Special considerations for treatment of type 2 diabetes mellitus in the elderly.

PURPOSE: The intensity and selection of therapy for the treatment of type 2 diabetes mellitus in elderly patients are discussed. SUMMARY: Glycemic control is fundamental in diabetes care; however, as glycemic goals are approached, the risk of hypoglycemia increases. This risk is even greater in the elderly due to many predisposing factors, including renal insufficiency, polypharmacy, drug-drug interactions, comorbidities, irregular meal patterns, and infrequent self-monitoring of blood glucose. When deciding on the desired intensity of diabetes treatment, the risk of hypoglycemic complications must be weighed against the potential benefit of reducing microvascular and macrovascular complications. Three large-scale, randomized controlled trials examining the effects of intensive versus standard glycemic control on microvascular and macrovascular outcomes in patients with type 2 diabetes have been published in recent years. In general, a glycosylated hemoglobin (HbA(1c)) goal of <7% is reasonable for most patients. A less-aggressive goal may be considered for patients at high risk of hypoglycemia or high risk of complications from hypoglycemia, as long as acutely symptomatic hyperglycemia is avoided. Chlorpropamide, glyburide, and rosiglitazone, which pose a great risk for hypoglycemia, should be avoided in the elderly. CONCLUSION: In the absence of clear evidence advocating strict glycemic targets goal of <7% is for elderly patients, an HbA(1c) reasonable for most patients; however, the risk of hypoglycemic complications must be weighed against the potential benefit of reducing microvascular and macrovascular disease. Metformin may be used as first-line therapy, but chlorpropamide and glyburide, which pose a great risk for hypoglycemia, should be avoided in the elderly. Due to increased cardiovascular risk, use of rosiglitazone in the elderly should also be avoided.

Calcium supplementation in postmenopausal women to reduce the risk of osteoporotic fractures.

PURPOSE: The most recent large-scale studies evaluating the effects of calcium supplementation for prevention of osteoporosis-related fractures in postmenopausal women are reviewed. SUMMARY: Osteoporosis is a very common disease associated with significant morbidity and mortality. For many years, use of a calcium supplement (preferably in combination with vitamin D to optimize calcium absorption) has been recommended for postmenopausal women to decrease fracture risk. However, five large-scale, randomized, controlled trials have called into question the benefits of calcium in reducing fracture risk, and four of the studies indicated that calcium users may be at increased risk for renal stones and gastrointestinal problems. However, all five studies had one or more important limitations, including possible selection bias and study participants' relatively high baseline calcium intake and generally low adherence to treatment regimens. Moreover, in some of the studies, vitamin D was not included in the treatment protocol or was not used at levels sufficient to optimize calcium absorption. In three of the five trials, subgroup analysis of the most treatment-adherent participants indicated significant reductions in osteoporotic fracture risk with calcium supplement use. CONCLUSION: Results of recent clinical trials indicate that calcium supplementation does not significantly reduce fracture risk in postmenopausal women. However, evidence from the same studies suggests that beneficial effects on fracture risk may be seen in women who are adherent to therapy. Postmenopausal women should continue calcium supplementation to reduce osteoporosis risk.

Risks and benefits of long-term bisphosphonate therapy.

PURPOSE: The risks and benefits of long-term bisphosphonate therapy were reviewed. SUMMARY: Bisphosphonates are used first line in the treatment of osteoporosis due to their demonstrated ability to reduce the risk of fracture. Benefits on bone mineral density (BMD) and fracture prevention appear to be sustained for 7-10 years; however, the lack of clinical trials extending beyond this treatment period has raised the question of how long therapy should be continued. Furthermore, some reports have suggested the potential for an increased risk of fragility fractures due to oversuppression of bone turnover with long-term bisphosphonate use. Though rare, these fragility fractures appear to have a specific fracture pattern and tend to occur after 3-8 years of bisphosphonate therapy. The use of a drug holiday has been considered as an option to avoid this risk. Data suggest that bisphosphonates have a residual therapeutic effect after being stopped and that fracture benefit appears to be sustained 2-5 years after discontinuation. This sustained benefit, however, was observed only in women with good adherence who were treated with bisphosphonate therapy for at least 2 years and whose BMD was not in the osteoporotic range before discontinuation. CONCLUSION: The benefits of long-term bisphosphonate therapy in patients at high risk of fracture likely outweigh the risks. In lower risk patients, such as those with a BMD in the osteopenic or normal range after two to five years of treatment and no history of fracture, consideration could be given to stopping therapy for two to five years.

Metformin use in renal dysfunction: is a serum creatinine threshold appropriate?

PURPOSE: The relationship among metformin use, plasma lactate levels, and lactic acidosis in patients with type 2 diabetes mellitus and the appropriateness of metformin use in patients with renal dysfunction are discussed. SUMMARY: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes recommends metformin therapy as first-line therapy along with lifestyle modification to treat type 2 diabetes mellitus. Despite this recommendation, metformin may be underutilized due to the fear of metformin-associated lactic acidosis and because its use is contraindicated in patients with renal dysfunction. Several studies have attempted to characterize the relationship among plasma metformin levels, plasma lactate levels, and lactic acidosis. However, a causal relationship between metformin and lactic acidosis has not been definitively established. In the United States, the estimated rate of lactic acidosis among diabetic patients treated with metformin is similar to that of diabetic patients not taking metformin. Despite specific guidelines advising against prescribing metformin in renal dysfunction, published reports indicate that metformin is continued in 25% of patients after the contraindication is discovered. Individual studies point to a possible correlation between metformin levels and plasma lactate levels, but mortality does not appear to correlate with plasma metformin levels. These results indicate that there may not be a direct relationship between plasma lactate and metformin levels. CONCLUSION: Current studies point to a weak causal relationship between metformin and lactic acidosis. In patients without comorbid conditions that would predispose them to lactic acidosis, elevated serum creatinine levels should be considered a risk factor for the development of lactic acidosis but not an absolute contraindication.

