gluten gradually [71,72]. (See "Clinical manifestations and diagnosis of celiac disease in children".)

Pediatric immunizations

The US Food and Drug Administration has licensed Hiberix, a Haemophilus influenzae type b (Hib) conjugate vaccine, for use as the booster dose in children aged 15 months through 4 years who have completed their primary series of Hib conjugate vaccines [73] .The Centers for Disease Control and Prevention (CDC) has recommended Hib immunization (with any available Hib vaccine) at the earliest opportunity for children aged 12 months through 4 years whose Hib booster was deferred because of vaccine shortage [73]. (See "Prevention of Haemophilus influenzae infection".)

The recommended target groups for pandemic H1N1 influenza vaccination differ from those for seasonal influenza. The US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has recommended the following order for administration of the pandemic H1N1 influenza vaccine, when available [74]:

• Pregnant women
• Household contacts and caregivers of children younger than six months of age
• Healthcare and emergency medical services personnel
• Individuals 6 months through 24 years of age
• Individuals 25 through 64 years of age with increased risk of influenza complications

(See "Prevention of pandemic H1N1 influenza ('swine influenza')".)

Pediatric infectious diseases

A randomized trial supports antimicrobial therapy for children with acute bacterial sinusitis (ABS) when ABS is defined by strict clinical criteria (symptoms for >10 days without improvement; acutely worsening symptoms; or temperature ≥102ºF (38.9ºC) and purulent nasal discharge for ≥3 consecutive days) [75]. (See "Acute bacterial sinusitis in children: Microbiology and treatment",)

The US Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antiviral medications during the 2009-2010 influenza season, to be updated as necessary (www.cdc.gov/flu/professionals) [76]. Antiviral medications are prioritized for:

• Individuals hospitalized with suspected or confirmed influenza
• Those at high risk of influenza-related complications (including children < two years, pregnant women, children receiving long-term aspirin therapy, and individuals with chronic disease)
• Suspected or confirmed influenza cases who are severely ill (eg, lower-respiratory-tract infection or rapid clinical deterioration), regardless of age or previous health

Laboratory confirmation with culture or polymerase chain reaction tests should not delay the initiation of antiviral therapy for individuals in whom therapy is indicated. Negative rapid tests do not exclude influenza. (See "Antiviral drugs for the prevention and treatment of influenza in children".)

Neonatology

The use of a pacifier is associated with a reduced risk of sudden infant death syndrome. Concerns that pacifier use might interfere with exclusive breastfeeding were not corroborated by a randomized trial that found that pacifier use did not effect the rate of exclusive breastfeeding at three months of age [77]. (See "Breastfeeding: Parental education and support".)

The US Preventive Services Task Force (USPSTF) concluded that data were insufficient to recommend universal bilirubin newborn screening to prevent kernicterus [78]. In a commentary, several neonatal experts agree that the evidence is limited but continue to recommend universal bilirubin newborn screening [79]. (See "Evaluation of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Universal screening'.)

The effectiveness of newborn screening was suggested by an Australian cohort study that found a lower incidence of death or significant intellectual and physical impairment at six years for the screened group of children compared to those who were unscreened [80]. (See "Newborn screening".)

A prospective study found no difference in the risk of significant clinical renal abnormalities in infants with an isolated single umbilical artery compared to matched controls [81]. (See "Care of the umbilicus and management of umbilical disorders".)

Pediatric nephrology

In a study of two-month-old infants with moderate unilateral hydronephrosis, 94 percent of infants had resolution of their hydronephrosis (defined as two consecutive ultrasounds with a renal pelvic diameter ≤ 5 mm) by 12 to 14 months of age [82]. (See "Postnatal management of antenatal hydronephrosis".)

Pediatric urology

In children, the most commonly used anticholinergic agent for overactive bladder (OAB) is oxybutynin. In a study based on data from the US Food and Drug Administration Adverse Event Reporting System, central nervous system side effects associated with oxybutynin occur red more frequently in children than adults and included hallucination, agitation, sedation, confusion, amnesia, and nightmares [83]. (See "Management of voiding dysfunction in children".)