ADULT MEDICINE

General internal medicine

Screening

Two large trials of prostate cancer screening have been published. In the European Randomized Study of Screening for Prostate Cancer (ERSPC), prostate cancer mortality was reduced by 20 percent with PSA screening, but the absolute reduction was only 0.71 deaths per 1000 men screened [1]. The United States Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial found no mortality benefit with screening; high screening rates in the control group may have diminished the potential to detect benefit [2]. Both studies require longer term follow-up. It appears that prostate cancer screening with PSA does reduce mortality, but that many screened patients with cancer will be treated with morbid therapies while only a few will have improved outcomes. Our suggestions have been modified for men who decide they desire screening. These include a lower PSA cutoff (3 ng/mL) for referral for biopsy, longer screening intervals (every two to four years), and a suggestion not to perform digital rectal examination as part of screening. (See "Screening for prostate cancer").

Use of postmenopausal hormone therapy increases breast density and interferes with the performance of screening mammography. Short-term (one to two months) cessation of hormone therapy in women prior to mammography, although advised by some clinicians, had no effect on mammography recall rates in a randomized trial [3].
(See "Breast imaging: Mammography and ultrasonography").

The largest ongoing randomized trial for ovarian cancer screening, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) has randomly assigned over 200,000 women aged 50 to 74 years to no screening, annual transvaginal ultrasound (TVUS), or multimodal screening (MMS) with annual CA 125 testing and TVUS follow-up [4]. At prevalence screening, specificity was lower for TVUS compared to MMS, resulting in 9 times as many surgeries performed for the TVUS group to detect one cancer. Half of the invasive cancers detected were stage I or II. (See "Screening for ovarian cancer").

Prevention

A prospective study of over one million women found that one alcoholic drink (10 g) per day increased the overall risk for cancer by 6 percent, including cancers of the oropharynx, esophagus, larynx, rectum, liver, and breast [5]. (See "Cancer prevention").

Overall, the use of supplemental vitamins and minerals to prevent cancer has been disappointing [6]. An eight-year observational study of over 160,000 women found no association between multivitamin use and risk of cancer [7]. The only prospective trial of vitamin supplementation (selenium, vitamin E and beta-carotene) to show a mortality effect was in a remote region of China where enrollees likely had baseline nutrient deficiencies [8]. (See "Cancer prevention").

Geriatrics

A randomized trial of elder patients with generalized anxiety disorder found that cognitive behavioral therapy (CBT), delivered in the primary care setting, compared with enhanced usual care (biweekly telephone contact) decreased worry symptoms and moderately improved depressive symptoms [9]. (See "Diagnosis and management of late-life depression").

A randomized trial compared mortality for patients with Alzheimer disease who were randomly assigned to continue their antipsychotic medication or switch to placebo [10]. Survival at 12 and 24 months was significantly greater for the group assigned to placebo. (See "Antipsychotic medications: Treatment issues").

Ophthalmology

Reduced risk for age-related macular degeneration was demonstrable by two years in a randomized trial in women ≥40 years at increased risk for cardiovascular disease and without baseline AMD [11]. Women were randomly assigned to vitamin supplementation (folic acid 2.5 mg/d, pyridoxine 50 mg/d, and cyanocobalamin 1 mg/day) or placebo. If confirmed in other populations, vitamin B preparations may be helpful in the prevention of AMD. (See "Age-related macular degeneration: Treatment and prevention").

Although cataract surgery is typically performed in older adults who are more likely to have medical comorbidities, a systematic review of three randomized trials found that routine preoperative medical testing increased surgical costs but did not reduce the risk of intraoperative or postoperative medical adverse events [12]. (See "Cataract in adults").

The alpha blocker tamsulosin has been more frequently associated with intraoperative floppy iris syndrome (IFIS) occurring during cataract surgery than other alpha blockers. A case control study found that the risk of adverse events related to cataract surgery was 2.3 times greater for those exposed to tamsulosin within two weeks of surgery [13]. Risk was not increased for other alpha blockers or earlier exposure to tamsulosin. However, the authors do not conclude that their data definitively support either stopping tamsulosin prior to surgery, or switching to another alpha blocker. (See "Cataract in adults").

Orthopedics and spinal disease

In a multicenter, randomized trial of patients with severe ankle sprains, those treated in a below-knee cast for 10 days had the greatest improvement in function at three-months, compared to patients treated in an Aircast™ brace, Bledsoe™ immobilization boot, or tubular compression bandage [14]. There was no significant difference among the treatment groups at nine months. (See "Ankle sprain").

