Kevin W. McConeghy

I.V. minocycline revisited for infections caused by multidrug-resistant organisms

PURPOSE The evidence supporting the potential use of i.v. minocycline for serious infections caused by multidrug-resistant organisms (MDROs) is summarized. SUMMARY Minocycline achieves good tissue penetration and excellent oral absorption. Minocycline achieves serum concentrations comparable to other tetracyclines, with peak serum concentrations ranging from 3 to 8.75 mg/L following i.v. administration of 200 mg. Minocycline retains antimicrobial activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus as well as many gram-negative pathogens, such as Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Stenotrophomonas maltophilia. Minocycline has been used to treat respiratory infections caused by Acinetobacter baumannii and bloodstream infections. The majority of these gram-negative infections were treated with combination therapy, with results similar to those seen with first-line agents. The ability to switch from parenteral to oral therapy and its favorable tissue penetration make minocycline an attractive option for severe respiratory or skin and skin structure infections. For A. baumannii infections, minocycline is the second most active agent in vitro and may be the only therapeutic option in certain cases. The overall clinical experience with minocycline supports its use to treat A. baumannii infections alone or in combination with other agents. Minocycline could be used to treat other MDRO gram-negative infections but only as an agent of last resort due to the limited data available. CONCLUSION The available pharmacokinetic and clinical data support the use of i.v. minocycline for the treatment of MDRO infections, including infections due to S. aureus coagulase-negative and gram-negative pathogens.

Fracture Risk Assessment in Long-term Care (FRAiL): Development and Validation of a Prediction Model

Background Strategies used to predict fracture in community-dwellers may not be useful in the nursing home (NH). Our objective was to develop and validate a model (Fracture Risk Assessment in Long-term Care [FRAiL]) to predict the 2-year risk of hip fracture in NH residents using readily available clinical characteristics. Methods The derivation cohort consisted of 419,668 residents between May 1, 2007 and April 30, 2008 in fee-for service Medicare. Hip fractures were identified using Part A diagnostic codes. Resident characteristics were obtained using the Minimum Data Set and Part D claims. Multivariable competing risk regression was used to model 2-year risk of hip fracture. We validated the model in a remaining 1/3 sample (n = 209,834) and in a separate cohort in 2011 (n = 858,636). Results Mean age was 84 years (range 65-113 years) and 74.5% were female. During 1.8 years mean follow-up, 14,553 residents (3.5%) experienced a hip fracture. Fifteen characteristics in the final model were associated with an increased risk of hip fracture including dementia severity, ability to transfer and walk independently, prior falls, wandering, and diabetes. In the derivation sample, the concordance index was 0.69 in men and 0.71 in women. Calibration was excellent. Results were similar in the internal and external validation samples. Conclusions The FRAiL model was developed specifically to identify NH residents at greatest risk for hip fracture, and it identifies a different pattern of risk factors compared with community models. This practical model could be used to screen NH residents for fracture risk and to target intervention strategies.

Defining hip fracture with claims data: outpatient and provider claims matter

SummaryMedicare claims are commonly used to identify hip fractures, but there is no universally accepted definition. We found that a definition using inpatient claims identified fewer fractures than a definition including outpatient and provider claims. Few additional fractures were identified by including inconsistent diagnostic and procedural codes at contiguous sites.IntroductionMedicare claims data is commonly used in research studies to identify hip fractures, but there is no universally accepted definition of fracture. Our purpose was to describe potential misclassification when hip fractures are defined using Medicare Part A (inpatient) claims without considering Part B (outpatient and provider) claims and when inconsistent diagnostic and procedural codes occur at contiguous fracture sites (e.g., femoral shaft or pelvic).MethodsParticipants included all long-stay nursing home residents enrolled in Medicare Parts A and B fee-for-service between 1/1/2008 and 12/31/2009 with follow-up through 12/31/2011. We compared the number of hip fractures identified using only Part A claims to (1) Part A plus Part B claims and (2) Part A and Part B claims plus discordant codes at contiguous fracture sites.ResultsAmong 1,257,279 long-stay residents, 40,932 (3.2%) met the definition of hip fracture using Part A claims, and 41,687 residents (3.3%) met the definition using Part B claims. 4566 hip fractures identified using Part B claims would not have been captured using Part A claims. An additional 227 hip fractures were identified after considering contiguous fracture sites.ConclusionsWhen ascertaining hip fractures, a definition using outpatient and provider claims identified 11% more fractures than a definition with only inpatient claims. Future studies should publish their definition of fracture and specify if diagnostic codes from contiguous fracture sites were used.

Facility and State Variation in Hip Fracture in U.S. Nursing Home Residents

To quantify the variation in hip fracture incidence across U.S. nursing home (NH) facilities and states and examine how hip fracture incidence varies according to facility‐ and state‐level characteristics.

Are non-allergic drug reactions commonly documented as medication “allergies”? A national cohort of Veterans' admissions from 2000 to 2014

Adverse drug reactions (ADRs) including medication allergies are not well‐described among large national cohorts. This study described the most common documented medication allergies and their reactions among a national cohort of Veterans Affairs (VA) inpatients.

Influenza Illness and Hip Fracture Hospitalizations in Nursing Home Residents: Are They Related?