Etiology and treatment of community-associated methicillin-resistant Staphylococcus aureus.

PURPOSE: Risk factors and treatment recommendations for community-associated methicillin-resistant Staphylococcus aureus are reviewed. SUMMARY: A new strain of methicillin-resistant Staphylococcus aureus (MRSA) has prompted researchers to examine the factors associated with infections acquired in outpatient settings as opposed to those that develop nosocomially. Infections of the skin, lungs, urinary tract, and bloodstream diagnosed within 24-72 hours of hospitalization and with no risk factors present were categorized as community-associated MRSA (CA-MRSA) and differentiated from health-care-associated methicillin-resistant S. aureus (HA-MRSA) on a molecular basis. Pulsed-field electrophoresis has been instrumental in genotyping the S. aureus organism to identify bacterial isolates. Molecular differences between community- and hospital-associated strains show that the organisms were genetically distinct and had not migrated to other settings. Some studies examining antibiotic resistance indicated a steady increase in the rate of MRSA infections. In addition, results of a 15-year longitudinal study indicated significant increases in CA-MRSA-positive isolates between 1991 and 2004. Race, age, sex, hygiene, living environment, and socioeconomic status have been shown to play a key role in the incidence of CA-MRSA. CONCLUSION: Health care providers should recognize how CA-MRSA and HA-MRSA are differentiated and what factors are associated with infections caused by the organisms. This will enable health care providers to quickly identify and initiate appropriate treatment for these infections.

Recent developments in the management of acute respiratory distress syndrome in adults.

PURPOSE: Recent developments in the management of acute respiratory distress syndrome (ARDS) in adults are reviewed. SUMMARY: Corticosteroids have been extensively studied in ARDS; however, they have not demonstrated clear benefit in patients with ARDS. Some trials have found increased complications and mortality related to corticosteroid use. The use of conservative fluid management has been associated with significant reductions in morbidity, highlighting the need to avoid fluid over-administration in patients with ARDS. A number of ventilatory strategies have also been studied. Studies have found that higher positive end-expiratory pressure settings do not appear to be harmful in patients with ARDS. In an effort to prevent alveolar overdistention, low tidal volume and plateau pressure ventilation is increasingly being used in patients with acute lung injury (ALI). Given the increasing evidence supporting the use of lower tidal volume ventilation, this strategy has become the new standard of care in patients with suspected ALI and ARDS. No clear benefit has been shown in the treatment of ARDS with nitric oxide and surfactant. Prostaglandins and acetylcysteine are not considered useful in the treatment of ARDS, while no conclusions can be drawn regarding the benefits of albuterol on mortality in patients with ARDS. The use of prone positioning should be discouraged in the treatment of ARDS based on its associated risks. CONCLUSION: Early administration of moderate-dosage corticosteroids likely helps decrease the time of ventilator dependence and duration of intensive care unit stay. Conservative fluid management and low tidal volume ventilation are becoming increasingly widespread in the management of patients with ARDS. Nitric oxide, surfactant, prostaglandins, albuterol, acetylcysteine, and prone positioning have not been shown to be beneficial in the treatment of ARDS.

Dosing factor VIIa (recombinant) in nonhemophiliac patients with bleeding after cardiac surgery.

PURPOSE: The dosing of factor VIIa (recombinant) in nonhemophiliac patients with cardiac-surgery-associated bleeding (CSAB) is discussed. SUMMARY: Factor VIIa (recombinant) is a vitamin K-dependent glycoprotein that is FDA-approved for use in patients with hemophilia A or B with inhibitors to factor VIII or IX and for patients with factor VII deficiency. Case reports and observational studies indicate that factor VIIa (recombinant) may be efficacious for the treatment of acute bleeding episodes related to trauma, surgery, and coagulopathies. The use of factor VIIa (recombinant) for CSAB is increasing. No controlled clinical trials have been conducted to determine the safety and efficacy of factor VIIa (recombinant) in the treatment of CSAB; therefore, the appropriate dosing scheme remains unclear. In addition, thromboembolic events associated with factor VIIa (recombinant) have been reported, so the safety of factor VIIa (recombinant) in patients with normal coagulation systems is unclear. Data from one randomized, controlled, clinical trial of the use of factor VIIa (recombinant) in intracerebral hemorrhage showed a dose-related trend toward adverse events when factor VIIa (recombinant) was compared with placebo. CONCLUSION: No particular dose of factor VIIa (recombinant) is strongly supported in the literature for off-label use, and thromboembolic events may be dose dependent. Use of the smallest possible dose is warranted because of the high cost of factor VIIa (recombinant) and the potential for thromboembolic events. A single dose of 2.4 or 4.8 mg or 45 microg/kg should be considered.