Cervical degenerative disc disease is more aptly a radiologic diagnosis, rather than a clinical syndrome, as it is common on x-ray studies in both symptomatic and asymptomatic patients. In one twelve-year prospective longitudinal study, changes on MRI indicating progressive disc degeneration were seen in 81 percent of subjects (mean age 39 years) who were asymptomatic at study onset [15]. (See "Evaluation of the patient with neck pain and cervical spine disorders").

Psychiatry

A meta-analysis of eight observational studies found that exposure to SSRIs in adolescents was associated with an increased risk for attempted or completed suicide (OR 1.92) but with a decreased risk in adults (OR 0.57) and particularly for adults >65 years (OR 0.46) [16]. (See "Effect of SSRIs and other newer antidepressants on suicide risk in adults").

Early treatment of post-traumatic stress disorder (PTSD) may prevent chronicity. A systematic review and meta-analysis found that trauma-focused cognitive behavioral therapy within three months of a traumatic event, compared to usual care, was effective for people with symptoms of acute stress or PTSD, but was not helpful for preventing PTSD in asymptomatic individuals [17]. (See "Overview of post-traumatic stress disorder").

A large observational study found that mental illness was not an independent predictor of violent behavior [18]. Any correlation could be explained by the association of mental illness with other factors that predict violence, including prior history of abuse and violence, substance abuse, divorce, unemployment, and victimization. (See "Schizophrenia: Clinical presentation, epidemiology, and pathophysiology").

Sleep

A trial randomly assigned 160 patients with persistent insomnia to cognitive behavioral therapy (CBT) plus zolpidem or CBT alone for six weeks [19]. There was no significant difference in the insomnia remission rate at six weeks but after six months, the insomnia remission rate was higher among patients who had received CBT plus zolpidem (56 versus 43 percent). (See "Treatment of insomnia").

The melatonin agonists tasimelteon (VEC-162) and ramelteon may become an alternative to melatonin for treating circadian rhythm disruptions, such as those associated with jet lag. Ramelteon is currently available in the United States for treatment of insomnia, and tasimelteon is an investigational agent. A randomized trial found that tasimelteon 50 mg, compared to placebo, induced faster and more efficient sleep in healthy people in whom transient insomnia was induced by advancing the sleep-wake cycle in a controlled setting [20]. (See "Jet lag").

Primary care cardiology

A randomized trial found that in patients with atrial fibrillation who are at high risk for embolic events but are not candidates for warfarin, treatment with aspirin plus clopidogrel reduced vascular events compared with aspirin alone [21]. However, dual therapy increased the risk of major bleeding to a rate comparable to that of warfarin therapy. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation").

The Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration voted in favor of approval of dronedarone, an antiarrhythmic drug that is similar to amiodarone but has fewer side effects, for the treatment of atrial fibrillation in patients without severe heart failure. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials").

The SYNTAX trial randomly assigned 1800 patients with three-vessel or left main coronary artery disease to either CABG or PCI with drug-eluting stents [22]. The risk for the composite primary endpoint (death from any cause, stroke, MI, or repeat revascularization) was greater in the PCI group, due to a higher rate of repeat revascularization procedures; strokes were significantly more common in the CABG group. (See "Bypass surgery versus percutaneous intervention in the management of stable angina pectoris: Clinical trials").

Data are inconclusive on the utility of anticoagulation to reduce thromboembolic events in patients with heart failure who are in sinus rhythm. A randomized trial found similar rates of the primary endpoint (time to occurrence of death, nonfatal myocardial infarction, or nonfatal stroke) in patients treated with aspirin, clopidogrel, or warfarin [23]. Patients treated with warfarin had a lower rate of nonfatal strokes, but more central nervous system bleeds and similar rates of fatal strokes compared to those treated with aspirin or clopidogrel. (See "Indications for anticoagulation in heart failure").

Timing of mitral valve repair in asymptomatic patients with severe mitral regurgitation is controversial. A prospective observational study suggested that in a setting with a high success rate of mitral valve repair and low operative mortality, a strategy of early surgery in patients with asymptomatic severe mitral regurgitation can result in superior outcomes [24]. (See "Indications for corrective surgery in severe chronic mitral regurgitation").

Primary care endocrinology

An international committee, including scientists from the American Diabetes Association, the International Diabetes Federation, and the European Association for the Study of Diabetes, released a consensus statement recommending the use of hemoglobin A1C (A1C) to diagnose diabetes mellitus [25]. (See "Diagnosis of diabetes mellitus").