Background Influenza illness may impact the risk of falls and fractures during acute illness due to unsteady gait or dizziness. We evaluated the association between influenza and hip fracture hospitalizations in long-stay (LS) nursing home (NH) residents. Methods We analyzed weekly rates of hospitalization in a retrospective cohort of LS NH residents between January 1, 2000 to December 31, 2009. Hip fracture and influenza like illness (ILI) hospitalizations were identified with Medicare fee-for-service part A claims. We evaluated unadjusted and adjusted models with the primary exposures, weekly rate of influenza-like illness hospitalizations, city-wide mortality, and NH influenza vaccination rate and primary outcome of weekly rate of hip fracture hospitalizations. Results There were 9,237 incident hip fractures in the cohort. Facility wide ILI hospitalization rate was associated with the hip fracture hospitalization rate in the unadjusted (incidence rate ratio [IRR] 1.13, 95% confidence interval [CI]: 1.08, 1.17) and adjusted (IRR 1.13, 95% CI: 1.09, 1.18) analyses. City-wide influenza mortality was associated with hip fracture hospitalization rates for the unadjusted (IRR 1.03, 95% CI: 1.02, 1.04), and adjusted (IRR 1.02, 95% CI: 1.01, 1.03) analyses. NH influenza vaccination rates were not associated with changes in hip fracture hospitalization rates. Conclusions ILI hospitalizations are associated with a 13% average increase in hip fracture hospitalization risk. In a given NH week, an increase in the number ILI hospitalizations from none to two was associated with an approximate one percentage point increase in hip fracture hospitalization risk. Strategies to reduce influenza risk should be investigated to reduce hip fracture risk.

A Quantitative Analysis of FDA Adverse Event Reports with Oral Bisphosphonates and Clostridium difficile

Studies have shown associations between Clostridium difficile infection (CDI) and non‐antimicrobial medications including proton pump inhibitors, osteoporosis medications, and antidepressants.

Administrative health data: guilty until proven innocent. Response to comments by Levy and Sobolev

Dear Editor, We thank the authors for their interest in our article and for raising several important issues [1]. The purpose of our study [2] was not to determine which claimsbased definition of hip fracture performs best, but instead, to simply describe the differences in hip fracture counts that will be obtained using several different definitions of fracture in the nursing home setting, and to encourage validation work. In our BLimitations^ section, we state that in the absence of a validation study with chart review, it is not possible to say which definition of hip fracture is preferable. We disagree with the authors’ claims that our results are misleading. First, the authors state that nonhospitalized hip fractures are Bimprobable.^ To the contrary, it is likely that some nursing home residents with hip fracture are not hospitalized given the frail status of nursing home residents and because many proxies designate a goal of comfort rather than life-prolonging measures. Previous studies suggest that as many as 11.8% of nursing home residents with hip fracture do not undergo surgical repair [3]. Non-hospitalized fractures are thus much more likely for the unique population in nursing homes. Second, in the nursing home setting, part B (outpatient) claims are typically generated from the primary care provider with the most comprehensive knowledge of the resident. Thus, the underlying process giving rise to the data differs for individuals residing in the nursing home, as compared with the community setting. Third, providers are now required to include diagnostic codes as part of outpatient claims. This practice has changed considerably since the early validation study the authors cite [4], and it is unclear whether the low prevalence of true hip fractures ascertained via outpatient codes is still applicable. Many contemporary studies do use both inpatient and outpatient claims to ascertain hip fracture [5–7], and indeed, Current Procedural Terminology (CPT) codes can only be found in outpatient claims. Fourth, we did not include diagnostic codes for pathologic fractures (ICD-9733.14) in order to avoid classifying non-osteoporotic fractures or fracture complications as incident fractures. We have separately looked at the proportion of hip fractures that would be obtained if we included the pathologic fracture code but excluded codes for cancer, aseptic necrosis, or other complications, and the proportions are quite similar. Presently, there is no gold standard definition of hip fracture via claims data that has been validated with a contemporary chart review, yet claims data remain a common and important method to study fracture. Our study suggests that at least in the nursing home setting, the addition of outpatient claims will identify 11% more hip fractures than inpatient claims alone, though we make no claim about which data source or hip fracture definition is most valid. We hope that our study will encourage investigators to publish the exact claims-based definition of hip fracture that they use, especially for unique settings like the nursing home where prior validation studies may not apply. We also strongly advocate for future * S. D. Berry sarahberry@hrca.harvard.edu

Epidemiology of hip fracture in nursing home residents with multiple sclerosis

BACKGROUND Hip fracture risk is high in young people with multiple sclerosis (MS), but has not been examined in an institutionalized aging population with MS. OBJECTIVE We aimed to compare the hip fracture risk in nursing home (NH) residents with and without MS; and (2) examine risk factors for hip fracture in those with MS. METHODS We conducted a retrospective cohort study using national NH clinical assessment and Medicare claims data. Participants included age-, sex- and race-matched NH residents with/without MS (2007-2008). Multivariable competing risk regression was used to compare 2-year hip fracture risk, and to examine risk factors. RESULTS A total of 5692 NH residents with MS were matched to 28,460 without MS. Approximately 80% of residents with MS vs. 50% of those without MS required extensive assistance in walking at NH admission. The adjusted incidence rate of hip fracture was 7.1 and 18.6 per 1000 person-years in those with or without MS, respectively. Wandering and anxiolytic exposure were the main hip fracture risk factors in transfer independent residents with MS; while pneumonia and antidepressant use were the main factors in dependent residents with MS. CONCLUSIONS In contrast to prior comparisons from non-NH populations, the incidence of hip fracture was lower in NH residents with MS as compared with matched controls. Residents with MS were much more functionally dependent, which likely explains these findings. Fracture prevention strategies should focus on fall prevention in independent residents; and possibly improvement of health status and facility quality of care in dependent residents.

Computer-Assisted Antimicrobial Recommendations for Optimal Therapy: Analysis of Prescribing Errors in an Antimicrobial Stewardship Trial

Clinician education and prospective audit and feedback interventions, deployed separately and concurrently, did not reduce antimicrobial use errors or rates compared to a control group of general medicine inpatients at our public hospital. Additional research is needed to define the optimal scope and intensity of hospital antimicrobial stewardship interventions. Infect Control Hosp Epidemiol 2017;38:857-859.