Philip S. Mehler

Intensive Blood Pressure Control Reduces the Risk of Cardiovascular Events in Patients With Peripheral Arterial Disease and Type 2 Diabetes

Background—Peripheral arterial disease (PAD) and diabetes are both associated with a high risk of ischemic events, but the role of intensive blood pressure control in PAD has not been established. Methods and Results—The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years; 480 of the subjects were normotensive (baseline diastolic blood pressure of 80 to 89 mm Hg). Patients randomized to placebo (moderate blood pressure control) had a mean blood pressure of 137±0.7/81±0.3 mm Hg over the last 4 years of treatment. In contrast, patients randomized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128±0.8/75±0.3 mm Hg (P <0.0001 compared with moderate control). PAD, which is defined as an ankle-brachial index <0.90 at the baseline visit, was diagnosed in 53 patients. In patients with PAD, there were 3 cardiovascular events (13.6%) on intensive treatment compared with 12 events (38.7%) on moderate treatment (P =0.046). After adjustment for multiple cardiovascular risk factors, an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment (P =0.009), but not with intensive treatment (P =0.91). Thus, with intensive blood pressure control, the risk of an event was not increased, even at the lowest ankle-brachial index values, and was the same as in a patient without PAD. Conclusions—In PAD patients with diabetes, intensive blood pressure lowering to a mean of 128/75 mm Hg resulted in a marked reduction in cardiovascular events.

Emergence of Fluoroquinolone Resistance in Outpatient Urinary Escherichia coli Isolates

BACKGROUND Because of high rates of trimethoprim-sulfamethoxazole resistance in Escherichia coli, Denver Health switched to levofloxacin as the initial therapy for urinary tract infections (UTIs) in 1999. We evaluated the effects of that switch 6 years later. METHODS Levofloxacin prescriptions per 1000 outpatient visits and levofloxacin resistance in outpatient E. coli were evaluated over time. E. coli isolated in 2005 were further characterized by specimen source and antimicrobial susceptibilities. Risk factors for levofloxacin-resistant E. coli UTI among nonpregnant adult outpatients were evaluated in a case-control study. RESULTS Between 1998 and 2005, levofloxacin use increased from 3.1 to 12.7 prescriptions per 1000 visits (P<.01) and resistance in outpatients increased from 1% to 9% (P<.01). Although prescriptions for sulfonamide antibiotics decreased by half during the same period, E. coli resistance to trimethoprim-sulfamethoxazole increased from 26.1% to 29.6%. Levofloxacin-resistant E. coli were more likely resistant to other antibiotics than levofloxacin-susceptible isolates (90% vs 43%, P<.0001). Risk factors for levofloxacin-resistant E. coli UTI were hospitalization (odds ratio for each week of hospitalization, 2.0; 95% confidence interval, 1.0-3.9) and use of levofloxacin (odds ratio, 5.6; 95% confidence interval, 2.1-27.5) within the previous year. CONCLUSION Fluoroquinolone prescriptions increased markedly after an institutional policy change for empiric treatment of UTI, and a rapid increase in fluoroquinolone resistance among outpatient E. coli followed. Risk factors for infection with resistant E. coli were recent hospitalization and levofloxacin use. Risk factors should be considered before initiating empiric treatment with a fluoroquinolone.

Skin and Soft-Tissue Infections Requiring Hospitalization at an Academic Medical Center: Opportunities for Antimicrobial Stewardship