In a two-year trial of 811 overweight and obese adults randomly assigned to one of four diets based upon macronutrient content, weight loss (3 to 4 kg) was similar in all groups [26]. (See "Dietary therapy for obesity").

In contrast to earlier reports, data from European national registers and records of Medicare beneficiaries in the US do not show an increased risk of esophageal cancer with use of oral bisphosphonates for osteoporosis or fracture [27,28]. (See "Bisphosphonates in the management of osteoporosis in postmenopausal women").

Primary care gastroenterology

A sham controlled trial in patients with dysplastic Barrett's esophagus found significantly higher rates of eradication of dysplasia and intestinal metaplasia with radiofrequency ablation [29]. Ablation was also associated with a lower rate of progression and esophageal cancer. (See "Management of Barrett's esophagus").

Primary care hematology

In a trial in asymptomatic patients on warfarin with an INR between 4.5 and 10, those randomly assigned to oral vitamin K 1.5 mg were more likely to achieve an INR in the range of 2.0 to 3.0 on the following day, compared to placebo [30]. Warfarin was held in both groups. (See "Correcting excess anticoagulation after warfarin").

Primary care infectious disease

The optimum time to initiate antiretroviral therapy (ART) in HIV infection is still unknown. In an analysis of a large cohort of asymptomatic treatment-naive patients, earlier initiation (both in patients with a CD4 count above 500 cells/µL and between 351 and 500 cells/µL) was associated with decreased mortality [31]. (See "When to initiate antiretroviral therapy in HIV-infected patients").

A large randomized trial found that use of a chlorhexidine gluconate-impregnated sponge in intravenous catheter dressings reduced catheter-related infections [32]. (See "Prevention of intravascular catheter-related infections").

A randomized trial in patients with S. aureus bacteremia and endocarditis demonstrated that daptomycin monotherapy is not inferior to low dose gentamicin plus an antistaphylococcal penicillin or vancomycin; those who received a regimen with gentamicin experienced greater reduction in creatinine clearance [33]. Low-dose aminoglycosides should NOT be combined routinely with antistaphylococcal penicillins or vancomycin for treatment of S. aureus bacteremia. (See "Treatment of Staphylococcus aureus bacteremia in adults" and see "Antimicrobial therapy of native valve endocarditis").

The United States Centers for Disease Control and Prevention distributed swine H1N1 influenza A seed stocks to vaccine manufacturers in late May 2009 for use in a vaccine, which will take several months to produce [34]. (See "Prevention of H1N1 influenza A (swine influenza)").

Primary care nephrology

Tolvaptan, an oral vasopressin receptor antagonist, was approved by the US FDA for the treatment of hypervolemic and euvolemic hyponatremia, including those with heart failure, cirrhosis, and SIADH [35]. The drug should only be initiated in the hospital. (See "Treatment of hyponatremia: SIADH and reset osmostat").

As observed in the 4-D trial, the AURORA trial found that the initiation of statin therapy in dialysis patients did not provide cardiovascular benefit despite marked lipid-lowering [36]. (See "Secondary prevention of cardiovascular disease in end-stage renal disease (dialysis)").

Primary care neurology

Transient ischemic attack (TIA) was originally defined as a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours, caused by a transient decrease in blood supply. New guidelines from the American Heart Association and American Stroke Association redefine TIA as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [37]. Ischemic stroke is now defined as an infarction of central nervous system tissue. The end point is now biologic (tissue injury) in both definitions. (See "Definition of transient ischemic attack").

Primary care oncology

For women with recurrent epithelial ovarian cancer, the issue of immediate (prompted by a rising CA-125 level) versus delayed chemotherapy (initiated for signs and/or symptoms) was addressed in an international randomized trial [38]. In a preliminary report, early chemotherapy based on a raised CA-125 level alone did not provide survival benefit or longer remission duration, and was associated with a worse quality of life. The authors concluded that these findings suggest there is no value for routine measurement of CA-125 in the follow-up of ovarian cancer patients. (See "Medical treatment for relapsed epithelial ovarian cancer").

Primary care pulmonology and critical care

A randomized trial found that proton pump inhibitor therapy does not improve asthma-specific outcomes in patients who do not have symptoms suggestive of GERD [39]. (See "Gastroesophageal reflux and asthma", section on Asymptomatic patients).

A meta-analysis of 18 randomized trials found an increase in risk of pneumonia among patients taking inhaled glucocorticoids (RR 1.60), although the absolute increase was very small [40]. Neither pneumonia-related mortality nor overall mortality was significantly increased. (See "Role of inhaled glucocorticoid therapy in stable COPD").

