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What's new in primary care internal medicine

Last literature review version 17.3: September 2009  |  This topic last updated: October 15, 2009   (More)

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.

GENERAL INTERNAL MEDICINE

Screening

A study that examined the number of men diagnosed and treated for prostate cancer in the United States each year after 1986, the year before PSA screening was introduced, until 2005 estimated that approximately 23 men had to be diagnosed and 18 men treated for prostate cancer to prevent one death [1]. The authors concluded that most of the additional cases of prostate cancer found since 1986 represent overdiagnosis. (See "Screening for prostate cancer", section on Overdiagnosis.)

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 12 month follow-up for a cohort of 290,000 women who underwent screening with both CBE and mammography, and another cohort of 58,000 women who were seen in centers where mammography alone was performed [2]. CBE (performed by trained nurses) plus mammography had greater sensitivity but a higher false positive rate (12.5 versus 7.4 percent). For each additional cancer detected by CBE, there were 55 additional false positive screens. (See "Screening for breast cancer", section on 'Clinical breast examination'.)

Interim results from the Norwegian Colorectal Cancer Prevention (NORCCAP) trial report follow-up at six to seven years [3]. Individuals aged 55 to 64 years were randomly assigned to screening (sigmoidoscopy or sigmoidoscopy plus immunochemical fecal occult blood) or to no screening. Compared to the control group, there was a significant reduction in mortality due to colorectal cancer (CRC) for those who participated in screening, and a trend toward reduction in CRC mortality for the group assigned to screening. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Sigmoidoscopy'.)

A study of patients with colonic adenomas found that patients with a history of an advanced (≥1 cm or advanced histology) adenoma or multiple (≥3) adenomas were at increased risk for recurrent advanced or multiple adenomas during surveillance colonoscopies even if no adenomas were detected on the first follow-up study [4]. Thus, delaying the second follow-up colonoscopy because of a negative first follow-up study is not warranted for patients with high risk adenomas. Extending surveillance intervals could still be considered in patients with a low risk adenoma followed by a negative surveillance colonoscopy. (See "Approach to the patient with colonic polyps", section on 'Surveillance'.)

The randomized Italian DANTE trial of spiral CT scan, compared with annual clinical follow-up, for lung cancer screening has reported interim results after baseline and five annual screens [5]. More stage I cancers were found in the CT-screened group, but the number of advanced lung cancer cases and lung cancer mortality were the same for screened and control patients. Longer follow-up may be required to detect differences in disease-specific mortality. (See "Screening for lung cancer", section on 'Ongoing trials'.)

A single question used to screen primary care patients for unhealthy drinking was found to have moderately good sensitivity and specificity [6]. Screening is considered positive when respondents reply 'at least once' to the question, "How many times in the past year have you had [5 for men, 4 for women] or more drinks in a day?". (See "Screening for and diagnosis of alcohol problems", section on 'Alcohol Use Disorder Identification Test'.)

A meta-analysis found an association between lipoprotein(a) Lp(a) levels and cardiovascular disease [7], and a Mendelian randomization study suggested a causative role for Lp(a) in cardiovascular disease [8]. (See "Lipoprotein(a) and cardiovascular disease", section on 'CVD risk'.)

Prevention

In a randomized trial, patients who had discontinued statin therapy because of myalgias tolerated treatment with red yeast rice at a rate similar to placebo, while achieving significant reductions in LDL-C [9]. However, there was no statin arm to see whether patients might have tolerated rechallenge with a dose of statin able to achieve similar LDL-C reductions. Additionally, there is a lack of standardization of red yeast rice products [10]. (See "Lipid lowering with diet or dietary supplements", section on Red yeast rice.)

In 2009, the United States Food and Drug administration required identical boxed warnings on bupropion and varenicline about the risk of serious neuropsychiatric symptoms including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behaviors, and attempted suicide [11]. The FDA noted the overlap with typical symptoms of nicotine withdrawal. (See "Management of smoking cessation", section on 'Safety' and "Management of smoking cessation", section on 'Safety concerns'.)

In a longitudinal study, participants who met criteria for four healthy lifestyle factors (never smoking, BMI < 30, physical activity >3.5 hours weekly, and a prudent diet) had approximately one-third the risk of cancer compared to those who met none of these criteria [12]. (See "Cancer prevention".)