BACKGROUND Although complicated skin and soft-tissue infections (SSTIs) are among the most common infections requiring hospitalization, their clinical spectrum, management, and outcomes have not been well described. METHODS We report a cohort of consecutive adult patients hospitalized for SSTI from 1 January through 31 December 2007 at an academic medical center. Cases meeting inclusion criteria were reviewed and classified as cellulitis, cutaneous abscess, or SSTI with additional complicating factors. RESULTS In total, 322 patients were included; 66 (20%) had cellulitis, 103 (32%) had cutaneous abscess, and 153 (48%) had SSTI with additional complicating factors. Injection drug use, diabetes mellitus, and alcohol abuse were common comorbidities. Serum inflammatory markers were routinely measured and blood cultures and imaging studies were routinely performed in each group. Of 150 patients with a positive culture result for an abscess, deep tissue, or blood, Staphylococcus aureus or streptococci were identified in 145 (97%). Use of antibiotics with broad aerobic gram-negative activity (61%-80% of patients) or anaerobic activity (73%-83% of patients) was frequent in each group. The median duration of therapy for cellulitis, cutaneous abscess, and SSTI with additional complicating factors was 13 (interquartile range [IQR], 10-14), 13 (IQR, 10-16), and 14 (IQR, 11-17) days, respectively. Treatment failure, recurrence, or rehospitalization due to SSTI within 30 days occurred in 12.1%, 4.9%, and 9.2% of patients, respectively. CONCLUSIONS Hospitalizations for SSTI were common; more than half were due to cellulitis or cutaneous abscess. Frequent use of potentially unnecessary diagnostic studies, broad-spectrum antibiotic therapy, and prolonged treatment courses in these patients suggest targets for antimicrobial stewardship programs.

Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial

The hypertensive and normotensive Appropriate Blood Pressure Control in Diabetes (ABCD) studies were prospective, randomized, interventional clinical trials with 5 years of follow-up that examined the role of intensive versus standard blood pressure control in a total of 950 patients with type 2 diabetes mellitus. In the hypertensive ABCD study, a significant decrease in mortality was detected in the intensive blood pressure control group when compared with the standard blood pressure control group. There was also a marked reduction in the incidence of myocardial infarction when patients were randomly assigned to initial antihypertensive therapy with angiotensin-converting-enzyme inhibition rather than calcium channel blockade. The results of the normotensive ABCD study included associations between intensive blood pressure control and significant slowing of the progression of nephropathy (as assessed by urinary albumin excretion) and retinopathy, and fewer strokes. In both the hypertensive and normotensive studies, mean renal function (as assessed by 24 h creatinine clearance) remained stable during 5 years of either intensive or standard blood pressure intervention in patients with normoalbuminuria (<30 mg/24 h) or microalbuminuria (30–300 mg/24 h) at baseline. By contrast, the rate of creatinine clearance in patients with overt diabetic nephropathy (>300 mg/24 h; albuminuria) at baseline decreased by an average of 5 ml/min/year in spite of either intensive or standard blood pressure control. Analysis of the results of 5 years of follow-up revealed a highly significant correlation of all-cause and cardiovascular mortality with left ventricular mass and severity of albuminuria.