A prospective study in 44 patients found identical pleural cytology results (23 positive for cancer) with analysis of a large (890 mL) or small (50 mL) volume of fluid [41]. (See "Diagnostic thoracentesis").

In a meta-analysis of five observational studies, the prevalence of pulmonary embolism was 20 percent among all patients having a COPD exacerbation and 25 percent in hospitalized patients having a COPD exacerbation [42]. (See "Management of acute exacerbations of chronic obstructive pulmonary disease").

The multicenter Normoglycemia in Intensive Care Evaluation Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial randomly assigned medical and surgical ICU patients to either intensive insulin therapy (target blood glucose 81 to 108 mg/dL [4.5 to 6 mmol/L]) or conventional glucose control (target glucose <180 mg/dL [<10 mmol/L]) [43]. The intensive insulin therapy group had a significantly higher incidence of severe hypoglycemia and 90-day mortality. (See "Glycemic control and intensive insulin therapy in critical illness").

A meta-analysis of 12 randomized trials in patients with severe sepsis or septic shock found that patients who received corticosteroid therapy had reduced 28-day mortality [44]. (See "Corticosteroid therapy in septic shock").

Primary care rheumatology

Febuxostat, a xanthine oxidase inhibitor used to prevent recurrent gouty arthritis, was approved in the US and represents a new treatment option for patients with hyperuricemia and chronic gout [45]. (See "Prevention of recurrent gout").

OBSTETRICS/GYNECOLOGY

Obstetrics

The Institute of Medicine (IOM) revised recommendations for weight gain for pregnant obese women: the lower limit of weight gain was reduced from 15 lbs (6.8 kg) to 11 lbs (5 kg) and an upper limit of weight gain (20 lbs [9 kg]) was added [46]. The IOM also recommended that all women should try to be within the normal body mass index range when they conceive. (See "Weight gain in pregnancy").

There is increasing evidence that adult male circumcision protects against some sexually transmitted infections. A randomized trial in Uganda found that circumcision of adult males had a protective effect on herpes simplex virus (HSV-2) seroconversion [47]. It is presumed that neonatal circumcision would offer a similar benefit. (See "Circumcision: Risks and benefits").

A systematic review found that even high levels of proteinuria (>5 grams) in pregnancy were not predictive of major maternal, fetal, or neonatal complications [48]. The authors concluded that determining the level of proteinuria was not useful for management of preeclampsia, but remains important in the diagnosis of preeclampsia. (See "Expectant management of severe preeclampsia").

Increased rates of spontaneous abortion and preterm birth have been reported among pregnant women with H1N1 influenza A, especially those with pneumonia [49]. (See "Epidemiology, clinical manifestations, and diagnosis of H1N1 influenza A (swine influenza)").

The risks and benefits of more than one course of antenatal glucocorticoids in women at risk of preterm delivery are controversial. A randomized trial of a second course of antenatal glucocorticoids for women less than 33 weeks of gestation and highly likely to deliver within seven days reported salvage therapy significantly reduced the incidence of neonatal respiratory distress syndrome [50]. (See "Antenatal use of glucocorticoids in women at risk for preterm delivery").

Gynecology

Office gynecology

A large randomized trial compared conventional Pap smear to liquid-based cytology [51]. There was no evidence that liquid-based cytology significantly improved detection of high grade squamous intraepithelial lesions, although it did detect more atypical squamous cells of undetermined significance and low grade squamous intraepithelial lesions. (See "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing").

The largest study of female sexual dysfunction in the US included over 30,000 female respondents [52]. The overall prevalence of sexual problems (low desire, low arousal, or orgasm dificulties) was 43 percent. (See "Sexual dysfunction in women: Epidemiology, risk factors, and evaluation").

Reproductive endocrinology

Lybrel (ethinyl estradiol 20 mcg and levonorgestrel 90 mcg) is the first low dose combination oral contraceptive (OC) designed to be taken 365 days a year. In a phase III trial, 18 of 21 women on this contraceptive conceived within 13 months after pill discontinuation, providing support that prolonged continuous use of OCs does not delay the return to fertility [53]. (See "Hormonal contraception for suppression of menstruation").

Gynecologic surgery

Elective oophorectomy at time of hysterectomy reduces risk of ovarian cancer and breast cancer, but may increase the risk of coronary heart disease. A prospective study of 29,380 women age 30 or older who underwent hysterectomy found a decreased risk of ovarian cancer for all women who had an oophorectomy compared with those who did not [54]. The decrease in breast cancer and increase in coronary heart disease were found only in women who underwent oophorectomy at less than 45 years of age. (See "Oophorectomy and ovarian cystectomy").

