Kevin G. Moores

Mini-Sentinel's systematic reviews of validated methods for identifying health outcomes using administrative and claims data: methods and lessons learned

To overview the methods used in the Mini‐Sentinel systematic reviews of validation studies of algorithms to identify health outcomes in administrative and claims data and to describe lessons learned in the development of search strategies, including their ability to identify articles from previous systematic reviews which used different search strategies.

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.

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.

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.

A systematic review of validated methods for identifying pancreatitis using administrative data

To systematically review algorithms identifying cases of pancreatitis in administrative data, with a focus on studies examining algorithm validity.

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.

A systematic review of validated methods for identifying systemic lupus erythematosus (SLE) using administrative or claims data

PURPOSE To examine the validity of billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify patients with systemic lupus erythematosus (SLE) in administrative and claims databases. METHODS We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to SLE. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. The two reviewers independently extracted data regarding participant and algorithm characteristics and assessed a studys methodologic rigor using a pre-defined approach. RESULTS Twelve studies included validation statistics for the identification of SLE in administrative and claims databases. Seven of these studies used the ICD-9 code of 710.0 in selected populations of patients seen by a rheumatologist or patients who had experienced the complication of SLE-associated nephritis, other kidney disease, or pregnancy. The other studies looked at limited data in general populations. The algorithm in the selected populations had a positive predictive value (PPV) in the range of 70-90% and of the limited data in general populations it was in the range of 50-60%. CONCLUSIONS Few studies use rigorous methods to validate an algorithm for the identification of SLE in general populations. Algorithms including ICD-9 code of 710.0 in physician billing and hospitalization records have a PPV of approximately 60%. A requirement that the code is obtained from a record based on treatment by a rheumatologist increases the PPV of the algorithm but limits the generalizability in the general population.

A systematic review of validated methods for identifying transfusion-related sepsis using administrative and claims data

To systematically review algorithms to identify transfusion‐related sepsis or septicemia in administrative data, with a focus on studies that have examined the validity of the algorithms.

Is double coverage of gram-negative organisms necessary?

PURPOSE The appropriateness of combination therapy for infections caused by gram-negative organisms is examined. SUMMARY Mortality from Pseudomonas aeruginosa infection is particularly high; therefore, empirical regimens are often selected to ensure coverage for this organism. The initial use of combination antimicrobial therapy for gram-negative infections is usually justified by one of three reasons: the potential for synergistic activity between two classes of antimicrobial agents, the broad empirical coverage provided by two antimicrobial agents with differing spectra of activity and resistance patterns, or the prevention of resistance development during antimicrobial therapy. Disadvantages of using combination therapy are increased drug toxicity, increased costs, and increased risk of superinfection with more-resistant bacteria or fungi. There are no clinical data that suggest that the combination of a β-lactam plus a fluoroquinolone results in improved patient outcomes compared with a β-lactam alone or a β-lactam plus an aminoglycoside. Results from studies that evaluate combination therapy versus monotherapy for gram-negative bacilli conflict with the common practice of use of double coverage. Strong evidence to support the administration of antimicrobials for double coverage of gram-negative organisms is lacking. Antimicrobial overuse may lead to antibiotic resistance, unnecessary adverse effects, and increased costs. CONCLUSION The available clinical evidence does not support the routine use of combination antimicrobial therapy for treatment of gram-negative infections. Patients with shock or neutropenia may benefit from combination therapy that includes an aminoglycoside.

Evidence-Based Practice in Health Care

Health care practice requires managing large amounts of information. Rapid advances are occurring in available evidence regarding effectiveness and efficiency of various health care services. The health care practitioner must have information management skills plus access to resources and technology. Evidence-based medicine is a philosophy of practice and an approach to decision making that values systematic evidence. There are many similarities in evidence-based practice and the systematic approach to drug information. New information resources and informatics technologies are available, and changes are occurring in health professional education that support an evidence-based practice. Implementation of principles and tools of evidence-based medicine are expected to improve the quality, effectiveness, and efficiency of care.