Diagnosis and Care of Patients with Anorexia Nervosa in Primary Care Settings

A 20-year-old woman presents to her internist because her mother is concerned about her amenorrhea, which has lasted for 5 months; before this, her periods were normal. The patient reports no headaches, hirsutism, change in vision, or medications. On examination, she is 69 inches (175.26 cm) tall and weighs 117 pounds (52.65 kg). Her blood pressure is 96/58 mm Hg, and her heart rate is 46 beats/min. The thyroid gland is normal, there are no signs of virilization, and results of visual field testing are normal. Could This Patient Have Anorexia Nervosa? The clinical diagnosis of anorexia nervosa is often obscured (1). Clinicians must be extremely vigilant for this diagnosis, since patients with mild cases usually seek help for nonspecific symptoms, such as asthenia, dizziness, and a lack of energy (2). Often, family members bring patients to the physician because they are concerned about amenorrhea or substantial weight loss. Patients with anorexia nervosa, in contrast to medically ill patients, are unconcerned about their weight loss; presentation is remarkable for its lack of complaints. Although some patients exhibit obvious indicators, such as potentially unhealthy weight-control practices, such features may be absent (3). Menstrual disorders are among the most common reasons that women seek medical attention (4). Secondary amenorrhea is a symptom, not a diagnosis, and a thorough history and physical examination are required to define its cause (5). Hypothalamic dysfunction and polycystic ovarian disease each account for 30% of cases, pituitary prolactinomas and ovarian failure each account for 15%, and uterine problems account for 5% (6). Since hypothalamic-induced amenorrhea is a universal feature of anorexia nervosa, it should be determined whether the amenorrheic patient has a history of recent moderate to marked weight loss. Other presenting symptoms and signs of anorexia nervosa depend on the diseases severity. Many patients with moderate and severe anorexia have fine lanugo-type hair on the sides of their faces and their arms, brittle nails, thinning hair, sensitivity to cold, abdominal pain, lightheadedness, and fatigue. The patient returns to discuss her blood tests results, all of which are normal. Results of a pregnancy test are negative. Further history reveals that she has lost 25 pounds (11.25 kg) over the previous 6 months, a fact she relishes. Her fathers comments about her weight motivated her to begin dieting. The patient lost weight by restricting her caloric intake and does not report purging behaviors. Does This Patient Meet the Criteria for Anorexia Nervosa? The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines anorexia nervosa as having an intense fear of gaining weight, putting undue emphasis on body shape, having a body weight that is less than 85% of the predicted weight, and missing three consecutive periods (7) (Table 1). Anorexia nervosa is further divided into restricting and purging subtypes. Patients with the more common restricting subtype drastically limit their food intakes, whereas patients with the purging subtype also engage in purging behaviors. In contrast to the bulimic patient, whose appearance is often unremarkable and whose disease may therefore initially go unrecognized in clinical settings (8, 9), the cachectic appearance of the patient with severe anorexia is readily noticeable. Although the differential diagnosis for weight loss is extensive (10, 11), the young age of most patients with anorexia nervosa simplifies the evaluation. Malabsorption and catabolic states can easily be excluded with a careful history and physical examination and judicious laboratory testing, including tests for levels of thyroid-stimulating hormone and serum albumin. Table 1. Criteria for Anorexia Nervosa Anorexia nervosa is common, with a prevalence of 1% to 2% (12). The yearly incidence has increased to a range of 17 to 20 cases per 100 000 (13). Bulimia is more common (14), and almost half of patients with anorexia eventually develop bulimic symptoms (15, 16). The female-to-male ratio for anorexia is 20:1, and homosexuality may be an associated factor in men (17). Anorexia nervosa is more common in industrialized nations (18, 19) and among white women of higher socioeconomic classes (20). Participation in activities that promote thinness, such as modeling and athletics, and type 1 diabetes mellitus in young women are associated with a higher prevalence of anorexia nervosa (21-24). Other proposed risk factors are perfectionism and negative comments from others about body appearance (25, 26). A recent controlled study suggests that overprotective parenting, linked to unresolved grief about a previous life event, is associated with development of anorexia nervosa (27). In addition, new evidence has established a genetic basis for increased risk (28). Adolescence and its rapid period of physical change are also commonly associated