Younger adults (< 30 years) are less likely to have preventive care visits than other age groups, are less likely to have medical insurance in the United States, and are at increased risk for depression and suicide, substance abuse including binge drinking, sexually transmitted disease, and HIV infection [13]. Particularly for this age group, these risks and other preventive health measures should be considered at nearly every medical encounter, with clinicians providing "continuous health maintenance" rather than "periodic health maintenance" where preventive care is addressed only at targeted complete physical examinations. (See "Overview of preventive medicine in adults", section on 'How to efficiently deliver prevention'.)

Regular exercise and the Mediterranean diet were independently associated with a decreased risk for Alzheimer disease in a prospective cohort study of 1880 older patients followed for 14 years [14]. (See "Overview of the benefits and risks of exercise" and "Prudent diet".)

Geriatrics

The benefits of exercise, including lower mortality and maintaining independence, have been associated with initiating, as well as continuing, exercise among older adults, including those ages 78 to 85 years [15]. (See "Geriatric health maintenance", section on 'Physical activity'.)

Orthopedics and spinal disease

For patients with persistent nonspecific low back pain, a systematic review found that spinal fusion surgery may be more effective than unstructured nonsurgical care, but equally effective compared to intense multidisciplinary rehabilitation [16]. Practice guidelines from the American Pain Society, based on this review, recommend that surgery be presented as an option to patients with persistent disabling nonradicular low back pain [17]. Shared decision making should take into account that most patients who undergo surgery will have some residual symptoms, and that interdisciplinary rehabilitation may be equally effective. (See "Subacute and chronic low back pain: Surgical treatment", section on 'Spinal fusion'.)

In two blinded trials comparing vertebroplasty with a sham procedure in patients with osteoporotic vertebral compression fractures, there was no immediate or delayed benefit of vertebroplasty for the reduction of pain [18,19]. (See "Clinical manifestations and treatment of osteoporotic thoracolumbar vertebral compression fractures", section on 'Vertebroplasty and kyphoplasty'.)

Preoperative management

Commonly ordered laboratory studies are often unnecessary for the preoperative evaluation of patients undergoing ambulatory surgery. In a pilot trial of 1061 patients randomized to preoperative testing or no testing, there was no difference in perioperative adverse events [20]. Studies for those randomized to testing were based on the indications of the Ontario Preoperative Testing Grid. A larger study is needed to determine if laboratory testing may be safely eliminated in selected patients undergoing ambulatory surgery. (See "Preoperative medical evaluation of the healthy patient".)

A randomized trial in patients undergoing elective vascular surgery found that fluvastatin (initiated at least 30 days before surgery) decreased myocardial ischemic events [21]. (See "Management of cardiac risk for noncardiac surgery", section on Statins.)

Psychiatry

Specific antidepressants may cause more weight gain than others. A systematic review of second-generation antidepressants found that mirtazapine and paroxetine were associated with more weight gain than fluoxetine, sertraline, trazodone, and venlafaxine [22]. (See "Initial treatment of depression in adults", section on Antidepressants, Side effects.)

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 [23]. In addition, specific antidepressants may be associated with an increased risk of diabetes. A nested case-control study 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 (incidence rate ratio 1.8) [24]. (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 [25]. (See "Initial treatment of depression in adults", section on Other Drugs, Antipsychotics.)

A meta-analysis involving 4640 patients found a significant association between a history of sexual abuse and lifetime diagnosis of functional gastrointestinal disorders, nonspecific chronic pain, psychogenic seizures, and chronic pelvic pain [26]. (See "Somatization", section on 'Pathogenesis'.)

PRIMARY CARE CARDIOLOGY

The RE-LY trial, which evaluated the efficacy and safety of two different doses of dabigatran relative to warfarin in over 18,000 patients with atrial fibrillation, is the first trial to demonstrate that an alternative oral anticoagulant may be superior to adjusted-dose warfarin [27]. Dabigatran 110 mg was safer than warfarin with equivalent efficacy, while dabigatran 150 mg was significantly more effective than warfarin with equivalent safety. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation", section on 'Dabigatran'.)

The decision to use antithrombotic therapy to prevent embolization in patients with nonvalvular atrial fibrillation (AF) is based upon an assessment of the absolute benefits and risks. A large observational study evaluated the net clinical benefit of warfarin [28]. Benefits in patients with CHADS2 scores below 2 were small and the confidence intervals around the results in such patients included the possibility of net harm with anticoagulation. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation", section on 'Net clinical benefit'.)