During dilation and curettage for indications not related to pregnancy, uterine perforation was three times more common in postmenopausal than premenopausal women [55]. Uterine perforation was the most common complication (0.9 percent) in a series of 5349 nonobstetric dilation and curettage procedures. (See "Uterine perforation during gynecologic procedures").

Urogynecology

In a prospective series, 261 women underwent repair of anterior or posterior vaginal wall prolapse or both with a nonabsorbable monofilament polypropylene mesh system [56,57]. At one-year postoperatively, the objective cure rate for all repair types was 85 percent and women reported significantly improved quality of life measures, but sexual function worsened. Bladder and rectal perforations occurred in 3.4 percent of patients and vaginal erosion in 11 percent. (See "Reconstructive materials in urogynecology: Clinical applications").

PEDIATRICS

General pediatrics

Reference ranges for heart rate, by age and temperature, were derived from a study of children aged 3 months to 10 years with suspected acute, self-limiting infection (show table 1) [58]. These reference ranges may facilitate detection of tachycardia out of proportion to fever, which may be an early sign of serious illness. (See "Pathophysiology and treatment of fever in infants and children").

Data from a prospective cohort indicate that rapid increases in weight-for-length from zero to six months of age are associated with an increased risk of obesity at age three years [59]. (See "Normal growth patterns in infants and prepubertal children").

The American Heart Association published nutritional strategies for the prevention and treatment of dyslipidemia in children greater than two years of age [60]. These guidelines include recommendations for daily moderate activity of 60 minutes, encouraging eating at home, and a diet high in vegetables, whole grains and low-fat dairy with reduction in salt and high glycemic intake. (See "Management of the child at-risk for atherosclerosis").

Criteria for the use of pharmacologic agents in children with dyslipidemia have been established by the American Heart Association and American Academy of Pediatrics. Based upon these guidelines and data from the 1999-2000 National Health and Nutrition Examination Survey, less than 1 percent of adolescents in the US would meet criteria for pharmacologic treatment [61]. (See "Management of the child at-risk for atherosclerosis").

Pediatric emergency medicine

Mothers who received education based on the Period of PURPLE crying program were almost twice as likely to walk away from their crying baby when frustrated than mothers in the control group [62]. (See "Physical abuse in children: Diagnostic evaluation and management").

Experts in the US have developed a field triage guideline to identify patients who warrant direct prehospital transportation to a trauma center (show table 2). These guidelines recommend that children "should be triaged preferentially to pediatric-capable trauma centers" [63]. (See "Trauma management: Approach to the unstable child").

Pediatric endocrinology

The Endocrine Society recommends AGAINST the use of propylthiouracil as first-line treatment for Graves' disease in children [64], based on reports of more severe and frequent side effects compared with methimazole [65,66]. (See "Treatment and prognosis of Graves' disease in children and adolescents").

Pediatric gastroenterology

In a randomized trial of infants with gastroesophageal reflux based on symptoms reported by their parents, there was no difference in response among infants treated with a proton pump inhibitor (PPI) compared with placebo [67]. (See "Gastroesophageal reflux in infants", section on Pharmacotherapy).

Pediatric infectious diseases

In a large multicenter trial of infants with bronchiolitis, combination bronchodilator-glucocorticoid therapy was associated with a decreased rate of hospitalization following emergency department visit [68]. This conflicts with findings of another trial in preschool children with acute virus-induced wheezing [69] and additional studies are warranted. (See "Treatment; outcome; and prevention of bronchiolitis in infants and children").

Pediatric neonatology

In a large retrospective study of newborn infants ≥35 weeks' gestation, the use of phototherapy for neonatal hyperbilirubinemia, based upon AAP guidelines, was shown to be effective in avoiding the need for exchange transfusion [70,71]. (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants").

The limit of gestational viability is defined as the stage of maturity that would ensure a reasonable chance of survival without severe deficits. A population-based prospective study from Sweden supports 22 weeks gestational age as the limit of viability [72]. (See "Incidence and mortality of the premature infant").

Pediatric ophthalmology

A screening algorithm based upon gestational age, birth weight, and weekly postnatal weight gain and serum insulin-like growth factor-I levels had a sensitivity of 100 percent and a specificity of 84 percent in predicting stage 3 retinopathy of prematurity (ROP) [73]. The algorithm requires additional validation. (See "Retinopathy of prematurity").

Vaccines

The AAP and United States Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices have issued updated guidelines for the prevention of rotavirus disease [74,75]. (See "Rotavirus vaccines").