with anorexia nervosa (29), as is depression (30). In addition, young adults who strive for unhealthy weight loss are more likely to engage in other harmful behaviors, such as substance abuse (31). Can Any Diagnostic Tools Help in the Identification of Anorexia Nervosa? Early detection and treatment improve prognosis (32). Questionnaires designed to screen for eating disorders, such as the Eating Attitude Test (EAT), have a variable performance record (33, 34). Recently, a new screening tool, SCOFF, has been developed (35) (Table 2). However, there are concerns about its applicability and reliability (36). Table 2. SCOFF Questions How Does the Clinician Rule Out Bulimia? Diagnostic criteria for bulimia are found in Table 3. Bulimia should be distinguished from anorexia nervosa not by a weight threshold but by the presence of binge eating and purging. Bulimic patients may purge through self-induced vomiting, abuse of laxatives or diuretics, or excessive exercise. Both bulimic and anorectic patients frequently engage in excessive amounts of exercise. Compulsive exercise training is associated with weight obsession (37). Abnormal eating behaviors are associated with a specific negative attitude toward running independent of the weekly mileage (38); runners experience withdrawal symptoms if they cannot run and are unable to stop running if they are sick or injured. In fact, excessive exercise often precedes the development of the formal eating disorder (39). One other eating disorder that could be considered is the night-eating syndrome, which is characterized by nocturnal binging, daytime anorexia, and insomnia (40) and is distinct from the established disorders of anorexia and bulimia. Table 3. Criteria for Bulimia Nervosa Bulimia is more common than anorexia, affecting up to 2% to 3% of adult women (41). Bulimic patients who purge through self-induced vomiting may present with sialadenosis, perimylolysis, or symptoms of reflux esophagitis. Persons who abuse laxatives may report abdominal cramping, diarrhea, or rectal bleeding. Laboratory studies are the most useful tool in evaluating bulimia. The specific pattern of serum and urine electrolytes helps to define the mode of purging. Metabolic alkalosis and hypokalemia are the most common abnormalities encountered and can be seen in patients who purge through self-induced vomiting or diuretic abuse (42). In contrast, anorectic patients who lose weight exclusively by restricting caloric intake usually have normal electrolyte levels. One week later, the patient has lost 2 pounds (0.9 kg). She denies dizziness, and vital signs are stable. Physical examination is unremarkable. The patient minimizes her obsession with weight loss but admits that she fears gaining weight. Would Additional Laboratory Tests Be Helpful in Diagnosing Anorexia Nervosa? One of the remarkable characteristics of anorexia is the consistent finding of normal results on blood chemistry tests despite extensive weight loss. On occasion, leukopenia and anemia may be present (43, 44), but these conditions invariably resolve with weight gain and have little clinical significance. In addition, hypoglycemia may be found and is indicative of a poor prognosis (45). The presence of hypokalemia or metabolic alkalosis should raise concern that the anorectic patient may be surreptitiously purging through vomiting or diuretic abuse (46, 47). Abnormalities on thyroid function tests are often present in the form of the euthyroid sick syndrome. Serum levels of l-thyroxine are normal to low, as are levels of triiodothyronine. Levels of thyroid-stimulating hormone seem normal, but levels of reverse triiodothyronine (reverse T3) are increased. With resolution of anorexia nervosa, all of these indicators return to normal. The important clinical point is that laboratory values generally remain normal until the very late stages of illness in anorectic patients who restrict their dietary intake; therefore, these values should not in any way independently influence decisions about the necessary intensity of treatment. What Criteria Are Used To Decide on the Appropriate Initial Course of Treatment for a Patient with Anorexia Nervosa? Clinicians must first decide what level of treatment is appropriate. Treatment can range from outpatient care to acute medical or psychiatric hospitalization. However, outpatient treatment is adequate for most patients. Anorexia nervosa can be classified as mild, moderate, or severe on the basis of the combination of the severity of body image distortion, the presence of physical complications, and the percentage of ideal body weight (48). Patients who are within 10% of ideal body weight and have only minimal distortion of body image are considered to have mild cases. Technically, because this degree of weight loss does not qualify as anorexia nervosa, these patients are classified as having a not-otherwise-specified eating disorder. This diagnosis is given to patients who do not meet all of the criteria for anorexia ne