Many patients who are at significant risk for embolization in atrial fibrillation (AF) cannot take anticoagulation therapy. A randomized trial of a device placed percutaneously to occlude the left atrial appendage found noninferiority compared with warfarin on an efficacy endpoint, but found more adverse events than with warfarin [29]. (See "Left atrial appendage amputation, ligation, or occlusion in patients with atrial fibrillation", section on 'Percutaneous LAA occlusion'.)

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 [30,31]. The results of these two trials 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", section on 'Adjunctive PCI'.)

Cardiac resynchronization therapy (CRT) benefits patients with more severe heart failure (HF). A randomized trial found benefits in patients with more mild HF as well, mainly in those patients with a QRS duration > 150 msec [32]. (See "Cardiac resynchronization therapy in heart failure", section on 'Efficacy in NYHA class I or II HF'.)

Early studies of primary first degree atrioventricular (AV) block suggested a benign prognosis. This view has been challenged by a large prospective community-based cohort study of individuals from the Framingham Heart Study [33]. Compared with those 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. (See "First degree atrioventricular block", section on 'Prognosis'.)

PRIMARY CARE DERMATOLOGY

In September 2009, the US Food and Drug Administration approved ustekinumab, a human monoclonal antibody that targets IL-12 and IL-23 for the treatment of moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy. (See "Treatment of psoriasis", section on 'Ustekinumab'.)

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 [34]. (See "Risk factors for the development of melanoma", section on 'Tanning beds'.)

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 new recommendations (in preliminary form) for PTU use [35]. 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 [36-40]. Until more data are available, there is insufficient evidence to make a recommendation against glargine. (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 previously treated with oral hypoglycemic agents, insulin, or both, there was no difference in the the risk of retinopathy progression (defined as an increase in three steps or more on the early treatment of diabetic retinopathy study (ETDRS) scale) in patients randomly assigned to twice daily NPH versus once daily glargine [41]. (See "General principles of insulin therapy in diabetes mellitus", section on 'Human versus analogs'.)

There have been 88 postmarketing case reports of acute pancreatitis in patients using sitagliptin [42]. Pancreatitis should be considered in patients with persistent severe abdominal pain (with or without nausea), and sitagliptin (or sitagliptin/metformin) should be discontinued in such patients. (See "GLP-1-based therapies for the treatment of type 2 diabetes mellitus", section on 'DPP-IV inhibitors'.)

Saxagliptin is a new DPP-IV inhibitor that reduces hemoglobin A1C by approximately 0.5 percentage points [43,44]. (See "GLP-1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Saxagliptin'.)

In a four-year trial of a low carbohydrate Mediterranean-style diet (≤50 percent complex carbohydrates, ≥30 percent mono and polyunsaturated fat) versus a low fat (<30 percent) diet in 215 overweight patients with newly diagnosed type 2 diabetes, patients randomly assigned to the Mediterranean diet were significantly less likely to require antihyperglycemic drugs (44 versus 70 percent) [45]. (See "Nutritional considerations in type 2 diabetes mellitus", section on 'Nutritional content'.)

In a large randomized trial in postmenopausal women with osteoporosis, denosumab compared with placebo signficantly reduced the incidence of new fractures [46]. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Denosumab'.)

PRIMARY CARE GASTROENTEROLOGY

A study of 2741 patients with dyspepsia without alarm symptoms who underwent upper endoscopy found that the risk of finding a cancer varied by age [47]. Although the American Gastroenterological Association 2005 guidelines suggest endoscopy be performed in patients with dyspepsia with or without alarm symptoms who are ≥55 years of age, performing an upper endoscopy only in patients older than 55 (554 patients) would have missed three cancers (0.5 percent) while performing an upper endoscopy in those older than 50 (829 patients) would have missed only one (0.1 percent). (See "Approach to the patient with dyspepsia".)

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) [48]. (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 [49]. 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 for hepatocellular carcinoma in patients with chronic hepatitis B 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 [50]. This reduction in potency 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", section on 'Effect of the change in heparin potency'.)