Treatment of osteopenia and osteoporosis in anorexia nervosa: A systematic review of the literature

OBJECTIVE To systematically review the evidence supporting treatment of osteopenia and osteoporosis in patients with anorexia nervosa (AN). DATA SOURCES We identified controlled clinical studies of interventions for low bone mass in AN via searches of MEDLINE; the Cochrane Library; EMBASE; PsycINFO; and cumulative index to nursing and allied health literature. Outcomes of interest were changes in bone mineral density and fracture incidence. RESULTS Six randomized controlled trials (RCTs) and two cohort trials examined five classes of medical therapy on bone mineral density outcomes. One RCT of bisphosphonates showed no benefit and a second flawed RCT showed some benefit; one RCT showed a benefit of insulin-like growth factor-I; none of the five trials evaluating estrogen therapy showed benefit. DISCUSSION Although patients with AN are often losing bone mass when they should be optimizing bone growth, there is no good evidence to guide medicinal interventions. Therefore, early detection and weight restoration are of utmost importance whereas ongoing trials define effective therapies.

Conventional and molecular epidemiology of trimethoprim-sulfamethoxazole resistance among urinary Escherichia coli isolates

BACKGROUND Antibiotic resistance is increasing in Escherichia coli, the most common cause of urinary tract infections, but its epidemiology has not been well described. We evaluated the epidemiology of trimethoprim-sulfamethoxazole-resistant E. coli in a large, public health care system in Denver, Colorado. METHODS Outpatients with E. coli urinary tract infections during the first 6 months of 1998 were evaluated retrospectively. A prospective study was then performed to confirm the rate of trimethoprim-sulfamethoxazole resistance. We used several strain-typing methods (pulsed-field gel electrophoresis, ribotyping, serotyping) to evaluate the molecular epidemiology of the resistance. RESULTS The rate of trimethoprim-sulfamethoxazole resistance was similar in the retrospective (24% [161/681]) and prospective (23% [30/130]) phases of the study (P = 0.89). Almost all trimethoprim-sulfamethoxazole-resistant strains (98%) were resistant to at least one other antibiotic. Risk factors for infection with a resistant strain included age < or =3 years, Hispanic ethnicity, recent travel outside the United States, and a prior urinary tract infection. However, rates of resistance were >15% among nearly all of the subgroups. Most strains had high-level resistance (>1000 microg/mL) to trimethoprim-sulfamethoxazole. Of the 23 resistant isolates evaluated, 10 (43%) belonged to the clone A group. There was no correlation between conventional epidemiologic characteristics and the molecular mechanism of resistance or strain type. CONCLUSION Resistance to trimethoprim-sulfamethoxazole among E. coli isolates among patients in a Denver public health care system is common, with high rates of resistance even among patients without risk factors.

Severe anorexia nervosa: Outcomes from a medical stabilization unit

OBJECTIVE We report data from the medical stabilization and refeeding of patients with severe anorexia nervosa admitted over a 15-month period. METHOD Through chart review and computerized data collection, we evaluated demographic and clinical data from 25 consecutive patients admitted to our medical stabilization unit from October 2008 to January 2010. RESULTS In this adult-patient population with a median body mass index (BMI) of 13.1 kg/m(2) (interquartile range, 11.0-14.4), 44% developed hypoglycemia, 76% had abnormal liver function, 83% had abnormal bone density, 45% developed refeeding hypophosphatemia, and 92% were hypothermic. Severe liver function abnormality predicted the development of hypoglycemia (p = 0.02, OR 9.78, CI: 1.55-61.65). No clinical features predicted hypophosphatemia, including admission BMI (p = 0.19), serum glucose level (p = 0.21), elevated liver function tests (p = 0.39 for AST), or initial amount of kilocalories consumed (p = 0.06). DISCUSSION Patients with the most severe cases of anorexia nervosa have a high prevalence of serious medical complications during initial refeeding.

Medical complications of bulimia nervosa and their treatments

OBJECTIVE To present a cogent and practical review of the medical complications and their treatment in patients with bulimia nervosa. METHOD Thorough review of the medical literature from 1990 to current in regards to the medical complications of bulimia nervosa and the therapeutic intervention that are effective to treat them. RESULTS Extensive and detailed review of the medical complications of bulimia nervosa.

Nutritional Rehabilitation: Practical Guidelines for Refeeding the Anorectic Patient

Weight restoration is crucial for successful treatment of anorexia nervosa. Without it, patients may face serious or even fatal medical complications of severe starvation. However, the process of nutritional rehabilitation can also be risky to the patient. The refeeding syndrome, a problem of electrolyte and fluid shifts, can cause permanent disability or even death. It is essential to identify at-risk patients, to monitor them carefully, and to initiate a nutritional rehabilitation program that aims to avoid the refeeding syndrome. A judicious, slow initiation of caloric intake, requires daily management to respond to entities such as liver inflammation and hypoglycemia that can complicate the bodys conversion from a catabolic to an anabolic state. In addition, nutritional rehabilitation should take into account clinical characteristics unique to these patients, such as gastroparesis and slowed colonic transit, so that measures can be taken to ameliorate the physical discomforts of weight restoration. Adjunct methods of refeeding such as the use of enteral or parenteral nutrition may play a small but important role in a select patient group who cannot tolerate oral nutritional rehabilitation alone.