PRIMARY CARE INFECTIOUS DISEASE

Although in children the live attenuated (intranasal) influenza vaccine may be more effective than the inactivated (intramuscular) vaccine, studies in adults have shown that the inactivated vaccine is either equivalent to or more effective than the live attenuated vaccine. In a randomized trial that included 1952 adults vaccinated during the 2007 to 2008 influenza season, the inactivated vaccine was superior to the live attenuated vaccine in preventing influenza infection (68 versus 36 percent absolute efficacy, respectively) [51]. (See "Seasonal influenza vaccination in adults", section on 'Comparisons of inactivated and live-attenuated vaccines'.)

There is currently a pandemic of a novel strain of H1N1 influenza that represents a quadruple reassortment of two swine strains, one human strain, and one avian strain of influenza. (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 [52]. (See "Meningococcal vaccines", section on Revaccination.)

The guidelines for rabies vaccine administration for post-exposure prophylaxis in unvaccinated persons changed in 2009. ACIP has advised that the five-dose schedule be changed to four doses, eliminating the last dose administered on day 28 [53]. (See "Rabies immune globulin and vaccine".)

Serum levels of procalcitonin (PCT) may help distinguish patients with bacterial from those with viral infection. A randomized noninferiority trial compared guidelines-directed usual care with use of a rapid PCT assay to guide antibiotic use in patients with moderately severe lower respiratory symptoms presenting to an emergency room [54]. Among the 150 patients with acute bronchitis in the study, patients who received usual care were significantly more likely to receive antibiotic treatment than those receiving PCT-guided treatment (50 versus 23.2 percent). The role and cost-effectiveness of PCT testing for patients presenting to primary care offices requires further investigation. (See "Acute bronchitis", section on 'Procalcitonin'.)

PRIMARY CARE NEPHROLOGY

The Cardio-Sis trial compared the effects of tight systolic blood pressure control (with a target of less than 130 mmHg) and usual control (with a target of less than 140 mmHg) among patients with established cardiovascular disease or at least one additional cardiovascular risk factor [55]. The prevalence of left ventricular hypertrophy was lower and there was a reduction in the risk of new onset atrial fibrillation and coronary revascularization among patients who had the lower blood pressure target. (See "Choice of antihypertensive drug and blood pressure goal in patients at increased risk for a cardiovascular event".)

Although bicarbonate supplementation preserves renal function in experimental models of chronic kidney disease, a beneficial effect had not been demonstrated in humans. 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 [56]. (See "Treatment of metabolic acidosis in chronic kidney disease" and "Overview of the management of chronic kidney disease in adults", section on 'Metabolic acidosis'.)

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 [57]. (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 the initial evaluation (n = 361) had an increased risk of infarct-like lesions on brain MRI 25 years later compared with those not reporting headache once or more per month at baseline (adjusted odds ratio 1.4) [58]. (See "Headache, migraine, and stroke", section on 'Subclinical brain lesions'.)

A randomized trial with 116 patients found that surgical decompression for carpal tunnel syndrome was more effective than nonsurgical treatment consisting of multimodal interventions [59]. However, the benefit of surgery was small and of modest clinical significance. (See "Treatment of carpal tunnel syndrome", section on 'Surgery'.)

PRIMARY CARE ONCOLOGY

In a phase III trial in men treated with androgen deprivation therapy for advanced prostate cancer without bone metastases, denosumab, a monoclonal antibody that binds RANKL, significantly decreased the incidence of new vertebral fractures [60]. (See "Managing the side effects of androgen deprivation therapy", section on 'Denosumab'.)

PRIMARY CARE PULMONOLOGY AND CRITICAL CARE

A meta-analysis including 7042 patients with COPD found no increased risk of pneumonia with inhaled budesonide [61]. (See "Role of inhaled glucocorticoid therapy in stable COPD", section on 'Adverse effects'.)

Roflumilast is a phosphodiesterase-4 inhibitor that is being studied for use in COPD. A 52-week randomized trial of 3091 patients with COPD found that roflumilast improved the prebronchodilator forced expiratory volume in one second (FEV1) and decreased the rate of moderate to severe exacerbations [62]. Similarly, in two 24-week trials, roflumilast improved the prebronchodilator FEV1 in patients with moderate to severe COPD when added to either salmeterol or tiotropium [63]. (See "Management of stable chronic obstructive pulmonary disease", section on 'Future directions'.)

PRIMARY CARE RHEUMATOLOGY

A randomized trial in 308 patients with Dupuytren's contractures found that injection of clostridial collagenase into the lesion was beneficial and may be an effective alternative to surgery [64]. (See "Dupuytren's contracture", section on 'Collagenase injection'.)

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